N° 17149 - Organisation Africaine de la Propriété Intellectuelle

ORGANISATION AFRICAINE DE LA PROPRIETE INTELLECTUELLE

Inter. CI.

N°

FASCICULE DE BREVET D’INVENTION

17149

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O.A.P.I. – B.P. 887, YAOUNDE (Cameroun) – Tel. (237) 22 20 57 00– Fax: (237) 22 20 57 27– Site web: http:/www.oapi.int – Email: [email protected]

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Abrégé : This document discloses molecules having the formula (I) and processes related thereto.

Titre : Pesticidal compositions and processes related thereto.

Numéro de dépôt : 1201400482 (PCT/US13/029608)

Titulaire(s) : Dow AgroSciences LLC,

9330 Zionsville Road, INDIANAPOLIS, Indiana 46268 (US) Date de dépôt : 07/03/2013

Priorité(s) : US n° 61/639,274 du 27/04/2012

Délivré le : 31/07/2015

Publié le : 28.03.2016

Inventeur(s) :

HUNTER, Ricky (US) BUYSSE, Ann M. (US) NIYAZ, Noormohamed M. (US) ZHANG, Yu (US) WALSH, Martin J. (US) KUBOTA, Asako (US) TRULLINGER, Tony K. (US) PATNY, Akshay (US) GARIZI, Negar (US) LOWE, Christian T. (US) KNUEPPEL, Daniel (US) DEMETER, David A. (US) LEPLAE, Paul Renee (US) WESSELS, Frank (US)

Mandataire : Cabinet Spoor & Fisher Inc. Ngwafor & Partners, Blvd. du 20 Mai, Immeuble Centre Commercial de l'Hôtel Hilton, 2è Etage, Porte 208A, B.P. 8211, YAOUNDE (CM).

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A01N 43/653 A01N 43/84 A01N 43/56

PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO

CROSS REFERENCES TO RELATED APPLICATIONS

This Application claims priority from, and benefit of, U.S. provisional application serial

5 number 61/639,274 — which was filed on April 27, 2012. The entire content of this provisional

application is hereby Incorporated by reference into this Application.

FIELD OF THE DISCLOSURE

This disclosure Is related to the field of processes to produce molecules that are useful

as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules,

10 and processes of using such molecules to control pests.

BACKGROUND

Pests cause millions of human deaths around the world each year. Furthermore, there

are more than ten thousand species of pests that cause losses in agriculture. The world-wide

agricultural losses amount to billions of U.S. dollars each year.

15 Termites cause damage to all kinds of private and public structures. The world-wide

termite damage losses amount to billions of U.S. dollars each year.

Stored food pests eat and adulterate stored food. The world-wide stored food losses

amount to billions of U.S. dollars each year, but more importantly, deprive people of needed

food.

20 There Is an acute need for new pesticides. Certain pests are developing resistance to

pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The

development of resistance to some of the older pesticides, such as DDT, the carbamates, and

the organophosphates, is well known. But resistance has even developed to some of the newer

pesticides.

25 Therefore, for many reasons, including the above reasons, a need exists for new

pesticides.

DEFINITIONS

The examples given in the definitions are generally non-exhaustive and must not be

construed as limiting the invention disclosed in this document. It is understood that a substituent

30 should comply with chemical bonding rules and steric compatibility constraints in relation to the

particular molecule to which it is attached.

"Alkenyl" means an acyclic, unsaturated (at least one carbon-carbon double bond),

branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl,

allyl, butenyl, pentenyi, and hexenyl.

35 -Alkenyloxy means an alkenyl further consisting of a carbon-oxygen single bond, for

example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

I

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sAlkoxya means an alkyl further consisting of a carbon-oxygen single bond, for example,

methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy.

-Alkyl means an acyclic, saturated, branched or unbranched, substituent consisting of

carbon and hydrogen, for example, methyl, ethyl, (C 3)alky1which represents n-propyl and

5 isopropyl), (C4)alkyl which represents n-butyl, sec-butyl, isobutyl, and tert-butyl.

"Alkynyr means an acyclic, unsaturated (at least one carbon-carbon triple bond),

branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl,

propargyl, butynyl, and pentynyl.

"Alkynyloxy" means an alkynyl further consisting of a carbon-oxygen single bond, for

10 example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.

'Aryl" means a cyclic, aromatic substituent consisting of hydrogen and carbon, for

example, phenyl, naphthyl, and biphenyl.

IC„-Cyr where the subscripts 're and "y" are integers such as 1, 2, or 3, means the

range of carbon atoms for a substituent — for example, (C 1 -C4)alkyl means methyl, ethyl, n-

15 propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl, each individually.

t ycloalkenyr means a monocyclic or polycyclic, unsaturated (at least one carbon-

carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl,

cyclopentenyl, cyclohexenyl, norbomenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,

hexahydronaphthy1, and octahydronaphthyl.

20 tycloalkenyloxy" means a cycloalkeny1further consisting of a carbon-oxygen single

bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbomenyloxy, and

bicyclo(2.2.2]octenyloxy.

tycloalkyr means a monocyclic or polycyclic, saturated substituent consisting of

carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbomyl,

25 bicyclo(2.2.2]octyl, and decahydronaphthyl.

t ycloalkoxy means a cycloalkyl further consisting of a carbon-oxygen single bond, for

example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbomyloxy, and

bicyclo[2.2.2]octyloxy.

"Halo" means fluoro, chloro, bromo, and iodo.

30 Ilaloalkoxy means an alkoxy further consisting of, from one to the maximum possible

number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-

difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and

pentafluoroethoxy.

Ilaloallryr means an alkyl further consisting of, from one to the maximum possible

35 number of, identical or different, halos, for example, fluoromethyl, trifluoromethy1, 2,2-

difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

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Ileterocyclyr means a cyclic substituent that may be fully saturated, partially

unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at

least one heteroatom, where said heteroatom Is nitrogen, sulfur, or oxygen. In the case of sulfur,

that atom can be in other oxidation states such as a sulfoxide and sulfone. Examples of

5 aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl,

benzolsoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, Imidazolyl,

indazolyl, Ind°lyl, Isoindolyl, isoquinolinyl, isothiazolyl, Isoxazolyl, oxadiazolyl, oxazolinyl,

oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimIdinyl, pyrrolyl,

quInazolinyl, quinolinyl, quinoxallnyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, trlazinyl, and

10 triazolyl. Examples of fully saturated heterocyclyls Include, but are not limited to, piperazinyl,

piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and

tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to,

1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-

isoxazolyl, and 2,3-dihydro-(1,3,4]-oxadiazolyl. Additional examples Include the following

\--1 Li 1 7 %.

\-1 r 1 s=.0 ii

15 S 0

thle anyl thietanyl-oxide thletanyl-dioxide.

DETAILED DESCRIPTION

This document discloses molecules having the following formula ("Formula One"):

7

A R8 N

I R6

20

wherein

(a) A Is either

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R4

attachment bond

Al or

attachment bond

II

RI Is1 R5 R3

A2

(b) RI is H, F, Cl, Br, I, CN, 140 2, substituted or unsubstituted C i -C,3 alkyl, substituted

or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or

unsubstituted Crete alkenyloxy, substituted or unsubstituted C rCI0 cycloalkyl, substituted or

5 unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted C8-C20 aryl, substituted or

unsubstituted C 1 -C20 heterocyclyl, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(=X1)R9, S(0)R9, S(0)0R9, S(0)N(R9)2, or R9S(0) nR9,

wherein each said RI, which is substituted, has one or more substituents

selected from F, CI, Br, I, CU, 1402, C1-C6 alkyl, CrCe alkenyl, C1-C6 haloalkyl, C 2-05

10

haloalkenyl, C1 -C6 haloalkyloxy, C-rC6 haloalkenyloxy, C3-C 10 cycloalkyl, C3-C10 cycloalkenyl,

C3-Cio halocycloalkyl, C3-C1e halocycloalkenyl, OR9, S(0)0R9, C5-C20 aryl, or C1-C2o

heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(c) R2 is H, F, CI, Br, I, CU, NO2, substituted or unsubstituted C1-C6 alkyl, substituted

or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-03 alkoxy, substituted or

15 unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C 1 0 cycloalkyl, substituted or

unsubstituted CrC10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

unsubstituted C1-C20 heterocyclyl, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(=X1)R9, 5R9, S(0),OR9, or R9S(0) nR9,

wherein each said R2, which is substituted, has one or more substituents

20 selected from F, Cl, Br, I, CN, NO2, C1-05 alkyl, CrC6 alkenyl, C1-C6 haloalkyl, CrCe

haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-Clo cycloalkenyl,

C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)0R9, C8-C20 aryl, or C1-Czo


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(d) R3 is H, F, CI, Br, I, CN, NO2, substituted or unsubstituted C1-03 alkyl, substituted

or unsubstituted C2-03 alkenyl, substituted or unsubstituted C 1-C6 alkoxy, substituted or

unsubstituted Crete alkenytoxy, substituted or unsubstituted C3-00 cycloalkyl, substituted or

unsubstituted C3-00 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

5

unsubstituted C1-C20 heterocyclyl, 0R9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(=X1)R9, SR9, S(0),OR9, or R9S(0)„R9,


selected from F, Cl, Br, I, CN, NO2, C1-03 alkyl, Crens alkenyl, C1-03 haloalkyl, CrCe

haloalkenyl, CI-Co haloalkyloxy, Crepe haloalkenyloxy, C3-00 cycloalkyl, C3-00 cycloalkenyl,

10 C3-C10 halocycloalkyl, C3-00 halocycloalkenyl, OR9, S(0)„0R9, 03-C20 aryl, or C 1 -Cm


(e) when A Is

(1) Al then Al is either

(a) All

attachment bond to carbon

attachment bond to nitrogen

R5

15 All

where R4 is H, NO2, substituted or unsubstituted C1-03 alkyl,

substituted or unsubstituted C2-C6 alkenyi, substituted or unsubstituted C 1-C6 alkoxy, substituted

or unsubstituted C3-C1 0 cycloalkyl, substituted or unsubstituted C3-00 cycloalkenyl, substituted

or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C20 heterocyclyl, C(=X1)R9,

20 C(=X1)0R9, C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, S(0)OR9, or R9S(0)„R9,

wherein each said R4, which Is substituted, has one or more

substituents selected from F, Cl, Br, I, CN, NO2, C1-C6 alkyl. C2-C6 alkenyl, C1-03 haloalkyl, Cr

Ce haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-00 cycloaikenyi,

C3-C10 halocycloalkyl, C3-00 halocycloalkenyl, OR9, S(0)0R9, C6-020 aryl, or 0-C2o

25 heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9), or

(b) Al2

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Al2

where R4 Is a CI-C6 alkyl,

(2) A2 then R4 Is H, F, CI, Br, I, CN, NO 2, substituted or unsubstituted C1-C6

5 alkyl, substituted or unsubstituted C 2-C6 alkenyl, substituted or unsubstituted C 1 -C6 alkoxy,

substituted or unsubstituted CrC e alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl,

substituted or unsubstituted C 3-C10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl,

substituted or unsubstituted C 1 -C20 heterocyclyl, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9) 2,

N(R9)2, N(R9)C(=X1)R9, SR9, S(0) 00R9, or R9S(0)„R9,

10 wherein each said R4, which Is substituted, has one or more substituents

selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, C2-C6 aikenyl, C I -C6 haloalkyl, C2-C6

haloalkenyl, C1-C6 haloalkyloxy, C2-CC haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl,

C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)00R9, C6-C20 aryl, or CI-Czo


15 (f) R5 Is H, F, Cl, Br, I, CN, NO2, substituted or unsubstituted C1-C6 alkyl, substituted

or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C I-C6 alkoxy, substituted or

unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or

unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, 0R9, C(X1)R9,

C(=X1)0R9, C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, 5R9, S(0)00R9, or R9S(0),R9,


selected from F, CI, Br, I, CN, NO 2, CI-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, C2-C6

haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-Ci0 cycloalkyl, C3-C13 cycloalkenyl,

C3-C 1 0 halocycloalkyl, CrC10 halocycloalkenyl, OR9, S(0)00R9, or C6-02o aryl, (each of which

that can be substituted, may optionally be substituted with R9);

25 (0) (1) when A is Al then R6 Is R1 1, substituted or unsubstituted C I-Co alkyl,

substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted

or unsubstituted Crete alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or

unsubstituted C3-C 10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

30 unsubstituted CI-C20 heterocyclyl, 0R9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(=X1)R9, SR9, S(0) 00R9, R9S(0),,R9, Ci-C6 alkyl C5-C20 aryl (wherein the alkyl and aryl

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can independently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9,

R9X2R9, C(=0)(C1-C6 alky0S(0)n(Ci-C6 alkyl), C(=0)(CI-C6 alky9C(=0)0(C1-Ce AA. (C1-C6

alky1)0C(=0)(Ce-C2o aryl), (C1-05 alky1)0C(=OXCI-05 alkyl), Cl-C6 alkyl-(CrC,0 cyclohaloalkYl),

or (C 1 -C6 alkeny9C(=0)0(CI-C6 alkyl), or R9X2C(=X1)X2R9,

5 wherein each said R6 (except R1 1), which Is substituted, has one or more

substituents selected from F, Cl, Br, I, CN, NO2, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkYl, Cr

Cs haloalkenyl, Ci-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl,

C3-C 1 0 halocycloalkyl, G3-C10 halocycloalkenyl, OR9, S(0)„0R9, C6-C20 aryl, or C1-C2o

heterocyclyl, R9aryl, (each of which that can be substituted, may optionally be substituted with

10 R9),

optionally R6 (except R1 1) and R8 can be connected In a cyclic

arrangement, where optionally such arrangement can have one or more heteroatoms selected

from 0, S, or, N, in the cyclic structure connecting R6 and R8, and

(2) when A Is A2 then R6 is R1 1, H, substituted or unsubstituted C I -Cs alkyl,

15 substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted CI-C6 alkoxy, substituted

or unsubstituted Crete alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or

unsubstituted GrC 1 0 cycloalkenyl, substituted or unsubstituted Cs-Cm aryl, substituted or

unsubstituted C 1 -C20 heterocyclyl, OR9, C(=X1 )R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(=X1)R9, SR9, S(0)0R9, R9S(0)nR9, C1-C6 alkyl C6-C20 aryl (wherein the alkyl and aryl

20 can Independently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9,

R9X2R9, C(=0)(C1-C6 alkyl)S(0),(CI-C6 alkyl), C(=0)(C1-C6 alkyl)C(=0)0(CI-C6 alkyl), (C 1-C8

alky1)0C(=0)(C6-C20 aryl), (C1 -C6 alky1)0C(=0)(Ci-C6 alkyl), CI-C6 alkyl-(C3-C10 cyclohaloalkyl),

or (C 1 -C6 alkeny0C(=0)0(C I -C6 alkyl), or R9X2C(=X1)X2R9,

wherein each said R6 (except R1 1), which Is substituted, has one or more

25 substituents selected from F, Cl, Br, I, CN, NO2, C1 -C6 alkyl, CrCe alkenyl, C 1 -C6 haloalkyl, Cr

Cg haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl,

CrCio halocycloalkyl, CrC10 halocycloalkenyl, OR9, S(0),OR9, C8-C20 aryl, or C1-C2o


R9),

30 optionally R6 (except R1 1) and R8 can be connected In a cyclic


from 0, S, or N, in the cyclic structure connecting R6 and R8;

(h) R7 is 0, S. NR9, or NOR9;

(I) R8 Is substituted or unsubstituted C 1 -C6 alkyl, substituted or unsubstituted C 2-C6

35

alkenyl, substituted or unsubstituted C 1 -C8 alkoxy, substituted or unsubstituted C2-C6

alkenyloxy, substituted or unsubstituted CrC ia cycloalkyl, substituted or unsubstituted CrCi0

cycloalkenyl, substituted or unsubstituted C8-C20 aryl, substituted or unsubstituted C1-C2o

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heterocyclyl, OR9, OR9S(0),R9, C(=X1)R9, C(=X1)0R9, R9C(=X1)0R9, R9X2C(=X1)R9X2R9,

C(=X1)N(R9)2, N(R9)2, N(R9)(R9S(0),R9), N(R9)C(=X1)R9, SR9, S(0),OR9, R9S(0),119, or

R9S(0)n(NZ)R9,


5 selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, C,-C8 alkenyl, C1-C6 haloalkyl, CrCe

haloalkenyl, C l-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-Cio cycloalkyl, C3-C10 cycloalkenyl,

Co-C lo halocycloalkyl, C3-C 10 halocycloalkenyl, N(R9)S(0)R9, oxo, OR9, S(0)„0R9,

R9S(0)R9, S(0)R9, C6-C20 aryl, or CI-C20 heterocyclyl, (each of which that can be substituted,

may optionally be substituted with R9)

10 alternatively R8 Is R13-S(0)-R13 wherein each R13 Is independently selected

from substituted or unsubstituted C 1 -C6 alkyl, substituted or unsubstituted C2-C6 alkenyl,

substituted or unsubstituted C 1 -C6 alkoxy, substituted or unsubstituted C2-C6 alkenyloxy,

substituted or unsubstituted C3-C 1 0 cycloalkyl, substituted or unsubstituted C3-C 10 cycloalkenyl,

substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted CI-C20 heterocyclyl,

15 substituted or unsubstituted S(0)CI-C6 alkyl, substituted or unsubstituted N(CI-C6alky92,

wherein each said substituted alkyl, substituted alkenyl, substituted alkoxy, substituted

alkenyloxy, substituted cycloalkyl, substituted cycloaIkenyl, substituted aryl, substituted

heterocyclyl, has one or more substituents Independently selected from F, Cl, Br, I, CN, NO2,

C I -C6 alkyl, G2-C6 alkenyl, C I -C6 haloalkyl, CrCe haloalkenyl, C I -C6 haloalkyloxy, G2-C6

20 haloalkenyloxy, C3-C10 cycloalkyl, C 3-C 1 0 cycloalkenyl, C3-C 1 0 halocycloalkyl, Co-Cw

halocycloalkenyl, OC I -C6 alkyl, 0C1-C6 haloalkyl, S(0)„C I -C6alkyl, S(0)nOCI-C6 alkyl, C8-C20

aryl, or C I -C20 heterocyclyl, Oren, alkynyl. CI-C6 alkoxy, N(R9)S(0)R9, OR9, N(R9) 2, R90R9,

R9N(R9)2, R9C(=X1)R9, R9C(=X1)N(R9)2, N(R9)C(=X1)R9, R9N(R9)C(=X1)R9, S(C)0R9,

R9C(=X1)0R9, R90C(=X1)R9, R9S(0)nR9, S(0)R9, oxo, (each of which that can be

25 substituted, may optionally be substituted with R9);

(j) R9 Is (each independently) H, CN, substituted or unsubstituted C 1 -C6 alkyl,

substituted or unsubstituted CrC6 alkenyl, substituted or unsubstituted C I -C6 alkoxy, substituted

or unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted Co-CID cycloalkyl, substituted or

unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

30 unsubstituted C I -G2oheterocyclyl, substituted or unsubstituted S(0)„C I -Ce alkyl, substituted or

unsubstituted N(C I -C.ealky1)2,


selected from F, Cl, Br, I, CN, NO2, C1-C6 alkyl, C2-C6 alkenyl, C I -C6 haloalkyl, Crete

haloalkenyl, CI-Co haloalkyloxy, CrC6 haloalkenyloxy. C3-C10 cycloalkyl, C 3-C 1 0 cycloalkenyl.

35 C3-00 halocycloalkyl, C 3-C 1 0 halocycloalkenyl, 0C I -C6 alkyl, 0C1-C6 haloalkyl, S(0) nCI-C6alkyl,

S(0)„OCI-C6 alkyl, C5-C20 aryl, or C 1-C20 heterocyclyl;

(k) n is 0, 1, or 2;

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(I) X Is N or CR.,, where R„, is H, F, CI, Br, I, CN, NO2, substituted or unsubstituted

C 1 -C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C i -C6

alkoxy, substituted or unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-C10

cycloalkyl, substituted or unsubstituted C3-C10cycloalkenyl, substituted or unsubstituted C6-C20

5 aryl, substituted or unsubstituted C1-C2oheterocyclyl, 0R9, C(=X1)R9, C(=X1)0R9,

C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, SR9, S(0)R9, S(0)0R9, or R9S(0),R9,

wherein each said R io which is substituted, has one or more substituents

selected from F, CI, Br, I, CU, NO2, C 1 -C6 alkyl, C2-C8alkenyl, C I-Co haloalkyl, C2-C6

haloalkenyl, C1 -C6 haloalkyloxy, C2-C6 haloalkenyloxy, CrC 1 0 cycloalkyl, C3-C10 cycloalkenyl,

10 C3-C 1 0 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)0R9, C6-C20 aryl, or C1-Cm


(m) X1 Is (each Independently) 0 or S;

(n) X2 Is (each Independently) 0, S, =NR9, or =NOR9;

(o) Z Is CU, NO2, C1-C8alkyl(R9), C(=X1)N(R9h;

15 (p) R11 Is a1(CEC)R12, wherein 011s a bond, substituted or unsubstituted C1- Ce

alkyl, substituted or unsubstituted CrC6 alkenyl, substituted or unsubstituted C2-C6alkynyl,

substituted or unsubstituted C3-C 10 cycloalkyl, substituted or unsubstituted C2-C 1 0 cycloalkoxy,

substituted or unsubstituted CI-C6alkylOR9, substituted or unsubstituted C I -C6alkylS(0)nR9,

substituted or unsubstituted C 1-C6 alkylS(0),(=NR9), substituted or unsubstituted C 1 -C6

20 alkylN(R9) (where (CEC) is attached directly to the N by a bond), substituted or unsubstituted

CI-Co alkylN(R9)2, substituted or unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted

CrCio cycloalkenyl, substituted or unsubstituted Ca-Co alkylC(=R7)Co-C6 alkyIR9, substituted or

unsubstituted Co-Co alkylC(=R7)0R9, substituted or unsubstituted C I-Co alkyl0C0-C6

alkylC(=R7)R9, substituted or unsubstituted C I-05 alkylN(R9)(C(=R7)R9), substituted or

25 unsubstituted C I-C6 alkylN(R9)(C(=R7)0R9), substituted or unsubstituted Co-C6 alkyl C(=R7)C0-

C6 alkylN(R9) (where (CEC) is attached directly to the N by a bond), substituted or unsubstituted

C0-C6alkylC(=R7)C0-Ce alkylN(R9)2 , 0R9, S(0)R9, N(R9)R9, substituted or unsubstituted C6-

C20 aryl, substituted or unsubstituted C I -C20heterocyclyl,

wherein each said a i , which Is substituted, has one or more substituents

30 selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, CrC6 alkenyl, Cree alkYnYI, C1-C6 habalkyl. Cr

Ce haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, CrCio cycloalkyl, CrC10 cycloalkenyli

CrC10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, SR9, S(0),119, S(0)0R9, C6-C20 aryl, or

CI-Cm heterocyclyI, R9aryl, CI-C6alkylOR9, C I -C6alkylS(0)nR9, (each of which that can be

substituted, may optionally be substituted with R9)

35 optionally O l and R8 can be connected in a cyclic arrangement, where optionally

such arrangement can have one or more heteroatoms selected from 0, S, or N, In the cyclic

structure connecting Oland R8;

9

17149

(q) R12 is Qi (except where 0 1 Is a bond), F, CI, Br, I, Si(R9)3(where each R9 is

Independently selected), or R9; and

(r) with the following provisos

(1) that R6 and R8 cannot both be C(=0)CH3,

5 (2) that when Al is All then R6 and R8 together do not form fused ring

systems,

(3) that R6 and R8 are not linked in a cyclic arrangement with only —CH r,

(4) that when A Is A2 then R5 is not C(=0)0H,

(5) that when A is A2 and R6 is H then R8 is not a -(C 1 -C6 alkyl)-0-

10 (substituted aryl), and

(6) that when A Is A2 then R6 Is not -(C ialkyl)(substituted aryl).

In another embodiment of this invention A is Al.

In another embodiment of this Invention A Is A2.

15 In another embodiment of this Invention R1 is H.

In another embodiment of this Invention R2 is H.

In another embodiment of this Invention R3 is selected from H, or substituted or

unsubstituted C i-C6 alkyl.

In another embodiment of this invention R3 Is selected from H or CH 3.

20 In another embodiment of the invention when A is Al then Al Is All.

In another embodiment of the invention when A is Al, and Al is Al 1, then R4 Is

selected from H, or substituted or unsubstituted C 1 -C6 alkyl, or substituted or unsubstituted C8-

C20 aryl.

In another embodiment of the Invention when A is Al, and Al is All then R4 Is selected

25 from CH3, CH(CH3)2, or phenyl.

In another embodiment of the invention when A is Al, and Al is Al2, then R4 is CH3.

In another embodiment of this Invention when A is A2 then R4 is selected from H, or

substituted or unsubstituted C I-C.6 alkyl, substituted or unsubstituted C2-03 alkenyl, substituted

or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C 6-C20 aryl, wherein each said

30 R4, which Is substituted, has one or more substituents selected from F, Cl, Br, or I.

In another embodiment of this Invention when A Is A2 then R4 is H or C i-C6 alkyl.

In another embodiment of this Invention when A Is A2 then R4 Is H, CH 3, CH2CH3,

CH=CH2, cyclopropyl, CH2CI, CF3, or phenyl.

In another embodiment of this invention when A is A2 then R4 Is Br or Cl.

35 In another embodiment of this invention R5 Is H, F, Cl, Br, I, or substituted or

unsubstituted C1-03 alkyl, substituted or unsubstituted C 1 -C8alkoxy .

In another embodiment of this Invention R5 is H, OCH 2CH3, F, CI, Br, or CH3.

10

17149

In another embodiment of this invention, when A is Al then R6 is substituted or

unsubstituted CrCe alkyl.

In another embodiment of this Invention when A Is A2 then R6 is selected from is

substituted or unsubstituted C I-Cc alkyl, substituted or unsubstituted CrC6 alkenyl, substituted

5 or unsubstituted C3-C 1 0 cycloalkyl, C(=X1)R9, C(=X1)X2R9, R9X2R9, C(=OXCI-Ce

alky0S(0)n(Ci-C6 alkyl), (C1-C8 alky1)0C(=0)(Ce-Czo arYl). (C1-C6 alkY1)0C(=O)(CI-C6 alkyl), or

R9X2C(=X1)X2R9.

In another embodiment of this invention when A Is A2 then R6 and R8 are connected In

a cyclic arrangement, where optionally such arrangement can have one or more heteroatoms

10 selected from 0, S, or, N, In the cyclic structure connecting R6 and R8.

In another embodiment of this invention R6 is C 1 -C6 alkyl, or C I -Cs alkyl-phenyl.

In another embodiment of this invention R6 is H, CH 3 , CH2CH3, CH2CH2CH3, CH(CI-13)2,

CH2phenyl, CH2CH(CH3)2, CH2cyclopropyl, C(=0)CH2CH2SCH3, C(=0)0C(CH3)3, CH2CH=CH2,

C(=0)0CH2CH3, C(=0)CH(CH3)CH2SCH3, cyclopropyl, CD3, CH20C(=0)phenyl, C(=0)CH3,

15 C(=0)CH(CH3)2, CH20C(=0)CH(CH3)2, CH20C(=0)CH3, C(=0)phenyl, CH2OCH3,

OH20C(=0 )CH2OCH2CH3, CH2CH2OCH3, CH20C(=0)0CH (OH3)2 1 CH2CH2OCH2OCH3,

CH2CH2OCH3, CH2CH20C(=0)CH3, CH 2CN.

In another embodiment of this Invention R6 Is methyl or ethyl.

In another embodiment of this Invention R7 is 0 or S.

20 In another embodiment of this Invention R8 Is selected from substituted or unsubstituted

CI-Cs alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted CrClo

cycloalkyl, substituted or unsubstituted C 6-C20 aryl, substituted or unsubstituted C1-C20

heterocyclyl, R9C(=X1)0R9, SR9, S(0)0R9, R9S(0) nR9, or R9S(0)n(NZ)R9.

In another embodiment of this Invention R8 Is CH(CH3)CH2SCH3, CH(CH3)2,

25 C(CH3)2CH2SCH3, CH2CH2SCH3, CH2CF3, CH2CH2C(=0)0CH3, N(H)(CH2CH2SCH3),

OCH2CH2SCH3, CH(CH2SCH3)(CH2Pherlyl), thiazolyl, oxazolyl, isothiazolyl, substituted-furanyl,

CH3, C(CH3)3, phenyl, CH2CH2OCH3, pyridyl, CH2CH(CH3)SCH3, OC(CH3)3, C(CH3)2CH2SCH3,

CH(CH3)CH(CH3)SCH3, CH(CH3)CF3, CH 2CHrthienyl, CH(CH3)SCF3,CH2CH2CI,

CH2CH2CH2CF3, CH2CH2S(=0)CH3, CH(CH3)CH2S(=0)CH3, CH 2CH2S(=0)2CH3,

30 CH(CH3)CH2S(=0)2CH3, NCH2CH3, N(H)(CH 2CH2CH3), C(CH 3)=C(H)(CH3), N(H)(CH2CH=CF12),

CH2CH(CF3)SCH3, CH(CF3)CH2SCH3, thietanyl, CH2CH(CF3)2, CH 2CH2CF(OCF3)CF3,

CH2CH2CF(CF3)CF3, CF(CH3)2, CH(CH3)phenyl-CI, CH(CH3)phenyl-F, CH(CH3)phenyl-OCF3,

CH2N(CH3)(S(=0)2N(CH3)2, CH(CH 3)0CH2CH2SCH3, CH(CH 3)0CH2CH2OCH3, OCH3 ,

CH(CH3)SCH3, CH2SCH3, N(H)CH 3, CH(Br)CH2Br, or CH(CH3)CH2SCD3.

35 In another more preferred embodiment of this invention R8 Is preferably R13-S(0) n-R13

wherein each R13 Is Independently selected from substituted or unsubstituted C 1 -C6 alkyl,

substituted or unsubstituted C2-00 alkenyl, substituted or unsubstituted CI-Ca alkoxy, substituted

11

17149

or unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or


unsubstituted CI-C2oheterocyclyl, substituted or unsubstituted S(0) nC1-C6 alkyl, substituted or

unsubstituted N(CI-Cealkyl)2, wherein each said substituted alkyl, substituted alkenyl,

5 substituted alkoxy, substituted alkenyloxy, substituted cycloalkyl, substituted cycloalkenyl,

substituted aryl, substituted heterocyclyl, has one or more substituents independently selected

from F, Cl, Br, I, CN, NO2, Ci-C6 alkyl, C2-C6 alkenyl, CI-Co haloalkyl, C2-C6 haloalkenyl, C 1 -05

haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, CerCIO cycloalkenyl, C3-C10 halocycloalkyl,

C3-C10 halocycloalkenyl, 0C1-C6 alkyl, 0C1-C6 haloalkyl, S(0) nC1-Cealkyl, S(0)nOCI-C6 alkyl. Cr

1 0 C20 aryl, or C1-C20 heterocyclyl, Crepe alkYnyl, C1-C6 alkoxy, N(R9)S(0)„R9, OR9, N(R9)2,

R90R9, R9N(R9)2, R9C(=X1)R9, R9C(=X1)N(R9)2, N(R9)C(=X1)R9, R9N(R9)C(=X1)R9,

S(0),OR9, R9C(=X1)0R9, R90C(=X1)R9, R9S(0) nR9, S(0)R9, oxo, (each of which that can

be substituted, may optionally be substituted with R9).

In another embodiment of this invention R8 Is (substituted or unsubstituted C I -C6 alkyl)-

! 5 S(0)-(substituted or unsubstituted C1-C6 alkyl) wherein said substituents on said substituted

alkyls are independently selected from F, Cl, Br, I, CN, NO2, CI-C6 alkyl, C2-C6 alkenyl, C 1 -C6

haloalkyl, C2-C6 haloalkenyl, C1 -C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-C10

cycloalkenyl, C3-C10 halocycloalkyl, CrCio halocycloalkenyl, OCI-C6 alkyl, 0C1-05 haloalkyl,

S(0)nCi-C6alkyl, S(0) nOCI-C6 alkyl, C6-020 aryl, or C1-C20 heterocycly1, C2-C6 alkynyl, C 1 -C6

20 alkoxy, N(R9)S(0)R9, OR9, N(R9)2, R90R9, R9N(R9)2, R9C(=X1)R9, R9C(=X1)N(R9)2,

N(R9)C(=X1)R9, R9N(R9)C(=X1)R9, S(0),OR9, R9C(=X1)0R9, R90C(=X1)R9, R9S(0)R9,

S(0)R9, oxo, (each of which that can be substituted, may optionally be substituted with R9).

In another embodiment of this invention R8 is selected from CH(CH3)SCH2CF3,

CH2C1125012C F3, CH2SCH2CF3, CH2SCHCICF31 C H(CH2CH3)SCH2C F3, CH(CH3)SCH2CH F2,

25 CH(CH3)SCH2CH2F, CH 2CH2SCH2CH2F, CH(CH3)S(=0)2CH2CF3, CH(CH 3)S(=0)CH2CF3,

CH(CH3)CH2SCF3, CH(CH3)CH2SCF3,CH(CH3)SCH2CH2CF3, and CH 2CH2SCH2CH2CF3.

In another embodiment of this invention R8 Is (substituted or unsubstituted C1-C6 alkyl)-

S(0)-(substituted or unsubstituted C I-C6 alkyl)-(substituted or unsubstituted CrCio cycloalkyl)

wherein said substituents on said substituted alkyls and said substituted cycloalkyls are

30 independently selected from F, Cl, Br, I, CN, NO2, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl,

CrCe haloalkenyl, C1-C6 haloalkyloxy, CrC6 haloalkenyloxy, Cs-C10 cycloalkyl, CrCio

cycloalkenyl, C3-C 10 halocycloalkyl, C3-C1 0 halocycloalkenyl, 0C 1 -C6 alkyl, 0C I-C6 haloalkyl,

S(0)nC1-C6alkyl, S(0)nOCI-C6 alkyl, C6-C20 aryl, or C1-C20 heterocyclyl, CrC6 alkynyl, C 1 -05

alkoxy, N(R9)S(0)R9, OR9, N(R9)2, R9OR9, R9N(R9)2, R9C(=X1)R9, R9C(=X1)N(R9)2,

35 N(R9)C(=X1)R9, R9N(R9)C(=X1)R9, S(0)0R9, R9C(=X1)0R9, R90C(=X1)R9, R9S(0) nR9,

S(0)R9, oxo, (each of which that can be substituted, may optionally be substituted with R9).

12

17149

In another embodiment of this Invention R8 Is selected from CH(CH 3)CH2SCH2(2,2

difluorocyclopropy0. CH2CH2SCH2(2,2 difluorocyclopropyl), CH 2CH2S(=0)CH2(2,2

difluorocyclopropyl), CH 2CH2S(=0)2CH2CH2(2,2 difluorocyclopropyl), and CH2CH(CF3)SCH2(2,2

difluorocyclopropyl).

5 In another embodiment of this invention R8 is (substituted or unsubstituted Ci-Ce alkYO -

S(0),;(substituted or unsubstituted C2-C8alkenyl) wherein said substituents on said substituted

alkyls and substituted alkenyls are Independently selected from F, Cl, Br, I, CN, NO2, C 1 -C6

alkyl, C2-C6 alkenyl, C1 -C6 haloalkyl, C2-C6 haloalkenyl, C 1 -C6 haloaikyloxy, C2-C6

haloalkenyloxy, C3-C10 cycloalkyl, C3-C1e cycloalkenyl, C3-C10 halocycloalkyl, C3-C10

10 halocycloalkenyl, 001-C6 alkyl, 0C 1 -Ce haloalkyl, S(0)nC1-C6alkyl, S(0),OCI-C6 alkyl, C6-C20

aryl, or C1-C2oheterocyclyl, CrC6 alkynyl, C1-C6 alkoxy, N(R9)S(0)R9, 0R9, N(R9)2, R90R9,

R9N(R9)2, R9C(=X1)R9, R9C(=X1)N(R9)2, N(R9)C(=X1)R9, R9N(R9)C(=X1)R9, S(0)0R9,

R9C(=X1)0R9, R90C(=X1)R9, R9S(0) nR9, S(0)R9, oxo, (each of which that can be

substituted, may optionally be substituted with R9).

15 In another embodiment of this invention R8 Is selected from CH2CH2SCH2CH=CCl2,

CH2SCH2CH=CCl2, CH(CH3)SCH2CH=CCl2, CH(CH3)SCH=CHF, CH2CH2S(=0)CH2CH2CF3.

and CH2CH2S(=0)2CH2CH2CF3.

In another embodiment of this Invention X Is CR,..1 where R ni Is H or halo.

In another embodiment of this Invention X Is CFt n, where Rm is H or F.

20 In another embodiment of this invention X1 is 0.

In another embodiment of this Invention X2 is 0.

In another embodiment of this invention R11 is substituted or unsubstituted C 1 -C8

alkylCECR12.

In another embodiment of this invention R11 is CH 2CECH.

25 The molecules of Formula One will generally have a molecular mass of about 100

Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from

about 120 Da!tons to about 900 Da!tons, and It Is even more generally preferred If the molecular

mass is from about 140 Da!tons to about 600 Da!tons.

The following schemes illustrate approaches to generating aminopyrazoles. In step a of

30 Scheme I, treatment of a 3-acetopyridine or a 5-acetopyrimidine of Formula II, wherein R1, R2,

R3 and X are as previously defined, with carbon disulfide and iodomethane In the presence of a

base such as sodium hydride and in a solvent such as dimethyl sulfoxide provides the

compound of Formula III. In step b of Scheme I, the compound of Formula III can be treated

with an amine or amine hydrochloride, in the presence of a base, such as triethylamine, in a

35 solvent such as ethyl alcohol to afford the compound of Formula IV, wherein R1, R2, R3, R6

and X are as previously defined. The compound of Formula IV can be transformed into the

aminopyrazole of Formula Va where R5 = H as In step c of Scheme I and as in

13

17149

Peruncheralathan, S. et al. J. Org. Chem. 2005, 70, 9644-9647, by reaction with a hydrazine,

such as methylhydrazine, In a polar protic solvent such as ethyl alcohol.

Scheme I

s./

a

1 1

III

IV

Va

5 Another approach to aminopyrazoles Is illustrated In Scheme II. In step a, the nitrile of

Formula VI wherein X, R1, R2 and R3 are as previously defined and R5 is hydrogen, is

condensed as in Dhananjay, B. Kendre et al. J. Het Chem 2008, 45, (5), 1281-86 with hydrazine

of Formula VII, such as methylhydrazine to give a mixture of arninopyrazoles of Formula Vb,

wherein R5 and R6 = H, both of whose components were Isolated.

10

Scheme II

VI VII Vb

Preparation of aminopyrazoles such as those of Formula XIla Is demonstrated In

Scheme III. The compound of Formula X in step a and as in Cristau, Henri-Jean et al. Eur. J.

15 Org. Chem. 2004, 695-709 can be prepared through the N-arylation of a pyrazole of Formula IX

with an appropriate aryl halide of Formula Villa where C1 Is bromo In the presence of a base

such as cesium carbonate, a copper catalyst such as copper (II) oxide and a ligand such as

salicylaldoxime In a polar aprotic solvent such as acetonitrile. Compounds of Formula IX, as

shown in Scheme III, wherein R4 = Cl and R5 = H, can be prepared as in Pelcman, B. et a/ WO

14

17149

2007/045868 Al. Nitration of the pyrldylpyrazole of Formula X as in step b of Scheme III and as

In Khan, Misbanul Ain et al. J. Heterocyclic Chem. 1981, 18, 9-14 by reaction with nitric acid and

sulfuric acid gave compounds of Formula Xla. Reduction of the nitro functionality of compounds

of Formula Xla In the presence of hydrogen with a catalyst such as 5% Pd/C In a polar aprotic

5 solvent such as tetrahydrofuran gave the amine of Formula Xlla, as shown in step c In Scheme

III. Reduction of the nitro functionality of compounds of Formula Xla, wherein R1, R2, R3, R4

and X are as previously defined and R5 = H. In the presence of hydrogen with a catalyst such

as 10% Pd/C in a polar protic solvent such as ethanol gave the amine of Formula Xlla, wherein

R5 = H, as well as the amine of Formula Xlla, wherein R5 = OEt, as shown in step d of Scheme

10 III. Compounds of Formula Xla, wherein R1, R2, R3, R5 and X are as previously defined and R4

= Cl, can be reduced In the presence of a reducing agent such as Iron In a mixture of polar

protic solvents such as acetic acid, water, and ethanol to give amines of Formula Ma, wherein

R1, R2, R3, R5 and X are as previously defined R4 = CI, as shown In step e of Scheme III.

Compounds of Formula Xla, wherein R1, R2, R3, R5 and X are as previously defined and R4 =

15 Cl, can be allowed to react under Suzuki coupling conditions with a boronic acid such as

phenylboronic add In the presence of a catalyst such as palladium tetrakis, a base such as 2M

aqueous potassium carbonate, and In a mixed solvent system such as ethanol and toluene to

provide cross-coupled pyrazoles of Formula Xlb, as shown in step f of Scheme III.

15

17149

R4

NO2

Scheme III

+ a

Ix

x

b N 02 c, d or e ---...

XIa x. Mk

x 1

Rr - 1\1 R3

XIb

In step a of Scheme IV, the compounds of Formula Xllb can be treated with

triethylorthoformate and an acid such as trifluoroacetic acid. Subsequent addition of a reducing

5 agent such as sodium borohydride in a polar protic solvent such as ethanol gave a compound of

Formula X111a, wherein R6 = methyl.

In step b of Scheme IV, the compound of Formula Xllb can be treated with acetone In a

solvent such as isopropyl acetate, an acid such as trifluoroacetic acid and sodium

triacetoxyborohydride to give compounds of Formula XIlla, wherein R6 = Isopropyl.

10

In step c of Scheme IV, the compounds of Formula Xllb can be acylated with an acid

chloride such as acetyl chloride in a polar aprotic solvent such as dichloromethane using the

conditions described in Scheme V. Reduction of the amide with a reducing agent such as

lithium aluminum hydride in a polar aprotic solvent such tetrahydrofuran gives compounds of

Formula XIlla, wherein R6 = ethyl.

16

17149

Alternatively, In step d ot Scheme IV, the compounds of Formula Xllb can be treated

with benzotriazole and an aldehyde In ethanol followed by reduction using, for example, sodium

borohydride, to afford compounds of Formula Xfila. In step e of Scheme IV, the compounds of

Formula Xllb can be treated with an aldehyde such as propionaldehyde and sodium

5 triacetoxyborohydride in a polar aprotic solvent such as dichloromethane to give compounds of

Formula X111a, wherein R6 = propyl. As in step f, acylation of compounds of Formula Xfila in

Scheme IV using the conditions described in Scheme IX affords compounds of Formula la,

wherein R1, R2, R3, R4, R5, R6, R8 and X are as previously defined.

Scheme IV

IH

N \ H

aorborcordore

XIlla

I

10 Ia

In step a of Scheme V. the compounds of Formula Vc, wherein R1, R2, R3, R4, R5 and

R6 and X are as previously defined, can be treated with an acid chloride of Formula XIV, in the

presence of a base such as triethylamine or N,N-dimethylaminopyridine In a polar aprotic

solvent such as dichloroethane (DCE) to yield compounds of Formula lb, wherein R8 Is as

15 previously defined. Additionally, when R6 = H the 2° amide may be subsequently alkylated In

step b of Scheme V with an alkyl halide such as iodoethane, In the presence of a base such as

sodium hydride and a polar aprotic solvent such as N,N-dimethylforrnamide (DMF) to yield the

desired compounds of Formula lb. The acid chlorides used in the acylation reactions herein are

either commercially available or can be synthesized by those skilled in the art.

20 Scheme V

17

17149

R2 Nit' R4

X i e) H Cly 118 aora,b R2 iti..N

I N 1 + X

R6 0 A N

1 R 1 N--. R6

Vc XIV lb In step a of Scheme VI and as In Sammelson et al. Bioorg. Med. Chem. 2004, 12, 3345-

3355, the aminopyrazoles of Formula Vd, wherein R1, R2, R3, R4, R6 and X are as previously

defined and R5 = H, can be halogenated with a halogen source such as N-chlorosuccinimIde or

5 N-bromosuccinimide In a polar aprotic solvent such as acetonitrile to provide the R5-substituted

pyrazole. In step b, acylation of this compound using the conditions described In Scheme V

affords the compound of Formula lc, wherein R1, R2, R3, R4, R5, R6, R8 and X are as

previously defined.

Scheme VI

Rd N+14

X N Li R2

10 Vd lc

In step a of Scheme VII, ureas and carbamates are made from the aminopyrazoles of

Formula Ve. Compounds of Formula ye, wherein X, R1, R2, R3, R4, R5 and R6 are as

previously defined are allowed to react with phosgene to provide the intermediate carbamoyl

chloride which Is subsequently treated with an amine, as shown In step b, or alcohol, as shown

15

in step c, respectively, to generate a urea of Formula Id or a carbamate of Formula le,

respectively, wherein R9 Is as previously defined.

18

17149

Scheme VII

R.4 R2

•■• —

XV

b / \ c R2 R 0

X ' 1 N % X

1" t,\1 N)L0 ,R9

0

R R6 A

et 1 H

RI N R6 1

3

Ie

In step a of Scheme VIII, compounds of Formula Xfic, wherein X, R1, R2, R3, R4 and

R5 are as previously defined, can be treated with di-tert-butyl dicarbonate (Boc 20) and a base

5 such as triethylamine In a polar aprotic solvent such as dichloromethane (DCM) to yield

compounds of Formula XVIa. Treatment of the carbamate functionality with an alkyl halide such

as lodomethane or Boc-anhydride in the presence of a base such as sodium hydride and In a

polar aprotic solvent such as DMF yields carbamates of Formula XVII, as shown In step b of

Scheme VIII, wherein R6 Is as previously defined, except where R6 Is hydrogen. The Boc-group

10 can be removed under conditions that are well-known In the art, such as under acidic conditions

such as trifluoroacetic acid (TFA) In a polar aprotic solvent like dichloromethane to give

compounds of Formula XIllb as in step c.

19

Id

17149

R2 N- /

eL7N /

)t, 5 R R I N R3

XVI I

\

R6

C

Scheme VIII

a b

XlIc XVIa

/H N \ R6

XIIIb

In steps a, b and c of Scheme IX, compounds of Formula XII1c, wherein X, R1, R2, R3,

R4, R5 and R6 are as previously defined, can be treated with a compound of Formula XVIII,

5 wherein R8 is as previously defined and R10 is either OH, OR9 or 0(C=0)0R9, to yield

compounds of Formula Id. When R10 = OH, compounds of Formula XIIIc can be converted to

compounds of Formula Id in the presence of a coupling reagent such as 1-(3-

dimethylaminopropy1)-3-ethylcarbodiimide hydrochloride (EDOHCI) and a base such as N,N-

dimethylamlnopyridine (DMAP) in a polar aprotic solvent such as dichloroethane (DCE), as

10 shown Instep a. When R10 = OR9, compounds of Formula XIIIc can be converted to

compounds of Formula Id In the presence of 2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-

a]pyrimidine in a polar aprotic solvent such as 1,4-dioxane under elevated temperature, as

shown Instep b. When R10 = 0(C=0)0R9, compounds of Formula XIIIc can be converted to

compounds of Formula Id in a polar aprotic solvent such as dichloromethane (DCM), as shown

15 in step c. Acylation of amides of Formula Id, when R6 = H, with an acid chloride in the presence

of a base such as dilsopropyl ethylamine in a polar aprotic solvent such as dichloroethane

(DCE) yields imides of Formula le, as shown In step d. Furthermore, alkylation of amides of

Formula Id, when R6 = H, with an alkyl halide or alkyl sulfonate In the presence of a base such

as sodium hydride in a polar aprotic solvent such as N,N-dimethylfonamide (DMF) yields

20 alkylated amides of Formula le, as shown in step e. Halogenation of compounds of Formula Id,

wherein R1, R2, R3, R4, R6, R8 and X are as previously defined and R5 = H, with a halogen

source such as N-bromosuccinimide in a polar aprotic solvent such as DCE or a halogen source

such as N-chlorosuccinimide in a polar aprotic solvent such as DCE or acetonitrile or a halogen

source such as Selectfluor® in a mixture of polar aprotic solvents such as acetonitrile and DMF

20

17149

XIIIc

give halogenated pyrazoles of Formula le, wherein R5 = halogen, as shown in step lof Scheme

IX. Amides of Formula Id can be converted to thioamides of Formula If In the presence of a

thionating agent such as Lawesson's reagent in a polar aprotic solvent such as dichloroethane

(DCE), as shown in step g.

5 Scheme IX

R4

R2 N /14 Rio -.8 R aorborc N--

N ± y‘

R6

It i N R3

XVIII

Id

d or e orf /

R6 0

Ie If

In step a of Scheme X, compounds of Formula XlIld, wherein X, 131, R2, R3, R4, R5 and

R6 are as previously defined, can be treated with compounds of Formula XIX, wherein R8 is as

previously defined, in a polar aprotic solvent such as dichloroethane (DCE) to yield compounds

10 of Formula XX. Additionally, when R6 = H and R8 contains a halogen, compounds of Formula

XX can be treated with a base, such as sodium hydride, in a polar aprotic solvent, such as THF,

to yield compounds of Formula XXI, where m is an Integer selected from 1, 2, 3, 4, 5, or 6, as

shown in step b of Scheme X.

21

17149

Scheme X

[0, S] ii C II N

48

a

XIIld XIX XX

b

XXI Oxidation of the sulfide to the sulfoxide or sulfone Is accomplished as in Scheme XI

where (-5—) can be any sulfide previously defined within the scope of R8 of this invention. The

5 sulfide of Formula XXIla, wherein X, R1, R2, R3, R4, R5 and R6 are as previously defined, Is

treated with an oxidant such as sodium perborate tetrahydrate in a polar protic solvent such as

glacial acetic acid to give the sulfoxide of Formula XXIII as in step a of Scheme XI. Alternatively,

the sulfide of Formula XXIla can be oxidized with an oxidant such as hydrogen peroxide in a

polar protic solvent such as hexafluorolsopropanol to give the sulfoxide of Formula XXIII as In

10 step d of Scheme XI. The sulfoxide of Formula XXIII can be further oxidized to the sulfone of

Formula )00V by sodium perborate tetrahydrate in a polar protic solvent such as glacial acetic

acid as In step c of Scheme XI. Alternatively, the sulfone of Formula XXIV can be generated in a

one-step procedure from the sulfide of Formula XXIla by using the aforementioned conditions

with >2 equivalents of sodium perborate tetrahydrate, as in step b of Scheme XI.

15

22

17149

a or d

XXIIa

XXIII

\b

/c

R I N it3

R2 N-- /

N x A ,

Scheme XI

XXIV

Oxidation of the sulfide to the sulfoximine is accomplished as in Scheme XII where (—S—) can be

any sulfide previously defined within the scope of R8 of this invention. The sulfide of Formula

5 XXIlb, wherein X, R1, R2, R3, R4, R5 and R6 are as previously defined, Is oxidized as in step a

with iodobenzene diacetate in the presence of cyanamide in a polar aprotic solvent such as

methylene chloride (DCM) to give the sulfilimine of the Formula XXV. The sulfilimine of Formula

XXV may be further oxidized to the sulfoxlmine of Formula XXVI with an oxidant such as meta-

Chloroperoxybenzoic acid ("mCPBK) in the presence of a base such as potassium carbonate in

10 a protic polar solvent system such as ethanol and water as in step b of Scheme XII.

23

17149

R4 0

N---- )—S— / // Nag

X R6

a

Scheme XII

XXIIb

?ON

R4 0 0

R2 N-- //

N / ‘ NCN X R6

XXVI

Iodination of the pyrazole of Formula Xb as Instep a of Scheme XIII and as In Potapov,

A. et al. Russ. J. Org. Chem. 2006, 42, 1368-1373 was accomplished by reaction with an

5 iodinating agent such as Iodine In the presence of acids such as iodic acid and sulfuric acid in a

polar protic solvent such as acetic acid gives compounds of Formula XXVII. In step b of

Scheme XIII and as In Wang, D. et al. Adv. Synth. Catal. 2009, 351, 1722-1726,

aminopyrazoles of Formula XIII° can be prepared from lodopyrazoles of Formula XXVII through

cross coupling reactions with an appropriate amine in the presence of a base such as cesium

10

carbonate, a copper catalyst such as copper (I) bromide, and a ligand such as 1-(5,6,7,8-

tetrahydroquinolin-8-ypethanone in a polar aprotic solvent such as DMSO.

Scheme XIII

b

b

A R5 RI N R3

A R5 RI N R3

24

17149

In step a of the Scheme XIV, compounds of the formula XXIX, wherein R4 is CI, R5 Is H

and r represents Cr, can be prepared according to the methods described In Acta. Pharm.

Suec. 22, 147-156 (1985) by Toll, Bo-Ragnar and Dahlbom, R. In a similar manner, compounds

of the Formula XXIX, wherein R4 is Br, X represents Br and R5 Is as defined previously, can

5 be prepared by treating compounds of the Formula XXVIII with hydrogen gas in the presence of

a metal catalyst such as 5% Pd on alumina and a solution of 50% aqueous HBr in a solvent

such as ethanol. Alternatively, In step a of Scheme XIV, compounds of the Formula XXIX,

wherein R4 Is Cl or Br, rrepresents Cr or Br and R5 is as defined previously, can be prepared

by treating compounds of the Formula XXVIII, wherein R5 is as defined previously, with a

10

hydrosilane such as triethyl silane in the presence of a metal catalyst such as 5% Pd on alumina

and an acid such as HCI or HBr, respectively, In a solvent such as ethanol.

In step b of the Scheme XIV, compounds of the Formula XXX, wherein R4 is Cl or Br

and R5 is as defined previously, can be prepared by treating the compounds of the Formula

XXIX, wherein R4 is Cl or Br, r represents cr or Br and R5 Is as defined previously, with di-

15

tert-butyl dicarbonate (Boc.20) In the presence of a mixture of solvents such as THF and water

and a base such as sodium bicarbonate.

In step c of the Scheme XIV, compounds of the Formula XVIa, wherein X, R1, R2, R3

and R5 are as defined previously and R4 Is Cl or Br, preferably Cl can be obtained by treating

compounds of the Formula XXX, wherein R4 Is CI or Br and R5 Is as defined previously,

20 preferably H, with compounds of the Formula VIllb, wherein X, R1, R2 and R3 are as defined

previously and Q is lodo, in the presence of a catalytic amount of copper salt such as CuC12, a

ligand such as an ethane-1,2-diamine derivative such as N 1 ,N2-dimethylethane-1,2-diamine and

a base such as K3PO4 in a polar aprotic solvent such as acetonitrile at a suitable temperature.

In step c pyrazoles of Formula XXX are coupled with compounds of the Formula VIllb,

25 preferably 3-iodo pyridine, in the presence of a metal catalyst, such as CuC12, and a diamine

ligand such as N 1 ,N2-dimethylethane-1,2-diamine, and an Inorganic base, such as K3PO4, The

reaction is carried out In a polar aprotic solvent such as acetonitrile. The reaction is conducted

at a temperature from about 60 *C to about 82 °C and preferably from about 75 °C to 82 °C.

Approximately, a 1:1.2 molar ratio of pyrazoles of Formula XXX to heterocyclyl Iodide of

30 Formula VIllb may be used, however, a molar ratios of about 5:1 to about 1:5 may also be used.

The reaction Is conducted at about atmospheric pressure, however, higher or lower pressures

can be used.

The Boc-group of compounds of Formula XVIa can be removed under conditions that

are well-known in the art such as under acidic conditions such as TFA In a polar aprotic solvent

35 such as dichloromethane to give compounds of Formula XIld, as shown in step d of Scheme

XIV.

Scheme XIV

25

17149

a

114 Q

N Hill

0 4

/ W \ 0-

R2 N\ N ,-0

Itl NH C

R2

XVIa

I ', VIIIb

124

R2 N

11■I / X --'L

NH2

R5 R5

XXVIII XXIX

I b N --

)--0

igi / NH

XIld

Bromopyrazoles of Formula XXXI, wherein R1, R2, R3, R5, R8 and X are as previously

defined, can be allowed to react under Suzuki coupling conditions with a boronic ester such as

vinylboronic acid pinacol ester or cyclopropylboronic acid pinacol ester In the presence of a

5 catalyst such as palladium tetrakis, a base such as 2 M aqueous potassium carbonate, and In a

mixed solvent system such as ethanol and toluene to provide compounds of Formula XXXII, as

shown In step a of Scheme XV.

26

17149

Scheme XV

Br 0 R4 o•

>--R5 N

\ H

N-- / a

N

X %. X

A R5 A R5 RI N R3 R I N R3

XXXI XXXII

The vinyl group of compounds of Formula XXXII!, wherein R1, R2, R3, R5, R6, R8 and X

are as previously defined, can be reduced In the presence of hydrogen with a catalyst such as

5 10% Pd/C In a polar protic solvent such methanol to give compounds of Formula XXXIV, as

shown In step a of Scheme XVI. Oxidation of the vinyl group of compounds of Formula XXXIII

using an oxidant such as osmium tetroxide In the presence of sodium periodate In mixture of a

polar protic solvent such as water and a polar aprotic solvent such as THF gave compounds of

Formula XXXV, as shown In step b of Scheme XVI. Reduction of the aldehyde of compounds of

10 Formula XXXV, as shown In step c of Scheme XVI, with a reducing agent such as sodium

borohydride In a polar protic solvent such as methanol gave the corresponding alcohol of

Formula XXXVI. Treatment of compounds of Formula XXXVI with a chlorinating agent such as

thionyl chloride In a polar aprotic solvent such as dichloromethane gave compounds of Formula

XXXVII, as shown instep d of Scheme XVI.

15

27

17149

Scheme XVI

a

XMCIII

C

XXXV I

Id

XXXVII In step a of Scheme XVII, an 0,0-unsaturated acid XXXVIII can be treated with a

nucleophile such as sodium thiomethoxide In a polar protic solvent such as methanol to give

5 acid )(XXIX.

28

17149

Scheme XVII

0

HO)L, CF3

XXX VI II

0 SMe a

H0)1 CF 3

XXXIX

In Step a of the Scheme XVIII, treatment of the compounds of Formula Ig, where A is

A2, R7 is 0 and R8 is tert-butoxy with a reagent such as propargyl bromide In the presence of a

5 base such as sodium hydride and in a polar aprotic solvent such as DMF yields compounds of

Formula lh, wherein R6 = R11.

Scheme XVIII

a

Ig lh

In step a of Scheme XIX, compounds of Formula XL, wherein X. R1, R2, R3, R4, R5 and

10 R6 are as previously defined, can be treated with an acid of Formula XLI, wherein R8 is as

previously defined, in the presence of a coupling reagent, such as 1-(3-dimethylaminopropy1)-3-

ethylcarbodilmide hydrochloride (EDDHCI), and a base, such as N,N-dimethylaminopyridine

(DMAP), in a polar aprotic solvent, such as dichloromethane (DCM), to yield compounds of

Formula XLII. In step b, compounds of the Formula XLII can be treated with a base, such as

15

sodium methoxide, In a polar solvent such as TI-W, followed by an alkyl halide R9-Hal to give

the compounds of the Formula XLIII.

29

17149

Scheme XIX

a

XL11

R9-hao

X

A R5 R6

R i N 113

XLIII Alternatively, In step a of Scheme XX, compounds of the Formula XL or the

corresponding HCI salt, wherein X, R1, R2, R3, R4, R5, and R6 are as previously defined, can

5 be coupled to acids of the formula XLIV , wherein R8 is as previously defined, In the presence of

a coupling reagent, such as 1-(3-dimethylaminopropyI)-3-ethylcarbodiimide hydrochloride

(EDC.HCI), and a base, such as N,N-dimethylaminopyridine, In a polar aprotic solvent, such as

dichloromethane, to yield compounds of the Formula XLV, wherein X, R1, R2, R3, R4, R5, R6

and R8 are as previously defined. In step 13 of Scheme XX, compounds of the Formula XLV,

10 wherein X, R1, R2, R3, R4, R5, R6 and R8 are as previously defined and Tr represents trityl

(triphenylmethyl), can be treated with an acid, such as 2,2,2-trifluoroacetic acid, In the presence

of a trialkyl silane, such as triethyl silane, In a polar aprotic solvent, such as methylene chloride,

to remove the trityl group to give thiols of the Formula XLVI, wherein X, R1, R2, R3, R4, R5, R6

and R8 are as previously defined. In step c of Scheme XX, thiols of the Formula XLVI , wherein

15 X, R1, R2, R3, R4, R5, R6 and R8 are as previously defined, can be treated with a base, such

as sodium hydride. In a polar aprotic solvent such as tetrahydrofuran, or cesium carbonate in

acetonitrile, or DBU In dimethylformamide, and an electrophile (R9-Hal), such as 2-

(bromomethyl)-1,1-difluorocyclopropane, in tetrahydrofuran, to give compounds of the Formula

XLVII. Alternatively, the modified conditions described by Pustovit and coworkers (Synthesis

20 2010, 7, 1159-1165) could be employed In the transformation of XLVI to XLVII.

R4 n ,c‘ S-119

R2 / N / N ■

30

17149

Scheme XX

N-- 1 NH _,. S—Tr N / ‘ , /

X R6 8 A 0:7„... R5 HO R 1 N R3

a

XL XLIV 1 b

XLV

SH

12,4 0 S-R9 1L-R18

X R6 R9-Hal

N X

A ,. R5 R I N R3 R 1 N R3

XLVII Alternatively, in step a of the Scheme XXI, compounds of the Formula XL or the

5 corresponding HCI salt, wherein X, 111, R2, R3, R4, R5, and R6 are as previously defined, can

be coupled to acids of the Formula XLVIII, wherein R9 is as previously defined, In the presence

of a coupling reagent such as EDC.HCI and a base such as DMAP in a polar aprotic solvent

such as DMF to yield compounds of Formula XLIX, where in X, 121, R2, R3, R4, R5, R6 and R9

are as previously defined. In step b of the Scheme XXI, compounds of the Formula XLIX,

10 wherein X, RI, R2, R3, R4, R5, R6 and R9 are as previously defined, can be treated with a thio

acid salt, such as potassium thloacetate, at an elevated temperature (about 50 'C) In a solvent,

such as DMSO, to give compounds of the Formula L, wherein X,111, R2, R3, R4, R5, R6 and

R9 are as previously defined. In step c of the Scheme XXI, compounds of the Formula L,

wherein X, R1, R2, R3, R4, R5, R6 and R9 are as previously defined, can be treated with an

15 equimolar amount of a base, such as sodium methoxide, prepared from mixing sodium hydride,

and methanol, followed by an electrophile (R9- Halo), such as 24bromomethy9-1,1-

difluorocyclopropane, In a solvent, such as tetrahydrofuran, to give compounds of the Formula

LI.

XLVI

31

17149

R9

XLVIII XL

l b

\

R6

Scheme )0(1

R9 \ R9 S

R4

N--

X

,A R$ R I N R3

LI In step a of Scheme XXII, compounds of the Formula XL, wherein X, R1, R2, R3, R4,

5 R5, R6, and halo are as previously defined, can be treated with an acid chloride of Formula LII

In the presence of a base, such as triethylamine or diisopropylethylamine in a polar aprotic

solvent, such as DCE, to yield compounds of the Formula LIII, wherein R8 Is either a substituted

or unsubstituted alkyl chain. In step b, compounds of the Formula LIII can be treated with

potassium thioacetate to provide compounds of Formula LIV after heating (about 60 °C) in a

10 polar aprotic solvent, such as acetone. As indicated In step c, a one-pot methanolysisialkylation

sequence can be achieved via treatment of compounds of the Formula LIV with one equivalent

of a base, such as sodium methoxide (Na0Me) in a polar aprotic solvent, such as

tetrahydrofuran (THF). An alkyl sulfonate or alkyl halide, such as 2-lodo-1,1,1-trifluoroethane,

can then be added to the reaction mixture to deliver compounds of the Formula LV, wherein R9

15 Is as previously defined. In step d compounds of the Formula LV may be obtained from

compounds of the Formula LIII via treatment with an alkyl thiol such as 2,2,2-trifluoroethanethiol

at elevated temperatures (about 50 °C) In a polar aprotic solvent, such as THF, in the presence

of sodium Iodide and a base, such as diisopropylethylamine. Alternatively, In step ( treating

compounds of Formula LIII with an alkyl thiol, such as sodium methanethiolate, in a polar

20 aprotic solvent, such as DMSO, at elevated temperatures (about 50 °C) will afford compounds

of Formula LV. As demonstrated in step e, when compounds of the Formula LIV are treated with

R9 C

X )I

R I _,

N

1 N

113

L

R9-Hal ‘ R9

R5 R6

32

17149

two or more equivalents of a base, such as Na0Me, followed by a 1,2,2-trihaloalkyl compound,

such as 2-bromo-1,1-difluoroethane, compounds of Formula LVI are obtained.

Scheme XXII

R

+ 0 X 0

CIA

Richalo a /

N R8 A Alai°

R3 R8 it6

II

LII LI

b I k'

1

XL

C

LV

C

LVI

5 In step a of Scheme 23, compounds of Formula 23.1, wherein X, R1, R2, R3, R4, R5,

R6 and R8 are as previously defined, can be treated with a base, such as aqueous 2M lithium

hydroxide, In a polar protic solvent, such as methanol, to give compounds of Formula 23.2.

Then in step b, compounds of Formula 23.2 can be treated with a base, such as sodium hydride

In a polar aprotic solvent, such as tetrahydrofuran, followed by an electrophile, such as an alkyl

10 halide or sulfonyl halide, to afford compounds of Formula 23.3.

33

17149

R2 N / N

X lie I 113

N R3

23.1 23.2

a

Scheme 23

R3

23.3

In step a of Scheme 24, compounds of Formula 24.1, where X, R1, R2, R3, R4, R5, R8

5 and halo are as previously defined, and R6 = H, can be treated with a base such as sodium

hydride, In a polar aprotic solvent, such as tetrahydrofuran (THF), to yield compounds of

Formula 24.2 where m Is an Integer selected from 0,1,2,3,4,5, or 6. In step b of Scheme 24,

compounds of Formula 24.2 can be treated with a base, such as triethylamine, and silylation

reagents, such as trImethylsilyltrifluoromethanesulfonate and dimethylmethylideneammonium

10 Iodide (Eschenmosers salt) In a polar aprotic solvent, such as dichloromethane (DCM), to yield

compounds of Formula 24.3. In step c of Scheme 24, compounds of Formula 24.3 can be

treated with a base, such as potassium hydroxide, and a nucleophile, such as S,S-dimethyl

carbonodithioate, In water and a polar aprotic solvent such as tetrahydrofuran (THF) to yield

compounds of Formula 24.4, wherein X, R1, R2, R3, R4, R5, R9 and m are as previously

15 defined.

34

17149

Scheme 24

24.1

24.2

C CH2

24.4

24.3

A route to compounds of Formula 25.2 Is described In Scheme 25. As demonstrated In

step a, when compounds of the Formula 25.1, wherein X, R1, R2, R3, R4, R5, R6 and R8 are

5 as previously defined, are treated with two or more equivalents of a base, such as sodium

methoxide, followed by a 1,2-dihaloalkyl compound, such as 1-fluoro-2-lodoethane, in a solvent,

such as tetrahydrofuran (THF), compounds of Formula 25.2, wherein R9 Is as previously

defined, are obtained.

Scheme 25

a ,Si■

129 R9

25.1 25.2 An alternative route to vinyl sulfides Is described In step a of Scheme 26. This route

utilizes conditions developed by Kao and Lee (Org. Lett. 2011, 13, 5204-5207) In which thiols of

the Formula 26.1, wherein X, R1, R2, R3, R4, R5, R6 and R8 are as previously defined, are

coupled with a vinyl halide, such as (E)-1-bromo-3,3,3-trifluoroprop-1-ene, In the presence of a

15 catalyst, such as copper(I) oxide, a base, such as potassium hydroxide, and a solvent, such as

dioxane, at elevated temperatures to afford products of Formula 26.2, wherein R9 Is as

previously defined.

10

35

17149

R'5 ' R9

26.1

27.2

Scheme 26

In step a of Scheme 27, an acrylamide of Formula 27.1, wherein X, R1, R2, R3, R4, R5,

5 and R6 are as previously defined, is reacted with a sulfonamide of Formula 27.2, wherein R9 Is

as previously defined, In the presence of a base, such as potassium carbonate, at elevated

temperatures In a polar aprotic solvent, such as dimethylformamide (DMF), to deliver

compounds of Formula 27.3. This product can then be treated with a base, such as sodium

hydride, and an alkyl halide, such as 2-bromoacetonitrile, In a polar aprotic solvent, such as

10 tetrahydrofuran (THF), to provide compounds of the Formula 27.4, as demonstrated In step b.

Scheme 27

92 P .R2

0‘ 0 CH2 a

e... Yi, —..- FI2N R9

7 Re

27.3

92 o b 0\ p

NicZ■ N Y. R9

I R3 R5 Re Rg

27.4 When compounds of the Formula 28.1, wherein X, R1, R2, R3, R4, R5, R6, R8 and halo

are as previously defined, are treated with amines of the Formula 28.2, wherein R9 Is as

15 previously defined, at elevated temperatures in a polar protic solvent, such as methanol,

compounds of the Formula 28.3 can be obtained, as demonstrated In step a of Scheme 28.

Compounds of the Formula 28.3 may be treated with a sulfonyl chloride, such as

methanesulfonyl chloride, in the presence of a base, such as diisopropylethylamine, and a polar

aprotic solvent, such as dichloromethane (DCM), to afford products of the Formula 28.4, as

20 shown in step b. As demonstrated In step c, when compounds of the Formula 28.3 are treated

with an alkyl halide, such as 3-bromo-1,1,1-trifluoropropane, at elevated temperatures and in

the presence of a base, such as potassium carbonate, and a polar aprotic solvent, such as

dimethylformamide (DMF), compounds of the Formula 28.5 may be obtained. Alternatively,

compounds of Formula 28.3 may be prepared via a two step process as described In steps d 36

17149

R2

NH

R3 R5 Re

+ 28.6

0 CH3

HOANy

0 CH3

- 111

0 CH3

28.7

a

28.2

28.1

1 b

R2 R2

ATh R9 X // ,,r4, ,R9

R9 A\ R3 R5 A, 00

28.4

Rat 0 R9

119 R9

R3 R5 Fte

28.5

28.8

and e of Scheme 28. Compounds of Formula 28.6 can be converted to compounds of Formula

28.8 when treated with compounds of Formula 28.7 in the presence of a coupling reagent such

as 1-(3-dimethylaminopropy1)-3-ethylcarbodiimide hydrochloride (EDC•FICI) and a base such as

N,N-dimethylaminopyridine (DMAP) In a polar aprotic solvent such as dichloroethane (DCE), as

5 shown In step d. The Boc-group can be removed under conditions that are well-known in the

art, such as under acidic conditions such as trifluoroacetic acid (TFA) in a polar aprotic solvent

like dichloromethane to give compounds of Formula 28.3 as in step e.

Scheme 28

10 In step a of Scheme 29, compounds of Formula 29.1, wherein X, R1, R2, R3, R4, R5,

R6 and R8 are as previously defined, can be reacted with either a cyclic or acyclic enone, such

as but-3-ene-2-one, under the conditions described by Chakraborti (Org. Lett. 2006, 8, 2433—

2436) to deliver compounds of the Formula 29.2, wherein R9 Is as previously defined. These

products may then be subjected to a fluorinating reagent, such as Deoxo-Fluor ®, and an

15

Initiator, such as ethanol, In a polar aprotic solvent, such as dichloromethane (DCM), to deliver

compounds of the Formula 29.3, as described In step b.

Scheme 29

37

17149

29.1

R4 0

1 Re

29.3

R2

R3 R5 Rg Rg

Step a of Scheme 30 depicts the hydrolysis of compounds of the Formula 30.1, wherein

X, R1, R2, R3, R4, R5, R6, R8, and R9 are as previously defined, via treatment with an acid,

such as aqueous hydrochloric acid, In a solvent, such as THF, to afford an Intermediate

5 aldehyde of the Formula 30.2. Compounds of the Formula 30.2 can be immediately reacted with

a fluorinating reagent, such as DeoxoFIuor®, In the presence of an Initiator, such as ethanol,

and a solvent, such as tetrahydrofuran (THF), to provide products of the Formula 30.3.

Scheme 30

OCH3

S , %, /L 8

R ' OCH3 --.'

30.1

b

30.3

10 In Scheme 31, compounds of the Formula 31.1, wherein R9 is as previously defined, are

converted to compounds of the Formula 31.2 via the procedure described In Dmowski (J. Fluor.

Chem., 2007, 128, 997-1006), as shown in step a. Compounds of Formula 31.2 may then be

subjected to conditions described In step b, In which a reaction with a thioate salt In a solvent,

such as dimethylformarnide (DMF), provides compounds of the Formula 31.3, wherein W Is aryl

15 or alkyl. As Indicated In step c, a one-pot deprotection/alkylation sequence can be achieved via

treatment of compounds of the Formula 31.3 with one equivalent of a base, such as sodium

methoxide (Na0Me), in a polar aprotic solvent, such as tetrahydrofuran (THF). A compound of

38

17149

CH H3C>L.

H3C Si'07CH2

32.1

H3C

,0 \N g

HO

the Formula 31.4, wherein X, R1, R2, R3, R4, R5, R6, R8 and halo are as previously defined,

may then be added to the reaction mixture to afford compounds of the Formula 31.5.

Scheme 31

rCH2 a I y- i< F

Rg Rg F

31.1 31.2

WySF

0 Rg F

31.3

R2 R4 X

Rt4N_

0 A

1:1 halo

R3 R5 Re

31.4

31.5 5 In Scheme 32, a neat mixture of an olefin of the Formula 32.1, where n is an integer

selected from 0, 1, 2, 3, 4, or 5, and trimethylsilyl 2,2-difluoro-2-(fluorosulfony9acetate can be

heated In the presence of sodium fluoride to deliver a substituted difluorocyclopropane of the

Formula 32.2, as Indicated In step a. In step b, this product was treated with

tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (THF) to afford an Intermediate

10 homoallylic alcohol of the Formula 32.3. This alcohol was not isolated, but rather Immediately

treated with p-toluenesulfonyl chloride in the presence of pyridine and dichloromethane to afford

a tosylate of the Formula 32.4, as shown in step c.

Scheme 32

32.4

32.3

39

17149

Compounds of the Formula 33.1, wherein X, R1, R2, R3, R4, R5, and R6 are as

previously defined, where X Is preferably carbon, R1, R2, R3, and R5 are hydrogen and R4 is

chloro, may be coupled with an acid chloride of the Formula 33.2, wherein R8 is as previously

defined, in the presence of a base, such as pyridine, diisopropylethylamine, or N,N-

5 dimethylaminopyridine (DMAP) , and a solvent, such as 1,2-dichloroethane or methylene

choride, to afford products of the Formula 33.3, as depicted in step a of Scheme 33.

In step a of Scheme 33 amines of Formula 33.1 are coupled with acid chlorides of

Formula 33.2 In the presence of a base, or combination of bases such as pyridine, N,N-

dimethylaminopyridine, or diisopropylethylamine. The reaction is carried out In a halogenated

10 solvent such as 1,2-dichloroethane or methylene chloride. The reaction is conducted at a

temperature from 0 °C to 80 °C and preferably from about 0 °C to 23 °C. Approximately, a 1:1

molar ratio of the amine of formula 33.1 to acid chloride of Formula 33.2 may be used, however,

molar ratios of about 5:1 to about 1:5 may also be used. The reaction Is conducted at about

atmospheric pressure, however, higher or lower pressures can be used.

15

Scheme 33

a

33.1

33.2

33.3

In step a of Scheme 34, the compounds of Formula 34.1, wherein R1, R2, R3, R4, R5

and R6 and X are as previously defined, can be heated with an acid of Formula 34.2, wherein

20 R8 is as previously defined, in the presence of AtiV-dicyclohexylcarbodiimide (DCC), and a

base, such as N,N-dimethylaminopyridine (DMA)'), in a solvent, such as diethyl ether (Et20), to

yield compounds of Formula 34.3.

Scheme 34

x

RC'

a X • ........k

R I

34.1 34.2

34.3

25 In step a of Scheme 35, aminopyrazoles of Formula 35.1, wherein X, R1, R2, R3, R4,

R5 and R6 are as previously defined, can be treated with phosgene and N,N-

dimethylaminopyridine (DMA)') at about 80 °C In a polar aprotic solvent such as dichloroethane

(DCE). Subsequently, treatment with an amine, as shown in step b, or an alcohol, as shown In

40

17149

,

8, C

a, d

R2 ,Rg

X m N

Rg R5 R6

35.2

R2 R4 0

X /

R5 116

35.3

R2 R4 0 \V ,Rg

N rS

he

35.1

step c, or a thiol, as shown In step d, generates a urea of Formula 35.2, a carbamate of

Formula 35.3, or a carbamothioate of Formula 35.4, wherein R9 is as previously defined,

respectively.

Scheme 35

5 35.4

In step a of Scheme 36, compounds of Formula 36.1, wherein X, R1, R2 and R3 are as

previously defined, can be treated with a base such as triethylamine, carbon disulfide and a

sulfonyl chloride such as 4-methylbenzene-1-sulfonyl chloride In a polar aprotic solvent such as

tetrahydrofuran (THF) to yield compounds of Formula 36.2. In step b of Scheme 36, oxazolidin-

10 2-one can be treated with an equimolar amount of a base, such as sodium hydride followed by

compounds of Formula 36.2, in a polar aprotic solvent such as dimethylformamide (DMF) to

give compounds of the Formula 36.3. Additionally, the product of step b, (previous to work-up)

can be treated with an electrophile such as lodomethane to give compounds of Formula 36.4 as

demonstrated in step c of Scheme 36.

15

41

17149

Scheme 36

a

36.2

C

36.4 36.3

In step a of Scheme 37, ureas of Formula 37.1, wherein R1, R2, R3, R4, R5, R6, R8,

and X are as previously defined, can be reacted with a base such as lithium

5 bis(trimethylsily0amide In a polar aprotic solvent such as THF followed by an acyl chloride such

as pivaloyl chloride to yield acylated ureas of Formula 37.2, wherein R1, R2, R3, R4, R5, R6,

R8, and X are as previously defined. In step b of Scheme 37, ureas of Formula 37.1, wherein

R1, R2, R3, R4, R5, R6, R8, and X are as previously defined, can be reacted with a base such

as lithium bis(trimethylsily0amide in a polar aprotic solvent such as THF followed by an alkyl

10 halide such as (chloromethyl)(methyl)sulfane to yield alkylated ureas of Formula 37.2, wherein

R1, R2, R3, R4, R5, R6, R8, and X are as previously defined. In step c of Scheme 37, ureas of

Formula 37.1, wherein R1, R2, R3, R4, R5, R6, R8, and X are as previously defined, can be

reacted with a base such as lithium bis(trimethylsilyl)amide in a polar aprotic solvent such as

THF followed by a sulfonyl chloride such as methanesulfonyl chloride to yield sulfonylated ureas

15 of Formula 37.3, wherein R1, R2, R3, R4, R5, R6, R8, and X are as previously defined.

42

17149

Scheme 37

a or b

37.1

N

37.2

0 R

8 ,— ' N N ‘s _ R

% /1 \ \ 8

Re 0 0

37.3

In step a of Scheme 38, amines of Formula 38.1, wherein R6 is H or Me, can be reacted

with an electrophile of Formula 38.2, wherein R8 and R9 are as previously defined, such as

5 naphthalen-2-ylmethyl 3-(methylthio)propanimidothioate hydrobromide in a polar protic solvent

such as ethanol followed by exposure to a base such as MP-Carbonate In a polar protic solvent

such as methanol to give amidines of Formula 38.3, wherein R6 Is H or Me, and R8 and R9 are

as previously defined.

C I

Scheme 38

HBr ,_, g., m

N A

S Rg

CI

N A

N Rg

R8

NH

Rg

+ a

10 38.1 38.2 38.3

In step a of the Scheme 39, compounds of the Formula 39.1, wherein X, R1, R2, R3, R4,

R5, R6 and R8 are as previously defined, can be treated with alcohols of the Formula 39.2,

wherein R9 Is as previously defined, In the presence of a base such as sodium hydride or

potassium fert-butoxIde in a polar aprotic solvent such as THF at appropriate temperatures, to

15 give the corresponding ethers of the Formula 39.3. Alternatively, In step b of Scheme 39,

thioethers of the Formula 39.5 can be obtained by treating compounds of the Formula 39.1,

wherein X, R1, R2, R3, R4, R5, R6 and R8 are as previously defined, with thiols of the Formula

39.4, wherein R9 Is as previously defined, in the presence of a base such as sodium hydride In

an aprotic solvent such as THF.

43

17149

Scheme 39

R9-0H

39.2 a

RiORg

39.1

R9—SH

39.4

R2 R4

R3 R5

39.5 (M)

In Scheme 40, compounds of the Formula 40.1, wherein X, R1, R2, R3, R4, R5, R6 and

R8 are as previously defined, can be treated according to the conditions of Estrada etal.

5 (Synlett, 2011 2387-2891), to give the corresponding sulfonamides of the Formula 40.2,

wherein R9 is as previously defined with the proviso that at least one of the R9 is not H.

Scheme 40

40.1 40.2

In step a of Scheme 41, compounds of the Formula 41.1, wherein X, R1, R2, R3, R4, R5

10 and R6 are as previously defined, can be coupled to acids of the Formula 41.2, wherein R8 and

R9 are as previously defined, In the presence of a coupling reagent such as EDDHCI and a

base such as DMAP in an aprotic solvent such as dichloromethane to give phosphonates of the

Formula 41.3. In step b of Scheme 41, phosphonates of the Formula 41.3, wherein X, R1, R2,

R3, R4, R5, R6, R8 and R9 are as previously defined, can be treated with carbonyl compounds

15 of the Formula 41.4, where R9 is as previously defined in the presence of a base such as

sodium hydride In an aprotic solvent such as THF to give the corresponding alkenes of the

Formula 41.5.

Scheme 41

44

17149

00 ii

X + HO )0R9)2 / \

NH

R3 R3 As 41.1

a

Re

41 2

R3 5 I1/4

R 3 R8

o b

41 5

In step a of the Scheme 42, compounds of the Formula 42.1, wherein X. R1, R2, R3, R4,

and R5, are as previously defined, can be treated with trifluoroacetic anhydride In the presence

of a base such as trlethylamine In an aprotic solvent such as dichloromethane to give amides of

5 the Formula 42.2, where X, R1, R2, R3, R4, and R5, are as previously defined. In step b of

Scheme 42, amides of the Formula 42.2, wherein X, R1, R2, R3, R4, and R5, are as previously

defined, can be treated with an alkylating agent such as lodomethane In the presence of a base

such as potassium tert-butoxide In a solvent such as THF to afford compounds of the Formula

42.3. In step c of the Scheme 42 amides of the Formula 42.3, wherein X, R1, R2, R3, R4, and

10

R5, are as previously defined can be treated under basic conditions such as potassium

carbonate and methanol to give the corresponding amines of the Formula 42.4.

Scheme 42

42.1 42.2

C

EXAMPLES

42.4

42.3

45

17149

The examples are for illustration purposes and are not to be construed as limiting the

Invention disclosed In this document to only the embodiments disclosed In these examples.

Starting materials, reagents, and solvents that were obtained from commercial sources

were used without further purification. Anhydrous solvents were purchased as Sure/Sear° from

5 Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt

capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford

Research Systems and are uncorrected. Molecules are given their known names, named

according to naming programs within ISIS Draw, ChemDraw or ACD Name Pro. If such

programs are unable to name a molecule, the molecule is named using conventional naming

10 rules. All NMR shifts are in ppm (5) and were recorded at 300, 400 or 600 MHz unless

otherwise stated. Examples using "room temperature" were conducted In climate controlled

laboratories with temperatures ranging from about 20 °C to about 24 °C.

Example 1, Step 1: Preparation of 3,3-bis-methylsulfanyl-1-pyridin-3-yl-propenone

0 S

N

15

To a room-temperature suspension of sodium hydride (NaH, 60% suspension In mineral

oil; 4.13g. 86 mmol) in dry dimethyl sulfoxide (DMSO, 60 mL) under an atmosphere of nitrogen

(N2) was added 3-acetylpyridine (5.00g. 41.3 mmol) dropwise over 30 minutes (min). The

mixture was stirred for an additional 30 minutes at the same temperature. Carbon disulfide

(CS2; 3.27 g, 43 mmol) was added dropwise with vigorous stirring followed by lodomethane

20

(12.21 g, 86 mmol) dropwise over a period of 45 min. Stirring was continued for an additional 18

hours (h) under N2. The reaction was quenched with cold water (H20, 50 mL). The dark solid

was filtered and washed with Ice-cold ethyl alcohol (Et0H) until the washings were colorless.

The off-white solid product was dried under vacuum at 60 °C to provide 3,3-bis-methylsulfanyl-

1-pyridin-3-yl-propenone as a brown solid (4.8 g, 51%): 1 H NMR (300 MHz, CDC13) 0 9.13 (d, J

25

= 1.8 Hz, 1H), 8.72 (dd, J = 4.8, 1.6 Hz, 1H), 8.23 (ddd, J = 7.9, 2, 2 Hz, 1H), 7.40 (dd, J = 7.9,

4.8 Hz, 1H), 6.73 (s, 1H), 2.58 (d, J = 9.4 Hz, 6H); MS m/z 226.2 (M+1).

1-(5-fluoropyridin-3-y1)-3,3-bis(methylthio)prop-2-en-1-one was prepared as described In

Example 1, Step 1: mp 150-152 °C; I FI NMR (400 MHz, CDC13) 58.93 (t, J = 1.6 Hz, 1H),

8.58(d, J = 2.8 Hz, 1H),7.94 (ddd, J = 8.9, 2.8, 1.7 Hz, 111)„ 6.69 (s, 1H), 2.60 (s, 3H), 2.57 (s,

30 3H).

Example 1, Step 2: Preparation of (4-3-methylamino-3-methylsulfanyl-1-pyrldin-3-yl-

propenone

46

17149

A solution of 3,3-bis-methylsulfany1-1-pyridin-3-yl-propenone (18.6g. 82.5 mmol) in

absolute alcohol (400 mL) under N2 was treated with methylamlne hydrochloride (27.86g. 412

mmol) followed by triethylamine (Et 3N; 58.5 mL, 412 mmol). The mixture was heated to reflux

5 for 3 h, cooled to room temperature and concentrated under reduced pressure. The solid

residue was dissolved in ethyl acetate (Et0Ac; 150 mL). The solution was washed with H20 (2 x

50 mL) and brine (50 mL), dried over Na2SO4., concentrated under reduced pressure and

purified by silica gel chromatography eluting with 10% Et0Ac in petroleum ether to yield (Z)-3-

methylamino-3-methylsulfany1-1-pyridin-3-yl-propenone as a pale yellow solid (8.6 g, 50%): 1 H

10 NMR (300 MHz, CDCI3) 0 11.8 (br s, 1H), 9.06 (s, 1H); 8.67 (d, J = 3.9 Hz, 1H), 8.26 (d, J = 8.0

Hz 1H), 7.46 (dd, J= 7.6, 4.9 Hz 1H), 5.62(s, 1H), 3.10(d, J = 5.2 Hz, 3H), 2.52 (s, 3H); MS

(m/z) 209.2 [M+1].

(Z)-3-(ethylamlno)-3(methylthio)-1-(pyridin-3-yl)prop-2-en-1-one was prepared as

described In Example 1, Step 2: 1 H NMR (400 MHz, CDCI3) 6 11.81 (bs, 1H), 9.04 (dd, J = 2.2,

15

0.7 Hz, 1H), 8.64 (dd, J = 4.8, 1.7 Hz, 1H), 8.29 — 7.98 (m, 1H), 7.35 (ddd, J = 7.9, 4.8, 0.9 Hz,

1H), 3.45 (q, J = 7.2, 5.6 Hz, 2H), 2.50 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H).

(Z)-3-(cyclopropylmethy9amino-3(methylthio)-1-(pyridin-3-ypprop-2-en-1-one was

prepared as described In Example 1, Step 2: 1 H NMR (400 MHz, CDCI3) 69.00 (s, 1H), 9.05

20 (dd, J = 2.2, 0.7 Hz, 1H), 8.64 (dd, J = 4.8, 1.7 Hz, 1H), 8.16 (dt,. J = 7.9, 2.0 Hz, 1H), 7.35 (ddd,

J = 7.9, 4.8, 0.8 Hz, 1H), 5.62 (s, 1H), 3.27 (dd, J = 7.0, 5.5 Hz, 2H), 2.50 (s, 3H), 1.20 — 1.07

(m, 1H), 0.73 — 0.49 (m, 2H), 0.41 — 0.17 (m, 2H).

Example 1, Step 3: Preparation of methyl-(2-methyl-5-pyriclin-3-pyrazol-3-y1)-amine

N-N/

.11

A solution of (Z)-3-methylamino-3-methylsulfany1-1-pyridin-3-yl-propenone (3.00g. 14

mmol) and methylhydrazine (729 mg, 15.4 mmol) in absolute Et0H (64 mL) was stirred at reflux

for 18 h under N2, cooled to room temperature and evaporated under reduced pressure. The

residue was dissolved In Et0Ac (50 ml), and the organic layer was washed with 1120 (2 x 30

30 mi.) and brine (30 mL), dried over Na2504, concentrated under reduced pressure and purified

using silica gel chromatography eluting with a gradient of 0-1% Et0H in Et0Ac to yield two

25

47

17149

regioisomers In a 1:2 ratio, with the major regloisomer as a brown solid (1.0 g, 27%): I HNMR

(300 MHz, CDCI3) 0 8.97(d, J= 1.3 Hz, 1H), 8.51 (dd, J= 3.6, 1.0 Hz, 1H), 8.07 (ddd, J= 5.9,

1.4, 1.4 Hz, 1H), 7.30 (dd, J= 5.9, 3.6 Hz, 1H), 5.82 (s, 1H), 3.69 (s, 3H), 2.93 (s, 3H); MS (m/z)

188.6 [M+1].

5 1-Ethyl-N-methyl-3-(pyridin-3-y1)-1H-pyrazol-5-amine was prepared as described In

Example 1, Step 3: ESIMS m/z 204 ([M+2H]).

N-ethyl-1-methyl-3-(pyridin-3-y1)-1H-pyrazol-5-amine was prepared as described In

Example 1, Step 3: ESIMS m/z 203 ([M+H]).

N-methyl-1-phenyl-3-(pyridin-3-y1)-1H-pyrazol-5-amine was prepared as described In

10 Example 1, Step 3: ESIMS m/z 252 ([M+2H]).

N-(cyclopropylmethyl)-1-methy1-3-(pyridin-3-y1)-1H-pyrazol-5-amine was prepared as

described In Example 1, Step 3: ESIMS m/z 230 ([M+2H]).

1-lsopropyl-N-methy1-3-pyridin-3-y1)-1H-pyrazol-5-amine was prepared as described In

Example 1, Step 3: 1 H NMR (300 MHz, CDCI3) 68.53 (s, 1H), 8.06 — 7.90 (m, J= 7.2 Hz, 2H),

15 7.13 (dd, J= 7.9, 5.6 Hz, 1H), 5.33(s, 1H), 3.70 (bs, 1H), 3.65 (dt, J= 13.2, 6.6 Hz, 1H), 2.31

(s, 3H), 0.88(d, J= 6.6 Hz, 6H); ESIMS m/z 217 ([M+H]).

3-(5-Fluoropyridin-3-y9-N, 1-dimethy1-1H-pyrazol-5-amine was prepared as described in

Example 1, Step 3: I li NMR (300 MHz, CDCI 3) 68.28 (s, 1H), 7.87 (t, J= 1.3 Hz, 1H), 7.60(m,

20 1H), 6.66 (s, 1H), 5.28 (bs, 2H), 3.12(s, 3H), 2.34(s, 3H); ESIMS m/z 206 ([M+H])

Example 2: Preparation of (4-chloro-2-methy1-5-pyriclin-3-y1-2H-pyrazol-3-y1)-methyt.

amine

N-N/

.H N I

N Cl

25 A mixture of methyl-(2-methyl-5-pyridin-3-y1-2H-pyrazol-3-y1)-amine (0.35g. 1.8 mmol)

and N-chlorosuccinimide (0.273 g, 2 mmol) was combined In acetonitrile (3 mL), stirred at room

temperature for 30 minutes, concentrated under reduced pressure and purified using silica gel

chromatography eluting with a gradient of Et0Ac in hexanes to yield the title compound as a

yellow oil (0.096 g, 23%): IR (thin film) 1581.6 cm -1 ; 1 H NMR (400 MHz, CDCI3) 0 9.12 (d, J=

30

1.5 Hz, 1H), 8.57 (dd, J= 4.8, 1.3 Hz, 1H), 8.15 (ddd, J= 7.8, 2.0, 2.0 Hz, 1H), 7.33 (dd, J= 8.1,

5.1 Hz, 1H), 3.80 (s, 3H), 2.91 (d, J= 5.8 Hz, 3H); ESIMS (m/z) 225.6 [M+2].

The reaction also gave 4-chloro-2-methyl-5-pyridin-3-y1-2H-pyrazol-3-ylamine as a green

gum (0.046 g, 13%): IR (thin film) 1720.5 cm'.; l EINMR (CDCI3, 400 MHz) 0139.13 (br s, 1H),

48

17149

8.57 (br s, 1H), 8.16 (dt, J = 8.0, 2.0 Hz, 1H), 7.33 (dd, J= 7.8, 4.8 Hz, 1H), 3.76 (s, 3H); ESIMS

(m/z) 207.0 [M-1].

Example 3: Preparation of 2,N-dimethyl-N-(2-methyl-5-pyridin-3-y1-211-pyrazol-3-y1)-3-

5 methylsulfanyl-propionamIde (Compound 1)

-NI 0

N I

N

To a solution of methyl-(2-methy1-5-pyridin-3-y1-2H-pyrazol-3-y1)-amine (150 mg, 0.8

mmol) under N2 in Ice-cold dichloroethane (DCE; 2 mL) was added dropwise via pipette a

solution of 2-methyl-3-methylsulfanyl-propionylchloride (146 mg, 0.9 mmol) in DCE (1.5 mL).

10 After stirring for 10 minutes (mm), a solution of 4-N,N-dimethylaminopyridine (DMAP; 107 mg,

0.9 mmol) in DCE (2 ml.) was added dropwlse. The Ice bath was removed after 30 min, and the

mixture was stirred at room temperature for 90 min and then at reflux for 14 h. The mixture was

concentrated under reduced pressure and was purified by silica gel chromatography eluting with

a gradient of Et0Ac In hexane. The product, 2,N-dimethyl-N-(2-methy1-5-pyridin-3-yI-2H-

15 pyrazol-3-09-3-methylsulfanyl-propionamide, was isolated as a yellow semi-solid (44 mg, 24%):

1 H NMR (400 MHz, CDCI 3) 0 9.00 (s, 1H), 8.58 (s, 1H), 8.08 (br d, J = 7.0 Hz, 1H), 7.35 (br dd,

J = 7.3, 4.8 Hz, 1H), 6.58 (br s, 0.5 H), 6.49 (br s, 0.5 H), 3.89-3.79 (m, 3H), 3.25 (s, 3H), 2.96-

2.80 (m, 1H), 2.42-2.40(m, 1H), 2.02-1.99 (m, 3H), 2.62 (m, 1H), 1.15(d, J= 6.0 Hz, 3H); MS

(m/z) 305.0 [M+11.

20 Compounds 2 - 6, 9 -10, 12, 18 - 21, 24 - 33, 477, 487, 509, 520, 556-557, 562-568

were made from the appropriate amines In accordance with the procedures disclosed In

Example 3.

Example 4: Preparation of 1-methyl-1-(2-methyl-5-pyriclin-3-y1-2H-pyrazol-3-y1)-3-(2-

methylsulfanyl-ethyl)-urea (Compound 7)

25

To a solution of methyl-(2-methy1-5-pyridin-3-y1-2H-pyrazol-3-y1)-amine (150 mg, 0.8

mmol) In Ice-cold DCE (2 mL) under N2 was added a solution of phosgene in toluene (20%, 0.43

ml., 0.88 mmol). The Ice bath was removed after 30 min, and the mixture was stirred at room

temperature for 1 h and at reflux for 2 h. The mixture was cooled to room temperature and then

30 more phosgene (0.86 mL, 1.76 mmol) was added. The mixture was stirred at reflux for 90 min

and then cooled In an ice bath. To this was added a solution of 2-methylthioethylamine (80 mg,

0.88 mmol) in DCE (2 ml.). The ice bath was removed after 10 min, and the reaction mixture 49

17149

was stirred at reflux for 14 h, cooled, and diluted with DCE (30 mL). The diluted reaction mixture

was washed with saturated NaHCO3 (20 mL), dried over MgSO4, adsorbed onto silica gel and

purified using silica gel chromatography eluting with a gradient of methanol in dichloromethane

to afford 1-methy1-1-(2-methy1-5-pyridin-3-y1-2H-pyrazol-3-y1)-3-(2-methylsulfanyl-ethyl)-urea as

5 a yellow gum (14 mg, 6%): 1 H NMR (400 MHz, CDCI3) 0 8.99 (d, J = 1.5 Hz, 1H), 8.57 (dd, J =

4.8, 1.5 Hz, 1H), 8.08 (ddd, J= 8.1, 2.1, 2.1 Hz, 1H), 7.34 (dd, J = 7.9, 4.8 Hz, 1H), 6.52 (s, 1H),

4.88 (br t, J = 5.5 Hz, 1H), 3.80 (s, 3H), 3.41 (q, J = 6.3 Hz, 2H), 3.24 (s, 3H), 2.61 (t, J = 6.3,

2H), 2.06 (s, 3H); ESIMS (m/z) 292.2 [M+2].

Compound 8 was made in accordance with the procedures disclosed In Example 4

10 using 2-(methylthio)ethanol in place of 2-methylthioethylamine.

Example 5: Preparation of 1-methy1-5-(pyridin-3-y1)-1H-pyrazol-3-amine and 1-methy1-3-

(pyridin-3-yI)-1H-pyrazol-5-amlne

\ I 2 2 1,

To ethanol (8.53 mL) was added 3-oxo-3-(pyridin-3-yl)propanenitrile (0.82 g, 5.61 mmol)

15 and methylhydrazine (0.25 g, 5.61 mmol) and stirred at reflux for 2 hours. The reaction was

cooled to room temperature and concentrated to dryness. The crude material was purified by

silica gel chromatography by eluting with 0-20% Me0H/dichloromethane to yield two products —

1-methyl-5-(pyridin-3-y1)-1H-pyrazol-3-amine (0.060 g; 6.14%): 1 H NMR (300 MHz, CDCI3) 0

8.72 (s, 1H), 8.53 (d, 1H), 7.76-7.63 (m, 1H), 7.43-7.33 (m, 1H), 5.75 (s, 1H), 3.76-3.57 (m, 5H)

20 and 1-methy1-34pyridin-3-y1)-1H-pyrazol-5-amine (0.150 g, 15.35%): 'H NMR (300 MHz, CDCI3)

68.88 (s, 1H), 8.48 (d, 1H), 7.99 (d, 1H), 7.38-7.07 (m, 1H), 585 (s, 1H), 3.80-3.59 (m, 5H).

Example 6, Step 1: Preparation of 3-pyrazol-1-yl-pyridine

VD/N

N

To a solution of 3-bromopyridine (5 g, 0.031 mol) In 50 ml of acetonitrile were added

25 pyrazole (2.6 g, 0.038 mol), Cs 2CO3 (16.5 g, 0.050 mol), Cu20 (0.226 g, 0.0016 mol), and

salicylaldoxime (0.867 g, 0.006 mol) under N2 atmosphere. The reaction mass was refluxed for

24 hrs at 80 °C. The reaction mass was concentrated and the crude was purified by column

chromatography using ethyl acetate and hexane (1:1) to afford the pyrazolyl pyridine as a dark

brown liquid (2 g, 43 %): 1 H NMR (400 MHz, CDCI 3) 0 8.99 (d, J = 2.8 Hz, 1H), 8.48 (dd, J =

30

4.8, 1.2 Hz, 1H), 8.11 — 8.08 (m, 1H), 7,99(d, J = 1.2 Hz, 1H), 7.78(d, J = 1.2 Hz, 1H), 7.38 —

7.35 (m, 1H), 6.53 (t, J = 1.2 Hz, 1H); MS (m/z) 146 [M+11.

50

17149

3-(3-chloro-1H-pyrazol-1-yOpyridine was prepared as In Example 6, Step 1: mp 98-106

°C; 1 H NMR (400 MHz, CDCI 3) 68.93 (d, J= 2.6 Hz, 1H), 8.57 (dd, J= 4.8, 1.4 Hz, 1H), 8.03

(ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.90 (d, J= 2.5 Hz, 1H), 7.42 (ddd, J= 8.3, 4.8, 0.7 Hz, 1H), 6.46

(d, J= 2.5 Hz, 1H); 13C (DMSO-d6) 148, 142, 140, 136, 131, 126, 125, 108.

5

2-methy1-3-(3-methyl-1H-pyrazol-1-yl)pyridine was prepared as In Example 6, Step 1: 1 H NMR

(400 MHz, CDCI3) 58.53 (d, J= 4.7 Hz, 1H), 7.67 (d, J= 7.9 Hz, 1H), 7.54 (t, J= 8.0 Hz, 1H),

7.27 - 7.19 (m, 1H), 6.27 (d, J= 1.4 Hz, 1H), 2.53 (s, 3H), 2.38 (s, 3H).

3-(3-(Trifluoromethy9-1H-pyrazol-1-y1)pyridine was prepared from the appropriate

10 starting materials as described In Example 6, Step 1: mp 59.0-61.0 °C; 1 F1 NMR (400 MHz,

CDCI3) 6 9.00 (s, 1H), 8.70 - 8.59 (m, 1H), 8.11 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 8.05 - 7.98 (m,

1H), 7.46 (dd, J= 8.3, 4.8 Hz, 1H), 6.79(d, J= 2.4 Hz, 1H); EIMS m/z 213.

3-Fluoro-5-(3-methyl-1H-pyrazol-1-yl)pyridine was prepared from the appropriate starting

materials as described In Example 6, Step 1: mp 70.0-72.0 °C; 1 H NMR (400 MHz, CDCI3) 6

15 8.76 - 8.73 (m, 1H), 8.37 - 8.33 (m, 1H), 7.88 - 7.85 (m, 1H), 7.84 - 7.79 (m, 1H), 6.34 - 6.29 (m,

1H), 2.37 (s, 3H); EIMS m/z 177.

3-(3-Chloro-1H-pyrazol-1-y1)-5-fluoropyridine was prepared from the appropriate starting

materials as described in Example 6, Step 1: mp 77.0-82.0 °C; 1 H NMR (400 MHz, CDCI3) 6

8.75 (d, J= 1.8 Hz, 1H), 8.43 (d, J= 2.3 Hz, 1H), 7.92 (d, J=2.6 Hz, 1H), 7.84 (dt, J=9.3,2.4

20 Hz, 1H), 6.48 (d, J= 2.6 Hz, 1H); EIMS m/z 198.

3-(3-methy1-1H-pyrazol-1-Apyridine was prepared as described in Example 6, Step 1:

1 H NMR (400 MHz, CDCI3) 6 8.94 (bs, 1H), 8.51 (d, J= 3.9 Hz, 1H), 8.02 (ddd, J= 8.3, 2.6, 1.5

Hz, 1H), 7.90 — 7.79 (m, 1H), 7.39 (dd, J= 8.2, 5.1 Hz, 1H), 6.30 (d, J= 2.4 Hz, 1H), 2.39 (s,

3H).

25 345-methyl-I H-pyrazol-1-y1)pyridine was prepared as In Example 6, Step 1: 1 H NMR

(400 MHz, CDCI3) 6 8.77 (d, J= 2.5 Hz, 1H), 8.65 (dd, J= 4.8, 1.5 Hz, 1H), 7.84 (ddd, J= 8.2,

2.5, 1.5 Hz, 1H), 7.63 (d, J= 1.6 Hz, 1H), 7.44 (ddd, J= 8.2, 4.8, 0.7 Hz, 1H), 6.225 (dd, J= 1.6,

0.7 Hz, 1H), 2.40 (s, 3H).

Example 6, Step 2: Preparation of 3-(4-nitro-pyrazol-111)-pyrldine

III,D--/ NO2

30 3-Pyrazol-1-y1-pyridine (2 g, 0.032 mol) was dissolved in concentrated H 2SO4 (32 mL

0.598 mmol) and cooled at —5 °C using an ice bath. To the reaction mass, a 1:1 mixture of

concentrated HNO3 (30 mL, 0.673 mmol) and concentrated H 2SO4(30m1, 15 Vol.) was added

dropwise over a period of 30 min. Cooling was discontinued and the reaction mixture was stirred

51

17149

at room temperature overnight. After the reaction was complete, the mixture was poured over

crushed Ice and neutralized with saturated NaHCO3, filtered, washed with water and dried to

furnish the nitro pyrazole as pale yellow solid (1.8 g, 68%): 1 H NMR (400 MHz, DMSO-do) fl

9.03 (d, J= 2.8 Hz, 1H); 8.70 (dd, J = 4.8, 1.6 Hz, 1H), 8.69 (s, 1H), 8.33 (s, 1H), 8.11 - 8.08(m,

5 1H), 7.51 (dd, J = 8.4, 4.8 Hz, 1H); MS (m/z) 191 [M+1].

3-(3-chloro-4-nitro-1H-pyrazol-111)pyridine was prepared as in Example 6, Step 2: mp

139-142 °C, 1 H NMR (400 MHz, CDCI3) 69.01 (d, J= 2.0 Hz, 1H), 8.73 (d, J- 4.9 Hz, 2H), 8.08

(ddd, J = 8.3, 2.5, 1.3 Hz, 1H), 7.52 (dd, J = 8.3, 4.8 Hz, 1H), EIMS m/z 224.

3-(5-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 2: 1 H

10 NMR (400 MHz, CDC13) 68.81 -8.71 (m, 2H), 8.32 (s, 1H), 7.83 (ddd, J = 8.2, 2.5, 1.6 Hz, 1H),

7.54 (dd, J = 8.2, 4.8 Hz, 1H), 2.72(s, 3H).

2-methyl-3-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example 6,

Step 2: 1 H NMR (400 MHz, drDMS0) 614.01 (s, 1H), 9.37 (d, J= 4.0 Hz, 1H), 8.69(t, J = 17.3

Hz, 1H), 8.21 (dd, J = 7.7, 4.8 Hz, 1H), 2.29 (s, 3H), 2.20 (s, 3H); . 13C 154, 150, 146, 135,

15 134.9, 134.8, 134.3, 122, 21, 14; EIMS m/z 218.

3-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 2: mp

122- 124°C; 1 H NMR (400 MHz, CDCI3) 69.01 (d, J = 2.5 Hz, 1H), 8.77 - 8.56 (m, 2H), 8.07

(ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.56 - 7.37 (m, 1H), 2.66 (s, 3H); EIMS m/z 208.

3-Fluoro-5-(3-methy1-4-nitro-1H-pyrazol-1-yl)pyridine was prepared from the appropriate

20 starting material as described In Example 6, Step 2: mp 90.0-92.0 °C; 1 H NMR (400 MHz,

CDCI3) 68.82 (d, J = 2.0 Hz, 1H), 8.69 (s, 1H), 8.54 (d, J = 2.5 Hz, 1H), 7.89 (dt, J = 8.9, 2.4

Hz, 1H), 2.66 (s, 3H); EIMS m/z 222.

3-(4-Nitro-3-(trifluoromethy9-1H-pyrazol-1-yOpyridine was prepared from the appropriate

starting material as described In Example 6, Step 2: mp 121.0-123.0 °C; 1 H NMR (400 MHz,

25 CDCI3) 6 9.04 (d, J = 2.5 Hz, 1H), 8.79 (s, 1H), 8.77 (d, J = 0.9 Hz, 1H), 8.13 (ddd, J = 8.3, 2.7,

1.4 Hz, 1H), 7.55 (dt, J = 10.8, 5.4 Hz, 1H); EIMS m/z 258.

3-(3-Chloro-4-nitro-1H-pyrazol-1-y1)-5-fluoropyridine was prepared from the appropriate

starting material as described in Example 6, Step 2: mp 109.5-111.0 °C; 1 H NMR (400 MHz,

CDCI3) 6 8.83 (d, J = 2.1 Hz, 1H), 8.75 (s, 1H), 8.60 (d, J = 2.4 Hz, 1H), 7.89 (dt, J = 8.6, 2.4 Hz,

30 1H); EIMS rrilz 242.

3-(3-Bromo-4-nitro-1H-pyrazol-1-yOpyridine was prepared from the appropriate starting

material as described In Example 6, Step 2: mp 139.0-141.0°C; 1 H NMR (400 MHz, CDCI 3) 6

9.01 (d, J = 2.5 Hz, 1H), 8.73 (dd, J = 4.7, 1.1 Hz, 1H), 8.71 (s, 1H), 8.15- 8.00(m, 1H), 7.52

(dd, J= 8.3, 4.8 Hz, 1H); ESIMS m/z 271 (1M+21').

35 Example 6, Step 3: Preparation of 1-pyrldln-3-yl-1H-pyrazol-4-ylamlne

52

17149

N

To a solution of 3-(4-nitro-pyrazol-1-y1)-pyridine (1.8 g, 0.009 mol) In dry THF (18 mL)

was added 5% Pd/C (180 mg) under nitrogen atmosphere. The mixture was then stirred under

hydrogen atmosphere until the reaction was complete. The reaction mixture was filtered through

5 a pad of celite, and concentrated to dryness to give an Impure dark brown solid (1.76 g): 'H

NMR (400 MHz, DMSO-do) 0 8.89 (dd, J = 2.8. 0.4 Hz, 1H); 8.48 (dd, J = 4.8, 1.2 Hz, 1H), 7.99

—7.96 (m, 1H), 7.54 (d, J = 1.2 Hz, 1H), 7.45 (d, J = 0.4 Hz, 1H), 7.38 — 7.35 (m, 1H), 4.81 (bs

1H); ESIMS (m/z) 161 [M+1].

5-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as in Example 6, Step 3: 'H

10 NMR (400 MHz, CDC13) 6 8.74 (d, J = 2.3 Hz, 1H), 8.63 — 8.50 (m, 1H), 7.81 (ddd, J = 8.2, 2.5,

1.5 Hz, 1H), 7.46 — 7.33 (m, 2H), 2.64 (bs, 1H)„ 2.29 (s, 3H); ' 3C (DMSO-c/a) 147, 144, 137,

133, 130, 129, 124, 123, 10; EIMS m/z 174

3-methy1-1-(pyrimidin-5-y1)-1H-pyrazol-4-amine was prepared as In Example 6, Step 3:

mp 211-215 °C; 'H NMR (400 MHz, CDCI3) 6 9.10— 8.87 (m, 3H), 7.51 (s, 1H), 3.24 (bs, 2H),

15 2.29 (s, 3H); ESIMS m/z 176 ([M+11]).

3-chforo-1-(pyrimidin-5-y1)-1H-pyrazol-4-amine was prepared as in Example 6, Step 3:

mp 146-148 °C; 'H NMR (400 MHz, CDCI3) 59.07 (s, 1H), 9.02 (s, 2H), 7.52 (s, 1H), 3.45 (s,

2H); ESIMS m/z 196 ((M+H]).

Example 7: Preparation of methyl-(1-pyrldin-3-y1-1H-pyrazol-4-y1)-amlne

Nc-\ .1-1 14J-1\

20

Method A:

To a 25 ml round bottom flask containing 1-pyridin-3-y1-1H-pyrazol-4-ylamine (1.76 g,

0.011 mol) In ethanol (26.4 mL) was added benzotriazole (1.31 g, 0.011 mol). The reaction was

cooled at 0 °C - 10° C and formaldehyde (0.36 mL, 0.0121 mol) was added slowly and kept for

25 30 mm at this temperature. The reaction was filtered and concentrated to dryness. The crude

material (2.56g, 0.009 mol) was dissolved In dry tetrahydrofuran (25.6 mL), cooled to 0°C and

sodium borohydride (0.326g. 0.00882 mot) was added over 15 min. The reaction was warmed

to room temperature and stirred for 2 hours. The reaction was poured Into water and extracted

using dichloromethane, the organic layer was dried over anhydrous Na2SO4 and concentrated

30 to dryness. Purified the crude material by silica gel chromatography eluting with 20%

methanol/chloroform to afford the desired product as a brown solid (0.610 g, 32 %): 'H NMR

(400 MHz, d6-DMS0) 0 8.92 (d, J = 2.4 Hz, 1H), 8.47 (dd, J = 4.8, 1.6 Hz, 1H), 8.01 —7.98 (m,

53

17149

1H), 7.45 (s, 1H), 7.30(s, 1H), 7.37 (dd, J= 8.0, 4.4 Hz, 1H), 2.84(s, 3H); ESIMS miz 175

([M+1]).

Method B:

1-pyridin-3-y1-1H-pyrazol-4-ylamine (1.0 g, 6.2 mmol) was dissolved in trlethyl

5

orthoforrnate (5 mL, 30 mmol) and to that was added trifluoroacetic acid (3-4 drops). The

reaction mixture was refluxed at 120°C for 3 hours and was then concentrated. The crude was

dissolved in ethanol (5 ml), cooled to 0°C and treated with sodium borohydride (0.6 g, 15.7

mmoI). After warming to room temperature, the mixture was refluxed for 3 hours. The mixture

was concentrated and the residue was suspended between water and diethyl ether. The diethyl

10 ether layer was separated and concentrated to dryness. The crude material was purified by

silica gel chromatography, eluting with 5% methanol/chloroform to afford the desired product as

a pale yellow solid (0.3 g, 27%): mp 65 - 67 °C; 1 H NMR (300 MHz, CDC13) 68.91 (bs, 1H),

8.46(d, J= 4.5 Hz, 1H), 7.99 (d, J = 8.3 Hz, 1H), 7.43(s, 1H), 7.41 (s, 1H), 7.36 (dd, J = 8.3,

4.7 Hz, 1H), 2.86(d, J = 12.4 Hz, 3H); ESIMS miz 175 ([M+1]).

15 Example 8: Preparation of ethyl-(1-pyridln-3-y1-1H-pyrazol-4-y1)-amine

Method A:

To 1-pyridin-3-yI-1H-pyrazol-4-ylamine (0.5 g, 3.12 mmol) In dichloromethane (5 mL)

was added acetyl chloride (0.28g. 3.75 mmol) followed by DMAP (0.57g. 4.68 mmol) and

20 stirred at room temperature for 3 hours. The reaction mixture was concentrated and purified by

silica gel column chromatography. The recovered material was dissolved In tetrahydrofuran (5

mt.) and lithium aluminum hydride (0.23g, 6.25 mmol) was added and stirred at room

temperature for 12 hours. The reaction was quenched with saturated Na2Sa4 and filtered

through celite. The filtrate was collected and concentrated to dryness. The crude material was

25 purified by silica gel column chromatography eluting with 0-5% methanol/chloroform and

resubjected to silica gel chromatography, eluting with 0-100% ethyl acetate/hexanes) to give the

desired product (0.080g. 14%): 1 H NMR (400 MHz, CDCI3) 68.90 (d, J= 2.7 Hz, 1H), 8.46 (dd,

J = 4.7, 1.3 Hz, 1H), 7.98 (ddd, J = 8.3, 2.6, 1.5 Hz, 1H), 7.41 (dt, J = 13.3, 6.6 Hz, 2H), 7.36

(ddd, J = 8.3, 4.7, 0.7 Hz, 1H), 3.10 (q, J = 7.1 Hz, 2H), 1.27 (t, 3H).

30 Method B:

To a solution of tert-butyl ethyl(1-(pyridin-3-y1)-1H-pyrazol-4-yOcarbamate (3.4 g, 11.79

mmol) in dichloromethane (4.54 ml.) was added trifluoroacetic acid (9 mt.), and the reaction

mixture was stirred for 1 hour at room temperature. Toluene was added and the reaction was

concentrated to near dryness. The reaction was poured Into a separatory funnel and carefully

54

17149

quenched with saturated aqueous NaHCO3 and extracted with dichloroethane. The organic

layer was dried (MgSO4), filtered and concentrated to dryness. The crude product was purified

by silica gel chromatography (0-10% Me0H/dichloromethane) to give the desired product as a

pale yellow oil (2.10 g, 95%): 'H NMR (400 MHz, CDCI3) 58.90 (dd, J = 1.8, 0.8 Hz, 1H), 8.51 -

5 8.39(m, 1H), 7.97 (ddt, J- 8.3, 2.7, 1.3 Hz, 1H), 7.41 (d, J = 0.8 Hz, 2H), 7.38 - 7.30 (m, 1H),

3.21 -2.93 (m, 2H), 1.34 - 1.19 (m, 3H).

3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as described in

Example 8, Method B: 'H NMR (400 MHz, CDCI3) 68.87 (d, J= 2.5 Hz, 1H), 8.47 (dd, J = 4.7,

1.2 Hz, 1H), 7.96 (ddd, J = 8.4, 2.6, 1.4 Hz, 1H), 7.38 - 7.32 (m, 2H), 3.11 (q, J = 7.1 Hz, 2H),

10 2.97 (bs, 1H), 1.31 (t, J = 7.1 Hz, 3H).

3-chloro-N-methyl-1-(pyridin-311)-1H-pyrazol-4-amine was prepared as In Example 8,

Method B: mp 108-118 C; 'H NMR (400 MHz, CDC13) 68.88 (d, J = 2.4 Hz, 1H), 8.48 (dd, J =

4.7, 1.4 Hz, 1H), 7.96 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.41 -7.29 (m, 2H), 2.87 (s, 3H); EIMS

m/z 208.

15 N,3-dimethy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as in Example 8, Method

B: 'H NMR (400 MHz, CDCI 3) 6 9.03 - 8.73 (m, 1H), 8.41 (dd, J= 4.7, 1.4 Hz, 1H), 7.95 (ddd, J

= 8.4, 2.7, 1.4 Hz, 1H), 7.42 - 7.27 (m, 2H), 2.85 (s, 4H), 2.25 (s, 3H); EIMS m/z 189

3-chloro-N-(cylopropylmethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as In

Example 8, Method B: 'H NMR (400 MHz, CDCI3) 68.86 (d, J= 2.5 Hz, 1H), 8.47 (dd, J= 4.7,

20 1.4 Hz, 1H), 8.03 - 7.89 (m, 1H), 7.40 - 7.29 (m, 2H), 3.21 (s, 1H), 2.91 (d, J = 4.4 Hz, 2H), 1.18

- 1.02 (m, 1H), 0.65 - 0.45 (m, 2H), 0.41 -0.12 (m, 2H).

3-chloro-N-propy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as In Example 8,

Method B: 'H NMR (400 MHz, CDCI3) 6 8.86 (d, J = 2.6 Hz, 1H), 8.47 (dd, J = 4.7, 1.4 Hz, 1H),

8.01 - 7.89(m, 1H), 7.42- 7.27(m, 2H), 3.23- 2.84(m, 3H), 1.77- 1.59(m, 2H), 1.03 (t, J = 7.4

25 Hz, 3H).

1-(5-Fluoropyridin-3-y1)-N,3-dimethyl-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described In Example 8, Method B: mp 142.0-143.5 °C; 'H NMR (400

MHz, CDC13) 8 8.67 (s, 1H), 8.26 (d, J = 2.3 Hz, 1H), 7.73 (dt, J = 10.0, 2.4 Hz, 1H), 7.27 (s,

1H), 2.92 - 2.81 (m, 4H), 2.24 (s, 3H); ESIMS m/z 207 ((M+Hr).

30 N-ethyl-1-(5-fluoropyridin-3-0)-3-methyl-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: mp 85.0-86.0 °C; 'H NMR (400

MHz, CDCI3) 68.66 (s, 1H), 8.25 (d, J = 2.5 Hz, 1H), 7.72 (dt, J = 10.0, 2.3 Hz, 1H), 7.27 (s,

1H), 3.07 (q, J = 7.1 Hz, 2H), 2.71 (s, 1H), 2.25 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); ESIMS m/z 221

([M+H]).

35 3-Methyl-N-propy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: mp 65.0-67.0 °C; 'H NMR (400

MHz, CDCI3) 8 8.86 (d, J = 2.4 Hz, 1H), 8.40 (dd, J = 4.7, 1.4 Hz, 1H), 7.94 (ddd, J = 8.3, 2.7,

55

17149

1.5 Hz, 1H), 7.35- 7.28(m, 2H), 3.00(t, J= 7.1 Hz, 2H), 2.26 (s, 3H), 1.76 - 1.58 (m, 2H), 1.03

(t, J = 7.4 Hz, 3H); ESIMS m/z 217 ([M+H]).

N-(cyclopropylmethy9-3-methy1-1-(pyridin-3-y0-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described In Example 8, Method B: mp 73.0-75.0 °C; 'H NMR

5 (400 MHz, CDCI3) §8.86 (d, J= 2.4 Hz, 1H), 8.40 (dd, J = 4.7, 1.3 Hz, 1H), 7.94 (ddd, J = 8.3,

2.6, 1.5 Hz, 1H), 7.35 - 7.28 (m, 2H), 2.87 (d, J = 6.9 Hz, 2H), 2.75 (s, 1H), 2.28 (s, 3H), 1.22 -

1.05 (m, 1H), 0.63 - 0.56 (m, 2H), 0.26 (q, J = 4.7 Hz, 2H); ESIMS rn/z 229 ((M+Hr).

N-Isopropyl-3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described In Example 8, Method B: IR (thin film) 3303 cre; 1 H NMR

10 (400 MHz, CDCI3) 6 8.86 (d, J = 2.3 Hz, 1H), 8.41 (dd, J = 4.7, 1.4 Hz, 1H), 7.94 (ddd, J = 8.3,

2.7, 1.5 Hz, 1H), 7.36- 7.28 (m, 2H), 3.30 (hept, J = 6.3 Hz, 1H), 2.25 (s, 3H), 1.24 (d, J = 6.3

Hz, 6H); EIMS m/z 216.

5-Ethoxy-1-(5-fluoropyridin-3-y9-N,3-dimethy1-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3340 cm -I ; 1 11

15 NMR (400 MHz, CDC13) 68.91 (s, 1H), 8.31 (d, J= 2.5 Hz, 1H), 7.88 - 7.80 (m, 1H), 4.24 (q, J=

7.1 Hz, 2H), 2.79 (s, 3H), 2.24(s, 3H), 1.36(t, J= 7.1 Hz, 3H); EIMS m/z 250.

5-Bromo-N-methy1-1-(pyridin-3-y1)-1H-pyrazol-4-amlne was prepared from the

appropriate Boc-amine as described in Example 8, Method B: mp 77.0-79.0 °C; I HNMR (400

MHz, CDCI3) 6 8.90(d, J = 2.0 Hz, 1H), 8.63(d, J = 3.9 Hz, 1H), 7.93 (ddd, J = 8.2, 2.4, 1.5 Hz,

20 1H), 7.51 (s, 1H), 7.43 (dd, J= 8.2, 4.8 Hz, 1H), 4.49 (s, 1H), 2.91 (s, 3H); ESIMS m/z 255

([M+2]).

5-Fluoro-N,3-dimethy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: 'H NMR (400 MHz, CDCI 3) 6 8.91

(t, J = 2.1 Hz, 1H), 8.50 (dd, J = 4.8, 1.5 Hz, 1H), 7.93 (ddt, J = 8.3, 2.8, 1.5 Hz, 1H), 7.37 (ddd,

25 J = 8.3, 4.8, 0.7 Hz, 1H), 2.86 (d, J = 1.6 Hz, 3H), 2.43 (s, 2H), 2.24 (s, 3H); EIMS m/z 206.

5-Bromo-N,3-dimethy1-1-(pyridin-3-y0-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: 'H NMR (400 MHz, CDCI 3) 6 8.86

(dd, J = 2.5, 0.5 Hz, 1H), 8.59 (dd, J = 4.8, 1.5 Hz, 1H), 7.88 (ddd, J = 8.2, 2.6, 1.5 Hz, 1H), 7.40

(ddd, J = 8.2, 4.8, 0.7 Hz, 1H), 2.85 (s, 3H), 2.69 (s, 1H), 2.35 (s, 3H); ESIMS m/z 268 ([M+Hr).

30 5-Chloro-N,3-dimethyl-1 -(pyridin-3-yI)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: 'H NMR (400 MHz, CDCI3) 6 8.87

(d, J = 2.3 Hz, 1H), 8.59 (dd, J = 4.8, 1.3 Hz, 1H), 7.90 (ddd, J = 8.2, 2.6, 1.5 Hz, 1H), 7.40

(ddd, J = 8.2, 4.8, 0.6 Hz, 1H), 2.87 (s, 3H), 2.45 - 2.19 (m, 4H); EIMS m/z 223.

3-Chloro-1-(5-fiuoropyridin-3-y1)-N-methy1-1H-pyrazol-4-amine was prepared from the

35 appropriate Boc-amine as described in Example 8, Method B: mp 117.5-119.0 °C; I H NMR (400

MHz, CDCI3) 6 8.68 (d, J = 1.1 Hz, 1H), 8.33 (d, J = 2.5 Hz, 1H), 7.75 (dt, J = 9.6, 2.4 Hz, 1H),

7.31 (s, 1H), 3.14(s, 1H), 2.87 (s, 3H); ESIMS mlz 227 (wr). 56

17149

3-Chloro-N-ethyl-1-(5-fiuoropyridin-3-y1)-1H-pyrazol-4-amine amine was prepared from

the appropriate Boc-amine as described in Example 8, Method B: 'H NMR (400 MHz, CDCI3) 6

8.70 — 8.63 (m, 1H), 8.32 (d, J= 2.4 Hz, 1E1), 7.74 (dt, J= 9.7, 2.4 Hz, 1H), 7.31 (s, 1H), 3.11 (q,

J= 7.2 Hz, 2H), 1.31 (t, J= 7.1 Hz, 3H).

5 1-(5-Fluoropyridin-3-0)-N-methyl-3-viny1-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: 105.0-107.0 °C; 'H NMR (400

MHz, CDCI3) 68.72 (s, 1H), 8.31 (d, J= 2.5 Hz, 1H), 7.81 (dt, J= 9.8, 2.4 Hz, 1H), 7.33(s, 1H),

6.75 (dd, J= 18.0, 11.6 Hz, 1H), 5.83 (dd, J= 18.0, 1.1 Hz, 1H), 5.46 (dd, J= 11.6, 1.1 Hz, 1H),

2.86 (s, 3H); ESIMS m/z 219 ([M+Hr).

10 3-Cyclopropy1-1-(5-fiuoropyridin-3-y1)-N-methy1-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described In Example 8, Method B: mp 118.0-119.5 °C; 'H NMR

(400 MHz, CDCI 3) 6 8.66 - 8.58 (m, 1H), 8.23 (d, J= 2.5 Hz, 1H), 7.75 - 7.68 (m, 1H), 7.25 (s,

1H), 3.09(s, 1H), 2.86 (s, 3H), 1.78- 1.63(m, 1H), 0.99- 0.90(m, 4H); ESIMS m/z 233

([M+Hr).

15 3-Chloro-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the appropriate Boc-

amine as described In Example 8, Method B: mp 137.9-139.9; 'H NMR (400 MHz, CDCI3) 6

8.84 (d, J= 2.4 Hz, 1H), 8.50 (dd, J= 4.7, 1.4 Hz, 1H), 7.95 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.52

(s, 1H), 7.37 (ddd, J= 8.4, 4.7, 0.7 Hz, 1H), 3.18 (s, 2H); ESIMS m/z 196 ([M+Hr).

2((3-Chloro-1-(pyridin-3-y0-1H-pyrazol-4-y0amino)acetonitrile was prepared from tert-

20 butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(cyanomethyl)carbamate as in Example 8,

Method B: mp 141-143 °C; 'H NMR (300 MHz, CDCI3) 68.91 (d, J= 2.7 Hz, 1H), 8.54 (dd, J=

5.1, 1.8 Hz, 1H), 7.97 (m, 1H), 7.62 (s, 1H), 7.38 (dd, J= 12.0, 7.5 Hz, 1H), 4.97 (d, J=6.9 Hz,

2H), 3.52 (m, 1H); EIMS m/z 235 atom. N-3-dimethy1-1-(pyrimidin-5-y1)-1H-pyrazol-4-amine was prepared as In Example 8,

25 Method B: mp 139-143 °C; 'H NMR (400 MHz, CDCI3) 69.02 (s, 2H), 9.00 (s, 1H), 7.30 (s, 1H),

2.87 (d, J= 11.5 Hz, 3H), 2.27 (s, 3H); ES1MS m/z 190 ([M+H1).

3-chloro-N-methy1-1-(pyrimidin-5-y01-1H-pyrazol-4-amine was prepared as In Example

8, Method B: mp 111-114 °C; 'H NMR (400 MHz, CDC13) 6 9.09 - 9.04 (m, 1H), 9.02 (s, 2H),

7.30 (s, 1H), 3.14 (bs, 1H), 2.88 (s, 3H); ESIMS m/z 196 ([M+H]).

30 1-(5-Fluoro-3-pyridy1)-3-methyl-N-(trideuterlomethyl)pyrazol-4-amine was prepared from

compound 380 using the procedure as described In Example 8, method B: mp 146-148 °C; 'H

NMR (400 MHz, CDCI3) 68.67 (s, 1H), 8.25 (d, J= 2.5 Hz, 1H), 7.73 (dt, J= 10.0, 2.3 Hz, 1H),

7.27 (s, 1H), 2.87 (s, 1H), 2.24 (s, 3H); ESIMS m/z 210 ([M+Hr); IR (Thin film) 1599 cm''.

3-Chloro-1-(3-pyridyI)-N-(trideuteriomethyl)pyrazol-4-amine was prepared from

35 compound 381 using the procedure as described In Example 8, method B: mp 104-106 °C; 'H

NMR (400 MHz, CD03) 6 8.87 (d, J= 1.9 Hz, 1H), 8.47 (d, J= 4.7 Hz, 1H), 8.00 - 7.90 (m, 1H),

7.40 - 7.30 (m, 2H), 3.10 (s, 1H); ESIMS m/z 212 ([M+Hr); IR (Thin film) 1579 cm'.

57

17149

3-Chloro-N-(cyclopropylmethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from

compound 361 using the procedure as described in Example 8, method B: mp 82-83 °C; 1 H

NMR (400 MHz, CDCI 3) 6 8.86 (d, J = 2.5 Hz, 1H), 8.47 (dd, J = 4.7, 1.3 Hz, 1H), 7.95 (ddd, J =

8.4, 2.7, 1.5 Hz, 1H), 7.38 — 7.32 (m, 2H), 3.22 (s, 1H), 2.90 (d, J = 6.9 Hz, 2H), 1.23— 1.06 (m,

5 1H), 0.65 — 0.53 (m, 2H), 0.31 —0.19 (m, 2H).; ESIMS m/z 249 ([M+Hr);

3-Chloro-N-propy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from compound

360 using the procedure as described In Example 8, method B: mp 92-94 °C; 1 H NMR (400

MHz, CDCI3) 6 8.86 (d, J = 2.6 Hz, 1H), 8.47 (dd, J = 4.7, 1.4 Hz, 1H), 7.95 (ddd, J = 8.3, 2.7,

1.5 Hz, 1H), 7.35 (ddd, J = 8.4, 4.7, 0.6 Hz, 1H), 7.33 (s, 1H), 3.22 - 2.94 (m, 3H), 1.75- 1.52

10 (m, 2H), 1.02(t, J = 7.4 Hz, 3H); ESIMS m/z 237 ([M+H]).

3-Chloro-1-(pyridin-3-y1)-N-(4,4,4-trifluorobuty1)-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described In Example 8, Method B: IR (thin film) 3416, 3089 crti l ;

1 H NMR (400 MHz, CDCI3) 6 8.86 (d, J = 2.5 Hz, 1H), 8.48 (dd, J = 4.7, 1.3 Hz, 1H), 7.95 (ddd,

J = 8.3, 2.7, 1.4 Hz, 1H), 7.42 - 7.31 (multiple peaks, 2H), 3.16 (dd, J = 13.0, 6.5 Hz, 2H), 3.08

15 (d, J = 5.6 Hz, 1H), 2.35 - 2.18 (m, 2H), 2.00 - 1.86 (m, 2H); ESIMS m/z 307 ([M+2H]).

3-Chloro-1-(pyridin-3-y1)-N-(5,5,5-trifluoropenty1)-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described In Example 8, Method B: IR (thin film) 3087 cm'; 1 H

NMR (400 MHz, CDCI3) 6 8.86 (d, J = 2.5 Hz, 1H), 8.48 (dd, J = 4.7, 1.4 Hz, 1H), 7.96 (ddd, J =

8.3, 2.7, 1.5 Hz, 1H), 7.36 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 7.34 (s, 1H), 3.10 (s, 2H), 3.04 (s, 1H),

20 2.30 — 1.98 (m, 2H), 1.84 — 1.69 (multiple peaks, 4H); 19F NMR (376 MHz, CDCI 3) 6-66.28;

ESIMS m/z 320 ([M+2Hr).

3-Chloro-N-(4-fluorobuty1)-1-(pyridin-3-y1)-1H-pyrazol-4-amlne was prepared from the

appropriate Boc-amine as described in Example 8, Method B: mp 82-83 °C; IR (thin film) 3348,

3086 cm -1 ; 1 H NMR (400 MHz, CDCI3) 68.86 (d, J= 2.5 Hz, 1H), 8.47 (dd, J= 4.7, 1.4 Hz, 1H),

25 7.95 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.38 - 7.33 (multiple peaks, 2H), 4.58 (t, J= 5.7 Hz, 1H),

4.50 - 4.42 (m, 1H), 3.11 (multiple peaks, 3H), 1.90- 1.76 (multiple peaks, 4H); ESNS ink 269

([M+H]).

3-Chloro-N-lsopropy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3318, 1583 cal l ; 1 H

30 NMR (400 MHz, CDCI3) 58.86 (d, J = 2.7 Hz, 1H), 8.47 (dd, J= 4.7, 1.4 Hz, 1H), 7.96 (ddd, J=

8.4, 2.7, 1.5 Hz, 1H), 7.36 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 7.31 (s, 1H), 2.87 (d, J = 6.8 Hz, 2H),

1.92 (dq, J= 13.4, 6.7 Hz, 1H), 1.02(d, J= 6.7 Hz, 6H); ESIMS m/z 251 ([M+H]).

3-Chloro-N-(2-methoxyethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3364, 1485 crti l ; 1 H

35 NMR (400 MHz, CDCI3) 68.86 (dd, J= 2.7, 0.7 Hz, 1H), 8.48 (dd, J = 4.7, 1.5 Hz, 1H), 7.96

(ddd, J = 8.4, 2.7, 1.5 Hz, 1H), 7.38 (s, 1H), 7.38 — 7.34 (m, 1H), 3.68 — 3.59 (m, 2H), 3.49 (s,

1H), 3.42 (s, 3H), 3.24(d, J = 7.3 Hz, 2H); ESIMS m/z 253 ([M+H]).

58

17149

3-Chloro-N-02,2-difiuorocyclopropyOmethy9-1-(pyridin-3-y9-1H-pyrazol-4-amine was

prepared from the appropriate Boc-amine as described In Example 8, Method B: 'H NMR (400

MHz, CDCI3) 6 8.87 (d, J= 2.6 Hz, 1H), 8.49 (dd, J= 4.7, 1.5 Hz, 1H), 7.96 (ddd, J= 8.4, 2.7,

1.4 Hz, 1H), 7.41 (s, 1H), 7.37 (ddd, J= 8.3, 4.7, 0.7 Hz, 1H), 3.19 (td, J= 15.5, 13.0, 6.8 Hz,

5 2H), 2.00- 1.84 (m, 1H), 1.55 (m, 1H), 1.26 (s, 1H), 1.23- 1.11 (m, 1H); 19F NMR (376 MHz,

CDCI3) 6-128.61 (d, J= 159.5 Hz), -143.58 (d, J= 160.0 Hz); ESIMS m/z 285 ([M+H] . ).

3-Chloro-N-(3-fluoropropy1)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3359 cm -1 ; 1 11 NMR

(400 MHz, CDC13) 6 8.87 (d, J= 2.7 Hz, 1H), 8.48 (dd, J= 4.7, 1.4 Hz, 1H), 7.95 (ddd, J= 8.3,

10 2.6, 1.4 Hz, 1H), 7.39- 7.34 (multiple peaks, 2H), 4.63 (dt, J= 47.2, 5.6 Hz, 2H), 3.25 (t, J= 6.7

Hz, 2H), 3.18 (br s, 1H), 2.17- 1.92 (m, 2H); ESIMS m/z 255 ([M+H]+ ).

N-ally1-3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the appropriate

Boc-amine as described In Example 8, Method B: IR (thin film) 3291 cm -1 ; I FINMR (400 MHz,

CDCI3) 68.85 (d, J= 2.6 Hz, 1H), 8.48 (dd, J= 4.8, 1.5 Hz, 1H), 7.95 (ddd, J= 8.3, 2.7, 1.4 Hz,

15 1H), 7.38- 7.35(m, 1H), 7.34 (s, 1H), 5.97 (ddt, J= 17.3, 10.6, 5.5 Hz, 1H), 5.34 (dq, J= 17.2,

1.6 Hz, 1H), 5.23 (dq, J= 10.3, 1.5 Hz, 1H), 3.73 (dt, J= 5.5, 1.6 Hz, 2H), 3.25(s, 1H); ESIMS

m/z 235 ([1■4+113').

2((3-Chloro-1-(pyridin-3-y1)-1H-pyrazol-4-ypamino)ethyl acetate was prepared from the

appropriate Boc-amlne as described in Example 8, Method B: IR (thin film) 3361, 1733 cm -1 ; 1 H

20 NMR (400 MHz, CDC13) 6 8.87 (s, 1H), 8.49 (d, J= 4.7 Hz, 1H), 7.96 (ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.43 (s, 1H), 7.37 (dd, J= 8.4, 4.7 Hz, 1H), 4.30 (dd, J= 5.9, 4.8 Hz, 2H), 3.34 (t, J= 5.5

Hz, 2H), 2.12 (s, 3H), 1.59 (s, 1H); ESIMS m/z 281 ([M+H]).

3-Chloro-N-(2-fiuoroethyl)-14pyridin-3-y1)-1H-pyrazol-4-arnine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3369 cm -1 ; I FI NMR

25 (400 MHz, CDCI3) 68.86 (d, J= 2.7 Hz, 1H), 8.49 (dd, J= 4.7, 1.4 Hz, 1H), 7.96 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.40(s, 1H), 7.37 (dd, J= 8.3, 4.7 Hz, 1H), 4.82- 4.53(m, 2H), 3.54 - 3.27

(multiple peaks, 3H); ESIMS m/z 241 ([M+Hr).

3-Chloro-1-(pyridin-3-y1)-N-(2-(pyrrolidin-1-ypethyl)-1H-pyrazol-4-amine was prepared

from the appropriate Boc-amine as described In Example 8, Method B: ESIMS m/z 292

30 ([M+Fli+ ).

3-Chloro-N-(2,2-difluoroethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described In Example 8, Method B: IR (thin film) 3295 cm 4 ; I FI NMR

(400 MHz, CDCI3) 68.87 (dd, J= 2.8, 0.7 Hz, 1H), 8.51 (dd, J= 4.7, 1.4 Hz, 1H), 7.95 (ddd, J=

8.4, 2.7, 1.5 Hz, 1H), 7.45 (s, 1H), 7.37 (ddd, J= 8.5, 4.7, 0.8 Hz, 1H), 5.96 (11, J= 55.9, 4.1 Hz,

35 1H), 3.69 - 3.26 (multiple peaks, 3H); 19F NMR (376 MHz, CDCI3) 6-122.15; ESIMS m/z 259

([M+1-1]+ ).

59

17149

3-Chloro-1-(pyridin-3-y1)-N-(2,2,2-trifluoroethyl)-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3309 cm''; 'H

NMR (400 MHz, CDCI3) 6 8.92 - 8.85 (m, 1H), 8.52 (dd, J = 4.8, 1.4 Hz, 1H), 7.98 (ddd, J = 8.4,

2.7, 1.5 Hz, 1H), 7.47(s, 1H), 7.40 (ddd, J = 8.4, 4.8, 0.7 Hz, 1H), 3.68 (q, J = 8.9 Hz, 2H), 3.49

5 (s, 1H); 19F NMR (376 MHz, CDCI3) 6-72.29; ESIMS tit& 277 ([M+Hr).

3-Chloro-N-(2-chloroethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3354 cm -'; 'H NMR

(400 MHz, CDCI3) 6 8.86 (dd, J = 2.7, 0.7 Hz, 1H), 8.50 (dd, J = 4.8, 1.5 Hz, 1H), 7.96 (ddd, J =

8.3, 2.7, 1.4 Hz, 1H), 7.40 (s, 1H), 7.37 (ddd, J = 8.5, 4.8, 0.8 Hz, 1H), 3.76 (dd, J = 6.0, 5.4 Hz,

10 2H), 3.54 (s, 1H), 3.43 (t, J = 5.7 Hz, 2H); ESIMS m/z 257 ([M+Hr).

3-Chloro-1-(pyridin-3-y1)-N-(3,3,3-trifluoropropy1)-1H-pyrazol-4-amine was prepared from

the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3366, 3081 ari l ;

'H NMR (400 MHz, CDCI3) 6 8.87 (dd, J = 2.6, 0.7 Hz, 1H), 8.50 (dd, J = 4.7, 1.4 Hz, 1H), 7.96

(ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.40- 7.35 (multiple peaks, 2H), 3.38 (q, J= 6.8 Hz, 214 3.22 (t,

15 J = 6.7 Hz, 1H), 2.48 (qt, J = 10.7, 7.0 Hz, 2H); F NMR (376 MHz, CDCI3) 6-64.99; ESIMS

m/z 291 ([M+Hr).

N-(but-2-yn-1-y1)-3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

appropriate Boc-amine as described In Example 8, Method B: IR (thin film) 3249, 3122 cm''; 'H

NMR (400 MHz, CDCI 3) 6 8.89 (dd, J = 2.7, 0.7 Hz, 1H), 8.49 (dd, J = 4.8, 1.5 Hz, 1H), 7.98

20

(ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.50 (s, 1H), 7.37 (ddd, J = 8.4, 4.8, 0.8 Hz, 1H), 3.93 - 3.68 (m,

2H), 3.33 (s, 1H), 1.83 (t, J= 2.4 Hz, 3H); ESIMS m/z 247 ([M+Hr).

3-Chloro-N-isobuty1-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as In Example 8,

Method B: 'H NMR (400 MHz, CDCI 3) 68.86 (d, J = 2.5 Hz, 1H), 8.47 (dd, J = 4.7, 1.3 Hz, 1H),

7.95 (ddd, J = 8.4, 2.7, 1.5 Hz, 1H), 7.35 (ddd, J = 8.3, 4.7, 0.6 Hz, 1H), 7.31 (s, 1H), 3.11(bs,

25

1H), 2.87 (t, J = 6.5 Hz, 2H), 1.93 (dp, J = 13.4, 6.7 Hz, 1H), 1.01(d, J = 6.7 Hz, 6H).

Example 9: Preparation of Isopropyl-(1-pyriclin-3-y1-1H-pyrazol-4-y1)-amlne

1-pyridin-3-y1-1H-pyrazol-4-ylamine (0.6 g, 3.7 mmol) was dissolved in isopropyl acetate

(8.5 mL). To the mixture, acetone (0.261 g, 4.5 mmol), trifluoroacetic acid (0.855 g, 7.5 mmol)

30 and sodium triacetoxyborohydride (0.945 g, 4.5 mmol) were added. The reaction was stirred

under nitrogen at room temperature for 4.5 hours and then quenched with 10% sodium

hydroxide solution until the pH reached — 9. The layers were separated, and the aqueous phase

was extracted with ethyl acetate. The organic extracts were combined, dried over sodium

sulfate and concentrated to dryness. The crude material was purified by silica gel

60

17149

chromatography (gradient elution of 5% methanol/dichloromethane) to give the title compound

as an off white solid (0.35g. 46%): mp 105- 107 °C; 1 H NMR (300 MHz, CDCI3)15 8.82 (d, J=

2.2 Hz, 1H), 8.63 (dd, J= 4.8, 1.5 Hz, 1H), 8.13 (d, J= 1.8 Hz, 1H), 8.03 (d, J= 2.7 Hz, 1H),

7.94 - 7.77 (m, 1H), 7.38 (dt, J= 15.2, 7.6 Hz, 1H), 6.99(t, 1H), 3.72 (m, 1H), 1.30(t, J= 10.0

5 Hz,6H). ESIMS 214 m/z (M+1).

Example 10: Preparation of propyl-(1-pyrldin-311-1H-pyrazol-4-yi-amine

,H 0,N../R

I

To 1-pyridin-3-y1-1H-pyrazol-4-ylamine (0.5 g, 3.12 mmol) In dichloromethane (5 mL)

was added propionaIdehyde (0.18g. 3.12 mmol) and sodium triacetoxy borohydride (0.99g.

10 4.68 mmol) and stirred at room temperature for 16 hours. The reaction was taken up In

dichloromethane and was washed with water and brine. The organic layer was dried (MgSO4),

filtered and concentrated to dryness. The crude material was purified by silica gel

chromatography eluting with 0-5% Me0H/Dichloromethane and resubjected In 0-100%

ethylacetate/hexanes) to give the title compound as a dark oil (0.05g. 7%): 1 H NMR (300 MHz,

15 CDCI3) 5 8.92 (d, J= 2.6 Hz, 1H), 8.48 (dd,J= 4.7, 1.4 Hz, 1H), 8.00 (ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.47 - 7.40 (m, 2H), 7.37 (dd, J= 8.3, 4.7 Hz, 1H), 3.04 (t, J= 7.1 Hz, 3H), 1.92 - 1.46 (m,

2H), 1.03 (t, J= 7.4 Hz, 3H).

Example 11: Preparation of N-methyl-N-(1-pyridin-3-y1-1H-pyrazol-4-y1)-isobutyramIde

(Compound 42)

20 N

A solution of isobutyryl chloride (0.138g. 1.3 mmol) in dichloroethane (1 mL) was pipetted at a

dropwise rate Into an Ice-cold suspension of methyl-(1-pyridin-3-y1-1H-pyrazol.4y1)-amine (0.15

g, 0.86 mmol) in dichloroethane (5 mL), stirred for 10 minutes and then treated at a dropwise

rate with a solution of 4-N,N-dimethylaminopyridine (0.11 g, 0.9 mmol) in dichloroethane (1.5

25 mL). The cooling bath was removed after 30 minutes, stirred under nitrogen at room

temperature for 14 hours, diluted with dichloroethane (40 mL), washed with water (30 mL), brine

(10 rut), dried over MgSO 4 and purified by reversed phase column chromatography to give a

yellowish gum (0.114g. 54%) 1 11 NMR (300 MHz, CDCI3) 5 9.01-8.93(m, 1H), 8.67 (s, 0.4H),

8.61 (d, J= 4.2 Hz, 0.6H), 8.54(d, 0.4H), 8.08-8.02 (m, 1H), 7.96 (s, 0.6H), 7.80 (s, 0.4H), 7.70

30

(s, 0.6H), 7.47-7.37 (m, 1H), 3.49 (s, 1.2H), 3.26 (s, 2.8H), 3.06-2.98 (m, 0.4H), 2.86 - 2.70 (m,

0.6H), 1.25 (d, J= 6.1 Hz, 2.4H), 1.09 (d, J= 6.6 Hz, 3.6H). ESIMS m/z 245 ([M+1]).

II

61

17149

Compounds 32 - 41, 43 - 52, 54 - 56, 59-61, 66, 73 - 75, 77 - 79, 82 - 85, 93 - 100,

113, 117 - 129, 131 - 134, 139-140, 142 - 144, 148, 160, 163, 173 - 175, 184 - 186, 197-198,

202, 208, 215-217, 252-253, 277, 282 - 285, 287 - 290, 314 - 316, 347, 350-351, 353 - 355,

365- 367, 370, 388, 395, 399 -403, 407, 409, 415- 418, 444-449, 452 -454, 462 - 463, 465,

5 467 - 469, 496 - 498, 506 - 507, 512, 525 - 527, 569, 577, 581, 591 and 592 were made from

the appropriate amines In accordance with the procedures disclosed in Example 11.

Example 12: Preparation of 4,4,4-trifluoro-2-methyl-N-(1-(pyridin-3-y1)-1H-pyrazol-4-

yi)butanamide (Compound 65)

1H), 2.92 - 2.61 (m, 2H), 2.32 - 2.05 (m, 1H), 1.38 (d, J = 6.6 Hz, 3H); ESIMS ink 300 ([M+2]).

Compounds 53, 58, 62-63, 72, 76, 80 - 81, 107 - 108, 136 - 138, 147, 151 - 159, 164 -

20 168, 176- 179, 187 -196, 201, 203 - 207, 209 - 214, 220, 224 - 249, 251, 259 - 275, 286,

292 - 296, 303 - 313, 323 - 326, 341 - 344, 356- 359, 371, 378 - 379, 382, 384, 419 - 426,

439 -443, 455, 458 - 461, 464, 466, 476, 486, 490 - 493, 505, 508, 517, 528 - 529, 536- 537,

Method A:

To a solution of 1-(pyridin-3-yI)-1H-pyrazol-4-amine (3 g, 18.73 mmol) in

30 dichloromethane (33.4 mL) was added triethylamine (3.13 mL, 7.68 mmol) and BOC-anhydride

Method A:

To a solution of 1-(pyridin-3-yI)-1H-pyrazol-4-amine (3 g, 18.73 mmol) in

30 dichloromethane (33.4 mL) was added triethylamine (3.13 mL, 7.68 mmol) and BOC-anhydride

2

,N-dimethylaminopyridine (0.23g, 1.87 mmol) followed by 1-(3-dimethylaminopropyI)-3-

ethylcarbodiimide hydrochloride (0.369, 1.87 mmol). The reaction stirred at room temperature

overnight. The reaction mixture was concentrated and the crude product was purified by silica

15 gel chromatography eluting with 0-5% Me0H/dichloromethane to give a white solid (0.159,

55%); mp 140-145°C; I HNMR (400 MHz, CDCI3) 69.00 (d, J= 2.4 Hz, 1H), 8.62 - 8.47 (m, 2H),

8.01 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.68 (s, 1H), 7.53 (bs, 1H), 7.40 (ddd, J = 8.3, 4.8, 0.6 Hz,

539-MI, 544 - 545, 549 - 554, 572 - 577, 578, 579 and 580 were prepared from the

appropriate amines In accordance with the procedures disclosed In Example 12.

25 Example 13: Preparation of tert-butyl 1-(pyridin-3-y1)-1H-pyrazol-4-ylearbamate

(Compound 57)

62

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(4.5 g, 20.60 mmol). The resulting solution was stirred at room temperature overnight. The

reaction mixture was partitioned between ethyl acetate and water. The organic portion was dried

(MgSO4), filtered and concentrated to dryness. The crude product was purified by silica gel

chromatography eluting with 0-100% ethyl acetate/hexanes to yield a white solid (2.0 g, 41%);

5 mp 108 — 112 °C; 1 H NMR (400 MHz, CDCI3) 59.02 (d, J = 2.2 Hz, 1H), 8.51 (t, J = 8.7 Hz, 1H),

8.37 (s, 1H), 8.30 (s, 1H), 7.98 (ddd, J = 8.3, 2.4, 1.3 Hz, 1H), 7.68 (s, 1H), 7.36 (dd, J= 8.2, 4.8

Hz, 1H), 1.52 (s, 9H); ESIMS ink 261 ([M+1]).

Compounds 64 and 130 were prepared In accordance with the procedures disclosed In

Example 13, Method A.

10 Method B:

To a solution of 1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.1 g, 0.624 mmol) and di-tert-butyl

dicarbonate (0.161 mL, 0.693 mmoI) In tetrahydrofuran (1.890 mL) and water (0.568 mL) was

added dropwise saturated aqueous sodium bicarbonate (0.572 mL, 0.687 mmol). The reaction

was stirred at room temperature overnight. The reaction was diluted with water and extracted

15 with ethyl acetate. The combined organic phases were concentrate to give tert-butyl 1-(pyridin-

3-y1)-1H-pyrazol-4-ylcarbamate (135 mg, 0.519 mmol, 83%), for which the analytical data was

consistent with that reported In Example 13, Method A.

Compounds 150, 172, 223, and 317 were prepared in accordance with the procedures

disclosed in Example 13, Method B. Compound 172 and 317 was also prepared in accordance

20 with the procedures disclosed In Example 17. These compounds, as well as, certain other

compounds, were made by altemative methods further illustrating certain embodiments.

Example 14: Preparation of fert-butyl methyl(1-(pyrklin-3-y1)-1H-pyrazol-4-yucarbamate

(Compound 67)

25 To a solution of tert-butyl 1-(pyridin-3-y1)-1H-pyrazol-4-ylcarbamate (1.6 g, 6.15 mmol) in

DMF (30.7 mL) at 0°C was added sodium hydride (0.34g. 8.61 mmol, 60% dispersion in

mineral oil) In one portion and the suspension was stirred for 30 minutes. The Ice bath was

removed and stirred for an additional 30 minutes. lodomethane (0.46 mL, 7.38 mmol) was

added In one portion and stirred overnight at room temperature. Water and ethyl acetate were

30 added and the resulting biphasic mixture was separated. The aqueous layer was extracted one

time with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO 4),

filtered and concentrated to dryness. The crude product was purified by silica gel

chromatography eluting with 0-35% ethyl acetate/hexanes to yield a light yellow semi-solid (0.85

g, 50%): IR (KBr) 1703 cm' l ; 1 11 NMR(400 MHz, CDCI 3) §8.98 (s, 1H), 8.52 (d, J = 3.8 Hz, 1H),

63

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8.32 (s, 0.5H), 8.13 - 7.97 (m, 1H), 7.84 (s, 0.5H), 7.74 (s, 1H), 7.39 (dd, J = 8.0, 4.8 Hz, 1H),

3.30 (s, 3H), 1.56 (s, 9H); ESIMS m/z 275 ([M+H]).

Compounds 68, 86 — 92, 105 - 106, 114 — 116, 141, 149, 161 - 162, 199 - 200, 254,

258, 291, 332, 352, 360 - 361, 380 - 381, 414, 430 -431, 450, 457, 474 - 475, 485, 488, 510 -

5 511, 515, 523, and 590 were prepared from the appropriate amides in accordance with the

procedures disclosed In Example 14.

Tert-butyl methyl(3-methy1-1-(pyridin-3-y1)-1H-pyrazol-4-y9carbamate was prepared as

in Example 14: 1 H NMR (400 MHz, CDCI3) 58.91 (d, J = 2.5 Hz, 1H), 8.51 (dd, J = 4.7, 1.3 Hz,

11-1), 8.00 (ddd, J = 8.3, 2.4, 1.4 Hz, 1H), 7.83 (s, 1H), 7.38 (dd, J = 8.3, 4.7 Hz, 1H), 3.20 (s,

10 3H), 2.22(s, 3H), 1.60 - 1.30 (m, 9H).

Example 15: Preparation of N-ethyl-N-(1-methyl-3-(pyridin-3-y1)-1H-pyrazol-5-

y1)1sobutyramide (Compound 23)

To a solution of N-(1-methy1-3-(pyridine-3-y9-1H-pyrazol-5-y9isobutyramide (0.089, 0.33

15 mmol) In DMF (0.66 mL) at 0°C was added sodium hydride (0.016 g, 0.39 mmol, 60%

dispersion in mineral oil) in one portion and the suspension was stirred for 30 minutes. The ice

bath was removed and stirred for an additional 30 minutes. lodoethane (0.06 g, 0.39 mmol) was

added In one portion and stirred overnight at room temperature. Water and ethyl acetate were

added and the resulting biphasic mixture was separated. The aqueous layer was extracted one

20 time with ethyl acetate. The combined organic extracts were washed with brine, dried (Mg504),


chromatography to give the title compound as a clear oil (27.5 mg, 30%): 1 H NMR (300 MHz,

CDCI3) 59.00 (bs, 1H), 8.57 (s, 1H), 8.09 (dd, J = 7.9 Hz, 1H), 7.34 (dd, 1H), 6.48(s, 11-9, 4.00

(m, 1H), 3.76 (s, 3H), 3.36 (m, 1H), 2.33 (m, 1H), 1.17 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 6.7 Hz,

25 6H); ESIMS m/z 273 (M+H).

Compound 22 was prepared in accordance with the procedures disclosed in Example

15.

Example 16: Preparation of 5-bromo-1H-pyrazol-4-amine, HBr

Br

HN N -

30 A mixture of 4-nitro-1H-pyrazole (10 g, 88 mmol) and 5% palladium on Al 203 (1 g) in a

mixture of ethanol (150 mL) and 50% aqueous HBr (50 ml..) was shaken In a Par apparatus

under hydrogen (10 psi) for 36 h. The mixture was filtered and the catalyst washed with ethanol.

NH2 .HBr

64

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1 The filtrate was concentrated In vacua to give a white solid. This solid was suspended In 10 mL

of ethanol. After swirling the flask for 5 mm, diethyl ether was added to complete the

crystallization. The solid was filtered, was washed with ether and dried under high vacuum to

afford 5-bromo-1H-pyrazol-4-amine, HBr (18.1 g, 84% yield) as a white solid: mp 24800 dec;

5 I H NMR (400 MHz, DMSO48) 6 11.47 (s, 1H), 10.00 (s, 1H), 7.79 (s, 1H).

Example 17: Preparation of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-yl)carbamate

(Compound 172)

Example 17, Step 1: Preparation of 3-chloro-1H-pyrazol-4-amine hydrochloride

CI

N NH Ha

H2 N

10 Into a 2 L three-necked round bottom flask affixed with an overhead stirrer, a

temperature probe, an addition funnel, and a nitrogen Inlet were added ethanol (600 mL) and 4-

nitro-1H-pyrazole (50.6g. 447 mmol). To this solution was added, In one portion, conc. HO (368

mL) (note: rapid exotherm from 15 00 to 39 00) and the resulting mixture was purged with

nitrogen for 5 minutes. Palladium on alumina (5%w/w) (2,6 g, Alfa, black solid) was added to the

15 mixture and stirred at room temperature while triethylsilane (2089, 1789 mmol) was added

drop-wise over 4 h. The reaction, which started to slowly exotherm from 35 00 to 55 00 over 2.0

h, was stirred for a total of 16 h and vacuum filtered through a plug of Celite ® to give a biphasic

mixture. The mixture was transferred to a separatory funnel, the bottom aqueous layer was

collected and rotary evaporated (60 00, 50 mmHg) to dryness with the aid of acetonitrile (3 x

20 350 mL). The resulting yellow solid was suspended in acetonitrile (150 mL) and allowed to stand

for 2 h at room temperature followed by 1 h at 0 00 in the refrigerator. The solids were filtered

and washed with acetonitrile (100 mL) to afford the titled compound 3-chloro-1H-pyrazol-4-

amine hydrochloride (84g. 97% yield, 80% purity) as a white solid: mp 190-193 °C; I H NMR

(400 MHz, DMSO-d8) 6 10.46 -10.24 ( bs, 2H), 8.03 (s, 0.54H), 7.75 (s, 0.46H), 5.95 (bs, 1H));

25 13C-NMR (101 MHz, DMSO) 6 128.24, 125.97, 116.71.

Example 17, Step 2: Preparation of tert-butyl (3-chloro-1H-pyrazol-1/21)carbamate

CI N 'NH

FIN

CrLO

+-

Into a 2 L round bottom flask was added 3-chloro-1H-pyrazol-4-amine hydrochloride

(100g. 649 mmol) and THF (500 mL). To this mixture were added di-ted-butyldicarbonate (156

g, 714 mmol) followed by sodium bicarbonate (1209, 1429 mmol) and water (50.0 ml). The

30 mixture was stirred for 16 h, diluted with water (500 mL) and ethyl acetate (500 mL) and

65

17149

transferred to a separatory funnel. This gave three layers; bottom- a white gelatinous

precipitate, middle- light yellow aqueous, top- auburn organic. The phases were separated

collecting the white gelatinous precipitate and the aqueous layer together. The aqueous was

extracted with ethyl acetate (2 x 200 mL) and the ethyl acetate extracts were combined, washed

5 with brine (200 mL), dried over anhydrous sodium sulfate, filtered and rotary evaporated to give

an auburn thick oil (160 g.). The thick oil was suspended in hexane (1000 mL) and stirred at 55

oC for 2 h. This gave a light brown suspension. The mixture was cooled to 0 0C and the solid

collected by vacuum filtration and rinsed with hexane (2 x 10 mL). The sample was air dried to

constant mass to afford (3-chloro-1H-pyrazol-4-yl)carbamate (102.97g. 72% yield, 80% purity)

10

as a light brown solid: mp 137-138 °C; 1 H NMR (400 MHz, CDCI3) 5 10.69 (s, 1H), 7.91 (s, 1H),

1.52 (s, 9H).

Example 17, Step 3: Preparation of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

yl)carbamate (Compound 172)

15 To a dry 2 L round bottom flask equipped with mechanical stirrer, nitrogen Inlet,

thermometer, and reflux condenser was charged the 3-lodopyridine (113.0 g, 551 mmol), (3-

chloro-1H-pyrazol-4-yOcarbamate (100g. 459 mmol), potassium phosphate (powdered in a

mortar and pestle) (195g, 919 mmol), and copper chloride (3.09, 22.97 mmol). Acetonitrile (1 L)

followed by M,AP-dimethylethane-1,2-diamine (101 g,1149 mmol) were added and the mixture

20 was heated to 81 °C for 4 hours. The mixture was cooled to room temperature and filtered

through a bed of Celite ®. The filtrate was transferred to a 4 L Erlenmeyer flask equipped with

mechanical stirrer and diluted with water until the total volume was about 4 L. The mixture was

stirred for 30 minutes at room temperature and the resulting solid was collected by vacuum

filtration. The solid was washed with water and washed with water and oven dried for several

25 days In vacua at 40°C to a constant weight to give tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-

pyrazol-4-yl)carbamate (117.8g. 87% yield, 80% purity) as a tan solid: mp 140-143 °C; 1 H NMR

(400 MHz, CDCI3) 6 8.96 (s, 1H), 8.53 (dd, J= 4.7, 1.2 Hz, 1H), 8.36 (s, 1H), 7.98 (ddd, J = 8.3,

2.7, 1.4 Hz, 1H), 7.38 (dd, J = 8.3, 4.8 Hz, 1H), 6.37 (s, 1H), 1.54 (s, 9H); ESIMS (m/z) 338 (IM-

t-Bur), 220 ([M-0-t-Bu]).

30 Compound 172 was also prepared in accordance with the procedures disclosed in

Example 13. Compound 317 was prepared In accordance with the procedures disclosed In

Example 17 from tert-butyl (3-bromo-1H-pyrazol-4-yOcarbamate and also In accordance with the

procedures disclosed in Example 13.

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Example 18: Preparation of 3-(3-methy1-1H-pyrazol-1-yl)pyridine and 315-methyl-IN-

pyrazol-1-yi)pyridine

N

To a solution of 3-methyl-1H-pyrazole (10.99g. 134 mmol) in N,N-dimethylformamide

5 (100 ml) at 0 °C was added sodium hydride (3.71 g, 154 mmol, 60% dispersion). The reaction

was stirred at 0 °C for 2 hours. 3-Fluoropyridine (10.0g. 103 mmol) was added, and the

reaction was stirred at 100 °C overnight. The reaction was cooled to room temperature and

water was added slowly. The mixture was extracted with dichloromethane and the combined

organic phases were washed with brine, concentrated and chromatographed (0-100% ethyl

10 acetate/hexanes) to afford 3-(3-methyl-1H-pyrazol-1-yl)pyridine (8.4g, 52.77 mmol, 51.2%) and

3-(5-methyl-1H-pyrazol-1-y1)pyridine (1.0 g, 6%). Analytical data of both products is consistent

with that reported under Example 6, Step 1.

3-(3-Bromo-1H-pyrazol-1-yOpyridine was prepared from 3-fluoropyridine and 3-

bromopyrazole, which was made as in W02008130021, as described Example 18: mp 89.5-

15 92.5 °C; 1 H NMR (400 MHz, CDCI3) 6 8.94 (d, J= 2.4 Hz, 1H), 8.62 - 8.49 (m, 1H), 8.03 (ddd, J

= 8.3, 2.7, 1.4 Hz, 1H), 7.87 (d, J=2.5 Hz, 1H), 7.42 (dd, J= 8.2, 4.7 Hz, 1H), 6.54 (d, J=2.5

Hz, 1H); ESIMS ink 224 pin

Example 19, Preparation of 3-chloro-1-(5-fluoropyrldin-3-y1)-1H-pyrazol-4-amine

Cl

NH2

N

20 To a stirred solution of 5-chloro-1H-pyrazol-4-amine, HCI (2 g, 12.99 mmol) and cesium

carbonate (8.899, 27.3 mmol) in DMF (13 ml..) was added 3,5-difluoropyridine (1.794 g, 15.58

mmol) and the mixture heated at 70 °C for 12 h. The mixture was cooled to room temperature

and filtered. The solids were washed with copious amount of ethyl acetate. The filtrates was

washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo to give a brown

25 solid. This solid was dissolved In ethyl acetate and the resulting solution was saturated with

hexanes to precipitate 3-chloro-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-amine (2.31g, 10.32 mmol,

79% yield) as a brown solid: 1 H NMR (400 MHz, DMSO-d6) 6 8.89 - 8.82(m, 1H), 8.45 (d, J=

2.5 Hz, 1H), 8.07 (d, J= 10.4 Hz, 1H), 7.94 (s, 1H), 4.51 (s, 2H); EIMS (m/z) 213 ([MO]+).

3-Bromo-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-amine was prepared from the

30 corresponding pyrazole as described in Example 19: mp 164-165 °C; 1 H NMR (400 MHz,

CDCI3) 68.65 (d, J= 1.7 Hz, 1H), 8.36 (d, J= 2.5 Hz, 1H), 7.76 (dd, J= 5.9, 3.6 Hz, 1H), 7.48 67

17149

(s, 1H), 3.22 (s, 2H). "C NMR (101 MHz, CDCI3) 6 160.87, 158.30, 135.36, 135.13, 134.39,

134.35, 131.16, 123.31, 114.02, 112.77, 112.54; EIMS (m/z) 258 ((M+11+).

Example 20: Preparation of 1-(5-fluoropyrldin-3-y1)-3-methyl-1H-pyrazo14-amlne

NH2

5 To a solution of 3-fluoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yOpyridine (3.133g. 14.10

mmoI) In ethanol (28.2 ml) was added ethyl acetate until all of the starting material went into

solution. The solution was degassed and 10% palladium on carbon (0.750g, 0.705 mmol) was

added and the reaction was stirred in a parr hydrogenator at 40 psi for 3 hours. The solution

was filtered through celite with ethyl acetate and concentrated to give 1-(5-fiuoropyridin-3-yI)-3-

10 methyl-1H-pyrazol-4-amine (2.000 g, 10.41 mmol, 73.8%) as a brown solid: mp 136.0-138.0°C;

1 H NMR (400 MHz, CDCI3) 6 8.67 - 8.59 (m, 1H), 8.27 (d, J = 2.5 Hz, 1H), 7.73 (dt, J = 9.9, 2.3

Hz, 1H), 7.45 (s, 1H), 3.01 (s, 2H), 2.28 (s, 3H); EIMS m/z 192.

1-(Pyridin-3-y1)-3-(trifluoromethyl)-1H-pyrazol-4-amine was prepared from the

appropriate nitropyrazole as described in Example 20: mp 112.5-115.0 °C; 1 H NMR (400 MHz,

15 CDCI3) 68.89 (d, J = 2.4 Hz, 1H), 8.57 (dd, J = 4.7, 1.4 Hz, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz,

1H), 7.56 (d, J = 0.7 Hz, 1H), 7.41 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 3.47 - 3.31 (m, 2H); EIMS m/z

228.

Example 21: Preparation of 3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-amine

Cl

N 2

20 To 3-(3-chloro-4-nitro-1H-pyrazol-1-y9pyridine (0.95g. 4,23 mmol) in acetic acid (8.46

mL), ethanol (8.46 mL) and water (4.23 mL) was added iron powder (1.18g. 21.15 mmol) and

the reaction was stirred at room temperature for 30 minutes. To this was added carefully 2 M

KOH and extracted with ethyl acetate. The ethyl acetate layers were combined, dried (MgSO4),


25 chromatography (0-10% methanoVdichloromethane) to give the desired product as a white solid

(0.66g. 80%): 1 H NMR (400 MHz, CDCI3) 6 8.84 (d, J = 2.6 Hz, 1H), 8.49 (dd, J = 4.7, 1.4 Hz,

1H), 7.95 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.53 (s, 1H), 7.37 (ddd, J = 8.4, 4.7, 0.6 Hz, 1H), 3.17

(bs, 2H).

3-methyl-1-(2-methylpyridin-3-yI)-1H-pyrazol-4-amine was prepared as described In

30 Example 21: 1 H NMR (400 MHz, CDCI3) 6 8.48 (dd, J = 4.8, 1.6 Hz, 1H), 7.62 (dd, J = 8.0, 1.6

Hz, 1H), 7.23 - 7.18 (m, 2H), 2.91 (bs, 2H), 2.55 (s, 3H), 2.28 (s, 3H); EIMS m/z 188.

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17149

3-Phenyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared from the appropriate

nitropyrazole as described in Example 21: IR (thin film) 3324 ari l ; I FINMR (400 MHz, CDCI3) 6

8.94 (d, J = 2.2 Hz, 1H), 8.47 (dd, J = 4.7, 1.4 Hz, 1H), 8.07 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.87

-7.80 (m, 2H), 7.60 (s, 1H), 7.50 - 7.44 (m, 2H), 7.40 - 7.34 (m, 2H), 3.86 (s, 2H); EIMS m/z

5 236.

3-Chloro-1-(5-fiuoropyridin-3-y1)-1H-pyrazol-4-amine was prepared from the appropriate

nitropyrazole as described In Example 21: mp 149.0-151.0 °C; I FI NMR (400 MHz, CDCI 3) 6

8.65(d, J= 1.6 Hz, 1H), 8.35(d, J = 2.4 Hz, 1H), 7.75 (dt, J= 9.5, 2.4 Hz, 1H), 7.51 (s, 1H),

3.21 (s, 2H); ESIMS m/z 213 ([Mr).

10 3-Bromo-Hpyridin-311)-1H-pyrazol-4-amine was prepared from the appropriate

nitropyrazole as described In Example 21: mp 143.0-146.0 °C; 1 H NMR (400 MHz, CDCI 3) 6


(s, 1H), 7.37 (ddd, J= 8.4, 4.7, 0.7 Hz, 1H), 3.21 (s, 2H); ESIMS m/z 241 ([M+2r).

Example 22: Preparation of tert-butyl (5-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-yi)carbamate

15 (Compound 281)

N

To a solution of (E)-tert-butyl 1-(dimethylamino)-3-oxobut-1-en-2-ylcarbamate (0.59g,

2.58 mmol) In ethanol (2.5 ml..) was added 3-hydrazinylpyridine, 2HCI (0.470 g, 2.58 mmol). The

reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was

20 concentrated and purified using silica gel chromatography (0-100 % ethyl acetate/hexanes) to

yield the title compound as an orange foam (0.235 g, 30%): IR (thin film) 3268, 2978 and 1698

cm'; 1 F1 NMR (400 MHz, CDCI3) 58.75 (dd, J= 2.5, 0.5 Hz, 1H), 8.62 (dd, J= 4.8, 1.5 Hz, 1H),

7.82 (ddd, J = 8.2, 2.6, 1.5 Hz, 1H), 7.78 (s, 1H), 7.43 (ddd, J = 8.1, 4.8, 0.6 Hz, 1H), 6.04 (s,

1H), 2.29 (s, 3H), 1.52 (s, 9H); ESIMS ink 275 ([M+Hr), 273 ([M-Ely).

25 Example 23: Preparation of tett-butyl 145-fluoropyrldin-3-yI)-3-methyl-1H-pyrazol-4'

ylcarbamate (Compound 111) and tert-butyl 5-ethoxy-1-(5-fluoropyridin-3-y1)-3-methyl-1 H-

pyrazo14-ylcarbamate (Compound 112)

N Pë h

To a solution of 3-fiuoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine (3.133 g, 14.10

30 mmol) in ethanol (28.2 ml) was added ethyl acetate until all of the starting material went into

69

17149

1 solution. The solution was degassed and 10% palladium on carbon (0.750g. 0.705 mmol) was

added and the reaction was stirred in a parr hydrogenator at 40 psi for 3 hours. The solution

was filtered through celite with ethyl acetate and the solvent was removed under reduced

pressure. The residue was dissolved in tetrahydrofuran (32.0 ml) and water (9.61 ml). Di-tert-

5 butyl dicarbonate (2.52 g, 11.55 mmol) was added followed by saturated aqueous sodium

bicarbonate (9.54 ml, 11.45 mmol). The reaction was stirred at room temperature overnight,

diluted with water and extracted with ethyl acetate. The combined organic phases were

concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give tert-butyl 1-(5-

fluoropyridin-3-y1)-3-methyl-1H-pyrazol-4-ylcarbamate (1.673g, 5.72 mmol, 41.0%) as a yellow

10

solid and the tert-butyl 5-ethoxy-1-(5-fiuoropyridin-3-y1)-3-methyl-1H-pyrazol-4-ylcarbamate

(0.250g. 0.74 mmol, 5.2%) as a brown oil:

Tert-butyl 1-(5-fluoropyridin-3-y1)-3-methyl-1H-pyrazol-4-ylcarbamate (Compound 111):

mp 131.5-133.0 °C; 1 H NMR (400 MHz, CDCI 3) 68.75 (s, 1H), 8.32 (d, J = 2.5 Hz, 1H), 8.28 (s,

1H), 7.77 (dt, J= 9.7, 2.4 Hz, 1H), 6.15 (s, 1H), 2.29 (s, 3H), 1.54(s, 9H); ES1MS tniz 293

15 ([M+Hr).

Tert-butyl 5-ethoxy-1-(5-fluoropyridin-3-y1)-3-methy1-1H-pyrazol-4-ylcarbamate

(Compound 112): IR (thin film) 1698 cm -1 ; 1 H NMR (400 MHz, CDCI3) 58.88 (s, 1H), 8.34 (d, J =

2.5 Hz, 1H), 7.83 (d, J = 9.9 Hz, 1H), 5.99 (s, 1H), 4.37 (q, J = 7.0 Hz, 2H), 2.17 (s, 3H), 1.50 (s,

9H), 1.37 (t, J = 7.1 Hz, 3H); ESIMS miz 337 ([M+H].).

20 Example 24: Preparation of Bis tert-t-butyl (1-(pyrldin-3-y1)-1H-pyrazol-4-yOcarbamate

(Compound 595)

0 y

--0

To a solution of tert-butyl (1-(pyridin-3-y1)-11-1-pyrazol-4-yl)carbamate (2.00g. 7.68 mmol)

In dry THF (21.95 mL) at 0 °C was added 60% sodium hydride (0.33 g, 8.45 mmol) In one

25 portion and stirred at that temperature for 30 minutes. To this was then added Boc-Anhydride

(1.84g. 8.45 mmol) In one portion and stirred for 5 minutes at 0 °C. The water bath was

removed and the reaction was warmed to room temperature and stirred at additional 30

minutes. The reaction was quenched with water and extracted with ethyl acetate. The ethyl

acetate layers were combined, dried (MgSO4), filtered and concentrated to dryness. The crude

30 material was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to give the

desired product as a white solid (2.0 g, 72%): 1 H NMR (400 MHz, CDCI 3) 6 9.12 - 8.86 (m, 1H),

8.55 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3.2.7, 1.5 Hz, 1H), 8.01 (d, J = 0.5 Hz, 1H), 7.84

-7.65 (m, 1H), 7.41 (ddd, J= 8.3, 4.8, 0.7 Hz, 1H), 1.51 (s, 18H).

Example 25: Preparation of 3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-amine (Compound 516) 70

17149

N

To tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-yOcarbamate (29, 6.79 mmol) In

dichloromethane (6.79 ml) was added trifluoroacetic acid (6.79 ml) and the mixture was left

stirring at room temperature for 2 hours. Toluene (12 ml.) was added and the reaction was

5 concentrated to near dryness. The mixture was poured into a separatory funnel containing

saturated aqueous sodium blcarbonated and was extracted with dichloromethane. The

combined organic layers were concentrated to give 3-chloro-14pyridin-3-y1)-1H-pyrazol-4-amine

(0.9549, 4.90 mmol, 72.2%) as a white solid: mp 137.9-139.9 °C; 'H NMR (400 MHz, CDCI3) 6


10 (s, 1H), 7.37 (ddd, J= 8.4, 4.7, 0.7 Hz, 1H), 3.18 (s, 2H); ESIMS m/z 196 ([M+H]').

Example 26: Preparation of N-ally1-1-(5-fluoropyridin-311)-3-methyl-1H-pyrazol-4-amine

hydrochloride

NH.HCI

N LI

To a solution of tert-butyl ally1(1-(5-fluoropyridin-3-y9-3-methyl-1H-pyrazol-4-

15

yl)carbamate (908 mg, 2.73 mmol) in dioxane (5 ml.) was added HCI (1M In ether) (13.65 mL,

13.65 mmol) and the mixture stirred at room temperature for 48 h. The resulting white solid was

filtered, washed with ether and dried under vacuum to give N-ally1-1-(5-fluoropyridin-3-y1)-3-

methy1-1H-pyrazol-4-amine, HCI (688 mg, 94% yield) as a white solid: mp 189-190 °C; 'H NMR

(400 MHz, CDCI3) 6 8.79 - 8.68 (m, 1H), 8.32 - 8.26 (m, 1H), 8.23 (s, 1H), 7.98 - 7.86 (m, 1H),

20

5.86 - 5.68 (m, 1H), 5.28 - 5.17 (m, 1H), 5.17 - 5.03 (m, 1H), 3.59 (d, J = 6.2 Hz, 2H), 2.11 (s,

3H); EIMS (in/z) 233 ([M+114-).

N-Ally1-3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-amine, HCI was prepared as described In

Example 26 from tert-butyl ally1(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-yl)carbamate: mp 172-174

°C; 'H NMR (400 MHz, CDCI3) 6 9.20(d, J= 2.5 Hz, 1H), 8.65 (dd, J= 5.3, 1.1 Hz, 1H), 8.61

25 (ddd, J = 8.6, 2.5, 1.1 Hz, 1H), 8.24 (s, 1H), 7.93 (dd, J = 8.6, 5.3 Hz, 1H), 3.66 (dt, J = 5.5, 1.3

Hz, 2H); EIMS (m/z) 235 ([M+1]+).

N-Ally1-3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine, HCI was prepared as described in

Example 26 from tert-butyl ally1(3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-y1): mp 195-197 °C; 'H

NMR (400 MHz, DMSO-do) 69.12 (d, J= 2.4 Hz, 1H), 8.58 (dd, J= 5.0, 1.2 Hz, 1H), 8.48 (s,

30

1H), 8.43 (d, J = 9.7 Hz, 1H), 7.77 (dd, J = 8.4, 5.0 Hz, 1H), 6.04 - 5.92 (m, 1H), 5.44 (dd, J =

17.2, 1.4 Hz, 1H), 5.32 (d, J = 9.4 Hz, 1H), 3.81 (d, J = 6.2 Hz, 2H); EIMS (m/z) 249 ([M-1]+).

71

17149

3-Bromo-1-(5-fluoropyridin-3-y1)-N-methyl-1H-pyrazol-4-amine, HCI was prepared as

described in Example 26 from tert-butyl 3-bromo-1-(5-fluoropyrldin-3-y1)-1H-pyrazol-4-

yl(methyl)carbamate: mp 167-168 °C; 'H NMR (400 MHz, CDCI 3) 68.93 (s, 1H), 8.50 (d, J = 2.5

Hz, 1H), 8.23 (s, 1H), 8.14 (dt, J= 10.4, 2.3 Hz, 1H), 2.73 (s, 3H).

5 3-Bromo-N-methyl-1 -(pyridin-3-y1)-1H-pyrazol-4-amine, HCI was prepared as described

In Example 26 from tert-butyl (3-bromo-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(methypcarbamate (160

mg, 0.45 mmol) in dioxane (1 ml) was added 4M HCI: mp. 226-228 °C; 'H NMR (400 MHz,

DMSO-d6) 6 9.26 - 9.06 (d, J = 2.6 Hz, 1H), 8.69 - 8.54 (m, 1H), 8.54 - 8.39 (d, J = 8.0 Hz, 1H),

8.33 - 8.14 (s, 1H), 7.90 - 7.72 (in, 1H), 2.82 - 2.67 (s, 3H); EIMS (m/z) 253 ([M+1]+), 255

10 (N1+2H]+).

3-Bromo-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine, HCI was prepared as described In

Example 26 from 3-bromo-N-ethy1-14pyridin-3-y1)-1H-pyrazol-4-amine, HCI: mp 216-217 °C; 'H

NMR (400 MHz, DMSO-d6) 6 10.66- 10.05 (s, 3H), 9.28 - 9.20 (d, J = 2.5 Hz, 1H), 8.74 - 8.67

(m, 1H), 8.67 - 8.56 (in, 3H), 7.96 - 7.84 (m, 1H), 3.21 -3.14 (m, 2H), 1.29- 1.22 (m, 3H); EIMS

15 (m/z) 267 ([M+11+).

3-Chloro-N-(2-methoxyethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine, HCI was prepared as

described In Example 26 from tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(2-

methoxyethyl)carbamate, HCI: mp 157-158 °C; 1 H NMR (400 MHz, DMSO) 6 9.22 - 9.14 (d, J =

2.5 Hz, 1H), 8.70 - 8.65 (s, 1H), 8.65 - 8.59 (m, 1H), 8.38 - 8.33 (m, 1H), 8.00 - 7.89 (m, 1H),

20 3.59- 3.50 (t, J = 5.8 Hz, 2H), 3.32- 3.27 (s, 3H), 3.22- 3.14 (m, 2H); E1MS (m/z) 253 ([M+11+).

Example 27: Preparation of 3-chloro-N-ethyl-1.(pyridln-3-y1)-1H-pyrazol-4-amlne

hydrochloride

CI

NH 2HCI

Into a 500 ml three-necked round bottom flask equipped with a magnetic stir bar was

25 added a solution of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1Xethyl)carbamate (21 g,

65.1 mmol) in 1.4-dioxane (35 mL). This pale yellow solution was placed Into an Ice bath and

cooled to 1 0C. A solution of 4M HCl/dioxane (65 mL, 260 mmol) was added in one portion.

After stirring for 20 minutes, the ice bath was removed and the suspension was stirred further at

ambient temperature for 16 hours. The reaction was diluted with 200 mL of ethyl ether and the

30 solid was filtered and washed with ether and placed In a vacuum oven at 40 00 for 18 hours.

The title compound was isolated as a pate yellow solid (18.2 g, 95%): 'H NMR (400 MHz,

Me0D) 69.52 (d, J = 2.5 Hz, 1H), 9.17 (s, 1H),. 9.14 (ddd, J = 8.7, 2.5, 1.1 Hz, 1H), 8.93 (ddd, J

= 5.7, 1.1, 0.6 Hz, 1H), 8.31 (ddd, J= 8.7, 5.7, 0.5 Hz, 1H), 3.58(q, J = 7.3 Hz, 2H), 1.48(t, J =

7.3 Hz, 3H); ESNS m/z 223 ((M+HJ*). 72

17149

3-Chloro-N-methyl-1-(pyridin-3-y1)-1H-pyrazole-4-amine, 2HCI was prepared as

described in Example 27: 1 H NMR (400 MHz, Me0D) 69.28 (d, J = 2.5 Hz, 1H), 8.86 (ddd, J =

8.7, 2.5, 1.2 Hz, 1H), 8.79 - 8.75 (m, 1H), 8.62 (s, 1H), 8.19 (ddd, J = 8.7, 5.6, 0.5 Hz, 1H), 3.06

(s, 3H); 13C NMR (101 MHz, Me0D) 6 141.42, 139.58, 137.76, 134.58, 134.11, 129.33, 127.55,

5 122.14,35.62): ESIMS m/z 209 ([M+H]).

Example 28: Preparation of 3-(4-nitro-3-phenyl-1H-pyrazol-111)pyricline

N / NO2

N

To a suspension of phenylboronic acid (0.546 g, 4.47 mmol) In toluene (6.63 ml) was

added 3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine (0.335 g, 1.492 mmol) followed by ethanol

10 (3.31 ml) and 2 M aqueous potassium carbonate (1.492 ml, 2.98 mmol). The solution was

degassed by applying vacuum and then purging with nitrogen (3 times). To the reaction mixture

was added palladium tetrakis (0.086 g, 0.075 mmol) and the flask was heated at 110 °C under

nitrogen for 16 hours. The aqueous layer was removed and the organic layer was concentrated.

The crude product was purified via silica gel chromatography (0-100% ethyl acetate/hexanes) to

15

give 3-(4-nitro-3-phenyl-1H-pyrazol-1-Apyridine (499 mg, 1.874 mmol, 80%) as a yellow solid:

mp 144.0-146.0 °C; 1 1-I NMR (400 MHz, CDCI3) 69.09 (d, J = 2.3 Hz, 1H), 8.82(s, 1H), 8.71

(dd, J = 4.8, 1.4 Hz, 1H), 8.16 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.82 - 7.74 (m, 2H), 7.55 - 7.48

(m, 4H); EIMS miz 266.

Example 29: Preparation of 5-bromo-1-(pyriclin-3-y1)-1H-pyrazol-4-yl(methyl)carbamate

20 (Compound 110)

Br N

To tert-butyl methyl(1-(pyridin-3-y1)-1H-pyrazol-4-y9carbamate (0.200 g, 0.729 mmol) in

dichloroethane (3.65 ml) was added 1-bromopyrrolidine-2,5-dione (0.260 g, 1.458 mmol) and

the reaction was stirred overnight at 50°C. The reaction was concentrated, diluted with

25 dichloromethane, and washed with water and saturated aqueous sodium thiosulfate. The

organic phase was concentrated to give tert-butyl 5-bromo-1-(pyridin-3-0)-1H-pyrazol-4-

yi(methyl)carbamate (256 mg, 0.725 mmol, 99 %) as a brown oil: IR (thin film) 1697 crn' 1 ; 1 H

NMR (400 MHz, CDCI3) 6 8.89 (s, 1H), 8.68 (d, J = 4.1 Hz, 1H), 7.93 (ddd, J = 8.2, 2.5, 1.5 Hz,

73

17149

1H), 7.69 (s, 1H), 7.46 (dd, J = 8.1, 4.8 Hz, 1H), 3.22 (s, 3H), 1.44 (s, 9H); ESIMS m/z 352 ([10-

HD. Example 30: Preparation of 131s tert-t-butyl (5-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

yOcarbamate (Compound 109)

5 To Bis tert-t-butyl (1-(pyridin-3-0)-1H-pyrazol-4-yl)carbamate (1.30g. 3.61 mmol) in

acetonitrile (21.22 mL) was added N-chlorosuccinimide (0.96g. 7.21 mmol) and the reaction

was stirred at 45 °C for 48 hours. The reaction was cooled to room temperature and poured into

water and extracted with dichloromethane. The dichloromethane layers were combined, poured

10 through a phase separator to remove water and concentrated to dryness. The crude material

was purified by silica gel chromatography (0-60% ethyl acetate/hexanes) to give the desired

product as a yellow solid (0.90g. 63%): mp 109-115 °C; 1 H NMR (400 MHz, CDCI 3) 68.90 (d, J

= 2.3 Hz, 1H), 8.68 (dd, J = 4.8, 1.5 Hz, 1H), 7.94 (ddd, J = 8.2, 2.5, 1.5 Hz, 1H), 7.70 (s, 1H),

7.47 (dtd, J = 11.0, 5.6, 5.5, 4.8 Hz, 1H), 1.49 (s, 18H); ESIMS m/z 395 ([M+Hr).

15

Tert-butyl (5-chloro-3-methy1-1-(pyridin-3-y1)-/H-pyrazol-411)(methyl)carbamate was

prepared from the appropriate pyrazole in dichloroethane as the solvent as described in

Example 30: ESIMS m/z 324 ([M+Fir).

Compounds 110 (see also procedure in Example 29) and 146 were prepared from

the appropriate pyrazoles using N-bromosuccinimide in accordance with the procedures

20 disclosed In Example 30.

Tert-butyl 5-bromo-3-methy1-1-(pyridin-3-y1)-1H-pyrazol-4-yl(methyl)carbamate was

prepared from the appropriate pyrazole in dichloroethane as described In Example 30: 1 H NMR

(400 MHz, CDCI3) 68.88 (d, J= 2.3 Hz, 1H), 8.69- 8.60(m. 1H), 7.96 - 7.86 (m, 1H), 7.48 -

7.39 (m, 1H), 3.18 (s, 3H), 2.26(s, 3H), 1.60 - 1.36 (m, 9H); ESIMS m/z 368 ([M+Hr).

25

Example 31: Preparation of bis fert-butyl (5-fluoro-1-(pyridin-3-y1)-1H-pyrazol-4-


0 y._

4 / --•::•

F

To a solution of bis tert-t-butyl (1-(pyridin-3-y1)-1H-pyrazol-4-yl)carbamate (0.075g.

0.208 mmol) In DMF (0.416 ml) and acetonitrile (0.416 ml) was added Selecfluor0 (0.184g,

30 0.520 mmol). The reaction was stirred at room temperature for one week. The reaction was

74

17149

concentrated, saturated aqueous ammonium chloride was added and the mixture was extracted

with ethyl acetate. The combined organic phases were concentrated and chromatographed (0-

100% ethyl acetatethexanes) to give bis tert-butyl (5-fluoro-1-(pyridin-3-yl)-1H-pyrazol-4-

yOcarbamate (16 mg, 0.042 mmol, 20.32 %) as an off-white solid: 1 H NMR (400 MHz, CDCI 3) 6

5

8.97 (t, J = 2.0 Hz, 1H), 8.61 (dd, J = 4.8, 1.4 Hz, 1H), 7.99 (ddt, J = 8.3, 2.6, 1.3 Hz, 1H), 7.57

(d, J = 2.5 Hz, 1H), 7.44 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 1.50 (s, 18H); ESIMS m/z 379 ((M+Hr).

Tert-butyl (5-fluoro-3-methy1-1-(pyridin-3-y1)-1H-pyrazol-4-y1Xmethy9carbamate was

prepared as described in Example 31: 1 H NMR (400 MHz, CDCI3) 6 8.94 (s, 1H), 8.57 (d, J =

4.2 Hz, 1H), 7.96 (d, J = 7.7 Hz, 1H), 7.41 (dd, J = 7.9, 4.7 Hz, 1H), 3.17 (s, 3H), 2.23 (s, 3H),

10 1.58- 1.40 (m, 9H); ESIMS m/z 307 ([M+H].).

Example 32: Preparation of N-cyclopropy1-3-methy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine

Example 32, Step 1: Preparation of 3-(4-lodo-3-methyl-1H-pyrazol-1-Apyridine

To a mixture of 3-(3-methyl-1H-pyrazol-1-yppyridine (6.7 g, 42.1 mmol), Iodic acid (2.96

15 g, 16.84 mmol), and diiodine (8.55 g, 33.7 mmol) in acetic acid (60.1 ml) was added

concentrated sulfur acid (3.74 ml, 21.04 mmol). The reaction mixture heated to 70 °C for 30

minutes. The reaction mixture was poured onto ice with sodium thiosulfate and was extracted

with diethyl ether. The combined organic phases were washed with saturated aqueous sodium

bicarbonate. The organic phases were then dried with magnesium sulfate, filtered and

20 concentrated In vacuo. The solid residue was dissolved in dichloromethane , applied to a 80g

silica gel column, and eluted with 0-80% acetone In hexanes to afford 3-(4-lodo-3-methyl-1 H-

pyrazol-1-yl)pyridine (11.3 g, 35.7 mmol, 85 %) as a white solid: mp 131 °C; 1 H NMR (400 MHz,

CDCI 3) 6 8.95 - 8.85 (m, 1H), 8.52 (dd, J = 4.8, 1.4 Hz, 1H), 8.00 - 7.94 (m, 1H), 7.91 (s, 1H),

7.38 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 2.34 (s, 3H); EIMS m/z 285.

25

75

17149

Example 32, Step 2: Preparation of N-cyclopropyi-3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-

amine

To a solution of 3-(4-lodo-3-methyl-1H-pyrazol-1-yl)pyridine (2.0 g, 7.02 mmol) in

5 dimethylsulfoxide (7.02 ml) was added 1-(5,6,7,8-tetrahydroquinolin-8-ypethanone (0.246g.

1.403 mmol), cyclopropanamine (0.486 ml, 7.02 mmol), cesium carbonate (6.86 g, 21.05 mmol)

and copper(I) bromide (0.101 g, 0.702 mmol). The reaction mixture was stirred at 35 °C for 2

days. The reaction mixture was diluted with water and extracted with dichloromethane. The

combined organics were washed with brine, concentrated and chromatographed (0-100% ethyl

10 acetate/hexanes) to give N-cyclopropy1-3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (269 mg,

1.255 mmol, 17.90%) as a yellow solid: mp 104,0-107.0°C; 1 H NMR (400 MHz, CDCI3) 68.89

(dd, J= 2.7, 0.5 Hz, 1H), 8.41 (dd, J= 4.7, 1.4 Hz, 1H), 7.96 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.51

(s, 1H), 7.33 (ddd, J= 8.3, 4.7, 0.7 Hz, 1H), 3.42 (s, 1H), 2.53 -2.42 (m, 1H), 2.22 (s, 3H), 0.72

- 0.65 (m, 2H), 0.60 - 0.53 (m, 2H); ESIMS m/z 215 ((M+Hr).

15 3-Methyl-N-(3-(methylthio)propy1)-1-(pyridin-3-y1)-1H-pyrazol-4-amine was prepared as

described in Example 32: IR (thin film) 3298 cm'; 1 H NMR (400 MHz, CDCI3) 68.87 (d, J= 2.3

Hz, 1H), 8.40 (dd, J= 4.7, 1.4 Hz, 1H), 7.93 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.35(s, 1H), 7.34 -

7.29 (m, 1H), 3.16 (t, J= 6.8 Hz, 2H), 2.89 (s, 1H), 2.64 (t, J= 7.0 Hz, 2H), 2.25 (s, 3H), 2.13 (s,

3H), 1.95 (p, J= 6.9 Hz, 2H); ESIMS m/z 263 ([M+Fi]).

20 3-Methyl-N-(2-methyl-3-(methylthio)propy1)-1-(pyridin-311)-1H-pyrazol-4-amine was

prepared as described in Example 32: IR (thin film) 3325 cm-1 ; 1 H NMR (400 MHz, CDCI 3) 6

8.86 (d, J= 2.5 Hz, 1H), 8.40 (dd, J= 4.7, 1.2 Hz, 1H), 7.93 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.35

(s, 1H), 7.32 (ddd, J= 8.3, 4.7, 0.5 Hz, 1H), 3.12 (dd, J= 11.5 1 6.1 Hz, 1H), 2.94 (dd, J= 11.9,

6.6 Hz, 1H), 2.62 (dd, J= 12.9, 6.9 Hz, 1H), 2.52 (dd, J= 12.9, 6.2 Hz, 1H), 2.26(s, 3H), 2.14

25 (s, 3H), 2.12 - 2.02 (m, 1H), 1.11 (d, J= 6.8 Hz, 3H); EIMS m/z 276.

76

17149

1 Example 33: Preparation of tert-butyl (3-cyclopropy1-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-

yi)carbamate (Compound 434) and tert-butyl (1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-


0 Y \-0

NH

N N

5 To a suspension of 2-cyclopropy1-4,4,5,54etramethyl-1,3,2-dioxaborolane (1.087 g, 6.47

mmol) In toluene (13.69 ml) was added tert-butyl (3-bromo-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-

yl)carbamate (1.1 g, 3.08 mmol) followed by ethanol (6.84 ml) and 2 M aqueous potassium

carbonate (3.08 mL, 6.16 mmol). The solution was degassed by applying vacuum and then

purging with nitrogen (3 times). To the reaction mixture was added palladium tetrakis (0.178g.

10 0.154 mmol) and the flask was heated at 100°C under nitrogen for 36 hours. Water (5 mL) was

added and the mixture was extracted with ethyl acetate. The combined organics were

concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give tert-butyl (3-

cyclopropy1-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y1)carbamate (705 mg, 2.215 mmol, 71.9 %

yield) as a yellow solid and tert-butyl (1-(5-fluoropyridin-3-y9-1H-pyrazol-4-yOcarbamate (242

15 mg, 0.870 mmol, 28.2% yield) as a yellow solid.

tert-Butyl (3-cyclopropy1-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y1)carbamate: mp 156.5-158.0; 'H

NMR (400 MHz, CDCI3) 6 8.73 (s, 1H), 8.30 (d, J = 2.5 Hz, 1H), 8.27 (s, 1H), 7.76 (dt, J = 9.8,

2.4 Hz, 1H), 6.43 (s, 1H), 1.55 (s, 9H), 1.01 -0.91 (m, 4H); ESIMS irk 319 ([M+Hr).

(1-(5-Fluoropyridin-3-y1)-1H-pyrazol-4-yOcarbamate: mp 121.0-123.0°C; 'H NMR (300

20 MHz, CDCI3) 68.78 (s, 1H), 8.37 (s, 1H), 8.28 (s, 1H), 7.81 (d, J = 9.6 Hz, 1H), 7.59 (s, 1H),

6.44 (s, 1H), 1.53 (s, 9H). ESIMS ink 278 pry

Compounds 340 and 404 were prepared as described in Example 33.

Example 34: Preparation of tert-butyl (3-ethy1-1-(5-fluoropyridln-3-y1)-1H-pyrazol-4-

y1)(methyl)carbamate (Compound 408)

7cs)Lc$

25 N

To a 142-purged solution of tert-butyl (1-(5-fluoropyridin-3-y1)-3-viny1-1H-pyrazol-4-

y1)(methyucarbamate (0.730g. 2.293 mmol) in methanol (15.29 ml) was added 10% palladium

on carbon (0.036 g, 0.339 mmol). The reaction was purged with hydrogen and run under 80 psi

of hydrogen at room temperature for 60 hours. The reaction gave less than 20% conversion.

30 The reaction mixture was filtered through celite, concentrated, and redissolved In ethyl acetate

77

"--0Y---- NH

17149

(4 mL) and transferred to a bomb. The reaction was heated at 50 °C at 600 psi of hydrogen for

20 hours. The reaction was only 50% complete. Methanol (1 mL) and 10% palladium on carbon

(36 mg) were added, and the reaction was heated at 80 °C at 650 psi of hydrogen for 20 hours.

The reaction was filtered through celite and concentrated to give tert-butyl (3-ethyl-1-(5-

5

fluoropyridin-3-y1)-1H-pyrazol-4-y1)(methyl)carbamate (616 mg, 1.923 mmol, 84% yield) as

yellow oil: IR (thin film) 1692 cm -1 ; I HNMR (300 MHz, CDCI3) 68.71 (t, J= 1.4 Hz, 1H), 8.35 (d,

J = 2.6 Hz, 1H), 7.83 (dt, J = 9.5, 2.3 Hz, 2H), 3.18 (s, 3H), 2.65 (q, J = 7.5 Hz, 2H), 1.44 (s,

9H), 1.25(t, J= 7.1 Hz, 3H); EIMS m/z 320.

Example 35: Preparation of N-(1-(5-fluoropyridin-3-y1)-3-formy1-1H-pyrazol-4-

10 yflisobutyramide (Compound 560)

0 0

)L( m Nv...3.../

N

To a solution of N-(1-(5-fluoropyridin-3-yI)-3-vinyl-1H-pyrazol-4-yl)isobutyramide (0.706

g, 2.57 mmol) In tetrahydrofuran (12.87 ml) and water (12.87 ml) was added osmium tetroxide

(0.164 ml, 0.026 mmol). After 10 minutes at room temperature, sodium periodate (1.101 g, 5.15

15 mmol) was added in portions over 3 minutes and the resulting solution was stirred at room

temperature. After 18 hours, the solution was poured Into 10 mL water and was extracted with 3

x 10 mL dichloromethane. The combined organic layers were dried, concentrated and

chromatographed (0-100% ethyl acetate/hexanes) to give N-(1-(5-fluoropyridin-3-y1)-3-formy1-

1H-pyrazol-4-ypisobutyramide (626 mg, 2.266 mmol, 88% yield) as a yellow solid: mp 140.0-

20 142.0 °C; lEINMR (300 MHz, CDCI 3) 6 10.12 (s, 1H), 9.14 (s, 1H), 8.90 (d, J = 2.0 Hz, 1H), 8.82

(s, 1H), 8.51 (d, J = 2.5 Hz, 1H), 7.92 (dt, J = 9.2, 2.4 Hz, 1H), 2.65 (dt, J = 13.8, 6.9 Hz, 1H),

1.31 (d, J = 6.9 Hz, 6H); ESIMS m/z 277 ([M+Hr).

Compound 369 was prepared In accordance with the procedures disclosed In Example

35.

25 Example 36: Preparation of N-(1-(5-fluoropyridin-3-y1)-3-(hydroxymethyl)-1H-pyrazol-4-

yl)lsobutyramide (Compound 435) and N-(1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-


HO 0

Frx KIN-DrNiCr

N

N

To a solution of N-(1-(5-fluoropyridin-3-y1)-3-formy1-1H-pyrazol-4-Aisobutyramide (0.315

30 g, 1.140 mmol) in methanol (5.70 ml) at 0°C was added sodium borohydride (0.086g. 2.280 78

17149

mmol). The reaction was stirred at 0 °C for 2 hours, and room temperature for 20 hours. 0.5 M

HCI was added, the reaction was neutralized with saturated aqueous sodium bicarbonate, and

the mixture was extracted with dichloromethane. The organic phases were concentrated and

chromatographed (0-100% ethyl acetate/hexanes) to give N-(1-(5-fluoropyridin-3-y9-3-

5 (hydroxymethy9-1H-pyrazol-4-ypisobutyramide (180 mg, 0.647 mmol, 56.7%) as a white solid

and N-(1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y9isobutyramide (9 mg, 0.036 mmol, 3.18%) as a

white solid.

N-(1-(5-fluoropyridin-3-y9-3-(hydroxymethyl)-1H-pyrazol-4-ylysobutyramide: mp 144.0-

146.0 °C; 1 H NMR (400 MHz, CDCI3) 58.74 (d, J = 1.1 Hz, 1H), 8.64 (s, 1H), 8.37 - 8.29 (m,

10

2H), 7.74 (dt, J = 9.5, 2.3 Hz, 1H), 4.95 (d, J = 3.0 Hz, 2H), 3.21 -3.06 (m, 1H), 2.63 - 2.48 (m,

1H), 1.26 (d, J = 6.9 Hz, 6H); ESIMS m/z 279 UM+Hr).

N-(1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y1)isobutyramide: IR (thin film) 1659 cm -1 ; 1 H

NMR (400 MHz, CDCI 3) 5 8.79 (d, J = 1.2 Hz, 1H), 8.60 (s, 1H), 8.38 (d, J = 2.5 Hz, 1H), 7.81

(dt, J= 9.5, 2.3 Hz, 1H), 7.68 (s, 1H), 7.54(s, 1H), 2.63 - 2.51 (m, 1H), 1.28(d, J= 6.9 Hz, 6H);

15 ESIMS m/z 249 ((M+Hr).

Example 37: Preparation of N-(3-(chloromethyl)-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-


0

'Lr N

To a solution of N-(1-(5-fluoropyridin-3-y1)-3-(hydroxymethy1)-1H-pyrazol-4-

20 yOisobutyramide (0.100 g, 0.359 mmol) in dichloromethane ( 3.59 ml) was added thionyl

chloride (0.157 ml, 2.151 mmol). The reaction was stirred at room temperature for 2 hours.

Saturated aqueous sodium bicarbonate was added, and the mixture was extracted with

dichloromethane. The combined organic phases were washed with brine and concentrated to

give N-(3-(chloromethy0-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-yOisobutyramide (100 mg, 0.337

25 mmol, 94% yield) as a white solid: mp 172.0-177.0 °C; 1 H NMR (400 MHz, CDCI 3) 58.79 (s,

1H), 8.67(s, 1H), 8.40(s, 1H), 7.80 (dt, J = 9.4, 2.3 Hz, 1H), 7.42(s, 1H), 4.77(s, 2H), 2.63

(hept, J = 6.9 Hz, 1H), 1.30(d, J = 6.9 Hz, 6H); ESNS m/z 298 ([M+H] . ).

Example 38: Preparation of N-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-

methoxyacetamIde (Compound 512) (see also Example 11)

CI 0 0—

N i

i 30

79

17149

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine, 2HCI (0.130 g,

0.502 mmol) and in DCM (2.508 ml) was added N-ethyl-N-Isopropylpropan-2-amine (0.257 ml,

1.505 mmol) followed by 2-methoxyacetyl chloride (0.109 g, 1.003 mmol) and the reaction

mixture was stirred at ambient temperature for 16 hours. The reaction was quenched by the

5 addition of saturated sodium bicarbonate. The organic layer was extracted with DCM. The

organic layer was dried over sodium sulfate, filtered, concentrated and purified using silica gel

chromatography (0-100% ethyl acetate/hexanes) to yield the title compound as a pale yellow oil

(0.12g. 77%): IR (thin film) 3514, 3091, 2978, 1676 crti l ; I ll NMR (400 MHz, CDCI3) 68.96 (d,

J= 2.4 Hz, 1H), 8.63 (d, J= 3.8 Hz, 1H), 8.09 - 8.03 (m, 1H), 7.99 (s, 1H), 7.47 (dd, J= 8.3, 4.8

10

Hz, 1H), 3.88 (s, 2H), 3.77 - 3.65 (m, 2H), 3.40 (s, 3H), 1.18 (t, J= 7.2 Hz, 3H); ESIMS raiz 295

([M+1-1]').

Compounds 71,478, 481, 483- 484, and 543 were prepared in accordance with the


Example 39: Preparation of N-(3-chloro-1-(5-fluoropyrldin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-

15 methyl-3-(methylthlo)butanamIde (Compound 182) and (Z)-N43-chloro-1-(5-fluoropyridin-

3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-methylbut-2-enamIde (Compound 183)

CI 0 / CI 0

N N

To a solution 2-methyl-3-(methylthio)butanoic acid (0.154g. 1.039 mmol) in

dichloromethane (1 mL) at room temperature was added 1 drop of dimethylformamide. Oxaly1

20 dichloride (0.178 ml, 2.078 mmol) was added dropwise and the reaction was stirred at room

temperature overnight. The solvent was removed under reduced pressure. The residue was

redissolved in dichloromethane (1 mL) and the solvent was removed under reduced pressure.

The residue was redissolved In dichloromethane (0.5 ml..) and the solution was added to a

solution of 3-chloro-N-ethyl-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-amine (0.100 g, 0.416 mmol)

25 and 4-dimethylaminopyridine (0.254g, 2.078 mmol) in dichloromethane (1.5 mL) and stirred at

room temperature overnight. The solvent was removed under reduced pressure and the residue

was purify by chromatography (0-100% ethyl acetate/hexanes) to give N-(3-chloro-1-(5-

fiuoropyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-2-methy1-3-(methylthio)butanamide (34 mg, 0.092

mmol, 22.06 %) as a faint yellow oil and (2)-N-(3-chloro-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y1)-

30 N-ethyl-2-methylbut-2-enamide (38 mg, 0.118 mmol, 28.3% yield) as a yellow oil.

N-(3-chloro-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-methyl-3-

(methylthio)butanamide: IR (thin film) 1633 cm -I ; I ll NMR (400 MHz, CDC1 3) 68.79 (d, J= 2.0

Hz, 0.66H), 8.77 (d, J= 2.0 Hz, 0.33H), 8.50 (d, J= 2.6 Hz, 0.33H), 8.49 (d, J= 2.5 Hz, 0.66H),

8.08 (s, 0.66H), 7.95 (s, 0.33H), 7.92 - 7.81 (m, 1H), 4.03 - 3.46 (m, 2H), 3.03 - 2.78 (m, 1H), 80

17149

2.59- 2.33(m, 1H), 2.04 (s, 2H), 2.02 (s, 1H), 1.32 (d, J = 6.7 Hz, 1H), 1.27(d, J= 6.2 Hz, 1H),

1.23 (d, J= 6.9 Hz, 2H), 1.18- 1.12(m, 5H); ESIMS m/z 371 min (2)-N-(3-chloro-1-(5-fluoropyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-methylbut-2-enamide:

1 H NMR (400 MHz, CDCI3) 68.73 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 2.4 Hz, 1H), 7.87 (d, J = 4.9

5

Hz, 1H), 7.84 (dt, J = 9.2, 2.4 Hz, 1H), 5.93 - 5.76 (m, 1H), 3.73 (q, J = 7.1 Hz, 2H), 1.72 (s, 3H),

1.58 (dd, J = 6.9, 0.9 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); ESNS ink 323 anin. Compounds 70, 180- 181, 389 - 392, 397- 398, 405 - 406, 427 - 429, 432, 456, 482,

521 -522, 532— 534, 555, and 589 were prepared from the corresponding Intermediates and

starting materials In accordance with the procedures disclosed In Example 39.

10 Example 40: Preparation of N-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-N-methyl-2-

(methylthio)acetamide (Compound 337)

N

To an Ice cold solution of 2-(methylthio)acetic acid (0.092 g, 0.863 mmol) In DCM (2 mL)

was added N-ethyl-N-Isopropylpropan-2-amine (0.111 g, 0.863 mmol) followed by isobutyl

15 chloroformate (0.099 ml, 0.767 mmol). Stirring was continued for 10 minutes. Next, the mixed

anhydride was added to a solution of 3-chloro-N-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine

(0.08 g, 0.383 mmol) in DCM (0.66 mL) and the reaction mixture was stirred at ambient

temperature for 2 hours. The reaction mixture was concentrated and purified using reverse

phase C-18 column chromatography (0-100% CH3CN/H20) to yield the title compound as a

20 pale yellow oil (0.075g. 66%): 1 H NMR (400 MHz, CDC1 3) 68.95 (d, J = 2.5 Hz, 1H), 8.62 (dd, J

= 4.8, 1.4 Hz, 1H), 8.13 (s, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.50 - 7.43 (m, 1H), 3.26 (s,

3H), 3.12 (s, 2H), 2.24 (s, 3H); "C NMR (101 MHz, CDCI3) 6 170.00, 148.61, 140.15, 140.03,

135.68, 126.56, 126.42, 125.33, 124.15, 37.16, 34.94, 16.22; ESIMS m/z 297 ([M+1-1]*).

Compounds 335, 336, and 542 were prepared In accordance with the procedures


Example 41, Preparation of N-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-methyl-

3-oxobutanamIde (Compound 499)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine, HCI (259 mg, 1

30 mmol) and ethyl 2-methyl-3-oxobutanoate (144 mg, 1.000 mmol) in dioxane (1 mL) was added

2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine (181 mg, 1.30 mmol) and the mixture was 81

17149

heated In a microwave (CEM Discover) at 150 °C for 1.5 h, with external IR-sensor temperature

monitoring from the bottom of the vessel. LCMS (ELSD) indicated a 40% conversion to the

desired product. The mixture was diluted with ethyl acetate (50 ML) and saturated aqueous

HNC! (15 mL) , and the organic phase was separated. The aqueous phase was extracted with

5 ethyl acetate (20 mL) and the combined organic phase was washed with brine, dried over

MgSas and concentrated In vacua to give an oily residue. This residue was purified on silica gel

eluting with mixtures of ethyl acetate and hexanes to give N-(3-chloro-1-(pyridin-3-y1)-1H-

pyrazol-4-y1)-N-ethyl-2-methyl-3-oxobutanamide (37 mg, 11 % yield, 96% purity) as a colorless

oil: I FI NMR (400 MHz, CDCI3) 6 9.02 - 8.92 (dd, J = 2.6, 0.8 Hz, 1H), 8.68- 8.60 (dd, J = 4.8,

10

1.5 Hz, 1H), 8.09 - 7.98 (m, 1H), 7.96 - 7.87 (s, 1H), 3.87 - 3.58 (d, J = 3.0 Hz, 2H), 3.49 - 3.38

(m, 1H), 2.16 - 2.08 (s, 3H), 1.39- 1.32 (d, J = 7.0 Hz, 3H), 1.22- 1.13 (m, 3H); EIMS (m/z) 321

won 319 (WAD.

Example 42: Preparation of N-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-N-

15 ethylcyclopropanecarboxamide (Compound 538)

CI 0

N -41

i N

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-0)-1H-pyrazol-4-amine monohydrochloride

(0.10g. 0.0.38 mmol) in dichloroethane (0.75 ml) was added cyclopropanecarboxylic acid (0.03

g, 0.38 mmol) and 4-N,N-dimethylaminopyridine (0.14g. 1.15 mmol) followed by 1-(3-

20 dimethylaminopropy9-3-ethylcarbodiimide hydrochloride (0.14g. 0.77 mmol). The reaction was

stirred at room temperature overnight. The reaction mixture was concentrated to dryness and

the crude product was purified by reverse phase silica gel chromatography eluting with 0-50%

acetonitrile/water to give a white solid (0.03g, 25%); mp 111-119 °C; l hi NMR (400 MHz, CDCI3)

6 8.96 (d, J = 2.5 Hz, 1H), 8.63 — 8.59 (m, 1H), 8.06 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 8.01 (s, 1H),

25 7.46 (dd, J= 8.3, 4.7 Hz, 1H), 3.73(q, J= 7.2 Hz, 2H), 1.46 (ddd, J= 12.6, 8.1, 4.7 Hz, 1H),

1.16 (t, J = 7.2 Hz, 3H), 1.04 (t, J = 3.7 Hz, 2H), 0.71 (dd, J = 7.7, 3.0 Hz, 2H); ESIMS m/z 291

([M+H]).

Compounds 69, 516, 524, 546, 558 - 559, 582-588, 593, and 594 were prepared from

the appropriate acids in accordance with the procedures disclosed in Example 42.

82

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Example 43: Preparation of N-(3-chloro-1-(pyrldln-3-y1)-1H-pyrazol-4-y1)-2-methyl-3-

(methylthio)-N-(3-(methylthlo)propanoyl)propanamIde (Compound 407)

CI 0 /

N

$ \

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-(methylthio)propanamide

5 (0.216 g, 0.728 mmol) In DCE (2.91 ml) in a 10 mL vial was added 2-methy1-3-

(methylthio)propanoyl chloride (0.244g. 1.601 mmol). The vial was capped and placed In a

Biotage Initiator microwave reactor for 3 hours at 100 °C, with external IR-sensor temperature

monitoring from the side of the vessel. The crude mixture was concentrated and purified using

reverse phase C-18 column chromatography (0-100% acetonitrile/water) to yield the title

10 compound as a pale yellow oil (67 mg, 22%): IR (thin film) 2916 and 1714 cm-1 ; 1 H NMR (300

MHz, CDCI3) 6 8.96 - 8.92 (d, J = 2.7 Hz, 1H), 8.64 - 8.59 (dd, J = 4.9, 1.4 Hz, 1H), 8.07 - 7.99

(m, 2H), 7.50 - 7.40 (dd, J = 8.4, 4.8 Hz, 1H), 3.39 - 3.28 (m, 1H), 3.10- 2.99 (td, J = 7.2, 3.9

Hz, 2H), 2.96 -2.86 (dd, J = 13.2, 8.7 Hz, 1H), 2.86 -2.79 (t, J = 7.3 Hz, 2H), 2.58 - 2.48 (dd, J

= 13.1, 5.8 Hz, 1H), 2.14 - 2.12 (s, 3H), 2.09- 2.06 (s, 3H), 1.30- 1.26(d, J= 6.9 Hz, 3H);

15 ESIMS Ink 413 ([M+Hr).

Compounds 383, 410, 433, 437, 451, 470, 530 and 531 were prepared In accordance

with the procedures disclosed In Example 43.

Example 44: Preparation of N-p-chloro-1-(3-pyridyl)pyrazol-4-y1]-2,2-dIdetiterio-N-ethyl-3-

methylsulfanyl-propanamIde (Compound 393)

a 0 /

2 20 N

To a 7 mL vial was added 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (111 mg,

0.5 mmol), 2,2-dideuterio-3-methylsulfanyl-propanoic acid (58.0 mg, 0.475 mmol) and followed

by DCM (Volume: 2 mL) . The solution was stirred at 0 °C. Then the solution of DCC (0.500 mL,

0.500 mmol, 1.0M in DCM) was added. The solution was allowed to warm up to 25 °C slowly

25 and stirred at 25 °C overnight. White precipitate formed during the reaction. The crude reaction

mixture was filtered through a cotton plug and purified by silica gel chromatography (0-100%

Et0Ac/hexane) to giveN[3-chloro-1-(3-pyridyl)pyrazol-4-y1]-2,2-dideuterio-N-ethyl-3-

methylsulfanyl-propanamide (97 mg, 0.297 mmol, 59.4% yield) as a colorless oil: 1 H NMR (400

MHz, CDCI3) 68.96 (d, J= 2.4 Hz, 1H), 8.63 (dd, J= 4.6, 0.9 Hz, 1H), 8.06 (ddd, J = 8.4, 2.7,

2-CD

83

17149

P ot, cr ,—NH

N

?

84

1.4 Hz, 1H), 7.98 (s, 1H), 7.52 - 7.40 (m, 1H), 3.72 (q, J = 7.2 Hz, 2H), 2.78 (s, 2H), 2.06 (s,

3H), 1.17 (t, J = 7.2 Hz, 3H); ESIMS m/z 327 ([M+Hr); IR (Thin film) 1652 cm'.

Compounds 394, 396, and 471 - 473 were prepared from the corresponding

Intermediates and starting materials in accordance with the procedures disclosed In Example

5 44.

Example 45: Preparation of 1-ethyl-3-(3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-yOurea

(Compound 145)

A C 7—NH

NH

N

To a solution of 3-methyl-1-(pyridin-3-0)-1H-pyrazol-4-amine (0.1 g, 0.574 mmol) In

10 DCM (5.74 ml) was added ethyl Isocyanate (0.041 g, 0.574 mmol) and the reaction mixture was

stirred at ambient temperature for 40 minutes. The reaction mixture had turned from a clear

solution to a suspension with white solid material. The reaction mixture was concentrated and

purified using silica gel chromatography (0-20% Me0H/DCM) to yield the title compound as a

white solid (0.135g. 95%): mp 197-200 °C; 'H NMR (400 MHz, CDCI 3) 58.94 (d, J = 2.3 Hz,

15 1H), 8.48 - 8.37 (m, 1H), 8.32 (s, 1H), 7.94 (d, J = 8.3 Hz, 1H), 7.52 (br s, 1H), 7.41 -7.25 (m,

1H), 5.79 (br s, 1H), 3.33 - 3.23 (m, 2H), 2.29 (d, J = 2.9 Hz, 3H), 1.16 (dd, J = 8.7, 5.7 Hz, 3H);

ESIMS m/z 246 ([M+Hr), 244 am-Hp. Compounds 169 - 171,221 - 222, 255 - 257, 278 - 280, 297 - 302, 318 - 322, 334, 345,

348, 375 - 377, 385 - 387, and 411 - 413 were prepared In accordance with the procedures


1-(3-Chloro-1-(pyridin-3-0)-1H-pyrazol-4-y1)-3-ethyl-1-methylthiourea (Compound

Y2048) was prepared In accordance with the procedure disclosed in Example 45 using DMAP

as a base, dioxane as a solvent, and heating the reaction In a microwave (CEM Discovere) with

external IR-sensor temperature monitoring from the bottom of the vessel at 120°C for 2 hours:

25 white solid; mp 160.0-162.0°C; 'H NMR (300 MHz, CDCI 3) 68.94 (d, J= 2.6 Hz, 1H), 8.62 (dd,

J = 4.8, 1.4 Hz, 1H), 8.05 - 7.98 (m, 2H), 7.46 (dd, J = 8.3, 4.7 Hz, 1H), 5.66 (s, 1H), 3.72 - 3.59

(m, 5H), 1.17 (t, J = 7.2 Hz, 3H); ESNS m/z 297 ([M+H]).

Example 46: Preparation of 3-butyl-1-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-1-

ethylurea (Compound 500)

30

17149

CI 0

""-- NH

To a solution of 3-chloro-N-ethy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine, 2HCI (0.130g.

0.502 mmol) in DCE (1.25 ml) was added N-ethyl-N-Isopropylpropane-2-amine (0.21 mL, 1.255

mmol) followed by 1-lsocyanatobutane (0.109g. 1.104 mmol) and the reaction mixture was

stirred at ambient temperature for 16 hours. The reaction mixture was concentrated and purified

5 using silica gel chromatography (0-20% Me0H/DCM) to yield the title compound as a beige

solid (0.131 g, 77%): IR (thin film) 3326, 2959, 2931, 1648 cm -1 ; 1 EINMR (400 MHz, CDCI3) 5

8.95 (s, 1H), 8.62 (d, J= 4.0 Hz, 1H), 8.08 - 8.01 (m, 1H), 7.97 (s, 1H), 7.46 (dd, J= 8.3, 4.7 Hz,

1H), 4.42 - 4.32 (m, 1H), 3.74 - 3.61 (m, 2H), 3.27 - 3.15 (m, 2H), 1.49- 1.37 (m, 2H), 1.37 -

1.22 (m, 2H), 1.19- 1.12(m, 3H), 0.94- 0.84 (m, 3H); ESIMS m/z 322 ([M+H]).

10 Compounds 479 - 480, 501 - 504, 513, 518 and 519 were prepared according to

Example 46.

Example 47: Preparation of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-yOlmidazoildin-2-one

(Compound 374)

15 To a solution of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-(2-chloroethypurea (0.1 g,

0.333 mmol) In THF (6.66 ml) was added sodium hydride (8.00 mg, 0.333 mmol) and the

reaction mixture was stirred at ambient temperature for 30 minutes. The reaction was quenched

by the addition of a solution of saturated ammonium chloride and the product was extracted with

ethyl acetate (2x). The combined organic layers were dried over sodium sulfate, filtered and

20 concentrated. The product was a beige solid which was pure and did not need any further

purification (63 mg, 72%): mp 167-170°C; 1 H NMR (400 MHz, CDCI3) 5 8.96(d, J = 2.2 Hz,

1H), 8.56 (dd, J= 4.7, 1.4 Hz, 1H), 8.33 (s, 1H), 7.99 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.40 (ddd,

J = 8.3, 4.8, 0.7 Hz, 1H), 5.00 (s, 1H), 4.14 - 4.07 (m, 2H), 3.68 - 3.58 (m, 2H); ESIMS m/z 264

([M+Hr).

25 Compound 349 was prepared in accordance with the procedures disclosed In Example

47.

Example 48: Preparation of S-tert-butyl (3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-

y1)(ethyl)carbamothloate (Compound 514)

85

17149

To a solution of 3-chloro-N-ethy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine, 2HCI (0.13g.

0.502 mmol) In DCM (2.508 ml) was added N-ethyl-N-isopropylpropan-2-amine (0.257 ml, 1.505

mmol) followed by S-tert-butyl carbonochloridothioate (0.153g. 1.003 mmol). The reaction

mixture was stirred at ambient temperature for 16 hours. The reaction was quenched by the

5 addition of saturated sodium bicarbonate. The organic layer was extracted with DCM. The

organic layer was dried over sodium sulfate, filtered, concentrated and purified using silica gel

column chromatography (0-100% ethyl acetate/hexanes) to yield the title compound as a white

solid (132 mg, 78%): mp 91-93 °C; I FI NMR (400 MHz, CDCI3) 58.96 (d, J = 2.5 Hz, 1H), 8.60

(dd, J = 4.7, 1.4 Hz, 1H), 8.08 - 8.03 (m, 1H), 7.97 (s, 11-1), 7.47 - 7.41 (m, 1H), 3.69 (q, J = 7.2

10 Hz, 2H), 1.47(s, 9H), 1.21 - 1.13(m, 3H); ESIMS m/z 339 ([M+H]).

Compounds 333, 338, 339, 346, 368 and 373 were prepared in accordance with the


Example 49: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-methyl•

3-(methio)propanethloamide (Compound 364)

C1 S

15 N

To a microwave reaction vessel was added N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-

N-ethy1-2-methy1-3-(methio)propanamide (0.07 g, 0.22 mmol) In dichloroethane (1.87 mL) and

Lawesson's reagent (0.05g. 0.12 mmol). The vessel was capped and heated in a Biotage

Initiator microwave reactor for 15 minutes at 130 °C, with external IR-sensor temperature

20 monitoring from the side of the vessel. The reaction was concentrated to dryness and the crude

material was purified by silica gel chromatography (0-80% acetonitrile/water) to give the desired

product as a yellow oil (0.33 g, 44%): IR (thin film) 1436 cm'; I FI NMR (400 MHz, CDCI3) 6 8.97

(d, J = 2.5 Hz, 1H), 8.77 - 8.52 (m, 1H), 8.11 -7.89 (m, 2H), 7.60 - 7.38 (m, 1H), 4.62 (bs, 1H),

4.02 (bs, 1H), 3.21 -2.46 (m, 3H), 2.01 (s, 3H), 1.35- 1.15 (m, 6H); ESIMS m/z 355 ([M+H)+ ).

25

Compounds 372, 438 and 548 were prepared In accordance with the procedures

disclosed in Example 49.

N-methyl-3-(methylthlo)propanethloamide was prepared in accordance with the

procedure disclosed in Example 49 and isolated as a clear oil; 1 FI NMR (400 MHz, CDCI3) 6

7.69(s, 1H), 3.20(d, J = 4.8 Hz, 3H), 2.99- 2.88(m, 4H), 2.15(s, 3H); ESIMS m/z 150

30 ([M+H]).

Example 50: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-4,4,4-

trifluoro-3-(methylsulfinyl)butanamide (Compound 570)

86

17149

N

To a 20 mL vial was added N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-419-N-ethyl-4,4,4-

trifluoro-3-(methylthio)butanamide (82 mg, 0.209 mmol) and hexafluoroisopropanol (1.5 ml.).

Hydrogen peroxide (0.054 mL, 0.626 mmol, 35% solution In water) was added In one portion

5 and the solution was stirred at room temperature. After 3 hours the reaction was quenched with

saturated sodium sulfite solution and extracted with Et0Ac (3 x 20 mL). The combined organic

layers were dried over sodium sulfate, concentrated and purified by chromatography (0-10%

Me0H/DCM) to give N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-4,4,4-trifluoro-3-

(methylsuIfinyl) butanamide (76 mg, 0.186 mmol, 89% yield) as white semi-solid: 1 H NMR (400

10 MHz, COCI3) 5 8.98 (d, J = 2.3 Hz, 1H), 8.63 (td, J = 4.8, 2.4 Hz, 1H), 8.14 - 8.01 (m, 2H), 7.46

(ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 4.26 (dd, J= 17.2, 8.4 Hz, 1H), 3.89 - 3.61 (m, 2H), 3.01 (dd, J =

17.6, 8.2 Hz, 1H), 2.77 (s, 2H), 2.48 (dd, J = 17.7, 3.3 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H) (only one

Isomer shown); ESIMS m/z 409 ([M+Hr); IR (Thin film) 1652 mi l .

Compound 571 was prepared from the corresponding Intermediates and starting

15 materials In accordance with the procedures disclosed in Example 50.

Example 51: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-411)-N-ethyl-3-

(methylsulflnyl)propanamide (Compound 362)

CI 0 / )\---7- q%

N °

) N

To N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-(methylthio)propanamide (0.08

20 g, 0.24 mmol) In glacial acetic acid (0.82 mL) was added sodium perborate tetrahydrate (0.05 g,

, 0.25 mmol), and the mixture was heated at 60 °C for 1 hour. The reaction mixture was

carefully poured into a separatory funnel containing saturated aqueous NaHCO 3 resulting in gas

evolution. When the gas evolution had ceased, ethyl acetate was added and the layers were

separated. The aqueous layer was extracted twice with ethyl acetate, and all the organic layers

25 were combined, dried over MgSO4 , filtered and concentrated under reduced pressure. The

crude material was purified by silica gel chromatography (0-10% methanol/ dichloromethane) to

give the desired product as a clear oil (0.03 g, 40%): IR (thin film) 1655 cm'; 1 H NMR (400

MHz, COCO 5 8.95 (t, J = 9.2 Hz, 1H), 8.63 (dd, J = 4.7, 1.4 Hz, 1H), 8.20 - 7.86 (m, 2H), 7.59 -

7.33 (m, 1H), 3.73 (ddt, J = 20.5, 13.4, 6.8 Hz, 2H), 3.23 - 3.06 (m, 1H), 2.94 - 2.81 (m, 1H),

30 2.74- 2.62 (m, 2H), 2.59 (s, 3H), 1.25- 1.07 (m, 3H); ESIMS m/z 341 ([M+H]).

87

17149

Compounds 101 - 102, 218, 328, 330, and 494 were prepared from the appropriate

sulfides In accordance with the procedures disclosed in Example 51.

Example 52: Preparation of N-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

(methylsulfonyl)propanamide (Compound 363)

Po ck /

N 0

)

5 N

To N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-(methylthio)propanamide (0.08

g, 0.25 mmol) In glacial acetic acid (0.85 ml..) was added sodium perborate tetrahydrate (0.11 g,

0.52 mmol), and the mixture was heated at 60 °C for 1 hour. The reaction mixture was carefully

poured Into a separatory funnel containing saturated aqueous NaHCO3 resulting in gas

10 evolution. When the gas evolution had ceased, ethyl acetate was added and the layers were

separated. The aqueous layer was extracted twice with ethyl acetate, and all the organic layers

were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The

crude product was purified by silica gel column chromatography (0 to 10%

methanol/dichloromethane) to give the desired product as a clear oil (0.04, 47%): (thin film)

15 1661 cm-1 ; I li NMR (400 MHz, CDCI3) 68.95 (t, J = 11.5 Hz, 1H), 8.64 (dd, J = 4.8, 1.4 Hz, 1H),

8.17 - 7.96 (m, 2H), 7.59 - 7.39 (m, 1H), 3.73 (d, J = 7.0 Hz, 2H), 3.44 (dd, J = 22.5, 15.7 Hz,

2H), 2.96 (s, 3H), 2.71 (t, J = 6.9 Hz, 2H), 1.18 (dd, J = 8.8, 5.5 Hz, 3H); ESIMS rrilz 357

([M+Fi]).

Compounds 103, 104, 219, 329, 331 and 495 were prepared from the appropriate

20 sulfides in accordance with the procedures disclosed In Example 52.

Example 53: Preparation of N-(3-methyl-1-(3-fluoropyridin-5-y1)-1H-pyrazol-4-yON-ethyl-2-

methyl-(3-oxido-0 4-sulfanylidenecyanamide)(methyl)propanamIde (Compound 250)

0

%

N N

To a solution of N-ethyl-N-(1-(5-fiuoropyridin-3-y1)-3-methyl-1H-pyrazol-4-y1)-2-methyl-3-

25 (methylthio)propanamide (0.30 g, 0.89 mmol) In dichloromethane (3.57 mL) at 0 °C was added

cyanamide (0.07 g, 1.78 mmol) and lodobenzenediacetate (0.31 g, 0.98 mmol) and

subsequently stirred at room temperature for 1 hour. The reaction was concentrated to dryness

and the crude material was purified by silica gel column chromatography (10% methanol/ethyl

acetate) to give the desired sulfilamine as a light yellow solid (0.28 g, 85%). To a solution of

30 70% mCPBA (0.25g. 1.13 mmol) in ethanol (4.19 mL) at 0°C was added a solution of

88

17149

potassium carbonate (0.31 g, 2.26 mmol) In water (4.19 mL) and stirred for 20 minutes after

which a solution of sulfilamine (0.28 g, 0.75 mmol) In ethanol (4.19 mL) was added In one

portion. The reaction was stirred for 1 hour at 0 °C. The excess mCPBA was quenched with

10% sodium thiosulfite and the reaction was concentrated to dryness. The residue was purified

5 by silica gel chromatography (0-10% methanol/dichloromethane) to give the desired product as

a clear oil (0.16g. 56%): IR (thin film) 1649 cm''; 'H NMR (400 MHz, CDCI3) 6 8.80 (dd, J =

43.8, 10.1 Hz, 1H), 8.51 -8.36 (m, 1H), 8.11 (d, J = 38.7 Hz, 1H), 7.96 - 7.77 (m, 1H), 4.32 -

3.92 (m, 2H), 3.49 - 3.11 (m, 6H), 2.32 (s, 3H), 1.27 - 1.05 (m, 6H); ES1MS m/z 393 ([M+H] °).

Example 54: Preparation of N-ethy141,4,4-trifluoro-3-methoxy-N-(3-methyl-1-(pyridin-3-y1)-

10 1H-pyrazol-4-y1)-3-(trifluoromethyl)butanamide (Compound 276)

o

0- OMe

CF3 CF3

N

To a solution of N-ethy1-4,4,4-trifluoro-3-hydroxy-N-(3-methy1-1-(pyridin-3-y1)-1H-pyrazol-

4-y1)-3-(trifluoromethyl)butanamide (184 mg, 0.448 mmol) in DMF (3 mL) stirring at 0°C was

added sodium hydride (26.9 mg, 0.673 mmol). The solution was stirred at 0 °C for 0.5 hour.

15 Then lodomethane (0.034 mL, 0.538 mmol) was added and Ice bath was removed and the

mixture was stirred at 25 °C overnight. Reaction was worked up by slow addition of water and

further diluted with 20 mL of water, then extracted with 4x20 mL of Et0Ac. The combined

organic layers were washed with water, dried over Na2504 and concentrated. Silica Gel

chromatography (0-100% Et0Ac/hexane) gave N-ethy1-4,4,4-trifluoro-3-methoxy-N-(3-methy1-1-

20 (pyridin-3-09-1H-pyrazol-4-09-3-(trifluoromethyl)butanamide (52 mg, 0.123 mmol, 27.3% yield)

as a white solid: mp = 83-86 °C; 'H NMR (400 MHz, CDCI3) 68.94 (d, J = 2.5 Hz, 1H), 8.59 (dd,

J = 4.7, 1.3 Hz, 1H), 8.01 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.85 (s, 1H), 7.44 (ddd, J = 8.3, 4.8,

0.6 Hz, 1H), 4.00 (brs, 1H), 3.73(s, 3H), 3.39 (brs, 1H), 2.86 (s, 2H), 2.26 (s, 3H), 1.16 (t, J=

7.1 Hz, 3H); ESIMS m/z 425 ([M+H] °); IR (Thin film) 1664 ce.

25 Compound 327 was prepared from the corresponding intermediates and starting

materials In accordance with the procedures disclosed in Example 54.

Example 55, Step 1: Preparation of N-(2-((tert-butyldimethylsilyi)oxy)ethyl)-N-(3-chloro-1-

(pyridin-3-y1)-1H-pyrazol-4-y1)-2-methyl-3-(methylthio)propanamide

CI 0

89

17149

A solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-2-methyl-3-

(methylthio)propanamide (0.150g. 0.483 mmot) in N,N-dimethylformamide (2.413 ml) was

cooled to 0 °C. Sodium hydride (0.039 g, 0.965 mmol, 60% dispersion) was added at and the

reaction was stirred at 0 °C for 30 minutes. (2-Bromoethoxy)(tert-butyl)dimethylsilane (0.231 g,

5 0.965 mmol) was added, the Ice bath was removed, and the reaction was stirred at room

temperature for 2 hours. The reaction was heated at 65 °C for 1.5 hours and then cooled to

room temperature. Brine was added and the mixture was extracted with dichloromethane. The

combined organic phases were concentrated and chromatographed (0-100% ethyl

acetate/hexanes) to give N-(2-((tert-butyldimethylsily0oxy)ethy0-N-(3-chloro-1-(pyridin-3-y0-1 H-

10 pyrazol-4-y1)-2-methyl-3-(methylthio)propanamide (0.120g, 0.243 mmol, 50.4%) as an orange

oil: IR (thin film) 1669 cm"'; 'H NMR (400 MHz, CDCI3) 6 8.88 (d, J = 2.5 Hz, 1H), 8.55 (dd, J =

4.7, 1.4 Hz, 1H), 8.05 (s, 1H), 7.98 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.41 (ddd, J = 8.4, 4.8, 0.5

Hz, 1H), 4.35 — 3.06 (m, 4H), 2.86 — 2.73 (m, 1H), 2.73 — 2.59 (m, 1H), 2.41 (dd, J = 12.8, 5.7

Hz, 1H), 1.94(s, 3H), 1.11 (d, J = 6.7 Hz, 3H), 0.80(s, 9H), 0.00(s, 3H), 0.01 (s, 3H); ESIMS

15 m/z 470 ([M+Hr).

Example 55, Step 2: Preparation of N-(3-chloro-1-(pyridin-3.11)-1H-pyrazol-411)-N-(2-

hydroxyethyl)-2-methyl-3-(methylthlo)propanamide (Compound 535)

CI 0 N

n' ? N OH

To a solution of N-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-Hpyridin-3-y1)-1H-

20 pyrazol-4-y1)-2-methyl-3-(methylthio)propanamide (0.180 g, 0.384 mmol) In tetrahydrofuran

(1.54 ml) was added tetrabutylammonlum fluoride (0.201 g, 0.767 mmol) and the reaction was

stirred at room temperature for 2 hours. Brine was added and the mixture was extracted with

ethyl acetate. The combined organic phases were concentrated and chromatographed (0-100%

water/acetonitrile) to give N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-(2-hydroxyethyl)-2-

25 methyl-3-(methylthio)propanamide as a white oil (0.081g, 0.217 mmol, 56.5 %): IR (thin film)

3423, 1654 cm'; 'H NMR (400 MHz, CDCI 3) 69.00 (d, J= 2.5 Hz, 1H), 8.62 (dd, J = 4.7, 1.2

Hz, 1H), 8.25 (s, 1H), 8.07 (ddd, J = 8.3, 2.4, 1.3 Hz, 1H), 7.47 (dd, J = 8.3, 4.7 Hz, 1H), 4.47 —

3.70 (m, 3H), 3.65 — 3.09 (m, 2H), 2.91 —2.68 (m, 2H), 2.48 (dd, J = 12.4, 5.0 Hz, 1H), 2.01 (s,

3H), 1.18 (d, J = 6.5 Hz, 3H); ESIMS m/z 356 ([M+H]).

30 Example 56: Preparation of 2-(N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-2-methyl-3-

(methylthio)propanamIdo)ethyl acetate (Compound 547)

90

17149

Cl

? No

0

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-(2-hydroxyethyl)-2-

methyl-3-(methylthio)propanamide (0.045g. 0.127 mmol) In dichloromethane (1.27 ml) was

added N,N-dimethylpyridin-4-amine (0.023g. 0.190 mmol) and triethylamine (0.019g. 0.190

5 mmol) followed by acetyl chloride (0.015g. 0.190 mmol). The reaction was stirred at room

temperature overnight. Water was added and the mixture was extracted with dichloromethane.

The combined organic phases were concentrated and chromatographed (0-100% ethyl

acetate/hexanes) to give 2-(N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-411)-2-methyl-3-

(methylthio)propanamido)ethyl acetate as a yellow oil (0.015 g, 0.034 mmol, 26.8 %): IR (thin

10 film) 1739, 1669 ce; 1 H NMR (400 MHz, CDCI3) 6 8.97 (d, J = 2.3 Hz, 1H), 8.64 (dd, J = 4.7,

1.4 Hz, 1H), 8.15 (s, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.47 (ddd, J= 8.3, 4.8, 0.7 Hz,

1H), 4.50 — 3.40 (m, 4H), 2.84 (dd, J = 12.7, 8.9 Hz, 1H), 2.78 — 2.63 (m, 1H), 2.46 (dd, J =

12.7, 5.4 Hz, 1H), 2.03(s, 3H), 2.01 (s, 3H), 1.16(d, J= 6.6 Hz, 3H); ESIMS ink 398 ([M+H]).

Example 57: Preparation of 2,2-dIdeuterio-3-methylsulfanyl-propanoic acid

0

HO SMe

15 D D

To a 100 mL round bottom flask was added 3-(methylthio)propanoic acid (3 g, 24.96

mmol), followed by D20 (23 mL) and KOD (8.53 mL, 100 mmoI) (40% wt solution in D20) , the

solution was heated to reflux overnight. NMR showed ca. 95% D at alpha-position. The reaction

was cooled down and quenched with concentrated HCI until pH<2. White precipitate appeared

20 in aqueous layer upon acidifying. Reaction mixture was extracted with 3 x 50 mL Et0Ac, the

combined organic layers were dried over Na2SO4, concentrated In vacuo to almost dryness. 100

mi. hexane was added and the solution was concentrated again to give 2,2-dideuterio-3-

methylsulfanyl-propanoic acid as a colorless oil (2.539 g, 20.78 mmol, 83%): IR (Thin film) 3430,

1704 cm-1 ; 1 H NMR (400 MHz, CDCI3) 62.76 (s, 2H), 2.14 (s, 3H); "C NMR (101 MHz, CDCI3)

25 6 178.28, 38.14-28.55(m), 28.55, 15.51; EIMS miz 122..

2-Deuterio-2-methy1-3-methylsulfanyl-propanoic acid was prepared as described In

Example 57 to afford a colorless oil (3.62 g, 26.8 mmol, 60.9 %): IR (Thin film) 2975, 1701 cm -1 ;

1 H NMR (400 MHz, CDCI3) 6 11.39 - 10.41 (bit, 1H), 2.88 - 2.79 (d, J = 13.3 Hz, 1H), 2.61 -

2.53 (d, J = 13.3 Hz, 1H), 2.16 - 2.09 (s, 3H), 1.32 - 1.25 (s, 3H); "C NMR (101 MHz, CDCI 3) 6

30 181.74, 39.74 - 39.02 (m), 37.16, 16.50, 16.03; EIMS ink 135.

Example 58: Preparation of 2-methy1-3-(trideuteriomethylsulfanyl)propanoic acid

91

17149

0

HO 1 To a 50 mL round bottom flask was added 3-mercapto-2-methylpropanoic acid (59, 41.6

mmol), followed by Me0H (15 mL), the solution was stirred at 25°C. Potassium hydroxide (5.14

g, 92 mmol) was added slowly as the reaction Is exothermic. lodomethane-d3 (6.63 g, 45.8

5 mmol) was added slowly and then the reaction mixture was heated at 65 °C overnight. The

reaction was worked up by addition of 2 N HCI until the mixture was acidic. It was then extracted

with Et0Ac (4x50 mL) and the combined organic layers were dried over Na2SO4, concentrated

and purified with flash chromatography, eluted with 0-80% Et0Adhexane to give 2-methy1-3-

(trideuteriomethylsulfanyl)propanoic acid (4.534 g, 33.0 mmol, 79 %) as colorless oil: IR (Thin

10 film) 3446, 1704 mi l ; 1 H NMR (400 MHz, CDCI3) 52.84 (dd, J = 13.0, 7.1 Hz, 1H), 2.80 - 2.66

(m, 1H), 2.57 (dd, J= 13.0, 6.6 Hz, 1H), 1.30(d, J= 7.0 Hz, 3H); EIMS rniz 137.

Example 59: Preparation of 2-hydroxy-3-(methylthio)propanoic acid

0

SMe OH

Sodium methanethiolate (4.50 g, 64.2 mmol) was added at 25 °C to a solution of 3-

15 chloro-2-hydroxypropanoic acid (2 g, 16.06 mmol) in Me0H (120 mL). The reaction mixture was

heated at reflux for 8 hours, then cooled to 25 °C. The precipitate was removed by filtration and

the filtrate was evaporated. The residue was acidified to pH 2 with 2 N HCI, extracted with

Et0Ac (3 x 30 mL), combined organic layers were dried with Na2SO4, concentrated to give 2-

hydroxy-3-(methylthlo)propanoic acid as a white solid, (1.898g. 13.94 mmol, 87% yield): mp

20 55-59 °C; IR (Thin film) 2927, 1698 cm'; 'H NMR (400 MHz, CDCI3) 66.33 (s, 3H), 4.48 (dd, J

= 6.3, 4.2 Hz, 1H), 3.02 (dd, J = 14.2, 4.2 Hz, 1H), 2.90 (dd, J = 14.2, 6.3 Hz, 1H), 2.20 (s, 3H);

EIMS m/z 136.

Example 60: Preparation of 2-methoxy-3-(methylthio)propanoic acid

o

HO SMe OMe

25 To a stirred solution of sodium hydride (0.176 g, 4.41 mmol) in DMF (5 ml.) was added a

solution of 2-hydroxy-3-(methylthio)propanoic acid (0.25 g, 1.836 mmol) in 1 mi. DMF at 25 °C

and stirred for 10 min. Vigorous bubbling was observed upon addition of NaH. Then

lodomethane (0.126 ml., 2.020 mmol) was added and the solution was stirred at 25 °C

overnight. The reaction was quenched by addition of 2 N HCI, extracted with 3 x 10 mL of

30 Et0Ac, the combined organic layers were washed with water (2 x 20 mL), concentrated and

purified by column chromatography, eluted with 0-100% Et0Ac/hexane, gave 2-methoxy-3-

(methylthio)propanoic acid (126 mg, 0.839 mmol, 45.7% yield) as colorless oil: I HNMR (400

92

HO

17149

MHz, CDCI3) 6 9.10 (s, 1H), 4.03 (dd, J = 6.9, 4.4 Hz, 1H), 3.51 (s, 3H), 2.98 - 2.93 (m, 1H),

2.86 (dd, J = 14.1, 6.9 Hz, 1H), 2.21 (s, 3H); EIMS m/z 150.

Example 61: Preparation of 2-(acetylthlomethyl)-3,3,3-trlfluoropropanoic acid

0 o

HO)HS)C CF3

5 To a 50 mL round bottom flask was added 2-(trifluoromethypacryfic acid (6 g, 42.8

mmol), followed by thioacetic acid (4.59 ml, 64.3 mmol). The reaction was slightly exothermic.

The mixture was then stirred at 25 °C overnight. NMR showed some starting material (-30%).

One more equiv of thioacetic acid was added and the mixture was heated at 95 °C for 1 hour,

then allowed to cool to room temperature. Mixture was purified by vacuum distillation at 2.1-2.5

10 mm Hg, fraction distilled at 80-85 °C was mostly thloacetic acid, fraction distilled at 100-110 °C

was almost pure product, contaminated by a nonpolar Impurity (by TLC). It was again purified by

flash chromatography (0-20% Me0H/ DCM), to give 2-(acetylthlomethy9-3,3,3-

trifluoropropanoic acid (7.78 g, 36.0 mmol, 84 % yield) as colorless oil, which solidified under

high vacuum to give a white solid: mp 28-30 °C; 1 H NMR (400 MHz, CDCI3) 67.52 (brs, 1H),

15 3.44 (dt, J = 7.5, 3.5 Hz, 2H), 3.20 (dd, J = 14.9, 11.1 Hz, 1H), 2.38 (s, 3H); 13C NMR (101 MHz,

CDCI3) 6 194.79, 171.14, 123.44 (q, J = 281.6 Hz), 50.47 (q, J = 27.9 Hz), 30.44, 24.69 (q, J =

2.6 Hz); 13F NMR (376 MHz, CDCI3) 6 -67.82.

Example 62: Preparation of 3,3,3-trifluoro-2-(methylthlomethyl)propanolc acid

0

HO CF3

20 To a solution of 2-(acetylthiomethyl)-3,3,3-trifluoropropanoic acid (649 mg, 3 mmol) in

Me0H (5 mL) stirring at 25 °C was added pellets of potassium hydroxide (421 mg, 7.50 mmol)

In four portions over 5 minutes. Reaction was exothermic. Then Mel was added in once, the

reaction mixture was then heated at 65°C for 18 hours. The reaction was then cooled down and

quenched with 2N HCI until acidic, and the aqueous layer extracted with chloroform (4 x 20 mL).

25 Combined organic layer was dried, concentrated in vacuo, purified with flash chromatography

(0-20% Me0H/DCM), to give 3,3,3-trifluoro-2-(methylthiomethyl)propanoic acid (410 mg, 2.179

mmol, 72.6% yield) as a light yellow oil: 1 H NMR (400 MHz, CDC13) 6 10.95 (s, 1H), 3.49 - 3.37

(m, 1H), 3.02 (dd, J = 13.8, 10.8 Hz, 1H), 2.90 (dd, J = 13.8, 4.0 Hz, 1H), 2.18 (s, 3H); 13C NMR

(101 MHz, CDCI3) 6 172.04 (q, J = 2.8 Hz), 123.55 (q, J = 281.2 Hz), 50.89 (q, J = 27.5 Hz),

30 29.62 (q, J = 2.3 Hz), 15.85; "F NMR (376 MHz, CDCI 3) 6-67.98.

Example 63: Preparation of 3-(methylthio)pentanoic acid

0

HO

93

17149

S,S-dimethyl carbonodithioate (1.467 g, 12.00 mmol) was added with vigorous stirring to

a solution of (E)-pent-2-enoic acid (2.002 g, 20 mmol) In 30% KOH solution (prepared from

potassium hydroxide (3.87g. 69 mmol) and Water (10 mL)). The reaction mixture was slowly

heated to 90°C over a period of 20-30 min. Heating was continued for 3 hours before the

5 reaction was cooled down to 25 °C and quenched slowly with NCI. The mixture was then

extracted with DCM (3 x 30 ml), combined organic layer dried and concentrated to give 3-

(methylthio)pentanoic acid (2.7g, 18.22 mmol, 91 % yield) as light orange oil: IR (Thin film)

2975, 1701 cm -1 ; 1 H NMR (400 MHz, CDC13) 6 2.92 (qd, J= 7.3, 5.6 Hz, 1H), 2.63 (d, J= 7.2

Hz, 2H), 2.08 (s, 3H), 1.75 - 1.51 (m, 2H), 1.03(t, J= 7.4 Hz, 3H); 13C NMR (101 MHz, CDC6) 6

10 178.14, 43.95, 39.78, 27.04, 12.95, 11.29; EIMS m/z 148.

4-methyl-3-(methylthio)pentanoic acid was prepared as described In Example 63 and

Isolated as a colorless oil: IR (Thin film) 2960, 1704 cm'; 'H NMR (400 MHz, CDCI3) 6 2.88

(ddd, J= 9.1, 5.4, 4.7 Hz, 1H), 2.68 (dd, J= 16.0, 5.5 Hz, 1H), 2.55 (dd, J= 16.0, 9.1 Hz, 1H),

2.13 (s, 3H), 2.01 - 1.90 (m, 1H), 1.03 (d, J= 6.8 Hz, 3H), 0.99 (d, J= 6.8 Hz, 3H); EIMS rn/z

15 162.

0 S' CH3

HOA CH3

3-(Methylthlo)hexanoic acid was prepared according to the procedure described In

Example 63 and Isolated as a colorless oil: IR (thin film) 2921, 1705 cm'; 1 H NMR (400 MHz,

CDCI3) 6 10.72 (s, 1H), 3.06 - 2.92 (m, 1H), 2.63 (dd, J= 7.2, 2.6 Hz, 2H), 2.08(s. 3H), 1.66 -

20

1.37(m, 4H), 0.94(t, J= 7.2 Hz, 3H); 13C NMR (101 MHz, CDCI 3) 6 178.19, 42.00, 40.20,

36.33, 20.05, 13.80, 12.86.

O CF3

HO' S

3-(Cyclopentylthio)-4,4,4-trifiuorobutanoic acid was prepared according to the procedure

described In Example 63 and isolated as a colorless oil: IR (thin film) 2959, 1714 mi l ; 'H NMR

25 (400 MHz, CDCI3) 6 9.27 (s, 1H), 3.74 - 3.53 (m, 1H), 3.36 (p, J= 6.9 Hz, 1H), 2.96 (dd, J=

16.9, 3.9 Hz, 1H), 2.61 (dd, J= 16.9, 10.6 Hz, 1H), 2.15- 1.92 (m, 2H), 1.84- 1.68 (m, 2H), 1.68

- 1.54(m, 311), 1.53 - 1.43 (m, 1H); EIMS m/z 242.

HO

3-Cyclopropyl-3-(methylthio)propanoic acid was prepared according to the procedure

30 described In Example 63 and Isolated as a colorless oil: IR (thin film) 3002, 1703 cm -1 ; 1 H NMR

(400 MHz, CDCI 3) 62.73 (dd, J= 7.1, 2.2 Hz, 2H), 2.39 (dt, J= 9.7, 7.1 Hz, 1H), 2.17(s, 3H),

94

17149

0.97 (dddd, J= 14.6, 13.0, 6.5, 3.6 Hz, 1H), 0.74- 0.52(m, 2H), 0.43 - 0.35 (m, 1H), 0.35 - 0.26

(m, 1H); "C NMR (101 MHz, CDCI 3) 6 177.60, 47.18, 40.66, 16.34, 13.61, 5.30, 4.91.

,CH3 0 S CH3

HOWCH3

5-Methyl-3-(methylthlo)hexanoic acid was prepared according to the procedure

5 described In Example 63 and isolated as a light orange oil: IR (thin film) 2955, 1705 cm -1 ; 1 1-I

NMR (400 MHz, CDCI3) 6 3.12 - 2.96 (m, 1H), 2.70 - 2.53 (m, 2H), 2.07 (s, 3H), 1.91 - 1.78 (m,

1H), 1.49 (ddd, J= 14.6, 9.1, 5.6 Hz, 1H), 1.38 (ddd, J= 14.1, 8.4, 5.9 Hz, 1H), 0.93(d, J= 2.4

Hz, 3H), 0.92 (d, J= 2.3 Hz, 3H); "C NMR (101 MHz, CDCI 3) 6 178.07, 43.35, 40.53, 39.99,

25.45, 22.91, 21.83, 12.38.

10 HO

2-(1-(Methylthio)cyclobutypacetic acid was prepared according to the procedure

described in Example 63 and Isolated as a white crystalline solid: mp 43-46 °C; IR (thin film)

2955, 1691 crti l ; I 11 NMR (400 MHz, CDCI3) 6 2.77 (s, 2H), 2.30 (tdd, J= 5.4, 3.9, 2.2 Hz, 2H),

2.23 - 2.13 (m, 3H), 2.04 (s, 3H), 2.00- 1.89 (m, 1H); "C NMR (101 MHz, CDCI3) 6 176.84,

15 47.08, 44.08, 33.27, 16.00, 11.72.

HO

3-(Methytthio)-3-phenylpropanoic acid was prepared according to the procedure

described In Example 63 and isolated as a white solid: mp 75-77 °C; IR (thin film) 2915, 1704

cm -1 ; I li NMR (400 MHz, CDCI 3) 6 7.35 - 7.29 (m, 4H), 7.29 - 7.20 (m, 1H), 4.17 (t, J= 7.6 Hz,

20 1H), 2.93 (dd, J= 7.6, 3.2 Hz, 2H), 1.91 (s, 3H); "C NMR (101 MHz, CDCI3) 6 176.98, 140.60,

128.61, 127.64, 127.56, 46.19, 40.70, 14.33.

CF3

HO S

3-(Methylthio)-3-(4-(trifiuoromethyl)phenyl)propanoic acid was prepared according to the

procedure described in Example 63 and isolated as a white solid: mp 106-108 °C; IR (thin film)

CH3

95

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2924, 1708 cm-1 ; 1 H NMR (400 MHz, CDCI 3) 67.59 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H),

4.21 (t, J = 7.6 Hz, 1H), 2.95 (qd, J = 16.3, 7.7 Hz, 2H), 1.92 (s, 3H); EIMS m/z (M-1) 263.

OMe

HO S'CH3

3-(3-MethoxyphenyI)-3-(methylthio)propanoic acid was prepared according to the

5 procedure described In Example 63 and isolated as a white solid: mp 61-63 °C; IR (thin film)

2921, 1699 cm'; 'H NMR (400 MHz, CDCI 3) 6 7.28 - 7.17 (m, 1H), 6.94 - 6.86 (m, 2H), 6.79

(ddd, J = 8.3, 2.5, 0.9 Hz, 1H), 4.14 (t, J = 7.6 Hz, 1H), 3.80 (s, 3H), 2.92 (d, J = 8.0 Hz, 2H),

1.92 (s, 3H); EIMS m/z 225.

N I

HO S,CH3

10 3-(Methylthio)-3-(pyridin-3-y9propanoic acid was prepared according to the procedure

described In Example 63 and isolated as a white semi-solid: IR (thin film) 3349, 1547 cni l ; i fl

NMR (400 MHz, CD30D) 68.54 (dd, J = 2.3, 0.8 Hz, 1H), 8.39 (dd, J = 4.9, 1.6 Hz, 1H), 7.90

(dt, J - 7.9, 2.0 Hz, 1H), 7.41 (ddd, J = 8.0, 4.9, 0.8 Hz, 1H), 4.26 (dd, J = 9.2, 6.5 Hz, 1H), 2.81

(dd, J = 14.7, 6.5 Hz, 1H), 2.71 (dd, J = 14.8, 9.2 Hz, 1H), 1.94 (s, 3H); EIMS m/z 198.

0 /

15 HO)L-SAH3 3-(Methyithio)-3-(pyridin-4-yl)propanoic acid was prepared according to the procedure

described in Example 63 and isolated as a white solid: mp 187-189 °C; IR (thin film) 1692 cm -1 ;

1 H NMR (400 MHz, CD300) 6 8.57- 8.38 (m, 2H), 7.55 - 7.37 (m, 2H), 4.19 (dd, J = 8.2, 7.3 Hz,

1H), 2.93 (dd, J= 7.7, 2.8 Hz, 2H), 1.94 (s, 3H); EIMS m/z 198.

20 Example 64: Preparation of ethyl 14hydroxymethyl)cyclopropanecarboxylate

0

HO o'

A 1M solution of lithium aluminum tri-tett-butoxyhydride in tetrahydrofuran (70.90 mL,

70.90 mmol) was added to a stirred solution of diethyl cyclopropane-1,1'-dicarboxylate (6 g,

32.20 mmol) in tetrahydrofuran (129 mL) at 23 °C. The resulting solution was heated to 65°C

25

and stirred for 24 h. The cooled reaction mixture was diluted with a 10% solution of sodium

bisulfate (275 mL) and extracted with ethyl acetate. The combined organic layers were dried

96

17149

(MgSO4), filtered, and concentrated to dryness to give the desired product as a pale yellow oil

(4.60, 91%): 1 H NMR (300 MHz, CDCI3) 64.16 (q, J = 7 Hz, 2H), 3.62 (s, 2H), 2.60 (br s, 1H),

1.22-1.30 (m, 5H), 0.87 (dd, J = 7, 4 Hz, 2H).

Example 65: Preparation of ethyl 1-((methylsulfonyloxy)methyl)cyclopropanecarboxylate

0

Triethylamine (5.57 mL, 40.00 mmol) and methanesulfonyl chloride (2.85 mL, 36.60

mmol) were sequentially added to a stirred solution of ethyl 1-

(hydroxymethyl)cyclopropanecarboxylate (4.80 g, 33.30 mmol) in dichloromethane (83 mL) at

23 °C. The resulting bright yellow solution was stirred at 23 °C for 20 h. The reaction mixture

10 was diluted with water and extracted with dichloromethane. The combined organic layers were

dried (MgSO4), filtered, and concentrated to dryness to give the desired product as a brown oil

(6.92g, 94%): 1 H NMR (300 MHz, CDCI3) 64.33 (s, 2H), 4.16 (q, J =7 Hz, 2H), 3.08(s, 3H),

1.43 (dd, J =7, 4 Hz, 2H), 1.26(t, J = 7 Hz, 3H), 1.04 (dd, J =7, 4 Hz, 211).

Example 66: Preparation of ethyl 1-(methylthlomethyucyclopropanecarboxylate

0

15 4::K

Sodium methanethiolate (4.36g. 62.30 mmol) was added to a stirred solution of ethyl 1-

((methylsulfonyloxy)methyl) cyclopropanecarboxylate (6.92g. 31.10 mmol) In Nisl-

dimethylformamide (62.30 mL) at 23 °C. The resulting brown suspension was stirred at 23 °C

for 18 h. The reaction mixture was diluted with water and extracted with diethyl ether. The

20 combined organic layers were dried (MgSO 4), filtered, and concentrated by rotary evaporation

to afford the title compound as a brown oil (5.43g. 100%): I FI NMR (300 MHz, CDCI 3) 64.14 (q,

J = 7 Hz, 2H), 2.83 (s, 2H), 2.16 (s, 3H), 1.31 (dd, J = 7, 4 Hz, 2H), 1.25 (t, J = 7 Hz, 3H), 0.89

(dd, J = 7, 4 Hz, 2H).

Example 67: Preparation of 1-(methylthlomethyncyclopropanecarboxylic acid

0

25 OH

A 50% solution of sodium hydroxide (12.63 mL, 243 mmol) was added to a stirred

solution of ethyl Hmethylthiomethypcyclopropanecarboxylate (5.43g. 31.20 mmol) in absolute

ethanol (62.30 mL) at 23 °C. The resulting solution was stirred at 23 °C for 20 h. The reaction

mixture was diluted with a 0.5 M solution of sodium hydroxide and washed with

30 dichloromethane. The aqueous layer was acidified to pHm1 with concentrated hydrochloric acid

and extracted with dichloromethane. The combined organic layers were dried (Na2SO4), filtered,

and concentrated and concentrated to dryness to give the desired product as a light brown oil

97

5

17149

(2.10 g, 46%): I H NMR (300 MHz, CDCI3) 62.82 (s, 2H), 2.17 (s, 3H), 1.41 (dd, J = 7, 4 Hz,

2H), 0.99 (dd, J = 7, 4 Hz, 2H).

Example 68: Preparation of 2,2-dimethy1-3-(methylthlo)propanoic acid

0

OH

5 2,2-Dimethy1-3-(methylthio)propanoic acid can be prepared as demonstrated In the

literature (reference Musker, W. K.; eta?. J. Org. Chem. 1996, 51, 1026-1029). Sodium

methanethiolate (1.0 g, 14 mmol, 2.0 equiv) was added to a stirred solution of 3-chloro-2,2-

dimethylpropanoic acid (1.0 g, 7.2 mmol, 1.0 equiv) in N,N-dimethylformamIde (3.7 mL) at 0 °C.

The resulting brown suspension was allowed to warm to 23 °C and stirred for 24 h. The reaction

10 mixture was diluted with a saturated solution of sodium bicarbonate (300 mL) and washed with

diethyl ether (3 x 75 mL). The aqueous layer was acidified to pH=1 with concentrated

hydrochloric acid and extracted with diethyl ether (3 x 75 mL). The combined organic layers

were dried (sodium sulfate), gravity filtered, and concentrated to afford a colorless oil (1.2 g,

99% crude yield). NMR (300 MHz, CDCI 3) 62.76 (s, 2H), 2.16 (s, 3H), 1.30 (s, 6H).

15 Example 69: Preparation of 4,4,4-trifluoro-3-(methylthlo)butanoic acid

0 SMe

HO)Li C F3

To a 100 mL round bottom flask was added (E)-4,4,4-trifluorobut-2-enoic acid (8 g, 57.1

mmol) and Methanol (24 mL), the solution was stirred In a water bath, then sodium

methanethiolate (10.01 g, 143 mmol) was added in three portions. Vigorous bubbling was

20 observed, the mixture was stirred at 25 °C overnight, NMR showed no more starting material.

To the reaction mixture was added 2 N HCI until acidic. The mixture was extracted with

chloroform (5 x 50 mL), combined organic layer was dried over Na2SO4, concentrated In vacuo

and further dried under high vacuum until there was no weight loss to give 4,4,4-trifluoro-3-

(methylthio)butanolc acid (10.68g. 56.8 mmol, 99% yield) as a colorless oil: 1 H NMR (400

25 MHz, CDCI3) 6 10.88 (s, 1H), 3.53 (dqd, J = 10.5, 8.3, 4.0 Hz, 1H), 2.96 (dd, J= 16.9, 4.0 Hz,

1H), 2.65 (dd, J= 16.9, 10.4 Hz, 1H), 2.29(s, 3H); 13C NMR (101 MHz, CDC13) 6 175.78 (s),

126.61 (q, Jc.F= 278.8 Hz), 44.99 (q, sic-F = 30.3Hz), 34.12(d, Jc-F = 1.7 Hz), 15.95(s); EIMS

ink 162.

Example 70: Preparation of 3-methyl-3-methylsulfanyl-butyric acid

0 H.

o 30

3-methy1-3-methylsulfanyl-butyric acid was made using the procedures disclosed in

J.Chem Soo Perkin 1, 1992, 10, 1215-21).

98

17149

Example 71: Preparation of 3-methylsulfanyl-butyric acid

0 1 H,

(:)9 3

3-Methylsulfanyl-butyric acid was made using the procedures disclosed In Synthetic

Comm.,1985, 15(7), 623-32.

5 Example 72: Preparation of tetrahydro-thiophene-3-carboxylic acid

0

Ls Tetrahydro-thiophene-3-carboxylic acid was made using the procedures disclosed in

Heterocycles, 2007, 74, 397-409.

Example 73: Preparation of 2-methyl-3-methylsulfanyl-butyric acid

0

10 Fi

2-Methy1-3-methylsulfanyl-butyric acid was made as described In J.Chem Soc Perkin 1,

1992, 10, 1215-21.

Example 74: Preparation of (1S,25)-2-(methylthio)cyclopropanecarboxylic acid

0 it. S

0 sive# A

15 (15,25)-2-(Methylthio)cyclopropanecarboxylic acid was made using the procedures

disclosed in Synthetic Comm., 2003, 33 (5); 801-807.

Example 75: Preparation of 2-(2-(methylthio)ethoxy)propanoic acid

0

HO 0.,./■s,'

2-(2-(Methylthio)ethoxy)propanoic acid was made as described in WO 2007/064316 Al.

20

99

17149

Example 76: Preparation of 2-((tetrahydrofuran-3-yl)oxy)propanolc acid

0

HO to 24(Tetrahydrofuran-3-yl)oxy)propanoic acid was made as described in WO

2007/064316 Al.

Example 77: Preparation of tert-Butyl 1-(5-fluoropyridin-3-y1)-3-methyl-1H-pyrazol-4-

yl(prop-2-ynyi)carbamate (Compound 601)

5 To an Ice cold solution of tert-butyl 1-(5-fluoropyridin-3-y1)-3-methy1-1H-pyrazol-4-

ylcarbamate (1200 mg, 4.11 mmol) in dry DMF (4 mL) under nitrogen was added 60% wt

sodium hydride (197 mg, 4.93 mmol) and the mixture stirred for 10 min. 3-Bromoprop-1-yne

(733 mg, 6.16 mmol) was then added and the mixture was stirred for additional 0.5 h at between

0 — 5 °C. The mixture was allowed to warm to ambient temperature and then stirred for

10 additional 3 h at room temperature. The brown reaction mixture poured Into saturated aqueous

NH4C1(20 mL), and diluted with ethyl acetate (50 mL). The organic phase was separated and

the aqueous phase extracted with ethyl acetate (20 mL). The combined organic phase was

washed with brine, dried over anhydrous MgSO4, filtered, and concentrated In vacuo to give a

brown oil. This oil was purified on silica gel eluting with mixtures of hexanes and ethyl acetate to

15 give the title compound as a light yellow solid (1103 mg, 81%); mp 81-82 °C; 1 H NMR (400

MHz, CDCI3) 6 8.73 (s, 1H), 8.37 (d, J = 2.5 Hz, 1H), 7.99 (s, 1H), 7.83 (dt, J = 9.5, 2.2 Hz, 1H),

4.31 (s, 2H), 2.29 (t, J = 2.4 Hz, 1H), 2.27 (s, 3H), 1.45 (s, 8H); ESIMS m/z 229.84 Dn. Compounds 596 and 606 were prepared in accordance with the procedure disclosed in

Example 77 from the corresponding amine.

20 Example 78: Preparation of 1-(5-fluoropyridin-3-y1)-3-methyl-N4prop-2-ynyl)-1H-pyrazol-4-

amine, hydrochloride

NH.HCI

‘1

To a solution of tert-butyl 1-(5-fluoropyridin-3-y1)-3-methy1-1H-pyrazol-4-yl(prop-2-

yrtyl)carbamate (1.03g. 3.11 mmol) In dioxane (5 mL) was added 4M HCI (3.9 mL, 15.5 mmol)

25 indioxane. The mixture was stirred at room temperature for 48 h and the resulting white solid

was filtered, washed with ether and dried under vacuum to give to give the title compound as a

100

17149

white solid (741 mg, 89%): mp 167-168 °C; I F1 NMR (400 MHz, DMSO do) 6 8.92 — 8.85 (m,

1H), 8.42 (d, J = 2.5 Hz, 1H), 8.15 (s, 1H), 8.12 — 8.02 (m, 1H), 3.85 (d, J = 2.5 Hz, 2H), 3.27 —

3.19 (m, 1H), 2.22 (s, 3H); ESIMS m/z 230.4 ((g). 3-Chloro-N-(prop-2-yny1)-1-(pyridin-3-y1)-1H-pyrazol-4-amlne, hydrochloride was

5 prepared In accordance with the procedure disclosed In Example 78 from (Compound 606): mp

180-182 °C; lE1 NMR (400 MHz, CDCI3) 59.22 (d, J= 2.5 Hz, 1H), 8.67 (dd, J= 5.3, 1.0 Hz,

1H), 8.64 (ddd, J = 8.6, 2.6, 1.2 Hz, 1H), 8.32 (s, 1H), 7.96 (dd, J = 8.6, 5.3 Hz, 1H), 3.81 (d, J =

2.4 Hz, 2H), 3.15 (t, J = 2.4 Hz, 1H); ESNS m/z 234 ([M+2]).

3-Methyl-N-(prop-2-yn-1-y1)-1-(pyrldin-3-y1)-1H-pyrazol-4-amine, hydrochloride was

10 prepared In accordance with the procedure disclosed In Example 78 from Compound 596: mp

161-163 °C; lEi NMR (400 MHz, DMSO-do) 68.46 (s, 1H), 8.05 (s, OH), 7.83 (d, J = 5.9 Hz, 1H),

7.57 (s, 1H), 7.29 (dd, J = 8.8, 5.6 Hz, 1H), 3.27 (d, J = 2.5 Hz, 2H), 1.52 (s, 3H); EIMS m/z

213.1 PM.

Example 79: Preparation of N-(1-(5-Fluoropyridin-3-y1)-3-methyl-1H-pyrazol-4-y1)-3-

15 (methylthlo)-N-(prop-2-ynyl)propanamide (Compound 605)

(4_/-s/

N Fn. I , N

To a stirred solution of 1-(5-fiuoropyridin-3-y1)-3-methyl-N-(prop-2-yn-1-y1)-1H-pyrazol-4-

amine, HCI (100 mg, 0.38 mmol) and N,N-dimethylpyridin-4-amine (115 mg, 0.94 mmol) In

CH2C12 (2 mL) was added 2-methy1-3-(methylthio)propanoyl chloride (69 mg, 0.45 mmol) and

20 the mixture stirred at room temperature for 24 h. The mixture was concentrated In vacuo to give

a brown oil, which was purified on silica gel eluting with mixtures of ethyl acetate and hexanes

to give the title compound as a colorless oil (80 mg, 61%): 1 1-1 NMR (400 MHz, CDCI3) 5 8.77 (d,

J = 1.7 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 8.05 (s, 1H), 7.86 (dt, J = 9.4, 2.3 Hz, 1H), 4.49 (s,

1H), 2.88 (dd, J = 12.8, 9.4 Hz, 1H), 2.74 (s, 1H), 2.45 (dd, J = 12.9, 5.0 Hz,1H), 2.34 (s, 3H),

25 2.24 (t, J = 2.5 Hz, 1H), 2.02 (s, 3H), 1.14 (d, J= 6.8 Hz, 3H); ESIMS m/z 347.5 ([M+H]).

Compounds 598, 599, 600, 602, 603, 607, 608 and 610 were prepared In accordance

with the procedure disclosed In Example 79 from the corresponding amines.

Example 80: Preparation of N-(3-Chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-4,4,4-trifluoro-3-

(methylthio)-N-(prop-2-yn-1-y1)butanamIde (Compound 613)

30

101

17149

To a 7 mt. vial was added 3-chloro-N-(prop-2-yn-1-y1)-1-(pyridin-3-)1)-1H-pyrazol-4-

amine (140 mg, 0.6 mmol), N,N-dimethylpyridin-4-amine (249 mg, 2.040 mmol), N1-

((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (276 mg, 1.440

mmol) followed by 4,4,4-trifluoro-3-(methylthio)butanoic acid (158 mg, 0.840 mmol) and DCE

5 (1.2 mt.). The solution was stirred at 25 °C for 18 hours, the crude reaction mixture was

concentrated and purified with silica gel chromatography (0-100% Et0Adhexane) to give the

title compound as a brown oil (237 mg, 0.588 mmol, 98%): (IR thin film) 1674 crti l ; I H NMR

(400 MHz, CDCI3) 6 8.97 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.7, 1.3 Hz, 1H), 8.13 (s, 1H), 8.07

(ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.48 (ddd, J = 8.3, 4.8, 0.5 Hz, 1H), 4.39 (s, 2H), 3.76 (dqd, J =

10

17.2, 8.6, 3.6 Hz, 1H), 2.67 (dd, J = 16.6, 3.6 Hz, 1H), 2.46 (dd, J = 16.5, 9.9 Hz, 1H), 2.29 (d, J

= 2.5 Hz, 4H); ESIMS a* 403 ([M+Hr).

Compounds 597, 604, 609, 614-616 were prepared in accordance with the procedure

disclosed In Example 80.

Example 81: Preparation of 3-Chloro-N-(prop-2-yny1)-1-(pyridin-311)-1H-pyrazol-4-amine

Cl

N / NH

15 N 1

To a solution of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(prop-2-yn-1-

yl)carbamate (2.2 g, 6.61 mmol) In dichloromethane (8.3 ml) was added 2,2,2-trifluoroacetic

acid (12.06 g, 106 mmol) and the reaction mixture was stirred at ambient temperature for 1

hour. The reaction was quenched by the addition of saturated sodium bicarbonate. The organic

20 layer was extracted with dichloromethane (2 x 20 mL). The organic layers were combined and

dried over sodium sulfate, filtered and concentrated without further purification to afford the title

compound as a beige solid (1.5 g, 6.12 mmol, 93%): I H NMR (400 MHz, CDCI3) 6 8.89 (d, J =

2.3 Hz, 1H), 8.50 (dd, J = 4.7, 1.4 Hz, 1H), 8.01 -7.93 (m, 1H), 7.54 (s, 1H), 7.37 (ddd, J = 8.3,

4.8, 0.7 Hz, 1H), 3.90 (s, 2H), 3.38 (s, 1H), 2.44- 2.09 (m, 1H); ESIMS miz 233 ([M+Hr).

25 Example 82: Preparation of N-(3-Chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-24methylthio)-N-

(prop-2-yn-1-yi)propanamIde (Compound 611)

CI 0

N/

To a solution of 2-(methylthio)propanoic acid (0.36 g, 3.00 mmol) In dichloromethane (3

mL) was added oxalyl dichloride (0.29 ml, 3.31 mmol) followed by one drop of N,N- 30 dimethylforrnamide. The reaction mixture was stirred for 30 minutes before all solvent was

evaporated. The resulting residue was dissolved In dichloromethane (2 mL) and It was added to

102

17149

a pre-stirred solution of 3-chloro-N-(prop-2-yn-1-y1)-1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.35 g,

1.50 mmol) and N-ethyl-N-Isopropylpropan-2-amine (0.57 ml, 3.31 mmol) in dichloromethane

(5.5 mL). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction

mixture was concentrated and the residue was purified using silica gel chromatography (0-100%

5 ethyl acetate/hexanes) to afford the title compound as a yellow oil (432 mg, 1.23 mmol, 85%):

1 H NMR (400 MHz, CDCI3) 6 8.97 (d, J = 2.5 Hz, 1H), 8.66 - 8.60 (m, 1H), 8.25 (s, 1H), 8.08 -

8.01 (m, 1H), 7.49 - 7.42 (m, 1H), 4.86 (s, 1H), 4.29 - 3.97 (m, 1H), 3.31 (d, J = 6.5 Hz, 1H),

2.30 - 2.24 (m, 1H), 2.09(s, 3H), 1.46(d, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCI3) 6 171.30,

148.66, 140.71, 140.18, 135.71, 127.87, 126.35, 124.11, 122.12, 78.53, 72.92, 53.39, 37.97,

10 16.42, 11.07; ESNS m/z 335 ([M+H]).

Compound 612 was prepared in accordance with the procedure disclosed In Example

82.

Example 83: Preparation of N-(3-Chloro-1-(pyridln-3-y1)-1H-pyrazol-4-y1)-2-

(methylsulflny1)-N-(prop-2-yn-1-y1)propanamide (Compound 617)

0

15 N

To a solution of N-(3-chloro-1 -(pyridin-3-y1)-1H-pyrazol-4-y1)-2-(methylthio)-N-(prop-2-yn-

1-yl)propanamide (0.1 g, 0.30 mmol) In hexafluoroisoproanol (2.0 ml) was added hydrogen

peroxide (35 wt %, 0.08 ml, 0.90 mmol) and the reaction mixture was stirred vigorously at

ambient temperature. The reaction was complete after 1 hour. The reaction was quenched with

20 saturated sodium sulfite solution and the organic layer was extracted with ethyl acetate (3 x 20

mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated.

The residue was purified using silica gel chromatography (0-20% methanol/dichloromethane) to

afford the title compound as an off-white foam (82 mg, 0.21 mmol, 78 %): 1 H NMR (400 MHz,

CDCI3) 6 8.98 (s, 1H), 8.65 (d, J = 4.6 Hz, 1H), 8.23 (s, 1H), 8.11 - 7.97 (m, 1H), 7.51 -7.41 (m,

25 1H), 4.88 (br s, 1H), 4.14 (br s, 1H), 2.64 (s, 1.2H), 2.55 (s, 1.8H), 2.33 - 2.27 (m, 1H), 1.47 (d, J

= 6.8 Hz, 3H); 13C NMR (101 MHz, CDCI 3) 6 168.11, 148.95, 148.78, 140.45, 140.33, 140.20,

135.56, 126.54, 124.10, 121.68, 121.58, 121.48, 77.69, 73.49, 38.60; ESIMS m/z 351 ([M+Hr).

Example 84: Preparation of N-(3-Chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-2-

(methylsulfony1)-N-(prop-2-yn-1-y1)propanamlde (Compound 618)

It-

30

103

c I o

17149

To a solution of N-(3-chloro-1-(pyridin-3-y9-1H-pyrazol-4-y1)-2-(methylthio)-N-(prop-2-yn-

1-yppropanamide (0.10 g, 0.30 mmol) and acetic acid (2.0 ml). To this solution was added

sodium perborate tetrahydrate (0.11 g, 0.74 mmol) and the vial was heated to 65 °C for 2 hours.

The reaction mixture was cooled to ambient temperature and neutralized with saturated sodium

5 bicarbonate. The organic layer was extracted with ethyl acetate (3x). The organic layers were

combined, dried over sodium sulfate, filtered and concentrated. The residue was purified using

silica gel chromatography (0-20% methanoVdichloromethane) to afford the title compound as a

yellow foam (84 mg, 0.21 mmol, 73%): 1 1-1 NMR (400 MHz, CDCI 3) 59.00 (s, 1H), 8.65 (s, 1H),

8.29 (s, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.54 - 7.39 (m, 1H), 4.89 (d, J = 16.9 Hz, 1H), 4.20 - 4.08

10 (m, 1H), 4.07 - 3.92 (m, 1H), 3.01 (s, 3H), 2.34 - 2.29 (m, 1H), 1.67 (d, J = 7.0 Hz, 3H); 13C NMR

(101 MHz, CDCI3) 5 166.97, 166.90, 148.77, 140.43, 140.24, 135.58, 129.36, 126.64, 124.14,

121.34, 73.80, 60.91, 38.78, 36.29, 13.97; ESIMS m/z 367 ([M+Hr).

104

17149

Example 85: Preparation of N-(3-chloro-1.(pyrldin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-methyl-

3-(tritylthio)propanamlde

N

To a solution of N,N-dimethylpyridin-4-amine (2.60 g, 21.31 mmol), 2-methyl-3-

5 (tritylthio)propanoic acid (4.41 g, 12.18 mmol) (prepared according to Ondetti, Miguel Angel

etal. DE 2703828) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine

hydrochloride (2.36 g, 15.22 mmol) in CH2Cl2 (20 ml) was added 3-chloro-N-ethy1-1-(pyridin-3-

yI)-1H-pyrazol-4-amine, 2HCI (3.0 g, 10 mmol). The mixture was stirred at 0 °C for 2 hours, then

at room temperature for additional 48 hours. The mixture was diluted with ethyl acetate (100

10 ml) and saturated aqueous WWI. The organic phase was separated, washed with brine, dried

over MgSa$ and concentrated In vacuo to give a light brown gum. This gum was purified on

silica gel eluting with mixtures of ethyl acetate and hexanes to give the title molecule as a pink

solid (2.97 g, 51%): mp 64-66 °C; 1 1-1 NMR (400 MHz, CDCI3) 6 8.89 (d, J = 2.7 Hz, 1H), 8.62

(dd, J = 4.7, 1.4 Hz, 1H), 7.93 - 7.86 (m, 1H), 7.82 (s, 1H), 7.41 (dd, J = 8.3, 4.7 Hz, 1H), 7.33 -

15 7.14 (m, 15H), 3.68 (d, J = 47.9 Hz, 2H), 2.72 (dd, J = 12.0, 8.8 Hz, 1H), 2.37 - 2.24 (m, 1H),

2.01 (dd, J = 12.0, 5.2 Hz, 1H), 1.14 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.7 Hz, 3H); ESIMS miz 568

([M+Hr).

Example 86: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-methyl-3.

(tritylthio)propanamIde

CI 0 v "......7---S

N / N \

20 N

To a solution of 3-chloro-N-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine, HCI (1.5 g, 6.12

mmol) In CH2Cl2 (10 mL) were added 3-(tritylthio)propanoic acid (2.359, 6.73 mmol) (prepared

according to Ondetti, Miguel Angel etal. DE 2703828). N,N-dimethylpyridin-4-amine (0.82 g,

6.73 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine, HCI (1.76 g,

25 9.18 mmol), and the mixture was stirred at room temperature for 16 h. The mixture was diluted

with CH2Cl2 (100 mL) and water (50 ml) and the organic phase separated. The aqueous phase

was extracted with ethyl acetate and the combined organic phase was washed with brine, dried

105

17149

over MgSO4 and concentrated In vacua to give the title molecule as a white powder (1.95g.

59%): mp 62-64 °C; 1 H NMR (400 MHz, CDCI3) 6 8.91 (d, J = 2.7 Hz, 1H), 8.67 - 8.61 (m, 1H),

8.06 - 7.96 (m, 1H), 7.81 (s, 1H), 7.49 - 7.46 (m, 1H), 7.25-7.45 (m, 15H), 3.17 (s, 3H), 2.56 -

2.46 (m, 2H), 2.09 - 1.97 (m, 2H); ESIMS m/z 540 ([M+Hr).

5 Example 87: Preparation of N-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-3-mercapto-N-

methylpropanamide

CI 0 ....f— SH

N-

\

N

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-methyl-3-

(tritylthio)propanamide (1.300g. 2.411 mmol) in CH2Cl2 (6.14g. 72.3 mmol) were added

10

triethylsilane (1.402g. 12.06 mmol) followed by 2,2,2-trifluoroacetic acid (2.75g. 24.11 mmol) at

room temperature. The mixture was stirred for 1 hour and quenched with saturated aqueous

NaHCO3. The mixture was diluted with CH 2Cl2 and the organic phase was separated. The

aqueous phase was extracted with CH2Cl2 and the organic phases were combined, washed with

brine dried over anhydrous MgSO4 and concentrated In vacua to give a light yellow oil. This oil

15 was purified on silica gel eluting with ethyl acetate and hexanes to give the title molecule as a

colorless oil (701 mg, 93%): IR (thin film) 3094, 2980, 1657, 1582 cm -1 ; 1 H NMR (400 MHz,

CDCI3) 6 8.95 (d, J = 2.6 Hz, 1H), 8.63 (s, 1H), 8.06 (s, 1H), 8.04 - 7.96 (m, 1H), 7.52 - 7.42 (m,

1H), 3.26 (s, 3H), 2.85 - 2.73 (m, 2H), 2.56 - 2.48 (m, 2H).

The following molecules were made in accordance with the procedures disclosed in

20 Example 87:

N-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-mercatopropanamide

P op SH

N

The title molecule was isolated as a light brown gum (902 mg, 64 %): IR (thin film) 3086,

2980, 2936, 2548, 1657 cm'; 1 H NMR (400 MHz, CDCI 3) 68.96 (dd, J= 2.7, 0.7 Hz, 1H), 8.63

25 (dd, J— 4.8, 1.5 Hz, 1H), 8.06 (ddd, J— 8.3, 2.7, 1.4 Hz, 1H), 7.97(s, 1H), 7.47 (ddd, J— 8.4,

4.7, 0.8 Hz, 1H), 3.72 (q, J = 7.1 Hz, 2H), 2.79 (dt, J = 8.5, 6.8 Hz, 2H), 2.49 (t, J = 6.7 Hz, 2H),

1.67(t, J= 8.4 Hz, 1H), 1.17(t, J= 7.2 Hz, 3H); ESIMS m/z 311 ([M+H]), 309 ([M-Hr).

N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-mercapto-2-methylpropanamide

106

17149

C l

SH

The title molecule was Isolated as a colorless oil which solidified upon standing: mp 94-

96 °C; 1 F4 NMR (400 MHz, CDCI 3) 6 8.97 (dd, J = 2.7, 0.7 Hz, 1H), 8.63 (dd, J = 4.8, 1.5 Hz,

1H), 8.05 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 8.02 (s, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 3.85

5 (m, 1H), 3.60 (m, 1H), 2.91 (ddd, J = 13.2, 9.4, 8.1 Hz, 1H), 2.41 (ddd, J = 13.2, 9.2, 4.9 Hz,

1H), 1.49 (dd, J = 9.2, 8.2 Hz, 1H), 1.18 (t, J = 7.2 Hz, 3H), 1.14 (d, J = 6.7 Hz, 3H); ESIMS m/z

325 ([M+Hr).

Example 88: Preparation of 3 -(((2,2-difluorocyclopropypmethyl)thio)propanolc acid

HO

10 Powdered potassium hydroxide (423 mg, 7.54 mmol) and 2-(bromomethyl)-1,1-

difluorocyclopropane (657 mg, 3.84 mmol) were sequentially added to a stirred solution of 3-

mercaptopropanolc acid (400 mg, 3.77 mmol) in methanol (2 mL) at room temperature. The

resulting white suspension was stirred at 65 °C for 3 h and quenched with 1N aqueous HCI and

diluted with ethyl acetate. The organic phase was separated and the aqueous phase extracted

15 with ethyl acetate (2 x 50 mL). The combined organic extracts were dried over MgSO4, filtered

and concentrated In vacuo to give the title molecule as a colorless oil (652 mg, 84%): IR (KBr

thin film) 3025, 2927, 2665, 2569, 1696 urn 1 H NMR (400 MHz, CDCI3) 62.85 (t, J = 7.0 Hz,

2H), 2.82 - 2.56 (m, 4H), 1.88- 1.72 (m, 1H), 1.53 (dddd, J = 12.3, 11.2, 7.8, 4.5 Hz, 1H), 1.09

(dtd, J = 13.1, 7.6, 3.7 Hz, 1H); ESIMS m/z 195.1 wo-Fin.

20 The following molecules were made In accordance with the procedures disclosed In

Example 88:

4-(((2,2-Difluorocyclopropyl)nethyl)thio)butanoic acid: 'H NMR (400 MHz, CDCI3) 6

11.31 (s, 1H), 2.71 -2.54 (m, 4H), 2.51 (t, J = 7.2 Hz, 2H), 2.01 - 1.86 (m, 2H), 1.85- 1.70 (m,

1H), 1.51 (dddd, J = 12.3, 11.2, 7.8, 4.5 Hz, 1H), 1.07 (dtd, J = 13.2, 7.6, 3.7 Hz, 1H); 13C NMR

25 (101 MHz, CDCI3) 6 179.6, 113.7 (dd, J = 286.4, 283.4 Hz), 32.7, 30.7, 28.7(d, J = 4.6 Hz),

24.2, 22.8 (t, J = 11.2 Hz), 16.6 (t, J = 10.8 Hz); 19F NMR (376 MHz, CDCI3) 5-128.12 (d, J =

156.8 Hz), -142.77 (d, J = 156.7 Hz).

4-((2,2,2-Trifluoroethyl)thio)butanoic acid: 1 H NMR (400 MHz, DMSO-d6) 6 3.47 (q, J =

10.8 Hz, 2H), 2.72 (dd, J = 7.8, 6.6 Hz, 2H), 2.32 (td, J = 7.3, 4.5 Hz, 2H), 1.96 — 1.81 (m, 2H).

30 Example 89: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol4-y1)-3-0(2,2-

difluorocyclopropygmethyl)thio)-N-ethylpropanamide (Molecule 626)

107

17149

N

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-)1)-N-ethyl-3-

mercatopropanamide (100 mg, 0.322 mmol) In THF (1 mL) was added sodium hydride (60%

dispersion in oil, 13.5 mg, 0.34 mmol). The resulting mixture was stirred at room temperature for

5

10 min followed by addition of 2-(bromomethyl)-1,1-difluorocyclopropane (60 mg, 0.35 mmol).

The mixture was stirred at room temperature for 24 h and diluted with saturated aqueous

ammonium chloride and ethyl acetate. The organic phase was separated and the aqueous

phase extracted with ethyl acetate (2x50 mL). The combined organic extracts were dried over

MgSO4, filtered and concentrated in vacuo to give a colorless oil. This oil was purified by

10 chromatography eluting with mixtures of ethyl acetate and hexanes to give the title molecule as

a colorless gum (101 mg, 78%): IR (thin film) 3092, 2975, 2931, 1659, 1584 cm'; I HNMR (400

MHz, CDCI3) 5 8.99 - 8.90 (m, 1H), 8.63 (dd, J = 4.8, 1.5 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.5

Hz, 1H), 7.96(s, 1H), 7.47 (ddd, J = 8.3, 4.7, 0.7 Hz, 1H), 3.72(q, J = 7.2 Hz, 2H), 2.87(t, J =

7.3 Hz, 2H), 2.63 - 2.55 (m, 2H), 2.46 (t, J = 7.3 Hz, 2H), 1.76 (ddq, J = 13.2, 11.4, 7.5 Hz, 1H),

15

1.48 (dddd, J = 12.3, 11.2, 7.8, 4.5 Hz, 1H), 1.17 (t, J = 7.2 Hz, 3H), 1.04 (dtd, J = 13.2, 7.6, 3.7

Hz, 1H); ESNS rniz 400 ([M+Hr).

Molecules 624, 625, 629, 633, 643 653 in Table 1 were made in accordance with the


Example 90: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-(((2,2-

20 difluorocyclopropygmethyl)sulfinyl)-N-ethylpropanamIde (Molecule 627)

0 0

N)C-5 L. o

N ?L4*

N

To a solution of N-(3-chloro-1-(pyridin-3-y)-1H-pyrazol-4-y1)-3-(((2,2-

difluorocyclopropyl)methyl)thio)-N-ethylpropanamide (100 mg, 0.25 mmol) In acetic acid (5 ml,

0.25 mmol) was added sodium perborate tetrahydrate (38.4 mg, 0.25 mmol) and the mixture

25 stirred at 50 °C for 1 hour. The mixture was cooled to room temperature, quenched with

saturated aqueous sodium bicarbonate and then diluted with ethyl acetate. The organic phase

was separated and the aqueous phase extracted with ethyl acetate. The combined organic

phase was washed with brine, dried over MgSO4 and concentrated In vacuo to give a colorless

oil. This oil was purified on silica gel eluting with methanol and CH2Cl2 (0-10% gradient) to give

108

17149

the title molecule as a colorless gum (91 mg, 88%): IR (thin film) 3448, 3092, 2976, 2933, 1659,

1585, 1440, 1012 crri l ; 1 H NMR (400 MHz, CDCI 3) 5 8.97 (d, J= 2.6 Hz, 1H), 8.63 (dd, J= 4.8,

1.5 Hz, 1H), 8.04 (m, 2H), 7.46 (ddd, J= 8.3, 4.8, 0.7 Hz, 1H), 3.72 (dq, J= 13.8, 7.0 Hz, 2H),

3.16 (ddd, J= 20.3, 13.9, 6.8 Hz, 1H), 3.00 - 2.79 (m, 3H), 2.69(m, 2H), 2.13 - 1.85 (m, 1H),

5 1.77- 1.62 (m, 1H), 1.41 - 1.21 (m, 1H), 1.18 (t, J= 7.2 Hz, 3H); ESIMS miz 417 ([M+Hr).

Molecules 622, 630, 645 In Table 1 were made In accordance with the procedures

disclosed In Example 90.

Example 91: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-(((2,2-difluoro

cyclopropyl)methyl)sulfony1)-N-ethylpropanamIde (Molecule 628)

Cl 0

6

F

10 N

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y9-3-(((2,2-

difluorocyclopropyOmethyl)thio)-N-ethylpropanamide (100 mg, 0.25 mmol) in acetic acid (5 ml,

0.25 mmol) was added sodium perborate tetrahydrate (77 mg, 0.499 mmol) and the mixture

stirred at 50 °C for 1 hour. The mixture was cooled to room temperature, quenched with

15 saturated aqueous sodium bicarbonate and then diluted with ethyl acetate. The organic phase

was separated and the aqueous phase was extracted with ethyl acetate. The combined organic

phase was washed with brine, dried over MgSO4 and concentrated in vacuo to give a brown oil.

This oil was purified on silica gel eluting with mixtures of ethyl acetate and hexanes to give the

title molecule as a colorless gum (90 mg, 83%): IR (thin film) 3104, 2980, 2934, 1662, 1486,

20 1460 cm-1 ; 1 H NMR (400 MHz, CDCI3) 5 9.00 - 8.90 (m, 1H), 8.64 (dd, J= 4.7, 1.4 Hz, 1H), 8.09

-8.00 (m, 2H), 7.47 (ddd, J= 8.4, 4.8, 0.7 Hz, 1H), 3.72 (d, J= 7.1 Hz, 2H), 3.43 (s, 2H), 3.30

(dd, J= 14.7, 6.8 Hz, 1H), 3.11 - 3.00(m, 1H), 2.72 (t, J= 6.9 Hz, 2H), 2.13 - 1.96 (m, 1H), 1.73

(tdd, J= 11.5, 8.3, 5.4 Hz, 1H), 1.45 (ddt, J= 16.1, 8.0. 3.8 Hz, 1H), 1.18 (t, J= 7.2 Hz, 311);

ESIMS Rik 433 ([M+H]).

25 Molecules 623, 631, 644 in Table 1 were made In accordance with the procedures

disclosed in Example 91.

Example 92: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-

(cyclopropylmethyl)-3-(((2,2-difluorocyclopropyl)methyl)thio)propanamid (Molecule 632)

F

do

N— ,.....x—S

* / N

F

109

N

17149

To a solution of 3-chloro-N-(cyclopropylmethyl)-1-(pyridin-3-y1)-1H-pyrazol-4-amine (108

mg, 0.43 mmol), N,N-dimethylpyridin-4-amine (53mg, 0.43 mmol) and 3-(((2,2-

difluorocyclopropyOmethyl)thio)propanoic acid (85 mg, 0.43 mmoI) in DMF (5 mL) was added

N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (101 mg, 0.65

5 mmol). The resulting brown-yellow mixture was stirred at ambient temperature for 2 h. The

mixture was diluted with saturated aqueous ammonium chloride and ethyl acetate. The organic

phase was separated and the aqueous phase extracted with ethyl acetate (2 x 50 mL). The

combined organic extracts were dried over MgSO4, filtered and concentrated In vacuo to give

the title molecule as a colorless oil (120 mg, 61%): IR (thin film) 3089, 3005, 2923, 1660 1584

10 cm'; 'H NMR (400 MHz, CDCI3) 58.95 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 4.8, 1.5 Hz, 1H), 8.05

(ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.99 (s, 1H), 7.47 (ddd, J = 8.3, 4.7, 0.7 Hz, 1H), 3.54 (s, 2H),

2.88 (t, J = 7.3 Hz, 2H), 2.69 - 2.54 (m, 2H), 2.48 (t, J = 7.3 Hz, 2H), 1.76 (ddt, J = 18.7, 13.3,

7.4 Hz, 1H), 1.53- 1.42 (m, 1H), 1.12 - 0.90 (m, 2H), 0.54- 0.44 (m, 2H), 0.20 (dt, J = 6.1, 4.6

Hz, 2H); ESIMS ink 427 ([M+1-1] .).

15 Molecule 646 In Table 1 was made in accordance with the procedures disclosed In

Example 92.

Example 93: Preparation of (E)-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-4,4,4-

trifluorobut-2-enamide

0 ,..."--CF3

N-

CI

14 / Ni

N

20

To a solution of 3-chloro-N-ethyl-Hpyridin-3-y0-1H-pyrazol-4-amine, 2HCI (1.0 g, 3.38

mmol), N,N-dimethylpyridin-4-amine (827 mg, 6.77 mmol), and (E)-4,4,4-trifluorobut-2-enoic

acid (474 mg, 3.38 mmol) in DMF (3 mL) was added N1-((ethylimino)methylene)-N3,N3-

dimethylpropane-1,3-diamine, HCI (973 mg, 5.07 mmol). The resulting brown-yellow mixture

was stirred at ambient temperature for 2 hours. The mixture was diluted with saturated aqueous

25 NH4CI and ethyl acetate and saturated with Nadi. The organic phase was separated and the

aqueous phase extracted with ethyl; acetate (22 x 5050 mL). The combined organic phase was

dried over MgSO 4 , filtered and concentrated In vacuo to give the title molecule as a light brown

gum (901 mg, 73%): IR (thin film) 3093, 2978, 2937, 1681, 1649, 1585, 1114 cm'; 1 H NMR

(400 MHz, CDC13)15 8.97 (d, J = 2.7 Hz, 1H), 8.65 (dd, J = 4.9, 1.4 Hz, 1H), 8.07 (ddd, J = 8.3,

30 2.7, 1.5 Hz, 1H), 7.99(s, 1H), 7.48 (dd, J = 8.3, 4.8 Hz, 1H), 6.84 (dq, J= 15.4, 6.8 Hz, 1H),

6.60 - 6.44 (m, 1H), 3.80 (q, J = 7.2 Hz, 2H), 1.22 (t, J = 7.2 Hz, 3H); ESIMS rra/z 345 ([M+H]).

Example 94: Preparation of S-(4-((3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)(ethyl)amino)-

1,1,1-trifluoro-4-oxobutan-2-y1) ethanethioate

n'

110

17149

To a solution of (E)-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-eth)l-4,4,4-

trifluorobut-2-enamide (465 mg, 1.349 mmol) in dry DMSO (5 mL) was added potassium

ethanethioacetate (616 mg, 5.40 mmol). The mixture was stirred at 50°C for 96 hours under

5 nitrogen. The mixture was quenched with saturated ammonium chloride and extracted twice

with ethyl acetate. The combined organic phase was washed with brine, dried over MgSO4,

filtered and concentrated In vacuo to give a brown gum. Purification of this gum on silica gel

eluting with mixtures of hexane and ethyl acetate gave the title molecule as a brown gum (265

mg, 44%): IR (thin film) 3099, 2976, 2936, 1708, 1666, 1585, 1102 mi l ; I FI NMR (400 MHz,

10 CDC13)15 9.03 - 8.93 (m, 1H), 8.64 (dd, J = 4.7, 1.5 Hz, 1H), 8.12 - 8.04 (m, 1H), 7.98 (s, 1H),

7.53- 7.42 (m, 1H), 4.78 (dd, J = 9.0, 4.4 Hz, 1H), 3.90- 3.54 (m, 2H), 2.76 (dd, J = 16.6, 4.4

Hz, 1H), 2.53 (dd, J— 16.6, 9.4 Hz, 1H), 2.41 (s, 3H), 1.16(t, J= 7.2 Hz, 3H); ESIMS m/z 421

([M+H]).

Example 95: Preparation of N-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-411)-3-(((2,2-

15 difluorocyclopropyl)methyl)thlo)-N-ethyl-4,4,4-trifluorobutanamicle (Molecule 634)

IS .rxN

I , N

To a solution of methanol (21.1 mg, 0.66 mmol) in THF (1 mL) was added sodium

hydride (26.5 mg, 0.66 mmol, 60% oil suspension). The resulting mixture was stirred for 10

minutes at room temperature and S-(44(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethyDamino)-

20 1,1,1-trifluoro-4-oxobutan-2-y1) ethanethioate (266 mg, 0.63 mmol) in THF (1 mL) was added.

After stirring for 30 minutes, 2-(bromomethyl)-1,1-difluorocyclopropane (130 mg, 0.76 mmol)

was added. The mixture was stirred at room temperature for an additional 4 hours and diluted

with saturated aqueous ammonium chloride and ethyl acetate. The organic phase was

separated and the aqueous phase extracted with ethyl acetate (2 x 50 mL). The combined ethyl

25 acetate extracts were dried over MgSa t, filtered and concentrated in vacuo to give a colorless

oil. Purification on silica gel eluting with ethyl acetate and hexanes gave the title molecule as a

brown oil (89 mg, 30% yield): IR (thin film) 3097, 2978, 2937 1664, 1440 cm'; 1 H NMR (400

MHz, CDCI3) •5 8.96 (d, J = 2.7 Hz, 1H), 8.64 (dd, J = 4.8, 1.4 Hz, 1H), 8.06 (ddd, J = 8.4, 2.8,

1.4 Hz, 1H), 7.98 (d, J = 2.1 Hz, 1H), 7.47 (dd, J = 8.3, 4.8 Hz,1H), 3.94 - 3.84 (m, 1H), 3.75 (s,

111

17149

2H), 2.97 (dd, J = 13.4, 7.5 Hz, 0.55H), 2.85 (s, 1H), 2.79 - 2.65 (m, 0.45H), 2.60 (m, 1H), 2.43

(dt, J= 16.3, 10.0 Hz, 1H), 1.89 (It, J= 12.2, 7.5 Hz, 1H), 1.63- 1.49(m, 1H), 1.23- 1.13(m,

4H); ESIMS miz 469 ([M+Hr).

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Example 96: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-2-

((cyclopropylmethyl)thio)-N-ethylpropanamide (Molecule 621)

CI t) N—

N \-1 I■1 /

To a solution of methanol (9.99 mg, 0.312 mmol) In THF (1 mL) was added sodium

5 hydride (12.4 mg, 0.31 mmol, 60% oil suspension). The mixture was stirred at room temperature

for 10 minutes and added S-(14(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y9(ethyDamino)-1-

oxopropan-2-y1) ethanethioate (100 mg, 0.28 mmol). After stirring the mixture for 30 min,

(bromomethyl)cyclopropane (38 mg, 0.28 mmol) was added and the mixture stirred for

additional 14 hours. The mixture was diluted with saturated aqueous ammonium chloride (5 ml..)

10 and ethyl acetate (15 mL), and the organic phase was separated. The aqueous phase was

extracted with ethyl acetate (5 mL) and the combined organic phase was washed with brine,

dried over MgSO4 and concentrated In vacuo to give an oily residue. This residue was purified

on silica gel eluting with mixtures of ethyl acetate and hexanes to give the title molecule as a

colorless gum (31 mg, 30%): IR (thin film) 3081, 2972, 2930, 2871, 1655, 1438 cm -1 ; 1 H NMR

15 (400 MHz, CDCI3) IS 8.96 (d, J = 2.8 Hz, 1H), 8.63 (dd, J = 4.8, 1.4 Hz, 1H), 8.13 (s, 1H), 8.04

(ddt, J = 8.3, 3.2, 1.6 Hz, 1H), 7.50 - 7.40 (m, 1H), 3.81 (bs, 1H), 3.59 (bs, 1H), 3.33 (d, J = 7.4

Hz, 1H), 2.58 - 2.41 (m, 2H), 1.47(d, J= 6.9 Hz, 3H), 1.17 (td, J= 7.1, 1.8 Hz, 3H), 0.84 (dt, J=

10.3, 7.4, 3.7 Hz, 1H), 0.56 - 0.38 (m, 2H), 0.25 - 0.07 (m, 2H); ESIMS ink 365 ([M+Hr).

Molecule 651 in Table 1 was made In accordance with the procedures disclosed in

20 Example 96.

Example 97: Preparation of N-(3-chloro-1-(pyrldln-3-y1)-1H-pyrazo14-y1)-3-

((cyclopropylmethyl)thlo)-N-ethylpropanamide (Molecule 619)

CI

1;1 N

To a solution of methanol (9.99 mg, 0.31 mmol) In DMSO (1 mL) was added sodium

25 hydride (12.4 mg, 0.31 mmol). The mixture was stirred at room temperature for 10 minutes and

added a solution of S-(3((3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethypamino)-3-oxopropyl)

ethanethioate (100 mg, 0.28 mmol). After stirring the mixture for 30 min,

(bromomethypcyclopropane (38 mg, 0.28 mmol) was added and the mixture stirred for an

additional 30 minutes. The mixture was diluted with saturated aqueous NH4Cland ethyl acetate

30 and the organic phase separated. The aqueous phase was extracted with ethyl acetate and the

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combined organic phase was washed with brine, dried over MgSO4 and concentrated In vacuo

to give a light brown oil. This oil was purified on silica gel eluting with mixtures of hexanes and

ethyl acetate to give the title molecule as a colorless gum (33 mg, 31%): IR (thin film) 3080,

2978, 2930, 1660, 1584 cril l ; 1 H NMR (400 MHz, CDCI3)05 8.95 (d, J = 2.8 Hz, 1H), 8.63 (dd, J

5 = 4.7, 1.5 Hz, 1H), 8.12 - 8.01 (m, 1H), 7.98 - 7.92 (m, 1H), 7.53- 7.40(m, 1H), 3.78 - 3.62 (m,

2H), 2.95 - 2.84 (m, 2H), 2.51 - 2.38 (m, 4H), 1.20- 1.11 (m, 3H), 0.94 (s, 1H), 0.60 - 0.34 (m,

2H), 0.24 - 0.09 (m, 2H); ESIMS nilz 365 ([M+H1° ).


((cyclopropytmethyl)thio)-N-ethylacetamide (Molecule 620)

a

10

To a solution of methanol (10.4 mg, 0.32 mmol) in DMSO (1 mL) was added sodium

hydride (13 mg, 0.32 mmol). The mixture was stirred at room temperature for 10 minutes and

cooled to 0-5 °C and added a solution of S-(2-((3-chloro-1-(pyridin-3-yI)-1H-pyrazol-4-

yl)(ethyl)amino)-2-oxoethyl) ethanethioate (100 mg, 0.29 mmol). After stirring the mixture for 30

15 mm, (bromomethypcyclopropane (39 mg, 0.29 mmol) was added and the mixture stirred for

additional 2 hours. The mixture was diluted with saturated aqueous ammonium chloride (5 mL)

and ethyl acetate (15 mL), and the organic phase was separated. The aqueous phase was

extracted with ethyl acetate (5 mL) and the combined organic phase was washed with brine,

dried over MgSO4 and concentrated In vacua to give an oily residue. This residue was purified

20 on silica gel eluting with ethyl acetate and hexanes to give the title molecule as a colorless gum

(38 mg, 37%): IR (thin film) 3080, 2975, 2931, 1657, 1584 cm -1 ; 1 H NMR (400 MHz, CDCI3)

8.96 (dd, J = 2.7, 0.7 Hz, 1H), 8.63 (dd, J = 4.8, 1.4 Hz, 1H), 8.08 (s, 1H), 8.04 (ddd, J = 8.4,

2.8, 1.5 Hz, 1H), 7.46 (ddd, J = 8.4, 4.7, 0.8 Hz, 1H), 3.6 (bs, 1H), 3.17 (s, 1H), 2.61 (d, J = 7.1

Hz, 2H), 1.17 (t, J = 7.2 Hz, 2H), 1.05 - 0.91 (m, 1H), 0.55 (dd, J = 7.9, 1.5 Hz, 2H), 1.21-1.10

25 (m, 3H), 0.24 (dd, J = 4.8, 1.4 Hz, 2H); ESIMS m/z 351 ([M+Hr).

Molecule 650 in Table 1 was made in accordance with the procedures disclosed in

Example 98.

Example 99: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-31(3,3-

dichloroallyl)thio)-Mmethylpropanamlde (Molecule 649)

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CI

ri— C1 Cl o

N- 141 /

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-mercapto-N-

methylpropanamide (100 mg, 0.34 mmol) In DMSO (1 mL) was added sodium hydride (14.8 mg,

0.37 mmol). The mixture was stirred at room temperature for 10 min and cooled to 0-5 °C. 1,1,3-

S Trichloroprop-1-ene (49.0 mg, 0.34 mmol) was added, and the mixture stirred for an additional

45 minutes. The mixture was diluted with saturated aqueous NH4CI and ethyl acetate and the

organic phase was separated. The aqueous phase was extracted with ethyl acetate and the

combined organic phase was washed with brine, dried over MgSO4 and concentrated In vacuo

to give a light brown oil. This oil was purified on silica gel eluting with mixtures of hexanes to

10 give the title molecule as a colorless gum (60 mg, 43.9 %): IR (thin film) 3078, 2926, 1659,

1583, 1458, 1437, 803 crn -1 ; 1 H NMR (400 MHz, CDCI3) 68.94 (dd, J = 2.7, 0.7 Hz, 1H), 8.63

(dd, J= 4.8, 1.5 Hz, 1H), 8.04 (ddd, J= 8.3, 2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.47 (ddd, J= 8.3,

4.7, 0.7 Hz, 1H), 5.30 (s, 1H), 3.51 (s, 2H), 3.25 (s, 3H), 2.87 (t, J = 7.3 Hz, 2H), 2.52 (t, J = 7.3

Hz, 2H); ESIMS mix 406 ([M+2]), 403.7 PAD.

15 Example 100: Preparation of 2-chloro-N-(3-chloro-1-(pyridln-3-y1)-1H-pyrazol-4-y1)-N-

ethylpropanamide

CI 0

NrCl

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (1.0 g, 4.49 mmol)

In 1,2-dichloroethane (44.9 ml) at 0 °C were added diisopropylethylamine (0.941 ml, 5.39 mmol)

20 and 2-chloropropanoyl chloride (0.436 ml, 4.49 mmol), sequentially. The reaction was allowed to

warm to ambient temperature and was stirred for 1.5 hr. The reaction was quenched with the

addition of aqueous NaHCO3 and the layers were quickly separated. The aqueous layer was

extracted with CH2Cl2 (3 x 50 mL) and the combined organics were dried over Na2SO4, filtered

and concentrated In vacuo. The crude residue was purified via flash chromatography (30 to

25 100% Et0Ac/Hex) to give the title molecule as a white solid (1.301 g, 93%): mp 94-105 °C; 1 H

NMR (400 MHz, CDCI 3) 68.97 (d, J = 2.7 Hz, 1H), 8.64 (dd, J = 4.8, 1.5 Hz, 1H), 8.09 (s, 1H),

8.04 (ddd, J = 8.4, 2.7, 1.5 Hz, 1H), 7.47 (dd, J = 8.3, 4.8 Hz, 1H), 4.27 (q, J = 6.5 Hz, 1H), 3.83

(s, 1H), 3.63(s, 1H), 1.64(d, J = 6.5 Hz, 3H), 1.19 (t, J = 7.2 Hz, 3H); ESIMS mix 313 ([M+H]).

The following molecules were made In accordance with the procedures disclosed in

30 Example 100:

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2-chloro-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-411)-N-ethylbutanamide

0 Cl

Mp 95-103 °C; NMR (400 MHz, CDCI3) 6 8.98 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.8,

1.4 Hz, 1H), 8.08 (s, 1H), 8.05 (ddd, J= 8.4.2.7, 1.4 Hz, 1H), 7.47 (dd, J = 8.3, 4.7 Hz, 1H),

5 3.99 (m, 1H), 3.86 (br. s, 1H), 3.60 (br. s, 1H), 2.13 (dt, J = 14.6, 7.3 Hz, 1H), 1.91 (dt, J = 14.5,

7.3 Hz, 1H), 1.19(t, J= 7.2 Hz, 3H), 0.97(t, J = 7.3 Hz, 3H); ESNS m/z 327 ([M+H]).

2-chloro-N-(3-chloro-14pyrldin-3-y1)-1H-pyrazol-4-y1)-N-ethylacetamIde (Compound

Y2007)

CI 0

10 Due to observed decomposition when left at ambient temperatures overnight, the title

molecule was immediately used in subsequent reactions: 'H NMR (400 MHz, CDCI3) 6 8.96 (d,

J = 2.6 Hz, 1H), 8.65 (dd, J = 4.7, 1.3 Hz, 1H), 8.07 - 8.01 (m, 2H), 7.47 (dd, J = 8.3, 4.7 Hz,

1H), 3.93 (s, 214 3.79 - 3.68 (bs, 2H), 1.19 (t, J = 7.2 Hz, 3H).

N-(3-chloro-1-(pyrldln-3-y1)-1H-pyrazol-4-y1)-2-((1-chloro-2,2,2-trifluoroethyuthlo)-N-

15 ethylacetamIde (Molecule 638)

Cl 0 F F

N -LSI)C F CI

Supporting analytical data for the title molecule can be found In Table 2.

Example 101: Preparation of S-(14(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethyl)amino)-

1-oxopropan-2-y1) ethanethloate (Molecule 685)

N CI

0

20 To a solution of 2-chloro-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-

ethylpropanamide (1.0 g, 3.19 mmol) in acetone (6.39 ml) was added potassium ethanethioate

(0.438 g, 3.83 mmol). Reaction vessel was capped and heated to 60 °C for 1.5 h. The reaction

was cooled and poured Into a separatory funnel containing water (20 mL) and Et0Ac (20 mL).

25 The layers were separated and aqueous layer was extracted with Et0Ac (3 x 20 mL). The

combined organic extract was dried over anhydrous Na2SO4, filtered and concentrated In vacuo.

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The crude residue was purified (flash chromatography, 20 to 100% Et0Ac/Hex) to give the title

molecule as a brown, highly viscous oil (1.07g, 90%).


Example 101:

5 S-(14(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)(ethyl)amlno)-1-oxobutan-211)

ethanethloate

Mp 116-122 °C; I FI NMR (400 MHz, CDCI 3) 6 8.97 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 4.8,

1.5 Hz, 1H), 8.13- 7.99(m, 2H), 7.46 (dd, J— 8.3, 4.7 Hz, 1H), 4.14(t, J = 7.3 Hz, 1H), 3.85 (br.

10

s, 1H), 3.57 (br. s, 1H), 2.27 (s, 3H), 1.98 (dt, J= 14.2, 7.1 Hz, 1H), 1.74 - 1.62 (m, 1H), 1.16 (t,

J = 7.2 Hz, 3H), 0.92 (t, J = 7.4 Hz, 3H); ESIMS m/z 367 ([M+Hr).

S-(24(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethyflamlno)-2-oxoethyl)

ethanethioate (Molecule 694)

CI 0

N sy

) 0

15 Mp 117-124 °C; I FI NMR (400 MHz, CDCI3) 68.98 (dd, J= 2.7, 0.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H), 8.09 (s, 1H), 8.06 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.7

Hz, 1H), 3.84- 3.65(m, 2H), 3.61 (s, 2H), 2.33 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H); ESIMS m/z 339

([M+H].).

Example 102: Preparation of N-(3-chloro-1-(pyriclin-3-y1)-1 H-pyrazol-4-y1)-N-ethyl-24(2,2,2-

20 trifluoroethyl)thlo)propanamide (Molecule 635)

N Cl 0 F je.F

3 F

To a dry round-bottom flask under N2 were added sodium hydride (0.018g. 0.446 mmol)

and THF (2.1 mL), followed by methanol (0.018 mL, 0.446 mmol). The reaction was allowed to

stir at ambient temperature until cessation of hydrogen evolution was observed (-45 min). The

25 reaction was then cooled at 0°C and S-(14(3-chloro-1-(pyridin-3-y1)-1H-pyrazoI-4-

y1)(ethyl)amino)-1-oxopropan-2-y1) ethanethioate (0.150 g, 0.425 mmol) in THF (2.1 mL) was

added. The reaction was warmed to ambient temperature and stirred for 30 min. The reaction

was again cooled at 0°C and 1,1,1-trifluoro-2-lodoethane (0.063 ml, 0.638 mmol) in THF (2.1

mL) was added. The reaction was warmed to room temperature and stirred overnight. The

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reaction was diluted In Et0Ac (20 mL) and quenched with H20 (5 mL). The layers were

separated and the aqueous layer was extracted with Et0Ac (3 x 10 mL). The combined organic

extracts were dried over Na2SO4, filtered and concentrated in vacuo to give a yellow oil. The

crude product was purified via flash chromatography (0 to 75% CH 2C12/Et0Ac) to give the title

5 molecule as an opaque, viscous oil (43 mg, 25%): IR (thin film) 1657 cm -1 ; 1 H NMR (400 MHz,

CDCI3) 68.96 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.8, 1.4 Hz, 1H), 8.14 - 7.96 (m, 2H), 7.47 (dd, J

= 8.3, 4.8 Hz, 1H), 3.82(s, 1H), 3.59 (s, 1H), 3.44(s, 1H), 3.25 (qd, J = 10.2, 3.8 Hz, 2H), 1.48

(d, J = 6.8 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H); 19F NMR (376 MHz, CDCI3) 6-66.16; ESIMS m/z

393 ([M+H1+ ).

10 Molecules 637, 639-642, and 652 In Table 1 were made in accordance with the


Example 103: Preparation of N-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-((2-

fluorovInyl)thlo)propanamIde (Molecule 654)

CI N_ 0

15 To a dry round-bottom flask under N 2 were added a 60% dispersion of NaH in mineral oil

(0.043 g, 1.063 mmol) and THF (2.1 mL), followed by methanol (0.086 mL, 2.126 mmol). The

reaction was allowed to stir at ambient temperature until cessation of hydrogen evolution was

observed (-45 min). The reaction was then cooled at 0°C and S-(14(3-chloro-Hpyridin-3-y1)-

1H-pyrazol-4-y1)(ethyl)amino)-1-oxopropan-2-y1) ethanethioate (0.150g. 0.425 mmol) In THF

20 (2.1 mL) was added. Reaction was warmed to room temperature and stirred for 30 min. The

reaction was again cooled at 0 °C and 2-bromo-1,1-difluoroethane (0.101 mL, 1.275 mmol) in

THF (2.1 mL) was added. Reaction was warmed to room temperature and stirred overnight. LC-

MS analysis indicated presence of two products, the major corresponding to the desired

elimination product and the minor corresponding to the initial alkylation. Therefore, the reaction

25 was cooled to 0 °C and transferred to a vial containing additional Na0Me (freshly prepared by

mixing NaH (5.86 mg, 0.147 mmol) and Me0H (5.93 Pt., 0.147 mmol) In THF (0.73 mL) at 0 °C.

After stirring an additional 18h, reaction was diluted in Et0Ac (5 mL) and quenched with H20 (5

mL). Aqueous layer was extracted with Et0Ac (3 x 10 mL) and the combined organic extracts

were dried over Na2SO4, filtered, and concentrated In vacua to give a yellow oil. The crude

30 residue was purified via flash chromatography (25-80% Et0Ac/Hex) to give an inseparable

mixture of olefin isomers (-3:2, EIZ) as an opaque, viscous oil (15 mg, 10%): IR (thin film) 3091,

1656 cm'; 'H NMR (400 MHz, CDCI3) 68.97 (m, 1H), 8.64 (dd, J = 4.7, 1.4 Hz, 1H), 8.13 (s,

0.4H), 8.04 (m, 1.6H), 7.54 - 7.41 (m, 1H), 6.79 (dd, J = 83.3, 11.0 Hz, 0.6H), 6.75 (dd, J = 82.7,

4.3 Hz, 0.4H), 5.97 (dd, J = 12.7, 11.0 Hz, 0.6H), 5.68 (dd, J = 39.8, 4.3 Hz, 0.4H), 3.82 (br. s,

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17149

1H), 3.72 -3.47 (m, 1H), 3.47- 3.20 (m, 1H), 1.50 (d, J = 6.9 Hz, 1.2H), 1.42 (d, J = 6.8 Hz,

1.8H), 1.17 (m, 3H); ESIMS rrilz 355 ([M+H]. ).

Example 104: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-34(2,2,2-

trifluoroethyl)thio)propanamIde (Molecule 636)

N_ Cl

0

NiCS -hC F 5 F F

To a solution of 3-chloro-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-

ethylpropanamide (100 mg, 0.32 mmol) In THF (0.3 mL) was added sodium Iodide (4.7 mg,

0.032 mmol), 2,2,2-trifluoroethanethiol (148 mg, 1.3 mmol), and N,N-di-lso-propylethylamine

(222 pl, 1.277 mmol). The reaction mixture was heated overnight at 50 °C, diluted with DCM

10 and washed with 5% KOH solution. The phases were separated, concentrated, and purified by

silica gel chromatography eluting with 0-40% acetone In hexanes to afford the title molecule as

a colorless oil (109 mg, 83%): 1 H NMR (400 MHz, CDCI3) 6 8.95(d, J= 2.4 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.96 (d, J = 7.1 Hz, 1H), 7.46 (ddd, J =

8.3, 4.8, 0.6 Hz, 1H), 3.72(q, J= 7.1 Hz, 2H), 3.10(q, J = 10.0 Hz, 2H), 2.96 (t, J = 7.0 Hz, 2H),

15

2.47 (t, J = 7.0 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H); 19F NMR (376 MHz, CDCI3) 6 -66.56 (s); ESIMS

m/z 393 ([M+H]).

Example 105: Preparation of N-(3-chloro-1.(pyridin-311)-1H-pyrazol-4-y1)-N,2-dimethyl-3-

((trifluoromethyl)thio)propanamide (Molecule 647)

F F Cl 0

20 To a solution of 2-methyl-3-((trifluoromethypthio)propanoic acid (0.200 g, 1.065 mmol) in

DCM (1.0 mL) was added oxalyl dichloride (0.093 mL, 1.065 mmol) and 1 drop of DMF and

stirred at ambient temperature for 1 hour (gas evolution was observed). The reaction mixture

was concentrated and the crude acid chloride was dissolved in DCM (0.3 mL) which was

subsequently added to a pre-stirred solution of 3-chloro-N-methy1-1-(pyridin-3-y1)-1H-pyrazol4

25

amine dihydrochloride (0.100 g, 0.355 mmol) and N,N-dimethylpyridin-4-amine (0.130 g, 1.065

mmol) in DCM(1.0 ml.) and stirred overnight at room temperature.. The reaction mixture was

diluted with saturated NaHCO 3 and extracted with DCM. The organic layer was dried over

Na2504, filtered and concentrated. The crude material was purified via flash chromatography

eluting with 0-100% Et0Ac/hexanes to give the title molecule as a yellow oil (93 mg, 65.7%): IR

30 (thin film) 1654 cm'; 1 H NMR (400 MHz, CDCI3) 6 8.96 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.7, 1.3

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17149

Hz, 1H), 8.08- 8.00(m, 1H), 7.98(d, J= 8.3 Hz, 1H), 7.51 - 7.44(m, 1H), 4.07 - 3.36 (m, 2H),

3.25- 3.11 (m, 1H), 2.94 - 2.77 (m, 2H), 1.22- 1.15 (m, 6H); ESIMS miz 394 ([M+H]r).

Molecule 648 In Table 1 was made In accordance with the procedures disclosed In

Example 105

5 Example 106: Preparation of N-methyl-N-(1-methyl-3-(pyridin-3-y1)-1H-pyrazol-5-y1)-3-

((3,3,3-trifluoropropyl)thio)propanamide (Compound 1011)

N—N'CH3

0

N)L-

CH3

A solution of 3((3,3,3-trifluoropropyl)thio)propanoic acid (75 mg, 0.372 mmol), DMAP

(110 mg, 0.903 mmol), and N,1-dimethy1-3-(pyridin-3-y1)-1H-pyrazol-5-amine (50 mg, 0.266

10 mmol) In dry diethyl ether (886 pL) was cooled to 0 °C under N2. N,N 1-Dicyclohexy1carbodiimide

(DCC) (132 mg, 0.638 mmol) was added and the reaction was warmed up to room temperature

under N2, then stirred at room temperature overnight. The reaction mixture was filtered using

additional diethyl ether (0.5 mL) to remove salts and concentrated under reduced pressure.

Purification by silica gel chromatography by eluting with 0-90% hexanes/Et0Ac afforded the title

15 compound as a clear oil (64 mg, 61%).

Example 107: Preparation of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(2-

hydroxyethyl)carbamate (Compound Y2151)

Cl 0 H3C

)<CH3

NO CH3

OH

To a solution of 2-((tert-butoxycarbonyl)(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

20 yl)amino)ethyl acetate (841 mg, 2.21 mmol) in Me0H (7.3 mL) was added potassium carbonate

(305 mg, 2.21 mmol). The reaction was stirred at room temperature overnight. The reaction

mixture was diluted with water (10 mL) and extracted with Et0Ac (2 x 10 mL). The organic layer

was washed with saturated aqueous NaHCO3 (10 mL), dried over MgSO4 and concentrated.

Et20 was added and the resulting precipitate was collected by filtration to afford the title

25 compound as a white solid (249 mg, 32%).

Example 108: Preparation of 2-((tert-butoxycarbonyl)(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-

4y1)amino)ethyl methanesulfonate

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17149

H 0 O.,

/ H3C

To a solution of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(2-

hydroxyethyl)carbamate (574 mg, 1.69 mmol) in dry CH2Cl2 (4.0 mL), triethylamine (260 pl, 1.86

mmol) was added under N2. Methanesulfonyl chloride (145 pl, 1.864 mmol) was added

5 dropwise and the reaction was stirred at room temperature for 4 h. After the reaction was

deemed complete by LCMS, the reaction mixture was diluted with CH 2C12 (10 mL) and washed

with water (2 x 10 mL) and brine (10 ml..). The organic layer was dried and concentrated under

reduced pressure. Purification by silica gel chromatography by eluting with 10-100%

hexanes/Et0Ac afforded the title compound as a colorless liquid (330 mg, 44%): I HNMR (400

10 MHz, CDCI3) 6 9.00 (s, 1H), 8.59 (dd, J = 4.9, 1.5 Hz, 1H), 8.12 (s, 1H), 8.06 (ddd, J = 8.4, 2.8,

1.3 Hz, 1H), 7.46 (dd, J = 8.4, 4.7 Hz, 1H), 4.52 - 4.31 (m, 2H), 3.89 (t, J= 5.1 Hz, 2H), 3.04(s,

3H), 2.19 (s, 3H), 1.68 - 1.32 (m, 6H); ESIMS rn/z 417 ([M+Hr).

Example 109: Preparation of tert-butyl (3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)(2-

(pyrroliclin-1-yi)ethyl)carbamate (Compound Y2152)

Cl 0 H3C A „)<CH3

0 CH3

15 To a solution of 2-((tert-butoxycarbonyl)(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

Aamino)ethyl methanesulfonate (129 mg, 0.309 mmol) In dry DMF (884 pl), triethylamine (51.8

pl, 0.371 mmol) and pyrrolidine (37.5 pl, 0.449 mmol) was added under N2. The reaction was

then heated at 80 °C under N2 overnight. After the reaction was deemed complete by LCMS,

20 the reaction mixture was diluted with water (10 mL) and saturated aqueous NaHCO3 (5 mL),

then extracted with Et0Ac (3 x 10 mL). The organic layer was dried over MgSO4 and

concentrated under reduced pressure. Purification by silica gel chromatography by eluting with

0-50% CH 2C12/Me0H afforded the title compound as an off-white solid (65 mg, 51%).

Example 110: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-411)-N-(oxlran-2-

25 ylmethyl)-3((3,3,3-trifluoropropyl)thlo)propanamide (Compound 928)

121

17149

A solution of N-(3-chloro-1-(pyridin-310-1H-pyrazol-4-y1)-3-((3,3,3-

trifluoropropyl)thio)propanamide (109 mg, 0.288 mmol) In dry DMF (882 pl) was cooled to 0 °C

In an ice bath under N2. Sodium hydride (16.11 mg, 0.403 mmol, 60% dispersion in mineral oil)

5 was carefully added and the reaction was stirred at 0 °C for 30 min. 2-(Bromomethyl)oxirane

(47.6 pl, 0.576 mmol) was then added and stirred for 30 min at 0 C. The reaction was slowly

warmed up to room temperature and stirred overnight under N2. The reaction mixture was

quenched with water (15 mL) and extracted with Et0Ac (3 x 10 ml). The organic layer was

dried over MgSO4 and concentrated under reduced pressure. Purification by silica gel

10 chromatography by eluting with 0-90% hexane/Et0Ac afforded the title compound as an yellow

oil (28 mg, 21%).

Example 111: Preparation of N-(3-chloro-14pyrldin-3-y1)-1H-pyrazol-4-y1)-N-

(ethylcarbamoy1)-34(3,3,3-trifluoropropyl)thlo)propanamIde (Compound 988)

Ci #14 0

HN/L0

H3C

15 To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-03,3,3-

trifluoropropypthio)propanamide (106 mg, 0.280 mmol) In dry CH2Cl2 (1.8 mL),

isocyanatoethane (44.3 pl, 0.560 mmol) was added. The reaction mixture was stirred at room

temperature overnight then refluxed for 2 h. The solvent was switched to THF and another

portion of isocyanatoethane (44.3 pl, 0.560 mmol) was added and refluxed for additional 2 h.

20 Toluene (1.9 ml) was added along with another portion of isocyanatoethane (44.3 pl, 0.560

mmol) and the reaction was refluxed overnight. A small amount of product formation was

observed by LCMS. The reaction mixture was poured into a 5 mL microwave vial with additional

toluene (0.5 ml) and acetonitrile (0.5 ml) along with another portion of isocyanatoethane (44.3

pl, 0.560 mmol). The reaction was capped and placed on a Blotage® Initiator microwave reactor

25 for total of 9 h at 120°C, then for 8 h at 125 °C, with external IR-sensor temperature monitoring

from the side of the vessel. The reaction mixture was concentrated under reduced pressure.

Purification by silica gel chromatography by eluting with 0-10% CH2C12/Me0H and a subsequent

122

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purification eluting with 0-100% water/acetonitrile afforded the title compound as a white solid

(36 mg, 27%). Reference: J. Org. Chem., 1951, 16, 1879-1890.

123

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Example 112: Preparation of 4-((3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethyflamino)-4-

oxobutanoic acid (Compound Y2187)

CI 0

OH

CH3

In a 100 ml round bottom flask (RBF), 3-chloro-N-ethy1-1-(pyridin-3-y1)-1H-pyrazol-4-

5 amine (500 mg, 2.25 mmol), DMAP (27.4 mg, 0.225 mmol), triethylamine (0.469 ml, 3.37

mmol), and dihydrofuran-2,5-dione (449 mg, 4.49 mmol) was added with dichloroethane (22.5

mL). The reaction was heated at 60 °C under N2 overnight. The reaction mixture was

concentrated and purified by silica gel chromatography by eluting with 0-15% CH2C121Me0H to

afford the title compound as an off-white solid (635 mg, 86%).

10 Example 113: Preparation of S-(3,3,3-trifluoropropyl) 41(3-chloro-1-(pyridin-3-y1)-1H-

pyrazol-4-y1)(ethyl)amino)-4-oxobutanethloate (Compound 979)

CI ,N 0

F CH3

A solution of 4((3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethyparnino)-4-oxobutanoic

acid (100 mg, 0.310 mmol), 3,3,3-trifluoropropane-1-thiol (42.0 pl, 0.387 mmol), and DMAP

15 (3.79 mg, 0.031 mmol) in dry CH 2Cl2 (620 pl) was cooled to 0 °C. DCC (63.9 mg, 0.310 mmol)

was added and the reaction was warmed up to room temperature under N2, then stirred

overnight. The reaction mixture was filtered using additional CI-4 2C12 (1 ml) to remove salts and

concentrated under reduced pressure. Purification by silica gel flash column chromatography

eluting with 10-90% hexanes/Et0Ac afforded the title compound as a slightly yellow clear

20 viscous semi-solid (83 mg, 60%). Reference: J. Am. Chem. Soc., 2009, 131, 14604-14605.

Example 114: Preparation of 3,3,3-trifluoropropyl 4-((3-chloro-1-(pyridin-3-y1)-1/1-pyrazol-

4-y1)(ethyflamino)-4-oxobutanoate (Compound Y2154)

N Cl

F OF

F CH3

A solution of 4((3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethypamino)-4-oxobutanoic

25 acid (101 mg, 0.313 mmol), sodium bicarbonate (526 mg, 6.26 mmol), and 3-bromo-1,1,1-

trifluoropropane (66.6 pl, 0.626 mmol) in DMF (1565 pl) was stirred at room temperature under

N2 overnight. The reaction was quenched with water (15mL) and extracted with CH 2Cl2 (3 x 10 124

F S F

NI

17149

ml.). The organic layer was dried and concentrated under reduced pressure. Purification by

silica gel chromatography by eluting with 0-100% hexanes/Et0Ac afforded the title compound

as a clear oil (36 mg, 26%). Reference: Syn. Commun., 2008, 38, 54-71.

Example 115: Preparation of 2((2,2,2 -trifluoroethyl)thio)ethyl (3 -chloro-1 -(pyridin-3-y1)-

5 1H-pyrazol -4-y1)(ethyl)carbamate (Compound 970)

CI N 0 F ,

Sj< r AO F

H3C

A solution of 3-chioro-N-ethy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine (170 mg, 0.763 mmol)

in dichloroethane (2 ml..) was cooled to 0 °C. Under N2, phosgene (708 pl, 0.992 mmol, 15 wt%

In toluene) was added and after 5 minutes N,N-dimethylpyridin-4-amine (196 mg, 1.603 mmol)

10 was added in one portion. The Ice bath was removed and the mixture was stirred at room

temperature for 5 minutes and at 80 °C for 50 min. The mixture was cooled to room temperature

and then 2-((2,2,2-trifluoroethyl)thio)ethanol (251 mg, 1.57 mmol) was added with CH2C12 (0.5

mL) followed by another portion of N,N-dimethylpyddin-4-amine (196 mg, 1.60 mmol). The

reaction mixture was heated under N2 at 80 °C for 2 h. The reaction mixture was diluted with

15 CH2Cl2 (10 mL) and saturated aqueous NR $C1(10 ml.). The organic layer was separated, dried,

and concentrated. Purification by silica gel chromatography by eluting with 0-100%

hexanes/Et0Ac and a subsequent purification eluting with 0-100% water/acetonitrile afforded

the title compound as a cloudy white oil (33 mg, 10%).

Example 116: Preparation of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-1-ethyl-3-(((3,3,3-

20 trifluoropropyl)thio)methyl)urea (Compound 990)

Ci N 0 F

F ,

...K. ,....„ ........„......)<

S F

LOH To a solution of 2((3,3,3-trifluoropropypthio)acetic acid (696 mg, 3.70 mmol) In CH2Cl2

(7.40 mL), oxalyl chloride (1.619 ml., 18.49 mmol) was added along with a drop of DMF at room

temperature. Once DMF was added, gas evolution was observed and continued for about 30

25 min. The reaction mixture was stirred at room temperature for total of 1 h then the solvent was

removed under reduced pressure. Acetone (18.50 mi.) was added to the concentrated material

and the reaction was cooled to 0 °C in an Ice bath. To that, a solution of sodium azide (265 mg,

4.07 mmol) in water (1 mL) was added dropwise. The reaction was stirred at 0 °C for 1 h. The

reaction mixture was diluted with water (15 mL) and stirred at room temperature for 5 min.

30 Dichloromethane (10 ml.) was added and the organic layer was separated, dried, and

125

)

17149

concentrated under reduced pressure to afford 2-((3,3,3-trifluoropropyl)thio)acetyl azide as dark

brown-green oil. Dry CH2Cl2 (4193 pl) was added to the crude azide and refluxed for 2 h. The

reaction was cooled to room temperature and 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-

amine (140 mg, 0.629 mmoI) was added. The reaction was stirred overnight at room

5 temperature. The reaction was concentrate under reduced pressure and purified by silica gel

chromatography by eluting with 0-10% CH2C12/Me0H to afford title compound as a light brown

solid (179 mg, 68%). Reference: J. Org. Chem., 2003, 68, 9453-9455.

Example 117: Preparation of 3-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-y1)-5-

(hydroxymethyl)oxazolidin-2-one (Compound Y2148)

Cl 0

A

OH

To a solution of tert-butyl (3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(oxiran-2-

ylmethyl)carbamate (321 mg, 0.915 mmol) in dry CH2Cl2 (915 pL), trifluoroacetic acid (915 pL)

was added under N2. The reaction mixture was stirred at room temperature for 90 min under 142.

The reaction mixture was diluted with toluene (10 mL) and concentrated under reduced

15 pressure to almost dryness. Et0Ac (5 mL) was added and the reaction was quenched with

saturated aqueous NaHCO3 (10 mL). The organic layer was separated and the aqueous layer

was further extracted with Et0Ac (3 x 5 mL), dried over MgSO4, and concentrated under

reduced pressure to afford the title compound as a white foam (134 mg, 47%).

Example 118: Preparation of N-((3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

20 yl)(ethyl)carbamoy1)-4-methoxybenzamIde (Compound Y2189)

Cl

IN ) H

A solution of 4-methoxybenzamide (61.1 mg, 0.404 mmol) and oxalyl chloride (44.2 pl,

0.505 mmol) In DCE (1684 pl) was refluxed for 15 h under N2 The reaction was cooled to room

temperature and 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (75 mg, 0.337 mmol) was

25 added and stirred overnight at room temperature. The reaction mixture was diluted with

saturated aqueous NaHCO3 (5 mL) and CH2C12 (3 mL). The phases were separated and the

aqueous layer was washed with CH2Cl2 (2 x 3 mL). The combined organic layer was dried and

concentrated. Purification by silica gel chromatography eluting with 15-100% hexanes/Et0Ac

N

I-13C o

126

17149

afforded the title compound as white solid (107 mg, 78%). Reference: J. Org. Chem., 1963, 73,

1805.

Example 119: Preparation of 143-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-1-ethylurea

(Compound Y2186)

A NH2 5 H3C

A solution of N-((3-chloro-1-(pyridin-3-y9-1H-pyrazol-i41)(ethyl)carbamoyObenzarnide

(300 mg, 0.811 mmol) in dry MOON (2028 pl) and 2 N aqueous NaOH (811 pl, 1.62 mmol) was

heated at 65 °C for 3 h. The reaction mixture was cooled to room temperature and neutralized

with 2 N aqueous HCI and concentrated under reduced pressure which produced yellow

10

precipitate. The precipitate was collected by fi ltration, washed with hexanes (3 mL), and dried

under vacuum to afford the title compound (109 mg, 48%).

Example 120: Preparation of Neethyl-N-(3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-4-

oxobutanamide (Compound Y2185)

H3C

15 A solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-4-hydroxybutanamide

(41 mg, 0.133 mmol) In dry CH 2Cl2 (1328 pl) was cooled to 0°C In an Ice bath under N2

Sodium bicarbonate (112 mg, 1.328 mmol) and Dess-Martin periodinane (64.8 mg, 0.153 mmol)

was added and the reaction was warmed up to room temperature and stirred for 5 h. LCMS

indicated no product formation so another portion of Dess-Martin periodinane (64.8 mg, 0.153

20 mmol) was added and stirred at room temperature overnight. The reaction mixture was diluted

with saturated aqueous NaHCO3 (5 mL) and extracted with CH2Cl2 (3 x 5 ml.). The organic layer

was dried, concentrated, and purified by silica gel chromatography eluting with 0-50%

CH2C12/Me0H to afford the title compound as clear oil (21 mg, 46%).

Example 121: Preparation of 1,1,1-trifluoro-7,7-dimethoxyheptan-4-ol

0,CH3

o,CH3

25 OH

In an oven dried vial with a stir bar, magnesium (77 mg, 3.17 mmol) was added and the

head space was purged with N2. Dry THF (4957 pL) was added with a crystal of 12 and heated

127

17149

with a heat gun until bubbles from Mg evolved. Slowly 3-bromo-1,1-dimethoxypropane (395 pL,

2.97 mmol) was added and heating continued with a heat gun until Mg was bubbling and the

Iodine color disappeared. The reaction mixture was refluxed for 1 h under N2 to give a cloudy

colorless solution. In a separate oven dried round bottom flask, 4,4,4-trifluorobutanal (208 pL,

5 1.983 mmol) was added with dry THF (10 mL, 0.2M) and cooled to 0 °C. Room temperature

Grignard reagent was added drop wise over 8 min and stirred at 0 °C for 30 min. The reaction

was warmed up to room temperature and stirred for 1.5 h. The reaction was quenched with

saturated aqueous NH4C1(15 mL) and extracted with CH2Cl2 (3 x 15 mL). The organic layer was

dried, concentrated, and purified by silica gel chromatography eluting with 0-10% CH 2C12/Me0H

10 to afford the title product as 85% pure clear semi-solid (372 mg, 69%): IR (thin film) 3442 mi l ;

I H NMR (400 MHz, CDCI3) 54.39 (t, J = 5.2 Hz, 1H), 3.65 (tq, J = 8.2, 3.9 Hz, 1H), 3.35 (d, J =

0.7 Hz, 6H), 2.40 (dd, J = 4.6, 0.7 Hz, 1H), 2.39 - 2.24 (m, 1H), 2.24 - 2.06 (m, 1H), 1.80- 1.72

(m, 2H), 1.72- 1.59 (multiple peaks, 3H), 1.52 (ddt, J = 15.7, 14.2, 7.0 Hz, 1H); I t NMR (376

MHz, CDCI 3) 5-66.37; HRMS-FAB (m/z)[M+Nar calcd for C 3H 17F3Na03, 253.1022; found,

15 253.1025.

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17149

Example 122: Preparation of 7,7,7-trifluoro-4-oxoheptanoic acid

F

F

OH

0

To a solution of 1,1,1-trifluoro-7,7-dimethoxyheptan-4-ol (372 mg, 1.616 mmol) in dry

THF (10.8 ml.), 1 N aqueous HC1(8079 pL, 8.08 mmol) was added at room temperature. The

5 reaction mixture was stirred for 1 h then diluted with water (10 mL) and Et20 (10 mL). The

organic layer was separated and the aqueous layer was washed with Et20 (2 x 10 mL). The

combined organic layer was washed with saturated aqueous NaHCO3 (10 mL), dried over

MgSO4, and concentrated. The concentrated crude material was dissolved In acetone (5 mt.)

and glacial acetic acid (0.5 mL). Then KMnO., (766 mg, 4.85 mmol) dissolved In water (10 mL)

10 was added to the stirring solution drop wise and stirred at room temperature for 2.5 h. GCMS

analysis showed incomplete conversion so more KMna, (510 mg) was added and the reaction

was left stirring overnight at room temperature. The reaction was diluted with AcOH (15 ml..; 2

mt. glacial AcOH in 13 mi. water) and CH 2Cl2 (10 ml.). The organic layer was separated and the

aqueous layer was extracted with CH2Cl2 (2 x 10 mL). The combined organic layer was washed

15 with water (15 mL), dried, and concentrated. Purification by silica gel chromatography eluting

with 0-10% CH 2C12/Me0H afforded the title compound as white solid (66 mg, 15%): IR (thin film)

1715 mil ; 1 H NMR (400 MHz, CDCI3) 62.81 -2.72 (multiple peaks, 411), 2.69 (ddd, J = 6.8, 5.5,

1.2 Hz, 2H), 2.50 - 2.35 (m, 214), 1.59 (br s, 1H); 19F NMR (376 MHz, CDCI3) 6-66.66.

Example 123: Preparation of M(3-chloro-1.(pyridin-3-y1)-111-pyrazol-4-y1)-N-ethyl-7,7,7-

20 trifluoro-4-oxoheptanamide (Compound Y2188)

CI il 0 F

H3C

A solution of 3-chloro-N-ethy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine (62 mg, 0.278 mmol),

7,7,7-trifluoro-4-oxoheptanoic acid (66.2 mg, 0.334 mmol), and DMAP (51.0 mg, 0.418 mmol) In

dry Et20 (928 pL) was cooled to 0°C In an Ice bath under N2. DCC (138 mg, 0.668 mmol) was

25 added and the reaction was warmed up to room temperature slowly. The reaction was stirred

under N2 overnight at room temperature. A white precipitate was filtered off with Et20 (1 mL)

and the filtrate was concentrated. Purification by silica gel chromatography eluting with 0-75%

hexanes/Et0Ac afforded the title product as brown viscous oil (59 mg, 50%).

Example 124: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-

30 hydroxypropanamide

129

17149

N -- i

I / ■ N

i H3C

0,-Li O ■s

t% 0

CH3

C I

CH3

N

To a solution of 14(3-chloro-1-(pyridin-3-y0-1H-pyrazol-4-y9(ethy9amino)-1-oxopropan-

2-ylacetate (2.4 g, 7.1 mmol) In methanol (8.9 mL) and tetrahydrofuran (8.9 mL) was added 2M

lithium hydroxide (7.1 mL, 14.2 mmol). The reaction mixture was stirred for 2 hours at 25 °C.

5 The reaction mixture pH was then made neutral by the addition of a 2M HCI. The mixture was

extracted with ethyl acetate, and the organic portions were combined, dried over MgSO4, filtered

and concentrated in vacuo to afford the title compound as a white solid (1.85g. 88%): mp 137-

138 °C; 'H NMR (400 MHz, DMSO) 69.08 (d, J = 2.5 Hz, 1H), 8.98(s, 1H), 8.58 (dd, J = 4.7,

1.1 Hz, 1H), 8.23 (ddd, J = 8.4, 2.6, 1.3 Hz, 1H), 7.59 (dd, J = 8.3, 4.7 Hz, 1H), 4.97 (d, J = 7.6

10

Hz, 1H), 4.08 (m, 1H), 3.57 (d, J = 50.6 Hz, 2H), 1.10 (d, J = 6.5 Hz, 3H), 1.07 (t, J = 7.1 Hz,

3H); ESIMS a* 295.6 ([M+H]).

Example 125:14(3-chloro-1-(pyridin-311)-1H-pyrazo14-y1)(ethyl)amlno)-1-oxopropan-2-y1

methanesulfonate (Compound Y2008)

15 To a solution of N-(3-chloro-1-(pyridin-3-y9-1H-pyrazol-4-0)-N-ethyl-2-

hydroxypropanamide (100 mg, 0.34 mmol) In tetrahydrofuran (1.1 mL) was added sodium

hydride (14.9 mg, 0.34 mmol). The mixture was stirred for 15 min and then methanesulfonyl

chloride (58.3 mg, 0.51 mmol) was added. The reaction mixture was stirred for 16 hours, diluted

with CH2Cl2, and washed with water. The phases were separated, dried, concentrated in vacuo

20 and purified by silica gel chromatography eluting with 0-70% acetone in hexanes to afford the

title compound as a light yellow oil (88 mg, 70%): IR (thin film) 2980, 2936, 1676 cm"'; 'H NMR

(400 MHz, CDCI 3) 69.00 (d, J = 2.5 Hz, 1H), 8.64 (dd, J = 4.8, 1.4 Hz, 1H), 8.12 (s, 1H), 8.02

(ddd, J= 8.3, 2.7, 1.4 Hz, 1H), 7.46 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 5.17(q, J = 6.7 Hz, 1H), 3.71

(m, 2H), 3.13 (s, 3H), 1.50 (d, J = 6.7 Hz, 3H), 1.19 (t, J = 7.2 Hz, 3H); ESIMS m/z 373.6

25 ([M+Hr).

Example 126: Preparation of N-(3-chloro-1-(pyrldln-3-y1)-1H-pyrazol-4-y1)-3-((3,3-

difluorocyclobutyl)thlo)-N-ethylpropanamIde (Compound 910)

130

17149

N

N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-((3-

oxocyclobutyl)thio)propanamide (100 mg, 0.264 mmol) was dissolved in CH2Cl2 (2 mL) and

stirred at 0 °C. Deoxofluore (0.083 mL, 0.449 mmol) and Et0H (2.312 pl, 0.040 mmol) was

5 added to the solution at 0 °C. The resulting solution was warmed to 25 °C slowly and stirred at

25 °C. After 4 hours, 1 more equivalent of Deoxofiuor® (50 pL) and another 2.5 pL of Et0H was

added. The reaction was worked up by slow addition of NaHCO3 solution and stirred for 30 min

at 25 °C. The mixture was diluted with water (20 ml..) and extracted with CH2Cl2 (3 x 20 mL).

The combined organic layer was washed with 0.01 M HCI, dried over Na2SO4 and purified with

10

silica gel chromatography (0-100% Et0Ac/hexane) to give the title compound as a light yellow

oil (19 mg, 18%).

Example 127: Preparation of N43-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

(vinyisulflnyl)propanamIde (Compound 1004)

Cl 0

(N■.

N*

N / N

)

H3C

n 0

15 To a 7 mL vial was added N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

mercaptopropanamide (0.050g, 0.161 mmol), 1,2-dibromoethane (0.907 g, 4.83 mmol) followed

by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0.024g, 0.161 mmol). The solution was stirred at

25 °C overnight, then it was concentrated and re-dissolved in hexafluoroisopropanol (1 mL).

Hydrogen peroxide (0.055 g, 0.483 mmol) was added and the solution was stirred at 25 °C for 2

20 hours, then worked up with sodium sulfite solution and extracted with CH 2Cl2. The crude

reaction mixture was purified by silica gel chromatography (0-10% Me0H/CH2C12) to give the

title compound as a brown oil (33 mg, 58%).

Example 128: Preparation of 3-(N-carbamoyi-S-methylsulfonlmidoy1)-N-(3-chloro-1-

(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethylpropanamide (Compound Y2099)

CI 0

N ,X—S

i , N / N

H3C)

131

17149

Cl 0 9 ICH3

I,

N

N-13-chloro-1-(3-pyrid)l)pyrazol-4-y1]-3-(N-cyano-S-methyl-sulfonimidoy1)-N-ethyl-

propanamide (320 mg, 0.840 mmol) was dissolved In conc. sulfuric acid (4 mL, 75 mmol) and

stirred at 25 °C for 16 h. The solution was poured Into a flask with Ice and solid NaHCO3 was

5 added slowly until the aqueous layer was neutral. The aqueous layer was extracted with CH2a2

and the combined organic layers were dried over Na2SO4 and concentrated. The crude reaction

mixture was purified by silica gel chromatography (0-10% Me0H/CH2C12) to give the title

compound as white solid (135 mg, 40%).

Example 129: Preparation of 4-chloro-N.(3-chloro-1-(pyriclin-3-y1)-1 H-pyrazol-4-

10 yObutanamide (Compound Y2166)

To a solution of 3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-amine (1.34 g, 6.89 mmol) In

CH2Cl2 (11 mL) cooled to 0 °C was added triethylamine (1.439 mL, 10.33 mmol) and 4-

chlorobutanoyl chloride (0.971 g, 6.89 mmol). The solution was allowed to slowly warm to 25 °C

15

and stirred for lh. The reaction was diluted with water (20 mL) and extracted with CH 2Cl2 (3 x

20 mL). The combined organic layers were dried, concentrated and purified with

chromatography (0-100% Et0Ac/hexane) to give the title compound as white solid (1.87g.

91%).

) o

H3C

132

17149

Example 130: Preparation of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-yi)pyrrolidin-2-one

(Compound Y2167)

()

A solution of 4-chloro-N-(3-chloro-1-(pyridin-3-y9-1H-pyrazol-4-yObutanamide (1.82 g,

5 6.08 mmol) in THF (50 mL) was cooled to 0 °C. NaH (0.280g. 7.00 mmol) was added and the

mixture was slowly warmed to 25 °C and stirred for 2 h. The mixture was diluted with water and

extracted with CH2C12 (3 x 20 mL). The combined organic layers were dried, concentrated and

purified with silica gel chromatography (0-10% Me0H/CH2C12) to give the title compound as

yellow solid (1.70 g, 96%).

10 Example 131: Preparation of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-

methylenepyrrolidin-2-one (Compound Y2168)

CI 0

CH2

A solution of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-411)pyrrolidin-2-one (1600 mg, 6.09

mmol) In CH2a2 (15 mL) was cooled to 0 °C. Triethylamine (1.273 mL, 9.14 mmol) and

15 trimethylsilyl trifluoromethanesulfonate (1.431 mL, 7.92 mmol) were added, and the resulting

deep red solution was stirred at 0 °C for 45 min. Eschenmoser's salt

(dimethylmethylideneammonium lodideX1465 mg, 7.92 mmol) was then added and the solution

was allowed to warm to 25 °C and stir overnight. The solution was diluted with CH2Cl2 (30 mL)

and 1N MCI (30 mL) was added and the mixture was stirred for 10 min before it was neutralized

20 with NaOH solution to pH =12. The mixture was extracted with CH2Cl2, and the combined

organic layers were dried, concentrated and purified with silica gel chromatography (0-10%

Me0H/CH2C12) to give the title compound as light yellow solid (866 mg, 52 %).

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Example 132: Preparation of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-

((methylthio)methyl)pyrrolidin-2-one (Compound 955)

CI 0

n' N

N /

N

1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-methylenepyrrolidin-2-one (400 mg, 1.46

5 mmol) was dissolved in THF (6 mL). Potassium hydroxide (384 mg, 5.82 mmol) dissolved in

water (1 mL) was added to the mixture, followed by S,S-dimethyl carbonodithloate (125 mg,

1.019 mmol). The mixture was heated to reflux for 3 hours, then it was diluted with water (20

mL) and extracted with CH 2Cl2 (3 x 20 mL). The combined organic layers were dried and

concentrated, and the crude mixture was purified by silica gel chromatography (0-10%

10 Me0H/CH2C12) to give the title compound as white solid (385 mg, 82%).

Example 133: Preparation of methyl 2-cyclobutylideneacetate

o

Me0

To a 250 mL round bottom flask was added methyl 2-

(triphenylphosphoranytidene)acetate (12.04g. 36 mmol) and benzene (90 mL). Cyclobutanone

15 (5.05g. 72.0 mmol) was added and the solution was heated to reflux for 2 days. The reaction

was cooled and hexane (70 mL) was added. The white precipitate was filtered off and the

solution was concentrated and purified by silica gel chromatography to give the title compound

as a colorless oil (3.22g. 71%): IR (thin film) 1714 cm-1 ; I FI NMR (400 MHz, CDCI 3) 65.60 (t, J

= 2.3 Hz, 1H), 3.68 (s, 3H), 3.13 (dddd, J = 9.0, 4.5, 2.2, 1.1 Hz, 2H), 2.90 - 2.76 (m, 2H), 2.09

20

(II, J = 11.4, 5.8 Hz, 2H); ' 3C NMR (101 MHz, CDCI3) 6 167.92, 166.95, 111.93, 50.79, 33.71,

32.32, 17.62.

Example 134: Preparation of 2-cyclobutylideneacetic acid

0

HO

To a solution of methyl 2-cyclobutylideneacetate (100 mg, 0.793 mop in Me0H (1.00

25 mt.) stirring at RT was added 2N LiOH solution (prepared from lithium hydroxide hydrate (100

mg, 2.378 mmoI) and water (1 mL)). The mixture was stirred at 25 °C overnight, then it was

worked up by addition of 2N HCI and extracted with CH 2Cl2. The combined organic layer was

dried to give a white solid, which was purified by silica gel chromatography (0-70%

Et0Ac/hexane) to give the title compound as a white solid (20 mg, 23%): IR (thin film) 2923,

30 1647 cm-1 ; I HNMR (400 MHz, CDCI 3) 6 10.89 (s, 1H), 5.60 (dd, J = 4.3, 2.1 Hz, 1H), 3.38 - 3.02

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(m, 2H), 2.97 - 2.71 (m, 2H), 2.10 (dq, J= 15.9, 8.0 Hz, 214); 13C NMR (101 MHz, CDCI3) •5

172.35, 171.33, 112.13.34.10, 32.58, 17.56.

Example 135: Preparation of 3-((3,3,3-trifluoropropyl)thlo)propanoic acid

Fr

0

HO

5 3-Mercaptopropanoic acid (3.2 g, 30.1 mmol) was dissolved in Me0H (20 mL) and

stirred at RT. Powdered potassium hydroxide (3.72 g, 66.3 mmol) was added to the solution,

followed by 3-bromo-1,1,1-trifluoropropane (6.14g, 34.7 mmol). The solution was then stirred at

65 *C for 3 h and then the reaction was quenched with IN HCI until the pH of the solution was

acidic. The mixture was extracted with CH 2Cl2 (3 x 30 mL) and the combined organic phases

10 were dried, concentrated and purified by silica gel chromatography (0-50% Et0Ac/hexane) to

give the title compound as colorless oil mixed with some white suspension (5.5 g, 90%): IR (thin

film) 2936, 1708 cm''; 1 14 NMR (300 MHz, CDCI3) l5 2.86 - 2.78 (m, 2H), 2.78 - 2.58 (m, 411),

2.52 - 2.25 (m, 214); EIMS tniz 202.

Example 136: Preparation of N-(3-chloro-1-(3-pyridyppyrazol-4-A-3-13-113-chloro-1-(3-

15

pyridyl)pyrazol-4-yil-methyl-amlno]-3-oxo-propylisulfanyl-N-ethyl-2-methyl-propanamide

(Compound 790)

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-eth)l-2-methyl-3-

mercatopropanamide (100 mg, 0.308 mmol) and 3-chloro-N-(3-chloro-1-(pyridin-3-y1)-1H-

20 pyrazol-409-N-methylpropanamide (100 mg, 0.334 mmol) In DMF (1 mL) was added sodium

hydride (60% dispersion in oil, 15 mg, 0.375 mmol). The mixture was stirred at room

temperature for 18 h and diluted with water and CH2Cl2. The organic phase was separated,

dried over Na 2SO4, filtered and concentrated In vacuo to give an orange oil. This oil was purified

by chromatography eluting with mixtures of methanol and methylene chloride to give the title

25 compound as a yellow oil (120 mg, 66%).

Example 137: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-((21(3-chloro-

1-(pyridin-3-y1)-1/1-pyrazol-4-y1)(methyl)amlno)-2-oxoethyl)thio)-N-ethylpropanamide

(Compound 789)

rie—F

135

17149

N

To a solution of N-(3-chloro-1-(pyridin-3-y1)-/H-pyrazol-4-y1)-N-ethyl-3-

mercaptopropanamide (100 mg, 0.322 mmol) In DMSO (1 mL) was added sodium hydride (60%

dispersion in oil, 15 mg, 0.375 mmol). Freshly prepared 2-chloro-N-(3-chloro-1-(pyridin-3-y1)-1 H-

5 pyrazol-4-y1)-N-methylacetamide (150 mg, 0.526 mmol) was added and the mixture was left to

stand for one hour with occasional swirling. The reaction mixture was diluted with saturated

sodium bicarbonate and Et20. To the organic phase was added ammonia in Me0H (7 M, 1 mL,

1 mmol) followed by Na2SO4. After standing 10 minutes, the mixture was filtered and

concentrated In vacuo to give an orange oil. The oil was purified by silica gel chromatography

10

eluting with mixtures of methanol and CH 2Cl2 to give the title molecule as an orange oil (120 mg,

66%).

Example 138: Preparation of tert-butyl ((1R,4S)-4-((3-chloro-1-(pyridin-3-y1)-1/1-pyrazol-4-

yl)(methyl)carbamoyl)cyclopent-2-en-1-yl)carbamate

Cl

N - ,CH3 H / 1 N / N.,d)

[ CH3 °-t-CH3

CH3

15 A solution of 3-chloro-N-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (200 mg, 0.96 mmol)

In THF (10 mL) was cooled to -78 °C. Lithium bis(trimethylsily0amide (1 mL, 1.00 mmol, 1M

solution In hexane) was added and the solution was stirred at -78 °C for 15 minutes. A solution

of (1R,4S)-tert-butyl 3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (201 mg, 0.96 mmol)

dissolved in THF (3 mL) was added to the solution at -78 °C in one portion. After stirring for 1

20 hour at -78 °C the cooling bath was removed and the reaction warmed to 20 °C. After stirring for

an additional five minutes, acetic acid (0.1 mL) was added to the solution. The reaction mixture

was concentrated and purified via silica gel chromatography utilizing a mobile phase of hexanes

and ethyl acetate to give the title compound as a white solid (250 mg, 59%): I FI NMR (400 MHz,

CDCI3) 6 9.01 - 8.93(d, J= 2.8 Hz, 1H), 8.66 - 8.60 (m, 1H), 8.11 - 8.02(m, 2H), 7.52 - 7.42 (m,

25

1H), 5.93 - 5.85 (m, 1H), 5.72 - 5.66 (m, 1H), 5.53 - 5.44 (d, J = 9.5 Hz, 1H), 4.80 - 4.67 (m, 1H),

3.58 - 3.47 (m, 1H), 3.30 - 3.21 (s, 3H), 2.35 - 2.22 (m, 1H), 1.90- 1.80 (m, 1H), 1.51 - 1.34 (s,

9H); 13C NMR (101 MHz, CDCI 3) 6 175.26, 155.23, 148.70, 140.31, 140.00, 135.61, 135.18,

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130.99, 126.34, 125.92, 125.78, 124.12, 79.04, 55.69, 47.33, 37.49, 35.55, 28.45; ESIMS m/z

418 [M+Hr, 416 (w-tir). Example 139: Preparation (1S,4R)-4-amino-N-(3-chloro-1 -(pyriclin-3-y1)-1H-pyrazol4-y1)-N-

methylcyclopent-2-enecarboxamIde 2,2,2-trifluoroacetate

CI

N FH3 /

NH2

I 0

FF.)L

N OH

5 F

To a solution of tert-butyl ((1 R,4S)-4-((3-chloro-1-(pyridin-3-yI)-1H-pyrazol-4-

y1)(methyl)carbamoyi)cyclopent-2-en-1-yl)carbamate (130 mg, 0.31 mmol) In CH2Cl2 (4 mL) was

added trifluoroacetic acid (4 mL). The reaction was left to stand for 20 minutes with occasional

swirling. The reaction mixture was concentrated In vacuo at 40 °C resulting In the Isolation of

10 the title compound as a clear oil (130 mg, 94%): I FINMR (400 MHz, CD30D) 69.02 (dd, J = 2.7,

0.7 Hz, 1H), 8.70 (s, 1H), 8.54 (dd, J = 5.0, 1.4 Hz, 1H), 8.30 (ddd, J = 8.4, 2.7, 1.4 Hz, 1H),

7.63 (ddd, J = 8.4, 5.0, 0.7 Hz, 1H), 6.09 (ddd, J = 5.6, 2.7, 1.0 Hz, 1H), 5.92 (dt, J = 5.6, 2.1

Hz, 1H), 4.16 (d, J= 7.7 Hz, 1H), 3.80- 3.72(m, 1H), 2.98(s, 3H), 2.29 (dt, J = 14.3, 7.9 Hz,

1H), 2.01 (dt, J = 14.3, 2.5 Hz, 1H); 13C NMR (101 MHz, CDCI3) 6 179.16, 163.52 (q, J = 19 Hz)

15

, 145.04, 142.05, 141.15, 137.81, 136.71, 134.11, 134.06, 132.73, 131.26, 129.77, 119.49 (q, J

= 289 Hz) 59.80, 51.85, 40.50, 36.87; ESIMS m/z 318 ([M+H]).

137

17149

Example 140: Preparation of (1S,4R)-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-

methyl-4-(methylsulfonamido)cyclopent-2-enecarboxamIde (Compound Y2054)

I N CH3

To a solution of (1S,4R)-4-amino-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-

5 methylcyclopent-2-enecarboxamide 2,2,2-trifluoroacetate (541 mg, 1.25 mmol) dissolved in

CH2Cl2 (15 mL) was added triethylamine (0.380 mg, 3.76 mmol) followed by methanesulfonyl

chloride (215 mg, 1.88 mmol). After stirring for 24 hours the reaction was diluted with saturated

aqueous sodium bicarbonate (15 ml..) and the phases were separated. The organic layer was

dried with anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was

10

purified by silica gel chromatography utilizing methanol and CH2Cl2 resulting in the isolation of

the title compound as a white foam (319 mg, 64%).

Example 141: Preparation of (1S,3R)-N-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-N-

methyl-3-(methylsulfonamido)cyclopentanecarboxamide (Compound Y2092)

Cl

z-N

I •■.

N

N /

0

pH3

sto

CH3

15 A solution of (1R,4S)-4-amino-N43-chloro-1-(pyridin-3-0)-1H-pyrazol-4-y1)-N-

methylcyclopent-2-enecarboxamide 2,2,2-trifluoroacetate (60 mg, 0.15 mmol) In methanol (1.5

mL) was passed through an H-Cubeal continuous flow hydrogenator equipped with a 10% Pd/C

cartridge (full H2, 25 °C, 1 mUmin flow rate). The resulting solution was concentrated and

purified by silica gel chromatography utilizing methanol and CH2a2 as a mobile phase to

20 provide the title compound as white solid (16 mg, 24%).

Example 142: Preparation of N-(3-chtoro.1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-3-(1H-tetrazol-5-

y1)-N-ethylpropanamide (Compound Y2178)

H3C

To a solution of N-(3-chloro-1-(pyridin-3-)1)-1H-pyrazol-4-y1)-3-cyano-N-

25 ethylpropanamide (0.176g. 0.579 mmol) in toluene (5.79 mL) at ambient temperature and

Cl

N pH3 / H

N N 5s00

,N

HN — NI

138

17149

under N2 were added azidotrimethylsilane (0.154 mL, 1.159 mmol) and dibutylstannanone

(0.014 g, 0.058 mmol). The reaction vessel was fitted with a condenser and heated to 110 °C.

The reaction was allowed to stir at the same temperature for 24 h at which point UPLC-MS

analysis indicated nearly complete conversion to a product of the desired mass. The reaction

5 was cooled, diluted (slowly) In Me0H (20 mL) and concentrated in vacua to afford a dark brown

oil. The residue was absorbed onto Celite and purified via reverse phase flash chromatography

(0 to 100% CH3CN/H20) to afford the desired product as a pale brown glassy solid (49 mg,

24%).


10 trifluoro-2-methylpropyl)thlo)propanamIde (Compound 919)

Cl 0 F

N)L-Srl<FF

H3C) CH3

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-34(2-

(trifluoromethyl)allypthlo)propanamide (0.056g. 0.134 mmol) In DME (2.5 mL) and water (0.5

ml.) were added 4-methylbenzenesulfonohydrazide (0.249 g, 1.337 mmol) and sodium acetate

15 (0.110 g, 1.337 mmol). The reaction was heated to 90 °C and was stirred for 1.5 h. UPLC-MS

analysis indicated —30% conversion to a product of the desired mass. The reaction was stirred

at 90 °C for an additional 1.5 h at which point UPLC-MS analysis Indicated —75% conversion to

a product of the desired mass. The reaction was cooled and an additional 5 equivalents of both

the hydrazide and sodium acetate were added. The reaction was again heated to 90 °C and

20 stirred for an additional 2 h. UPLC-MS Indicated only minor amount of starting material

remaining. Therefore, an additional 5 equivalents of both hydrazide and sodium acetate were

added. The reaction was stirred at 90 °C for additional 3 h. The reaction was cooled, diluted in

Et0Ac (10 ml.) and washed with water (2 x 5 mL) and brine (1 x 5 mL). The organic layer was

dried over Na2504, filtered and concentrated in vacua to afford a yellow oil. The crude residue

25 was purified via normal phase flash chromatography (0 to 100% Et0Ac./CH 2Cl2) to afford the

desired product as a pale yellow oil (46 mg, 79%).

139

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(vinylthlo)propanamicle (Compound 787)

Cl 0

S

H3C CH3

To a dry round bottom flask under N2 were added sodium hydride (0.043g. 1.063 mmol,

5 60% dispersion In mineral oil) and THF (2.126 ml.), followed by methanol (0.086 mL, 2.126

mmol). The reaction was allowed to stir at ambient temperature until cessation of gas evolution

was observed (-45 min). The reaction was then cooled to 0°C and S-(14(3-chloro-1-(pyridin-3-

y1)-1H-pyrazol-4-y1)(ethyl)amino)-1-oxopropan-2-y1) ethanethioate (0.150g, 0.425 mmol) In THE

(2.126 mL) was added. The reaction was warmed to ambient temperature and stirred for 30

10 mm. The reaction was again cooled to 0°C and 1-fluoro-2-iodoethane (0.104 ml., 1.275 mmol)

In THF (2.126 mL) was added. The reaction was warmed to ambient temperature and stirred

ovemight. The reaction was diluted In Et0Ac (5 ml.) and quenched with H20 (1 ml.). The layers

were separated and the aqueous layer was extracted with Et0Ac (3 x 10 ml.). The combined

organic extracts were dried over Na2SO4, filtered and concentrated in vacua to give a brown oil.

15 The crude residue was purified via flash chromatography (25-80% Et0M/Hexanes) to give the

desired product as an opaque oil (29 mg, 20%).

Example 145: Preparation of (E)-N-(3-chloro-1-(pyridin-3y1)-1H-pyrazol-4-y1)-N-ethyl-3.

((3,3,34r1fluoroprop-1-en-1-yl)thio)propanamIde (Compound 890)

CI 0

N)L,

S^)<

F

H3C

20 To an oven-dried microwave vial under N2 were added dioxane (0.241 mL), Cu 20 (3.45

mg, 0.024 mmol), KOH (0.0154g. 0.965 mmol), (E)-1-bromo-3,3,3-trifluoroprop-1-ene (0.563

ml., 4.83 mmol), and N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

mercaptopropanamide (0.150g. 0.483 mmoI), sequentially. The reaction was capped and

placed on a Biotage® Initiator microwave reactor for 3 h at 110 °C, with external IR-sensor

25 temperature monitoring from the side of the vessel. During this time, the reaction mixture went

from a thick, yellow mixture to a black mixture. The heterogeneous mixture was cooled to room

temperature and diluted with Et0Ac (20 mL). The mixture was filtered through a pad of Celite

(Et0Ac wash) and the filtrate was concentrated in vacua to give an dark brown oil. The crude

residue was purified via normal phase flash chromatography (0 to 100% Et0Ac/CH2C12) to

140

17149

afford the desired product as a pale yellow oil (71 mg, 35%). Reference: Kao, H.-L.; Lee, C.-F.

Org. Lett. 2011, 13, 5204-5207.

Example 146: Preparation of N43-chloro-1.(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

(methylsulfonamido)propanamide (Compound Y2145)

CI 00

JL N

YS.CH3

5 H3C

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethylacrylamide (0.538g.

.1.944 mmol) in DMF (19.44 mL) at ambient temperature were added K2CO3 (0.672 g, 4.86

mmol) and methanesulfonamide (0.277 g, 2.92 mmol). The reaction was fitted with a reflux

condenser and heated to 80 °C. After stirring for 1 h, the reaction was cooled to ambient

10 temperature and diluted in Et0Ac (50 mL) and water (50 ml). The layers were mixed vigorously

for 2 min and then separated. The aqueous phase was extracted with Et0Ac (3 x 50 ml) and

the combined organic extracts were washed with brine (3 x 100 mL), dried over Na 2SO4, filtered

and concentrated In vacuo to afford a clear oil. The crude residue was purified via normal phase

flash chromatography (0 to 30% Me0H/Et0Ac) to afford the desired product as a clear semi-

15 solid (524 mg, 69%).

Example 147: Preparation of N-(3-chloro-1.(pyridin-3-y1)-1H-pyrazol-4-y1)-3-(N-

(cyanomethyl)methylsulfonamido)-N-methylpropanamide (Compound 803)

CI 0 00

% CH3

CH3

N

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-methyl-3-

20 (methylsulfonamido)propanamide (0.085g, 0.238 mmol) In THF (2.376 mL) at 0 °C was added

NaH (9.98 mg, 0.249 mmol, 60% dispersion In mineral oil). The reaction was allowed to stir for

10 min at which point 2-bromoacetonitrile (0.025 ml, 0.356 mmol) was added. The reaction was

allowed to warm to room temperature and was stirred for lh. The reaction was quenched with

the addition of water (5 mL) and was diluted In Et0Ac (10 ml). The layers were separated and

25 the aqueous layer was extracted with Et0Ac (3 x 10 ml). The combined organic extracts were

dried over Na2SO4, filtered and concentrated In vacuo. The crude residue was purified via flash

chromatography (0 to 10% Me0H/CH 2Cl2) to give the desired product as a pale yellow foam (86

mg, 87%).

141

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trlfluoropropyl)amlno)propanamide

F F

To a microwave vial were added Me0H (2.0 mL), 3,3,3-trifluoropropan-1-amine (0.386 g,

5 3.42 mmol) and 3-chloro-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethylpropanamide

(0.107g. 0.342 mmol), sequentially. The reaction was capped and placed in a Biotage® Initiator

microwave reactor for 3 h at 100 °C, with external IR-sensor temperature monitoring from the

side of the vessel. After cooling, the reaction was concentrated In vacuo and purified via normal

phase flash chromatography (0 to 15% Me0H/Et0Ac) to afford the desired product as an

10 opaque viscous oil (127 mg, 94%): NMR (400 MHz, CDCI 3) 68.94 (dd, J= 2.8, 0.7 Hz, 1H),

8.63 (dd, J= 4.7, 1.5 Hz, 1H), 8.04 (ddd, J= 8.3, 2.7, 1.4 Hz, 1H), 7.95(s, 1H), 7.46 (ddd, J=

8.4, 4.8, 0.8 Hz, 1H), 3.71 (q, J= 7.2 Hz, 2H), 2.93 - 2.80 (m, 4H), 2.35(t, J= 6.2 Hz, 2H), 2.28

(ddt, J= 14.6, 7.3, 3.6 Hz, 2H), 1.16 (t, J= 7.2 Hz, 3H); "F NMR (376 MHz, CDCI3) 6 -65.13;

ESIMS m/z 390 ([1v1+H1).

15 N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-(methylamlno)propanamide was

prepared as In Example 148: 1 H NMR (400 MHz, CDCI 3) 6 9.01 (d, J= 2.6 Hz, 1H), 8.61 (dd, J

= 4.8, 1.4 Hz, 1H), 8.23 (s,1 H), 8.06 (ddd, J= 8.3, 2.7, 1.4 Hz, 1H), 7.45 (dd, J= 8.3, 4.8 Hz,

1H), 7.24 (s, 1H), 3.68 (q, J= 7.2 Hz, 2H), 3.14 (t, J= 6.1 Hz, 2H), 2.71 —2.56 (m, 5H), 1.14 (t,

J= 7.2 Hz, 3H); "C NMR (101 MHz, CDCI3) 6 172.1, 148.6, 140.8, 140.1, 135.6, 126.6, 126.3,

20 124.1, 123.8, 47.1, 43.8, 36.1, 33.5, 13.1; ESIMS m/z 308 ([1v1+11 ° ).

N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-eth)l-3-((4,4,4-

trifluorobutyl)amino)propanamide was prepared as in Example 148: I HNMR (400 MHz, CDCI 3)

6 9.04 (d, J= 2.7 Hz, 1H), 8.61 (dd, J= 4.7, 1.5 Hz, 1H), 8.36 (s, 1H), 8.08 (ddd, J=8.4,2.8,

1.5 Hz, 1H), 7.45 (ddd, J=8.4,4.8,0.7 Hz, 1H), 3.69 (q, J=7.2 Hz, 2H), 3.18 (t, J= 6.0 Hz,

25 2H), 3.02(t, J= 7.7 Hz, 3H), 2.75(t, J= 6.0 Hz, 2H), 2.25 (tdt, J= 16.1, 10.6, 5.5 Hz, 2H), 2.14 -

1.98(m, 2H), 1.16 (t, J= 7.2 Hz, 3H); "F NMR (376 MHz, CDCI3) 5-66.03; ESNS m/z 404

([M+Hj').

N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-(ethylamino)propanamide was

prepared as In Example 148: 1 H NMR (400 MHz, CDCI3) 69.05 (s, 1H), 8.61 (s, 1H), 8.41 (dd, J

30 = 7.6, 2.1 Hz, 1H), 8.09 (dd, J= 8.3, 1.4 Hz, 1H), 7.44 (dd, J= 8.4, 4.8 Hz, 1H), 3.83 - 3.59 (m,

2H), 3.21 (t,J= 6.0 Hz, 2H), 3.14 - 2.97 (m, 2H), 2.86 (s, 2H), 1.52 - 1.32 (m, 3H), 1.23 - 1.06

142

17149

(m, 3H); "C NMR (101 MHz, CDCI3) 6 170.7, 148.5, 140.5, 140.0, 135.6, 128.1, 126.4, 124.0,

122.4, 44.0, 43.3, 43.3, 30.1, 12.8, 11.4; ESIMS m/z 322 ([M+Hr).

N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-(phenylamino)propanamide was

prepared as In Example 148: 1 H NMR (400 MHz, CDCI3) 68.81 (d, J= 2.7 Hz, 1H), 8.60 (dd, J

5 = 4.8, 1.4 Hz, 1H), 7.89 (ddd, J= 8.3, 2.7, 1.5 Hz, 1H), 7.54(s, 1H), 7.42 (ddd, J = 8.3, 4.8, 0.8

Hz, 1H), 7.17- 7.05(m, 2H), 6.64 (tt, J = 7.3, 1.1 Hz, 1H), 6.59 - 6.49 (m, 2H), 4.22 (s, 1H),

3.70 (dt, J = 14.8, 7.4 Hz, 2H), 3.48 (t, J = 6.0 Hz, 2H), 2.45 (t, J - 6.2 Hz, 2H), 1.14 (t, J = 7.1

Hz, 3H); ESIMS m/z 370 ([M+H]).

Example 149: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-(N-

10 (3,3,3-trifluoropropyl)methylsulfonamido)propanamide (Compound 978)

Cl N 0 0\ 0

)c/■NZ

CH3

,„ n) L. rns..

F F

To a solution of N-(3-chloro-1 ..(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-03,3,3-

trifluoropropyl)amino)propanamide (0.085 g, 0.218 mmol) in CH2Cl2 (2.181 mL) at ambient

temperature and under N2 were added diisopropylethylamine (0.152 mL, 0.872 mmol) and

15

methanesulfonyl chloride (0.025 mL, 0.327 mmol). The reaction was allowed to stir overnight

after which the reaction was diluted In CH202 (5 mL) and water (3 mL). The phases were mixed

and then separated by a phase separator. The organic layer was concentrated In vacuo to

afford a dark orange oil. The crude product was purified via normal phase flash chromatography

(0 to 100% Et0Ac/CH2C12) to afford the desired product as a pale yellow, viscous oil (78 mg,

20 73%).

F

143

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Example 150: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

(methyl(3,3,3-trlfluoropropyl)amino)propanamIde (Compound Y2146)

u 3n) 11%.•

To a solution of but-3-en-2-one (0.040 mL, 0.444 mmol) in water (0.370 mL) and dioxane

20 (0.370 mL) was added N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-

mercaptopropanamide (0.115 g, 0.370 mmol) at ambient temperature. The reaction was allowed

to stir for 1 h at which point the reaction was diluted In CH2a2 and the mixture was stirred

vigorously for 1 h. The mixture was then passed through a phase separator and the remaining

aqueous phase was washed with CH2Cl2 (3 x 5 mL). The combined organic extracts were

25 concentrated In vacua to provide the desired product as an orange oil that was analytically pure

by 1 /1 NMR and UPLC-MS analyses (140 mg, 94%). Reference: Khatik, G. L.; Kumar, R.;

Chakraborti, A. K. Org. Lett. 2006, 8, 2433-2436.

Example 152: Preparation of N-(3-chloro-1-(pyridin-314)-1H-pyrazol-4-y1)-3-((3,3-

difluorobutypthio)-N-ethylpropanamide (Compound 889)

CI p 0 F

)

N 1

CH3 H3C

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-

5 (methylamino)propanamide (0.139 g, 0.452 mmol) in DMF (4.52 mL) at ambient temperature

were added K2CO3 (0.125g. 0.903 mmol) and 3-bromo-1,1,1-trifluoropropane (0.060 mL, 0.565

mmol). The reaction was fitted with a condenser, heated to 70 °C, and stirred overnight. UPLC-

MS analysis Indicated the presence of unreacted starting material. Therefore, an additional 3

equivalents of 3-bromo-1,1,1-trifluoropropane were added and reaction was left to stir at 70°C

10 for 3h. UPLC-MS analysis indicated complete consumption of starting material and conversion

to product of the desired mass. The reaction was cooled, diluted in Et0Ac (20 mL) and filtered

through a pad of Celite. The filtrate was then washed with half-saturated brine (3 x 20 ml..), dried

over Na2504, filtered and concentrated In vacuo. The crude residue was purified via normal

phase flash chromatography (0 to 15% Me0H/CH2C12) to afford the desired product as a clear

15 oil (84 mg, 44%).

Example 151: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-((3-

oxobutyl)thio)propanamIde (Compound 877)

CI N 0 0

S .-"\..A..r, u %al 13

144

17149

H3C

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-34(3-

oxobutypthio)propanamide (0.184g. 0.483 mmol) In CH2Cl2 (4.83 mL) at 0 °C was added

Deoxo-Fluors (0.534 mL, 2.90 mmol) followed by Et0H (0.017 mL, 0.290 mmol). The reaction

5 was stirred at ambient temperature for 48 h during which time the solution went from pale yellow

to dark brown. The reaction was diluted In CH2Cl2 (10 mL) and quenched with the careful

addition of NaHCO3(m) (5 mL). The layers were separated and the aqueous phase was

extracted with CH2Cl2 (3 x 10 mL). The combined organic extracts were dried over Na2SO4,

filtered and concentrated In vacua. The crude residue was purified via normal phase flash

10 chromatography (0 to 100% Et0AcJCH2a2) to afford the desired product as a pale yellow oil (43

mg, 21%).

Example 153: Preparation of N-(3-chloro-1-(pyridln-3-y1)-1H-pyrazol-4-y1)-3-((3,3-

difluoropropyl)thio)-N-ethylpropanamide (Compound 927)

CI 0

H3C

15 To a solution of N-(3-chbro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-((3,3-

dimethoxypropahlo)-N-ethylpropanamide (0.307 g, 0.743 mmol) In THF (7.43 mL) was added

a 1.0M aqueous solution of HCI (7.43 mL, 7.43 mmol). The reaction was allowed to stir at

ambient temperature for 1 h at which point TLC/UPLC-MS analysis indicated complete

hydrolysis to the desired aldehyde product had occurred. The mixture was diluted In Et0Ac (20

20 mL) and water (10 mL). The layers were mixed, separated, and the aqueous layer was

extracted with Et0Ac (3 x 20 mL). The combined organic extracts were washed with NaHCO3(1

x 25 mL), water (1 x 25 mL) and brine (1 x 25 mL) and then dried over Na2SO4, filtered and

concentrated In vacua. The crude product was dried via azeotropic distillation from toluene (3 x

10 mL) and then placed under N2. To the flask was added CH2C12 (7.44 mL) and the solution

25 was cooled to 0 °C. Deoxo-Fluor® (0.686 mL, 3.72 mmol) and Et0H (4.34 pl, 0.074 mmol) were

added and the reaction was warmed to ambient temperature. After 18 h, the reaction was

diluted In CH2Cl2 (10 mL) and quenched with the careful addition of NaHCO 30,43) (5 mL). The

layers were separated and the aqueous phase was extracted with CH2Cl2 (3 x 10 mL). The

combined organic extracts were dried over Na 2SO4, filtered and concentrated In vacua. The

145

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crude material was purified via normal phase flash chromatography (0 to 100% Et0AdCH2C12)

to afford the desired product as a pale yellow oil (151 mg, 50%).

Example 154: Preparation of 1,1,14rIfluoro-3-lodo-5-methylhexane

CH3

F

I F

5 To a microwave vial equipped with a magnetic stir bar were added water (5.94 mL),

acetonitrile (5.94 mL), sodium dithionite (0.569 g, 3.27 mmol), sodium bicarbonate (0.499 g,

5.94 mmol), and 4-methylpent-1-ene (0.379 mL, 2.97 mmol). The vessel was sealed with a

microwave cap (crimped), cooled to -78 °C and evacuated under house vacuum. Next,

trifluorolodomethane (0.873 g, 4.46 mmol) (approximate) was condensed Into the reaction

10 vessel. After warming to ambient temperature, the reaction was stirred for 2.5 h. Prior to

removing the cap, the reaction was vented with a needle and substantial gas evolution was

observed. The reaction was then diluted In water (5 mL) and the mixture was extracted with

Et20 (3 x 20 mL) and the combined extracts were dried over MgSO4, filtered and concentrated

In vacuo to afford a clear oil (740 mg, 80%). Crude I FI NMR analysis Indicated desired product

15 to be of -90% purity. Product was therefore used in subsequent reactions without further

purification: 'H NMR (400 MHz, CDCI3) 6 4.25 - 4.06 (m, 1H), 2.94 (dqd, J = 15.5, 10.6, 6.1 Hz,

1H), 2.77 (dqd, J = 15.5, 10.0, 7.5 Hz, 1H), 1.92- 1.74 (m, 2H), 1.45- 1.28 (m, 1H), 0.98 (d, J =

6.5 Hz, 3H), 0.87 (d, J = 6.5 Hz, 3H); 19F NMR (376 MHz, CDCI3) 6 -63.63. Reference:

Ignatowska, J.; Dmowski, W. J. Fluor. Chem., 2007, 128, 997-1006.

20 (4,4,4-trifluoro-2-lodobutyl)benzene was prepared as In Example 154: 1 H NMR (400

MHz, CDCI 3) 67.41 -7.27 (m, 3H), 7.23 - 7.16 (m, 2H), 4.33 (dq, J= 8.2, 6.7 Hz, 1H), 3.31 -

3.15(m, 2H), 2.96 - 2.72 (m, 2H); 19 F NMR (376 MHz, CDCI3) 6-63.63; EIMS m/z 314.

1-(4,4,4-trifluoro-2-lodobuty1)-1H-imidazole was prepared as in Example 154: 1 H NMR

(400 MHz, CDCI3) 67.61 (t, J = 1.1 Hz, 1H), 7.12(t, J = 1.1 Hz, 1H), 7.00(t, J = 1.4 Hz, 1H),

25 4.46 -4.31 (m, 3H), 2.88 - 2.66 (m, 2H); 19F NMR (376 MHz, CDCI3) 6 -63.57; EIMS m/z 304.

1,1,1-trifluoro-3-lodopentane was prepared as in Example 154: 1 H NMR (400 MHz,

CDCI3) 64.20 (tdd, J = 7.9, 6.2, 4.4 Hz, 1H), 3.01 -2.84 (m, 1H), 2.84 - 2.69 (m, 1H), 1.84- 1.74

(m, 2H), 1.06 (t, J = 7.1 Hz, 3H); 19F NMR (376 MHz, CDCI 3) 6-64.06; EIMS m/z 252.

Example 155: Preparation of S-(1,1,1-trifluoro-5-methylhexan-3-y1) benzothioate

H3C

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17149

To a solution of 1,1,1-trifluoro-3-lodo-5-methylhexane (0.047 g, 0.168 mmol) in DMF

(1.678 mL) at ambient temperature was added potassium benzothioate (0.035g, 0.201 mmol).

The reaction was allowed to stir for 18 h at which point the reaction was diluted in water (3 mL)

5 and Et0Ac (5 mL). The layers were mixed and then separated. The aqueous layer was

extracted with Et0Ac (3 x 5 mL) and the combined organic extracts were washed with water (1

x 10 mL) and half saturated brine (2 x 10 ml..), dried over Na2504, filtered and concentrated in

vacuo. Residue was purified via flash chromatography (0 to 30% Et0Ac./Hexanes) to afford the

desired product as a clear oil (37 mg, 68%): 1 1-INMR (400 MHz, CDC13)5 7.99 - 7.92 (m, 2H),

10 7.62 - 7.55 (m, 1H), 7.50 - 7.41 (m, 2H), 4.10 - 3.95 (m, 1H), 2.73 - 2.56 (m, 1H), 2.56 - 2.40 (m,

1H), 1.94- 1.73(m, 1H), 1.73 - 1.61 (m, 2H), 0.97(d, J = 6.6 Hz, 3H), 0.94(d, J = 6.5 Hz, 3H);

19F NMR (376 MHz, CDCI3) -62.89.

S-(4,4,4-trifluoro-1-phenyibutan-2-y1) benzothioate was prepared as in Example 155: 1 H

NMR (400 MHz, CDCI3) 57.97- 7.89 (m, 2H), 7.58 (ddt, J = 7.9, 6.9, 1.3 Hz, 1H), 7.49- 7.41

15

(m, 2H), 7.39 - 7.26 (m, 5H), 4.29 - 4.15 (m, 1H), 3.11 (d, J = 7.2 Hz, 2H), 2.54 (qd, J = 10.6, 6.6

Hz, 2H); 19F NMR (376 MHz, CDCI3) -62.86; EIMS m/z 324.

S-(4,4,4-trifluoro-1-(1H-Imidazol-1-yl)butan-2-y1) benzothioate was prepared as in

Example 155: 1 H NMR (400 MHz, CDCI3) 57.98- 7.89 (m, 2H), 7.68 - 7.60 (m, 1H), 7.56 (t, J =

1.1 Hz, 1H), 7.53 - 7.45 (m, 2H), 7.11 (t, J= 1.1 Hz, 1H), 7.05(t, J = 1.3 Hz, 1H), 4.42 - 4.18 (m,

20 3H), 2.64 - 2.39 (m, 2H); 19F NMR (376 MHz, CDCI3) -62.98; EIMS m/z 314.

S-(1,1,1-trifluoropentan-3-y1) benzothioate was prepared as in Example 155: 1 11 NMR

(400 MHz, CDCI3) 5 8.02 - 7.91 (m, 2H), 7.64 - 7.55 (m, 1H), 7.51 -7.40 (m, 2H), 4.06 - 3.90 (m,

1H), 2.70 - 2.41 (m, 2H), 2.02- 1.86 (m, 1H), 1.86- 1.71 (m, 1H). 1.05 (t, J -. 7.3 Hz, 3H); 19F

NMR (376 MHz, CDCI3) 5 -63.32; EIMS m/z 262.

25 Example 156: Preparation of N-(3-chloro-1-(pyrldln-3-y1)-1H-pyrazol4i1)-N-ethyl-3-((1,1,1-

trIfluoro-5-methylhexan-3-y1)thio)propanamide (Compound 1053)

147

17149

To a suspension of NaH (60% in mineral oil, 0.012g. 0.300 mmol) in THF (2.86 mL) at

ambient temperature and under N2 was added Me0H (0.058 mL, 1.429 mmol). The reaction

became homogenous and gas evolution was observed. After stirring for 30 min, the reaction

was cooled to 0°C and a solution of S-(1,1,1-trifluoro-5-methylhexan-3-y1) benzothloate (0.083

5 g, 0.286 mmol) In THF (2 ml) was added slowly. The reaction was warmed to ambient

temperature, stirred for 45 min, and then returned to 0 °C. To the reaction was added a solution

of 3-chloro-N-(3-chloro-1-(pyridin-3-y9-1H-pyrazol-4-y9-N-ethylpropanamide (0.090 g, 0.286

mmol) In THF (2 ml). The reaction was warmed to ambient temperature and stirred for 18 h.

The reaction was diluted in Et0Ac (20 mL) and water (10 mL). The layers were mixed and then

10 separated. The aqueous layer was extracted with Et0Ac (3 x 20 mL) and the combined organic

extracts were dried over Na2SO4, filtered and concentrated In vacuo. The crude residue was

purified via normal phase flash chromatography (0 to 100% Et0Ac/CH2C12) to afford the desired

product as a pale yellow oil (63 mg, 45%).

Example 157: Preparation of tert-buty1(2-(2,2-difluorocyclopropyl)ethoxy)diphenylsilane

CH H3C>L

H3C Si t

15

To an oven-dried 3-neck round bottom flask equipped with reflux condenser and addition

funnel under N2 were added (but-3-en-1-yloxy)(tert-buty0diphenylsilane (3.6 g, 11.59 mmol) and

sodium fluoride (7.30 mg, 0.174 mmol) (For preparation of starting olefin, see: Waser, J.;

Gaspar, B.; Nambu, H.; Carreira, E. M. J. Am. Chem. Soc. 2006, 128, 11693-11712). To the

20 closed addition funnel was added trimethylsilyl 2,2-difluoro-2-(fluorosulfony9acetate (4.57 mL,

23.19 mmol). The reaction vessel and its contents were heated to 120°C and the addition

funnel was then opened to allow the sulfonyl fluoride to add over 1 h. Once the addition was

complete, the reaction was allowed to continue stirring at 120 °C for 30 min. The reaction was

cooled to ambient temperature, diluted In CH2Cl2 (50 ml) and washed with NaHCO3( n) (2 x 50

25 mL). The organic phase was separated, dried over Na 2SO4, filtered and concentrated In vacuo

to provide a brown oil. The crude residue was purified via normal phase flash chromatography

(0 to 15% CH2Cl2/Hexanes) to provide the desired product as a clear oil (3.07g. 73%): 1 H NMR

(400 MHz, CDCI3) 5 7.72 - 7.63 (m, 4H), 7.49 - 7.34 (m, 6H), 3.73 (t, J = 6.0 Hz, 2H), 1.88- 1.73

(m, 1H), 1.73 - 1.55 (m, 2H), 1.42- 1.27(m, 1H), 1.06 (s, 9H), 0.94 - 0.81 (m, 1H); 19F NMR

30 (376 MHz, CDCI 3)15 -128.54(d, J = 156.2 Hz), -143.96(d, J= 155.5 Hz); 13C NMR (101 MHz,

CDCI 3) 5 135.5, 133.7 (d, J = 3.7 Hz), 129.6, 127.7, 114.5, 62.8, 30.0 (d, J= 3.5 Hz), 26.8, 19.9

(t, J= 10.9 Hz), 19.2, 15.9 (t, J = 11.0 Hz).

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17149

Example 158: Preparation of 2-(2,2-difluorocyclopropyl)ethyl 4-methylbenzenesulfonate

0 0 zAr S,

o

H3C

To a solution of tert-buty1(2-(2,2-difluorocyclopropyl)ethoxy)diphenylsilane (0.386 g,

1.071 mmol) in THF (10.71 ml..) at 0 °C was added a 1.0M solution of TBAF (3.21 mL, 3.21

5 mmol) In THF. The reaction was warmed to ambient temperature and stirred for 3 h. The

reaction was quenched with the addition of NH,Cl( 1q) (1 mL) and the mixture was partitioned

between water (15 mL) and Et0Ac (15 mL). The layers were mixed well and then separated.

The aqueous layer was extracted with Et0Ac (3 x 20 mL) and the combined organic extracts

were dried over Na2SO4, filtered and concentrated in vacua. The crude residue was then taken

10 up in CH2Cl2 (7.15 mL). To the solution were then added pyridine (0.434 mL, 5.36 mmol) and p-

toluenesulfonyl chloride (0.614g. 3.22 mmol). The reaction was stirred at ambient temperature

for 48 h at which point the reaction was partitioned between CH2Cl2 (50 mL) and water (25 mL).

The layers were separated and the organic layer was washed with 1N HCI 0,4) (20 mL), water (20

mL) and brine (20 mL). The organic layer was then dried over Na2SO4, filtered and concentrated

15 in vacuo. The crude residue was purified via normal phase flash chromatography (0 to 50%

Et0Ac/Hexanes) to afford the desired product as a clear oil (142 mg, 46%, 2 steps): 1 H NMR

(400 MHz, CDCI 3) 6 7.89 - 7.71 (m, 2H), 7.42- 7.29 (m, 2H), 4.20- 3.96 (m, 2H), 2.46 (s, 3H),

1.92 - 1.81 (m, 1H), 1.81 - 1.69(m, 1H), 1.63- 1.48(m, 1H), 1.39 (dddd, J= 12.2, 11.2, 7.7, 4.3

Hz, 1H), 0.93 (dtd, J= 13.0, 7.6, 3.5 Hz, 1H); "C NMR (101 MHz, CDCI3) 6 145.0, 132.9, 129.9,

20 127.9, 113.5 (t, J= 282.4 Hz), 69.0 (d, J=2.2 Hz), 26.6 (d, J=4.3 Hz), 21.7, 18.9 (t, J=11.1

Hz), 15.9 (t, J= 11.0 Hz); 19F NMR (376 MHz, CDCI3) 6-129.09 (d, J= 157.8 Hz), -144.18 (d, J

= 158.1 Hz).

Example 159: Preparation of N-(3-chloro-1-(pyridln-3-y1)-1H-pyrazol-4-y1)-N-

methylacrylamide (Compound Y2098)

C l 0

Il 25 CH3

To a solution of 3-chloro-N-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.526g. 2.52

mmol) In 1,2-dichloroethane (25.2 mL) at 0 °C were added diisopropylethylamine (0.484 mL,

2.77 mmol) and acryloyl chloride (0.205 mL, 2.52 mmol). The reaction was allowed to warm to

ambient temperature and was stirred for 1 h. The reaction was quenched with the addition of

30 NaHCO34,1) and was diluted with CH2Cl2. The layers were separated and the aqueous layer was

extracted with CH 2Cl2. The combined organic extracts were dried over Na 2SO4 , filtered and

CH2

149

17149

concentrated In vacuo. The crude product was purified via flash chromatography (0 to 10%

Me0H/CH 2C12) to give the desired product as an orange solid (634 mg, 91%).

Example 160: Preparation of N-(3-chloro-1-(pyridin-3-y1)-111-pyrazol-4-y1)-N-ethyl-3-((3,3,3-

trlfluoropropyl)thio)propanamide (Compound 653)

CI ,INI jOF

NS F

I<FF

5 H3C)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (10g. 44.9 mmol)

In CH2Cl2 (100 ml) at 0°C and under N2 were added pyridine (5.45 ml, 67.4 mmol), 4-

dimethylaminopyridine (DMAP) (2.74g. 22.45 mmol), and 3-((3,3,3-

trifluoropropyl)thio)propanoyl chloride (9.91 g, 44.9 mmol), sequentially. The reaction was

10 warmed to ambient temperature and stirred for 1 h. The reaction was poured into water (100

ml) and the resulting mixture was stirred for 5 min. The mixture was transferred to a separatory

funnel and the layers were separated. The aqueous phase was extracted with CH2Cl2 (3 x 50

ml) and the combined organic extracts were dried over Na2SO4, filtered and concentrated In

vacuo. The crude product was purified via normal phase flash chromatography (0 to 100%

15 Et0Ac/CH2C12) to afford the desired product as a pale yellow solid (17.21 g, 89%).

Example 161: Preparation of N-(1-(5-fluoropyridin-3-y1)-3-methy1-1H-pyrazol-4-y1)-2-

oxooxazolidine-3-carbothloamide (Compound Y2032)

0

CH3 S )..,

N H

N

To a solution of 1-(5-fluoropyridin-3-y1)-3-methyl-1H-pyrazol-4-amine (0.10g. 0.52 mmol)

20 and triethylamine (0.24 mL, 1.71 mmol) In dry THF (0.52 ml) was added carbon disulfide (0.03

ml, 0.52 mmol) via syringe over 15 minutes. After stirring for 1 hour, the mixture was cooled In

an ice bath and 4-methylbenzene-1-sulfonyl chloride (0.11 g, 0.57 mmol) was added in one

portion, stirred for 5 minutes at 0° C and then warmed to 25 °C and stirred for 1 hour. The

reaction mixture was quenched with 1N HCI and extracted with diethyl ether. The ether layers

25 were combined, washed with water and half saturated aqueous sodium bicarbonate, dried

(MgSO4), filtered and concentrated to dryness to give the desired isothiocyanate (0.12g. 98%).

To a solution of oxazolidin-2-one (0.05 g, 0.61 mmol) dissolved in dry DMF (2.05 mL) was

added sodium hydride (0.03g. 0.61 mmol, 60% dispersion In mineral oil) in one portion and the

suspension was stirred for 20 minutes. The reaction mixture was cooled to 0 °C and 3-fluoro-5-

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17149

(4-lsothlocyanato-3-methyl-1H-pyrazol-1-y9pyridine (0.12g. 0.51 mmol) was added In one

portion in a minimum amount of dry DMF and stirred for 20 minutes. Water and ethyl acetate

were added and the resulting biphasic mixture was separated and the aqueous layer was

extracted one time with ethyl acetate. The combined organic extracts were washed with 1:1

5 hexanes/water, dried (MgSO4), filtered and concentrated to dryness. The crude product was

purified by silica gel chromatography eluting with 0-75% ethyl acetate/hexanes to give the

desired product as a white solid (0.03 g, 18%).

Example 162: Preparation of 3-(4-isothiocyanato-3-methyl-1H-pyrazol-1-yOpyridine

CH3

10

To a solution of 3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.50 g, 2.87 mmol) and

triethylamine (1.3 mL, 1.71 mmol) in dry THF (2.8 mL) was added carbon disulfide (0.17 mL,

2.87 mmol) via syringe over 15 minutes. After stirring for 1 hour, the mixture was cooled in an

ice bath and 4-methylbenzene-1-sulfonyl chloride (0.60g, 0.3.16 mmol) was added In one

15

portion, stirred for 5 minutes at 0 °C and then warmed to 25 °C and stirred for 1 hour. The

reaction mixture was quenched with 1N HCI and extracted with diethyl ether. The ether layers

were combined, washed with water and half saturated aqueous NaHCO3, dried (MgSO4),


chromatography eluting with 0-100% ethyl acetate/hexanes to give the desired product as a

20 light yellow solid (0.48g. 78%): 1 H NMR (400 MHz, CDCI3) 68.89 (d, J = 2.6 Hz, 1H), 8.56 (dd,

J = 4.7, 1.4 Hz, 1H), 7.96 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.89 (s, 1H), 7.40 (ddd, J = 8.3, 4.8,

0.7 Hz, 1H), 2.40 (s, 3H); ESIMS ink 218 ([M+1-1]').

Example 163: Preparation of N-(3-methyl-1-(pyridin-2-y9-1H-pyrazol-4-y1)-2-

oxooxazolidine-3-carbothiamide (Compound Y2034)

0 CH3 s

0

NH

I

25

To a solution of oxazolidin-2-one (0.06g. 0.66 mmol) dissolved in dry DMF (2.2 mL) was

added sodium hydride (0.03 g, 0.67 mmol, 60% dispersion in mineral oil) In one portion and the

suspension was stirred for 20 minutes. The reaction mixture was cooled to 0 °C and 3-(4-

Isothlocyanato-3-methyl-1H-pyrazol-1-yppyridine (0.12g. 0.56 mmol) was added In one portion

151

17149

In a minimum amount of dry DMF and stirred for 20 minutes. Water and ethyl acetate were

added and the resulting biphasic mixture was separated and the aqueous layer was extracted

one time with ethyl acetate. The combined organic extracts were washed with 1:1

hexanes/water, dried (MgSO4), filtered and concentrated to dryness. The crude product was

5

purified by silica gel chromatography eluting with 0-75% ethyl acetate/hexanes to give the

desired product as a white solid (0.07 g, 41%).

Example 164: Preparation of methyl N-(3-methy1-1-(pyrldln-3-y1)-1H-pyrazol-4-y1)-2-

oxooxazoildlne-3-carbimidothloate (Compound Y2035)

,CH3 0 CH3 s'

0

N / N

10 To a solution of oxazolidin-2-one (0.05 g, 0.66 mmol) dissolved In dry DMF (2.22 mL)

was added sodium hydride (0.03 g, 0.66 mmol, 60% dispersion In mineral oil) In one portion and

the suspension was stirred for 20 minutes. The reaction mixture was cooled to 0 °C and 3-(4-

isothlocyanato-3-methy1-1H-pyrazol-1-yl)pyridine (0.12g. 0.55 mmol) was added in one portion

In a minimum amount of dry DMF and stirred for 20 minutes. lodomethane (0.04 mL, 0.66

15 mmol) was added and the reaction was monitored by TLC. Aqueous ammonium chloride and

50% ethyl acetate/hexanes were added and the resulting biphasic mixture was separated and

the organic extract washed with water and saturated aqueous sodium bicarbonate and

concentrated to dryness. The crude product was purified by silica gel chromatography eluting

with 0-10% methanol/CH 2C12 to give the desired product as a light yellow solid (0.14g. 82%).

20 Example 165: Preparation of N-acetyl-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

yl)cyclopropanecarboxamide (Compound Y2060)

CI

e—CH3 0

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y0cyclopropanecarboxamide

(0.15g. 0.57 mmol) In dichloroethane (2.5 mL) was added diisopropylethylamine (0.12 mL, 0.68

25 mmol) followed by acetyl chloride (0.54 g, 0.68 mmoI) and the reaction was stirred at room

temperature overnight Saturated aqueous NaNCO 3 was added and the mixture was extracted

with CH2Cl2. The combined organic phases were concentrated to dryness and purified by silica

gel chromatography eluting with 0-100% ethyl acetate/hexanes to give the desired product as a

white solid (10 mg, 6%). 152

17149

Ci 0 /—j

/ N / N

) H3C

CF3

Example 166: Preparation of S-methyl (3-chloro-5-(methylthlo)-1-(pyridin-3-y1)-1H-pyrazol-

4-ylflethyl)carbamothloate (Compound Y2076)

Cl 9‘ /CH3 t—S

N

\--CH3 IS

N H3C

To a solution of THF (1.35 mL) and diisopropyiethylamine (0.07 mL, 0.40 mmol) was

5 added 2.5M n-butyllithium (0.16 mL, 0.40 mmol) and the reaction was stirred for 30 minutes.

The reaction was cooled further to -78 °C and to this was added dropwise S-methyl (3-chloro-1-

(pyridin-3-y1)-1H-pyrazol-4-y1)(ethy9carbamothloate (0.10 g, 0.33 mmol) in a minimum amount

of dry THF and stirred for 45 minutes. To this was then added 1,2-dimethyldisulfane (0.049,

0.37 mmol) and the reaction was stirred for additional 20 minutes. The reaction was poured into

10 water and extracted with ethyl acetate. The ethyl acetate layers were combined, dried (MgSO4),


chromatography eluting with 0-100% ethyl acetate/hexanes to give the desired product as a

clear oil (53 mg, 46%).

Example 167: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-(3,3,3-

15 trifluoropropyl)thio)propanamide (Compound 653)

I N

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

mercaptopropanamide (0.10 g, 0.32 mmol) dissolved in dry THF (1.07 mL) and cooled in an ice

bath was added sodium hydride (0.02 g, 0.34 mmol, 60% dispersion in mineral oil) in one

20 portion and the reaction was stirred for 10 minutes. To this was added 3-bromo-1,1,1-

trifluoropropane (0.06 g, 0.35 mmol) In one portion In a minimum amount of dry DMF and the

reaction was stirred at room temperature for 2 hours. The reaction mixture was poured into

water and extracted with ethyl acetate. The ethyl acetate layers were combined and


25 with 0-75% ethyl acetate hexanes to give the desired product as a clear oil (83 mg, 63%).

Example 168: Preparation of tett-butyl (21(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

y1)(ethyflamino)-2-oxoethyl)(methyl)carbamate

N /

N

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17149

N-

N /

H3C

H3C H33 CH3

Cl 0

N - CH3 0

/

N* H3C

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.40g. 1.79 mmol)

In dichloroethane (3.59 mL) was added 2-((tert-butoxycarbonyl)(methyDamino)acetic acid (0.37

g, 1.97 mmol), 4-N,N-dimethylaminopyridine (0.249 ' 1.97 mmol) and 1-(3-

5 dimethylaminopropy9-3-ethylcarbodlimide hydrochloride (0.51 g, 2.69 mmol) and the reaction

was stirred overnight at room temperature. The reaction mixture was concentrated to dryness

and the crude product was purified by silica gel chromatography eluting with 0-100% ethyl

acetate/hexanes to give the desired product as a white semi solid (0.61 g, 87%): IR (thin film)

1673 cm'; 'H NMR (400 MHz, CDCI3) 58.96 (d, J = 2.4 Hz, 1H), 8.63 (dd, J = 5.3 Hz, 1H), 8.11

10 -7.86 (m, 2H), 7.51 -7.36 (m, 1H), 3.92 - 3.57 (m, 4H), 2.96 - 2.81 (m, 3H), 1.50- 1.37 (s, 9H),

1.20- 1.11 (m, 3H); ESIMS ink 394 ([M+Fi]+ ).


Example 168:

tert-Butyl (2((3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(methyl)amino)-2-

15 oxoethyl)(methyl)carbamate: 'H NMR (400 MHz, CDCI 3) 6 8.95(d, J = 2.5 Hz, 1H), 8.62(d, J =

4.8 Hz, 1H), 8.14 - 7.84 (m, 2H), 7.59 - 7.35 (m, 1H), 3.85 (d, J = 25.9 Hz, 2H), 3.31 -3.15 (m,

3H), 2.99 - 2.81 (m, 3H), 1.53- 1.31 (s, 9H).

tert-Butyl (24(3-chloro-1-(pyridin-3-y9-1H-pyrazol-4-y1)(cyclopropylmethyDamino)-2-

oxoethyl)(methyl)carbamate: IR (thin film) 1675 cm-1 ; 'H NMR (400 MHz, CDCI 3) 58.95 (bs,

20 1H), 8.63 (dd, J = 5.1 Hz, 1H), 8.17 - 7.88 (m, 2H), 7.54 - 7.36 (m, 1H), 3.99 - 3.41 (m, 4H), 2.97

-2.82 (m, 3H), 1.44 (s, 9H), 1.12 - 0.83 (m, 1H), 0.59 - 0.39 (m, 2H), 0.28 - 0.08 (m, 2H); ESIMS

Ink 420 ([M+H]+).

Example 169: Preparation of N-(3-chloro-1-pyriclin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-

25 (methylamlno)acetamide

H3C

CI 0 isimi

To a solution of tert-butyl (24(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)(ethyl)amino)-2-

oxoethyl)(methyl)carbamate (0.57 g, 1.44 mmol) In CH 2Cl2 (1.44 mL) was added trifluoroacetic

154

17149

acid (1.44 mL) and the reaction was stirred at room temperature for 1 hour. Toluene was added

and the reaction was concentrated to near dryness. The mixture was poured Into a separatory

funnel containing saturated aqueous NaHCO3 and was extracted with CH2Cl2. The CH2C12

layers were combined and concentrated to dryness. The crude product was purified by silica gel

5 chromatography eluting with 0-15% methanol/CH 2C12 to give the desired product as a yellow oil

(0.31 g, 73%): IR (thin film) 1666 cm -1 ; 1 H NMR (400 MHz, CDCI3) 6 8.98 (d, J = 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz, 1H), 8.06 (m, 2H), 7.47 (dd, J= 8.3, 4.8 Hz, 1H), 3.72(q. J= 7.1 Hz,

2H), 3.30 (s, 2H), 2.48 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H); ESIMS m/z 294 ([M+Hr).

The following compounds were made In accordance with the procedures disclosed In

10 Example 169:

N-(3-Chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-methyl-2-(methylamino)acetamide: IR

(thin film) 1666 cm-1 ; 1 H NMR (400 MHz, CDCI3) 6 8.96 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.8, 1.3

Hz, 1H), 8.11 -7.94 (m, 2H), 7.47 (dd, J = 8.4, 4.4 Hz, 1H), 3.30 (s, 2H), 3.27 (s, 3H), 2.47(5,

3H); ESIMS m/z 280 ([M+Hr).

15 N-(3-Chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-(cyclopropylmethyl)-2-

(methylamino)acetamide: IR (thin film) 1667 cm -1 ; 1 H NMR (400 MHz, CDCI3) 68.98 (d, J = 2.6

Hz, 1H), 8.63 (dd, J = 4.7, 1.3 Hz, 1H), 8.11 (s, 1H), 8.06 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.47

(dd, J = 8.3, 4.8 Hz, 1H), 3.53 (bs, 2H), 3.27 (bs, 2H), 2.49 (s, 3H), 1.02- 0.91 (m, 1H), 0.55 -

0.44 (m, 2H), 0.22 - 0.15 (m, 2H); ESIMS m/z 320 ([M+H]).

20

Example 170: Preparation of N-(3-chloro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-(N-

methylmethylsulfonamido)acetamide (Compound 800)

H3C

a 0 % 9% /CH3 N-s

II

N 0

H3C)

N


25 (methylamino)acetamide (0.10 g, 0.34 mmol) In CH2Cl2 (0.68 mL) was added methanesulfonyl

chloride (0.06 g, 0.51 mmol) followed by diisopropylethylamine (0.12 mL, 0.68 mmol) and the

reaction was stirred overnight at room temperature. The reaction mixture was poured Into

saturated aqueous NaHCO3 and extracted with CH2Cl2. The CH2C12 layers were combined and


30 with 50-100% ethyl acetate/hexanes to give the desired product as a white semi-solid (81 mg,

64%).

Example 171: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-((3,3,3-

trifluoropropyl)sulfinyl)propanamide (Compound 861) 155

17149

N /

N CH3

r/CF3

N

Method A: To N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-((3,3,3-

trifluoropropyl)thio)propanamide (0.17 g, 0.43 mmol) in glacial acetic acid (4.35 mL) was added

sodium perborate tetrahydrate (0.07 g, 0.45 mmol), and the mixture was heated at 55 °C for 1

5 hour. The reaction mixture was carefully poured Into a separatory funnel containing saturated

aqueous NaHCO3 resulting In gas evolution. When the gas evolution had ceased, ethyl acetate

was added and the layers were separated. The aqueous layer was extracted twice with ethyl

acetate, and the organic layers were combined, dried over MgSO4, filtered and concentrated

under reduced pressure. The crude material was purified by silica gel chromatography eluting

10 with 0-5% methanol/ CH 2Cl2 to give the desired product as a dark oil (60 mg, 33%).

Method B: To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-

((3,3,3-trifluoropropyl)thio)propanamide (500 mg, 1.229 mmol) In hexafiuoroisopropanol (5 mL)

stirring at room temperature was added 30% hydrogen peroxide (523 mg, 4.92 mmol). The

solution was stirred at room temperature for 15 min. It was quenched with saturated sodium

15

sulfite solution and extracted with CH2Cl2. Silica gel chromatography (0-10% Me0H/CH2C12)

gave the title compound as white semi-solid (495 mg, 95%).


(methylamlno)propanamide

H3C CI 0 1,1, H

N/ H3C

20 2-chloro-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethylpropanamide (0.51 g, 1.62

mmol) and methylamine (4.05 mL, 32.6 mmol, 33% in ethanol) were placed in a 25 mL vial on a

Biotagee Initiator microwave reactor for 45 minutes at 100 °C, with external IR-sensor

temperature monitoring from the side of the vessel. The reaction was concentrated to dryness

and purified by silica gel chromatography (0-10% methanol/CH2C12 to give the desired product

25 as a yellow solid (0.21 g, 43%): 1 FI NMR (400 MHz, CDCI 3) 68.96 (d, J = 2.6 Hz, 1H), 8.64 (dd,

J = 4.7, 1.3 Hz, 1H), 8.06 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.47 (dd, J = 8.3, 4.8 Hz,

1H), 3.93 - 3.57 (m, 2H), 3.25 - 3.11 (m, 1H), 2.34 (s, 3H), 1.21 - 1.17 (m, 6H).

156

17149

The following compound was made In accordance with the procedures disclosed in

Example 172:

N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-(methylamino)propanamide

Cl 0 ,CH3

rK H3C

) ■ N*

5 1 H NMR (400 MHz, Acetone) 69.12 (dd, J = 6.7, 2.6 Hz, 1H), 8.90 (s, 1H), 8.58 (dd, J =

4.7, 1.4 Hz, 1H), 8.25 (m, 1H), 7.56 (m, 1H), 3.67 (q, J = 7.1 Hz, 2H), 3.01 (t, J = 6.5 Hz, 2H),

2.66 (t, J = 6.4 Hz, 2H), 2.50 (s, 3H), 1.12 (t, J = 7.2 Hz, 3H); LC/MS (ESI) ink 308.4 ((M+Hr);

IR (KBr thin film) 3055, 2971, 2773, 1656 crtt l .

Example 173: Preparation of N-(3-chloro-1-(pyridin-319-1/1-pyrazol-4-y1)-N-ethyl-2-(2-

10 methoxyethoxy)acetamide (Compound Y2195)

Cl

H3C

To a stirred solution of 2-methoxyethanol (0.07 mL, 0.87 mmol) in THF (4 mL) at 0 °C

was added sodium hydride (0.032 g, 0.80 mmol, 60% dispersion in oil). After stirring for 10 min

2-chloro-N-(3-chloro-1-(pyridin-3-y0-1H-pyrazol-4-y1)-N-ethylacetamide (0.2 g, 0.7 mmol) was

15 added in one portion. The reaction was stirred for 20 minutes then the reaction vessel was

removed from the ice bath and allowed to warm to room temperature and was stirred overnight

(ca 16 h), at which point the reaction was deemed complete by TLC. The reaction mixture was

diluted with water and ethyl acetate and the layers were separated. The aqueous layer was

extracted with ethyl acetate once. The combined organic layers were dried over MgSO4,

20 concentrated under reduced pressure, and purified by flash chromatography (S102, 100-200

mesh; eluting with 0 to 20% methanol In CH2Cl2) to afford the title compound as a tan solid

(0.045g. 20%).

Example 174: Preparation of N-((3-chloro-1-(pyridin-3-y1)-1N-pyrazol-4-

y1)(methyl)carbamoy1)-N-ethylplvalamIde (Compound Y2082)

0 CI o /CH3

MCH3 N v.." CH3

bH3 CH3

25

, N

157

17149

To a solution of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-ethyl-1-methylurea (0.075

g, 0.268 mmol) In THF (2.68 mL) at -78 °C was added 1 M lithium bis(trimethylsily0amide

(LIHMDS) (0.282 mL, 0.282 mmol) In toluene. The reaction was stirred at-78 °C for 15 min and

pivaloyl chloride (0.036 mL, 0.295 mmol) was added and the reaction was stirred at -78 C for 10

5 min and room temperature for 30 min. Brine was added and the reaction was extracted with

Et0Ac. The combined organic phases were concentrated and purified by flash chromatography

(0-15% Me0H/CH2C12) to give the title compound as a yellow oil (54 mg, 55%): IR (thin film)

2969, 1681 cm -1 ; 1 H NMR (400 MHz, CDCI3) 68.93 (d, J = 2.5 Hz, 1H), 8.61 (dd, J = 4.7, 1.3

Hz, 1H), 8.06 (s, 1H), 8.00 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.44 (dd, J = 8.3, 4.7 Hz, 1H), 3.58 (q,

10 J = 7.0 Hz, 2H), 3.35 (s, 3H), 1.25- 1.13 (m, 12H); ESIMS m/z 365 ([M+Hr).


(methylthio)propanimidamide (Compound 706)

Pt HN /CH3

15 To a solution of 3-chioro-1-(pyridin-3-y9-1H-pyrazol-4-amine (0.058g, 0.297 mmol) in

Et0H (0.992 mL) was added naphthalen-2-ylmethyl 3-(methylthio)propanimidothloate

hydrobromide (0.106g. 0.297 mmol). The reaction was stirred at 0°C for 1 hour. The solvent

was removed under reduced pressure and water and Et 20 were added. The phases were

separated and the aqueous phase was concentrated to give a crude mixture. The residue was

20 dissolved In Me0H (1 mL) and MP-carbonate (0.281 g, 0.892 mmol) was added. The reaction

was stirred at room temperature for 1 hour. The reaction was filtered, concentrated and purified

by flash chromatography (0-15% Me0H/hexanes) to give the title compound as light brown solid

(32 mg, 31%): mp 137 °C; 1 H NMR (300 MHz, CDCI3) 68.86 (d, J = 2.6 Hz, 1H), 8.49 (dd, J =

4.8, 1.2 Hz, 1H), 7.95 (ddd, J = 8.3, 2.5, 1.3 Hz, 1H), 7.68 (s, 1H), 7.37 (dd, J = 8.3, 4.8 Hz, 1H),

25

5.29 (br s, 2H), 3.02 - 2.73 (m, 2H), 2.64 (t, J = 7.1 Hz, 2H), 2.18 (s, 3H); ESIMS m/z 297

([M+H]).

Example 176: Preparation of naphthalen-2-ylmethyl 3-(methylthio)propanimldothioate

hydrobromide

158

17149

HBr

NH

).............--..,s

,..CH3 S

To a solution of 3-(methylthio)propanethioarnIde (0.062g. 0.458 mmol) In CHCI 3 (1.146

ml.) was added 2-(bromomethyl)naphthalene (0.101 g, 0.458 mmol). The mixture was heated at

reflux for 1.5 hours. The reaction was cooled to room temperature, Et 20 was added and a

5 precipitate formed. The solvent was removed under reduced pressure. Et 20 was added and

subsequently decanted. The residual solid was dried under reduced pressure to give the title

compound as a faint yellow solid (109 mg, 67%): 1 H NMR (300 MHz, DMSO-d6) 6 11.78 (br s,

1H), 8.00 (s, 1H), 7.98 - 7.85 (m, 3H), 7.59 - 7.49 (m, 3H), 4.74 (s, 2H), 3.10 (t, J = 7.1 Hz, 2H),

2.84 (t, J = 7.2 Hz, 2H), 2.08 (s, 3H). Reference: Shearer, B. G. et al. Tetrahedron Letters 1997,

10 38, 179-182.

Naphthalen-2-ylmethyl N-methy1-3-(methylthio)propanimIdothioate hydrobromide was

prepared In accordance with the procedure disclosed in Example 176 and isolated as an off-

white semi-solid; 1 FI NMR (400 MHz, DMSO-d6) 58.08 (s, 1H), 8.02 — 7.93 (m, 3H), 7.63 — 7.56

(m, 3H), 5.02 (s, 2H), 3.40 — 3.32 (m, 2H), 3.21 (s, 3H), 2.89 — 2.83 (m, 2H), 2.13 (s, 3H);

15 ESIMS m/z 290 ([M+H]).

Naphthalen-2-ylmethyl N-methylethanimIdothioate hydrobromide was prepared in

accordance with the procedure disclosed in Example 176 and isolated as a white solid; 1 H NMR

(400 MHz, DMSO-d6) 6 8.02(s, 1H), 8.01 — 7.92 (m, 3H), 7.61 — 7.53 (m, 3H), 4.93(s, 2H), 3.15

(d, J= 1.1 Hz, 3H), 2.81 (d, J = 1.1 Hz, 3H); ESIMS m/z 230 ((M+Hr).

20 Naphthalen-2-ylmethyl ethanimidothioate hydrobromide was prepared as described In

Shearer, B. G. eta?. Tetrahedron Letters 1997, 36, 179-182.

Naphthalen-2-ylmethyl cyclopropanecarbimidothloate hydrobromide was prepared In

accordance with the procedure disclosed In Example 176 and isolated as a yellow solid; 1 H

NMR (400 MHz, DMSO-d6) 6 11.58 (s, 1H), 8.01 (s, 1H), 7.99 — 7.88 (m, 3H), 7.59 — 7.51 (m,

25

3H), 4.77 (s, 2H), 2.42 — 2.29 (m, 1H), 1.46— 1.37 (m, 2H), 1.36— 1.29 (m, 2H); ESIMS m/z 242

([M+H]).

Example 177: Preparation of ethyl N-(3-chtoro-1-(pyriclin-3-y1)-1H-pyrazol-4-y1)-Ntethyl-N-

methylcarbamlmidothloate (Compound Y2049)

159

17149

/ N

Cl NrCH3

N

bH3

N

To a solution of 1-(3-chloro-1-(pyridin-3-0)-1H-pyrazol-4-y1)-3-ethyl-1-methylthiourea

(0.085g. 0.287 mmol) In ethanol (1.916 mL) In a microwave vial was added iodoethane (0.028

mL, 0.345 mmol). The reaction was heated In a microwave (CEM DiscoverV) with extemal IR-

5 sensor temperature monitoring from the bottom of the vessel at 80 °C for 6 hours. The reaction

was concentrated and purified by flash chromatography (0-100% Et0M/Hexanes) to give the

title compound as a yellow oil (56 mg, 57%): IR (thin film) 3050, 2931, 1583 cm; I H NMR (300

MHz, CDCI3) 6 9.05 (d, J = 2.6 Hz, 1H), 8.91 (s, 1H), 8.59 - 8.48 (m, 1H), 8.13- 8.04 (m, 1H),

7.40 (dd, J = 8.4, 4.8 Hz, 1H), 3.81 (q, J = 7.2 Hz, 2H), 3.73 (s, 3H), 2.95 (q, J= 14.1, 7.0 Hz,

10 2H), 1.44- 1.28 (m, 6H); ESIMS ink 325 aM+Hr).

Example 178: Preparation of N-(3-chloro-1-(pyridln-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-(N-

methyl-N-(3,3,3-trlfluoropropyl)sulfamoyi)propanamide (Compound 965)

H3C F 0 IR N(-F

N --

N)Lrl( F

)

0

H3C N

To a stirred solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-0)-N-ethyl-3-

15 mercaptopropanamide (200 mg, 0.64 mmol), tetrabutylammonium chloride (715 mg, 2.57 mmol)

and water (29 mg, 1.61 mmol) in acetonitrile (30 mL) at 0 °C was added 1-chloropyrrolidine-2,5-

dione (258 mg, 1.93 mmol) in portions over 3 min. After stirring for 1 hour, 3,3,3-trifluoro-N-

methylpropan-1-amine (82 mg, 0.64 mmol) was added and the reaction was stirred for

additional 14 hours at room temperature. The mixture was filtered and concentrated In vacuo to

20 give a brown residue. Purification of this residue on silica gel eluting with CH2Cl2 and methanol

afforded the title compound as an off-white gum (71 mg, 22%).

Example 179: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-((1-chloro-

2,2,2-trifluoroethyl)thio)-N-ethylpropanamIde (Compound 859)

CI isl 0 CI

iL-S) < F ) F F

Cl

H3C

160

17149

Cl 0

H3C

To a suspension of N-(3-chbro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-

mercaptopropanamide (0.100g. 0.322 mmol), sodium dithionite (0.070g. 0.338 mmol) and

sodium bicarbonate (0.028g. 0.338 mmol) In DMSO (3.22 mL) at 40 °C was added 2-bromo-2-

chloro-1,1,1-trifluoroethane (0.079g. 0.402 mmol) dropwise. The reaction was stirred at the

5 same temperature for 3 h after which the reaction was cooled, poured Into water (10 mL) and

extracted with Et0Ac (3 x 20 mL). The combined organic extracts were washed with water (2 x

50 mL) and half-saturated brine (3 x 50 mL) and then dried over Na2SO4, filtered and

concentrated in vacua. The crude residue was purified via normal phase flash chromatography

(0 to 100% Et0Ac/CH2C12) to afford the desired product as a clear, viscous oil (111 mg, 77%).

10 (Reference: Pustovit, et al., Synthesis, 2010. 7, 1159-1165).

Example 180: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-3-((3-

(mesitylamino)-3-oxopropyl)thio)propanamide (Compound 1024)

CH3

H3C 0

ri—NH CH3

To a stirred solution of N-(3-chloto-1-(pyridin-3-y1)-1H-pyrazol-4-0)-N-ethyl-3-

15 mercaptopropanamide (0.20g. 0.64 mmol) in acetonitrile (2.1 mL) was added 3-bromo-N-

mesitylpropanamide (0.17 g, 0.64 mmol) and cesium carbonate (0.23g. 0.70 mmol) and the

reaction was stirred overnight at room temperature. The reaction was loaded directly onto celite

and placed In a vacuum oven overnight at 25 °C. The crude product was purified by silica gel

chromatography eluting with 0-75% ethyl acetate/hexanes to give the desired product as a white

20 semi-solid (226 mg, 53%).

Example 181: Preparation of two enantiomers of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-

y1)-N-ethyl-34(3,3,3-trlfluoropropyl)sulfinyl)propanamIde (Compounds 1028 and 1029)

CF3

CI

N S`‘o

N N \

H3C

161

17149

The two enantiomers of the title molecule were separated by chiral HPLC using a

RegisCellTm semi-preparative column (25 cm x 10.0 mm, 5 micron) using 0.1% TFA in hexane

and isopropanol as the mobile phase (15 to 30% gradient IPA/hexane In 15 minutes, then hold

to 20 minutes) with a flow rate of 15 mUmin at ambient temperature. Under these conditions

5 compound 1028 was collected at a retention time of 6.0 min and possessed an optical rotation

of [0103° = +25.9 (c 0.27% in CDCI3). Compound 1029 was collected at a retention time of 7.5

min and possessed an optical rotation of [010 3° = -27.4 (c 0.27% in CDCI3). Characterization

data for these molecules are listed in Table 2.

Example 182: Preparation of N-(3-chloro-1.(pyridin-3-y1)-1H-pyrazol-4-y1)-4,4,4-trifluoro-N-

10 methyl-3-(methylsulfonyl)butanamIde (Compound 714)

F3c F 0 /CH3

S% II

%Q

0

N

To a 20 mL vial was added N-(3-chloro-1-(pyridin-3-0)-1H-pyrazol-4-)0-4,4,4-trifluoro-N-

methyl-3-(methylsulfinyl)butanamide (130 mg, 0.329 mmol) and DCM (3 mL). m-CPBA (83 mg,

0.362 mmol) was added and the solution was stirred at room temperature for 3 hours. The

15 reaction was quenched by the addition of sodium sulfite solution, extracted with DCM and

concentrated. Purification with silica gel chromatography (0-100% Et0Adhexane) afforded N-

(3-chlor o-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-4,4,4-trifluoro-N-methyl-3-(methylsulfonyl)butanamide

as a white solid (25 mg, 18%).

Example 183: Preparation of enantlomers of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-11)-

20 Neethyl-2-methyl-3-(methylsulfinyl)propanamide (Compounds 804-807)

CH3

C S:b

0

, CH3

) H3C

N / Isi‘

CH3

C l

N

The four stereoisomers of the title compound were separated by chiral HPLC using

Chiralpak IC column (30 x 250 mm) using 0.2% TFA and 0.2% isopropylamine in hexane and

Isopropanol as the mobile phase (25% IPA In hexane) at ambient temperature. Under these

25 conditions compound 804 was collected at a retention time of 8.4 minutes and possessed an

optical rotation of [D]o ° = -43.8 (c 0.5% In CDCI3). Compound 805 was collected at a retention

time of 11.9 minutes and possessed an optical rotation of (DV = +48.2 (c 0.5% in CDCI3).

Compound 806 was collected at a retention time of 16.4 minutes and possessed an optical

162

17149

N --- I / NH2

Cl

rotation of Plow = +113.4 (c 0.5% In CDCI3). Compound 807 was collected at a retention time

of 20.6 minutes and possessed an optical rotation of [DV ° = -93.0 (c 0.5% in CDCI3).

Characterization data for these molecules are listed in Table 2.

Example 184: Preparation of 3((3,3,3-trifluoropropyl)thio)propanoyl chloride

5 Cl

A dry 5 L round bottom flask equipped with magnetic stirrer, nitrogen inlet, reflux

condenser, and thermometer, was charged with 3((3,3,3-trifluoropropyl)thio)propanoic acid

(188g. 883 mmol) In dichloromethane (3 L). Thionyl chloride (525 g, 321 mL, 4.42 mol) was

then added dropwise over 50 minutes. The reaction mixture was heated to reflux (36 °C) for two

10 hours, then cooled to ambient temperature. Concentration under vacuum on a rotary

evaporator, followed by distillation (40 Torr, product collected from 123- 127 °C) gave the title

compound as a clear colorless liquid (177.3 g, 86%): 'H NMR (400 MHz, CDCI3) 63.20 (t, J =

7.1 Hz, 2H), 2.86 (t, J = 7.1 Hz, 2H), 2.78 - 2.67 (m, 2H), 2.48 - 2.31 (m, 2H); 19F NMR (376

MHz, CDCI3) 6-66.42, -66.43, -66.44, -66.44.

15 Example 185: Preparation of 3-chloro-1-(5-chloropyridin-3-y1)-1H-pyrazol-4-amine

Cl

To a solution of tert-butyl (3-chloro-1H-pyrazol-4-y1) carbamate (5 g, 22.97 mmol) in a

mixture of DMF-H20 (9:1) (40 mL) was added copper Iodide (0.13g. 0.69 mmol, 0.03 eq),

cesium carbonate (14.97g. 45.9 mmol), 8-hydroxy quinoline (0.33g. 2.30 mmol) and 3-bromo-

20 5-chloropyridine (5.299, 27.5 mmol). The mixture was heated at 140°C under nitrogen for 11

hours. The reaction mixture was cooled to room temperature, quenched with ammonium

hydroxide (15 mL), filtered through celite and the filtrate was extracted with ethyl acetate (3 x 50

ml). The combined organic layer was washed with brine (1 x 50 ml) dried over anhydrous

Na2SO4, filtered, and evaporated to dryness under reduced pressure. The crude product was

25 purified on silica gel using 0-100% ethyl acetate In hexane as eluent to give the title compound

as dark brown amorphous solid (1.35g. 26%): 1 H NMR (400 MHz, DMSO-d6) 68.93 (d, J= 2.24

Hz, 1H), 8.48 (d, J = 2.00 Hz, 1H), 8.25 (t, J = 2.16 Hz, 1H), 7.96 (s, 1H), 4.52 (bs, 2H); ESIMS

m/z 231 ([M+2H] +).


30 Example 185:

1-(5-Bromopyridin-3-y1)-3-chloro-1H-pyrazol-4-amine: ESIMS ink 274 ((M+HI).

163

17149

H3C CH3 CI 0 Y—CH 3

/ NH Cl

3-Chloro-1-(5-methoxypyridin-3-y1)-1H-pyrazol-4-amine: ESIMS m/z 225 ([M+Hr).

3-Chloro-1-(5-methylpyridin-3-yI)-1H-pyrazol-4-amine: 'H NMR (400 MHz, DMSO-de ,

D20): 6 8.68 (s, 1H), 8.27 (s, 1H), 7.86 (d, J = 5.64 Hz, 2H), 2.34 (s, 3H); ESIMS m/z 209

aM+HI).

5 Example 186: Preparation of tert-butyl (3-chloro-1-(5-chloropyriclin-3-y1)-1H-pyrazol-4-

yucarbamate

To a solution of amine 3-chloro-1-(5-chloropyridin-3-y1)-1H-pyrazol-4-amine (1.00 g, 4.4

mmol) and triethylamine (666 mg, 6.6 mmol) In dry THF (10 mL) was added di-tert-butyl

10 dlcarbonate anhydride (960 mg, 4.62 mmol) over 30 minutes and the reaction was allowed to

stir at room temperature for 18 hours. The reaction was diluted with water (10 mL) and extracted

with ethyl acetate (50 mL x 2). The organic phase was washed with brine (10 mL), dried over

Na2SO4, and concentrated under reduced pressure. Purification by silica gel column

chromatography using hexanes as an eluent afforded the titled compound (651 mg, 46%):

15 ESIMS m/z 330 (IM+HI).


Example 186:

tert-Butyl (1-(5-bromopyridin-3-09-3-chloro-1H-pyrazol-4-yOcarbamate: ESIMS m/z 372

Wv1 + 111.).

20

tert-Butyl (3-chloro-1-(5-methylpyridin-3-y1)-1H-pyrazol-4-yl)carbamate: ESIMS m/z 309

([M+H]).

Example 187: Preparation of tert-butyl (3-chloro-1-(5-chloropyrldin-3-y1)-1H-pyrazol-4-

y1)(methyl)carbamate

Cl

N -- 1

CI N /

H3C CH3 Y—CH3

isk CH3

25 To a solution of tett-butyl (3-chloro-1-(5-chloropyridin-3-y9-1H-pyrazol-4-Acarbamate

(501 mg, 1.5 mmol) In dry THF (10 mL) was added potassium tert-butoxide (1.5 mL, 1 M

164

17149

solution in THF) and the reaction was stirred for 30 min. Methyl Iodide (317 mg, 2.25 mmol) was

added slowly at 0 °C and stirred for an additional 18 hours at room temperature. The mixture

was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (2 x

20 mL). The combined organic extract was washed with brine solution (1 x 20 mL), dried over

5 Na2SO4 and evaporated to dryness under reduced pressure. The crude product was purified on

silica gel using hexanes and ethyl acetate as eluent (0-10%) to give the title compound (220 mg,

42%): ESIMS m/z 345 UM+Hr).

The following molecules were made in accordance with the procedures disclosed In

Example 187:

10 tert-Butyl (1-(5-bromopyridin-3-y1)-3-chloro-1H-pyrazol-4-y1)(methyl)carbamate: ESIMS

tniz 387 ([M+H]. ).

tett-Butyl (3-chloro-1-(5-methylpyridin-3-0)-1H-pyrazol-4-y1)(methyl)carbamate: ESIMS

m/z 265 ([M-t-Bu] ).

Example 188: Preparation of 3-chloro-1.(5-chloropyrldin-3-y1)-N-methyl-1H-pyrazol-4-

15 amine

Cl

N 1 / Nti N /

CH3

N

tert-Butyl (3-chloro-1-(5-chloropyridin-3-y1)-1H-pyrazol-4-y1)(methyl)carbamate (343 mg,

1 mmol, 1.0 eq) was dissolved In 1,4-dioxane (10 mL) and the solution was cooled to 0 °C. A

solution of HCI in dioxane (5 mL, 4 M) was added dropwise, and the mixture was stirred for 2

20 hours, then concentrated under reduced pressure. The residue was diluted with CH2Cl2 (50 mL),

and the solution washed with aqueous sodium bicarbonate, water (10 mL) and brine (10 mL).

The organic layer was dried over Na2SO4, and concentrated under reduced pressure to give the

title compound (148 mg, 61%): ESMS m/z 244 ([M+H] +).

The following molecule was made In accordance with the procedures disclosed in

25 Example 188:

1-(5-Bromopyridin-3-y1)-3-chloro-N-methyl-1H-pyrazol-4-amine: ESIMS m/z 289

((M+Hl+ ).

Example 189: Preparation of N-(3-chloro-1-(5-methoxypyrldin-311)-1H-pyrazol-4-y1)-2,2,2-

trlfluoroacetamide

Cl

165

17149

CI 0

N -- ,--CF3

Me0

N

To a solution of 3-chloro-1-(5-methoxypyridin-3-y1)-1H-pyrazol-4-amine (1.0 g, 4.46

mmol) and pyridine (530 mg, 6.69 mmol) In dry dichloromethane (10 mL) was added

trifluoroacetic anhydride (1.0 eq) dropwise at 0 °C. The reaction mixture was slowly warmed to

5 room temperature and stirred for 4 hours. The reaction mixture was diluted with water (10 mL)

and extracted with ethyl acetate (2 x 50 mL). The organic phase was washed with brine (10

mL), dried over Na2SO4 and concentrated under reduced pressure. The crude product was

purified over silica eluting with hexanes and ethyl acetate to afford the title compound (700 mg,

49 %): ESIMS miz 321 ([M+H] ° ).

10 Example 190: Preparation of N-(3-chloro-1-(5-methoxypyriclin-3-y1)-1H-pyrazol-4-y1)-2,2,2-

trifluoro-N-methylacetamide

d o

N --. ,—CF3

1 / N

‘CH3

N

To a solution of N-(3-chloro-1-(5-methoxypyridin-3-y1)-1H-pyrazol-4-y1)-2,2,2-

trifluoroacetamide (700 mg, 2.18 mmol) In dry THF (10 mL) was added potassium tert-butoxide

15 (1 M solution in THF, 0.32 mL, 3.2 mmol) at 0 °C and the reaction was stirred for 30 min. Methyl

iodide (466 mg, 3.28 mmol) was added slowly at 0 °C and the reaction was stirred for an

additional 18 hours at room temperature. The reaction was quenched with saturated ammonium

chloride solution and extracted with ethyl acetate (2 x 20 mL). The combined organic extract

was washed with brine (1 x 20 mL), dried over Na2SO4 and evaporated to dryness under

20 reduced pressure. The crude product was purified on silica eluting with hexanes and ethyl

acetate (0-30%) to give the title compound (426 mg, 58% yield): ESNS ink 335 ([M+Hn.

Example 191: Preparation of 3-chloro-1-(5-methoxypyriclin-3-y1)-N-methyl-1H-pyrazol-4-

amine

Me0

Me0

166

17149

Cl 0 /

N -- , I , N N /

25

) H3C

To a suspension of N-(3-chloro-1-(5-methoxypyridin-3-y1)-1H-pyrazol-4-y1)-2,2,2-trifluoro-

N-methylacetamide (410 mg, 1.23 mmol) In methanol (10 mL) was added K2CO3 (254 mg, 1.8

mmol) and the mixture stirred at room temperature for 4 hours. The reaction was concentrated

under reduced pressure and the residue suspended In dichloromethane (50 mL), and washed

5 with water (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4, and

concentrated under reduced pressure to give the title compound (206 mg, 71% ): ESIMS ink

239 ([M+H]° ).

Example 192: Preparation of diethyl(2((3-chloro-1-(pyridin-311)-1H-pyrazol-4-

y1)(ethyl)amino)-2-oxoethyl)phosphonate

Cl 0

N I,

H3c ) 00

pi /"CH3 --0

H3C 10 N

To a solution of 3-chloro-N-ethy1-14pyridin-3-0)-1H-pyrazol-4-amlne (2.00g. 8.98

mmol), 2-(diethoxyphosphoryl)acetic acid (1.94 mg, 9.88 mmol) and N,N-dimethylpyridin-4-

amine (2.20 g, 17.96 mmol) In dry DMF (10 mL) was added N I-((ethylimino)methylene)-N3,N3-

dimethylpropane-1,3-diamine hydrochloride (2.58 g, 13.47 mmol), and the mixture was stirred at

15 0 °C for 2 hours. The mixture was diluted with water and extracted with ethyl acetate (75 mL x

2). The combined organic extract was washed with saturated aqueous WWI, sat aqueous

NaHCO3 and brine, dried over MgSO4, filtered and concentrated In vacuo to give a brown

residue. This residue was purified on silica gel eluting with CH2Cl2 and methanol to give the title

compound as a brown solid (2.62 g, 69%): mp 46-48 °C; 'H NMR (400 MHz, CDCI3) 6 9.00 (dd,

20 J = 2.7, 0.7 Hz, 1H), 8.62 (dd, J = 4.7, 1.4 Hz, 1H), 8.35(s, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz,

1H), 7.44 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 4.28 - 4.02 (m, 4H), 3.79 (m, 2H), 2.89 (d, J = 22.0 Hz,

2H), 1.40- 1.22 (m, 6H), 1.17 (t, J = 7.2 Hz, 3H); ESIMS fit& 401 [(M+Hr] 399 [(M-Hy].

Example 193: Preparation of (E)-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-411)-N-ethyl-5,5,5-

trifluoropent-2-enamide (Compound Y2177)

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To a solution of diethyl (2((3-chloro-1-(pyridin-310-1H-pyrazol-4-y1)(ethyDamino)-2-

oxoethyl)phosphonate (500 mg, 1.25 mmol) In THF (4 mL) was added sodium hydride (55 mg,

1.37 mmol, 60% wt. oil suspension) and the mixture stirred at 0 °C for 20 min. The mixture was

cooled to -78 °C and 3,3,3-trifluoropropanal (210 mg, 1.87 mmol) was added and the reaction

5 was stirred for 1 hour. The mixture was then warmed to room temperature and stirred at room

temperature for 2 hours. Additional NaH (30 mg, 0.75 mmol, 60% wt. oil suspension) was added

and the mixture stirred at room temperature for 0.5 h. The mixture was diluted with water and

ethyl acetate and the organic phase separated, washed with brine, dried over MgSat and

concentrated In vacuo to give a brown oily residue. This residue was purified on silica gel eluting

10 with CH2Cl2 and methanol to give the title compound as a light yellow gum (230 mg, 51%).

Example 194: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-34(3,3-

difluoroallyl)thio)-N-ethylpropanamide (Compound 918)

CI 0

NI N

) I-13C

F ry-F

15 To a solution of 34(3-bromo-3,3-difluoropropyl)thio)-N-(3-chloro-1-(pyridin-3-y1)-1H-

pyrazol-4-y1)-N-ethylpropanamide (100 mg, 0.21 mmol) In dioxane (1 mL) was added

2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (32 mg, 0.21 mmol) and the mixture stirred at

120 °C for 30 min in a Biotage® Initiator microwave reactor with extemal IR-sensor temperature

monitoring from the side of the vessel. The mixture was diluted with ethyl acetate and then

20 washed with saturated aqueous ammonium chloride and brine, dried over Mg504 and

concentrated In vacuo to give a brown gum. This gum was purified on silica gel eluting with

methylene chloride and methanol to give the title compound as a light yellow oil (76 mg, 92%).

Example 195: Preparation of 1-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-ethyl-1,3-

dimethylurea (Compound Y2012)

/

CI 0 rCH3

,- N' Ni% ‘CH3

CH3

168

25

17149

To a solution of 3-chloro-N-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.100g. 0.48

mmol) in CH2Cl2 (1.9 ml) was added N-ethyl-N-isopropylpropan-2-amine (0.21 ml, 1.20 mmol)

followed by ethyl(methyl)carbamic chloride (0.117g. 0.959 mmol) and the reaction mixture was

stirred at ambient temperature for 2 hours. The reaction was quenched by the addition of

5 saturated sodium bicarbonate. The aqueous layer was extracted with CH2Cl2. The combined

organic layers were dried over sodium sulfate, filtered, concentrated in vacuo and purified via

silica gel column chromatography (0-100% ethyl acetate/hexanes) to afford the title compound

as a yellow oil (57 mg, 36%).

Example 196: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-(2,2,2-

10 trifluoroethoxy)propanamIde (Compound Y2001)

Cl 0 F

0j< F F

H3C

To a solution of 2,2,2-trifluoroethanol (128 mg, 1.3 mmol) In DMF (1.3 mL) was added

sodium hydride (51.1 mg, 1.3 mmol). The reaction mixture was stirred for 30 min until the

mixture became clear and no H2 evolution was observed. To this solution was added 2-chloro-

15 N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y1)-N-ethylpropanamide (200 mg, 0.64 mmol) and the

reaction mixture was stirred at 50 °C overnight. The reaction mixture was diluted with CH2Cl2

and washed with water, the phases were separated with a Biotagee Phase separator and then

concentrated. The residue was purified by silica gel chromatography eluting with 0-50% acetone

in hexanes to afford the titled compound as a white solid (156 mg, 64%).

20 Example 197: Preparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethyl-2-

((methylthio)methoxy)propanamide (Compound Y2199)

CI N 0 ,

OS„,, un3

H3C) CH3


hydroxypropanamide (100 mg, 0.34 mmol) In THF (1.1 mL) was added sodium hydride (60% in

25

mineral oil, 33.9 mg, 0.85 mmol). The mixture was stirred for 15 min and then

(chloromethyl)(methyl)sulfane (33.6 it, 0.41 mmol) was added. After stirring at ambient temp

overnight the reaction mixture was diluted with CH2Cl2 and washed with water. The phases

were separated and dried with a Biotage® Phases Separator° and concentrated In vacuo. The

) CH3

169

17149

residue was purified by silica chromatography eluting with 0-70% acetone In hexanes to afford

the titled compound as an off white solid (73 mg, 63%).

Example 198: Preparation of N-(3-chloro-1-(pyrldin-3-yI)-1 H-pyrazol-4-y1)-2,2-difluoro-N-

5 methyl-2-(methylthlo)acetamide (Compound Y2021)

CI 0

ir CH3

CH3 F F

To a solution of 2-bromo-N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-2,2-difluoro-N-

methylacetamide (250 mg, 0.684 mmol) In DMSO (2.3 mL) was added methanethiol, sodium

salt (96 mg, 1.37 mmol). The reaction mixture was heated to 50 °C for 3h and then diluted with

10 water and extracted with CH2Cl2. The organic phases were dried with Mg304, filtered and

concentrated In vacuo. The residue was purified by silica gel chromatography eluting with 0-

80% acetone in hexanes to afford the titled compound as a red oil (188 mg, 83%).

Example 199: Preparation of 3-chloro-N-ethyl-1-(pyrldin-3-y1)-1H-pyrazol-4-amine

To a 100 mL round bottom flask charged with 3-chloro-N-ethy1-1-(pyridin-3-y1)-111-

15 pyrazol-4-amine-bis HCI salt (2 g, 6.77 mmol) was added DCM (20 mL) and the suspension was

stirred at room temperature. To this suspension was added saturated NaHCO3 solution slowly

until the bubbling stopped and the aqueous layer became basic. The mixture was loaded Into a

separatory funnel, the organic layer was separated and the aqueous layer was extracted with

DCM (2 x 10 mL). The combined DCM layers were dried and concentrated to give the title

20

compound as an off-white solid (1.41 g, 94%). Analytical data of 3-chloro-N-ethy1-1-(pyridin-3-

yI)-1H-pyrazol-4-amine can be found In Example 8.

Example A: BIOASSAYS ON GREEN PEACH APHID ("GPA") (Myzus perskae) (MYZUPE).

GPA is the most significant aphid pest of peach trees, causing decreased growth,

shriveling of the leaves, and the death of various tissues. It is also hazardous because it ads as

25 a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to

members of the nightshade/potato family Solanaceae, and various mosaic viruses to many

other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower,

daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes,

tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental

30 crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA

has developed resistance to many pesticides.

Certain molecules disclosed In this document were tested against GPA using

procedures described In the following example. In the reporting of the results, Table 3: GPA

170

17149

(MYZUPE) and sweetpotato whitefly-crawler (BEMITA) Rating Table' was used (See Table

Section).

Cabbage seedlings grown In 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used

as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph

5 stages) one day prior to chemical application. Four pots with Individual seedlings were used for

each treatment Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1:1)

solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted

5X with 0.025% Tween 20 in H20 to obtain the solution at 200 ppm test compound. A hand-held

aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until

10 runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by

volume of acetone/methanol (1:1) solvent. Treated plants were held in a holding room for three

days at approximately 25 *C and ambient relative humidity (RH) prior to grading. Evaluation was

conducted by counting the number of live aphids per plant under a microscope. Percent Control

was measured by using Abbott's correction formula (W.S. Abbott, "A Method of Computing the

15 Effectiveness of an Insecticide" J. Econ. Entomol. 18 (1925), pp.265-267) as follows.

Corrected % Control = 100 * (X - Y) / X

where

X = No. of live aphids on solvent check plants and

Y = No. of live aphids on treated plants

20 The results are indicated In the table entitled 'Table 4. Biological Data for CPA

(MYZUPE) and sweetpotato whitefly-crawler (BEMITA)" (See Table Section).

Example B: Insecticidal test for sweetpotato whitefly-crawler (Bemista tabacl) (BEMITA)

In foliar spray assay

Cotton plants grown In 3-inch pots, with 1 small (3-5 cm) true leaf, were used as test

25 substrate. The plants were placed In a room with whitefly adults. Adults were allowed to deposit

eggs for 2-3 days. After a 2-3 day egg-laying period, plants were taken from the adult whitefly

room. Adults were blown off leaves using a hand-held Devilbiss sprayer (23 psi). Plants with

egg infestation (100-300 eggs per plant) were placed in a holding room for 5-6 days at 82 °F

and 50% RH for egg hatch and crawler stage to develop. Four cotton plants were used for each

30 treatment. Compounds (2 mg) were dissolved In 1 mL of acetone solvent, forming stock

solutions of 2000 ppm. The stock solutions were diluted 10X with 0.025% Tween 20 in H20 to

obtain a test solution at 200 ppm. A hand-held Devilbiss sprayer was used for spraying a

solution to both sides of cotton leaf until runoff. Reference plants (solvent check) were sprayed

with the diluent only. Treated plants were held in a holding room for 8-9 days at approximately

35 82°F and 50% RH prior to grading. Evaluation was conducted by counting the number of live

nymphs per plant under a microscope. Insecticidal activity was measured by using Abbott's

171

17149

correction formula and presented in "Table 4. Biological Data for GPA (MYZUPE) and

sweetpotato whitefly-crawler (BEMITA)" (see column "BEMIT/C):

Corrected % Control = 100 ' (X - Y)/ X

where X = No. of live nymphs on solvent check plants

5 Y = No. of live nymphs on treated plants

PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, SOLVATES,

ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND RADIONUCLIDES

Molecules of Formula One may be formulated into pesticidally acceptable acid addition

salts. By way of a non-limiting example, an amine function can form salts with hydrochloric,

10 hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric,

oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic,

methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids.

Additionally, by way of a non-limiting example, an acid function can form salts including those

derived from alkali or alkaline earth metals and those derived from ammonia and amines.

15 Examples of preferred cations include sodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By way of a non-

limiting example, a salt derivative can be prepared by contacting a free base with a sufficient

amount of the desired acid to produce a salt. A free base may be regenerated by treating the

salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide

20 (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, In many

cases, a pesticide, such as 2,4-D, Is made more water-soluble by converting It to its

dimethylamine salt..

Molecules of Formula One may be formulated into stable complexes with a solvent, such

that the complex remains intact after the non-complexed solvent is removed. These complexes

25

are often referred to as "solvates." However, it Is particularly desirable to form stable hydrates

with water as the solvent.

Molecules of Formula One may be made into ester derivatives. These ester derivatives

can then be applied In the same manner as the invention disclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs. Polymorphism

30 Is important In the development of agrochemicals since different crystal polymorphs or

structures of the same molecule can have vastly different physical properties and biological

performances.

Molecules of Formula One may be made with different Isotopes. Of particular importance

are molecules having 2H (also known as deuterium) In place of 1 H.

35 Molecules of Formula One may be made with different radionuclides. Of particular

Importance are molecules having 13C or "C.

STEREOISOMERS

172

17149

Molecules of Formula One may exist as one or more stereoisomers. Thus, certain

molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art

that one stereoisomer may be more active than the other stereoisomers. Individual

stereolsomers may be obtained by known selective synthetic procedures, by conventional

5 synthetic procedures using resolved starting materials, or by conventional resolution

procedures. Certain molecules disclosed In this document can exist as two or more isomers.

The various isomers Include geometric isomers, diastereomers, and enantiomers. Thus, the

molecules disclosed in this document Include geometric isomers, racemic mixtures, Individual

stereoisomers, and optically active mixtures. It will be appreciated by those skilled In the art that

10 one isomer may be more active than the others. The structures disclosed In the present

disclosure are drawn in only one geometric form for clarity, but are Intended to represent all

geometric forms of the molecule.

COMBINATIONS

Molecules of Formula One may also be used In combination (such as, in a compositional

15 mixture, or a simultaneous or sequential application) with one or more compounds having

acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, Insecticidal, molluscicidal,

nematicidal, rodenticidal, or virucidal properties. Additionally, the molecules of Formula One

may also be used in combination (such as, In a compositional mixture, or a simultaneous or

sequential application) with compounds that are antifeedants, bird repellents, chemosterilants,

20 herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters,

plant activators, plant growth regulators, or synergists. Examples of such compounds in the

above groups that may be used with the Molecules of Formula One are - (3-

ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-

methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-lodobenzoic acid, 2,3,6-TBA,

25 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium,

2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-

butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-Isoctyl, 2,4,5-T-isopropyl,

2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine,

2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-

30 DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4DB-

sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-

diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium,

2,4D-Isobutyl, 2,4-D-lsoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-

meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-0-propyl, 2,4-D-sodium,

35 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-

hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-

phenylphenol, 3,4-DA, 3,4DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-

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17149

sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-

phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid,

acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen,

acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile,

5 acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb,

aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-

sodium, allyt alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin,

ametridione, ametryn, amibuzin, amicarbazone, amicarthlazol, amidithion, amidoflumet,

amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl,

10 aminocyclopyrachlor-potassium, aminopyralid, amlnopyralid-potassium, aminopyralid-tris(2-

hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate,

amitraz, amitrole, ammonium sulfamate, ammonium a-naphthaleneacetate, amobam,

ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu,

apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-

15 sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride,

azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-

methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh,

barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl,

benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium,

20 bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil,

benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide,

bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-

isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride,

benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon,

25 benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl,

benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin,

beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi,

bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bloallethrin, bioethanomethrin,

biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium,

30 bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid,

boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate,

brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin,

bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-

DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil,

35 bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,

brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate,

buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos,

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17149

butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate,

butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic

acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium

polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph,

5 carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim

sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion,

carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamld,

cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt

mixture, chinomethionat, chitosan, chlobenthlazone, chlomethoxyfen, chloralose, chloramben,

10 chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-

methylammonium, chloramben-sodium, chloramlne phosphorus, chloramphenicol,

chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl,

chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane,

chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos,

15 chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole,

chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron,

chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon,

chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlomidine,

chlomitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform,

20 chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon,

chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium,

chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,

chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-

monomethyl, chlorthiamid, chelorthlophos, chlozolinate, choline chloride, chromafenozide, cinerin

25 I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin,

clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet,

clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop,

cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potasslum,

clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam,

30 cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,

codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper

carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride,

copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos,

coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,

35 crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron,

cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos,

cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanillde,

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17149

cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxydim,

cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl,

cyhalothrin, cyhexatin, cymiazole, cymlazole hydrochloride, cyrnoxanil, cyometrinil,

cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole,

5 cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate,

daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide,

dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb,

decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-

0, demephlon-S, demeton, demeton-methyl, demeton-O, demeton-0-methyl, demeton-S,

10 demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-

fanshiluquebingjutil, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon,

dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-

dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl,

dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon,

15 dichlobenil, dichlofenthlon, dichlofluanld, dichlone, dichloralurea, dichlorbenzuron,

dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop,

dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-

ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-

ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium,

20 dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine,

diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil,

dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl,

diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole,

difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate,

25 difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,

diflumetorlm, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron,

dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn,

dimethenamid, dimethenamld-P, dimethipin, dimethirimol, dimethoate, dimethomorph,

dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano,

30 dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M,

dinitramlne, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton,

dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamlne, dinoseb-

sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon,

diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium,

35 diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat,

diquat dibromide, disparlure, disul, disulflram, disulfoton, disul-sodium, ditalimfos, dithlanon,

dithIcrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-

176

17149

potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin,

dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin,

drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl,

emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-

5 diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN,

epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon,

ergocalciferol, erlujixiancaoan, esdOpallethrine, esfenvalerate, esprocarb, etacelasil,

etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,

ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion,

10 ethlozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos,

ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl a-

naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene

oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate,

ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid,

15 etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur,

fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin,

fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim,

fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb,

fenoprop, fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl,

20 fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil,

fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb,

fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,

fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion,

fenteracol, fenthlaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin

25 chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam,

ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl,

flamprop-M-Isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamld,

florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl,

fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-

30 sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonii, fluenetil,

fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-

ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac,

flumiciorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram,

fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl,

35 fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam,

flupropacil, fiupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron,

flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-

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17149

butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-

meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-

methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen,

fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate,

5 formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine,

fosamlne-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,

frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl,

furamethrin, furametpyr, furathlocarb, furcarbanil, furconazole, furconazole-cis, furethrin,

furfural, furilazole, furrnecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH.

10 genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P,

glufoslnate-P-ammonium, gIufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-

diammonium, glyphosate-dimethylammonium, glyphosate-lsopropylammonium, glyphosate-

monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,

glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate,

15 halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,

haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl,

haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil,

heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene,

hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos,

20 hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon,

hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA,

lcaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl,

Imazamox, Imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-

lsopropylammonium, Imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium,

25

Imazethapyr, Imazethapyr-ammonium, lmazosulfuron, Imibenconazole, Imicyafos, imidacloprid,

imidaclothiz, iminoctadine, Iminoctadine triacetate, Iminoctadine trialbesilate, imiprothrin,

Inabenflde, indanofan, Indaziflam, indoxacarb, inezin, iodobonil, lodocarb, lodomethane,

iodosulfuron, Iodosulfuron-methyl, lodosulfuron-methyl-sodium, lofensulfuron, iofensulfuron-

sodium, ioxynil, ioxynil octanoate, loxynil-lithium, ioxynil-sodium, Ipazine, ipconazole,

30 ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP,

isamidofos, isazofos, isobenzan, isocarbamid, Isocarbophos, isocil, isodrin, Isofenphos,

lsofenphos-methyl, isolan, Isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin,

Isoprothiolane, isoproturon, Isopyrazam, isopyrimol, Isothioate, isotianil, isouron, isovaledione,

Isoxaben, Isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, Isoxapyrifop, Isoxathion,

35 ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid,

jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile

hormone I, juvenile hormone II, Juvenile hormone III, kadethrin, karbutilate, karetazan,

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17149

karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan,

ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen,

lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin,

linuron, lirimfos, Mire, looplure, lufenuron, lvdingjunzhi, Ivxlancaolin, lythidathion, MAA,

5 malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb,

mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-

butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-Isobutyl, MCPA-lsoctyl,

MCPA-Isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-

thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil,

10 mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-

dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-lsoctyl, mecoprop-

methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-

Isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine,

medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-

15 diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon,

mepanipyrim, mepeffluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat

pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride,

merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen,

mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium,

20 metamifop, metamitron, metam-potassium, metam-sodium, metazachior, metazosulfuron,

metazoxolon, metconazole, metepa, mefflurazon, methabenzthiazuron, methacrifos,

methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion,

methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methluron,

methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl,

25 methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl

bromide, methyl eugenol, methyl Iodide, methyl isothiocyanate, methylacetophos,

methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury

dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram,

metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin,

30 metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron,

metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime,

milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron,

monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester,

monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine

35 hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin,

N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene,

naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide,

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napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-

°famine, nicosulfuron, nicotine, nifluddide, nipyraclofen, nitenpyram, nithiazine, nitralin,

nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide,

norflurazon, nomicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl

5 ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene,

orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl,

oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-

sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole

fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxylluorfen,

10 oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-

dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,

parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron,

pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor,

penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril,

15 phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl,

phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury

acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury

nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan,

phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb,

20 phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl,

picloram-lsoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-

triethylammonium, picloram-tris(2-hydroxypropy0ammonium, picolinafen, picoxystrobin,

pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene,

piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos,

25 pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim,

polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate,

potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate,

potassium a-naphthaleneacetate, pp'-DDT, prallethrin, precocene I, precocene II, precocene III,

pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz,

30 prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,

profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione,

prohexadione-calcium, prohydrojasnnon, promacyl, promecarb, prometon, prometryn, promurit,

propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb

hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine,

35 propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone,

propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler,

prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothlocarb, prothiocarb hydrochloride,

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pmthioconazole, prothiofos, prothoate, protrifenbute, proxan, proxart•SOdillffi, wynachlor, pydanon, pymetrozine, pracarbolid, pyradotos, pradonil l pyraclostrobin, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobln, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulturon-ethyl, pyrazothion, pyrazoxyfen,

5 pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-lsopropyl, pyribambenz-propyI,

pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,

pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil,

pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone,

pyriprole, pyripropanol, pyriproxyfen, pyrithlobac, pyrithiobac-sodium, pyrolan, pyroquilon,

10 pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate,

quinalphos, quinalphos-methyl, quinazamid, quindorac, quinconazole, quinmerac,

quinoclamine, quinonamld, quinothion, quinoxyfen, quintiofos, quintozene, quizalolop,

quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryi, quwenzhi, quyingding,

rabenzazole, rafoxanide, rebern. ide, resmethrin, rtiodethanil, rhodojaponin-Ill, ribavirin,

15 rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, salsentong, salicylanilide, sanguinarine,

santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin,

semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin,

siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton,

simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate,

20 sodium fluoride, sodium fluomacetate, sodium hexafluorosilicate, sodium naphthenate, sodium

orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulflde, sodium thiocyanate,

sodium a-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen,

spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol,

sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid,

25 sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime,

sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate,

tavron, tazimc,arb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-

sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam,

tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione,

30 tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor,

terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos,

tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin,

tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor,

thlamethoxam, thiapronil, thiazaflumn, thiazopyr, thicrofos, thicyofen, thidiazimln, thidiazuron,

35 thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide,

thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam

oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal,

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thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide,

thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa,

thiram, thuringiensin, tiadinil, tiaopean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl,

tolfenpyrad, tolylfluanid, tolyimercury acetate, topramezone, tralkoxydim, tralocythrin,

5 tralomethrin, tralopyril, transfluthrin, transperrnethrin, tretamine, triacontanol, triadimefon,

trladimenol, triafamone, tri-allate, triamiphos, triapenthenol, trlarathene, triarimol, triasulfuron,

triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos,

tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr,

triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane,

10 trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium,

triflumizole, triflumuron, trifluralin, trifiusulfuron, triflusulfuron-methyl, trifop, trifop-methyl,

trifopsime, triforine, trihydroxytriazine, trimediure, trimethacarb, trimeturon, trinexapac,

trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call,

uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone,

15 vamidothion, vangard, vaniliprole, vemolate, vinclozoiin, warfarin, warfarin-potassium, warfarin-

sodium, xiaochongliulin, xinjunan, xlwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing,

zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc

thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, a-chlorohydrin, a-ecdysone, a-

multistriatin, and a-naphthaleneacetic acid. For more information consult the 'COMPENDIUM OF

20 PESTICIDE COMMON NAMES" located at http://www.alanwood.net/pesticideslindex.html . Also

consult "THE PESTICIDE MANUAL: 14th Edition, edited by C D S Tomlin, copyright 2006 by British

Crop Production Council, or its prior or more recent editions.

BIOPESTICIDES

Molecules of Formula One may also be used In combination (such as in a compositional

25 mixture, or a simultaneous or sequential application) with one or more biopesticides. The term

ablopestidde" is used for microbial biological pest control agents that are applied in a similar

manner to chemical pesticides. Commonly these are bacterial, but there are also examples of

fungal control agents, including Trichoderma spp. and Ampelomyces quisqualis (a control agent

for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and

30 rodents have also been controlled with microbial agents. One well-known insecticide example is

Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because It

has little effect on other organisms, it is considered more environmentally friendly than synthet

pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

35 2. entomopathogenic nematodes (e.g. Stelnemema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

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Other examples of entomopathogenic organisms include, but are not limited to,

baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia.

Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as

microbial toxins; Insect tolerant or resistant plant varieties; and organisms modified by

5 recombinant DNA technology to either produce insecticides or to convey an insect resistant

property to the genetically modified organism. In one embodiment, the molecules of Formula

One may be used with one or more biopesticides in the area of seed treatments and soil

amendments. The Manual of Biocontrol Agents gives a review of the available biological

Insecticide (and other biology-based control) products. Copping L.G. (ed.) (2004). The Manual

10 of Biocontrol Agents (formerly the Blopesticide Manual) 3rd Edition. British Crop Production

Council (BCPC), Farnham, Surrey UK.

OTHER ACTIVE COMPOUNDS

Molecules of Formula One may also be used In combination (such as in a compositional

mixture, or a simultaneous or sequential application) with one or more of the following:

15 1. 3-(4-chloro-2,6-dimethylpheny1)-4hydroxy-8-oxa-1-azaspiro[4,51dec-3-en-2-one;

2. 3-(4'-chloro-2,4-dimethyl[1,1s-blphenyl]-3-y1)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-

one;

3. 4-[[(6-chloro-3-pyridinyl)methylimethylamino]-2(5/1)-furanone;

4. 4-[[(6-chloro-3-pyridinyOmethyl]cyclopropylamino]-2(5M-furanone;

20 5. 3-chloro-N2-[(15)-1-methy1-2-(methylsulfonypethyli-N142-methy1-441,2,2,2-tetrafluoro-1-

(trifluoromethy9ethyl]pheny1]-1,2-benzenedicarboxamide;

6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;

7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;

8. 2-cyano-3-difiuoromethoxy-N-ethyl-4-fiuoro-benzenesulfonamide;

25 9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;

10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;

11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;

12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;

13. 3-(difluoromethyl)-N42-(3,3-dimethylbutyl)pheny1]-1-methy1-1H-pyrazole-4-carboxamide;

30 14. N-ethy1-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-p-toly1) hydrazone;

15. N-ethy1-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-a,a,a-trifluoro-p-

toly1) hydrazone nicotine;

16. 0-{(E-)42-(4-chloro-pheny1)-2-cyano-1-(2-trifluoromethylphenyl)-vinylft S-methyl

thiocarbonate;

35 17. (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;

18. 146-chloropyridin-3-ylmethy9-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-Imidazo[1,2-

a)pyridin-5-ol;

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19. 4[4-chlorophenyl-(2-butylidine-hydrazono)methyOlphenyl mesylate; and

20. N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-

alpha,alpha,a/pha-trifluoro-p-tolyphydrazone.

SYNERGISTIC MIXTURES

5 Molecules of Formula One may be used with certain active compounds to form

synergistic mixtures where the mode of action of such compounds compared to the mode of

action of the molecules of Formula One are the same, similar, or different. Examples of modes

of action include, but are not limited to: acetylcholinesterase Inhibitor, sodium channel

modulator; chitin biosynthesis inhibitor, GABA and glutamate-gated chloride channel antagonist;

10 GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist;

acetylcholine receptor antagonist; MET I inhibitor, Mg-stimulated ATPase inhibitor; nicotinic

acetylcholine receptor, Midgut membrane disrupter, oxidative phosphorylation disrupter, and

ryanodine receptor (RyRs). Generally, weight ratios of the molecules of Formula One in a

synergistic mixture with another compound are from about 10:1 to about 1:10, in another

15 embodiment from about 5:1 to about 1:5, and in another embodiment from about 3:1, and In

another embodiment about 1:1.

FORMULATIONS

A pesticide is rarely suitable for application in Its pure form. It is usually necessary to add

other substances so that the pesticide can be used at the required concentration and in an

20 appropriate form, permitting ease of application, handling, transportation, storage, and

maximum pesticide activity. Thus, pesticides are formulated Into, for example, baits,

concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules,

microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets,

water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra

25 low volume solutions. For further Information on formulation types see "Catalogue of Pesticide

Formulation Types and International Coding System" Technical Monograph n°2, 5th Edition by

CropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsions prepared from

concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or

30 emulsifiable formulations are either solids, usually known as wettable powders, or water

dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous

suspensions. Wettable powders, which may be compacted to form water dispersible granules,

comprise an Intimate mixture of the pesticide, a carrier, and surfactants. The concentration of

the pesticide Is usually from about 10% to about 90% by weight. The carrier Is usually selected

35 from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the

purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the

wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates,

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naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-Ionic surfactants such

as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenient concentration of a

pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that

5

is either a water miscible solvent or a mixture of water-Immiscible organic solvent and

emulsifiers. Useful organic solvents Include aromatics, especially xylenes and petroleum

fractions, especially the high-boiling naphthalenic and olefinIc portions of petroleum such as

heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic

solvents Including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex

10

alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are

selected from conventional anionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed In

an aqueous carrier at a concentration in the range from about 5% to about 50% by weight.

Suspensions are prepared by finely grinding the pesticide and vigorously mixing It into a carrier

15 comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural

gums may also be added, to Increase the density and viscosity of the aqueous carrier. It Is often

most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture

and homogenizing It In an Implement such as a sand mill, ball mill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that are particularly useful for

20 applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by

weight of the pesticide, dispersed In a carrier that comprises clay or a similar substance. Such

compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying

it to a granular carrier which has been pre-formed to the appropriate particle size, In the range of

from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough

25 or paste of the carrier and compound and crushing and drying to obtain the desired granular

particle size.

Dusts containing a pesticide are prepared by Intimately mixing the pesticide in powdered

form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the

like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be

30 applied as a seed dressing or as a foliage application with a dust blower machine.

It is equally practical to apply a pesticide in the form of a solution In an appropriate

organic solvent, usually petroleum oil, such as the spray oils, which are widely used In

agricultural chemistry.

Pesticides can also be applied In the form of an aerosol composition. In such

35 compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure-generating

propellant mixture. The aerosol composition is packaged in a container from which the mixture

is dispensed through an atomizing valve.

r

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Pesticide baits are formed when the pesticide Is mixed with food or an attractant or both.

When the pests eat the bait they also consume the pesticide. Baits may take the form of

granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure and hence can exist

5 as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the

fumigant is proportional to Its concentration and the exposure time. They are characterized by a

good capacity for diffusion and act by penetrating the pest's respiratory system or being

absorbed through the pest's cuticle. Fumigants are applied to control stored product pests under

gas proof sheets, In gas sealed rooms or buildings or in special chambers.

10 Pesticides can be microencapsulated by suspending the pesticide particles or droplets in

plastic polymers of various types. By altering the chemistry of the polymer or by changing

factors In the processing, microcapsules can be formed of various sizes, solubility, wall

thicknesses, and degrees of penetrability. These factors govern the speed with which the active

ingredient within is released, which in turn, affects the residual performance, speed of action,

15 and odor of the product.

Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the

pesticide In solution. Oil solutions of a pesticide usually provide faster knockdown and kill of

pests than other formulations due to the solvents themselves having pesticidal action and the

dissolution of the waxy covering of the Integument increasing the speed of uptake of the

20 pesticide. Other advantages of oil solutions Include better storage stability, better penetration of

crevices, and better adhesion to greasy surfaces.

Another embodiment Is an oil-in-water emulsion, wherein the emulsion comprises oily

globules which are each provided with a lamellar liquid crystal coating and are dispersed in an

aqueous phase, wherein each oily globule comprises at least one compound which is

25 agriculturally active, and is Individually coated with a monolamellar or oligolamellar layer

comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non-ionic

hydrophilic surface-active agent and (3) at least one Ionic surface-active agent, wherein the

globules having a mean particle diameter of less than 800 nanometers. Further information on

the embodiment is disclosed In U.S. patent publication 20070027034 published February 1,

30 2007, having Patent Application serial number 11/495,228. For ease of use, this embodiment

will be referred to as "OIWE".

For further information consult - insect Pest Management" 2nd Edition by D. Dent,

copyright CAB International (2000). Additionally, for more detailed Information consult

"Handbook of Pest Control — The Behavior, Life History, and Control of Household Pests" by

35 Arnold Mains, 9th Edition, copyright 2004 by GIE Media Inc.

OTHER FORMULATION COMPONENTS

186

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Generally, when the molecules disclosed in Formula One are used in a formulation, such

formulation can also contain other components. These components include, but are not limited

to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers,

penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam

5 agents, cleaning agents, and emulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid Increases the spreading or

penetration power of the liquid by reducing the interfacial tension between the liquid and the

surface on which it is spreading. Wetting agents are used for two main functions In

agrochemical formulations: during processing and manufacture to Increase the rate of wetting of

10 powders In water to make concentrates for soluble liquids or suspension concentrates; and

during mixing of a product with water in a spray tank to reduce the wetting time of wettable

powders and to improve the penetration of water into water-dispersible granules. Examples of

wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule

formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates;

15 and aliphatic alcohol ethoxyiates.

A dispersing agent is a substance which adsorbs onto the surface of particles and helps

to preserve the state of dispersion of the particles and prevents them from reaggregating.

Dispersing agents are added to agrochemical formulations to facilitate dispersion and

suspension during manufacture, and to ensure the particles redisperse into water in a spray

20 tank. They are widely used In wettable powders, suspension concentrates and water-dispersible

granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto

a particle surface and provide a charged or steric barrier to reaggregation of particles. The most

commonly used surfactants are anionic, non-Ionic, or mixtures of the two types. For wettable

powder formulations, the most common dispersing agents are sodium lignosulfonates. For

25 suspension concentrates, very good adsorption and stabilization are obtained using

polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates.

Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene

oxide condensates and EO-PO block copolymers are sometimes combined with anionics as

dispersing agents for suspension concentrates. In recent years, new types of very high

30 molecular weight polymeric surfactants have been developed as dispersing agents. These have

very long hydrophobic 'backbones' and a large number of ethylene oxide chains forming the

'teeth' of a 'comb' surfactant. These high molecular weight polymers can give very good long-

term stability to suspension concentrates because the hydrophobic backbones have many

anchoring points onto the particle surfaces. Examples of dispersing agents used in

35 agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate

formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol

ethoxylates; alkyl ethoxylates; EC-PO block copolymers; and graft copolymers.

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17149

An emulsifying agent is a substance which stabilizes a suspension of droplets of one

liquid phase In another liquid phase. Without the emulsifying agent the two liquids would

separate into two immiscible liquid phases. The most commonly used emulsifier blends contain

alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil-soluble

5 calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance ("FILB")

values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can

sometimes be Improved by the addition of a small amount of an EO-PO block copolymer

surfactant.

A solubilizing agent Is a surfactant which will form micelles in water at concentrations

10 above the critical micelle concentration. The micelles are then able to dissolve or solubilize

water-Insoluble materials Inside the hydrophobic part of the micelle. The types of surfactants

usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate

ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additives such as mineral or

15 vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the

pesticide on the target. The types of surfactants used for bioenhancement depend generally on

the nature and mode of action of the pesticide. However, they are often non-Ionics such as:

alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.

A carrier or diluent In an agricultural formulation Is a material added to the pesticide to

20 give a product of the required strength. Carriers are usually materials with high absorptive

capacities, while diluents are usually materials with low absorptive capacities. Carriers and

diluents are used In the formulation of dusts, wettable powders, granules and water-dispersible

granules.

Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil-in-

25 water emulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent,

granular formulations. Sometimes mixtures of solvents are used. The first main groups of

solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main

group (and the most common) comprises the aromatic solvents such as xylene and higher

molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are

30 useful as cosolvents to prevent crystallization of pesticides when the formulation Is emulsified

into water. Alcohols are sometimes used as cosolvents to Increase solvent power. Other

solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation of suspension

concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the

35 liquid and to prevent separation and settling of the dispersed particles or droplets. Thickening,

gelling, and anti-settling agents generally fall Into two categories, namely water-insoluble

particulates and water-soluble polymers. It is possible to produce suspension concentrate

188

17149

formulations using clays and silicas. Examples of these types of materials, Include, but are not

limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-

soluble polysaccharides have been used as thickening-gelling agents for many years. The types

of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are

5 synthetic derivatives of cellulose. Examples of these types of materials include, but are not

limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium

carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling

agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide.

Another good anti-settling agent is xanthan gum.

10 Microorganisms can cause spoilage of formulated products. Therefore preservation

agents are used to eliminate or reduce their effect. Examples of such agents Include, but are not

limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts;

benzoic acid and Its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p-hydroxybenzoate;

and 1,2-benzisothiazolin-3-one (BIT).

15 The presence of surfactants often causes water-based formulations to foam during

mixing operations in production and in application through a spray tank. In order to reduce the

tendency to foam, anti-foam agents are often added either during the production stage or before

filling Into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-

silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-

20 silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both

cases, the function of the anti-foam agent is to displace the surfactant from the air-water

Interface.

"Green" agents (e.g., adjuvants, surfactants, solvents) can reduce the overall

environmental footprint of crop protection formulations. Green agents are biodegradable and

25 generally derived from natural and/or sustainable sources, e.g. plant and animal sources.

Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl

polyglucosides.

For further information, see 'Chemistry and Technology of Agrochemical Formulations'

edited by D.A. Knowles, copyright 1998 by Kluwer Academic Publishers. Also see 'Insecticides

30 in Agriculture and Environment — Retrospects and Prospects' by A.S. Perry, I. Yamamoto, I.

Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

PESTS

In general, the molecules of Formula One may be used to control pests e.g. beetles,

earwigs, cockroaches, flies, aphids, scales, whiteffies, leafhoppers, ants, wasps, termites,

35 moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks,

nematodes, and symphylans.

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In another embodiment, the molecules of Formula One may be used to control pests In

the Phyla Nematoda and/or Arthropods.

In another embodiment, the molecules of Formula One may be used to control pests in

the Subphyla Chellcerata, Myriapoda, and/or Hexapods.

5 In another embodiment, the molecules of Formula One may be used to control pests in

the Classes of Arachnids, Symphyla, and/or Insects.

In another embodiment, the molecules of Formula One may be used to control pests of

the Order Anoplura. A non-exhaustive list of particular genera Includes, but Is not limited to,

Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyp/ax spp. A

10 non-exhaustive list of particular species Includes, but is not limited to, Haematopinus asini,

Heematopinus suls, LInognathus setosus, LInognathus ovillus, Pediculus humanus capitis,

Pediculus humanus humanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used to control pests In

the Order Coleoptera. A non-exhaustive list of particular genera includes, but Is not limited to,

15 Acanthoscelides spp., Agriotes spp., Anthonomus spp., Aplon spp., Apogonla spp.,

Aulacophora spp., Bruchus spp., Cerostema spp., Cerotoma spp., Ceutorhynchus spp.,

Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica

spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp.,

Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp.,

20 Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Trlbolium spp. A

non-exhaustive list of particular species Includes, but Is not limited to, Acanthoscelides obtectus,

Agrilus planipennls, Anoplophora glabripennis, Anthonomus grandis, Ateenius spretulus,

Atomaria linear's, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus,

Carpophilus hemipterus, Casside vittata, Cerotoma trifurcate, Ceutorhynchus assimilis,

25 Ceutorhynchus napl, Conoderus scalar's, Conoderus stigmosus, Conotrachelus nenuphar,

Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusiffus, Cryptolestes

turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes larder/us, Dermestes

maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera post/ca,

Hypothenemus hampel, Lasloderma serricome, Leptinotarsa decemlineata, Llogenys fuscus,

30 Liogenys suture/is, Lissorhoptrus oryzophilus, Maecolaspis Joliveti, Melanotus communis,

Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Otyctes rhinoceros,

Otyzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae,

Phyffophaga cuyabana, Pop//lie japonica, Prostephanus truncatus, Rhyzopertha dominice„

Sitona lineatus, Sitophilus granarius, Sitophilus otyzae, Sitophilus zeamais, Stegoblum

35 paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus

tenebrioides.

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the Order Dermaptera.


the Order Blattarla. A non-exhaustive list of particular species includes, but is not limited to,

5 Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana,

Periplaneta australasiae, Periplaneta brunnea, Perklaneta fuliginosa, Pycnoscelus

surinamensis, and Supella longipalpa.


the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to,

10 Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp.,

Chtysops spp., Cochliomyla spp., Contarinia spp., Cu/ox spp., Dasineura spp., Delia spp.,

Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp.,

Tabanus spp., and Tipula spp. A non-exhaustive list of particular species Includes, but Is not

limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa,

15 Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Cereals

capitata, Dasineura brassicae, Delia platura, Fannie canicularis, Fannie scalaris, Gasterophilus

intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Uriomyza brassicae,

Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, OscineIla kit, Pegomya

betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis

20 mosellana, and Stomoxys calcitrans.


the Order Hemlptera. A non-exhaustive list of particular genera includes, but Is not limited to,

Adelges spp., Aulacaspls spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp.,

Chlonaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepldosaphes spp.,

25 Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus

spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum

spp., Saissetia spp., Therloaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp.,

Triatoma spp. and Unaspls spp. A non-exhaustive list of particular species Includes, but Is not

limited to, Acrostemum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus

30 dispersus, Aleurothrixus floccosus, Amrasca biguttula bigullula, Aonidiella aura ntii, Aphis

gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisla Wad,

Blissus leucopterus, Brachycorynella asparagi, Brevennia rehl, Brevicotyne brassicae, Calocoris

norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus,

Dichelops furcatus, Diuraphis noxla, Diaphorina citri, Dysaphis plantaginea, Dysdercus

35 suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus heros,

Euschistus servus, Helopeltis antonii, Helopeltis theivora, ketya purchasi, ldioscopus nitidulus,

Laodelphax striatellus, Leptocorisa orator/us, Leptocorisa varicomis, Lygus hesperus,

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Macon°Ilicoccus hirsutus, Macrosiphum euphorblae, Macrosiphum granarium, Macroslphum

rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis

longicomis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula,

Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphl, Peregrinus maldis, Phylloxera

5 vitifoliae, Physokermes please s , Phytocoris califomicus, Phytocoris relativus, Piezodorus

guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus

brevipes, Quadraspidiotus pemiciosus, Rhopalosiphum maid/s, Rhopalosiphum pad!, Salssetia

oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera,

Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia

10 entrerriana.


the Order Hymenoptera. A non-exhaustive list of particular genera Includes, but is not limited

to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium

spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and

15 Xylocopa spp. A non-exhaustive list of particular species Includes, but is not limited to, Athalia

rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis,

Solenopsis Invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopes

xyloni, and Tapinoma sessile.


20 the Order lsoptera. A non-exhaustive list of particular genera Includes, but Is not limited to,

Coptotermes spp., Comitermes spp., Crypt otermes spp., Heterotermes spp., Kalotermes spp.,

Incisitermes spp., Macrotermes spp., Marginiterrnes spp., Microcerotermes spp.,

Procomitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A

non-exhaustive list of particular species Includes, but is not limited to, Coptotemms

25 curvignathus, Coptotermes french!, Coptotermes formosanus, Heterotermes aureus,

Microtermes obesl, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes tlavipes,

Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensls, Reticulitermes

speratus, Reticulitermes tibialis, and Reticulitermes virginlcus.


30

the Order Lepldoptera. A non-exhaustive list of particular genera includes, but is not limited to,

Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chita spp.,

Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp.,

Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp.,

Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Perldroma spp.,

35 Phyllonorycter spp., Pseudaletia spp., Sesamla spp., Spodoptera spp., Synanthedon spp., and

Yponomeuta spp. A non-exhaustive list of particular species Includes, but Is not limited to,

Achaea Janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana,

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Amyelols transitella, Anacamptodes defectarie, Anarsla lineatella, Anomis sabulifera, Anticarsla

gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenhe citrana, Auto grapha gamma,

Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiefia, Capua reticulana, Carposina

niponensis, Chlumetia transverse, Choristoneura rosaceana, Cnaphalocrocis medinalis,

5 Conopomorpha cramerella, Cossus cossus, Cydia =yam, Cydia funebrana, Cydia molesta,

Cydia nigricana, Cydia pomonella, Dame diducta, Diatraea saccharalis, Diatraea grandioselle,

Earias insulana, Ear/as vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia

cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana,

Erlonota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata,

10 Helicoverpa armigera, Helicoverpa zea, Heliothls virescens, Hefiula undalis, Keiferia

lycopersicefia, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia

botrana, Loxagrotis albicoste, Lymantria dispar, Lyonetia clerkefia, Mahasena corbetti,

Mamestra brassicae, Maruca testulalis, Met/se plane, Mythimna unlpuncta, Neoleucinodes

elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia,

15 Pandemis cerasana, Pandemis heparana, Pep/I/o demodocus, Pectinophora gossypiella,

Per/drama saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris

rapae, Plathypena scabra, Plodia interpunctella, Plutefia xylostella, Polychrosls viteana, Prays

endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusla Includens, RachiplusIa nu,

Scirpophaga Incertulas, Sesamia inferens, Sesamia nonegrioldes, Setora nitens, Sitotroga

20 cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera

eridania, Thecla basllides, Tineola bisselliefia, Trichoplusia ni, Tuta absolute, Zeuzera coffeae,

and Zeuzera pyrina.


the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to,

25 Anaticola spp., Boy/cola spp., Chelopistes spp., Con/odes spp., Menacanthus spp., and

Trichodectes spp. A non-exhaustive list of particular species includes, but Is not limited to,

Bovicola boy/s, Boy/cola caprae, Boy/cola ovis, Chelopistes meleagridis, Goniodes dissimilis,

Con/odes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes can/s.


30

the Order Orthoptera. A non-exhaustive list of particular genera includes, but Is not limited to,

Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is

not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa austral/s, Gryllotalpa

brachyptera, Gryllotelpe hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca

gregaria, and Scudderia furcate.

35 In another embodiment, the molecules of Formula One may be used to control pests of

the Order Slphonaptera. A non-exhaustive list of particular species includes, but is not limited

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to, Ceratophyffus gaffinae, Ceratophyllus nlger, Ctenocephalides can's, Ctenocephalides fells,

and Pulex irritans.


the Order Thysanoptera. A non-exhaustive list of particular genera includes, but Is not limited

5

to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of

particular sp. Includes, but is not limited to, Franklinieffa fusee, Franklinieffa occidentalis,

Frankliniella schultzeI, Franklin/elle williamsI, Hellothrips haemorrholdalis, Rhipiphorothrips

cruentatus, Scirtothrlps citri, ScirtothrIps dorsalis, and Taenlothrips rhopalantennalis, Thrips

hawaliensls, Thrips nigropilosus, Thrips orientalis, Thrips tabaci.

10 In another embodiment, the molecules of Formula One may be used to control pests of

the Order Thysanura. A non-exhaustive list of particular genera Includes, but is not limited to,

Lepisma spp. and Thermobia spp.


the Order AcarIna. A non-exhaustive list of particular genera Includes, but is not limited to,

15 Acorns spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp.,

Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., RhIzoglyphus spp., and

Tetranychus spp. A non-exhaustive list of particular species includes, but Is not limited to,

Acarapis woodi, Acarus siro, Aceria manglferae, Aculops lycopersici, Aculus pelekassi, Aculus

schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenlcis,

20 Dermacentor variabffis, Dermatophagoldes pteronyssinus, Eotetranychus carp/n/, Notoedres

cat/, Oligonychus coffeae, Oligonychus ilicis, Panonychus citrl, Panonychus ulml, Phyllocoptruta

oleivora, Polyphagotarsonemus lotus, Rhlpicephalus sanguineus, Sarcoptes scab/el,

Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used to control pest of

25 the Order Symphyla. A non-exhaustive list of particular sp. Includes, but is not limited to,

Scutigerella Immaculata.


the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to,

Aphelencholdes spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp.,

30 Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus

spp. A non-exhaustive list of particular sp. Includes, but Is not limited to, Dirofilaria Immitis,

Heterodera zeae, Meloidogyne incognita, Meloldogyne Javanica, Onchocerca volvulus,

Radopholus slmilis, and Rotylenchulus renifortnis.

For additional Information consult 'HANDBOOK OF PEST CONTROL - THE BEHAVIOR, LIFE

35 HISTORY, AND CONTROL OF HOUSEHOLD PESTS" by Arnold Maths, 9th Edition, copyright 2004 by

GIE Media Inc.

APPLICATIONS

194

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Molecules of Formula One are generally used In amounts from about 0.01 grams per

hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per

hectare to about 500 grams per hectare are generally preferred, and amounts from about 1

gram per hectare to about 50 grams per hectare are generally more preferred.

5 The area to which a molecule of Formula One is applied can be any area inhabited (or

maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder

species, vines, turf and ornamental plants, are growing; where domesticated animals are

residing; the Interior or exterior surfaces of buildings (such as places where grains are stored),

the materials of construction used In building (such as Impregnated wood), and the soil around

10 buildings. Particular crop areas to use a molecule of Formula One include areas where apples,

corn, sunflowers, cotton, soybeans, mid% wheat, rice, sorghum, barley, oats, potatoes,

oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds,

sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be

planted. It Is also advantageous to use ammonium sulfate with a molecule of Formula One

15 when growing various plants.

Controlling pests generally means that pest populations, pest activity, or both, are

reduced In an area. This can come about when: pest populations are repulsed from an area;

when pests are incapacitated in or around an area; or pests are exterminated, In whole, or in

part, in or around an area. Of course, a combination of these results can occur. Generally, pest

20 populations, activity, or both are desirably reduced more than fifty percent, preferably more than

90 percent. Generally, the area Is not in or on a human; consequently, the locus Is generally a

non-human area.

The molecules of Formula One may be used In mixtures, applied simultaneously or

sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root

25 system, to better withstand stressful growing conditions). Such other compounds are, for

example, compounds that modulate plant ethylene receptors, most notably 1-

methylcyclopropene (also known as 1-MCP). Furthermore, such molecules may be used during

times when pest activity is low, such as before the plants that are growing begin to produce

valuable agricultural commodities. Such times include the early planting season when pest

30 pressure is usually low.

The molecules of Formula One can be applied to the foliar and fruiting portions of plants

to control pests. The molecules will either come in direct contact with the pest, or the pest will

consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the

pesticide. The molecules of Formula One can also be applied to the soil, and when applied in

35 this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule

taking it up into the foliar portions of the plant to control above ground chewing and sap feeding

pests.

195

17149

Generally, with baits, the baits are placed in the ground where, for example, termites can

come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of

a building, (horizontal, vertical, or slant surface) where, for example, ants, termites,

cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can

5 comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed on the surface of

a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers

in diameter) to micrometer size (about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resist certain pesticides,

10 repeated applications of the molecules of Formula One may be desirable to control newly

emerged larvae.

Systemic movement of pesticides in plants may be utilized to control pests on one

portion of the plant by applying (for example by spraying an area) the molecules of Formula One

to a different portion of the plant. For example, control of foliar-feeding insects can be achieved

15

by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting

soil drench, or by treating the seeds of a plant before planting.

Seed treatment can be applied to all types of seeds, including those from which plants

genetically modified to express specialized traits will germinate. Representative examples

include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringlensis or

20 other insecticidal toxins, those expressing herbicide resistance, such as Roundup Ready" seed,

or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance,

nutrition-enhancement, drought resistance, or any other beneficial traits. Furthermore, such

seed treatments with the molecules of Formula One may further enhance the ability of a plant to

better withstand stressful growing conditions. This results in a healthier, more vigorous plant,

25 which can lead to higher yields at harvest time. Generally, about 1 gram of the molecules of

Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits,

amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide

better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is

expected to provide even better benefits.

30 It should be readily apparent that the molecules of Formula One may be used on, in, or

around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or

other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked'

foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, or any

other beneficial traits.

35 The molecules of Formula One may be used for controlling endoparasites and

ectoparasites In the veterinary medicine sector or in the field of non-human animal keeping. The

molecules of Formula One are applied, such as by oral administration in the form of, for

196

17149

example, tablets, capsules, drinks, granules, by dermal application in the form of, for example,

dipping, spraying, pouring on, spoiling on, and dusting, and by parenteral administration in the

form of, for example, an injection.

The molecules of Formula One may also be employed advantageously In livestock

5 keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed

advantageously In pets such as, horses, dogs, and cats. Particular pests to control would be

fleas and ticks that are bothersome to such animals. Suitable formulations are administered

orally to the animals with the drinking water or feed. The dosages and formulations that are

suitable depend on the species.

10 The molecules of Formula One may also be used for controlling parasitic worms,

especially of the intestine, In the animals listed above.

The molecules of Formula One may also be employed in therapeutic methods for human

health care. Such methods include, but are limited to, oral administration in the form of, for

example, tablets, capsules, drinks, granules, and by dermal application.

15 Pests around the world have been migrating to new environments (for such pest) and

thereafter becoming a new invasive species In such new environment. The molecules of

Formula One may also be used on such new invasive species to control them in such new

environment.

The molecules of Formula One may also be used in an area where plants, such as

20 crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels

(even no actual presence) of pests that can commercially damage such plants. The use of such

molecules In such area is to benefit the plants being grown in the area. Such benefits, may

Include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g.

increased biomass and/or Increased content of valuable ingredients), Improving the vigor of a

25 plant (e.g. Improved plant growth and/or greener leaves), improving the quality of a plant (e.g.

Improved content or composition of certain ingredients), and improving the tolerance to abiotic

and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy

evaluation processes by various govemmental authorities (local, regional, state, national, and

30 International). Voluminous data requirements are specified by regulatory authorities and must

be addressed through data generation and submission by the product registrant or by a third

party on the product registrant's behalf, often using a computer with a connection to the World

Wide Web. These govemmental authorities then review such data and if a determination of

safety Is concluded, provide the potential user or seller with product registration approval.

35 Thereafter, In that locality where the product registration is granted and supported, such user or

seller may use or sell such pesticide.

197

17149

A molecule according to Formula One can be tested to determine its efficacy against

pests. Furthermore, mode of action studies can be conducted to determine If said molecule has

a different mode of action than other pesticides. Thereafter, such acquired data can be

disseminated, such as by the Internet, to third parties.

5 The headings In this document are for convenience only and must not be used to

Interpret any portion hereof.

TABLE SECTION

Table 1: Compound number, appearance, and structure

Corn-

pound

No.

Appear

ance Structure

1 yellow

gum

-N/CH3

/CH3

N 1 cH 3 cH 3

2 yellow

solid

/CH3

0 —N CH 3

V N I C H 3 C H 3

3 yellow

gum

-N,

C 113 0

H3 s/C

N 1 FFH3 CH3 3

198

17149

4 yellow

oil N

/CH3

—N

V N 1 cH3

s,C H3

5 yellow

oil

/CH 3

N—N

0

, N 1 CH 3

6 yellow

gum

7 % cti,

a,CFI 3

7 yellow

gum

cti, /

, N 141 % at,

199

17149

8 yellow

gum

CH 3 me 0 " ,W...... /.....,.."'"CH3

N ° % cit,

beige

gum

1C 113 0 —.N H3 s/C

N 1

Cl CH

10 colorles

s gum

C H3 0 0 113 )...../......s/C

1 cH 3

12 colorles

s glass

—N

CH, / - 0

CH 3

V N k ,, CH 3 Cn3

200

17149

18 Brown

oil

H C —N

N s/

C H3

N 1 cH 3 cH 3

19 Yellow

oil N

H 3 C\

N CH 3

N 1 cH3

20 Yellow

oil

H C

\ N

N CH 3

N 1 CH 3 CH 3

21 Yellow

oil

H C —N

N N s/

CH3

N 1 1-€113 cH 3

201

17149

22 clear oil

CH 3 0 CH 3

N-4

CH3 H3C

23 clear oil

CH3 0 CH3

H 3 C

24

11 3

CH3

H 3 C' ...-- \ / N--

H3e

25 H3C°

0

N \ /

202

17149

26

CH 3

N---c 113C).--N

thc H3C

'tic

/

27 H C N

H 3 C

28

1

H 3 C /

,N

H 3 C

29

/

H C N

H 3 C

203

17149

30

o / 11 3 c

iI 3 C's

II3C

1 N

31

\

11 & 13

ItN

32 Gold

syrup

N I cit 3

s,

CII3

01 3 cn,

33 Brown

solid /

N

0 , CH3

204

17149

34

Off

white solid

N

)0\ (CH 3

CH 3 n H

0 \ CH 3

N

(

>

CH 3 Off I CH 3

35 solid

white

I N

0\

Off I 36 white

solid

N H F\---F

N..-- * I N White

37 solid

,

I N

205

17149

38 Off

white solid

I N

H3C-0 0\ )

N..— ) I

N H

39 White solid ..N

I N

H3C—S

0\ )

N I )t

H

40 Pale

yellow solid

0 %

111D-1 Ce N , H

41 thick mass

*Brown N

CH3

CH 3

206

17149

42

Pale

yellow

solid

semi

N .•

N I

N

I

CH3

CH3 \ CH3

43

Pale

yellow

solid I N

rn■-/N

N

(1/4

/1 F

CH3F)T

44 White

solid

N

I-1 3 C—S

0) )

N \ CH 3

45

Brown

mass

thick

N

CH3

( CH 3

CH 3

CF!

207

17149

46

Pale yellow thick mass

H 3 C

N IN

>--CH3 CH 3

N

( > ci

CH 3

47

Pale

thick mass

yellow

, I

H3

H3C

N I

>—CH 3

/ C' S

48

Pale green thick mass

I

NH3

N

H 3 C

I N

C S/

49 Pale

solid yellow

N I

N.--- CH 3

I N \ CH 3

208

17149

50

Brown

thick

mass

N

N

113C----)

N C113

(CH3

> 0

51

Pale

yellow

thick

mass

N

H3C-S

Oiy

CH 3

CH3

52 tan

solid --,

N I

N N \CH3

/ N

53

White

Solid

N

/ N H 3 c 0-1 3

/ 3CH

s

209

17149

54 Clear

Oil

N 1

N

CH 3

s/

CH 3

55

White

Semi

Solid

N

N

CH3

/ CH 3

H 3 C

56 Brown

Solid

N.--- 1

N

HC 3 s/

57 White

Solid

N

H 3 C cH 3 0

)-0)LCH3 N H

210

17149

58 Clear

Oil

CH 3 0

N

N /

H CH3 8/

cH 3

59 White

Solid

N

N

C u 0 /

CH3

CH 3

60 White

Solid

N

N

CH 3 0 C H 3

C H 3

61

Light

Yellow

Solid

.,

N

N

CH3 0 /cH3 >Cr-8

N H

211

17149

62 Clear

Oil

11 3 C

H 3 C CH3

--C113

N

63

Light

Yellow

Solid

CH 3 /

N.-- I , N / CH 3

64 White

Solid

H3C CH 3 CU 3 0 y....

CH 3 N 0

N

65 White

Solid --.

N I N / CH 3

212

17149

66

White

Semi

Solid

H C

N M■1

—CH3

67

Yellow

Semi

Solid

N I /

H3C cH 3 % y..... 7'0

CH3

N\ CH 3

68 Clear

Oil

I N

Cl

N i

H 3 C CH 3

0 Y—CH 3

0

N CC113

CH3

69

Dark

Brown

Oil

Cl

N

N

1

cH 3

213

17149

70

Viscous

Pale

Yellow

Oil

CI

N N N CH 3 \-.

CH 3

71 White

Solid

CI io

N ,....7--C1

N N

) H 3 C

72

White

Semi

Solid

/CH 3

S

C

N

CH 3

H 3 C

73

White

Semi

Solid

..

CH 0 CH 3

N

N / N\ CH3 CH3

214

17149

74 Clear Clear

Oil

CH3 ID

N 3j

N / N\ CH3

75

White

Semi

Solid

N

N

CH3 0 CH3 /

CH 3 CH3

76 Clear

Oil

N

N

CH 3 co

N \CH3

s/CH3

CH3

77 White

Solid

N I

N

CI

/

CH3

CH3

215

17149

78 White

Solid

N

CI 0

N

C H3 /

79 White

Solid

N

N

CI

/ H

CH 3 /

CH 3

80 White

Solid

N

N

CI

/CH3

S

CH3

CH 3

81 White

Solid

N

N

CI

216

17149

82 White

Solid

F

N

N /

F CH,

0 / ' ,.....X--5

til

83 White

Solid

F

N

N /

F

/CH 3

S

CH 3

84 White

Solid NI N

CH3

y / CH3

85

Off-

White

Solid

N

N

CH3 cH 3 ja /

,....../"—S

N H

217

17149

86 Yellow

Solid

H3C CH3 CH3 0 V

N 0

N

H 3 C

87 Yellow

Solid I

H3 CH3 CH3 0

N CH3

i N

CH 3

88 White

Solid

CH 3 N I N / N

\ CH3 CH3

89 White

Solid

CH 3 0 H35E13

CH3

N N

H 3 C

218

17149

90 Clear

Oil I

N

113 CH3 CH3 0

CH3 N 1

N

91

Faint

Yellow

Oil

F F

0

N-- F

1

C H3

sC 113

92

Faint

Yellow

Oil

F F

N

N / N\ cH3

s/

CH3

CH 3

93 White

Solid

CH co

N.-- 1 i N / )

H3C

CH 3

CH3

219

17149

94 Clear

Oil

CH3 0 /CH3

S N

N

CH 3

95 Clear

Oil I

CH3 0 /CH3

I N N

96 Yellow

Solid

CH30 /CH3

N

,...7--S

N / N\

/ H 3 C

97 Yellow

Oil

CH30 /C3H

S N

N / CH 3

H 3 C

220

17149

98 Yellow

Oil N

CH 3 0 /

N

)—CH 3 H 3 C

99 Yellow

Solid

a

N /

CH3

N / 11

100 Clear

Oil

N /

CH3

CH)) N / N .....r-s/

0

101 Clear

Oil /*

N.-- 1

N

/CH3

CH 3 0 S \ \\

0

H 3 C

221

17149

102 Clear

Oil

N I

[ZIJr-N

CH30

CH3 /

S \\ 0

CH3

H 3 C

103 Clear

Oil

N I

N

CH30 /CH3

/—Szto / II

0

H3C

104

Faint

Yellow

Oil

N

N

c n 3 co /c 113

Cr-0 0

CH3

H 3 C

105

Off-

White

Solid

CH3 0

N N N

\ cti3

/C113

222

r

17149

Faint *

/C 3H

N

0yy—s

106 Yellow

Oil CH 3

CH3 0 C H 3

N

107 White N / C H3 Solid

/ CH3

/C 3H

S Cl

Clear N 108

Oil N CH 3

0‘x H 334CH3

N

Yellow 109

Solid --0 CH 3 CI 0 y_i_ u

%raa3

H 3 C

223

17149

Brown

H3C cH 3 % V 7---CH3

110 Oil CH 3

CH 3 cH 3 0

N CH 3

Yellow N 111

Solid

CH 3 CH 3 0 CH 3

N

Brown N 112

Oil

Th CH 3

CH 3 0 /

N )....y--3

I Yellow

113 CH 3 Oil

224

17149

114 Brown

Oil

11 3 C cH 3 cH3 0

cii 3

N / N\ cH 3

cH 3

115 Brown

Solid

Light

H 3 C CH 3 cH 3 0

N )■0)LCH3

cH3

116 Yellow

Solid

H 3 C cH 3 cH 3 0

N )C0X-cH3

N

) H 3 C

117 Yellow

Oil

cH 3 /

N I 1 r4 N / •\ CH 3

ci-1 3 Br

225

17149

118 Oil

Brown

CH 3 N I

\ CH3 CH3

Br

119 Brown

Oil

cti 3 0 /C H 3

N ,.....7----S

N I \ cti3

CH 3

120 Oil

Brown

cH 3 0

N

3cH s/

ctt3 cti3

cH 3

121

Off-

White

Solid

CH3 0

N

cH 3 s/

cH 3 N N \ cH3

226

17149

i

122

Faint

Yellow

Solid

5CH 3 0 CH 3

N

N / N\ CH 3 CH3

123 Clear

Oil

NN

cH3 0 /CH3

--s

is---C--

) H 3 c

124 Yellow

Solid

N

N

cH 3 o

H 3 c

c3H s/

cH 3

125 White

Solid

N I

N

CH3 0

H 3 C

CH 3

CH3

227

17149

126 Yellow

Oil

CH 3 c) CH3 /

N-- 1

N / cH 3

s cH 3

127 Yellow

Oil

CH3 ()

N--- ,.......rs/C

H3

1

CH 3

128

Neon

Yellow

Oil

-,,

CH3 o ,c3 ......—S

N-- ,/.

1 N / isk

CH 3

129

Neon

Yellow

Oil

CH 3

CH 3 0 /

N N N \ CH 3

cH 3

228

17149

130 Pink

Solid N I

N

ti

11 3 o

131 Red Oil

N

CH3 0

CH 3 CH 3

/ CH3

132 Yellow

Oil

N

CH3 0 /CH3

N \ CH 3

133 Yellow

Oil

N

N

CI

H 3 C

CH 3

s/CH3

229

17149

Clear

Oil 134

N I

cii, a o /

)___/--6

/ 11 3 C

135

Off-

White

Solid

--.„

N

N

CH 3

C H3

X—C 11 3 H 3 C cH 3

136 Yellow

Oil

F .....

N

N

CH 3

S

N \ cH3 cH3

1 37 Yellow

Oil

F

144

C11 3 CH3

/

0 S

CH3

H 3 C

230

17149

Yellow

CH 3

F F

138 N l‘k Oil CH 3

CH3 Is, /CH3

N )......y--S

Faint N

139 Yellow \CH3

Oil CI

CH 3 c) CH 3 /

N I

Faint / N‘ CH 3 140 CH 3

Yellow CI

H 3 C CH 3

CH 3 0\

CH3

Light N 141 Yellow I

N /

Solid CH 2

231

17149

142 Clear

Oil

N

N

CI s/

C H3

CH3

1-1 3 )

143 Calorie

ss Oil

N

cli3 o-I 3 0 r i

/

„

Cr12

144 Colorle

ss Oil c 113

N

N

C11 3 /

CII 3 0\\ CS

, N7

/ \----

cH 2

145 White

Solid I N

N I

N

CHP CH 3

232

17149

146 Gray

Oil

CH CH3 3 43

CH 3 N

N \ CH 3

147 Calorie

ss Oil

CH 3

N

F

0 / ( F

F

) i N /

\---- CH 2

148 olid Solid

White / N /

CH 3 0 CH 3 \ (

) cH 3

,

\--%, u ....11 2

149 Yellow

Solid F

N

N

H 3 C 0113

H3 0 Y-CH3

0

\ CH2

233

17149

150 White

Solid

cl

N

N

H cH 3

CH 3

151 Clear

Oil

N

N

CH 3 0

/ CH3

CH 3

CHi

S / a

152 Clear

Oil -.

N

N

H 3 C CH 30

N \

CH3

s/

CH3

153 White

Solid

N 1

N

CH 0

, N / - \

CH3

234

17149

154

Faint

Orange

Oil

-..

N

N

CH 3 0

\C113

F

F CH3 N

1 55 Clear

Oil

N

N

CH30

H 3 C

/C113

S

CH3

H 3 C

156 Clear

Oil

N

N

0130 H3C

/ CH3

S

CH 3 /

H 3 c

157 Clear

Oil --,.

N

N

CH3

H 3 C

H3C CH3 /

S

235

17149

158 Clear

Oil

LNJ

N

N

CH 30 F

H3C

159 Clear

Oil

N

N

CH 30 F

F CH3

H3C

160 Solid

White

N

N

CI 0 )Crs/CH3

) H 3 c

161 Brown

Oil

F

N

N

CH 3 cl

CH3

H 3 C

236

17149

162

Light

Brown

Solid

CH3 CI

CH3 N

N \ N cH3

163 White

Solid

CI CH 3

N

N CH 3

H C

164 White

Solid

F....................

I N

Cl 0 s/

CH3

N I

H3c

165 White

Solid ..,

CH 3 CH3 n /

N-- —,i2,---S

I , N N ." \

CH 3

237

17149

166 Yellow

Oil

CH30 s/

C I-I 3

N )--7— N N

H 3C)

167 Grey

Oil

CH• CI 0 s/ '

N ,--V--

N

) H 3 C

168

Faint

Purple

Oil

-,

CI

N

N

H 3 c

169 White

Solid I /-

N

C H 9 CH3

N I

N

) H 3 C

238

17149

170 White

Solid I N

N

CH 3

H3C

171 White

Solid

N

N

H3 0 j-/CH3

) H

H

172 White

Solid

H 3 C cH 3 CI

Y---CH 3 N 0

N

173 White

Solid

F -,

CI CH 3

N

N N

‘ CH 3 CH3

239

17149

174 Clear

Oil

N

N

Cl 0

N \ c03

113

175 White

Solid

N

N

Cl

N ‘

at, CII 3

c0 3 /

176 Yellow

Oil

N

N

CI CH3

1%kCH3

177 White

Solid

F

N

N

CI 3

0 s/

CH3

cti3

240

17149

Yellow

CI F

178 CH 3 Oil

Cl F

N F

White - N CH 3 179 CH 3

Solid

Cl

N

180 Yellow N CH 3

Solid H 3 C

Cl 0 /cH 3 S

Faint N

181 Yellow

Oil

N Cl, CH,

241

17149

182

Faint

Yellow

Oil

N

N

11 ci 43

s/

C1I3

or) /

ti 3 c

CI OH

183 Yellow

Oil

N

N CH 3 / )

H 3 C It

H3 0 /c H3

rS \

N Colorle

184 N SS Oii

CH2

N

o) CH 3

i (-5

185 White

N CH 3

Solid

CH2

242

17149

186 White

Solid

F- ,. .N

N

CH p

N I

CH 3

( CH 3

I \--- CH2

187 Yellow

Solid

CH co F

N F N / CH3

H3C

188 Yellow

Oil

CH3 0 F

N

N /

H 3 c

189 Yellow

Oil

cH 3 0

N

N /

H3C

H3 / 113

CH 3

243

17149

190 Yellow

Oil

N i

N

C" 3 0 S'CII 3

/

H 3 c

191 Yellow

Oil

F ....,

N

N

cH 3 cH,

S

N \ CH3

192 Yellow

Oil

F

N

N

CH) CH.

S

Hic

193 Yellow

Solid

.....,

N

N

Cl!3 0

CH 3

F

F CH 3

244

17149

194 White

Solid

F

N

N

CH 0 F

CH 3

195 White

Solid

N

N

C113 o

N \ Cu,

s--cti 3

196 Tan

Solid

N I

N , /

CI

CH 3

CH3

197 White

Solid .-

N I

N /

Cl

/CH 3

S

CH 3

245

17149

198 an

T

/CH 3

S

N

Solid N /

Cl

H 3 C cH 3 CI 0 y.

CH 3 N 0

Gold 199 N

Solid

H C

H 3 C CH 3 CI 0 V_ /—CH 3

N 0 Yellow

200 N N Oil \

CH3

H3 CH 3 S/

N-- I

Gold N / cH 3 201

Oil CI

246

17149

202

White

Semi

Solid

CI CH 3

N.-- I , N / CH 3

r> H 3 1.-

203 Yellow

Oil

N

N

CI

H C

H 3 C

s/CH3

204 Yellow

Oil

N

N /

H 3C

H C CH+ S

C H3

205 Yellow

Oil -.,..

N

N

0

)1

AND Enantiomer

s/C 11 3

-

H 3 C

247

17149

206 Yellow

Oil

CI

N I N / \

I-13C/

207 White

Solid --,.

CI

N I,

N / CH 3

H 3 C

208 White

Solid

Cl C H3

N i

N / N CH3 \ CH 3

209 Yellow

Cu

Cl s/CH3

N

N / N\ CH 3 cH3

248

17149

210 Oil

Yellow

CI / CH3

S N

CH3

211 Yellow

Oil

CI CH 3 s/

N

N / N‘ CH 3

212 Oil

Yellow

CI C 3H 0 /

N \ S

cH3

213 Yellow

Oil ...,

Cl

N I

5

t, 74

N - \ CH3

249

17149

214 Yellow

Oil -■,

CI

N I ,

N 7 N C113 \CH3

215 Clear

Oil

(111 30

I N

/c 113

cs/

CH 3 Is, N

216

Cream

Colored

Solid

F /

cup

N

CH 3 / cs

cH 3 CH3

N

ti3c

217 Clear

Oil

N

cHp I

cif ],

csi

CH 3

CH 3

N

250

17149

218 Clear

Oil

.....)/

N

N

CH30 /CH3 ck\ 0

1.4) cH 3

) 113C

219 Clear

Oil F.N-

N 1

/7..,1 N

I N

CH30 /CH3

crn-0 c 0

CH 3

H 3 C

220 Yellow

Oil

N

N

CH 3 0

ti 3 c

F

221 White

Solid

N 1

N

H3 0

1,

cl H2

II

H 3 C)

251

17149

222 White

Solid -..

N

N

C H p 11 2

223 White

Solid

N

N

H3c CH3

CH3

224 Colorle

ss Oil

N 1 , N t

CH 30

N A

cH 3

s/

CH3

225

Light

Yellow

Oil

N 1

N

cH3c) / cH 3

H3C

252

17149

N

CH3 0

226 White N / N\

Solid CH 3

CH 30

White N F 227

Solid -...„. N CH3

F F

CH 3 (3 F N

Colorle 228 N

SS Oil 01 3

F

CH 3 0

Colorle N \ cti 3

229 ss Oil

a

253

17149

230 Colorle

ss Oil

CH 3 0 CH 3

N

N / N\ CH 3 CH 3

231 Colorle

ss Oil *.

Cl

c H 3 0 410 N

N c H 3 CH3

232 White

Solid

CII 3 0 .

N

N crt,

233 White

Solid ••....

F cH 3 0 ---N N I

N

CH3 CH3

254

17149

White -.

CI1 30

N f CII3 \ I

N CH3

234 Solid

CH 3 0

N N

Colorle N 235

SS Oil

-, \CH3

CH3 0 F F N

F Colorle N\ N / OH

236 CH 3 SS Oil

F F F

CH 3 0

N F

237 White ■,... N / ---OH

Solid H 3 C F F

F

255

17149

238 Colorle

ss Oil

N 1 N /

,

FE

CH 30 /

CH3

)

II 3 C

239 Colorle

ss Oil

--

N

N

CH 30 /

CH3

H3C

240 White

Solid

N

IT

CH3 0

1-1 3 C

241 Calorie

ss Oil -,

N

N

CH 30

F

H 3 C

256

17149

242 Colorle

ss Oil

F

C11 3 (3

N

N

cH3

243 Colorle

SS Oil

CH30

N i

N / CH3

244 White

Solid

CH3 0 F C H

3

N.-- , \(

I N N ) CH 3

H 3C

245 White

Solid \.

Cl

CH 3 0 * N-

N / CH 3

II 3C

257

17149

246 Calorie

SS Oli -..,

N N

C11 3 0 •

F F

't ic

247 White

Solid

LNJ

N

N

CH 30

/

H3C

F

N I

N■CH3

248 Colorle

ss Oil

,,,

N N

C113 0

T C H3 \ I

113C

249 White

Solid

N

N

CH3 0

/

H 3 C

258

17149

Clear

CH3 0 0 A ,CH 3 "

N

N / 250

Oil H 3 c

F

CH 3 o% / ( F

F

251 Brown I' d ,

/ Oil

CH 2

CH3 0

N-- )........7---S

/ .51 Off

1 , N s■ -/-:;.■/ 252 White I

Solid '■N%

113 IC

Br S 0

Off N

253 White CH 3 /

Solid

259

17149

254 Brown

Solid .N.

N

N

CH3

CH3

cH3

255 White

Solid

N

N

cl 0 ?

jH 2 r

N H

H

256 Solid

White

I c

N*--

N i

CI 0\ i—CH 3

> N

H

257 White

Solid

N

N

cl 0 cH 3

260

17149

258 Brown

Oil

N

N

Qr

H3C CI

CH3

CH3

CH 2

259 White

Solid

N-

N

CH30 CH3 /

H 3 C

260 CCalorie

ss Oil

N /

N I ,

cH 30

Hi c

cH• / '

261 White

Solid

F

N

N

CH 3 0

/

H 3 C

261

17149

White N

CH 3 c) F

262 1 Solid F\/-•,' N

I H3C N

F

cH3 0 F F

N

263 Calorie

ss Oil .., N

H 3 C

F

CH3 0 F

N Colorle

264 ss Oil

N

CH 3 0 CH 3

N

265 White N / ) CH

Solid H 3 C

262

17149

Colorle

SS N clho

CI

4 266

Semi- N CH3

Solid H 3 C

CH 0 110 1 Colorle

267 ss Oil

tt 3 c

F CH 3 0 ---N

White N I 268 N

Solid -,, N

1-1 3 c

\ c11 3

N

cif 3 0

\ 1 -. N t13

White 269 11 3 c

Solid

263

17149

270 White

Solid

N

CH"-, - --,___0z:

F

H 3C/

271 Colode

ss Oil

N I

N

H 3

, z

I-1 3 C

F

272 White

Solid

N

N

CH3c)

H3c

‘C H 3

273 Colode

ss Oil

N

N

CH 3 c3

/ N,

H 3 C

*

CH 3

264

17149

274 Colode

ss Oil

olio 41

cH 3

H 3 c

275 White

Solid

N

N

cti, 0 II, 0

II cH 3 -1---1‘r

0 ‘CII3

ii 3 c

276 White

Solid

N i

N

113 0

I-1 3 C

1-13C

F

\ 0

F

277

Brown

Amorph

ous

Solid

N / Is?

113 s/C c CH 3

CH 3

265

17149

278 White

Solid

N I

N

CH p CH 3

\ CH 3

279 White

Solid

N

N

CH 3

CH

cH 3

280 White

Solid

N

N

C H p\\

/47—H

\CH3

281 Orange

Foam

H3

N

CH3

°--7( c CH3

0

N

266

17149

282 Colode

ss Oil

N

N

CH3

s/

Cl 0 /—

\ CH2

283 Calorie

SS Oil

N

N

/CH3

CI 0cS

CH3

CH2

284 Calorie

ss Oil

N

N

Cl 0 CH 3

CH3

\nu loll2

285 Clear

Oil

N

N

CH3 , CH,

rt—s '

N

)—cH 3 o

267

17149

286 Oil

Yellow

N

N

Fr

CH 3 0 Y---F

/ N\ /

H ic

287 Yellow

Oil

N i

N

CH 3 /CFI3

rt--S

CH 3

cH 3

288 Yellow

Oil I .,., Cr N

CH 3 cH 3 /

)--- CH3

289

Dark

Yellow

Oil

-■, 1

N

N

CH3 /

CH 3 rir-s

s \ cH 3

268

17149

CH 3 /C H3

I 290

Yellow --,. N CH 3

Oil I s \ CH 3

a 11 3 C

c CH 3

Clear N

291 N Oil CH 3

H 3C

C II 3

a......../.....s,,CH 3

Tan ! ,j 1 292

Solid

oil,

0........„,-......ce.0 H 3

Clear 1I 3 1 293

Oil

269

17149

Yellow

Oil 294

Cl')

/N 0 F

295

White

Semi-

Solid

r N

cti 3

/ ott

t tt,

296 Colorle

ss Oil

•-. I

a N

F F

CI 0 /----X

F N isZ

N

CH 2

297 White

Solid

Br 0

f—C

H 3

N H I

FNH

270

17149

298 White

Solid F

N-- I

N

CH 3

299 White

Solid F

N

N

Br 0

300 White

Solid

N I

N CH3

Cl 0 CH 3

N \

301 White

Solid

N

N

Cl

CH 3

rH

Isk CH 3

271

17149

302 White

Solid

Cl 0

N

N CH3

303 Colorle

ss Oil

Cl N

N /

H 3 C

HC 3

s/

304

Light

Yellow

Oil

Cl

N

N...5

H 3C

CH 3

305 Solid

--. licWhite

CI

N ,

H C

272

17149

306 Grey

Solid

Cl

N F

N

H 3 C

307 Colorle

ss Oil

Cl

N i N /

NF

H 3 C

308 Coforte

ss Oil

CI

N

Cl

• .

N CH 3

H3C

309 Colorle

ss Oil

CI

dN

N

F OH

F F

H 3C

273

17149

310

Light

Yellow

Semi-

Solid

CI

N *

H 3 C

311 Colorle

SS Oil ..,

CI

N

F

N

I-1 3 C

312 White

Solid \..

CI

N-- I ,

F

---N I

N \rot, •-a- 13

N z

H 3 C

313

Light

Yellow

Solid

■„.

Cl

N \ I I CII3 N

11 3 c

274

17149

Faint N I

N

cH 3 0 CH 3 s/

314 Yellow 1

Oil

cH 3 0 cH 3 /

N Faint N cH 3

315 Yellow 1

Oil

CH 3 0 C H3

Faint N

316 Yellow N CH 3

Solid I

H 3 C CH 3

CH 3 N

317 White

N Solid

275

17149

Brown

cH 3 CI 0

N

N 318 F Solid

CI 0

N Brown

319 F N Solid

0 0‘\

N

ii—CH 3

i N7 H

N Yellow 320

) Solid I -...., ..4:- H3C N

CH 3

Cl 0

N Yellow

321 N Solid

H 3 C

276

17149

322 Yellow

Solid N

/112

CI Co‘\ d

Is I I 3 C

Colode

ss Oil 323 %.%.

N

CH3 0

CH 3

C H3

324 White

Solid -.

N

N

H3C C H3

C H3

H 3 C

325 White

Solid

F

N

N

CH 30

/

H 3 C

CH 3

277

17149

326 Colorle

ss Oil -■,.

N

N

CI CH 3

H 3 C

327 White

Solid

N

N

H 3 c 113 o \0

F

H 3 c

328 White

Foam

N

N

CH 3 /

Cl 0 cs \\ 0

CH3

CH 3

329 White

Foam

N

N

irT:ji-

CH3 /

Cl

0 CH3

CH3

278

17149

330 White Foam

CH3

CI 0 s/

\\ N 0 / CH 3 N

H 3C

331 White

Foam /

CH3 /

Cl 0 C rIrcs- °

N 0 5 CH 3

N

H 3 C

332

Clear Yellow

Oil O

N

H 3 C CH 3

CI 0 Y—CH 3

N 0 I

\--SF

333 Clear

Oil

Cl

o/CH 3

111--- N

H 3 C

279

17149

Light N

N

Cl 0 irCH 3

H

334 Brown

Solid

CI —CH 3

N

White N / N\ CH 3 335

Solid CH 3

CI CH 3 0

CH 3 White N / N\

336 Solid

CH 3

CI (3

N

,.......1—cH 3

Pale IN / N\

337 Yellow CH 3

Oil

280

17149

Cl 0 r-CH3 N

_ 0

N

14,

Clear

Oil H3C)338

Cl

N Clear I

339 N Oil

H 3 C

H C H3 CH3

CH3 N

White 340 FN

Solid

H C H 3 CH3 0 1C S

N Yellow

341 N ■„

Oil I

281

17149

342 Yellow

Oil I \1>

N

N

CH30 /CH 3

343 Yellow

Oil I

N

N

CH 3 0

344 Yellow

Oil -.

I

N

N

CH 30

CH 3

345

Yellow

Solid

N

N

CI 0 CH 3

11 H

CH 3

282

17149

White

Solid H3C)346

N

CI 0 H3

S

347

Pale

Yellow

Oil

\

N I

N

a s/CH3

3

H 3 c

348 Brown

Solid

N

N

CI

Cl / 0

349 Beige

Solid ■••.%,N

I N

N-- I

CH3 0

Na

283

17149

350 Colorle

ss oil

CH3

Br i 0r

7 , cll,

351 White

Solid

N J3

0 CH 3

CH3 N /

CH 3

352 Yellow

Solid 1 \ I

CH 3

N dN

CH3

CH3

353 Yellow

Oil

H CH3 0 /

N ,..„7---s

N lisk CH3

284

17149

354 Yellow

Oil

N

N Cu) CH 3

s/

CH 3

355 Yellow

Solid

N

N

CH 3

CH3 / N \ CH 3

356 Yellow

Oil

N

N

0

CH3

s/

CH3

357 Yellow

Oil

H

N

N CH3

/CH3

285

17149

358

Off-

White

Solid

N

/ CH 3

359

Off

White

Solid

/

N 1

N N / \ CH 3

360 White

Solid 1

N

N

CI CH 3

CH 3

CH 3

361 Tan

Solid 1

N

N

CI 113C cH 3

CH3

286

17149

Clear

N

N

Cl /C Ii 3

S \\ 0

362 Oil

Cl o 0 CH S

N \\ 0

Clear N 363

Oil LNJ H3

Cl /CH3

S N

Yellow N CH 3 364

Oil H 3 C

Cl CH 3

Yellow N N 365

Oil CH 3

287

17149

366 Yellow

Oil

N

CI 0 /CH 3

14 )---CS CH 3

CH3

367 Clear

Oil %.

IC H 3 Cl 0

N c..<CH3

CH3

368 White

Solid

CI CH3

N

N

H 3 C

369

Light

Brown

Oil

CH 3

N CH3

N N I CH3

288

17149

370 Colorle

ss Gum /

N

/

H 3 C TH 3

0 ,—S is?

CH3

371 Colorle

ss Gum

N

CH 3 /

S

\C H3

/

3 72 Yellow

Oil

N

N

CI /CH3

S

11 3 C

373 White

Solid

N 1

N

CI

H 3 C

Cti 3

289

17149

374 Beige

Solid I

N

1 .N

Cl 0

375 White

Solid

N

N

H3 0

H

H3

376 White

Solid F

N

N

CH 3

377 White

Solid F

N

N

H3 (3

290

17149

378 White

Solid

,„

N

CH30 N

\ A N ■ ,..,„, ...... 3

H 3 C

379 Solid

White

CI ---N N.--

H3C

ti\CH3

380 White

Solid

CH 3 cH 3 0

CH3 N

N D

381 White

Solid

H 3 C cH, CI 0 y____ J

/ NN D

Y--D D

291

17149

382 Oil

Clear

N

CI 13

F‘ ,F

7--F

N

) H3C

383

Pale

Yellow

Oil

N

N

CI

0 CH 3

CH, s/

'

H 3 c

s\C H3

384 Colorle

SS 011

N

N

CH3 ci

/ \ CH 3

CH3

385 White

Solid

CH

N

CH 3

CH3 N

292

17149

White N I

cH 3

cH 3 386

Solid F N

N White

387 FN Solid

\CH3

CH3 0

N I , NI

White N / .‘ Br 3 88 CH 3

Solid

D

CH 3

t—D

Colorle N

>....{-6

389 SS Oil

N / N) CH 3

H 3 C

293

17149

390

Off-

White

Solid

cti 3 0

N S

N 5 CH 3

H 3 C

391 Colorle

SS 011 -...„,

D‘ fp

Cl 0

N ,__C-Sic."-D

N I\ CH 3 CH3

392 Colorle

ss Oil

Dup C I 0

N ,....C-Sic"-

J-D

- ..., N N\ CH 3 CH3

Calorie

ss Oil

CH3 CI /

S N

N

H 3C

294

17149

394 Calorie

ss Oil

N

N

CH 0

H 3 c

/CH3

395 Solid

Pink

N

CI

\ CH3

396 Calorie

ss Oil

Cl

N

N / \ CH3

/cH 3

397 Calorie

ss Oil

N

N

C11 3 0

,---7--S

/C113

N‘ p

)(---o 13

295

17149

398 White

Solid

F ....,

CH3 0

N

N

CH3

s/

ct1 3 D

399 White

Solid I

FN

. INK

Br

N.---- I /

/

o CH3

CH3

400 Yellow

Oil

...., I

N

N

cH 3 CH3 /

S

c

s\

CH3

401 Yellow

Oil

........

N

CH3

N

/CH3

CH 3 o

tt

\ cH 3

296

17149

402 Yellow

Oil

CH 3

NrCS

iCH3

cH 3

H3

CH3

403 Yellow

Oil

N

N

CH3 /

HC 3

s

cH 3 0

) H 3 C

404 Yellow

Solid --

H C

N

•

CH 3

CH3 N

405 Colorle

ss Oil

N

N

cl 0

x ID

)1---D D

/CH3

297

17149

406 Colorle

ss Oil

Cl

N

CH 3

/CH3

S

N D

407

Pale

Yellow

Oil

Cl

N

0 CH3

N

H 3 c 0

s\CH3

408 Yellow

Oil

H 3 C

N

N

CH 3

CH3

N

CI

H3

409 White

Solid

N-

N

CHp

FF

CH3 S S. CH3

298

17149

410 Orange

Oil

\

I

CH 3 CI 0 /

N

N o

s\ cH 3

411 Beige

Solid

-.

N

N

H3 0 i-CH3

H

) H3C

412 White

Solid

N

N

CH3 H3 0

H 3 c

413 White

Solid F

N

N

14 3 c

299

17149

414 Yellow

LJ Oil

CH3

CH3 N

N

415

Off-

White

Solid

■,..

1-1 3 C CH 3 a 0 yCH3

N--- 0 I N / CH3

T CH 3

416 Yellow

Oil

H3C

0 /113

N )C jr-S

N 1\ CH3

417 Yellow

Oil

H3C

s/CH3

N

N N \ CH3 CII3

300

17149

418 Yellow

Solid

H 3 C

CH3 N

N / N\ CH 3 CH 3

419 Yellow

OH

H 3 C

0

N s/

CH3

N N \ cH 3

420 Yellow

Oii ■,,

H 3 c

N

C 3H s/

N / N\ CH 3

421

Light

Yellow

Oil •.,.

cti 3 0

N

N

H 3 C

H 3 S S

di

301

17149

Light

ti 3

S

a *

422 Yellow N

Oil N ...

11 3 2

CH3 0 CH3

Light N

423 Yellow N

Oil H3C

CH3 so

N

Tan N / 424

Solid Ei 3 C

lik F

Colorle 425

ss Oil 't ic

302

17149

426 Calorie

ss Oil

CI F

IP olc

427 Yellow

Oil

N

N

0,c

ci o c0 2

S

C11 3

428 Yellow

Oil

O

-. N

CI 0

N ) 0 3 c

c0 2 7....."

429 Yellow

Oil

.,

N

N

Cl o s_y-tz--c0 2

'CH,

0 3 c

303

17149

430

Light

Yellow

Oil

N

N

Cl

CH 3

CH 3 •

o .

431 White

Solid -...

N

N

CH 3

CH3

CH3

432 Yellow

Oil

N I

N

Cl 0 )„../S—C H 3

/ N /

H 3 C

)

433 Yellow

..., Oil

N

Cl op s/CH3

,---C N

0

304

17149

434 White

Solid

H 3 C cH 3

N N H

435 White

Solid \

HO

N CH 3

CH 3

N

436 White

Solid

■„.

N CH 3

CH3

Yellow

Oil I

N CI 0,_cs

I

CH 3 i

N N / CH 3

CH3

CH 3

305

17149

Cl

N

CH 3 /

438 Yellow N \

CH3 CH3

011

013 0

I

439 White

Solid

F .......N

1

I\CH3

N

cH 3 0 CH 3

N

White N

440 c H3 Solid

CH 3 0

N

Yellow N 441

Solid CH 3

306

17149

442 White

Solid F

N

N

CH 3 co

N \CH3

443 White

Solid

N

N

CH3 0

CH3

444 Brown

Solid

N

cti 3 0

N \ at,

,c11 3

445 Brown

Solid

N

a o

T'k ctI 3

,CH3

307

17149

446 Yellow

Solid

N

cti 3 0

N \ CII 3 cti,

/if c,

447 Dark

Oil

N

C l

N \ CII 3 cit 3

/cti 3

448 Brown

Solid N

N /

N

CH 3 0

N \ CH 3

C113

CH 3

449 Tan

Solid N

N

N

CI

N \ CH 3

CH3

CH 3

308

17149

450 White

Oil

N

N

Cl

VCH3

cH 3

cH 3

rc cH 3

451 Yellow

Oil

K ,isi

0 N

N 1

Cl 0 / HC 3

,..x--S

/ N\ CH 3

Ort_ CH 3

452 Colorle

ss Oil

I N

CH 3

Isk cH 3

453 White

Solid

N

N

CH3 s/

CH3 CH 3

309

17149

454 White

Solid

Br

N

0

, (

CH 3

CH3 N\

CH3

I i N /

455 Colorle

ss Gum /

N

CH3 N

456 Yellow

Oil

CI

N.-- I N / N

457 White

Oil F1

CI

N S

cn 3

cut 3

CH3

N

0

310

17149

458 White

Solid

AND Enantiomer

CH3

S/

N

tti / CH 3

Colode

ss Oil 459

H3C TH3

Br 0

,

)—S

N-

CH3

460 White

Solid

Br 0 \ /S—C H 3

i , i•?' N / N

C H 3

461 Colorle

ss Gum

F F

Br 0\

N--- CH 3 I /

N \f, u ‘.....3

311

17149

462 White

Solid

N

N

Br 0

CH 3 /

rs I,

/ )

I-1 3 C

463 White

Solid

N N

CH3 /

S

CH3 /

H 3 C

464 Colorle

ss Gum

N

N

F F

CH 3 /

465 White

Solid I

N

c\,. ,/%1

N I

(

C H 3

CH 3 / /

H 3)

312

17149

466 White

Solid

N-

Br 0

AND Enantiomer

C H3

i

467 Colorle

ss Gum

N

lisi

H 3 C TH 3 o )--S

IL CH 3 /

468

Light

Yellow

Solid

N

N

Br 1S—C H 3

/ CH3

469 White

Solid /''•./

I ..... ....,;,--e. N

N

IV

Br

---

0 S—C H3

/ CH3

CH 3

313

17149

470

Light

Yellow

OH

N

N /

I / HC 3

CH 3

*

471

Light

Yellow

Oil

N I

N

Cl

\CH 3

s

,CH3

CH 3

472

Light

Yellow

Oil

N

N

Cl o

H 3 C

CH 3 /

S

CH 3

473

Light

Purple

Solid

N

N

cH 3 c)

H3c

s/CH 3

cH 3

314

17149

Yellow ,,

N

N /

CI

H 3

cH3 474

Oil ? cH 3

CI

N CH 3 S .

Light -. N CH 3

475 Yellow

Oil cH3

CH 3 CH 3

N --- Br 0\

-

S—CH 3 Y c H 3 476

White

Solid

Ill / \CH3

CH3 0 /

N--N , CH3 Off- N\ /

477 white CH3

Solid

315

17149

478 Clear

Oil

0

NT-D, I N / 5

H 3 C

CH 3 /

479 Beige

Solid

C's CH 3

N I

N

H 3 C

480 White

Solid I N

I—CI-1 3

N I , N.T.D._

H 3 C

11

481

Light

Yellow

Oil

CO

N

Cl

N

H 3 C

316

17149

Beige

CI

N —CH 3

482 Solid

H 3 C

CH 3 CI

CH 3 Clear N

483 Viscous N /

Oil I-1 3 C

CH 3

C113 Clear N--

1 y

484 Viscous N /

Oil

)

H 3 C

CI

N V

C H3

White N

cH 3 485

Oil

317

17149

486

Off

White

Solid

-.

IC H 3 CI c)

N

N /

11 3 C

487

Off-

white

Gum

CH 3 0 H3

N--d CH 3

H3C

/ \ CH 3

488

Light

Yellow

Solid

N

H 3 C CH 3

CI 0 y_ c H3

0

N /

0 /

113C

489 Yellow

Solid

CH3

CH3 N

N

318

17149

490

Light

Yellow

Oil

Cl

N I ,

N •\%. / CH 3

CH3

491

Light

Yellow

Oil -.

a

N

N

H 3 C

CH 3

492 White

Solid

CI0

N

N cH3

cH 3 s/

CH 3

493

Light

Orange

Oil

F

N.-- I , N /

H 3 C

F F

s/

CH 3

319

17149

4 94

Yellow

Oil -,

N

N

CI H C CH•

\\ 0

H 3 c

495 Clear

Oil

N

N

CI ii-c

3 0 cH a

S \\ 0

I-1 3 C

496

Light

Yellow

Oil

-.

N

it:

Cl 0

/ \—s\

CH 3

/0

H 3 C

497

Light

Yellow

Oil

N

N

Cl 0 CH3

1% CS CH3

0 /

H 3 C

320

17149

498

Light

Yellow

Oil

,.■.,,

I N

Cl 0

\

CH 3

( CH 3

N

0

I / N

/ H3C

499 Calorie

ss Oil

Cl % H3C

CH 3 N

I 1 / NJ

H3C

500 Beige

Solid

N

N

CI 0 cH 3

II 3 C

501 White

Solid \ N

N

CI o

CII 3

I

II 3 C

321

17149

502

Thick

Yellow

Oil

N-- 1

CH3

H 3 c

503 Beige

Solid

N

N

11 3 C CH3

CI 0 / ) H

H 3 C

504 Beige

Solid

N

N

H 3 C CH 3 % V

)--H 1

I-13C

505 Colorle

ss Gum

N

tis1

Br 0

S \ /

H3C CH 3 F F

322

17149

506

Clear

Colorle

ss Oil I

CH 3 CI 0 /

N )-7---S

N N

507

Clear

Colorle

ss Oil I

CI

N

N

CH 3 s/

CH 3

508

Clear

Colode

ss Oil I

CI 0

N I

N

CH 3 /

S

509

Pale

Yellow

Gum

CH 3 0 /

N

I N

CH 3 / \

CH 3

323

17149

510 Yellow

Oil

--.....

I

CH3 Cl o /

N

NCH3

4--o o

......3 H3C

511 White

Oil ...,

CI /H ' Cl

s N

N CH3

o—Th

0—C H3

512

Pale

Yellow

Oil

........

Cl 0

N--- 3

i , N N /

) H 3 C

513

Thick

Clear

Oil ...„.

cH 3

N--- ti i

N

1-1 3 c

324

17149

514 White

Solid

N

N

Cl

H 3 C

H3C CH 3

Y--CH 3 S

515 White

Oil

N

NI

CH3

CI

) H 3 c

S CH 3

516

Dark

Brown

Oil ..„

N

N

Cl

CH3

517 White

Solid

N

N

CI 0 F

325

17149

518 White

Solid

N N

oyiii s—c[1 3

1. H3C

519 White

Solid

N

N

CI 0

S-CH 3

N H

11 3 C

520 Brown

Gum

■%

I

N

H 3 C

) NN

CH3 N\

CH 3

CH3

521 Beige

Solid I

CI

N

N

—CH 3

CH3

326

17149

522 White

Solid

Cl 13"--C H3

N

N / CH 3

H 3 C

523 Yellow

Solid

cH 3

cH 3 N

N / N‘ c11 3

524

Light

Brown

Solid

Cl

N

N / H 3 C H 3 c

525

Faint

Yellow

Solid

s/

N

0

)\--7—

3cH

N \CH3

327

17149

526

Faint

Yellow

Solid

F• N

I N

N 1

CH 3 CH3

C113 /

527 Yellow

Oil .,.

N I

N / N \C H3

CH 3

CH3

528

Light

Brown

Oil

N

N H3

0

C

s/

CH3

529

Faint

Yellow

Solid ■,,

N

N cH 3

s/

CH3

328

17149

530 Clear

Oil

-.

CI 0 F

N I

N CH 3

5 \ CH 3

531 Yellow

Oil I

F

CI 0

N

N cif,

‘ c11 3

532 White

Solid

CI —C H 3

N I

N CH 3

0 11 3 C

/

533 Orange

Oil I N.--

Cii

CI 0

N 113

N N

o H3 C

/

329

17149

CI

N

N

S--C113

534 Red Oil

CI

N CH3

White N

I cH 3

535 Oil

OH

CI CH3

111---- 536

White N CH 2 Solid

H3C

F

Cl (3

Clear N 537

Oil N

H3C

330

17149

538 White

Solid

CI

11--- N

H3C

539 Clear

Oil

CI CH3

N

N

H C

540 Clear

Oil I _ \N%

Cl

N I N /

113C

541

Light

Yellow

Oil

TH 3 s

1 o

N

N /

0 /

11 3 C

331

17149

542 Colorle

ss Oil

N

N

Cl CH3

CH3

543 White

Solid

N

N

Cl CH3 c)

L-CH3

544 White

Solid

N I

N

Cl

,

—CH 3

/ CH 3

545

White

Fluffy

Solid

N

N

CI S—C H 3

332

17149

546 Brown

Solid -.....

H Cl

N

Br N / N\ CH 3

547 Yellow

Oil

i

Cl

N s

N cH3

548

White-

Yellow

Oil

cH 3 CI

s/

N

N CH 3

549 Colorle

ss Oil

CH 3

Cl C H 3

N

N CH 3

333

17149

550 Calorie ss Oil

N

N

Cl

CH 3

CH3 S/

H 3 C

551 Calorie

ss Oil ._

N

N

Cl

CH 3

c H, / ' S

552 Calorie

ss Oil I

N

N

Cl CH 3 /

S

553 Calorie

ss Oil

N

N ci Cl

CH 3

CH 3

334

17149

554 ss Oil

Colode

I ■N#

cl

N I

cH 3

555 Yellow

Oil

CI

N

N N \C H 3

556 Yellow

Gum

Pale

H3C

/ N . \CI-I 3 \CH 3

557

Pale

Yellow

Gum

H 3 C

CH3

CH3

CH 3

( CH 3

335

17149

558

Faint

Yellow

Oil

..,

N

N

ci

\ I

H3C

559

Faint

Yellow

Oil

N

ON

cl

H 3 C

560 Yellow

Solid

CH3 N I ,

N / CH3

561 White

Solid

N CH3 N

CH 3

336

17149

5 62 Brown

Gum

11 3 C CH 3

CH 3

S \CH 3

563

Pale

Yellow

Gum

.

N

CH 3

CH 3 \CH3

564

Pale

Yellow

Gum

CH3 co _d S

n \ Cri 3 CH 3

565

Pale

Yellow

Gum

C113 0 C11 3 /

S

/

337

17149

Pale

CH3 0

N

H3

S/

C

566 Yellow

Gum

CH 3 0

-41 CH3

Off- / N

567 white \ CH 3 CH3

Solid

cH 3 o t N---14

Pale

568 Yellow CH3 \ CH 3

Gum

CI CH 3

N

Colorle N / 569

ss Oil CI H3C

338

17149

570

White

Semi-

Solid

CI

Ntd I

N

II 3 C

s/

CH 3

\\ 0

571

White

Semi-

Solid

N

N

CI 0 /

C 113 S \\ 0

F

H 3 C

572 Calorie

ss Oil .,

N

N

CI •0

N \ CH 3

573 Colorle

ss Oil

N

N

CI 0

CH 3

339

17149

574 Colorle

ss Oil

N-- I

..

I

N

cl

CH 3

575 Colorle

ss Oil ..,

N I N

CI so

576 Colorle

SS Oil .,

N

N

CI 11 0

N \C H 3

CH 3

s/C H3

577 Colorle

ss Oil

N

N

CI 11 3

0

CH3

CH3 /

CH 3

340

17149

578 Colorle

ss Oil

........

(3 CH 3

7 K-s , )? N /

CH 3 ›-CH 3

H3c

579 Colorle

ss Oil

....... cr CI 0 CH3

7 K—s , ), N /

H 3 C H 3 c

Colorle

ss Oil 5680

1 0 CH 3

N K-S N / )—cH 3

cH3 H 3 c

581 Colorle

ss Solid

Eli i fil 3

0"CC113 N

ycii: N

II 3 Ci

341

17149

582 Clear

Oil ...

N

N

CI 7"--N

11

--

..,

14 3 C

5 H 3 C

583 Brown

Oil

N

N

a NH

* H 3 C

584

Da rk

Yellow

Oil

N

N

cl

Nfl

H 3 c

585 White

Solid -...,.

LN

N /

N

CI

H3C H 3 C

S

342

17149

Yellow N

CI H

586 Br Solid Solid

H 3 C

CI 0 / N

N N

587 Purple N \

CH3 H3C

Solid

ci Dark

N 588 Yellow

Oil N

CH3

I-1 3C Ol

CI N

Colorle 589

ss Solid N

H 3 C

343

17149

590 Brown

Solid

N i

N

H 3 C

Cl

0, 0

N

CH 3

Y—CH 3

\---N

591

Light

Yellow

Solid ---,

N I

N

0 CH 3

C 11 3 / /

N

592 Brown

Oil

N

N

CI

SCH 3

cH3 ...._,

--- N

593 Brown

Oil -.„

N

N

Cl

I

N \ cH 3

344

17149

594 Yellow

Solid

Faint

CI

N

/ NH

N

CH 3 *

595 White

solid

Ox‘ H 33e.CH3

N-- "--0 CH3 I N N

----0 CH 3 0 Y—CH3

H 3 C

596 Brown

Solid

ti 3 c cit 3 11 3 o ctt 3

N /

=en

597 Colorle

SS Oil

CH 3 o

N---

tj / -CH

345

17149

598 Calorie

SS Oil

cif, i

11 3 c1/4 r-s

N 11- N /

\=C11

599 Calorie

SS Oil

Cli i o IC II)

N

N / C11 3

=CH

600 White

Solid

C113 0

N

CH3

( CH3

=CH N /

601 Yellow

Solid

cup

N

N

it at, cif,

=CH

602 Calorie

ss Oil

Clip CH ] i

N

N CH3

-CH

346

17149

603

Light

Brown

Solid

N

N

Clip C113

( CII3

=C II

604 Brown

Gum N

II 0

/ =en

605

Light

Brown

Oil

N

N

clip C11 3

1

=CH

606

Light

Brown

Oil

N

N or 0

il CtI3

cti 3

=CH

607 Colorle

ss Oil N

N

CI 0

C113 r

=CH

347

17149

608 Colorle

ss Oil

crt, i

Cl 0 (—S

N

N C113

=CH

609 Colorle

ss Oil

CI o

N

N =CH

610 Yellow

Solid

CI 0

(

CH 3

N CH3

N —CH

611 Yellow

Oil Oil

CI S--cii 3

N

cu

// 1IC

612 Beige

Solid

N )...7S—CH 3

NN

it c1 348

17149

613 Brown

Oil NN

F F F

CH, s/

—CFI

614 Colorle

ss Oil

N

N

F CII3

=CII

615 Colorle

SS Oil

CI

N

F

F

F

or —CII N

616 White

Solid

113

N

CH,

C113

I N 1

tic

617

Off-

White

Foam

CI

N

N

i

0 \\

S—C/I3

CiI3

349

17149

618 Yellow

Foam

0 a \\

\\ N

II 3

o I

N CII 3

I

619 Colode

ss Oil

CI ci N--- 14 / N

2

620 Colorle

ss Gum

CI 0 s.....?

1$ —. \---/ N / 1̀ 1‘

/

621 Colorle

ss Gum

CI 0 N--- 14 /

622 Colorle

ss Oil

CI 0

NiC-S

/ L tnr

623 Colorle

ss Gum

a o N S .N7 L. 6

624 Colorle

ss Gum

a N- 14 /

350

17149

625 Colorle

ss Oil

CI 0

N-I:4

626 White

Solid

F

CI 0

N

n- ) N

627 Colorle

ss Gum

C 0 — jc F N

14 / N r\:71, F L. 0

628 Colorle

ss Gum

CI 0 N F 14 NiC 9 rVIC F

L. 0

629 Colorle

ss Oil

F

CI 0

,....y—S

I■1 NN \

630 Colorle

ss Oil

C 0 N— 1,4 / N SI.F

\ 6

631 Calorie

ss Oil

Cl 0 0 F NA„,.......r,...vc

\ 0 F

351

17149

632 ss oil

Colorle do

N- k 1 N n- .,/N 633

Colo rle

ss Gum

F CI 0 r-ci----F

N)\-7-S .e. e.14

Q j N

634 Brown

Oil

F

CI 0 N /4

635 Clear

Oil

F F F-S(

CI 0 si N

i■.

636 Colorle

ss Oil

F F CI op r--3(

,\...y---S F / N

i

637

Pale

Yellow,

Viscous

Oil

F F

a 0

IS 1---/ - 7 N / -

638

Viscous

Brown

Oil.

F CI 0 F

N- CI 14 /

352

17149

639

Pale

Yellow,

Viscous

Oil

F‘F

Cl 0 s—lc—F N I■1

640

Opaqu

e

Viscous

Oil.

ci 0

IS N

641

Opaqu

e,

Viscous

Oil.

CI 0 N gI

642

Opaqu

e,

Viscous

Oil.

IS

F‘F

CI 0

N

643 Oil

do r.... F

N— ,...."—S

/(1 N

i

644

White

Semi-

Solid.

CI 0„0 F F

\ N

‘K)<F

)

645

White

semi-

solid.

CI 0 0 F g je F

N .• -% F

)

646 White

Solid

F F

Cl 0 SY-F

lil N /

353

17149

6 47 Oil

Yellow

F F Cl 0

S

6 48 Yellow

Oil

F F CI 0 y-F

S /

649 Colorle

ss Oil

Cl

Cl

/ N \

650 Colorle

ss Gum

CI 0 ...x....z<C1

1:1 \.....dS Cl

N N

)

651 Colorle

ss Gum

CI o

N — Cl 141 N

)

652

Opaqu

e

Viscous

Oil.

Cl 0

\ S F

N -..)"...$

) F F

653 Oil

F F

CI ci ri-F

Is_ ..../—S

N / N

)

354

17149

654

Opaqu

Viscous

Oil.

e

CI 0 N-

Table 1: Continued

Corn-

pound

No.

Appearance Structure

Prepared

as In

Example:

655 Colorless Oil

CI 0 CH3 To-N C-1

\ - / CH3 }—CH3 H 3 C

51

656 Light Brown

Gum

CI 0 CH 3

51

N-S_ 9 ItT i N

) s

■ ' 1 ).—CH 3

H 3 C H 3 C

657 Colorless

Gum

CI 0 CH 3

NITIS-N C—g9 \ ' i b H 3 —CH 3 0

H 3 C 52

355

17149

658 Colorless Oil

„CH 3 CI ID N

N-S 14 / 11-74-0

íçí

..

) N H 3 C W3 C' ‘CH 3

149

659 Solid

Faint Yellow FN / 1;1 0

CH 3 35

660 Yellow Oil

0 CH 3

N-- 0

3\

I■I / HO C 3 3

35

661 Clear Oil

CH 3 S.

Ci

IS— N /

H 3 C CH 3

11

662 Clear OH

CH 3 S.

CI 0” j NS. 1:1 / N

H 3 C

11

356

17149

663 Clear Oil

CH S. 3

CI

N1$5/ Nt CH3

Cf )---CH 3 H3 C

11

664 Clear Oil

CH, Se "

CI 00

NIS-5/ N 11

665 Clear Oil

CI

I■1" k/'— N

CH, S. "

CH3 11

666 Clear Oil CI

N-ii /

H 3 C

F F F

12 0

N )

667 White Solid

Cl

Nt1-5/ 0- N

CH3 H3 0

SIC H3

12 N ? CH3

357

17149

668

H CH3

CI 03 N— S'

C H3

12 White Solid ■

669 White Solid

do H 3 H3 CH3 C

12 N b H3

670 White Solid

ci 0H 3 CC H3 S.CH3

12 IS- xi N / ii

/ H 3 C

671 Colorless

Gum

Cl N— 4 /4 / N

■ CH3C H 3 106

672 Colorless

Gum

Cl 0 .1z1-5 NA,„, s 140

■ N f bH 3 106

358

17149

673 Colorless

Gum

Cl N— * 14 /

CH3 H C

106

674 Colorless

Gum

Cl 0 -- dic., 40 V / N %. NS' t S

‘...CH 3 106

675 Light Brown

Gum

Cl 0 ;1 ""/ NASNicCH 3

N Cil l

6-1 3 CH3 - 101

676 Light Brown

Gum

Cl N— 40 14 , N

CH 3C H 3 8 51

677 Colorless Oil

a o ri-S.NA.

H 3 C/ * 101

359

17149

678 White Foam 106

CI * 0 *

N bH 3

*

679 Colorless Oil

CH 3 CI 0

S'CH3 12 ' i N

\ CH 3

680 Colorless Oil

CH 3 CI 0

iii— S'

CH3

12 ■ N r5

H 3 Cl

681 Colorless Oil

CH 3 CI 0

SeCH3 N— 12

0-A v1\l'

682 Colorless Oil Cl 0

iii— S'CH3

12

C H 3

360

17149

683 Colorless Oil CI

N— I■1 /

H3 Cl

0 S.

0 H3 12

k

684 Colorless Oil Cl

/

0 S' CH) 12

685 Tan Solid

Cl 0 g/C H3

1$ Sa)--C H3C1

101

686 Colorless Oil

Cl N—

0,/■1 /

l‘r

o '' CH,

S 12 ?

CH3

687 White Solid

CI N—

F

o e CH3 S.

50 b scii 3

361

17149

688 Light Yellow

Oil

FI 3 C

Cl 0

tH 3

CH3 CH 3 5 12

689 Light Brown

Oil

H3C

Cl 0 CH 3 CH 3 5 12 N—

I■1 / ‘ ■ /

1-1 3 C

690 Colorless Oil

I

H 3 C

CI CH 3

5CH3

12 N5..

691 White Solid

CI CI 0

NS. \--...C.S 14 / N

bi 3

F F F

89

692 Oil

Light Brown

Cl

H C

0

101

362

17149

693 Light Brown

Oil

F F

CI \

CI ci N=:( .--../— N j—N

H 3 C)

89

694 Tan Solid

CI 0 c_ECH3

101 ili / N

) H 3 C

695 Oil

Light Brown

\

H 3 C CI 0 )--Z---CH

74 j—N )

H3 C

89

696 Faint Yellow

Oil ■

Cl NCH3 CH 3

"....d--S.

/ N H

175

697 Beige Solid

S—C H3 Ni CI 0

0—N u CH3 b 1 '3 39

363

17149

698 White Solid

CI 0 5

C N- 14 /

H3

N CH 3

12

699 White Solid

CI 0 S.

0 H3

NIS'S" N‘

H3C/

12

700 White Solid

C'0 S.CH3

N- IV /

H3Ci

12

701 White Solid

a

I

0 s.

CH3

12

702 Pale Yellow

Oil

Cl 0 q 5—CH 3

NVSN ■ i

- CH 3 CH 3

51

364

17149

703 White Foam

Cl 0 q S-CH

3 .0 NIS-3r 1 E43 C11 3 52

704 Orange Oil

Cl so S-CH 3

NIS-5/ Nt

113C1 CH 3

39

705 Clear Thick

Oil

CI 0 CH 3

NIS-5/ NI i

CH 3 H 3 C

51

706 Light Brown

Solid

H Cl g c113

N .--/---S. -i--N

H 175

707 Light Brown

Oil

H 3 C CI 0 )--CH 3

r2_ )Lx-S

Nj— N,_

(j 1' H 3

97

365

17149

708 Colorless

Gum

H 3 C CI 13

Nt---c /4 j--N

Ii3C)

97

709 Colorless

Gum

CI 0 c___,CH3 NS_ )\-.../-1 14 / N CH 3

H3 C) 97

710 Colorless

Gum

/ CH

CI 0 /

VS_ .--/ CH 3 N / 11

H3 Cl

97

711 Colorless

Gum

Cl o

.■ 11■11 -S-Nt

H3 C1 97

712 Colorless Oil

H 3 C 0 CH

Cl 0 WA. 3 VS_ 7,--‹ b N / ii CH3

1 H 3 C

149

366

17149

713 Colorless Oil

H C . H 3 C a kart,

d o144. ‘.... 3

V -5H b .. N / •,‘ CH 3

1-13C1

149

714 White Solid

F

CI 0 CH 3

/1■11-5N 0 ° OH 3N.

182

715 White Solid

CH 3 S. F n

CI 0, }......? t. N ,

F N S

H

12

716 Colorless

Clear Gum

\ C10

1■15._ N N. / N,

Lc H 3

717 Colorless

Gum

CI 0 S--(

C113

V5- CH N / N CH 3

H3C) 3 97

367

17149

718 Gum

Colorless

CI CI 0 F

N

H3C)

97

719 Gum

Colorless

C'0

S

113C) 97

720 Colorless

Gum

CI 0 *

CH3

t , g.,1 ny...

97

721 Colorless

Gum

CI 0 *

VS_ IR N.. N / -i CH 3CH3

l H3C

97

722 Colorless

Gum

CI 0

VS ■

ri

1 nr

,.,_. F F 97

368

17149

723 Colorless

Gum

Cl CI(:) F F

1;1-$)

--‹ ‘ / N / 1 CH3

H3 Ci

97

724 Clear Oil

o_c H 3

CI 0 s$ NJ N / nt CH 3

H3 d

102

725 Clear Oil

'IC

CI 0 s

1■1-5.7QH N / • CH 3

H3 d

102

726 Clear Oil

Cl 0 /

V S_, 1\H N / •-‘ CH 3

H3 d

102

727 Clear Oil

H3C

Cl S 102

N / CH3

H3C

369

17149

728 Clear Oil

S—CH 3

Cl 0 s$

VS_ NH QI

N / • i CH 3

H3e

102

729 Clear Oil

CI 0 CH 3

N / IS CH 3 CH3

H 3 C 102

730 Clear Oil

CH3

Cl 0 s_rO

VS_ N / 1•1‘

H3C1

102 I

731 Brown Oil

CH • CI 0 s..../

V — 11—/ N / • -‘ ■ cr H3e 102

732 Clear Oil

C 0 CH3

N-

H 3)

C

102

370

17149

733 Clear Oil

(CH3

0

C'0 s_ri

V -5 14,--/ 0

N / • i ■ H

i 3 C

102

734 Clear Oil

H3C b

Sa o N- ,---7-S 1415-N

) 14 3 C

102

735 Brown Oil

[IC

C'0 1

N-A ,--/—S

■ 14 j--N )

H 3 C

102

736 Clear Oil

N (/

CI 0 N- ,---r-S /4.--N

\

H3C>

102

737 Clear Oil

CH 3

C'0

1■1*- ,--7-sS ■ Nj Nx

H3C1

102

371

17149

738 Clear Oil

CI-1 3 cCH 3

CI o Nr4 ----/-S

■ /4 j-N

H3C)

102

739 Clear Oil

0 tor-CH 3

CI 0

II*_- ,---/-S N J Is(

H3CI

102

740 Pink Solid * * Cl 0

V p

42

N / Nk.... CH 3 CH3

741 Colorless

Gum

CH

CI 0 _ fr

1 / N ci, 3 CH3 45

n li

r, ur,) 97

742 Colorless

Gum

CI 0 N

1■13_, TR N • *s CH 3

H 3 e

97

372

17149

743 Light Brown

Oil

CH, Se '

F

■ 14 N F

t 0

S.0 H3

11

744 Light Yellow

Oil

F F F

CI .CH3

12

745 Light Yellow

Oil

do C H 3

S

11 C H3 ■

746 Light Yellow

Oil

F F F

CI .CH3

IS" 12

747 Light Yellow

Oil

Cl H C

.C

— 12

1-1 3

IS N / ■

373

17149

748 Colorless Oil

H 3 C CI

97

Cs N \--.7--S 1;1 --- --N

\

H3C)

749 Light Yellow

Oil

CI 0

1■15_1\HS—C1-13

N / ? CH 3

? F

12

750 Light Yellow

Oil

CI 43 CH3

N— 1■I CH 3

11

751 Brown Solid

F

CI CH 3 N— S'

50 /4 N II fl- •CH3 0

752 Light Yellow

Oil

H C CH CI 5" 3 1■1— N ,

I 11

374

17149

753 Colorless

Gum

F F

CI 0 N Nst( ,--reS I■I -1`,1 ■, C H3

89

754 Colorless

Gum

/1— N F %

CI 0 Nr---( ,---/—

■ 1■Ij-1`,1 CH3

89

755 Light Yellow

Oil

CI 0 S—CH VS_ T‘H 3 N / — CH 3

() N

12

756 Light Yellow

Oil

F F F

CI C H3

, *. I F

12

757 Light Yellow

Oil

Cl H C .CH 3

■ F

12

375

17149

758 Light Yellow

Oil

--"A , S - C H 3 3l.. n It/ in

CH3 n- ) F . F N

12

759 Light Yellow

Oil

CI 0 ,C H 3 I■1- N C H3

F F 11

760 Colorless

Gum

Cl VS_

■ N / N CH3 , 101

761 Colorless

Gum

CH 3 Cl 0 S \

VS_ N / NI,

L.H 3 rr

101

762 Colorless

Gum

Cl

;6"-- N,)LV S N CH 3 C H3

101

376

17149

763 Clear Oil ■

Cl 0 S—CH 3

12 N i:i / N

H3C)

764 Colorless Oil

Cl 0

NS. S

b H 3

CH 3

CH 3 101

765 Amorphous

Solid

CI 0 CH3

V5-xy A N / A S CH 3 bli3 8 91

766

Colorless

Amorphous

Solid

Cl 0 CH3

N / NA

.)t .,kCH 3 S CH 3

buil 8 91

767

Colorless

Amorphous

Solid

*.

Br

N CH 3

F F

CH3

8 91

377

17149

768 Light Yellow

Oil

F F F •CH 3 CI

■ 12

769 Oft-White

Solid

CI 0

V-5HS-C H3

N / - CH 3

....;

F

12

770 Light Yellow

Oil

a o 013

N- N CH 3

FF

11

771 Light Yellow

Oil

110. Cl IDCH,

I■1"- S' J

/ N -. C H3

12

772 Light Yellow

Oil

* CI 0CH3

N- S'

cri■I / N

H3 C)

12

378

17149

773 Light Yellow

Oil

110 Cl 0

S"C H3

12

■

774 Light Yellow

Oil

CI 0 • CH

3

— ---/—S

12 N5-N 14,

n' N FI

775 Oil

Light Yellow

CI 0 CH 3

/ N .■

F

12

776 Light Yellow

Oil

CI 0 , CH 3

V ,...7--J.

.,. N /

F F

12

777 White Solid

H CH 3

Cl o• CH, S: a

N.JN b b H 3

50

379

17149

778 White Semi-

Solid

H C CI 0

■ tS-1`lt i

H3 C

CH 3

S :CH3

b 50

779 Tan Solid

Ci 0

NV-SrNI )

H 3 C

s...t H3

0 CH 3 101

780 Light Yellow

Oil

F F F

11, Ci 0 cH 3 12

Nt1-5/ NCH3

781 Oil

F F F

12 Light Yellow

CI 0

•■ ti— l‘lx )

H 3 C

782 White Solid

F

CI Nd /

CH, St a b 50

380

17149

783 Yellow Oil

CI 0 IP N-

14 / N‘ CH 3 1

11 3 C

89

784 Clear

Colorless Oil

CI 0 N— 141 / Ny C H 3

H3 Ci

89

785 Clear

Colorless Oil

CH3

Cl 0 S IS-5m N / LI cH 3

i H 3 C

89

786 Clear

Colorless Oil

0 ryor-C H 3

CI S N—

i CI IZI / v c H 3

H 3 C

89

787 Opaque

Viscous Oil

C

Cl0 S--PH, - N— ,---< N / Nt CH 3

1 H 3 C

144

381

17149

788 White Solid

CI 0 C H3

N /5 1,--‹ 0

— CH 3 1C 11 3 101

789 Orange Oil

rCH3

137 VS_ 0 )z--N N / N,_ CI C H3

790 Pale Yellow

Oil

4C1 0 —N S k

Nisi)—/ N ) c H 3 C

136

791 Light Yellow

Oil

JN

/ CI as•

V-- S'

C H3

N / N. ■ CH3

12

792 Light Yellow

Oil

/ CI 0 CH,

N— S' '

) II 3 C

12

382

17149

793 Light Yellow

Oil

JN

\ / CI CH 3 12

, I

794 Light Yellow

Oil

H3 C b

110 Cl 0 C H3

Se 12

■ CH 3

795 Light Yellow

Oil

H 3 C b

1110 Cl 0 CH3 12

N-

■ 14 / ‘

I-13 C/

796 Light Yellow

Oil

H 3 c b *

CI 0 CH," S 12

IS— ■. N /

797 Yellow Solid

(:). N1-12

CI 0 ›-C H3

16- '--7-S

N / N ) HC

89

383

17149

798 Colorless

Gum

CH 3 Sae)1-4"- CH 3

CH ).—CH 3 3 CI 0

LNJ

N_. -7—S

■, ) 11 3 C

89

799 Oil

r J—EN CI 0

N—c— ,--/—S

) H 3 C

89

800 White Semi

Solid

H3C 0, cH

CI 0 WS' 3 IS-5 7,,,---/ b N / =I

I H3C

170

801 White Solid

H 3 C 0, cH Cl

_ --/ b V-5 N / _ N cH3 170

802 White Semi

Solid

_ H 3 C 0, in u

,--/ b N

■- 170

384

17149

803 Foam

Pale Yellow

\ " CI ily 0 .7.% q. p

CH 3 c.N

147

804

Colorless

Gummy

Liquid

I N

CI 0 /

S

0 183

805

Colorless

Gummy

Liquid

I

Cl o /

183

/

806

Colorless

Gummy

Liquid

I

Cl 0 s/

o 183

/

807

Colorless

Gummy

Liquid

I

Cl 0 s/ 183

/ N o

385

17149

808 Brown Solid

H C 0 Cl 0 3 ig a ••

VS_IsH liCi

N / —,_ CH? 149

809 White Solid

H C 0

N g...I ru ....5 )1,....?"„ — —3

.. N / N,_ u H3 — 149

810 White Solid

CI 0 H3 14. 9 1SS_ IR d N / • i_ CH, ■ CH 3 - 149

811 Yellow Oil

CI 0 H

3 C k le

VS— is?L( O 4 N / - ,_ CH,

CI

C H3 - 149

812 Light Yellow

Semi-solid

‘ / CI 0

S• N CH3

/ N ■ ICH 3

12

386

17149

813 Light Yellow

Semi-Solid

■..

\

CI 0 CH 3 N— S'

) H 3 C

12

814 Light Yellow

Semi-Solid CI co

•_ S-C H3 L: H3

12

815 Pale Orange

Foam

i Cl

0 9 N'AyS-CH 3

H3 c) C H3 51

816 Pale Orange

Solid

, CI 0 q. .9

• -"NiCrS-C H 3

H3 C) C H3 52

817 Brown Gum ■

CI 0

N- F F ,,■ , Nh (

94 /

'I ) S F H 3 C —CH 3

0

387

17149

818 Opaque,

Viscous Oil

CI 0

H 3 C 102

819 Pale Yellow,

VISCOUS Oil

CI 0

1/4-A NriL s.v.*C 11 2

H3 C) 102

820 Opaque,

Viscous Oil

CI Pitt 0

N •--. NI)LrsCH2

H C) C H3 102

821 Opaque,

Viscous Oil

CI F F

102 H 3 C)

822 Opaque,

Viscous Oil

CI 0

N 102

388

17149

681

30 I,

Eno, e f ii 1

'AXN m 13 0 0 N ID

110 sno3s1/4

ienbed0 LZ9

ZOI. D E H a 1

A e'Y'SN.v1r A r \ / 0 -- /4

13

HO snoosIA amoneA

939

96 0 (OH

EH D

iLA (1•1 %r,‘ ‘ )

0 *.--/4 \ ID

110 snoom

. e n b e d 0 939

301. tHD (OH

N

HO snoos1/4

tenbed0 $38

/ 0

13 Ad

614 D E ll

EH3 p

tHa- g b 0 it--14 0

13

Lund enbed0 EZ9

17149

828 Pale Yellow

Oil

\ Pr<C1

0 F r \--•** A.......1 ..".....7k . N S F

1-1 3 C) Fe% F F

102

829 Opaque,

Viscous Oil

/ \ Plitt CI

0

\---^N-Les."- S-......A F F

H 3 C) 12

830 White Solid

CH 3 CI 0, _FS.

N-i_ IV / 11 Cln.

i INI'

11

831 Off White

Solid cl ......

i

cH 3 S

CI 0 11 1■1-S-/

N ' H

832 Off White

Solid

r

/ \ ,‘„.. H CH 3 N

-CH 3 0

CI

11

390

17149

833 Off White

Solid H3 C-0 H

%all)

.b14.Z 0 Cl

11

834 Off White

Solid

1-13 C—CI

/ \

Cl

N;I NYLc s,CH 3 H C H3

11

835 Off White

Solid

H3 C Cl 0

N H

11

836 Off White

Solid

H C

/

Cl 0

N ,C H3

H H

11

837 Yellow Liquid

Cl Cl o

79

‘NJ.L s,c1-1 3

6113

391

17149

838 Yellow Liquid

Cl N CI

W1/41 °11 _ ril NMS' —3 tH3CH3 79

839 Yellow Liquid

Pir-..(CI

0 C H,

/ \-e-A l■IjC.7 S° 4

H3C-0 CH 3 79

840 Brown

Gummy

H 3 C-0 CI 0

/ \ ,C 113 I■1 C H 3 C H 3

79

841 Pale Yellow,

Viscous Oil

Cl 0 F

89 \--A NA-Ve S(1%- F

F F H 3 C)

842 White Solid 12

11 3 C .

392

17149

843 White Solid 42 CI 0

1■/—,

* N

N • H 1.1

844 White Solid

F

CI 0 /3/4--•4*-- F

Nk_ ,--C—S ■.. ItIr 11

42

845 Colorless Oil

N----..(C1

o

1/4-- INI FF

H3 C

AS'e•-'1(

) F 89

846 Opaque,

Viscous Oil

Plz..-leCI

0 F F

‘. I‘I)L-VS)Cr F F

H 3 C) 89

847 Clear,

Viscous Oil

I-1 3 C

CI 0 0

INIA S

H3 C)

89

393

17149

848 White Solid

CI 0 F

F N riC F

CH 2 89

849 Clear,

Viscous Oil

Ptt(CI

0

89

F F

‘•NjC.S )CIC F F F

H 3 C)

850 Opaque Film

a 0 F

fl —N iCIC F

SF F 89

851 Light Yellow

Oil

FuF CI-1 3 0 /-.../-- F

NS_ ,--T—S b H 3

12

852 Light Yellow

Oil

F F CH 3 0

NS_ ,---7—S 14 / N

■ )

H 3 C

12

394

17149

853 Light Yellow

Oil

F F CH3 0 /.....)C F

12 th-N., t.,H 3

854 Light Yellow

Oil

F F CH 30

N-Sa ,----C-S 14 / N

) H3 C

12

855 Light Yellow

Oil

Cl F F

12 N51‘1% 1

H 3 C

856 Light Yellow

Oil

F F 30

,--7--S 145-N

■ S )

H 3 C 12

857 Brown Oil

F CI 0

F>L4C H2

,.....r- S NS_ iti / 11

1—CH 3 89

395

17149

858 Opaque,

Viscous Oil

Cl 0

/ /%1S.%r F

F HC)

89

859 Clear,

Viscous Oil

CI 0 CI

F

H3C) 179

860 Yellow Oil

F F

CI 0 rie-F

N "...y-S

1.4 / N IC H 3

12

861 Dark Oil

F F

CI c) ril-F

N-k-- )\--7-0

H3C)

171

862 Yellow Oil

F F

Cl cl, o rie- F Tfr ,-.../1

I-13Ci

91

396

17149

863 Light Yellow

Oil ■

N.5..CH3o:Lr

14 / N 1C H3 12

864 Yellow Oil .,,

CH30 F

N--S. ,---/—Sr I

N / 1`1,,, %A-1 3

F

12

865 White Solid ,,

H 3 C 0 CI 0 lin

,

N-S.. N / 1%1%

i H 3 C

170

866 Clear Yellow

Oil

H 3 C 0

Cl 0 NanSr--"C7 VS_ ‘1,—( b N / Li CH 3

H 3 Ci 170

867 Brown Oil

■

9 ci 0 N S_)--c 6 14 j .. F

' V...r Li - ..3F

CI

ci 149

397

17149

868 Liquid

ct Br O1-.-N

11

.,„ / H 3 C., sN i' l

CH3

869 Pale Brown

Solid

B

0 Cl r

/ \ H 3 C N 's CH 3 CH 3 11

870 White Solid

F F CI

N

NS_ ,--C—S

•••• H 12

871 Yellow Oil

F F

CI 0

V*,— 1,FrS ■ N.,1 - i F F

Or\._ /JCF S

12

872 White Solid

F F

CI s pie— F

. ,--- /4 /

raS NS N

H

49

398

17149

873 Viscous

Clear al

CI

vrA.N

A..„..".. S.---....X F F

\l'

F F

12

874 Clear

Viscous Oil

Cl 0

/ N jL-VS )C F

F

F 12

F F F

875 White Foam

CI 0 F F

N VNXVIC F HO OH 89

876 White Cloudy

Viscous Oil

CI 0

12

CH 3

877 Orange Oil

CI 0 0

......}1.. -\;: tsirj S CH 3

) H 3 C 151

399

17149

878 White Solid

CI o

. CI

89

879 Cloudy White

Viscous Oil

N00 F F

N)L.SC F

\ F

12

880 Clear Yellow

Viscous Oil

CI o

12

881 Light Yellow

Solid

a *

CH s , 3

N- ---ta a / N 14 S

.

H 49

882 Brown Oil

Cl 0, N-5 ,---7-- 14 / N

\

H3 C)

F / F

89

400

17149

883 Light Yellow

Oil

CI co NS.

■ /4 i N

) H3 C

\

89

884 Yellow

Viscous Oil

Cl 0 F F

\- 1•1)L-5.)( F cr,C H 3

CH 3

12

885 White Solid

Cl 0 CH 3

N,---7-1.' 0

H 51

886 White Solid ■

CI 0 .CH3 N— 0 /4 / CH 3

51

887 Yellow

Viscous Oil

Cl 0 F

F NJC. -)C S F

0-C H3

12

401

17149

888 Clear,

Viscous Oil

., Cl r:----( 0 9. 9 \--ThsljL7% ' N S i< FF

H3C) CH 3 F 149

889 Pale Yellow

Oil

Cl 0 F F

NiC-7.%S.)( CH 3

H 3d 152

890 Pale Yellow

Oil

Cl 0

H 3 C) 145

891 Yellow

Viscous Oil

Cl 0 F

F evf- NiL7 S IC F LvEs.,. F 12

892 Light Yellow

Viscous Oil

Cl 0

/ N

12

402

17149

893 Clear Oil

pz....rCI 0 F F

\-AN-iys,-,7kF

H3 C) C H3 102

894 White Solid

F F H 3 C

W OriCF Cl 0 a g

N ,---/ b

> H 3 C

170

895 Clear Oil

F p 11 3 C0 V

Cl 0 _gr- F

, - i 170

- - b N N)

H 3 C

896 Yellow

Viscous Oil

CI 0 F

.A.._.e F N . s..e.„...kF

CH 2

106

897 Light Orange

Viscous Oil

0 F n-ccCH, NjC. S

F F

1) C H2

106

403

17149

898 Clear Oil

F F 0-k

CI 0 Srj F N— ,--/— 14 N

H3 C)

89

899 Pink Semi

Solid

F F

Cl co W.a ge--Ar

li15_12—/ a b F N / "k

H 3 Ci

170

900 Clear

Viscous Viscous Oil

Pitzf CI

0 F F

C -- N

106

901 Clear Oil

Przr CI

0 F F

N.-- NiL'SIC F

) H 3 C 102

902 Oil

Pale Orange

ishz.(CI 0

S.N IC FF H3 C) F 102

404

17149

903 Clear Oil

CI 0

\ F jYS 'V V( FI

H3 c,) C H3 102

904 White Solid

N00 F

Nic.-.. s..........k

F F

-, 0 )0 JeCH 3 H3 CCH 3

106

905 Light Brown

Oil

F F

Br 0 ri-F

,...../-S I■15- N / N;,

1/4. H3

79

906 Clear

Colorless Oil

F F ry-F

Cl 0 89

TS"- N / P

_,,, k CH 3

H3 C2

907 Clear Oil

F F

CI 0 lie- F

N--r-c ,---r-S

H3d

11

405

17149

908 Light Yellow

Oil \

Cl 89

43 N-S. ---7- /■/ / N

H3 C)

909 Light Yellow

Cu \

0

CI 0 # NS. ,--r-S

/4 / N

H 3 d

89

910 Light Orange

Oil

F

Cl 0 0--F

v__.{ ,.._/"- S NI - 1`1‘

) H 3 C

126

911

F F

42

Br 0 S / NS_ ,--r

/4 / 1%1 CH 3

\

912 Clear Oil N

Cl 0

\.--..A. NiLy■ S H3 C)

151

406

17149

913 Clear Oil

CI 0 OCH3

N S LOCH3 89

914 Light Yellow

Oil

FuBr Cl0 r.../"-F

ii.A ,___/"-S

NJ-Nk "- CH 3

89

915 Clear Yellow

Oil

F F

CI SriF b 51

CH 3

çí H 3 C

916 Colorless

Gum

F CI CI 0 F

N5._ ,—/-- :, / N ■ '1 LC H 3

89

917 Light Yellow

Oil

F F

CI 0 rfiF

175_

N / 1st i

H 3 C

,.-

89

407

17149

918 Light Yellow

Oil

F re- F

CI 0, 194 N-- iii / IN1)

H3 C

919 Pale Yellow

Oil

Nr.:(CI

0 F F

vs:ANS .Y1C F CH 3 H3C)

143

920 White Solid

CI Parf 00

SN.7 ic F F

u c,) CH 3 F 11 3

52

921

Tacky,

colorless

solid

CI Ni joLly

N SN.7Nic F

F ) F

H3 c CH 3 51

922 Colorless Oil

F F

CI 0

N5_ , N

Oh . -- CH 3

43

408

17149

923 Clear Oil

CI 0 CH 3 F F

\ NiL.V. YL)C F

H 3 C) 89

924 Clear

Colorless Oil

F F

Cl 0 sril-F

Nt- /--<41-N

,--r0 4C H 3

51

925

Viscous

Slightly

Yellow Oil

CI 0 F

F NjC-VS71CF

OtO

CH 3

106

926 Pale Yellow

Oil

CI 0

/ \ Dec F

N)L-fl-N

VS F

H 3 C) 152

927 Pale Yellow

Oil

Nt:(CI

0 F

N NSF

H 3 C) 153

409

17149

928 Yellow

Viscous Oil

CI 0

N 110

929 Clear Oil

CI 0 007a,

N 11 C H3

H3C

149

930 Yellow

Viscous Oil

Cl 0 F

N.Ice.s.e.......-k

F F

F

106

931 Slightly

Yellow Oil

CI 0 F

N.k..7.s.e...7k

F F

C1 21 ‘

\__,

106

932 White Solid

F F 0 ry—F

CI 0. „re NS. ,---/ ' 16 14 / N

1CH 3

91

410

17149

933 Clear Oil

cr CH 3

CI 0

N— ,--/—S TO—N

H3 C)

89

934 Clear Yellow

Oil

F F

CI s ri-F

"--/—S lil .._-- ? -;_ c H 3

49

935 Clear Yellow

Oil ■

F F

CI s rif--F

lit *ThFrs

i 1-1 3 C

49

936 Pate Red Oil

CI 0 0 .0

) C H3 1-13 C

149

937 Opaque Film

/ CI

0 (It 9

149 CH 3

411

17149

938 Opaque Film

• CI

0 00

N)L N&%ICF

ell 3 F F 149

939 Clear Oil

/

CI 0

H3C

o p

II CH 3

* 149

F

FF

940 Clear Oil

CI

N

H3C )

0 0 0

lir H 3 C a

4 149

941 Clear Oil

CI 0

H C

q• 9

IIC-H 3 40 149

942 Clear Oil

CI Ni 0

N

H 3

ck P

C

o .0- 149

412

17149

943 Clear Oil

ci 0 012 4

F

N N°

H 3 C) &I3

149

944 Opaque Oil

CI 0 o. o

l‘rj NI .SYAN-C H3

H3 C) CH3Nrd

0

00

149

945 White Solid

CI

H3CN

N' 61-1 3 * ,CH3

erb 149

946 Clear Glass

Cl o N

6"6 52

947 Clear Glass

CI 0

■ N

0 5 1 H 3 C)

413

17149

948 Yellow Oil

F F

F CI 0 F

N-5 ,----7- F

H3 C)

89

949 Colorless Oil

Br

F Cl 0

N-5 ,---,- 14 / N

) H 3 C

89

950 Yellow Oil

0 51Cl

F 106

951 Oil

Light Yellow

F F

Br 0, j—/F

N -S.. 14 / N )

H 3 C

79

952 Orange Oil

/

F F

Cl 0

N 106

414

17149

953 Yellow Oil

CI 0

Cl

106

954 Yellow Oil

/

CI 0

N S F 106

955 White Solid ..

CI 0

1■1— S-C 113 N / 132

956 White Solid

C' 0

.

,c H 3 /

8 50

957 Colorless Oil

F F ry- F

Br 0, j--S, 0 N -S_

is, i 14

H 3 C

)

51

415

17149

958 White Solid

CI 0

\ N

* H 3 C

106

959 Yellow Oil

F F

F

89 CI 0 111

/16-1 1̀‘ /

1-1 3 C

960 Clear Yellow

Oil

F

89

CI 0 . N-

14 / N

H3 C)

961 Clear Yellow

Oil

/ \ 4-- F N—

7sr0----/

N F 14 / N

)

--..

H 3 C

89

962 Colorless Oil

CI 0 1‘13... y-CCo 14 / N

) H 3 C

89

416

17149

963 Light Yellow

Oil

F F F

Cl so F

N

■. ) 14 3 C

89

964 Opaque Oil •N S F

0 H3C)

51

965 Off White

Gum

MC F

C I 0 d isl-rf-F NS_ ,■/-:t

11 / N w F

4 )

H 3 C 178

966 Colorless Oil

F CI r::• F

1■15_ ,----7- FF

■ N / N‘

H3 CI

89

967 Colorless Oil

CI Cs Fric;

F

Br

N- ,---7-S ki--N

) H 3 C

89

417

17149

968 Clear

VISCOUS Oil

A0 8. C H3

LC H 3 115

969 Clear Yellow

Oil

F F

CI s , riLF

51 NS_ /4 / N

çí ) H 3 C

970 Cloudy White

Oil

14=-(CI

0

N \ NAO SICE. FF LC H3

115

971 Opaque

Viscous Oil

Pz---(CI

o F

N. i'L/S■)C F N F

H 3 C) 12

972

Light Yellow

Clear

Viscous Oil

o r

0 .... j/.. e t F

N .. er 0' F L C H3

115

418

17149

973 Clear

Colorless Oil

*F

12 CI 0 N— ,----/— 5 TZI / N

> H 3 C

974 Off-White

Solid

Cl 0 F

L C H3 115

975 Colorless Oil

CI 0 FF

N-5 ,---/— b 14 / N

H 3 C cx ) 50

976 Colorless Oil

CI 0 Sr-r F" N— . F

1 0 NS ‘ . i

H 3 C

50

977

Slightly

Orange

Clear

Viscous Oil

Cl \ P:--( 0

v .F v N Cee%ri .

CH I F L C H 3 a 115

419

17149

978 Pale Yellow,

Viscous Oil

CI 0

\ N

0=,L d C H 3 149

979

Slightly

Viscous

Semi-Solid

Yellow Clear

CI liz---7 0

F

L i, 0 F .._. • . 3

113

980 Colorless Oil

H 3 C

Cl 0 k-C H 3 N— .---/--S O—N

■ )

H3 C

89

981 Opaque,

Viscous Oil

Cl 0

N H3 C

) 8 51

982 Clear

Viscous Oil

CI 0

N 8 83

420

17149

983 Dark Orange

Oil 89 113„ T‘Fr

N / .‘ F F

H3 Cl

984 Light Yellow

Solid

Prz(CI

o F

\-- NA /%1 --"rtF

H3 C) F 116

985 Colorless Oil

CI le 0

N F

H3 C)

156

986 Colorless Oil

P19,CI

o /

\I•IjCr Fr 61-1 3 CH 3 F " 102

987 Clear Oil

Cl Nzze 0 F

‘1"k /%1jY F F 611-13CH3 102

421

17149

988 White Solid

Cl 0

111 N

N'40

H 3 C)

989 Light Brown

Solid

1%6(0 0 F

N hr S F

H3 C) 116

990 Light Brown

Solid

Cl 0 F

NN S F

H 3 C) 116

991 Yellow Oil

iNFF c ,.....v

hi CI 0 IF

N---(-- ,---/— S /4 j--N

H3 C>

89

992 White Solid

kr CI 0 0 0 I'Ll.

N)Y1C F 611 3 C H 3 F F 52

422

17149

993 White Solid

CI Nzi 0 9

14‘Al■liYSF

F

CH 3 CH 3 F 51

994 White Solid

N Cl

•..*N s 'N.. C F a H3CH3 52

995 White Solid

I • 1, . % C I 0 9

N .„. N jLrsies

aillft3CH3

F

F 51

996 Semi-Solid

Light Yellow

Cl

H3C) F 116

997 Light Yellow

Semi-Solid

Cl

\ ...\ANANiestF

) H3C

F

CH3F 116

423

17149

998 Yellow Oil

CI o

89 i;i —N

H3 C>

999 Light Yellow

Viscous Oil

NztfCI

0 F

\-- NA'N'.%%'' S-•-71.-F F

11 3 C) 116

1000 Clear Oil

F

115 N Oe .V. Sr F LC H 3

1001 Colorless

Gum

F F F

Cl 0 89

1■15-- 0 CH 3

N f isi)

H 3 C

1002 Colorless Oil

CI CI 0 ,-....,

N.—A ----7—S

) 11 3 C

180

424

17149

1003 White Semi-

Solid

Cl C'0 r--/ N— —/.--- 6

■ 14S- N

H3 C)

50

1004 Brown Oil

CI 0 vr,A ss 2

■ NJ-1\1x 1

H 3 C 127

1005 Light Yellow

Gum

F F

89 CI 0

1■1— /

H 3 C

1006 Opaque,

Viscous Oil

, CI os 9

•--'N)L7"Nes- c11 3

11 3 C) 149

1007 Orange,

Viscous OH

CI 0

00

NiL-"% N' S's CH 3

H3 C) L

C H3 149

425

17149

1008 Light Yellow

Gum

F F F

89 CI 0

N--

LNJ " )

H 3 C

1009 Light Yellow

Oil

Cl

Nilli— Nt—C-

S

f H 3 C

89

1010 Colorless Oil

CI 0 /.....ra N-5 ,----71 IZI / N

) H 3 C

50

1011 Clear Oil

F F

FH30 riC-F

/4-1%1

I N 1CH3

106

1012

Colorless,

Tacky Semi-

Solid

Cl 0 0 \ Nc..), N

iCrS- C H 3 6113CH3 51

426

17149

1013

Yellow

Viscous

Oil/Semi

Solid

Fr riC-F

plio N -N

>...../--S

I N ..

106

1014 Orange Oil

Nr..... 1 CI 1/4,14

156 Nt-le 0 \

•-• 'Isl-k.%-S

H3 C)

1015 Light Brown

F F F F

Cl 0 FF CH

3( i N N 136

Gum N k / H

) 0 CI 3 C

1016 Light Yellow

Oil

F F F

CI 0 CH3

Si 136 N-S..

11 3 C

1017 Yellow Oil

,C H 3 0...Z11 0 F

INI— NiS 106

,c),.F

CV

427

17149

1018 Clear

Colorless Oil 89

CI 0

CH * N— /4 / N

I-13C)

1019 Yellow Oil 89

CI 0 110 N— F

/ N 14 0—E F

H3 C) F

1020 Clear

Viscous Oil

F F

ore Fll3 O.,

N-N >\----/ b I N

-. 84

1021 Yellow Oil

F F

CI 0

• 89

NIS-3r x N /

H 3 C

1022 Yellow Oil ■.,

H 3 C

89

Cl 0 110 F N— 74 / N

) H 3 C

428

17149

1023

Clear

Colorless

Semi Solid 14 .

0 *

180 CI c•

j—N

H3C>

1024 White Semi

Solid

H3C)

`■

CH3

180

HdC S N c H 3

CI ID s ,---/—

1025 Clear

Colorless Oil

\

180

ilfr Cl sp

NS_ ,/— CH 3 14 / N

H3 C)

1026 Clear

Colorless Oil

•-..

180

p CI so

N-5 ,--7—

H 3 C)

1027 Orange Oil

%...

180 CI 0

1■1-57‘1,-j— N / •

H 3 e

429

17149

1028 White Solid

r jCF3

CI 0 181

(+)- /

I HC"

1029 White Semi-

Solid

c/CF3

CI 0S, '0

181

(4- / Cr H)

,

1030 Colorless Oil

H3 C

CI 0 C H3

-. Nt'N‘

H3 Ci

180

1031 Colorless Oil CI 0 /---A

H3 C)

180

1032 Colorless Oil CI 0

N -K-- ,---7-S fk,-N \

H3 C)

180

430

17149

1033 Off-White

Solid

CI 0 N-5 —.S ---/

/ N ■ )

H 3 C

\ F

180


N— i;1 / N

) H 3 C

\ 180


N-S. ,--C-S /4 / N

) H 3 C

1

180

1036 Yellow Oil CI 0

■ N / I"( 1

H 3 C

F

\

180

1037 Colorless Oil CI 0 NS_ —/— 14 /

,- N )

H 3 C

4 F 180

431

17149

1038 Colorless Oil

* F

CI 0 N-5 ,--7—

/ N /4 )

H3C

180

1039 Colorless Oil

F F

F

4 Cl 0

N— S ' / N

H3 C)

180

1040 Colorless Oil CI 0 ri)

N— ,--C—S N 16--)

H3 C

180

1041 Colorless Oil

C H3 CI 0

N-5 . ---7.—S /4 / N

H3 C)

180

1042 Colorless Oil

CI 0 r•S:,C H3

180 /45- N

H3 C)

432

17149

1043 Light Yellow

Oil

Ph CI 0 P-S; NS_ is 0

0 ■

74 / N

El 3c

180

1044 Colorless Oil

0,9 ask a 0 r....

71117S-1,—/--S lir

H3 C)

180

1045 Colorless Oil

0,9 at a 0

-N /-S V 74 .S-N

ç í- H 3 C)

180

1046 Colorless Oil

0 ,0

1,, Cl 0 rd 3

N- ,-- f-S 745-N

> 14 3 C

180

1047 Colorless Oil

C'0 * N-

74 / N )

14 3 C

180

433

17149

1048 Ught Yellow

Oil

CI 0 N3

N ,—/-- 14 / N

LNdJ >

H 3 C

180

1049 Colorless Oil

H 3 0.0 H3c

4 Cl ID

1■15_71/4,,--r N / Li H3 d

180

1050 Light Yellow

Oil

r N

Cl 0 N-4 ---..

I■15 _ ,-7--S//

• CH 3

N / Nit

H3 d

180

1051 Colorless Oil

do

N.d— NI

H3 d F

180

1052 Colorless Oil

s.,; 9 do F

N 180

■ gi / N )

H 3 C

434

17149

1053 Pale Yellow

Oil

CH 3 0

OH

N F

H ) 3 C

156

1054 Light Yellow

Oil

F r fil--F

9130 N—N

I N

CCH3

106

1055 Pale Orange

Oil

CI H C 0 3

N 56

1

1056 Clear Really

Viscous Oil

Fr CF

83 FH3 0

N—N ....../,--s b

I N LCH3-,.

1057

Clear/White

Viscous

Semi-Solid

Fr

pi() t

■. N

L-CH3

84

435

17149

1058 Clear Semi-

Solid

P-130 N-N

N brt3

106

1059 Light Yellow

Gum

F F

89 CI 0

N- 14 / N

) H 3 c

1060 Yellow

Viscous Oil

c N-N

H3 0

I N \---CH3

106

1061 Clear

Viscous Oil

F F

FH30 N-N 6,--/—s%

I N ‘---cH3

83

1062 Orange Oil

Cl 0 S *

89

IS" F

■ F F /

H 3 C

436

17149

1063 Yellow Solid

0 CH3 Cl 0 %% ,......e. NJ )\— Nr--C % C H 3

/ 1sh!

CH3LCH 3 174

1064 Faint Yellow

Oil

Cl 0 CH 3 NS_ )\--N r—S. 14 / N k_

. CH 3 CH 3 174

Y2000 Colorless

Solid

CI 0

1

t_fl

1■11-5 CC H 3 ■. H3C

i 100

Y2001 White Solid

F F

CI

, ii CH 3

H3 C1

196

Y2002 Gummy

White Solid

CI 0

iii-- ,--0 N / 14%

H3C) 12

437

17149

Y2003 White Solid

CI 0 OH 1■15_1—<

CH 3

H3 C1 124

Y2004 Yellow Oil .■

,-," H 3 H t.,n3cC ci y_cii

N— )\--0 3 IV / 11

Y2005 Yellow Oil

H 3 C ell

CH 3ij ye ll

V— --0 3 N / 1̀ 1‘

F ( CH 3

31

Y2006 Yellow Oil

CI s3 N-- .-C ,—S

Br

Nst- N,_ F F CH 3 100

Y2007 Light Yellow

Gum

Cl 0

N

H3 C) 100

438

17149

Y2008 Ught Yellow

Oil

C I 0 Hes40 N. .-5. )\-..< t• 14 / 1%1% CH°

H3 Ci

3 125

Y2009 White Solid

a 011 3C CH 3

/ N -. t H3 12

Y2010 Faint Yellow

Solid

N

ICH3 CI

N— i -CH3 i N / NH 175

Y2011 White Solid

H CI Ns

"--CH 3 / N

.CH 3 175

Y2012 Yellow Oil

CI 0 rCH 3 ri.-3_ N ky / N CH 3

■ " .CH 3 195

439

17149

Y2013 Brown Solid

CI 0 CI 1■15_ 7sH

■ CH 3 100

Y2014 Yellow Solid

do eN

1■1-5 )L-7 N / n i

te H3 12

Y2015 Light Yellow

Solid

a 0.

_ --7

V5

N

■. N / N‘ /

H 3 C 12

Y2016 Light Yellow

Semi-Solid

Ci 0

._ CH I ■ CH 3 - 12

Y2017 Light Yellow

Semi-Solid

CI o

■ N.S— Pt CH 3 1

113C 12

440

17149

Y2018 Oil

Light Yellow Yellow

CI

N CH 3 12

Y2019 Colorless Oil ■

CI 0

P—N S 1-1 sili' b H 3 87

Y2021 Light Brown

Oil

H C CI ot •a3 . 8

11-5Ny-iF

N t bli3 198

Y2022 Yellow Oil

Cl 0

42 N% i

113C

Y2023 Yellow Oil

ti

Cl 0

Nr-c

1%1

k-;

42 1-13C

441

17149

Y2024 Off-White

Solid

CI 0

42 V .... ky / six CH3 ■ 1 H3C

Y2025 Yellow Oil

Cl 0 \

o / ) CH3

H 3 C 42

Y2026 Off-White

Semisolid

Cl 0 N Nttl

Ii15_ '--7- \--j / N b H 3 42

Y2027 Off-White

Solid

C 045

42 N CH ■ 4CH 3 3

Y2028 Light Brown

CI 0 \ I

42 Semisolid

V — , x, Nml CH3 i

CH3

442

17149

Y2029 Yellow Oil CI 0 411

11 VS ±S

H3 d

Y2030 White Solid

H 3 C

C'0 )--CH 3

N / ist

H3 e

11

Y2031 White Solid

Cl o r(C H 3

1■1-5_1"-S CH 3 N / -

C H3 ) 11

Y2032 White Solid

CHB q N-5 ,-NnO /4 / N t...1

■ li

163

Y2033 Brown Solid

CI o CH3

Nr" ,--r‘o /1 j-N ■ .C14 3 40

443

17149

Y2034 White Solid

0 CH it.

1;13._ , - N. 9 N / cc H 163

Y2035 Light Yellow

Solid

CH3 / 0 CH3s a

N-5, .....Nr-'0 164

Y2036 White Solid

F F CI 0

NIS- N., 5/ L.H 3 12

Y2037 White Solid

F F a 0 JCF

N- 14 / N

H3 C)

12

Y2038 Colorless Oil

do

I,

F

12

444

17149

Y2039 White Solid

CI H 3 C CH 3 0 v

NS_ 14 / N 14

Y2040 White Solid

H 3 C CH 3 CI 0 y_c H VS_

N / N?

? F

14

Y2041 Light Brown

Solid

t N#

Cl FIN N ----.(1 i NH N

175

White Solid Y 2042

CI 0 Ni...11—<1

N ° CH 3 12

Y2043 Clear Oil

CI 0 IzI-*_)---1 N.., ‘......1

12

445

17149

Y2044 Yellow Oil

CI 0 CH3

12

INI -5/ N. CH 3

Y2045 Clear Oil

C 0 CH 3

IS -- ■. N /

12

Y2046 Yellow Oil

Co N-

N, CH 3 12

Y2047 Clear Oil

Cl o N—

12

Y2048 White Solid

r-CH CI N 3

S / N

CH 3 45

446

17149

Y2049 Yellow Oil

rCH

CI N 3 N...5 ,...1-CH 3

14 / N \ b H3

177

Y2050 Yellow Solid

CI 0 C II 1■15_ 7%fr 3 N / • i ■ 1

H 3 C 11

Y2051 White Solid

H 3 C cH 3 CI 0 v /—C

N....1— N 14

Y2052 White Solid

Cl N-

• /4 / N SH

■ ) CH 3 H 3 C

87

Y2053

Salmon

Colored

Foam

CI N— CH 3

■ 14 / N .,0

••.. 411%"c-, 0 CH 3

140

447

17149

Y2054 White Foam

CI N- C11 3

%. /4 / N

•

0 .cCO

0 Ils-• CH 3 140

Y2055 Light Yellow

Oil

H3C CH3 a °

$ oY-CH 3

,-- V _ N N /

...FF

F

14

Y2056 White Solid

CI 0

/ 11

Y2057 Yellow Oil

C'0 TI.--5.11-1

%. N H 3 C-0)

14

Y2058 Yellow Oil

CI 0

/ ‘ ■ 0

1 14

IP

448

17149

Y2059 Yellow Oil

do ils:1175.1-1

o)

0

0 ( CH 3

14

Y2060 White Solid

C'0 t.I5.11-1

.■ N f % o—C H 3 0 14

Y2061 White Solid

CI op

14 ■ C

CH 3

Y2062 Faint Orange

Oil

H C CH CI 0 3 y..c II 3

Ni 0-- N.!-- e H 3 F

31

Y2063 Faint Yellow

Oil

H H CHD 3 C C 3i

1;! ._ N / N b H3

F 31

449

17149

Y2064 White Semi

Solid

Cleat/ CI 0.

NS_ N, N-N

■ H3C1

H36 11

Y2065 Yellow Semi

Solid

Cl 0 N— IV / N.

11 ,..,

CH 3

Y2066 Yellow Oil 3 CI 0,5

ISS 11

Y2067 Clear Oil

H 3 C cH CH30 >cal

N—

F *

31

Y2068 Yellow Oil

H 3 C

Cl 0 it N— N 14 / ,_ ... ell CF3

3 11

450

17149

Y2069 White Solid

CI 0 N

VS--N \ 14 rt4 N %,,....... 3 H3 6 H 3 C 11

Y2070 Yellow Oil

CI o3

N

■ N31, \ 14 CH3 H 3 L; H 3 C 11

Y2071 Light Brown

Gum

CI 0 1/5_ ,Th (F F

42 1\1) N / F

H 3 C

Y2072 Brown Gum

01 0 CI

I■1 5—, NM (F

F 42

N • ) F H 3 C

Y2073 White Semi-

Solid

S. 3 CI ct

53

/43. / N d

■ ) N / H 3 C

451

17149

Y2074 Yellow Oil

CI 01 ISK -- N * CI 14."-- N_ ,

CH 3L

CH 3 174

Y2075 Clear Oil

CI n 3— H IV-3_ ,--S.0

■ H3 d

11

Y2076 Clear Oil

CI 0 CH N ,—S. 3

■ ‘.—C H3 S 11 3 C

166

Y2077 White Solid

CI ip a

NV-5/ 1—C—CH .. ,..

H3 C>

100

Y2078 White Solid

CH3 0

N ,----CH3 / N NH

11

452

17149

Y2079 Yellow Oil

I 1%1*

,N

n 0

)\---

N

N/ N

CI o sip

/ N Lnu L.41 3

bH3

174

Y2080 Yellow Oil

0H30

,

)\--0H3 N N

11).

14

Y2081 Yellow Oil

0 C'0 1■15_ N

--, N / I‘L H3LC H 3 174

Y2082 Yellow Oil

C 0I 0 t_ ,C H 3 NS. ,--isrThCH3

1:4 / /1 CH3 ■ CH 3 CH 3

174

Y2083 Off-White

Solid F

CH3 S

N -- )\—r.14 ......3 / N / N 49

453

17149

Y2084 White Solid

Cin 0 c) Ln )....N, —CH3

/ , m N f . L ■_ CH3

UH3

174

Y2085 White Semi-

Solid ■

0 CH

CI 0, ,.4. 3 N-S. ,----/ IN

14 / N g

> N'' H3C

53

Y2088 Yellow Solid

n 0 CI c) %-ii/

--Ikt---- C

CH3 ‘CH3

174

Y2089 Dark Yellow

Oil

r, 0 CI is, N Cl

N ,--1‘1' \ I 4 , N CCH3

bH3

174

Y2090 Brown Gum (3 CI 0 N

/.6._ , —I

H 3 C/

148

454

17149

Y2091 Gum

Light Brown

INI

CI 0 la

■ '1 H3C

) 148

Y2092 White Solid

CI NS_ CH3

N 0 14 / ,N II CH 3

0 r 1; 141

Y2093 Light Brown

Solid

CI 0 ,....f-SH

j, / N IN )

H 3 C 87

Y2094 Opaque,

Waxy Solid

CI 0 NS_ 1.4 / N

) H 3 C

159

Y2097 Opaque,

Viscous Oil

Ncr isIJCV. CI 513 100

455

17149

Y2098 Bright Yellow

Solid

Cl 0

Nv/AN)L*CH 2

a H3 159

Y2099 White Solid ■

0 CH

CI 0 'W 3 NS_ siiN H 2

14 / N

H3 C) 0 128

Y2102 Colorless,

Viscous Oil /

CI 0 0 p

td)L.N:S:CH3 7 H CH3

146

Y2104 Light Yellow

Semi-Solid .■

.CH 3 Cl 0

/ N CH 3 CH

I.: =N

‘ 3 53

Y2105 Light Yellow

Semi-Solid ■

Ci 0 .0 H 3

14

NtiSr N,_ C H

s

3 —N CH 3 - 53

456

17149

Y2106 White Solid \

CI 0

NANH

H3C) cH3

45

Y2107 Faint Yellow

Oil I

Cl 0

42 N

H3 C)

Y2108 Yellow Oil

CI 0 \

42 N >

H 3 C

Y2109 Yellow Oil N 14

C'0

1H 3

S N'S

CH3 42 N

H 3 C

Y2110 Yellow Oil N 14

Cl o —

0. CH3

42 / N )

H 3 C

457

17149

Y2111 Yellow Oil

Ci 0

N— 425

■ 14 N

> H 3 C

Y2112 Faint Yellow

Oil

Ci 0 11,

42 j—Nx F-7(

H3 C1 F F

Y2113 White Semi-

Solid

0, CH

Cl 0 ig 3

IS — „, =N

N.. -- LI CH 314 — -. CH 3 53

Y2114 White Solid

0 CH CI 0 3

N—

53 '11—eN

14 / N_ 0-13 ... CH3

Y2115 Pale Orange

Oil

CI pit( 0 .,A Niyc H3

til 3 CH 2 159

458

17149

Y2116 White Foam

Nzt-(C1 N

O N

--\ - isliLC S% CH 3

H3c) CH3

53

Y2117 White Solid

CI \ Przi 0 9, 111•1-e'N

\--- NiCr S% CH 3 u r,) CH3 L. 3 .-

53

Y2118 White Solid

CI 0 k./ VS_ ,---/ IN

■ H3C

/

12

Y2119 Colorless Oil

CI 0 N--(-- ,---7-NL,

H3C) 12

Y2120 White Solid

rr.N\ d I 0

V -5_, tsfr .. N . - k

H3C1

12

459

17149

Y2121 White Solid

CI so N ,---/–N\r„,1 N-5

) ■

/4/ N

113C 12

Y2122 White Solid

rrNi)

CI 0 s N

,--/N

eg S_

14 / N \

H3 C)

12

Y2123 Colorless Oil

d o N N

14S-N —N \

H 3 C) 12

Y2124 White Solid

CI

N21 1 / N CH 3 5

N H k ) 0 c H 3

IN1'

11

Y2125 Off White

Solid

CI

w-Sil ,/, / N Cl,„"y" >Th_

tt. 0 cF, N

11

460

17149

Y2126 Off White

k )

N'

Solid

CI 0, j—CF3

N-S_

Y2127 Yellow Solid H3 C••0

\ H CH 3

,.....,y NyLC H3

IA 0 a

11

Y2128 Off White

Solid N

F3C_1i 0

Cl

\ 74 O

' L 0-1 3

11

Y2129 Ash White

Solid

H3 C Nrzi

CI 0

\ I‘IjL(CH3 H r ti .3

11

Y2130 Yellow Solid

H C N,

W CI 0

N 11

F 11 / \

461

17149

Y2131 Dark Brown

Solid

CH3 L,i CI O

CH3

\ A.-- - Nt H3

.1%1=Sy

CI

79

Y2132 Off White

Solid

CI CI

79

141%1 Lt 0

\--A N ell3

Y2133 Brown Solid

CI 0 C H 3

N.--_ H Itl / N CH 3

Br...r.i. " C H 3 ne )

1%1

79

Y2134 Solid

Off White

Br Przf

CI 0

/

CH3 79

Y2135 Off White

Solid

\ / N ..11....r.C11 3

H 3 C-0 a H 3 C H3 79

462

17149

Y2136 Brown Liquid

CI

/ •.1- /%1)LIC F

79 F H3 C-0 CH 3 F

Y2137 Brown Solid

CI

/ vf/A NAr.0 H 3

H C ell3CH3 79

Y2138 Brown solid

H C _. CI / \ , IsiNy

e H 3 F F 79

Y2139 White Solid

CI 0

Nr II 87

Y2140 Off White

Solid

0 CI

)--- N/

.,0 H3 CyLNA- " /

CH 3 CH 3 Br 79

463

17149

Y2141 Off White

Solid

F..,,,,11-1r--, \ / F

F CH3 Br 79

Y2142 White Solid

\ pttCI

0 j.„4„.cH 2

H 3 C) 159

Y2143 Oil

Clear Hard

CI

N— CI CH 3

) CH3 H3C

12

Y2144 White Solid

Cl 0 ciii

‘.. NAO,I<CH3 CH 3

11 F

14

Y2145 Clear Semi-

Solid CI

N i.L .N:s:CH3

H3C)

146

464

17149

Y2146 Clear Oil

Cl 0

\ N

CH3 150

Y2147

Viscous

Clear Light

Yellow Oil

Cl o CH3

1/4.A. A )cCH 3 N 0 CH 3

CV 14

Y2148 Light Yellow

Solid

Cl

N OH 117

Y2149

Slightly

Yellow Clear

Oil

/

CI

PIN. ...i. 0 ycli A

d

6._ ....H 3 N 0 CH 3

LI 0,t0

CH 3

14

Y2150 Clear Oil N

F F

CI 0 rrs

- ) H 3 C

465

17149

Y2151 Clear

VISCOUS Oil

Cl 0 CH 1

NO CH 3

OH

107

Y2152 Off-White

Solid

Cl C113

A jeuH 3 No 'CH 3

e tsI

\__/

109

Y2153 Clear Light

Yellow Oil

CI CH 3 A M H3

No CH 3

F

14

Y2154 Clear

Viscous Oil

Cl 0 Isir.:( F fl- \I•liC.Vr° ,.,,i,F

LC H3 0 F 114

Y2155 Light Brown

Oil

Cl 0 F A ,-,)< F

N 0 F LC H3

115

466

17149

Y2156 Light Brown

Oil

\ Pi rc(C1

0 F F

LC H3 F 115

Y2157 Light Yellow

Oil

PL-.(CI

0 F / \ NA IV.-k

F F

( CH3 CH 3

115

Y2158 White Solid

P--(CI

o F

N N F LC H3

115

Y2159 Light Pink

Viscous Oil

1•1-cf CI

o F /

N S F LC H3

115

Y2160 White Foamy

Solid

CI

\C-I‘IILI‘ll'F

L F C H3

115

467

17149

Y2161 Light Yellow

oil

o cili . ,....A A ,,ICLI13

N 0 CH3 Fy

F

14

Y2162 Clear Yellow

Oil

CI (:) CH 3 _

14

jccH3 N 0 CH3

F4)

F

Y2163 Clear Yellow

Oil

a y ,...e ID CH 3 / v/A A )<cH 3

N 0 CH3

Cl

14

Y2164 Clear Oil

/ No.fk A ,-■ 1,F N N T

CH 3 F CH 3

115

Y2165 White Solid

CI PI, I F F

F LC FI 3 115

468

17149

Y2166 White Solid

CI

129 NV-5/ N H

Y2167 Yellow Solid

CI 0 N 14 / S_ n- Na

Tsr 130

Y2168 Light Yellow

Solid

CI 0

1S -

5 CH 2 N / N n-

N 131

Y2169 Light Brown

Solid

CI

/ pIji

jccii 3 0 CH3

NnO C H 3

H3 C,

14

Y2170 Clear Oil

Light Yellow

Cl 0

LC H3 F 115

469

17149

Y2171 Light Yellow

Oil

CI o

•-, 1:1 / S_ N• CH3 12

Y2172 White Solid

r-......‘ a 0 N. N

■ Net N. CH 3

12

Y2173 Colorless Oil

CI 0 N,_

N . / N S_

C H 3 12

Y2174 Colorless Oil

Cl

NSK_/—N

V--N / N .

CH3 12

Y2175 Off-White

Solid

Cl 0

\---NA

N * L C H 3

45

470

17149

Y2176 White Solid

PzieCI

0

N)L. •• N

H 3 C) 42

Y2177 Light Yellow

Gum

F F F

CI 0

193 I■1 N— / N ■ ) H3 C

Y2178 Pale Brown,

Glassy Solid CI

\ 0

NiC7 r- Isl •N

H3C

142

Y2179 Light Yellow

Oil

F F F

Cl 0 SH 87 NS_

) H 3 C

Y2180 Pale Yellow,

Oil

Cl 0 00

N N'c H3 *Viscous 149

471

17149

Y2181 White Solid

4

42

CI,

1 7S.(NJLVVN \

a

Y2182 Clear Oil

CI 0

N e H3 42

Y2184 Light Yellow

Solid

Nt---(CI

0 0

NA N ti IN) I Ire

* 45

Y2185 Clear Oil

/ P1=1CI 0

H3C) 120

Y2186 Off-White

Solid

P-----(C1

o ‘..A

NA

N H2

H3C) 119

472

17149

Y2187 Light Brown

Solid

CI 0

N1/4---NA%.7r0H

LCH3 0 112

Y2188 Viscous Oil

Brown

N a (3

LC H3 0 123

Y2189 White Solid / \---

H 3 C

Cl ( o o

NA

N ) H

a ir CY

CH3

118

Y2190 Off-White

Solid

/

CI 0 NN,

‘. N N IS

) H H 3 C 1.

F F

0 F

118

Y2191 White Solid

,,, Cl nz--1 0 0

CY_ LNAN la j H

H3C' F

F

ir

118

473

17149

Y2192 White Solid , '

ci P- o o islA

N H )

H 3 C CI

* CI 118

Y2193 Slightly

Yellow Solid / \

CI 0 0 Nr-T(

v•-•A N

A H N

) H 3 C

IS CH,,

118

Y2194 White Solid \ PI-----(

0 00

vs•ANil

N

H3 c) H

118 *

Y2195 Tan Solid

C 0 _

I / cr

CH3

H 3 C 173

Y2196 White Solid

CI

/ 12

474

17149

Y2197 Yellow Oil

C F

/ N '•.r' F n ,..,) lir-

173

Y2198 Yellow Oil

C F F _ < OS

/ N T F

H3 C) C H3 173

Y2199 Off White

Solid

CI 0

N5_, 7?—eMS-CH i 14 • • i CH 3 -

H3Ci 197

Y2200 White Solid

ets1

CI 0 ki

1■15_7fr-/ N / • -,,,

L14 3 12

Y2201 White Solid

e.N CI 0 ki

12 V5_ ---1 / N

neN .dN

Table 2: Compound number and analytical data

475

17149

Corn-

pound

No.

MP

(°C) IR (cm-1 ) MASS HNMR NMR

596 73-75 ESIMS m/z

312[M+1]+

1 H NMR (300 MHz,

DMSO-c4) 69.04 (d, J

= 2.4 Hz, 1H), 8.60 (s,

1H), 8.49 (dd, J= 4.7,

1.4 Hz, 1H), 8.17 (ddd,

J= 8.4, 2.7, 1.4 Hz,

1H), 7.52 (ddd, J= 8.4,

4.7, 0.6 Hz, 1H), 4.30

(d, J= 2.1 Hz, 2H),

3.23 (s, 1H), 2.18 (s,

3H), 1.39 (s, 9H).

597

ESIMS

m/z 337

([M+Hr)

1 H NMR (400 MHz,

CDCI3) 58.97 (d, J=

2.5 Hz, 1H), 8.59 (dd, J

= 4.7, 1.3 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7,

1.5 Hz, 1H), 8.01 (s,

1H), 7.44 (ddd, J= 8.3,

4.8, 0.4 Hz, 1H), 4.44

(s, 2H), 2.61 - 2.43 (m,

2H), 2.43 - 2.33 (m,

2H), 2.30 (s, 3H), 2.26

(t, J= 2.5 Hz, 1H).

"C NMR (101

MHz, CDCI3) 5

192.20,

170.37,

148.49,

148.04,

140.21,

136.04,

126.23,

125.26,

124.16,

124.01, 78.59,

72.69, 38.69,

29.57, 29.26,

26.69, 11.14

476

17149

598

ESIMS

m/z 315

([M+H])

1 FINMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.4 Hz, 1H), 8.58 (dd, J

= 4.7, 1.4 Hz, 1H),

8.04 (ddd, J= 8.3.2.7,

1.5 Hz, 1H), 8.01 (s,

1H), 7.43 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 4.45

(s, 2H), 2.79(t, J= 7.3

Hz, 2H), 2.45(t, J=

7.3 Hz, 2H), 2.31 (s,

3H), 2.24(t, J= 2.5

Hz, 1H), 2.06 (s, 3H).

13C NMR

(101 MHz,

CDCI3) 6

171.73,

148.71,

147.93,

140.17,

136.09,

126.15,

125.41,

124.55,

123.99, 78.85,

72.51, 38.35,

33.80, 29.57,

15.96, 11.20

599

ESIMS m/z

283 ((M-

SMe+Hr)

1 H NMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.5 Hz, 1H), 8.58 (dd, J

= 4.7, 1.4 Hz, 1H),

8.04 (ddd, J= 6.9, 2.7,

1.5 Hz, 2H), 7.48 -

7.38 (m, 1H), 4.47 (s,

1H), 2.88 (dd, J= 12.7,

9.2 Hz, 1H), 2.77 (s,

1H), 2.44 (dd, J= 12.8,

5.1 Hz, 1H), 2.34 (s,

3H), 2.24 (s, 1H), 2.01

(s, 3H), 1.14(d, J= 6.7

Hz, 3H).

477

17149

600 89-90

ESIMS

m/z 283

([M+1-1]*)

1 FINMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.5 Hz, 1H), 8.57 (dd, J

= 4.7, 1.3 Hz, 1H),

8.04 (ddd, J= 8.3, 2.7,

1.5 Hz, 1H), 8.00(s,

1H), 7.43 (dd, J= 8.3,

4.8 Hz, 1H), 4.43 (s,

1H), 2.60 (dt, J= 13.5,

6.8 Hz, 1H), 2.29 (s,

3H), 2.23 (t, J= 2.5

Hz, 1H), 1.08(d, J=

6.7 Hz, 6H).

"C NMR (101

MHz, CDCI3) 6

177.64,

148.89,

148.85,

147.83,

140.13,

136.13,

126.06,

125.08,

125.02,

123.97, 79.12,

72.41, 38.23,

31.05, 19.52,

11.16.

601 81-82

ESIMS m/z

329 ([M-

Fi))

I FI NMR (400 MHz,

CDCI3) 68.73 (s, 1H),

8.37 (d, J= 2.5 Hz,

1H), 7.99 (s, 1H), 7.83

(dt, J= 9.5, 2.2 Hz,

1H), 4.31 (s, 2H), 2.29

(t, J= 2.4 Hz, 1H),

2.27 (s, 3H), 1.45 (s,

8H).

478

17149

602

ESIMS m/z

347

((WM')

1 H NMR (400 MHz,

CDCI3) 6 8.77 (d, J=

1.7 Hz, 1H), 8.43(d, J

= 2.5 Hz, 1H), 8.05 (s,

1H), 7.86 (dt, J= 9.4,

2.3 Hz, 1H), 4.49 (s,

1H), 2.88 (dd, J= 12.8,

9.4 Hz, 1H), 2.74 (s,

1H), 2.45 (dd, J= 12.9,

5.0 Hz,1H), 2.34 (s,

3H), 2.24 (t, J= 2.5

Hz, 1H), 2.02 (s, 3H),

1.14(d, J= 6.8 Hz,

3H).

603 99-

100

ESIMS

m/z 299

((M-Hr)

I FI NMR (400 MHz,

CDCI3) 6 8.77 (d, J=

1.5 Hz, 1H), 8.43(d, J

= 2.5 Hz, 1H), 8.01 (s,

1H), 7.86 (dt, J= 9.4,

2.3 Hz, 1H), 4.43 (s,

2H), 2.57 (dt, J= 13.5,

6.7 Hz, 1H), 2.29 (s,

3H), 2.23 (t, J= 2.5

Hz, 1H), 1.08 (d, J=

6.7 Hz, 6H).

479

17149

604 ESIMS m/z

353 ([Mr)

1 H NMR (400 MHz,

CDCI3) 58.77 (d, J=

1.9 Hz, 1H), 8.44(t, J

= 4.4 Hz, 1H), 8.03 (s,

1H), 7.87 (dt, J = 9.3,

2.4 Hz, 1H), 4.44 (s,

2H), 2.56 - 2.42 (m,

3H), 2.36 (dd, J = 12.7,

5.5 Hz, 2H), 2.30 (s,

3H), 2.27 (s, 1H).

13C NMR (101

MHz, CDCI 3) 6

170.26,

149.03,

136.33,

136.28,

136.05,

135.42,

135.29,

126.49,

125.48,

124.59,

113.48, 78.51,

72.81, 38.62,

26.73, 11.13.

605

ESIMS

m/z 333

([M+H])

1 H NMR (400 MHz,

CDCI3) 6 8.76 (d, J = 1.6 Hz, 1H), 8.44(d, J

= 2.5 Hz, 1H), 7.86 (dt,

J = 9.3, 2.3 Hz, 1H),

4.45 (s, 2H), 2.79 (t, J

= 7.3 Hz, 2H), 2.43 (t,

J = 7.3 Hz, 2H), 2.30

(s, 3H), 2.25 (t, J = 2.5

Hz, 1H), 2.06 (s, 3H).

480

17149

606

ES I MS m/z

276 ([M-t-

Bu])

1 H NMR (400 MHz,

CDCI3) 6 8.94 (d, J=

2.5 Hz, 1H), 8.58 (dd, J

= 4.7, 1.3 Hz, 1H),

8.07 (s, 1H), 8.05-

7.92 (m, 1H), 7.42 (dd,

J= 8.3, 4.8 Hz, 1H),

4.36 (s, 2H), 2.29 (t, J

= 2.4 Hz, 1H), 1.46 (s,

9H).

' 3C NMR (101

MHz, CDCI3)

6 170.97,

154.09,

148.02,

139.81,

136.83,

135.90,

133.69,

133.53,

126.02,

124.26,

123.96,

117.87,

106.89, 81.33,

60.31, 28.08.

607

ESIMS

m/z 335

([M+H])

1 1-1 NMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.5 Hz, 1H), 8.64 (dd, J

= 4.7, 1.3 Hz, 1H),

8.12 (s, 1H), 8.06 (ddd,

J= 8.4, 2.7, 1.4 Hz,

1H), 7.47 (dd, J = 8.3,

4.8 Hz, 1H), 4.48 (s,

1H), 2.81 (t, J= 7.4

Hz, 2H), 2.50 (t, J=

7.4 Hz, 2H), 2.27 (t, J

= 2.5 Hz, 1H), 2.08 (s,

3H).

13C NMR (101

MHz, CDCI3) 6

175.54,

148.75,

140.82,

140.16,

135.66,

126.41,

124.12,

122.68, 78.61,

77.33, 77.02,

76.70, 72.86,

37.83, 37.22,

18.11, 16.54.

481

17149

608

ESIMS m/z

349

([M+H])

I HNMR (400 MHz,

CDCI3) 58.97 (d, J=

2.5 Hz, 1H), 8.64 (dd, J

= 4.7, 1.3 Hz, 1H),

8.16 (s, 1H), 8.05 (ddd,

J= 8.3, 2.7, 1.4 Hz,

1H), 7.47 (dd, J=8.3,

4.8 Hz, 1H), 5.30 (s,

2H), 2.87 (dd, J= 12.8,

8.8 Hz, 1H), 2.75 (d, J

= 6.3 Hz, 1H), 2.49

(dd, J= 12.9, 5.4 Hz,

1H), 2.26(t, J= 2.5

Hz, 1H), 2.03 (s, 3H),

1.18 (d, J= 6.7 Hz,

3H).

"C NMR (101

MHz, CDCI3) 6

171.42,

148.77,

140.68,

140.10,

135.65,

127.00,

126.48,

124.14,

122.73, 78.58,

72.91, 37.82,

33.86, 29.41,

15.92.

609

ESIMS

m/z 357

([M+Hr)

1 FINMR (400 MHz,

CDCI3) 6 8.97 (d, J=

2.5 Hz, 1H), 8.65 (dd, J

= 4.7, 1.3 Hz, 1H),

8.12 (s, 1H), 7.48 (dd,

J= 7.5, 3.9 Hz, 1H),

4.46 (s, 2H), 2.61 -

2.35 (m, 4H), 2.29 (dd,

J = 4.7, 2.4 Hz, 1H).

"C NMR (101

MHz, CDCI3)

6 170.10,

148.90,

140.16,

139.27,

126.82,

126.57,

124.14,

123.89,

122.29, 78.32,

73.09, 72.50,

38.13, 36.29,

26.71.

482

17149

'H NMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.2 Hz, 1H),

ESIMS m/z 8.09 (s, 1H), 8.06 (ddd,

J= 8.3, 2.7, 1.5 Hz, 610 98-99 303

([M+H]) 1H), 7.46 (dd, J= 8.4,

4.8 Hz, 1H), 2.76 -

2.44 (m, 1H), 2.24 (t, J

=2.4 Hz, 1H), 1.57(s,

1H), 1.11 (d, J = 6.7

Hz, 6H).

I4C NMR (101

I FINMR (400 MHz, MHz, CDCI3) 6

CDCI3) 58.97 (d, J= 171.30,

2.5 Hz, 1H), 8.66- 148.66,

8.60 (m, 1H), 8.25 (s, 140.71,

ESIMS 1H), 8.08 - 8.01 (m, 140.18,

1H), 7.49 - 7.42 (m, 135.71, 611 m/z 335

([M+H]) 1H), 4.86 (s, 1H), 4.29

-3.97 (m, 1H), 3.31 (d,

127.87,

126.35,

J = 6.5 Hz, 1H), 2.30- 124.11,

2.24 (m, 1H), 2.09 (s, 122.12, 78.53,

3H), 1.46 (d, J= 6.9 72.92, 53.39,

Hz, 3H). 37.97, 16.42,

11.07. _

483

17149

612 65-68

ESIMS

m/z 321

([M+Hr)

I ll NMR (400 MHz,

CDCI3) 6 8.96 (s, 1H),

8.63 (d, J= 4.2 Hz,

1H), 8.21 (s, 1H), 8.09

- 8.00 (m, 1H), 7.50 -

7.43 (m, 1H), 4.53 (br

s, 2H), 3.12 (s, 2H),

2.28 (t, J= 2.5 Hz,

1H), 2.23 (s, 3H).

"C NMR (101

MHz, CDCI 3) 6

169.20,

148.57,

140.58,

140.10,

127.82,

126.47,

122.27, 99.98,

78.37, 73.07,

37.90, 35.01,

15.96.

613 (IR thin

film) 1674

ESIMS m/z

403

([M+H])

1 H NMR (400 MHz,

CDCI3) 6 8.97 (d, J=

2.6 Hz, 1H), 8.64 (dd, J

= 4.7, 1.3 Hz, 1H),

8.13 (s, 1H), 8.07 (ddd,

J= 8.3, 2.7, 1.5 Hz,

1H), 7.48 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 4.39

(s, 2H), 3.76 (dqd, J=

17.2, 8.6, 3.6 Hz, 1H),

2.67 (dd, J=16.6, 3.6

Hz, 1H), 2.46 (dd, J=

16.5, 9.9 Hz, 1H), 2.29

(d, J= 2.5 Hz, 4H).

484

17149

1 614

(IR thin

film) 1671

ESIMS m/z

353

((WM+)

I FI NMR (400 MHz,

CDCI3) 58.97 (d, J =

2.5 Hz, 1H), 8.64 (dd, J

= 4.7, 1.4 Hz, 1H),

8.12 (s, 1H), 8.07 (ddd,

J = 8.3, 2.7, 1.4 Hz,

1H), 7.47 (ddd, J = 8.3,

4.8, 0.4 Hz, 1H), 4.47

(s, 2H), 2.48 - 2.35 (m,

2H), 2.35 - 2.16 (m,

3H), 1.60 (t, J = 18.4

Hz, 3H).

615 (IR thin

film) 1676

ESIMS ink

407

((M+H]+ )

1 H NMR (400 MHz,

CDCI3) 6 8.97 (d, J =

2.5 Hz, 1H), 8.65 (dd, J

= 4.7, 1.2 Hz, 1H),

8.13 (s, 1H), 8.07 (ddd,

J = 8.3, 2.7, 1.5 Hz,

1H), 7.48 (dd, J = 8.3,

4.7 Hz, 1H), 4.47 (s,

2H), 2.58 - 2.39 (m,

4H), 2.29 (t, J= 2.5

Hz, 1H).

485

17149

'H NMR (400 MHz,

CDCI3) 6 8.97 (d, J=

2.5 Hz, 1H), 8.64 (dd, J

= 4.7, 1.1 Hz, 1H),

8.17 (s, 1H), 8.06 (ddd,

J= 8.3, 2.7,1.4 Hz,

1H), 7.47 (dd, J= 8.3,

4.7 Hz, 1H), 4.92 - ESIMS m/z

(IR thin 4.10 (m, 2H), 3.06 616 377

film) 1662 (ddd, J= 7.7, 6.2, 4.3 ([11/41+Hr)

Hz, 1H), 2.45 (s, 1H),

2.44 (d, J= 2.4 Hz,

1H), 2.27 (t, J= 2.5

Hz, 1H), 2.11 (s, 3H),

1.97- 1.85(m, 1H),

0.96 (d, J= 6.7 Hz,

3H), 0.88 (d, J= 6.8

Hz, 3H).

"C NMR (101

MHz, CDCI3) 6

1 H NMR (400 MHz, 168.11,

CDCI3) 68.98 (s, 1H), 148.95,

8.65(d, J= 4.6 Hz, 148.78,

1H), 8.23 (s, 1H), 8.11 140.45,

ESIMS m/z -7.97 (m, 1H), 7.51 - 140.33,

617 351 7.41 (m, 1H), 4.88 (br 140.20,

([M+Hr) s, 1H), 4.14 (br s, 1H), 135.56,

2.64(s, 1.2H), 2.55 (s, 126.54,

1.8H), 2.33 - 2.27 (m, 124.10,

1H), 1.47 (d, J = 6.8 121.68,

Hz, 3H). 121.58,

121.48, 77.69,

73.49, 38.60.

486

17149

1 H NMR (400 MHz,

13C NMR (101

MHz, CDCI3) 8

CDCI3) 69.00 (s, 1H), 166.97,

8.65 (s, 1H), 8.29 (s, 166.90,

1H), 8.03 (d, J=8.0 148.77,

ESIMS m/z Hz, 1H), 7.54 - 7.39 140.43,

618 367 (m, 1H), 4.89 (d, J = 140.24,

([M+H]) 16.9 Hz, 1H), 4.20- 135.58,

4.08 (m, 1H), 4.07- 129.36,

3.92 (m, 1H), 3.01 (s, 126.64,

3H), 2.34 - 2.29 (m, 124.14,

1H), 1.67 (d, J = 7.0 121.34, 73.80,

Hz, 3H). 60.91, 38.78,

36.29, 13.97.

1 H NMR (400 MHz,

CDCI3) 8 8.95 (d, J = 2.8 Hz, 1H), 8.63 (dd, J

= 4.7, 1.5 Hz, 1H),

(thin film) 8.12 - 8.01 (m, 1H),

3080, ESIMS m/z

7.98- 7.92 (m, 1H),

2978, 7.53 - 7.40 (m, 1H), 619 365

2930, ([M+Hr)

3.78- 3.62 (m, 2H),

1660, 2.95 - 2.84 (m, 2H),

1584 2.51 -2.38 (m, 4H),

1.20 - 1.11 (m, 3H),

0.94 (s, 1H), 0.60 -

0.34 (m, 2H), 0.24 -

0.09 (m, 2H)

487

17149

620

(thin film)

3080,

2975,

2931,

1657,

1584

ESIMS m/z

351

(rM+Hr)

1 1-I NMR (400 MHz,

CDCI 3) 6 8.96 (dd, J=

2.7, 0.7 Hz,1H), 8.63

(dd, J= 4.8, 1.4 Hz,

1H), 8.08 (s, 1H), 8.04

(ddd, J= 8.4, 2.8, 1.5

Hz, 1H), 7.46 (ddd, J=

8.4, 4.7, 0.8 Hz, 1H),

3.6 (bs, 1H), 3.17 (s,

1H), 2.61 (d, J= 7.1

Hz, 2H), 1.21-1.10

(m,3H),1.17 (t, J= 7.2

Hz, 2H), 1.05 - 0.91

(m, 1H), 0.55 (dd, J=

7.9, 1.5 Hz, 2H), 0.24

(dd, J= 4.8 1 1.4 Hz,

2H)

621

(thin film)

3081,

2972,

2930,

2871,

1655,

1438

ESIMS m/z

365

([M+Fi])

'H NMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.8 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H),

8.13(s, 1H), 8.04 (ddt,

J= 8.3, 3.2, 1.6 Hz,

1H), 7.50 - 7.40 (m,

1H), 3.81 (bs, 1H),

3.59 (bs, 1H), 3.33 (d,

J= 7.4 Hz, 1H), 2.58 -

2.41 (m, 2H), 1.47 (d, J

= 6.9 Hz, 3H), 1.17 (td,

J = 7.1, 1.8 Hz, 3H),

0.84 (dt, J= 10.3, 7.4,

3.7 Hz, 1H), 0.56 -

0.38 (m, 2H), 0.25 -

0.07 (m, 2H)

488

17149

622

(thin film)

3420,

3080,

2975,

1660,

1584

ESIMS m/z

381

([M+H])

1 H NMR (400 MHz,

CDCI3) 6 9.02 - 8.90

(m, 1H), 8.63 (dd, J=

4.8, 1.4 Hz, 1H), 8.09 -

7.99 (m, 2H), 7.45

(ddd, J= 8.3, 4.7, 0.7

Hz, 1H), 3.73 (dq, J=

13.7, 6.7 Hz, 2H), 3.18

(dt, J= 13.1, 7.7 Hz,

1H), 2.89 (dt, J= 13.0,

6.3 Hz, 1H), 2.73 (ddd,

J= 26.6, 12.9, 6.5 Hz.

3H), 2.58 (dd, J= 13.3,

7.7 Hz, 1H), 1.17 (t, J

= 7.2 Hz, 3H), 1.10

(ddt, J=9.1,7.5,3.9

Hz, 1H), 0.79 - 0.64

(m, 2H), 0.45 - 0.28

(m, 2H)

623

(thin film)

3580,

3099,

2975,

2933,

1661,

1584,

1115

ESIMS m/z

397

([M+Hr)

1 H NMR (400 MHz,

CDCI3) 6 8.97 (dd, J=

2.7, 0.7 Hz, 1H), 8.63

(dd, J= 4.7, 1.4 Hz,

1H), 8.09 - 8.01 (m,

2H), 7.46 (ddd, J= 8.3,

4.7, 0.7 Hz, 1H), 3.77 -

3.69 (m, 2H), 3.42 (t, J

= 7.2 Hz, 2H), 3.17 -

2.91 (m, 2H), 2.72 (t, J

= 7.1 Hz, 2H), 1.30 -

1.12(m, 1H), 1.12(m,

3H), 0.82- 0.70 (m,

2H), 0.44 (dt, J= 6.3,

4.9 Hz, 2H)

489

17149

624

(thin film)

3082,

2974,

2933,

1655,

1584

ESIMS m/z

379

([M+Hr)

'H NMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.8 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H),

8.05 (ddd, J= 8.3, 2.8,

1.5 Hz, 1H), 8.02 (s,

1H), 7.46 (ddd, J= 8.4,

4.7, 0.8 Hz, 1H), 3.84

(m, 1H), 3.61 (m, 1H),

2.92 (dd, J= 12.5, 8.9

Hz, 1H), 2.76 - 2.62

(m, 1H), 2.57 (dd, J=

12.6, 5.4 Hz, 1H), 2.45

- 2.30 (m, 2H), 1.17

(dd, J=7.8, 6.9 Hz,

6H), 0.96 - 0.81 (m,

1H), 0.51 (dq, J= 8.0,

1.8 Hz, 2H), 0.23 -

0.07 (m, 2H)

490

17149

625

(thin film)

3091,

2974,

2933,

2875,

1655,

1584

ESIMS i nk

414

' ([M+H])

I FI NMR (400 MHz,

CDCI3)15 8.96 (d, J=

2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H),

8.04 (ddd, J= 8.3, 2.7,

1.5 Hz, 1H), 7.99 (d, J

= 2.5 Hz, 1H), 7.46

(dd, J= 8.3, 4.7 Hz,

1H), 3.82 (m, 1H), 3.62

(m, 1H), 2.93 (dd, J=

12.7, 9.2 Hz, 1H), 2.68

(m, 1H), 2.56 (m, 3H),

1.83- 1.64(m, 1H),

1.47 (tdt, J= 12.0, 8.1,

4.2 Hz, 1H), 1.21 -

1.11 (m, 6H), 1.02

(ddq, J= 16.7, 8.0, 3.9

Hz, 1H)

491

17149

626 60-61

(thin film)

3092,

2975,

2931,

1659,

1584

ESIMS m/z

400

((WM')

1 FINMR (400 MHz,

CDCI3) 6 8.99 - 8.90

(m, 1H), 8.63 (dd, J =

4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.96 (s, 1H),

7.47 (ddd, J = 8.3, 4.7,

0.7 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.87 (t,

J = 7.3 Hz, 2H), 2.63-

2.55 (m, 2H), 2.46 (t, J

= 7.3 Hz, 2H), 1.76

(ddq, J= 13.2, 11.4,

7.5 Hz, 1H), 1.48

(dddd, J = 12.3, 11.2,

7.8, 4.5 Hz, 1H), 1.17

(t, J = 7.2 Hz, 3H),

1.04 (dtd, J = 13.2, 7.6,

3.7 Hz, 1H)

627

(thin film)

3448,

3092,

2976,

2933,

1659,

1585,

1440,

1012

ES I MS m/z

417

([M+Hr)

1 1-1 NMR (400 MHz,

CDCI3) 6 8.97 (d, J =

2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H),

8.04 (m, 2H), 7.46

.(ddd, J = 8.3, 4.8, 0.7

Hz, 1H), 3.72 (dq, J =

13.8, 7.0 Hz, 2H), 3.16

(ddd, J = 20.3, 13.9,

6.8 Hz, 1H), 3.00 -

2.79 (m, 3H), 2.69 (m,

2H), 2.13- 1.85(m,

1H), 1.77- 1.62(m,

1H), 1.41 -1.21 (m,

1H), 1.18 (t, J = 7.2

Hz, 3H)

492

17149

628

(thin film)

3104,

2980,

2934,

1662,

1486,

1460

ESIMS nik

433

([101-1])

'H NMR (400 MHz,

CDCI3) 6 9.00 - 8.90

(m, 1H), 8.64 (dd, J=

4.7, 1.4 Hz, 1H), 8.09 -

8.00 (m, 2H), 7.47

(ddd, J= 8.4, 4.8, 0.7

Hz, 1H), 3.72 (d, J=

7.1 Hz, 2H), 3.43 (s,

2H), 3.30 (dd, J= 14.7,

6.8 Hz, 1H), 3.11 -

3.00 (m, 1H), 2.72 (t, J

= 6.9 Hz, 2H), 2.13 -

1.96(m, 1H), 1.73 (tdd,

J= 11.5, 8.3, 5.4 Hz,

1H), 1.45 (ddt, J=

16.1, 8.0, 3.8 Hz, 1H),

1.18(t, J= 7.2 Hz,

3H),

629

(thin film)

3094,

2924,

1660,

1583

ESIMS m/z

387

([M+H]t )

'H NMR (400 MHz,

CDCI3) 6 8.94 (d, J=

2.8 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H),

8.04 (ddd, J= 8.3, 2.7,

1.4 Hz, 1H), 7.98 (s,

1H), 7.46 (ddd, J= 8.4,

4.7, 0.8 Hz, 1H), 3.25

(s, 3H), 2.88 (t, J= 7.2

Hz, 2H), 2.61 (ddt, J=

7.0, 2.7, 1.3 Hz, 2H),

2.49 (t, J= 7.3 Hz,

2H), 1.76 (ddq, J=

13.1, 11.2, 7.4 Hz, 1H),

1.48 (dddd, J= 12.3,

11.2, 7.8, 4.5 Hz, 1H),

1.05 (dtd, J= 13.2, 7.7,

3.7 Hz, 1H)

493

17149

(thin film)

1 H NMR (400 MHz,

CDCI3) 58.96 (d, J=

2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H),

8.07 (d, J= 1.8 Hz,

3439, ESIMS ink 1H), 8.03 (ddd, J= 8.3,

2992, 403 2.7, 1.4 Hz, 1H), 7.46 630

1662, ([M+Hr), (ddd, J= 8.3, 4.8, 0.7

1584, 401 am-Hp Hz, 1H), 3.30 (s, 3H),

1013 3.24 - 3.07 (m, 1H),

2.99 - 2.59 (m, 5H),

2.04- 1.87(m, 1H),

1.77- 1.64(m, 1H),

1.41- 1.21 (m, 1H)

'H NMR (400 MHz,

CDCI3) 58.96 (d, J=

2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H),

8.04 (m, 2H), 7.47

(thin film) (ddd, J= 8.3, 4.8, 0.8

3584, ESIMS miz Hz, 1H), 3.43 (t, J=

3104, 419 6.9 Hz, 2H), 3.37 - 631

2929, ([M+Hr), 3.28 (m, 1H), 3.27 (s,

1662, 417 (EM-Hr) 3H), 3.13 - 3.00 (m,

1584 1H), 2.76 (t, J=7.0

Hz, 2H), 2.09- 1.96

(m, 1H), 1.74 (tdd, J=

11.4, 8.3, 5.3 Hz, 1H),

1.46 (ddd, J= 12.4,

7.9, 4.0 Hz, 1H)

494

17149

1 H NMR (400 MHz,

CDCI3) 68.95 (d, J=

2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7,

1.5 Hz, 1H), 7.99 (s,

(thin film) 1H), 7.47 (ddd, J= 8.3,

3089, ESIMS nilz

4.7, 0.7 Hz, 1H), 3.54

3005, (s, 2H), 2.88 (t, J= 7.3 632 427

2923,

1660 ([M+H])

Hz, 2H), 2.69 - 2.54

(m, 2H), 2.48 (t, J= 7.3

1584 Hz, 2H), 1.76 (ddt, J=

18.7, 13.3, 7.4 Hz, 1H),

1.53- 1.42 (m, 1H),

1.12- 0.90(m, 2H),

0.54 - 0.44 (m, 2H),

0.20 (dt, J= 6.1, 4.6

Hz, 2H)

1 FI NMR (400 MHz,

CDCI3) 6 8.96 (s, 1H),

8.64 (d, J= 4.6 Hz,

1H), 8.11 (s, 1H), 8.06

(ddd, J= 8.4, 2.7, 1.4

(thin film) Hz, 1H), 7.47 (dd, J=

3298, ESI MS m/z

8.4, 4.8 Hz, 1H), 4.47

3097, (s, 2H), 2.88 (t, J= 7.2 633 411

2923,

1668, ([M+Hr)

Hz, 2H), 2.61 (ddd, J=

6.6, 5.1, 2.3 Hz, 2H),

1584 2.51 (t, J= 7.3 Hz,

2H), 2.27 (t, J= 2.5

Hz, 1H), 1.83 - 1.67

(m, 1H), 1.54 - 1.40

(m, 1H), 1.05 (dtd, J=

13.3, 7.7, 3.7 Hz, 1H)

495

17149

634

(thin film)

3097,

2978,

2937

1664,

1440

ESIMS m/z

469

aki+Hr)

'H NMR (400 MHz,

CDCI3) 58.96 (d, J=

2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H),

8.06 (ddd, J= 8.4, 2.8,

1.4 Hz, 1H), 7.98(d, J

= 2.1 Hz, 1H), 7.47

(dd, J= 8.3, 4.8 Hz,

11-1), 3.94 - 3.84 (m,

1H), 3.75 (s, 2H), 2.97

(dd, J= 13.4, 7.5 Hz,

0.55H), 2.85 (s, 1H),

2.79- 2.65 (m, 0.45H),

2.60 (m,1H), 2.43 (dt, J

= 16.3, 10.0 Hz, 1H),

1.89 (tt, J= 12.2, 7.5

Hz, 1H), 1.63 - 1.49

(m, 1H), 1.23 - 1.13

(m, 4H)

635 (thin film)

1656

ESIMS m/z

394

([M+2H]. )

I FI NMR (400 MHz,

CDCI3) 6 8.97 (d, J=

2.6 Hz, 1H), 8.70 -

8.52 (m, 1H), 8.08 -

7.99 (m, 2H), 7.47(dd,

J= 8.3, 4.8 Hz, 1H),

3.97- 3.35 (m, 3H),

3.25 (qd, J= 10.2, 4.2

Hz, 2H), 1.50 (d, 3H),

1.17 (t, J= 7.2 Hz,

3H).

496

17149

636

ESIMS m/z

393

([M+Hr)

1 1-I NMR (400 MHz,

CDCI3) 5 8.95 (d, J=

2.4 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7,

1.4 Hz, 1H), 7.96(d, J

= 7.1 Hz, 1H), 7.46

(ddd, J= 8.3, 4.8, 0.6

Hz, 1H), 3.72(q, J=

7.1 Hz, 2H), 3.10(q, J

= 10.0 Hz, 2H), 2.96 (t,

J= 7.0 Hz, 2H), 2.47

(t, J= 7.0 Hz, 2H),

1.17(t, J= 7.2 Hz, 3H)

637 (KBr)

1658

ESIMS m/z

379

((WM + )

1 FINMR (400 MHz,

CDCI3) 5 8.95 (d, J=

2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H),

8.06 — 8.01 (m, 2H),

7.47 (dd, J= 8.4, 4.7

Hz, 1H), 3.72 (m, 2H),

3.33 (q, J= 9.9 Hz,

2H), 3.26 (s, 2H), 1.18

(t, J= 7.2 Hz, 3H)

638 (KBr)

1659

ESIMS m/z

413

([MM]. )

'H NMR (400 MHz,

CDCI3) 58.96 (d, J=

2.7 Hz, 1H), 8.65 (dd, J

= 4.8, 1.4 Hz, 1H),

8.07- 8.01 (m, 2H),

7.48 (dd, J=8.5,4.7

Hz, 1H), 5.66(q, J=

6.7 Hz, 1H), 3.85 -

3.62 (m, 2H), 3.55 -

3.37 (m, 2H), 1.19 (t, J

= 7.2 Hz, 3H)

497

17149

639 (KBr)

1657

ESIMS m/z

407

([M+H]+ )

1 FINMR (400 MHz,

CDCI3) 6 8.98 (d, J=

2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H),

8.09 (s, 1H), 8.04 (ddd,

J= 8.4, 2.7,1.4 Hz,

1H), 7.47 (dd, J= 8.3,

4.8 Hz, 1H), 3.88 (br.

s, 1H), 3.53 (br. s, 1H),

3.28 (qd, J= 10.2, 2.2

Hz, 2H), 3.09 (br. s,

1H), 2.15- 1.95(m,

1H), 1.67 (ddd, J=

13.6, 7.4, 6.0 Hz, 1H),

1.17(t, J= 7.2 Hz,

3H), 0.96 (t, J= 7.3

Hz, 3H)

640 (KBr)

1656

ESIMS m/z

375 ([M+H]

*)

I FI NMR (400 MHz,

CDCI3) 58.97 (d, J=

2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H),

8.09 (s, 1H), 8.04 (ddd,

J= 8.3, 2.7, 1.5 Hz,

1H), 7.47 (dd, J= 8.3,

4.7 Hz, 1H), 5.82 (tt, J

= 56.7, 4.4 Hz, 1H),

3.84 (br. s, 1H), 3.58

(br. s, 1H), 3.48 - 3.34

(m, 1H), 3.14 - 2.83

(m, 2H), 1.47 (d, J=

6.8 Hz, 3H), 1.17(t, J

= 7.2 Hz, 3H)

498

17149

641 (KBr)

1656

ESIMS m/z

357 ([M+H]

4 )

I FI NMR (400 MHz,

CDCI3) 6 8.97 (d, J=

2.8 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H),

8.11 (s, 1H), 8.04 (ddd,

J= 8.3, 2.7, 1.5 Hz,

1H), 7.46 (dd, J=8.4,

4.7 Hz, 1H), 4.48 (dt, J

= 47.1, 6.4 Hz, 2H),

3.84 (br. s, 1H), 3.58

(br. s, 1H), 3.38 (d, J=

7.5 Hz, 1H), 2.91 (dt, J

= 22.1, 6.2 Hz, 2H),

1.47 (d, J= 6.8 Hz,

3H), 1.17 (t, J= 7.2

Hz, 3H)

642

ESIMS m/z

379 ([M+H] i

IH NMR (400 MHz,

CDCI3) IS 8.95 (d, J=

2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H),

8.11 (s, 1H), 8.02 (ddd,

J= 8.3, 2.7, 1.5 Hz,

1H), 7.47 (dd, J=8.3,

4.7 Hz, 1H), 3.61 -

3.47 (in, 1H), 3.37 -

3.13 (m, 5H), 1.48 (d, J

= 6.9 Hz, 3H)

499

17149

1 H NMR (400 MHz,

CDCI3) 6 8.96 (bs, 1H),

8.63 (d, J= 4.2 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.97

(s, 1H), 7.47 (dd, J=

ESIMS m/z 8.3, 4.8 Hz, 1H), 4.53 (thin film)

643 1657

359 (dt, J= 47.1, 6.4 Hz,

([M+21-1]'), 2H), 3.72 (q, J= 7.2

Hz, 2H), 2.88 (t, J=

7.2 Hz, 2H), 2.81 (t, J

= 6.4 Hz, 1H), 2.76 (t,

J= 6.4 Hz, 1H), 2.46

(t, J= 7.3 Hz, 2H),

1.17(t, J= 7.2 Hz, 3H)

'H NMR (400 MHz,

CDCI3) 6 8.99 (d, J=

2.7 Hz, 1H), 8.71 —

8.59 (m, 1H), 8.18 (s,

(KBr) 1H), 8.06 — 7.94 (m,

644 1652,

ESIMS m/z

425

1H), 7.46 (dd, J= 8.4,

4.7 Hz, 1H), 4.25 (dq, J 1322,

1141 ((M+Hr) = 14.9, 9.5 Hz, 1H),

4.16 — 3.87 (m, 3H),

3.65 — 3.46 (m, 1H),

1.67 (d, J= 7.0 Hz,

3H), 1.22 (t, J= 7.2

Hz, 3H)

500

17149

645

(KBr)

1653,

1079

ESIMS m/z

409 ([M+H]

+)

1 H NMR (400 MHz,

CDCI3) 6 8.99 (d, J=

2.5 Hz, 1H), 8.66 (dd, J

= 4.8, 1.4 Hz, 0.55H),

8.62 (dd, J= 4.8, 1.4

Hz, 0.45H), 8.17 (s,

0.45H), 8.11 (s,

0.55H), 8.05 (ddd, J=

8.3, 2.9, 1.5 Hz,

0.55H), 7.99 (ddd, J=

8.4, 2.8, 1.5 Hz,

0.45H), 7.48 (dd, J=

8.4, 4.7 Hz, 0.55H),

7.44 (dd, J= 8.4, 4.8

Hz, 0.45H), 4.25 (br. s,

0.45H), 4.07 (q, J= 6.7

Hz, 0.55H), 4.02 - 3.75

(m, 1.45H), 3.75 - 3.33

(m, 2H), 3.18 (dq, J=

14.4, 10.1 Hz, 0.55H),

1.54(d, J= 6.8 Hz,

3H), 1.20 (dt, J= 14.2,

7.2 Hz, 3H)

501

17149

1 H NMR (400 MHz,

CDCI3) 58.97 (d, J=

2.6 Hz, 1H), 8.64 (d, J

= 4.9 Hz, 1H), 8.56

(dd, J= 4.7,1.4 Hz,

1H), 7.99 (ddd, J= 8.4,

111.0- ESIMS m/z 2.7, 1.4 Hz, 1H),7.56

646 113.5 366 (s, 1H), 7.41 (ddd, J=

([M+1-1]+) 8.3, 4.8, 0.6 Hz, 1H),

3.22 (ddd, J= 14.0,

8.9, 0.6 Hz, 111), 3.04

(dd, J= 14.1, 5.5 Hz,

1H), 2.98 - 2.75 (m,

1H), 1.40(d, J=6.9

Hz, 3H)

1 H NMR (400 MHz,

CDCI3) 5 8.94 (d, J =

2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.3 Hz, 1H),

ESIMS m/z 8.06 - 7.98 (m, 2H),

(thin film) 7.47 (dd, J= 8.3, 4.8 647 380

1659 ((M+1-1]+)

Hz, 1H), 3.27 (s, 3H),

3.20 (dd, J= 13.6, 9.3

Hz, 1H), 3.02 - 2.89

(m, 1H), 2.85 (dd, J=

13.9, 5.4 Hz, 1H), 1.19

(d, J= 6.8 Hz, 3H)

502

17149

648 (thin film)

1657

ESNS m/z

394

([M+H]')

1 H NMR (400 MHz,

CDCI3) 6 8.96 (d, J =

2.6 Hz, 1H), 8.64 (dd, J

= 4.7, 1.3 Hz, 1H),

8.08 - 8.00 (m, 1H),

7.98 (d, J = 8.3 Hz,

1H), 7.51 - 7.44 (m,

1H), 4.07 - 3.36 (m,

2H), 3.25 - 3.11 (m,

1H), 2.94 - 2.77 (m,

2H), 1.22- 1.15 (m,

6H)

649

(thin film)

3078,

2926,

1659,

1583,

1458,

1437, 803

ESIMS m/z

406

([M-I-2Hr)

403.7([M-

HD

1 H NMR (400 MHz,

CDCI3) 58.94 (dd, J=

2.7, 0.7 Hz, 1H), 8.63

(dd, J = 4.8, 1.5 Hz,

1H), 8.04 (ddd, J = 8.3,

2.7, 1.4 Hz, 1H), 7.98

(s, 1H), 7.47 (ddd, J =

8.3, 4.7, 0.7 Hz, 1H),

5.30 (s, 1H), 3.51 (s,

2H), 3.25 (s, 3H), 2.87

(t, J = 7.3 Hz, 2H),

2.52 (t, J = 7.3 Hz, 2H)

650

(thin film)

3359,

3083,

2926,

1662,

1585,

1440

ESNS m/z

406

([M+2F1]. )

'H NMR (400 MHz,

CDCI3) 58.95 (d, J =

2.7 Hz, 1H), 8.64 (dd, J

= 4.7, 1.4 Hz, 1H),

8.08 - 8.00 (m, 2H),

7.46 (ddd, J = 8.3, 4.7,

0.7 Hz, 1H), 6.23 (s,

1H), 3.72 (bm, 4H),

3.22(s, 2H)„ 1.18 (t, J

= 7.2 Hz, 3H)

503

17149

'H NMR (400 MHz,

CDCI3) 6 8.98 (d, J=

2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.5 Hz, 1H), (thin film)

8.11 (s, 1H), 8.05 (ddd, 3081,

J= 8.3, 2.7, 1.5 Hz, 2972, ESIMS miz

1H), 7.47 (ddd, J= 8.3, 651 2930, 417.1

4.8, 0.8 Hz, 1H), 6.02 1655, ([111+Hr)

(s, 1H), 3.79 (d, J= 1584,

14.1 Hz, 2H), 3.50 (bs, 1485, 802

1H), 3.39(d, J= 14.1

Hz, 2H), 1.55 (d, J=

6.7 Hz, 3H), 1.17 (t, J

= 7.2 Hz, 3H)

'H NMR (400 MHz,

CDCI3) 6 8.96 (d, J=

2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H),

8.09 (s, 1H), 8.04 (ddd,

J= 8.3, 2.7, 1.5 Hz,

ESIMS m/z 1H), 7.47 (dd, J= 8.3,

652 407 ((WM 4.8 Hz, 1H), 3.79 (d, J

1 = 18.2 Hz, 1H), 3.62

(s, 1H), 3.35 (d, J= 7.8

Hz, 1H), 2.86 - 2.75

(m, 2H), 2.46 - 2.25

(m, 2H), 1.49 (d, J=

7.0 Hz, 3H), 1.18(t, J

= 7.2 Hz, 3H)

504

17149

653 (thin film)

1659

ESIMS m/z

409

([M+2Hr)

I 11 NMR (400 MHz,

CDCI3) 6 8.95 (d, J=

2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.3 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7,

1.4 Hz, 1H), 7.96 (s,

1H), 7.47 (dd, J= 8.3,

4.8 Hz, 1H), 3.72 (q, J

= 7.1 Hz, 2H), 2.84 (t,

J= 7.2 Hz, 2H), 2.66

(m, 2H), 237 (t, J= 7.2

Hz, 2H), 2.44 (m, 2H),

1.17(t, J=7.2 Hz, 3H)

654

(KBr)

3091,

1656

ESIMS m/z

355

([M+Hr)

1 FINMR (400 MHz,

CDCI3) 68.97 (m, 1H),

8.64 (dd, J= 4.7,1.4

Hz, 1H), 8.13 (s, 0.4H),

8.04 (m, 1.6H), 7.54 -

7.41 (m, 1H), 6.79 (dd,

J = 83.3, 11.0 Hz,

0.6H), 6.75 (dd, J=

82.7, 4.3 Hz, 0.4H),

5.97 (dd, J= 12.7, 11.0

Hz, 0.5H), 5.68 (dd, J

= 39.8, 4.3 Hz, 0.4H),

3.82 (br. s, 1H), 3.72 -

3.47 (m, 1H), 3.47 -

3.20 (m, 1H), 1.50 (d, J

= 6.9 Hz, 1.2H), 1.42

(d, J= 6.8 Hz, 1.8H),

1.17 (m, 3H)

505

17149

655

(thin film)

3432, 2969,

2932, 1659

ESIMS tniz

369 ([M+H])

'H NMR (DMSO-de) 09.04

(dd, J= 2.8, 0.8 Hz,

0.65H), 8.99 (d, J= 2.6 Hz,

0.35H), 8.62 - 8.58 (m,

1H), 8.32 (s, 0.65H), 8.23

(s, 0.35H), 8.07 - 7.99

(m,1H), 7.46 - 7.38 (m,

1H), 3.32 (s, 0.65H), 3.29

(s, 2H), 3.25 (s, 1H), 3.24 -

3.19 (m, 0.35H), 3.08 (m,

1H), 2.86 - 2.71 (m, 1H),

2.58 (dd, J= 12.8, 7.0 Hz,

0.35H), 2.51 -2.46 (m,

0.65H), 1.33 (s, 1H), 1.31 -

1.29 (m, 2H), 1.28 - 1.23

(m, 2H), 1.21 (d, J= 6.9

Hz, 4H)

656

(thin film)

2970, 2931,

1658

ESIMS m/z

383.91((M+H

)

T H NMR (400 MHz, CDCI3)

5 9.05- 9.00 (m, 1H), 8.65 -

8.53 (m, 1H), 8.28 -8.19

(m, 1H), 8.12 - 8.00 (m,

1H), 7.48 - 7.36 (m, 1H),

3.36 (m, 1H), 3.28 - 3.17

(m, 1H), 3.07(t, J= 11.9

Hz, 1H), 2.88 - 2.69 (m,

2H), 2.53 - 2.42 (m, 1H),

1.39- 1.27(m, 6H), 1.22 -

1.10 (m, 6H)

506

17149

657

(thin film)

2977, 2935,

1662, 1583.

ESIMS

m/z 385

([M+H])

'H NMR (400 MHz, CDCI3)

69.01 (d, J= 2.7 Hz, 1H),

8.62 - 8.59 (m, 1H), 8.28

(s, 1H), 8.03 - 7.99 (m,

1H), 7.46 - 7.41 (m, 1H),

3.79 - 3.68 (m, 1H), 3.42 -

3.35 (m, 1H), 3.27 (s, 3H),

3.14 - 3.04 (m, 1H), 2.78 -

2.71 (m, 1H), 1.40 (dd, J=

7.0, 1.9 Hz, 6H), 1.22 (d, J

= 7.0 Hz, 3H)

658

ESIMS m/z

415.6

([M+H]+ )

1 H NMR (400 MHz, CDCI 3)

69.01 (d, J = 2.4 Hz, 1H),

8.62 (dd, J= 4.7, 1.4 Hz,

1H), 8.09 (s, 1H), 8.07

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.45 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 3.71 (d, J

= 6.8 Hz, 2H), 3.52 (t, J=

6.9 Hz, 2H), 2.82 (d, J=

3.7 Hz, 3H), 2.76 (s, 6H),

2.49 (t, J= 6.8 Hz, 2H),

1.16(t, J= 7.2 Hz, 3H)

' 3C NMR (101

MHz, 00013) 6

171.17(s),

148.58 (s),

140.53 (s),

140.36 (s),

135.72 (s),

127.12 (s),

126.43 (s),

124.06 (s),

123.57 (s),

47.72 (s),

43.81 (s),

38.04 (s),

36.17 (s),

33.07 (s),

13.05 (s)

507

17149

'H NMR (400 MHz, CDCI 3)

510.11 (s, 1H), 8.91 (d, J

= 1.8 Hz, 1H), 8.58(d, J=

ESIMS m/z 2.4 Hz, 1H), 8.24 (s, 1H),

659 355 ((WM')

7.99 (dt, J=8.9,2.3 Hz,

1H), 3.41 (t, J= 7.0 Hz,

2H), 3.26 (s, 3H), 2.96 (s,

3H), 2.69 (t, J= 6.9 Hz,

2H)

IFI NMR (400 MHz, CDCI3)

510.13 (d, J = 0.7 Hz, 1H),

8.93(d, J= 1.9 Hz, 1H),

8.57 (d, J=2.5 Hz, 1H),

(thin film) 8.36 (s, 1H), 7.95 (dt, J= ESIMS m/z

660 2932, 1697, 369 ((M+Hr)

8.9, 2.3 Hz, 1H), 3.83 (dd,

1657, 1600 J= 13.6, 10.6 Hz, 1H),

3.28 (m, 4H), 2.96 (s, 3H),

2.87 (dd, J= 13.8, 2.8 Hz,

1H), 1.11 (d, J= 7.0 Hz,

3H)


58.96 (d, J= 2.5 Hz, 11-1),

8.65 - 8.59 (m, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.98 (s, 1H), 7.46 (dd,

J= 8.3, 4.8 Hz, 1H)„ 3.95 (IR thin film) ESIMS m/z

661 -3.71 (bs, 1H), 3.31 -3.10 1658 367 ([M+H] . )

(bs, 1H), 2.92 - 2.80 (m,

1H), 2.78 - 2.66 (m, 1H),

2.53 - 2.42 (m, 1H), 2.02

(s, 3H), 1.88- 1.74 (m,

1H), 1.16 (d, J= 6.7 Hz,

3H), 1.02 - 0.90 (m, 6H),

508

17149

1 F1 NMR (400 MHz, CDCI3)

15 9.04 -8.90 (m, 1H), 8.64

(d, J= 4.1 Hz, 1H), 8.12 -

8.00 (m, 1H), 7.92 (s, 1H),

(thin film) ESIMS m/z 7.51 -7.41 (m, 1H), 5.04 662

1657 339 ((WM') (hept, J= 6.7 Hz, 1H), 2.85

-2.72 (m, 2H), 2.47 - 2.26

(m, 2H), 2.06 (s, 3H), 1.16

(d, J= 6.7 Hz, 3H), 1.06 (d,

J= 6.8 Hz, 3H)

1 H NMR (400 MHz, CDCI3)

15 8.97(d, J= 2.4 Hz, 1H),

8.66 - 8.55 (m, 1H), 8.08 -

7.99 (m, 1H), 7.99 - 7.90

(thin film) ESIMS m/z (s, 0.7H), 7.88 (s, 0.3H),

663 7.50 - 7.39 (m, 1H), 5.15 - 1652 353 ([WM1

4.94 (m, 1H), 2.98 - 2.87

(m, 0.3H), 2.85 - 2.74 (m,

0.7H), 2.69 - 2.36 (m, 2H),

2.05 (s, 1H), 1.96 (s, 2H),

1.24- 1.01 (m, 9H)


6 8.95 (d, J= 2.5 Hz, 1H),

8.67 - 8.61 (m, 1H), 8.08 -

8.01 (m, 1H), 8.00 (s, 1H),

7.50 - 7.42 (m, 1H), 4.39 (thin film) ESIMS ink

664 (d, J= 14.2 Hz, 1H), 3.18 1664 387 ([M+Hr)

(bs, 1H), 2.85 - 2.74 (m,

2H), 2.52 - 2.43 (m, 2H),

2.07 (s, 3H), 1.97- 1.80

(m, 1H), 1.55- 1.42(m,

1H), 1.18- 1.02(m, 1H)

509

17149

1 1-1NMR (400 MHz, CDCI 3 )

68.96 (d, J= 2.8 Hz, 1H),

8.64 (d, J=4.3 Hz, 1H),

8.12 - 7.95 (m, 2H), 7.51 -

(thin film) ESIMS m/z 7.40 (m, 1H), 4.40 (bs,

665 1667 401 ([M+Hr)

1H), 3.16 - 2.91 (bs, 1H),

2.91 -2.59 (m, 2H), 2.56 -

2.37 (m, 1H), 2.03 (s, 2H),

2.01 (s, 1H), 1.55- 1.44

(m, 1H), 1.29 - 1.06 (m,

5H),


68.96 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.07 - 8.02 (m, 1H),

7.97 (s, 1H), 7.49 - 7.43

(thin film) ESIMS m/z (m, 1H), 3.94 - 3.62 (m, 666

1665 447 ((WM') 3H), 3.45 - 3.28 (m, 1H),

2.69 - 2.55 (m, 1H), 2.48 -

2.34 (m, 1H), 2.13 - 1.93

(m, 2H), 1.84- 1.70 (m,

2H), 1.71 - 1.40 (m, 4H),

1.21- 1.12(m, 3H)

510

17149

667 (thin film)

1638,

ESIMS m/z

382 ([M+Hr)


5 8.95(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.99 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 3.64 (d, J

= 61.3 Hz, 2H), 3.06 (ddd,

J= 7.7, 6.4, 4.2 Hz, 1H),

2.40(s, 1H), 2.39(d, J=

2.0 Hz, 1H), 2.11 (s, 3H),

1.96- 1.84(m, 1H), 1.57

(dt, J= 14.9, 7.5 Hz, 2H),

0.98 - 0.90 (m, 6H), 0.87

(d, J= 6.8 Hz, 3H)

668 (thin film)

1657

ESIMS m/z

393 ([M+H])


15 8.96 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.2 Hz,

1H), 8.06 (ddd, J= 8.2,

2.6, 1.4 Hz, 2H), 7.51 -

7.43 (m, 1H), 3.80 - 3.38

(m, 2H), 3.07 (ddd, J= 7.6,

6.3, 4.2 Hz, 1H), 2.47 -

2.37 (m, 2H), 2.11 (s, 3H),

1.91 (dtd, J= 13.5, 6.8, 4.2

Hz, 1H), 1.01 - 0.93 (m,

4H), 0.88 (d, J= 6.8 Hz,

3H), 0.54 - 0.45 (m, 2H),

0.25 - 0.16 (m, 2H)

511

17149

669 (thin film)

1650

ESIMS m/z

340 ([M+Fir)

'H NMR (400 MHz, CDCI 3 )

•5 8.95 (d, J= 2.6 Hz, 1H),

8.63 (dd, J=4.7,1.3 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.02 (s,

1H), 7.58 - 7.39 (m, 1H),

3.23 (s, 3H), 2.50 (s, 2H),

1.96 (s, 3H), 1.45 (s, 6H)

670 (thin film)

1655

ESIMS m/z

354 ([M+H])


6 8.96 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.2 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.99 (s,

1H), 7.52 - 7.42 (m, 1H),

3.78 - 3.57 (m, 2H), 2.46

(s, 2H), 1.96 (s, 3H), 1.45

(s, 6H), 1.16 (t, J= 7.2 Hz,

3H)

671

(thin film)

2972, 2930,

1714, 1659.

ESIMS

m/z 387

([M+H])


.5 8.68 - 8.52 (m, 2H), 7.76

(d, J= 8.0 Hz, 1H), 7.47(s,

1H), 7.20 - 7.06 (m, 5H),

6.93 (s, 1H), 3.41 -3.27

(m, 1H), 3.23(m, 1H), 3.24

(s, 3H), 2.74 (m, 1H), 1.22

(d, J= 6.6 Hz, 3H)

512

17149

672

(thin film)

3058, 1636,

1568

ESIMS

miz 371

([M+H])

I FI NMR (400 MHz, CDCI3)

6 8.96 - 8.92 (m, 0.6H),

8.90 (d, J= 2.6 Hz, 0.4H),

8.67 - 8.60 (m, 1H), 8.06 -

8.04 (m, 0.4H), 8.02 (d, J=

1.5 Hz, 0.6H), 8.00 (s,

0.4H), 7.98 (s, 0.6H), 7.84

(m, 0.6H), 7.80 (m, 0.4H),

7.57 - 7.2 (m, 5H), 5.97 (d,

J= 10.1 Hz, 0.4H), 5.93 (d,

J = 10.0 Hz, 0.6H), 5.74 (d,

J = 14.8 Hz, 0.6H), 5.65 (d,

J = 15.0 Hz, 0.4H), 3.34 (s,

1.8H), 3.27 (s, 1.2H)

673

(thin film)

3057, 2973,

2932, 1708

ESIMS

rniz 401

([M+H]i

'H NMR (400 MHz, CDC13)

68.87 (d, J = 2.6 Hz, 1H),

8.60(d, J= 4.8 Hz, 1H),

8.52 - 8.44 (m, 1H), 8.00 -

7.91 (m, 1H), 7.34 (s, 1H),

7.17 - 7.08 (m, 5H), 3.28 -

3.16 (m, 1H), 3.16 - 3.06

(m, 2H), 2.95 (dd, J= 13.8,

5.0 Hz, 1H), 2.85 (m, 1H),

1.22 (d, J= 6.7 Hz, 3H),

1.18 - 1.10 (m, 3H)

674

(thin film)

3058, 2974,

1632, 1567

ESIMS nilz

385 ((M+Hr)


68.96 (m, 1H), 8.92

(m,1H), 8.67 - 8.56 (m,

1H), 8.08 - 8.00 (m, 1H),

7.12 (m, 7H), 5.86 (d, J =

9.9 Hz, 0.7H), 5.65 (d, J =

15.0 Hz, 0.3H), 3.81 (m,

1.4H), 3.73 (m, 0.6H), 1.23

(t, J = 7.1 Hz, 2.1H), 1.18 -

1.13 (m, 0.9H)

513

17149

675

(thin film)

3057, 2960,

1663

ESIMS miz

339 ([M+H] s )


5 8.98 - 8.89 (m, 1H), 8.66

- 8.59 (m, 1H), 8.11 (s,

1H), 8.07 - 8.00 (m, 1H),

7.50 - 7.43 (m, 1H), 3.25

(s, 3H), 3.19 (s, 2H), 1.28

(s, 9H)

676

(thin film)

3058, 2924,

1660

ESIMS

nilz 404

([M+Hr)


5 9.13 - 8.95 (m, 1H), 8.62

(s, 1H), 8.38 (s, 0.6H),

8.19 (s, 0.4H), 8.13 - 8.03

(m, 1H), 7.61 (d, J = 1.7

Hz, 2H), 7.56 - 7.42 (m,

3H), 7.35- 7.28 (m, 1H),

3.34 (S, 2.4H), 3.32 - 3.22

(m, 1H), 3.18 (s, 1.6H),

2.85 - 2.72 (m, 0.4H), 2.72

-2.63 (m, 0.6H), 1.31 (d, J

= 6.8 Hz, 1.2H), 1.17(d, J

= 6.7 Hz, 1.8H)

677

(thin film)

3057, 2962,

1659

ESIMS rniz

373 ([M+H])


5 8.89 - 8.82 (m, 1H), 8.66

-8.57 (m, 1H), 8.02 - 7.93

(m, 1H), 7.68 (s, 1H), 7.49

-7.42 (m, 1H), 7.42 - 7.34

(m, 2H), 7.26 (s, 3H), 3.71

(s, 2H), 3.55 (s, 2H), 1.21 -

1.11 (m, 3H)

514

17149

678 ESIMS m/z

540 ([M+Hr)

1 H NMR (400 MHz, CDCI3 )

68.91 (d, J= 2.7 Hz, 1H),

8.67 - 8.61 (m, 1H), 8.06 -

7.96 (m, 1H), 7.81 (s, 1H),

7.49 (m, 1H), 7.46 (m, 4H),

7.20-7.46 (m, 9H), 7.31 (s,

2H), 2.56 - 2.46 (m, 2H),

2.09- 1.97 (m, 2H) 1.25

(m, 3H)


6 8.95 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.2 Hz,

1H), 8.04 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 8.02 (s,

(thin film) ESIMS m/z 1H), 7.47 (ddd, J= 8.3,

679 1658 354 ([M+Hr)

4.8, 0.4 Hz, 1H), 3.26 (s,

3H), 3.15 - 3.06 (m, 1H),

2.49 (dd, J= 15.7, 7.5 Hz,

1H), 2.38 (dd, J= 15.7, 6.5

Hz, 1H), 2.03 (s, 3H), 1.60

- 1.32 (m, 4H), 0.91 (t, J=

7.1 Hz, 3H)


6 8.96 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.2 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.99 (s,

1H), 7.49 - 7.43 (m, 1H),

680 (thin film) ESIMS m/z 3.73 (qd, J= 13.5, 6.7 Hz,

1584 368 ([M+Hr) 2H), 3.17 - 3.04 (m, 1H),

2.45 (dd, J= 15.7, 7.4 Hz,

1H), 2.35 (dd, J= 15.7, 6.5

Hz, 1H), 2.03 (s, 3H), 1.59

- 1.32 (m, 4H), 1.17 (t, J=

7.2 Hz, 3H), 0.90 (t, J= 7.1

Hz, 3H)

515

17149


6 8.96(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.02 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 3.56 (s,

(thin film) ESIMS tn/z 2H), 3.19 - 3.06 (m, 1H), 681

1657 394 ([M+Hr) 2.48 (dd, J= 15.6, 7.2 Hz,

1H), 2.37 (dd, J= 15.7, 6.6

Hz, 1H), 2.03 (s, 3H), 1.58

- 1.34 (m, 4H), 0.98 (tt, J=

7.8, 4.8 Hz, 1H), 0.95 -

0.86 (m, 3H), 0.54 - 0.46

(m, 2H), 0.20 (q, J= 4.7

Hz, 2H)


6 8.96 (d, J = 2.3 Hz, 1H),

8.66 - 8.60 (m, 1H), 8.05

(ddd, J= 8.4, 2.7, 1.5 Hz,

1H), 8.03 (s, 1H), 7.47 (dd,

J=8.4, 4.7 Hz, 1H), 3.26

(thin film) ESIMS mix (s, 3H), 2.68 - 2.43 (m, 682

1659 352 ([M+Hr) 3H), 2.14 (s, 3H), 0.82

(tdd, J= 9.4, 4.8, 3.1 Hz,

1H), 0.67 - 0.56 (m, 1H),

0.55 - 0.46 (m, 1H), 0.37

(td, J= 9.7, 5.0 Hz, 1H),

0.28 (dt, J=14.5, 4.8 Hz,

1H)

516

17149

I FI NMR (400 MHz, CDCI 3)

6 8.97 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.71 1.4 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.00 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.86 - (thin film) ESIMS ink

683 3.63 (m, 2H), 2.64 - 2.43 1656 366 ((M+Hr)

(m, 3H), 2.13(s, 3H), 1.18

(t, J= 7.2 Hz, 3H), 0.91 -

0.72 (m, 1H), 0.74 - 0.57

(m, 1H), 0.57 - 0.45 (m,

1H), 0.37 (td, J= 9.6, 5.1

Hz, 1H), 0.29 (td, J= 9.5,

5.0 Hz, 1H)


15 8.96 (d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.07 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.03 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.57 (s,

(thin film) ESIMS raiz 2H), 2.61 -2.47 (m, 3H), 684

1656, 392 ([M+Hr) 2.13 (s, 3H), 0.99 (11, J=

7.8, 4.8 Hz, 1H), 0.82 (ddd,

J=12.4,6.3,3.1 Hz, 1H),

0.66 - 0.57 (m, 1H), 0.56 -

0.44 (m, 3H), 0.37 (dt, J=

9.5, 5.0 Hz, 1H), 0.31 (dt, J

= 9.3, 4.6 Hz, 1H), 0.21

(qd, J= 5.0, 3.3 Hz, 2H)

517

17149

685 ESIMS m/z

353 ([M+Hr)


5 8.99 (d, J = 2.5 Hz, 1H),

8.6 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H) 8.40 (bs, 1H),

8.30(dd, J= 4.7, 1.4 Hz,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 4.33 —

4.21 (q, J= 7.1 Hz, 1H),

3.99 — 3.40 (m, 2H), 2.25

(s, 3H), 1.43 (d, J= 7.1 Hz,

3H), 1.16 (t, J = 7.2 Hz,

3H)

686 (thin film)

1656

ESIMS m/z

340 ([M+H])

I ll NMR (400 MHz, CDCI3)

5 8.96(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.98 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.63 (s,

2H), 2.59 - 2.43 (m, 3H),

2.13 (s, 3H), 1.67- 1.48

(m, 2H), 0.94 (t, J= 7.4 Hz,

3H), 0.81 (ddd, J= 12.3,

8.4, 3.6 Hz, 1H), 0.69 -

0.57 (m, 1H), 0.57- 0.44

(m, 1H), 0.37 (td, J= 9.6,

5.1 Hz, 1H), 0.29 (dt, J=

9.5, 4.7 Hz, 1H)

518

17149

687 (thin film)

1667

ESIMS m/z

396 ([M+11]+)


ö 8.97 (t, J= 2.2 Hz, 1H),

8.70- 8.60(m, 1H), 8.15

(s, 1H), 8.08 - 7.99 (m,

1H), 7.46 (ddd, J= 8.4,

4.8, 0.6 Hz, 1H), 4.34 -

4.17(m, 1H), 3.29(d, J=

1.8 Hz, 3H), 3.06 (dd, J=

17.7, 8.3 Hz, 1H), 2.78 (s,

3H), 2.50 (dd, J= 17.7, 3.2

Hz, 1H)

688 (thin film)

1659,

ESIMS m/z

368 ([M+Hr)

1 FINMR (400 MHz, CDCI3 )

15 8.95(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 8.02 (s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.5 Hz, 1H), 3.26 (s,

3H), 3.22 - 3.10 (m, 1H),

2.50 (dd, J= 15.6, 7.6 Hz,

1H), 2.36 (dd, J= 15.6, 6.1

Hz, 1H), 2.01 (s, 3H), 1.86

-1.71 (m, 1H), 1.35 (ddd, J

= 7.7, 6.3, 3.9 Hz, 2H),

0.92 (d, J= 6.6 Hz, 3H),

0.90 (d, J= 6.7 Hz, 3H)

519

17149

689 (thin film)

1657

ESIMS miz

382 ([M+H))


68.96 (d, J = 2.5 Hz, 1H),

8.63 (dd, J = 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.99 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 3.73 (tp, J

= 13.9, 7.0 Hz, 2H), 3.23 -

3.04 (m, 1H), 2.46 (dd, J =

15.6, 7.6 Hz, 1H), 2.33 (dd,

J= 15.6, 6.2 Hz, 1H), 2.01

(s, 3H), 1.88- 1.69(m,

1H), 1.35 (ddd, J= 7.7,

6.4, 2.5 Hz, 2H), 1.17 (t, J

= 7.2 Hz, 3H), 0.92 (d, J =

6.6 Hz, 3H), 0.89 (d, J =

6.6 Hz, 3H)

690 (thin film)

1658

ESIMS Ink

408 ([M+Hr)


6 8.96(d, J = 2.5 Hz, 1H),

8.63 (dd, J = 4.7, 1.4 Hz,

1H), 8.06 (ddd, J = 8.3,

2.7, 1.4 Hz, 1H), 8.02 (s,

1H), 7.55 - 7.39 (m, 1H),

3.55 (s, 2H), 3.26- 3.06

(m, 1H), 2.49 (dd, J = 15.5,

7.4 Hz, 1H), 2.35 (dd, J=

15.6, 6.3 Hz, 1H), 2.02 (s,

3H), 1.80 (td, J = 13.3, 6.6

Hz, 2H), 1.44- 1.32 (m,

2H), 0.92 (d, J = 6.6 Hz,

3H), 0.90 (d, J = 6.6 Hz,

3H), 0.59- 0.44 (m, 2H),

0.21 (q, J= 4.8 Hz, 2H)

520

17149

691 ESIMS m/z

477 ([M+Hr)


6 8.87 (d, J= 2.6 Hz, 1H),

8.63 - 8.57 (m, 1H), 8.49 -

8.42 (m, 1H), 8.02 - 7.95

(m, 1H), 7.91 (s, 1H), 7.65

(d, J= 2.0 Hz, 1H), 7.48 -

7.40 (m, 1H), 3.53 - 3.46

(m, 2H), 3.27 (s, 3H), 2.69

-2.60 (m, 2H)

692 ES I MS m/z

353 ([M+H])

I hl NMR (400 MHz, CDCI3)

6 8.98 - 8.93 (m, 1H), 8.63

(dd, J= 4.7, 1.4 Hz, 1H),

8.10- 8.02(m, 1H), 7.96

(s, 1H), 7.52 - 7.41 (m,

1H), 3.76 - 3.65 (m, 2H),

3.16 - 3.05 (m, 2H), 2.48 -

2.41 (m, 2H), 2.28 (s, 3H),

1.21 - 1.10 (m, 3H)

693

(thin film)

3057, 2967,

1661

ESIMS m/z

491 ([M+H])

I FI NMR (400 MHz, CDCI3 )

6 8.88 (d, J= 2.7 Hz, 1H),

8.72 - 8.55 (m, 1H), 8.51 -

8.40 (m, 1H), 8.03 - 7.97

(m, 1H), 7.89 (s, 1H), 7.64

(d, J= 1.9 Hz, 1H), 7.45(d,

J=4.8 Hz, 1H), 3.78 - 3.64

(m, 2H), 3.55 - 3.42 (m,

2H), 2.62 (m, 2H), 1.18 (t,

J=7.2 Hz, 3H)

521

17149

694 ESIMS m/z

339 ([M+H]+)


6 8.98 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.11 —8.02 (m, 2H),

7.47 (ddd, J= 8.3, 4.8, 0.6

Hz, 1H), 3.72 (bd, J= 6.8

Hz, 2H), 3.61 (s, 2H), 2.33

(s, 3H), 1.17 (t, J= 7.2 Hz,

3H)

695

(thin film)

3294, 3092,

2974, 2930,

1656

ESIMS

m/z 363

((WM+)


6 9.07 - 8.84 (m, 1H), 8.63

(dd, J= 4.8, 1.5 Hz, 1H),

8.13 - 8.00 (m, 1H), 7.96

(s, 1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 3.60 (m,

1H), 3.10 - 2.93 (m, 2H),

2.51 (t, J= 7.4 Hz, 2H),

2.27 (d, J= 2.4 Hz, 1H),

1.46 (d, J= 7.0 Hz, 3H),

1.17(t, J= 7.2 Hz, 3H)

696

(thin film)

3287, 2917,

1618

ESIMS

m/z 311

((Whi])


68.89 (d, J)= 2.5 Hz, 1H),

8.50 (dd, J= 4.7, 1.3 Hz,

1H), 7.98 (dd, J= 8.3, 1.0

Hz, 1H), 7.57(s, 1H), 7.38

(dd, J= 8.2, 4.6 Hz, 1H),

5.30 (s, 1H), 2.96 (s, 3H),

2.67 (t, J= 6.9 Hz, 2H),

2.54 (t, J= 6.9 Hz, 2H),

2.07 (s, 3H)

522

17149

697

ESIMS

m/z 325

((Whin

1 FI NMR (300 MHz, CDCI3)

68.84 (d, J= 2.6 Hz, 1H),

8.48 (dd, J= 4.7, 1.1 Hz,

1H), 8.12 (s, 1H), 7.92

(ddd, J= 8.3, 2.5, 1.4 Hz,

1H), 7.33 (dd, J = 8.3, 4.7

Hz, 1H), 3.13 (s, 3H), 2.97

- 2.87 (m, 1H), 1.94(s,

3H), 1.93- 1.83(m, 1H),

1.53 (dt, J= 13.8, 6.7 Hz,

1H), 0.81 (t, J= 7.3 Hz,

3H)

698 (thin film)

1657

ESIMS m/z

352 ([M+Hr)

Ihi NMR (400 MHz, CDCI3 )

68.95 (s, 1H), 8.63 (d, J=

3.7 Hz, 1H), 8.06 - 8.02

(m, 1H), 8.02 (s, 1H), 7.46

(dd, J= 8.3, 4.7 Hz, 1H),

3.24 (s, 3H), 2.64 (s, 2H),

2.40 - 2.27 (m, 2H), 2.19 -

2.11 (m, 3H), 1.93 (s, 3H),

1.93 - 1.86 (m, 1H)

699 (thin film)

1658

ESIMS m/z

366 ([101-1]+ )

1 FINMR (400 MHz, CDCI3)

6 8.96 (d, J= 2.2 Hz, 1H),

8.63 (d, J = 4.1 Hz, 1H),

8.05 (ddd, J= 8.4, 2.7, 1.4

Hz, 1H), 7.98 (s, 1H), 7.46

(dd, J= 8.3, 4.7 Hz, 1H),

3.72 (d, J= 6.9 Hz, 2H),

2.60 (s, 2H), 2.34 (s, 2H),

2.22 - 2.08 (m, 3H), 1.93

(s, 3H), 1.92- 1.86 (m,

1H), 1.17 (t, J= 7.2 Hz,

3H)

523

17149


68.95 (d, J= 2.6 Hz, 1H),

8.62 (dd, J=4.7,1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.97 (s,

(thin film) ESIMS m/z 1H), 7.46 (ddd, J= 8.3, 700

1658, 340 ([M+H]. ) 4.8, 0.4 Hz, 1H), 3.61 (br s,

2H), 2.60 (s, 2H), 2.34 (s,

2H), 2.21 - 2.09 (m, 3H),

1.99- 1.85 (m, 4H), 1.58

(dd, J= 15.2, 7.5 Hz, 2H),

0.93 (t, J= 7.4 Hz, 3H)


6 8.95 (d, J = 2.6 Hz, 1H),

8.62 (dd, J= 4.7, 1.3 Hz,

1H), 8.05 (ddd, J= 8.3,

ESIMS 2.7, 1.4 Hz, 1H), 8.02 (s,

(thin film) 1H), 7.46 (dd, J= 8.4, 4.7 701 m/z392

1658 Hz, 1H), 3.55 (s, 2H), 2.62 ([M+H])

(s, 2H), 2.35 (s, 2H), 2.22 -

2.06 (m, 3H), 2.00- 1.85

(m, 4H), 1.05 - 0.89 (m,

1H), 0.55 - 0.44 (m, 2H),

0.20 (q, J= 4.8 Hz, 2H)

524

17149


6 8.98 (dd, J= 7.5, 2.5 Hz,

1H), 8.62 (ddd, J= 9.3,

4.7, 1.2 Hz, 1H), 8.24 (s,

0.5H), 8.24 (s, 0.5H), 8.04

- 7.95 (m, 1H), 7.44 (ddd, J

= 10.2, 8.5, 4.8 Hz, 1H),

(thin film) ESIMS tri/z 4.01 (br s, 0.5H), 3.80 (dd,

702 1655, 1584. 341 ([M+H]

J= 11.3, 3.1 Hz, 0.5H),

3.33 (d, J= 12.4 Hz, 3H),

2.66 (s, 1.5H), 2.55 (s,

1.5H) 2.06 (ddd, J= 13.0,

11.3, 7.2 Hz, 0.5H), 1.84

(br s, 0.5H), 1.73 (br s,

0.5H), 1.51 (br s, 0.5H),

1.01 (td, J= 7.3, 3.9 Hz,

3H)

T H NMR (400 MHz, CDCI3 )

6 8.98 (d, J= 2.5 Hz, 1H),

8.66 - 8.60 (m, 1H), 8.28

(s, 1H), 7.99 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.45 (dd,

(thin film) ESIMS m/z J= 8.3, 4.8 Hz, 1H), 3.91 703

1659, 1585. 357 ([M+H]1 (dd, J= 11.5, 3.1 Hz, 1H),

3.35 (s, 3H), 3.00 (s, 3H),

2.17 (td, J= 12.1, 11.5, 7.2

Hz, 1H), 2.10- 1.99(m,

1H), 1.00 (t, J = 7.4 Hz,

3H)

525

17149

704 (thin film)

1655, 1585.

ESIMS

m/z 339

([WM)

1 H NMR (300 MHz, CDCI 3 )

68.93 (s, 1H), 8.59 - 8.51

(m, 1H), 8.12 (s, 1H), 8.06

-7.97 (m, 1H), 7.48 -7.38

(m, 1H), 3.79 (br s, 1H),

3.51 (br s, 1H), 2.89 (br s,

1H), 2.00 (s, 3H), 2.00 -

1.84 (m, 1H), 1.60 (dq, J=

13.7, 7.7, 7.3 Hz, 1H), 1.16

- 1.08 (m, 3H), 0.88 (t, J=

7.3 Hz, 3H)

705 (thin film)

1657, 1585.

ESIMS

m/z 355

([M+Hr)


6 8.99 (d, J= 5.4 Hz, 1H),

866 - 8.59 (m, 1H), 8.25

(br s, 0.5H), 8.17 (br s,

0.5H), 8.06 - 7.97 (m, 1H),

7.45 (td, J= 10.6, 9.5, 4.9

Hz, 1H), 3.97 (br s, 1H),

3.72 (dd, J= 11.2, 3.0 Hz,

1H), 3.51 (br s, 1H), 2.64

(s, 1.5H), 2.53 (s, 1.5H),

2.12 - 2.02 (m, 0.5H), 1.83

(br s, 0.5H), 1.69 (br s,

0.5H), 1.46 (br s, 0.5H),

1.22 - 1.17 (m, 3H), 1.02(t,

J=7.3 Hz, 3H)

706 ESIMS m/z

297 ((M+Hr)


6 8.86 (d, J = 2.6 Hz, 1H),

8.49 (dd, J= 4.8, 1.2 Hz,

1H), 7.95 (ddd, J= 8.3,

2.5, 1.3 Hz, 1H), 7.68 (s,

1H), 7.37 (dd, J= 8.3, 4.8

Hz, 1H), 5.29 (br s, 2H),

3.02 - 2.73 (m, 2H), 2.64 (t,

J=7.1 Hz, 2H), 2.18 (s,

3H)

526

17149


IS 8.94 (dd, J = 2.7, 0.7 Hz,

1H), 8.63 (dd, J = 4.8, 1.4

Hz, 1H), 8.04 (ddd, J = 8.4,

(thin film) ESIMS Ink 2.7, 1.4 Hz, 1H), 7.98 (s,

339 ([M+H]), 1H), 7.46 (ddd, J = 8.3, 707 3093, 2958,

1661 337.4 ([M-Hr 4.7, 0.7 Hz, 1H), 3.25 (s,

) 3H), 2.94 - 2.85 (m, 1H),

2.83 (dd, J = 8.0, 7.1 Hz,

2H), 2.46 (I, J = 7.5 Hz,

2H), 1.23(d, J = 6.7 Hz,

6H)


6 8.94 (dd, J = 2.7, 0.7 Hz,

1H), 8.64 (dd, J = 4.8, 1.5

Hz, 1H), 8.04 (ddd, J = 8.4,

2.7, 1.4 Hz, 1H), 7.82 (s,

1H), 7.47 (ddd, J= 8.3,

(thin film) 4.7, 0.7 Hz, 1H), 7.32 - ESIMS miz

708 3088, 2958,

1661 415 ((Whi])

7.20 (m, 4H), 7.15 (m, 1H),

3.90 (q, J= 7.0 Hz, 1H),

3.67 (q, J = 7.2 Hz, 2H),

2.73 - 2.49 (m, 2H), 2.24

(ddd, J = 8.4, 6.7, 5.2 Hz,

2H), 1.52(d, J= 7.0 Hz,

3H), 1.12 (t, J = 7.2 Hz,

3H)

527

17149

709 (thin film)

2967, 1661

ESIMS m/z

339.66

([M+H]+)


6 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.07 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.46 (ddd, J= 8.3,

4.7, 0.8 Hz, 1H), 3.71 (d, J

= 8.4 Hz, 2H), 3.13 (s, 2H),

3.14 - 3.02 (m, 1H), 1.26

(d, J= 6.7 Hz, 6H), 1.17(t,

J= 7.2 Hz, 3H)

710

(thin film)

3293, 3093,

2975, 2930,

1658

ESIMS m/z

349 (WM')

'H NMR (400 MHz,

Chloroform-d) 68.95 (d, J

= 2.7 Hz, 1H), 8.63 (dd, J=

4.8, 1.5 Hz, 1H), 8.04(m,

2H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.84 (m,

1H), 3.42(d, J= 14.3 Hz,

2H), 3.28(d, J= 14.3 Hz,

1H), 2.28 (d, J= 2.3 Hz,

1H), 1.50 (d, J= 7.1 Hz,

4H), 1.17 (t, J = 7.2 Hz,

3H)

711

(thin film)

3069, 2976,

2931, 1667

ESIMS m/z

442.8

(Win


6 8.96 (dd, J= 2.7, 0.7 Hz,

1H), 8.62 (dd, J= 4.8, 1.5

Hz, 1H), 8.14 (s, 1H), 8.03

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.61 (ddd, J= 8.1,

7.5, 0.8 Hz, 1H), 7.45 (ddd,

J= 8.3, 4.8, 0.8 Hz, 1H),

7.40 (d, J= 8.1 Hz, 1H),

7.32 (dd, J= 7.5, 0.8 Hz,

1H), 3.90 (bs, 2H), 3.74 (q,

J= 7.2 Hz, 2H), 1.17 (t, J=

7.2 Hz, 3H)

528

17149

712

(thin film)

3391, 2894,

2675, 2496,

1666

ES I MS m/z

386.5

([M+H])


69.00 (d, J= 2.4 Hz, 1H),

8.61 (dd, J = 4.7, 1.3 Hz,

1H), 8.05 (s, 1H), 8.01

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.42 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 4.66 (q, J

= 7.0 Hz, 1H), 3.89(d, J=

42.5 Hz, 1H), 3.42 (s, 1H),

2.98 (s, 3H), 2.78 (s, 3H),

1.33 (t, J= 9.1 Hz, 3H),

1.16(t, J= 7.2 Hz, 3H)

713

(thin film)

3101, 2934,

1671

ESIMS m/z

415 ([M+Hr)


6 9.00 (d, J= 2.5 Hz, 1H),

8.60 (dd, J= 4.8, 1.4 Hz,

1H), 8.08 (s, 1H), 8.02

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.43 (ddd, J= 8.3,

4.8.0.6 Hz, 1H), 4.56 (q, J

= 7.0 Hz, 1H), 3.94 (s, 1H),

3.41 (s, 1H), 2.94 (s, 3H),

2.72(s, 6H), 1.33(d, J=

7.0 Hz, 3H), 1.15(t, J=7.2

Hz, 3H)

714 (thin film)

1660

ESIMS m/z

412 ([M+Hr)


68.97 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.2 Hz,

1H), 8.10 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.5 Hz, 1H), 4.70 (pd,

J=8.1,3.6 Hz, 1H), 3.30

(s, 3H), 3.19 - 3.08 (m,

4H), 2.59 (dd, J= 17.1, 3.6

Hz, 1H)

529

17149

715 (thin film)

1658

ESIMS m/z

365 ([M+Hr)


68.98 (d, J = 2.6 Hz, 1H),

8.65 (s, 1H), 8.61 -8.51

(m, 1H), 8.00 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.48 -

7.37 (m, 2H), 3.79 - 3.61

(m, 1H), 3.03 (dd, J= 15.7,

3.5 Hz, 1H), 2.61 (dd, J=

15.7, 10.6 Hz, 1H), 2.34 (s,

3H)

716

(thin film)

3091, 2976,

1659

ES I MS m/z

457.0

([M+11]. ),

455.5 (EM-Hr )


6 8.82 (dd, J= 2.7, 0.7 Hz,

1H), 8.60 (dd, J= 4.8, 1.4

Hz, 1H), 7.97 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.80 (s,

1H), 7.54 (t, J=7.8 Hz,

1H), 7.43 (ddd, J= 8.2,

4.7, 0.7 Hz, 1H), 7.26 (s,

1H), 7.21 (dd, J= 7.5, 0.8

Hz, 1H), 3.72(q, J= 7.1

Hz, 2H), 3.44 (t, J= 6.9

Hz, 2H), 2.71 (t, J= 6.9

Hz, 2H), 1.16(t, J= 7.2

Hz, 3H)

717

(thin film)

3083, 2962,

1644

ESIMS m/z

353 ([M+Hr)


6 9.03 - 8.88 (m, 1H), 8.63

(dd, J=4.7,1.4 Hz, 1H),

8.05 (bs, 1H), 8.04 (ddd, J

= 8.3, 2.7, 1.4 Hz, 1H),

7.46 (ddd, J= 8.4, 4.7, 0.8

Hz, 1H), 3.79 (m, 2H), 3.32

(bs, 1H), 2.96 (p, J= 6.7

Hz, 1H), 1.49 (d, J= 6.8

Hz, 3H), 1.20 (d, J = 6.9

Hz, 6H), 1.11 (m, 3H)

530

17149

718

(thin film)

3091, 2976,

1663

ESIMS m/z

476.9

([M+Hr)


15 8.89 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J= 4.8, 1.4

Hz, 1H), 8.43 (dt, J= 2.0,

1.0 Hz, 1H), 8.07 - 7.95

(m, 2H), 7.69(d, J= 2.0

Hz, 1H), 7.45 (ddd, J--: 8.3,

4.8, 0.8 Hz, 1H), 4.00 (s,

2H), 3.74 (t, J= 7.1 Hz,

2H), 1.19 (t, J= 7.2 Hz,

3H)

719

(thin film)

3091, 2972,

2928, 1668

ESIMS m/z

422 (CM+Hr)

I FI NMR (400 MHz, CDCI 3 )

15 8.96 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.05 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.99 (s,

1H), 7.46 (ddd, J= 8.3,

4.7, 0.8 Hz, 1H), 6.93 (d, J

= 0.8 Hz, 1H), 3.76 (d, J=

0.8 Hz, 2H), 3.71 (q, J=

7.2 Hz, 2H), 2.82 (t, J= 7.3

Hz, 2H), 2.66 (s, 3H), 2.43

(t, J= 7.4 Hz, 2H), 1.15(t,

J=7.2 Hz, 3H)

531

17149


58.88 (d, J= 2.8 Hz, 1H),

8.62 (dd, J=4.7,1.5 Hz,

1H), 7.99 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.81 (bs,

(thin film) ESIMS m/z

1H), 7.45 (ddd, J= 8.4,

720 3087, 2969,

2927, 1658 401 ([M+H])

4.8, 0.8 Hz, 1H), 7.24 -

7.15 (m, 5H), 4.20 (q, J=

7.1 Hz, 1H), 3.70 (bm, 2H),

2.93 (d, J= 14.4 Hz, 1H),

2.84 (d, J = 14.3 Hz, 1H),

1.56 (d, J= 7.3 Hz, 3H),

1.15(t, J= 7.2 Hz, 3H)

I HNMR (400 MHz, CDCI 3 )

i5 8.87 (d, J= 2.7 Hz,

0.55H), 8.80 (d, J= 2.6 Hz,

0.45H), 8.64 (ddd, J=

11.1, 4.8, 1.4 Hz, 1H),8.03

-7.91 (m, 1H), 7.62 (s,

0.55H), 7.47 (ddd, J=

13.4, 8.4, 4.7 Hz, 1H), 7.30 (thin film)

ESIMS m/z (m, 3.45H), 7.20 - 7.10 (m, 721 3068, 2969,

415 ([M+Hr) 1H), 7.03 (dd, J= 8.3, 7.1 1655

Hz, 1H), 3.97(m, 1H),

3.40- 3.80 (m, 2H), 3.30 (q,

J= 6.9 Hz, 0.55H), 3.08 (q,

J= 6.7 Hz, 0.45H), 1.48 (d,

J= 7.1 Hz, 1.65H), 1.45

(dd, J= 6.9, 1.9 Hz, 3H),

1.29(d, J= 6.9 Hz, 1.35H),

1.09 (m, 3H)

532

17149

722

(thin film)

3091, 2976,

2932, 1659

ESIMS m/z

456 ([M+H]),

454.4 (EM-Hr )


6 8.79 (d, J= 2.7 Hz, 1H),

8.58 (dd, J= 4.7, 1.4 Hz,

1H), 8.30 (s, 1H), 7.94

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.57 (t, J=7.8 Hz,

1H), 7.41 (ddd, J= 8.4,

4.7, 0.8 Hz, 1H), 7.31 (d, J

= 8.1 Hz, 1H), 7.24 (s, 1H),

4.79(q, J= 7.0 Hz, 1H),

3.80(m, 1H), 3.51 (m, 1H),

1.50(d, J= 7.1 Hz, 3H),

1.14(t, J=7.2 Hz, 3H)

723

(thin film)

3091, 2976,

2933, 1659

ESIMS m /z

489 ([m-Hr)

I FINMR (400 MHz, CDCI3 )

58.67 (s, 1H), 8.58 (dd, J

= 4.8, 1.4 Hz, 1H), 8.21 (s,

1H), 7.86 (s, 2H), 7.61 (d,

J= 2.0 Hz, 1H), 7.39 (dd, J

= 8.4, 4.7 Hz, 1H), 4.87 (d,

J=6.9 Hz, 1H), 3.74 (s,

2H), 1.57 (d, J= 8Hz, 3H),

1.18 (t, J = 7.2 Hz, 3H)

724 (thin film)

1661

ESIMS m/z

369 ([M+Hr)

I HNMR (400 MHz, CDCI3)

68.97 (bs, 1H), 8.63 (d, J

= 4.3 Hz, 1H), 8.15(s, 1H),

8.05 (ddd, J= 8.3, 2.6, 1.4

Hz, 1H), 7.46 (dd, J= 8.3,

4.7 Hz, 1H), 3.80 (bs, 1H),

3.60 (bs, 1H), 3.48(t, J=

6.4 Hz, 2H), 3.41 -3.30

(m, 1H), 3.29 (s, 3H), 2.78

(td, J= 6.4, 1.2 Hz, 2H),

1.44 (d, J= 7.1 Hz 3H),

1.11 (t, J= 7.2 Hz, 3H)

533

17149

I li NMR (400 MHz, CDCI 3)

•5 8.97(d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.12 (s, 1H), 8.04

ESIMS m/z (ddd, J= 8.3, 2.7, 1.5 Hz,

725 350 1H), 7.46 (dd, J= 8.3, 4.8

([M+2Hr) Hz, 1H), 3.89 - 3.72 (m,

1H), 3.71 -3.49 (m, 3H),

3.40 - 3.18 (m, 2H), 1.47

(d, J= 7.1 Hz, 3H), 1.18(t,

J= 7.2 Hz, 3H)

1 Fi NMR (400 MHz, CDCI3)

o 9.00(d, J= 2.2 Hz, 1H),

8.63 (d, J=4.6 Hz, 1H),

8.26 (s, 1H), 8.04 (ddd, J=

8.3, 2.5, 1.3 Hz, 1H), 7.46

ESIMS m/z (dd, J= 8.3, 4.7 Hz, 1H),

(thin film) 3.94- 3.51 (m, 2H), 3.36 726 365

1654 ((M+2Hr)

(bs, 1H), 2.97 (dt, J= 13.3,

6.6 Hz, 1H), 2.84 (dt, J=

13.6, 6.9 Hz, 1H), 3.04-

2.90 (m, 1H), 2.66 - 2.53

(m, 1H), 1.52 (d, J= 7.1

Hz, 3H), 1.19 (t, J = 7.2

Hz, 3H)


0 8.96(d, J= 2.2 Hz, 1H),

8.62 (d, J=4.6 Hz, 1H),

8.13(s, 1H), 8.05 (d, J=

ESIMS m/z 8.4 Hz, 1H), 7.46 (dd, J= (thin film)

727 354 8.3, 4.8 Hz, 1H), 3.90 - 1655

([M+2Hr) 3.47 (m, 2H), 3.36 - 3.20

(m, 1H), 2.61 -2.43 (m,

2H), 1.57- 1.42 (m, 5H),

1.17 (d, J= 7.1 Hz, 3H),

0.94(t, J= 7.3 Hz, 3H)

534

17149

728 (thin film)

1655

ESIMS m/z

385 ([M+H])

IHNMR (400 MHz, CDCI3)

(5 8.98(d, J= 2.7 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.16 (s, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.46 (ddd, J= 10.5,

4.8, 2.7 Hz, 1H), 3.88 -

3.54 (m, 2H), 3.33 (d, J=

5.3 Hz, 1H), 2.88 - 2.79

(m, 2H), 2.67 - 2.58 (m,

2H), 2.10 (s, 3H), 1.49 -

1.45 (m, 3H), 1.17 (t, J=

7.2, 2.6 Hz, 3H)

729 (thin film)

1656

ESIMS m/z

381 ([M+Hr)


58.96 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7,1.3 Hz,

1H), 8.11 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 3.91 -3.49 (m,

2H), 3.37- 3.22 (m, J= 5.7

Hz, 1H), 2.66 (p, J= 6.2

Hz, 1H), 1.60- 1.35(m,

7H), 1.16 (t, J= 7.2 Hz,

3H), 0.93 (t, J= 7.3 Hz,

3H), 0.84 (t, J= 7.3 Hz,

3H)

535

17149

730 (thin film)

1658

ESIMS m/z

355 ([M+H]. )


68.96 (d, J = 2.3 Hz, 111),

8.63(d, J=4.5 Hz, 1H),

8.09 (s, 1H), 8.05 - 8.01

(m, 1H), 7.46 (dd, J= 8.3,

4.8 Hz, 1H), 3.80 - 3.62

(m, 2H), 3.58 (t, J= 6.2 Hz,

2H), 3.34 (s, 3H), 3.16 (s,

2H), 2.86 (t, J= 6.2 Hz,

2H), 1.17 (t, J = 7.2 Hz,

3H)

731 (thin film)

1655

ESIMS m/z

335 ([M+H]')


58.96 (d, J= 2.5 Hz, 1H),

8.63 (d, J=4.5 Hz, 1H),

8.09- 8.00 (m, 2H), 7.47

(dd, J= 8.3, 4.8 Hz, 1H),

3.80 -3.63 (d, J= 6.8 Hz,

2H), 3.41 (s, 2H), 3.32 (s,

2H), 2.20 (t, J= 2.6 Hz,

1H), 1.18 (t, J=7.1 Hz,

3H)

732 (thin film)

1659

ES I MS m/z

340

([1V14-2Hr)


68.96 (d, J= 2.5 Hz, 1H),

8.63(d, J= 4.7 Hz, 1H),

8.10 (s, 1H), 8.04 (ddd, J=

8.3, 2.6, 1.4 Hz, 1H), 7.46

(dd, J= 8.3, 4.7 Hz, 1H),

3.76 -3.65 (m, 2H), 3.09

(s, 2H), 2.63 (t, J= 7.63

Hz, 2H), 1.68- 1.54 (m,

2H), 1.17(t, J = 7.2 Hz,

3H), 0.97 (t, J= 7.3 Hz,

3H)

536

i

17149

733 (thin film)

1658

ESIMS m/z

397 ([M+Hr)


6 8.96 (d, J = 2.6 Hz, 1H),

8.63 (dd, J=4.7,1.3 Hz,

1H), 8.10 (s, 1H), 8.04 (m,

1H), 7.46 (dd, J=7.9,4.7

Hz, 1H), 4.23-4.05 (m, 2H),

3.72 (bs, 2H), 3.13 (s, 2H),

2.93 (t, J= 7.1 Hz, 2H),

2.64 (t, J= 7.1 Hz, 2H),

1.25 (t, J= 7.2 Hz, 3H),

1.18(t, J= 7.2 Hz, 3H)

734 (thin film)

1658

ESIMS ink

369 ([M+H]t)


6 8.97 (bs, 1H), 8.63 (bs,

1H), 8.06 (ddd, J= 8.3,

2.6, 1.3 Hz, 1H), 8.00 (s,

1H), 7.47 (dd, J=8.3,4.7

Hz, 1H), 3.72 (q, J= 7.1

Hz, 2H), 3.52 (t, J= 6.5

Hz, 2H), 3.33 (s, 3H), 2.86

(t, J= 7.4 Hz, 2H), 2.67 (t,

J=6.5 Hz, 2H), 2.45 (t, J=

7.4 Hz, 2H), 1.16 (t, J = 7.2

Hz, 3H)

735 (thin film)

1656

ESIMS ink

349 ([M+Hr)


6 8.96 (d, J = 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.98 (s,

1H), 7.50 - 7.43 (m, 1H),

3.72 (q, J= 7.2 Hz, 2H),

3.22 (d, J= 2.6 Hz, 2H),

2.98 (t, J= 7.3 Hz, 2H),

2.52 (t, J= 7.3 Hz, 2H),

2.17(t, J= 2.6 Hz, 1H),

1.17(t, J= 7.2 Hz, 3H)

537

17149


5 8.98(d, J= 2.5 Hz, 1H),

8.63 (bs, 1H), 8.07 (dd, J=

2.7, 1.4 Hz, 1H), 8.05 (s,

1H), 7.47 (dd, J= 8.3, 4.7 (thin film) ESIMS m/z

736 Hz, 1H), 3.73 (q, J= 7.1 1657 364 ([M+Hr)

Hz, 2H), 2.89 (t. J= 7.0

Hz, 2H), 2.82 - 2.74 (m,

2H), 2.69 - 2.61 (m, 2H),

2.48 (t, J= 7.0 Hz, 2H),

1.17(t, J= 7.2 Hz, 3H)

IFI NMR (400 MHz, CDC13)

15 8.96(d, J= 2.4 Hz, 1H),

8.63 (bs, 1H), 8.06 (ddd, J

= 8.3, 2.7, 1.4 Hz, 1H),

7.99 (s, 1H), 7.47 (dd, J= (thin film) ESIMS m/z

737 8.3, 4.8 Hz, 1H), 3.72 (q, J 1657 353 ([M+H]+ )

= 7.2 Hz, 2H), 2.84 - 2.74

(m, 2H), 2.50 - 2.37 (m,

4H), 1.65- 1.47 (m, 2H),

1.16 (t, J=7.2 Hz, 3H),

0.94 (t, J= 7.3 Hz, 3H)

1 11 NMR (400 MHz, CDCI 3 )

58.95 (bs, 1H), 8.63 (d, J

= 4.3 Hz, 1H), 8.05 (ddd, J

= 8.3, 2.7, 1.4 Hz, 1H),

7.96 (s, 1H), 7.46 (dd, J=

738 ESIMS m/z 8.4, 4.7 Hz, 1H), 3.71 (q, J

381 ([M+H]) = 7.2 Hz, 2H), 2.77 (t, J=

7.6 Hz, 2H), 2.50 - 2.34

(m, 3H), 1.62- 1.48 (m,

4H), 1.16 (t, J= 7.2 Hz,

3H), 0.93 (t, J= 7.4 Hz,

6H)

538

17149

1 1-I NMR (400 MHz, CDCI3 )

6 9.00 (d, J= 9.3 Hz, 1H),

8.63 (bs, 1H), 8.14 b(s,

1H), 8.07 (s, 1H), 7.47 (dd,

J= 7.5, 5.0 Hz, 1H), 4.20 -

(thin film) ESIMS m/z 4.05 (m, 2H), 3.72 (dd, J= 739

1659 410 ([M+H]) 13.9, 6.9 Hz, 2H), 2.88 -

2.80 (m, 2H), 2.80 - 2.70

(m, 2H), 2.61 -2.52 (t, J=

7.1 Hz, 2H), 2.53 - 2.38

(m, 2H), 1.28- 1.21 (m,

3H), 1.20- 1.12 (m, 3H)


158.89 (d, J= 2.7 Hz, 1H),

8.62 (dd, J= 4.7, 1.4 Hz,

1H), 7.89 (d, J= 8.3 Hz,

1H), 7.80 (s, 1H), 7.41 (dd,

(thin film) J= 8.4, 4.7 Hz, 1H), 7.34 - ESIMS m/z

740 3065, 2973,

2931, 1656 568 ([M+H])

7.11 (m, 15H), 3.71-3.62

(m, 2H), 2.72 (dd, J= 12.0,

8.8 Hz, 1H), 2.31 (ddd, J=

8.7, 6.8, 5.3 Hz, 1H), 2.01

(dd, J= 11.9, 5.2 Hz, 1H),

1.14(t, J= 7.1 Hz, 3H),

0.95 (d, J= 6.8 Hz, 3H)

IHNMR (400 MHz, CDCI3)

5 8.96 (t, J = 2.7 Hz, 1H),

8.71 -8.56 (m, 1H), 8.17 - (thin film)

ESIMS m/z 7.94 (m, 2H), 7.52 - 7.38 741 3392, 3090,

2974, 1654 363 ([M+H]) (m, 1H), 3.96 - 3.46 (m,

3H), 2.16 (d, J= 2.4 Hz,

1H), 1.52 (m, 4H), 1.44(m,

3H), 1.18 (m, 3H)

539

17149

1 FI NMR (400 MHz,

Chloroform-d) 5 8.93 (dd, J

= 2.7, 0.8 Hz, 1H), 8.62

(dd, J= 4.7, 1.4 Hz, 1H),

8.08 - 7.96 (m, 2H), 7.45 (thin film)

ESIMS m/z (ddd, J= 8.2, 4.7, 0.8 Hz, 742 3091, 2971,

2926, 1654 423 ([M+Hr) 1H), 6.90(d, J= 0.8 Hz,

1H), 3.92 - 3.79 (m, 2H),

3.67 (m, 2H), 3.45 (q, J=

6.7 Hz, 1H), 2.60 (s, 3H),

1.50(d, J= 6.8 Hz, 3H),

1.13 (t, J= 7.1 Hz, 3H)

1 FINMR (400 MHz, CDCI 3 )

6 8.96 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.9, 1.4 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.03 (s,

(thin film) ESIMS tn/z 1H), 7.47 (ddd, J= 8.4,

743 469 4.8, 0.6 Hz, 1H), 3.78 - 1716

([M+H+1r) 3.65 (m, 1H), 3.26 (dd, J-

17.9, 3.5 Hz, 1H), 3.09 (dd,

J= 17.9, 10.0 Hz, 1H),

2.98 - 2.91 (m, 2H), 2.81

(dd, J= 10.6, 3.7 Hz, 2H),

2.30 (s, 3H), 2.13 (s, 3H)

540

17149


6 8.96(d, J= 2.6 Hz, 1H),

8.65 (dd, J=4.8,1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.98 (s,


744 4.8, 0.6 Hz, 1H), 3.89 - 1670 476 ([M+H])

3.66 (m, 3H), 2.64 (dd, J=

16.2, 3.8 Hz, 1H), 2.43 (dd,

J= 16.2, 10.1 Hz, 1H),

2.29 (s, 3H), 2.28 - 2.12

(m, 2H), 1.93 - 1.74 (m,

2H)


68.96 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7,1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.01 (s,

1H), 7.47 (ddd, J= 8.3,

(thin film) ESIMS m/z 4.8, 0.5 Hz, 1H), 4.15 - 745

1662 422 ([M+H]) 3.37 (m, 2H), 2.84 (dd,J=

12.4, 9.7 Hz, 1H), 2.73 (s,

1H), 2.48 (dd, J=12.5,4.8

Hz, 1H), 2.35- 2.10(m,

2H), 2.03 (s, 3H), 1.90 -

1.74 (m, 2H), 1.16 (d,J=

6.7 Hz, 31-1)

541

17149

746 (thin film)

1668

ESIMS m/z

440 ([M+H])


68.96 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.99 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 4.55 (t, J

= 5.6 Hz, 1H), 4.43 (t, J=

5.3 Hz, 1H), 3.75 (tdd, J=

12.3, 8.5, 3.7 Hz, 3H), 2.63

(dd, J= 16.3, 3.7 Hz, 1H),

2.42 (dd, J= 16.3, 10.0 Hz,

1H), 2.29 (s, 3H), 1.86 -

1.66 (m, 4H)

747 (thin film)

1660

ESIMS m/z

386 ([M+H)*)

'H NMR (400 MHz, CD0 3)

6 8.96(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.98 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 4.54 (t, J

= 5.7 Hz, 1H), 4.42 (t, J=

5.5 Hz, 1H), 3.88 - 3.56

(m, 2H), 3.34 - 3.14 (m,

1H), 2.48 (dd, J=15.7, 6.5

Hz, 1H), 2.28 (dd, J= 15.7,

7.6 Hz, 1H), 2.06 (s, 3H),

1.85 - 1.65 (m, 4H), 1.29

(d, J= 6.8 Hz, 3H)

542

17149


15 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J= 4.8, 1.4

Hz, 1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.96 (s,

(thin film) ES I MS m/z

1H), 7.47 (ddd, J= 8.2,

748 3091, 2966,

2927, 1659 353 ([M+Hr)

4.7, 0.7 Hz, 1H), 3.72 (q, J

= 7.1 Hz, 2H), 2.95 - 2.86

(m, 1H), 2.83 (dd, J= 8.0,

7.1 Hz, 2H), 2.42 (dd, J=

8.0, 7.0 Hz, 2H), 1.23 (d, J

=6.6 Hz, 6H), 1.16 (t, J =

7.2 Hz, 3H)


6 8.96 (d, J = 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.13 (s, 1H), 8.03

(ddd, J= 8.3, 2.7, 1.4 Hz,

(thin film) ESIMS m/z 1H), 7.51 -7.43 (m, 1H), 749

1659 372 ([M+Hr) 4.55 (td, J= 5.7, 2.8 Hz,

1H), 4.49 - 4.37 (m, 1H),

4.10 - 3.35 (m, 2H), 3.27

(d, J=6.5 Hz, 1H), 2.08(s,

3H), 1.87- 1.65(m, 4H),

1.44 (d, J= 6.9 Hz, 3H)

543

17149

750 (thin film)

1658,

ESIMS m/z

386 ([M+Hr)


58.96 (d, J = 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.07 - 7.96 (m, 2H),

7.50 - 7.42 (m, 1H), 4.55 (t,

J= 5.7 Hz, 1H), 4.43 (t, J =

5.4 Hz, 1H), 3.72 (d, J=

152.4 Hz, 2H), 2.85 (dd, J

= 12.6, 9.2 Hz, 1H), 2.72

(s, 1H), 2.47 (dd, J= 12.7,

5.2 Hz, 1H), 2.02 (s, 3H),

1.91 - 1.66(m, 4H), 1.16

(d, J= 6.7 Hz, 3H)

751 (thin film)

1670


6 8.97 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.10(s, 1H), 8.09 -

7.98 (m, 1H), 7.47 (ddd, J

= 8.3, 4.8, 0.6 Hz, 1H),

4.35 - 4.15 (m, 1H), 3.29

(s, 3H), 3.01 (dd, J= 17.2,

7.0 Hz, 1H), 2.75 - 2.56

(m, 4H)

19F NMR (376

MHz, CDCI3) 6

-63.15.

544

17149


68.96 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,


2.7, 1.4 Hz, 1H), 7.98 (s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.5 Hz, 1H), 3.87 - 752

1663 422 ([M+H].) 3.61 (m, 2H), 3.23 (h, J=

6.8 Hz, 1H), 2.48 (dd, J=

15.6, 6.9 Hz, 1H), 2.28 (dd,

J=15.7, 7.3 Hz, 1H), 2.26

-2.13 (m, 2H), 2.07 (s,

3H), 1.89- 1.76(m, 2H),

1.29(d, J= 6.8 Hz, 3H)

I FI NMR (400 MHz,

Chloroform-d) 6 8.90 - 8.81

(m, 1H), 8.65 (d, J= 5.0

(thin film)

Hz, 1H), 8.61 (dd, J= 4.7,

1.4 Hz, 1H), 7.97 (ddd, J= ESIMS m/z

753 3092, 2935,

1662 443 ([M+H])

8.3, 2.7, 1.4 Hz, 1H), 7.89

(s, 1H), 7.44 (ddd, J= 8.4,

4.7, 0.8 Hz, 1H), 7.17 (d, J

=5.0 Hz, 1H), 3.44 (t, J =

7.0 Hz, 2H), 3.26 (s, 3H),

2.72 (t, J= 7.0 Hz, 2H)

1 H NMR (400 MHz,

Chloroform-d) 6 8.93 (d, J

= 1.1 Hz, 1H), 8.90 (dd, J=

(thin film)

2.7, 0.7 Hz, 1H), 8.62 (dd,

J= 4.8, 1.4 Hz, 1H), 8.02 - ESIMS m/z

754 3091, 2934,

1661 443 ([M+Hr)

7.97 (m, 1H), 7.94(s, 1H),

7.45 (ddd, J= 8.3, 4.8, 0.8

Hz, 1H), 7.42(d, J= 1.3

Hz, 1H), 3.52 (t, J= 6.9

Hz, 2H), 3.27 (s, 3H), 2.67

(t, J= 6.9 Hz, 2H)

545

17149


6 8.96(s, 1H), 8.64 (d, J=

3.8 Hz, 1H), 8.12 (s, 1H),

8.03 (ddd, J= 8.3, 2.6, 1.4

Hz, 1H), 7.47 (dd, J= 8.3, (thin film) ESIMS m/z

755 4.7 Hz, 1H), 4.05 - 3.43 1662 408 ((WM')

(m, 2H), 3.27 (d, J= 6.7

Hz, 1H), 2.27 - 2.13 (m,

2H), 2.11 (d, J= 18.1 Hz,

3H), 1.94- 1.70 (m, 2H),

1.44 (d, J= 6.9 Hz, 3H)


6 8.96 (s, 1H), 8.65 (s,

1H), 8.05 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.96 (s,

1H), 7.48 (dd, J=8.3,4.7 (thin film) ESIMS m/z

756 1672 490 ([101-1]+)

Hz, 1H), 3.82 - 3.63 (m,

3H), 2.63 (dd, J= 16.3, 3.7

Hz, 1H), 2.42 (dd, J= 16.2,

10.1 Hz, 1H), 2.29 (s, 3H),

2.24 - 2.07 (m, 2H), 1.69 -

1.62 (m, 4H)

1H NMR (400 MHz, CDCI 3)

6 8.96 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.96 (s,

1H), 7.53 - 7.40 (m, 1H),

(thin film) ESIMS m/z 3.81 -3.58 (m, 2H), 3.31 - 757

1661 436 ([M+11] +) 3.16 (m, 1H), 2.48 (dd, J=

15.6, 6.6 Hz, 1H), 2.28 (dd,

J=15.6, 7.5 Hz, 1H), 2.22

-2.09 (m, 2H), 2.06 (s,

3H), 1.72- 1.55 (m, 4H),

1.29(d, J= 6.8 Hz, 3H).

546

17149

758 (thin film)

1660

ESIMS m/z

422 ([M+H])


5 8.95 (d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.11 (s, 1H), 8.03

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.46 (dd, J= 8.3.4.8

Hz, 1H), 3.97 - 3.41 (m,

2H), 3.26 (d, J= 6.7 Hz,

1H), 2.22 - 2.10 (m, 2H),

2.08 (s, 3H), 1.70- 1.61

(m, 4H), 1.44 (d, J= 6.9

Hz, 3H)

759 (thin film)

1659

ESIMS m/z

436 ([M+Hr)

I HNMR (400 MHz, CDCI 3)

58.96 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 8.00 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.70 (d, J

= 121.1 Hz, 2H), 2.84 (dd,

J=12.6, 9.4 Hz, 1H), 2.72

(s, 1H), 2.48 (dd, J= 12.6,

5.0 Hz, 1H), 2.16(d, J=

4.4 Hz, 2H), 2.02 (s, 3H),

1.78- 1.53(m, 4H), 1.16

(d, J= 6.7 Hz, 3H).

547

17149

760

(thin film)

3095, 2920,

1659

ESIMS

m/z 394

([M+H])

1 11 NMR (400 MHz,

Chloroform-d) 58.85 (dd, J

= 2.8, 0.7 Hz, 1H), 8.62

(dd, J= 4.7, 1.5 Hz, 1H),

8.00 - 7.93 (m, 1H), 7.87

(s, 1H), 7.49 - 7.38 (m,

1H), 6.63 (q, J= 1.0 Hz,

1H), 3.44 (t, J=6.8 Hz,

2H), 3.25 (s, 3H), 2.74 (t, J

= 6.8 Hz, 2H), 2.24 (d, J=

1.0 Hz, 3H)

761

(thin film)

3093, 2919,

1659

ESIMS m/z

408 ([M+Hr)

1 H NMR (400 MHz,


= 2.7, 0.6 Hz, 1H), 8.61

(dd, J= 4.7, 1.5 Hz, 1H),

7.98 (ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.88 (s, 1H), 7.44

(ddd, J= 8.3, 4.8, 0.7 Hz,

1H), 3.37 (t, J=6.8 Hz,

2H), 3.25 (s, 3H), 2.72 (t, J

= 6.8 Hz, 2H), 2.18 - 2.14

(m, 3H), 2.11 (d, J= 0.9

Hz, 3H)

762

(thin film)

3096, 2960,

1661

ES I MS m/z

436 anin

I FI NMR (400 MHz,


= 2.7, 0.6 Hz, 1H), 8.61

(dd, J= 4.8, 1.4 Hz, 1H),

7.96 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.85 (s, 1H), 7.43

(ddd, J= 8.4, 4.8, 0.8 Hz,

1H), 6.61 (s, 1H), 3.46 (t, J

= 6.7 Hz, 2H), 3.25 (s, 3H),

2.77 (t, J= 6.8 Hz, 2H),

1.16 (s, 9H)

548

17149

763 (thin film)

1656

ESIMS m/z

339 ([M+H])


6 8.96 (d, J = 2.5 Hz, 1H),

8.62 (dd, J= 4.7, 1.3 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.95 (s,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 3.70 (q, J= 7.1

Hz, 2H), 2.49 (t, J= 7.0

Hz, 2H), 2.27 (t, J= 7.2

Hz, 2H), 2.04 (s, 3H), 1.93

(p, J= 7.1 Hz, 2H), 1.16 (t,

J= 7.2 Hz, 3H)

764

(thin film)

3092, 2959,

1661

ESIMS miz

338 ([M-

Me)

1 H NMR (400 MHz,

Chloroform-d)15 8.93 (d, J

= 2.7 Hz, 1H), 8.63 (dd, J=

4.8, 1.5 Hz, 1H), 8.03 (ddd,

J= 8.3, 2.7, 1.5 Hz, 1H),

7.98 (s, 1H), 7.46 (dd, J=

8.3, 4.7 Hz, 1H), 3.25 (s,

3H), 2.82 (dd, J= 8.2, 7.2

Hz, 2H), 2.44 (t, J= 7.7

Hz, 2H), 1.30 (s, 9H)

765

(thin film)

3420, 3066,

2967, 1663

ESIMS m/z

355 ([M+Hr)


58.96 (dd, J= 2.8, 0.7 Hz,

1H), 8.62 (dd, J= 4.8,1.5

Hz, 1H), 8.08 (s, 1H), 8.02

(d, J= 1.4 Hz, 1H), 7.45

(ddd, J= 8.3, 4.8, 0.7 Hz,

1H), 3.269 (s, 3H), 3.14 -

3.02 (m, 1H), 2.85 - 2.61

(m, 4H), 1.32 (d, J= 6.9

Hz, 3H), 1.29 (d, J= 6.9

Hz, 3H)

549

17149

766

(thin film)

3105, 2971,

1657

ESIMS m/z

369 ([M+H])

'H NMR (400 MHz, CIDC13)

58.96 (dd, J= 2.6, 0.7 Hz,

1H), 8.62 (dd, J= 4.7, 1.4

Hz, 1H), 8.08 (s, 1H), 8.03

(ddd, J= 8.4, 2.7, 1.5 Hz,

1H), 7.45 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.26 (s,

3H), 3.04 - 2.92 (m, 1H),

2.82 - 2.57 (m, 3H), 1.27

(s, 9H)

767

(thin film)

3108, 2964,

1659

ESIMS m/z

439 ([M+1-1]+ )


5 9.04 - 8.88 (m, 1H), 8.70

- 8.58 (m, 1H), 8.08 (d, J=

16.1 Hz, 1H), 8.04 (ddd, J

= 5.8, 2.7, 1.4 Hz, 1H),

7.50 - 7.42 (m, 1H), 4.25

(m, 1H), 3.29 (s, 3H), 3.05

(dd, J= 17.7, 8.2 Hz, 1H),

2.76 (s, 3H), 2.49 (dd, J=

17.7, 3.3 Hz, 1H)

768 (thin film)

1675

ESIMS m/z

462 ([M+1-1]. )

I FINMR (400 MHz, CDCI 3 )

6 8.97 (d, J = 2.6 Hz, 111),

8.66 (dd, J= 4.7, 1.3 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.00 (s,

1H), 7.48 (dd, J= 8.3, 4.8

Hz, 1H), 4.06 - 3.80 (m,

2H), 3.79 - 3.66 (m, 1H),

2.63 (dd, J= 16.4, 3.7 Hz,

1H), 2.59 - 2.47 (m, 2H),

2.42 (dd, J= 16.4, 9.9 Hz,

11-9, 2.29 (s, 3H)

550

17149

1 H NMR (400 MHz, CDC1 3)

8 8.96 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.15 (s, 1H), 8.03

(thin film) ESIMS nilz (ddd, J= 8.3, 2.7, 1.5 Hz, 769

1657 394 ([M+H]) 1H), 7.52 - 7.42 (m, 1H),

4.14 - 3.61 (m, 2H), 3.34 -

3.21 (m, 1H), 2.64 - 2.34

(m, 2H), 2.08 (s, 3H), 1.44

(d, J= 6.9 Hz, 3H)


68.96 (d, J = 2.5 Hz, 1H),

8.65 (dd, J=4.7,1.2 Hz,

1H), 8.04 (ddd, J= 8.3,

(thin film) ESIMS nilz 2.8, 1.5 Hz, 2H), 7.47 (dd,

770 J = 8.4, 4.7 Hz, 1H), 4.14 - 1666 408 ([M+H])

3.65 (m, 2H), 2.84 (dd, J=

12.7, 9.1 Hz, 1H), 2.77 -

2.64 (m, 1H), 2.64 - 2.39

(m, 3H), 2.02 (s, 3H), 1.16

(d, J= 6.7 Hz, 3H)


68.89 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.03 (ddd, J= 8.3,

(thin film) ESIMS nth 2.7, 1.4 Hz, 1H), 7.47 (dd, 771

1661, 388 ([M+H]) J= 8.4, 4.7 Hz, 2H), 7.31 -

7.27 (m, 5H), 4.33 (dd, J=

7.9, 6.6 Hz, 1H), 3.17 (s,

3H), 2.79 - 2.64 (m,

2H), 1.90 (s, 3H).

551

17149


68.89 (s, 1H), 8.63 (dd, J

= 4.7, 1.2 Hz, 1H), 8.03

(ddd, J= 8.3, 2.5, 1.4 Hz,


772 1659 402 ([M+H])

Hz, 1H), 7.32 - 7.24 (m,

6H), 4.33 (dd, J= 8.3, 6.3

Hz, 1H), 3.79 - 3.45 (m,

2H), 2.67 (qd, J= 14.9, 7.3

Hz, 2H), 1.91 (s, 3H), 1.07

(t, J= 7.1 Hz, 3H)


6 8.88 (s, 1H), 8.63 (dd, J

= 4.7, 1.3 Hz, 1H), 8.03 (d,

J= 8.0 Hz, 1H), 7.47 (dd, J

= 8.4, 4.7 Hz, 1H), 7.31 -

(thin film) ESIMS m/z 7.26 (m, 6H), 4.33 (dd, J= 773

1659 428 ([M+Hr) 8.4, 6.2 Hz, 1H), 3.64 -

3.33 (m, 2H), 2.70 (qd, J =

15.0, 7.4 Hz, 2H), 1.91 (s,

3H), 0.94 - 0.78 (m, 1H),

0.53 - 0.32 (m, 2H), 0.19 -

0.09 (m, 2H).

IFINMR (400 MHz, CDCI3)

68.96 (d, J= 2.7 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.98 (s,

(thin film) ESIMS m/z 1H), 7.48 (dd, J= 8.4, 4.8 774

1664 408 ([M+Hr) Hz, 1H), 3.74(t, J= 7.2

Hz, 2H), 2.79 (t, J= 7.3

Hz, 2H), 2.47 (t, J= 7.2

Hz, 2H), 2.26 - 2.11 (m,

2H), 2.07 (s, 3H), 1.83 (dt,

J=15.1, 7.4 Hz, 2H)

552

17149


5 8.96 (d, J = 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.05 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.98 (s,

1H), 7.47 (dd, J= 8.4, 4.8

(thin film) ESIMS m/z Hz, 1H), 4.54(t, J= 5.7 775

1661 372 ([M+Hr) Hz, 1H), 4.42(t, J= 5.4

Hz, 1H), 3.79 - 3.61 (m,

2H), 2.79 (t, J= 7.3 Hz,

2H), 2.46 (t, J= 7.3 Hz,

2H), 2.07 (s, 3H), 1.83 -

1.74 (m, 1H), 1.74- 1.66

(m, 3H)

'H NMR (400 MHz,


=2.7 Hz, 1H), 8.64 (dd, J=

4.8, 1.4 Hz, 1H), 8.05 (ddd,

J = 8.3, 2.7, 1.5 Hz, 1H),

7.96(s, 1H), 7.47 (dd, J= (thin film) ESIMS m/z

776 8.3, 4.7 Hz, 1H), 3.69 (t, J 1662 422 ([M+H])

= 6.6 Hz, 2H), 2.79 (t, J=

7.3 Hz, 2H), 2.46 (t, J= 7.3

Hz, 2H), 2.13 (dtd, J=

10.8, 7.8, 3.9 Hz, 2H), 2.07

(s, 3H), 1.66- 1.62 (m,

4H).

553

17149


5 8.97(d, J= 2.6 Hz, 1H),

8.62 (dd, J= 4.8, 1.6 Hz,

1H), 8.16 (s, 1H), 8.11 -

7.98 (m, 1H), 7.45 (dd, J=

8.3, 4.8 Hz, 1H), 3.37 - (thin film) ESIMS ink

777 1660 384 ([M+Hr)

3.28 (m, 1H), 3.27 (s, 3H),

2.99 - 2.86 (m, 1H), 2.55

(s, 3H), 2.22 (dd, J= 17.6,

4.0 Hz, 1H), 2.03- 1.89

(m, 1H), 1.04(d, J=6.8

Hz, 3H), 0.98 (d, J= 6.8

Hz, 3H)

1 H NMR (400 MHz,


(m, 1H), 8.63 (ddd, J= 8.3,

4.7, 1.4 Hz, 1H), 8.12 (s,

1H), 8.09 - 7.98 (m, 1H),

7.45 (dt, J= 8.6, 4.4 Hz,

(thin film) ESIMS m/z 1H), 3.89 - 3.56 (m, 2H), 778

1654 384 ([M+Hr) 2.89 (dd, J= 17.7, 6.8 Hz,

1H), 2.54 (s, 3H), 2.20 (dd,

J= 17.8, 4.0 Hz, 1H), 2.07

- 1.89 (m, 1H), 1.18 (t, J=

7.2 Hz, 3H), 1.04 (d, J=

6.8 Hz, 3H), 0.98 (d, J=

6.8 Hz, 3H).

554

17149

779 ESIMS m/z

367 ([M+H])

'H NMR (CDCI3) 6 8.97 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4•8, 1.5 Hz, 1H), 8.13 -

7.99 (m, 2H), 7.46 (dd, J=

8.3, 4.7 Hz, 1H), 4.14 (t, J

= 7.3 Hz, 1H), 3.85 (br s,

1H), 3.57 (br s, 1H), 2.27

(s, 3H), 1.98 (dt, J= 14.2,

7.1 Hz, 1H), 1.74 - 1.62

(m, 1H), 1.16 (t, J= 7.2 Hz,

3H), 0.92 (t, J= 7.4 Hz,

3H)

780 (thin film)

1662

ESIMS m/z

456 ([M+H])

'H NMR (400 MHz,


= 2.7 Hz, 1H), 8.64 (dd, J=

4.7, 1.4 Hz, 1H), 8.02 (ddd,

J = 8.4, 2.8, 1.5 Hz, 1H),

7.78 (s, 1H), 7.56 (d, J =

8.1 Hz, 2H), 7.50 - 7.46

(m, 1H), 7.43 (t, J= 9.0 Hz,

2H), 4.38 (dd, J = 8.1, 6.5

Hz, 1H), 3.18 (s, 3H), 2.81

- 2.59 (m, 2H), 1.90 (s,

3H).

555

17149

781 (thin film)

1661

ESIMS Ink

470 ((WM+)

I ll NMR (400 MHz, CDCI 3 )

5 8.95 (d, J = 2.7 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.02 (ddd, J= 8.5,

2.9, 1.5 Hz, 1H), 7.55 (d, J

= 8.1 Hz, 2H), 7.53 - 7.46

(m, 1H), 7.43 (t, J= 9.3 Hz,

3H), 4.38 (dd, J= 8.1.6.4

Hz, 1H), 3.62 (td, J= 15.4,

13.5, 8.3 Hz, 2H), 2.69 (qd,

J= 15.7, 7.3 Hz, 2H), 1.90

(s, 3H), 1.09 (t, J= 7.2 Hz,

3H)

782 (thin film)

1680

ESIMS m/z

382 (IM+Hr)

1 H NMR (400 MHz,

DMSO-c4) 5 10.31 (s, 1H),

9.05(d, J= 2.7 Hz, 1H),

8.86 (s, 1H), 8.55 (dt, J=

4.7, 1.3 Hz, 1H), 8.22 (ddd,

J= 8.4, 2.8, 1.5 Hz, 1H),

7.64- 7.44 (m, 1H), 4.34

(dt, J= 10.7, 5.7 Hz, 1H),

3.27 (dd, J= 17.6, 5.5 Hz,

1H), 2.87 (dd, J= 17.7, 5.9

Hz, 1H), 2.71 (s, 3H)

556

17149


58.94 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.02 (ddd, J= 8.4,

2.6, 1.4 Hz, 1H), 7.92 (s,

1H), 7.45 (dd, J=8.3,4.7

(thin film) ESIMS m/z Hz, 1H), 7.28 - 7.10 (m,

783 1654 414 ([M+H])

5H), 3.69- 3.56 (bs, 2H),

3.62 (q, J= 8 Hz, 2H) 2.82

(dd, J= 12.7, 9.0 Hz, 1H),

2.63 (d, J= 7.4 Hz, 1H),

2.40 (dd, J= 12.7, 5.3 Hz,

1H), 1.17 (t, J= 7.2 Hz,

3H), 1.12 (d, J= 6.7 Hz,

3H)


59.00 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.12 (s, 1H), 8.05 (thin film) ESIMS m/z

784 1654 378 (1M+Hr)

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.46 (dd, J=8.3,4.2

Hz, 1H), 3.93 - 3.54 (bd,

2H), 2.95 - 2.54 (m, 7H),

1.22 - 1.11 (m, 6H)


6 8.96 (d, J = 2.7 Hz, 1H),

8.65 - 8.54 (m, 1H), 8.10 -

7.94 (m, 2H), 7.46 (dd, J=

8.3, 4.8 Hz, 1H), 3.96 -

(thin film) ESIMS m/z 3.46 (bd, J= 95.1 Hz, 2H), 785

1656 395 ((M+Hr) 2.85 (dt, J= 12.3, 8.5 Hz,

1H), 2.65 (t, J= 6.5 Hz,

2H), 2.52 - 2.43 (m, 1H),

1.45- 1.25(m, 4H), 1.23 -

1.13 (m, 9H), 0.90 - 0.82

(m, 3H)

557

17149


69.01 (d, J= 2.5 Hz, 1H),

8.62 (dd, J= 4.7, 1.3 Hz,

1H), 8.19 (s, 1H), 8.08

(ddd, J= 8.3, 2.7, 1.4 Hz,


786 Hz, 1H), 4.13 (q, J= 7.1 1727, 1657 425 ([M+H])

Hz, 2H), 4.00 — 3.42 (bd,

2H), 2.97 — 2.82 (m, 1H),

2.78 — 2.63 (m, 3H), 2.62 —

2.43 (m, 3H), 1.25 (t, J=

7.1 Hz, 3H), 1.21 — 1.10

(m, 6H)

'H NMR (CDCI3) 6 8.96 (d,

J=2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H), 8.09 (s,

1H), 8.04 (ddd, J= 8.4, (thin film)

2.7, 1.5 Hz, 1H), 7.46 (dd, 3091, 2973,

J= 8.4, 4.7 Hz, 1H), 6.44 2929, 1656, ESIMS ink

787 (dd, J= 16.8, 9.9 Hz, 1H), 1584, 1485, 337 ([M+Hr)

5.29 (d, J= 5.5 Hz, 1H), 1438, 1250,

5.26 (d, J=1.5 Hz, 1H), 944

3.83 (s, 1H), 3.60 (s, 1H),

3.42(q, J= 6.8 Hz, 1H),

1.51 (d, J= 6.8 Hz, 3H),

1.17(t, J= 7.1 Hz, 3H)

I FI NMR (CDC13) 68.98

(dd, J= 2.7, 0.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.16 (s, 1H), 8.05

ESIMS m/z (ddd, J= 8.3, 2.7, 1.5 Hz, 788

339 ([M+Hr) 1H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 4.37 (q, J

= 7.1 Hz, 1H), 3.26 (s, 3H),

2.26 (s, 3H), 1.43 (d, J=

7.1 Hz, 3H)

558

17149

' 3C NMR (101

MHz, CDCI3) 15

171.25,

1 H NMR (400 MHz, CDCI3) 170.20,

6 9.03 (d, J= 2.6 Hz, 1H), 148.55,

8.97(d, J=2.6 Hz, 1H), 148.49,

8.61 (dt, J= 4.8, 1.7 Hz, 140.66,

2H), 8.23 (s, 1H), 8.18 (s, 140.12,

1H), 8.10 (ddd, J=8.4, 139.89,

ESIMS ink 2.7, 1.5 Hz, 1H), 8.04 (ddd, 135.66, 789

559 ([M+Hr) J= 8.4.2.7, 1.5 Hz, 1H), 135.60,

7.50 — 7.43 (m, 2H), 3.70 127.03,

(q, J= 7.1 Hz, 2H), 3.19 (s, 126.83,

3H), 3.12 (s, 2H), 2.90 (t, J 126.29,

= 7.1 Hz, 2H), 2.51 (t, J= 125.03,

7.1 Hz, 2H), 1.14 (t, J= 7.2 124.06,

Hz, 3H) 123.58, 43.84,

37.15, 34.13,

33.58, 28.04,

13.07

559

17149

790 ESIMS miz

587 ([M+Hr)


8 9.06 (dd, J= 7.4, 2.7 Hz,

2H), 8.62 (ddd, J= 4.9,

2.5, 1.5 Hz, 2H), 8.47—

8.21 (m, 2H), 8.12 (tdt, J=

6.2, 2.8, 1.5 Hz, 2H), 7.46

(ddt, J= 8.3, 4.7, 1.0 Hz,

2H), 3.93 (s, 1H), 3.49 (s,

1H), 3.25(s, 3H), 2.84—

2.65 (m, 4H), 2.57 — 2.38

(m, 3H), 1.16 (t, J= 7.1 Hz,

3H), 1.11 (d, J= 6.5 Hz,

3H)

13C NMR (101

MHz, CDCI3) 8

175.58,

171.99,

148.57,

148.45,

140.69,

140.20,

140.16,

135.76,

135.71,

126.58,

126.23,

125.48,

124.06,

124.03,

123.66, 43.78,

37.48, 37.03,

33.35, 28.25,

18.41, 12.99;

791 (thin film)

1661

ESIMS ink

389 ([M+Hr)


8 8.95 (d, J = 2.7 Hz, 1H),

8.64 (dd, J= 4.8, 1.5 Hz,

1H), 8.59 - 8.54 (m, 1H),

8.50 (dd, J= 4.8, 1.6 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.82(s,

1H), 7.64 (dt, J= 7.9, 2.0

Hz, 1H), 7.48 (dd, J= 8.4,

4.6 Hz, 1H), 7.24 (ddd, J=

7.8, 4.8, 0.8 Hz, 1H), 4.34

(dd, J= 8.2, 6.5 Hz, 1H),

3.18(s, 3H), 2.75 (qd, J=

15.8, 7.3 Hz, 2H), 1.92 (s,

3H)

560

17149

'H NMR (400 MHz,


= 8.0, 2.7 Hz, 1H), 8.64

(ddd, J= 4.2, 2.8, 1.4 Hz,

1H), 8.55 (d, J= 2.5 Hz,

1H), 8.50 (dd, J= 4.8,1.6

Hz, 1H), 8.06 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.75 (d, J (thin film) ESIMS raiz

792 = 15.6 Hz, 1H), 7.63 (dt, J 1656 403 ((WM+ )

= 7.9, 2.0 Hz, 1H), 7.53 -

7.45 (m, 1H), 7.24 (ddd, J

= 7.8, 4.8, 0.8 Hz, 1H),

4.34 (dd, J= 8.3, 6.3 Hz,

1H), 3.70-3.56 (m, 2H),

2.80 - 2.58 (m, 2H), 1.92

(s, 3H), 1.08 (t, J= 7.2 Hz,

3H).

561

17149

1 H NMR (400 MHz,


= 2.7 Hz, 1H), 8.64 (dd, J=

4.7, 1.5 Hz, 1H), 8.56 (d, J

= 2.7 Hz, 1H), 8.50 (dd, J=

4.8, 1.7 Hz, 1H), 8.14 -

7.96 (m, 1H), 7.64 (dt, J =


7.9, 2.0 Hz, 1H), 7.48 (ddd,

J = 8.4, 4.7, 0.8 Hz, 1H),

7.24 (ddd, J= 7.8, 4.8, 0.8 793

1658 429 ([WM) Hz, 1H), 4.34 (dd, J = 8.5,

6.2 Hz, 1H), 3.47 (d, J =

6.8 Hz, 2H), 2.74 (qd, J =

15.7, 7.4 Hz, 2H), 1.92 (s,

3H), 0.89 (d, J = 6.3 Hz,

1H), 0.45 (d, J = 8.4 Hz,

2H), 0.20 - 0.03 (m, 2H).

(one aromatic proton not

located)

1 11 NMR (400 MHz,


= 2.6 Hz, 1H), 8.63 (dd, J=

794 (thin film) ESIMS m/z

4.8, 1.5 Hz, 1H), 8.02 (ddd,

J = 8.3, 2.7, 1.5 Hz, 1H),

7.46 (dd, J= 8.4, 4.8 Hz,

1H), 7.21 (t, J= 7.9 Hz,

1662 418 ([M+Hr) 1H), 6.91 - 6.75 (m, 3H),

4.30 (t, J = 7.3 Hz, 1H),

3.73 (s, 3H), 3.17 (s, 3H),

2.70 (dd, J= 7.3, 1.7 Hz,

2H), 1.92 (s, 3H).(one

aromatic proton not

located)

562

17149

795 (thin film)

1659

ESIMS m/z

432 ([MOH] . )

'H NMR (400 MHz,


= 2.8 Hz, 1H), 8.63 (dd, J=

4.8, 1.4 Hz, 1H), 8.03 (ddd,

J = 8.3, 2.8, 1.5 Hz, 1H),

7.46 (dd, J = 8.2, 4.7 Hz,

1H), 7.20 (t, J = 7.9 Hz,

1H), 6.91 - 6.76 (m, 3H),

4.30 (dd, J = 8.3, 6.3 Hz,

1H), 3.72 (s, 3H), 3.71 -

3.46 (m, 2H), 2.73 - 2.52

(m, 2H), 1.92 (s, 3H), 1.06

(t, J = 7.1 Hz, 3H). (One

aromatic proton not

located)

796 (thin film)

1659

ESIMS m/z

458 ([M+Hr)


6 8.90 (s, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.03 (d,

J= 7.6 Hz, 1H), 7.54 - 7.41

(m, 1H), 7.20 (t, J= 7.9 Hz,

1H), 6.95 - 6.68 (m, 3H),

4.30 (dd, J = 8.2, 6.4 Hz,

1H), 3.72 (s, 3H), 3.63 -

3.03 (m, 2H), 2.68 (dd, J=

7.3, 4.2 Hz, 2H), 1.93 (s,

3H), 0.96 - 0.75 (m, 1H),

0.43 (d, J = 8.1 Hz, 2H),

0.19 - 0.04 (m, 2H). (One

aromatic proton not

located)

563

17149

797 (thin film) ESIMS Ink

382 ((WM')

1 H NMR (400 MHz,

Chloroform-d) 5 8.99 (bs,

1H) 8.63 (bs, 1H), 8.08

(ddd, J= 8.3, 2.6, 1.3 Hz,

1H), 7.99(s, 1H), 7.48 (dd,

J=8.3,4.7 Hz, 1H), 6.80

(bs, 1H), 5.38 (bs, 1H),

3.72 (hept, J= 6.7 Hz, 2H),

3.37(q, J=7.3 Hz, 1H),

2.87 (hept, J= 6.6 Hz, 2H),

2.48 (td, J=6.8, 2.2 Hz,

2H), 1.44 (d, J= 7.3 Hz,

3H), 1.17(t, J= 7.2 Hz,

3H)

798

(thin film)

3323, 3082,

2968, 1649

ESIMS m/z

438 ([M+H])

1 H NMR (400 MHz,


(m, 1H), 8.63 (dd, J= 4.8,

1.5 Hz, 1H), 8.07 (ddd, J=

8.3, 2.7, 1.4 Hz, 1H), 7.99

(s, 1H), 7.46 (ddd, J = 8.3,

4.7, 0.8 Hz, 1H), 6.55 (bs,

1H), 3.71 (tt, J= 13.6, 6.9

Hz, 2H), 3.23 (q, J= 7.2

Hz, 1H), 2.81 (t, J = 7.0

Hz, 2H), 2.46 (td, J= 7.0,

3.7 Hz, 2H), 1.37 (d, J=

7.2 Hz, 3H), 1.33 (s, 9H),

1.16 (t, J= 7.2 Hz, 3H)

564

17149

799 (thin film)

1658

ESIMS m/z

380

([M+2Hr)


58.97 (d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.00 (s,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 3.72(q, J=7.1

Hz, 2H), 2.81 (t, J= 7.2

Hz, 2H), 2.64 (t, J= 6.9

Hz, 2H), 2.47 (dt, J= 18.0,

7.1 Hz, 4H), 1.93 (p, J=

6.9 Hz, 2H), 1.17 (t, J= 7.2

Hz, 3H)

800 (thin film)

1673

ESIMS m/z

372 ([M+H])


68.96 (d, J= 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.02 (m, 2H), 7.47

(ddd, J= 8.3, 4.8, 0.6 Hz,

1H), 3.93 (bs, 2H), 3.70 (q,

J= 7.2 Hz, 2H), 3.05 (s,

3H), 3.00 (s, 3H), 1.18 (t, J

= 7.2 Hz, 3H)

801 (thin film)

1671

ESIMS m/z

358 ([101-1]+ )


5 8.95 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.03 (m, 2H), 7.47

(dd, J= 8.3, 4.8 Hz, 1H),

3.97 (bs, 2H), 3.26 (s, 3H),

3.05 (s, 3H), 3.00 (s, 3H)

565

17149

I FINMR (400 MHz, CDCI3)

68.95 (d, J = 2.5 Hz, 1H),

8.64 (dd, J = 4.8, 1.4 Hz,

1H), 8.04 (m, 2H), 7.47 (thin film) ESIMS m/z

802 1667 398 ([M+Hr)

(dd, J = 8.3, 4.8 Hz, 1H),

3.96 (bs, 2H), 3.53 (bs,

2H), 3.05 (s, 3H), 3.00 (s,

3H), 0.98 (m, 1H), 0.53 (m,

2H), 0.21 (m, 2H)

'H NMR (CDCI3) 68.96 (d, ' 3C NMR

J = 2.7 Hz, 1H), 8.62 (dd, J (CDCI3) 6

= 4.8, 1.4 Hz, 1H), 8.05 (s, 171.3, 148.7,

1H), 8.02 (ddd, J= 8.3, 140.2, 139.9,

ESIMS m/z 2.7, 1.5 Hz, 1H), 7.45 (dd, 135.6, 126.4, 803

397 ((WM') J = 8.4, 4.7 Hz, 1H), 4.44 124.9, 124.1,

(s, 2H), 3.57(t, J= 5.8 Hz, 115.4, 67.1,

2H), 3.26 (s, 3H), 3.00 (s, 44.6, 37.5,

3H), 2.63(t, J = 5.8 Hz, 37.3, 37.1,

2H) 34.4.

'H NMR (400 MHz,


= 2.7 Hz, 1H), 8.60 (dd, J =


4.8, 1.5 Hz, 1H), 8.24 (s,

1H), 8.02 (ddd, J = 8.3,

2.7, 1.5 Hz, 1H), 7.41 (dd,

J = 8.3, 4.7 Hz, 1H), 4.12 804

1650 356 ([M+Hj + ) (s, 1H), 3.37 (s, 1H), 3.28

— 3.10 (m, 2H), 2.60 (s,

3H), 2.57 (d, J = 2.9 Hz,

1H) 1.22 (d, J = 6.6 Hz,

3H), 1.18 (t, J = 7.2 Hz,

3H).

566

17149

805 (thin film)

1650

ESIMS m/z

356 ([M+Hr)


6 9.04(d, J= 2.7 Hz, 1H),

8.60 (dd, J= 4.8, 1.5 Hz,

1H), 8.25 (s, 1H), 8.03

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.41 (dd, J= 8.3, 4.8

Hz, 1H), 4.13 (s, 1H), 3.37

(s, 1H), 3.30 — 3.06 (m,

2H), 2.60 (s, 4H), 1.22 (d,

J= 6.6 Hz, 3H), 1.18(t, J=

7.2 Hz, 3H)

806 (thin film)

1650

ESIMS m/z

356 ([M+H])


6 8.99 (dd, J= 2.7, 0.8 Hz,

1H), 8.61 (dd, J= 4.7, 1.5

Hz, 1H), 8.18 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.44 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.96 (s,

1H), 3.47(s, 1H), 3.17

(tdd, ../= 9.3, 5.9, 2.7 Hz,

2H), 2.78 — 2.65 (m, 1H),

2.60(s, 3H), 1.33 — 1.23

(m, 3H), 1.16 (t, J= 7.2 Hz,

3H)

567

17149

807 (thin film)

1650

ESIMS m/z

356 ([M+H])


6 8.99 (dd, J= 2.7, 0.8 Hz,

1H), 8.61 (dd. J= 4.7, 1.5

Hz, 1H), 8.18 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.44 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.96 (s,

1H), 3.47 (s, 1H), 3.17

(tdd, J= 9.3, 5.9, 2.7 Hz,

2H), 2.78 — 2.65 (m, 1H),

2.60 (s, 3H), 1.33 — 1.23

(m, 3H), 1.16(t, J= 7.2 Hz,

3H)

808 ESIMS m/z

398 ([M+Hr)

1 1-INMR (400 MHz, CDCI3 )

69.00 (d, J= 2.5 Hz, 1H),

8.61 (dd, J= 4.7, 1.3 Hz,

1H), 8.10 (s, 1H), 8.01

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.42 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 4.73 (q, J

= 7.0 Hz, 1H), 3.25 (s, 3H),

2.99 (s, 3H), 2.23 (II, J=

8.0, 4.9 Hz, 1H), 1.36 (d, J

= 7.0 Hz, 3H), 1.10(m,

2H), 0.96 (m, 2H)

809

(thin film)

2996, 2924,

1670

ESIMS m/z

372 (WM+)


69.00 (s, 1H), 8.62 (d, J=

4.2 Hz, 1H), 8.09 (s, 1H),

8.01 (d, J= 8.2 Hz, 1H),

7.43 (dd, J=8.1,4.8Hz,

1H), 4.76 (q, J= 7.1 Hz,

1H), 3.25 (s, 3H), 3.00 (s,

3H), 2.80 (s, 3H), 1.32 (d,

J= 7.1 Hz, 3H)

568

17149

810 ESIMS m/z

469 ([M+H]i


/5 8.99 (d, J= 2.3 Hz, 1H),

8.63(d, J= 4.6 Hz, 1H),

8.08 (s, 1H), 8.01 (m, 1H),

7.44 (dd, J= 8.3, 4.8 Hz,

1H), 4.75 (q, J= 7.1 Hz,

1H), 3.24 (s, 3H), 3.02 (s,

3H), 2.96 (d, J= 3.4 Hz,

2H), 2.26 (m, 2H), 2.06 (m,

2H), 1.34 (d, J= 7.1 Hz,

3H)

19F NMR (376

MHz, CDCI3) 0

-66.12 (s)

811 ESIMS m/z

487 ([M+H]. )

l Ei NMR (400 MHz, CDCI3)

09.02 (d, J = 2.2 Hz, 1H),

8.62 (d, J= 3.8 Hz, 1H),

8.18(s, 1H), 8.04 (ddd, J=

8.3, 2.6, 1.4 Hz, 1H), 7.73

(t, J= 8.1 Hz, 1H), 7.43

(dd, J= 8.3, 4.7 Hz, 1H),

7.21 (m, 2H), 4.93 (q, J=

7.1 Hz, 1H), 3.23 (s, 3H),

2.97 (d, J= 0.9 Hz, 3H),

1.19 (d, J= 7.1 Hz, 3H)

19F NMR (376

MHz, CDCI3) 0

-106.12 (s)

812 (thin film)

1660

ESIMS m/z

389 ([M+H]t )


15 9.02 - 8.91 (m, 1H), 8.72

-8.62 (m, 1H), 8.57 - 8.50

(m, 2H), 8.10 - 7.98 (m,

1H), 7.87 - 7.72 (m, 1H),

7.52 - 7.44 (m, 1H), 7.26 -

7.15 (m, 2H), 4.30 (dd, J=

8.0, 6.5 Hz, 1H), 3.18 (s,

3H), 2.72 (qd, J= 15.9, 7.3

Hz, 2H), 1.94- 1.80 (m,

3H)

569

17149

813 (thin film)

1657

ESIMS m/z

403 ((M+H] . )

1 11 NMR (400 MHz, CDCI3)

6 8.96 (d, J= 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.54 (dd, J= 4.5, 1.6

Hz, 2H), 8.07 - 7.99 (m,

1H), 7.83 - 7.65 (m, 1H),

7.54- 7.43(m, 1H), 7.24

(d, J = 6.1 Hz, 2H), 4.30

(dd, J= 8.2, 6.4 Hz, 1H),

3.75 - 3.50 (m, 2H), 2.68

(qd, J= 15.8, 7.3 Hz, 2H),

1.91 (s, 3H), 1.10(t, J=

7.2 Hz, 3H)

814 (thin film)

1657

ESIMS m/z

389 ([M+H]+ )


6 8.90(d, J= 2.5 Hz, 1H),

8.62 (dd, J= 4.7, 1.4 Hz,

1H), 8.54 - 8.44 (m, 2H),

7.97(d, J=8.0 Hz, 1H),

7.49 - 7.40 (m, 1H), 7.11

(dd, J= 4.5, 1.5 Hz, 2H),

3.39 (ddd, J= 13.4, 11.2,

6.6 Hz, 2H), 3.19 (s, 3H),

2.87 (dd, J= 12.3, 4.1 Hz,

1H), 2.19 (s, 3H). (One

aromatic proton not

located)

570

17149

815

(thin film)

3447, 3072,

2975, 2933,

1652, 1485,

1439, 1035

ESIMS m/z

341 ([M+H])

I FI NMR (CDCI3) 6 8.98 (d,

J=2.7 Hz, 1H), 8.66 - 8.60

(m, 1H), 8.21 -8.08 (m,

1H), 8.06 - 7.98 (m, 1H),

7.51 -7.40 (m, 1H), 4.18 -

3.91 (m, 1H), 3.87 (q, J=

6.8 Hz, 1H), 3.64 (br. s,

1H), 2.64 (s, 1.35H), 2.54

(s, 1.65H), 1.44 (d, J= 6.8

Hz, 1.65H), 1.37 (br. s,

1.35H), 1.23 - 1.15 (m, 3H)

816

(thin film)

2930, 1660,

1299, 1132,

945

ESIMS m/z

357 ((M+Hr)

'H NMR (CDCI3) 68.98 (d,

J= 2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H), 8.18(s,

1H), 8.00 (ddd, J= 8.5,

2.7, 1.4 Hz, 1H), 7.45 (ddd,

J= 8.3, 4.7, 0.7 Hz, 1H),

4.05 - 3.91 (m, 2H), 3.60 -

3.47 (m, 1H), 3.01 (s, 3H),

1.65 (d, J= 7.0 Hz, 3H),

1.21 (t, J = 7.2 Hz, 3H)

817

(thin film)

3099, 2976,

2936, 1708,

1666

EIMS m/z

421 ((M+Fir)

I FI NMR (400 MHz,


(m, 1H), 8.64 (dd, J= 4.7,

1.5 Hz, 1H), 8.12 - 8.04

(m, 1H), 7.98 (s, 1H), 7.53

-7.42 (m, 1H), 4.78 (pd, J

= 9.0, 4.4 Hz, 1H), 3.90 -

3.54 (m, 2H), 2.76 (dd, J=

16.6, 4.4 Hz, 1H), 2.53 (dd,

J= 16.6, 9.4 Hz, 1H), 2.41

(s, 3H), 1.16(t, J= 7.2 Hz,

3H)

571

17149

'H NMR (CD03) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

ESIMS m/z 1H), 7.96 (s, 1H), 7.47 (dd, 19F NMR

818 J= 8.5, 4.7 Hz, 1H), 5.86 (CDCI3) 6 - 375 ((M+Hr)

(tt, J= 56.6, 4.4 Hz, 1H), 113.24

3.72 (q, J= 7.2 Hz, 2H),

2.97 - 2.77 (m, 4H), 2.46 (t,

J = 7.1 Hz, 2H), 1.17 (t, J=

7.2 Hz, 3H)

I FI NMR (CDCI 3) 68.96 (d,

J= 2.8 Hz, 1H), 8.62 (dd, J 13C NMR

= 4.7, 1.5 Hz, 1H), 8.11 (s, (CDCI3) 6

1H), 8.04 (ddd, J= 8.3, 169.7, 148.6,

2.7, 1.5 Hz, 1H), 7.46 (dd, 140.6, 140.1,

ESIMS rniz J= 8.4, 4.8 Hz, 1H), 5.80 136.4, 135.6, 819

351 ([M+H]) (ddt, J= 16.9, 10.1, 6.6 Hz, 127.3, 126.3,

1H), 5.11 - 4.99 (m, 2H), 124.1, 123.4,

3.84 - 3.59 (m, 2H), 3.12 116.2, 44.0,

(s, 2H), 2.74 (t, J= 7.4 Hz, 33.5, 33.3,

2H), 2.41 - 2.29 (m, 2H), 31.8, 13.0

1.17 (1, J= 7.2 Hz, 3H)

572

17149

820 ESIMS m/z

365 ([M+H]. )

'H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.15 (s,

1H), 8.05 (ddd, J= 8.4,

2.8, 1.5 Hz, 1H), 7.47 (dd,

J=8.4,4.8 Hz, 1H), 5.77

(ddt, J= 16.9, 10.2, 6.6 Hz,

1H), 5.10 - 4.96 (m, 2H),

3.81 (s, 1H), 3.62 (s, 1H),

3.40 - 3.23 (m, 1H), 2.64

(tt, J= 8.3, 4.4 Hz, 2H),

2.32 - 2.20 (m, 2H), 1.47

(d, J= 6.8 Hz, 3H), 1.17 (t,

J= 7.1 Hz, 3H)

13C NMR

(CDCI3) 6

172.0, 148.6,

140.8, 140.1,

136.5, 135.6,

127.3, 126.3,

124.1, 123.2,

116.0, 44.0,

38.1, 33.7,

28.0, 17.7,

13.0

821 ESIMS m/z

387 ((WM+ )

'H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.5 Hz, 1H), 8.06 (s,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.46 (dd,

J=8.4,4.8 Hz, 1H), 3.84-

3.61 (m, 2H), 3.18 (s, 2H),

2.78 (dt, J= 7.4, 1.6 Hz,

2H), 1.94 - 1.75 (m, 1H),

1.50 (dddd, J= 12.4, 11.3,

7.8, 4.6 Hz, 1H), 1.17 (t, J

= 7.2 Hz, 3H), 1.15 - 1.07

(m, 1H)

19F NMR

(CDCI3) 6 -

128.02(d, J=

156.7 Hz), -

142.82 (d, J=

156.6 Hz)

573

17149

1 H NMR (CDCI3) 6 8.96 (d,

J=2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.4, 2.7, 1.5 Hz,

1H), 7.97 (s, 1H), 7.47 (dd,

J=8.3,4.8 Hz, 1H), 4.51 19F NMR

822 ESIMS m/z (dt, J= 47.2, 5.7 Hz, 2H),

(00013) 6 371 ((lvt+Hr) 3.72 (q, J= 7.2 Hz, 2H),

16.20 2.82 (t, J= 7.3 Hz, 2H),

2.60 (t, J= 7.2 Hz, 2H),

2.45 (t, J= 7.3 Hz, 2H),

1.94 (dtt, J= 25.9, 7.1, 5.7

Hz, 2H), 1.17 (t, J = 7.2

Hz, 3H)

I HNMR (CDC13) 6 9.02 (d,

J= 2.7 Hz, 1H), 8.62 (dd, J 130 NMR

= 4.8, 1.5 Hz, 1H), 8.12- (CDCI3) 6

8.03(m, 2H), 7.45 (dd, J= 171.0, 148.6,

8.4, 4.7 Hz, 1H), 6.41 (dd, 140.5, 140.4,

ESIMS m/z J= 16.6, 9.9 Hz, 1H), 6.19 135.7, 132.2, 823

398 ([M+H]+ ) (d, J= 16.6 Hz, 1H), 5.99 128.0, 127.2,

(d, J= 9.9 Hz, 1H), 3.72 (q, 126.4, 124.1,

J= 7.2 Hz, 2H), 3.38(t, J= 123.5, 47.1,

6.7 Hz, 2H), 2.82 (s, 3H), 43.9, 36.3,

2.51 (t, J= 6.7 Hz, 2H),

1.17(t. J = 7.2 Hz, 3H)

34.1, 13.1

574

17149

824 ESIMS m/z

401 ([M+H]+ )

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H), 8.10(s,

1H), 8.07 - 7.99 (m, 1H),

7.46 (ddd, J= 8.3, 4.7, 0.7

Hz, 1H), 3.81 (s, 1H), 3.60

(s, 1H), 3.44 -3.25 (m,

1H), 2.88 - 2.70 (m, 1H),

2.70- 2.56 (m, 1H), 1.80 -

1.65 (m, 1H), 1.55 - 1.38

(m, 4H), 1.22 - 1.12 (m,

3H), 1.12 - 0.96 (m, 1H)

19F NMR

(CDC!) 6 -

127.81, -

128.23

825 ESIMS m/z

367 ((M+Hr)

1 H NMR (CDCI3) 69.00 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.09

(ddd, J= 8.4, 2.8, 1.5 Hz,

1H), 8.06 (s, 1H), 7.47 (dd,

J= 8.3, 4.7 Hz, 1H), 3.71

(q, J= 7.1 Hz, 2H), 3.21 (s,

2H), 2.78 (t, J= 7.1 Hz,

2H), 2.45 (t, J= 7.1 Hz,

2H), 2.25 (s, 3H), 1.16 (t, J

= 7.2 Hz, 3H)

"C NMR

(CDCI3) 6

203.8, 171.0,

148.6, 140.8,

140.1, 135.7,

126.7, 126.4,

124.1, 123.7,

43.9, 42.4,

34.0, 27.9,

27.6, 13.1

826 ESIMS m/z

419 ((WM')

1 FI NMR (CDCI3) 68.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.06

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.97 (s, 1H), 7.47

(ddd, J= 8.3, 4.8, 0.7 Hz,

1H), 3.72(q, J= 7.2 Hz,

2H), 2.84(t, J= 7.3 Hz,

2H), 2.69 (t, J= 7.0 Hz,

2H), 2.62 - 2.48 (m, 2H),

2.44 (t, J= 7.3 Hz, 2H),

1.17 (t, .1= 7.2 Hz, 3H)

19F NMR

(CDCI3) 6 -

103.97 (dd, J=

85.8, 32.6 Hz),

-122.37 - -

124.03(m), -

174.73 - -

176.48 (m)

575

17149

827 ESIMS m/z

587 ((WM + )

T H NMR (CDCI3) 6 9.01 (d,

J= 2.3 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.11 (s,

1H), 8.08 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.46 (ddd,

J= 8.3, 4.8, 0.7 Hz, 1H),

3.69(q, J= 7.1 Hz, 2H),

2.76 (t, J= 7.0 Hz, 2H),

2.43 (t, J= 7.0 Hz, 2H),

1.15(t, J=7.2 Hz, 3H)

' 3C NMR

(CDCI3) 6

171.4, 148.5,

140.8, 140.1,

135.7, 126.9,

126.3, 124.1,

123.8, 44.0,

34.0, 27.7,

13.1

828 ESIMS m/z

475 ((WM')

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.96 (s, 1H), 7.47

(ddd, J= 8.3, 4.7, 0.7 Hz,

1H), 3.72(q, J= 7.1 Hz,

2H), 3.28 - 3.13 (m, 1H),

2.96 - 2.84 (m, 4H), 2.45 (t,

J= 7.0 Hz, 2H), 1.17 (t, J=

7.2 Hz, 3H)

19F NMR

(CDCI3) 6-

66.96

829 ESIMS m/z

415 ([M+H]+ )

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.96 (s, 1H), 7.46 (dd,

J=8.3,4.8 Hz, 1H), 3.70

(q, J= 7.2 Hz, 2H), 2.65-

2.50(m, 4H), 2.28(t, J=

6.9 Hz, 2H), 1.99 - 1.86

(m, 2H), 1.83 - 1.65 (m,

1H), 1.47 (dddd, J= 12.3,

11.2, 7.8, 4.5 Hz, 1H), 1.16

(t, J= 7.2 Hz, 3H), 1.04

(dtd, J= 13.2, 7.7, 3.7 Hz,

1H)

19 F NMR

(CDCI3) 6 -

128.06 (d, J=

157.2 Hz), -

142.88(d, J=

156.8 Hz)

576

17149

830

1 1.1NMR (400 MHz,

DMSO-d6): 69.93 (s, 1H)

9.04 (s, 1H), 8.96 (s, 1H),

8.59(s, 1H), 8.44(d, J=

2.12 Hz, 1H), 2.74 (t, J=

3.68 Hz, 4H), 2.10 (s, 3H)

831 ESIMS m/z

346 ([M+H])

I ll NMR (400 MHz, Me0D

): 68.95 (d, J=2.16 Hz,

1H), 8.76 (s, 1H), 8.51 (d,

J= 1.96 Hz, 1H), 8.29(t, J

= 2.16 Hz, 1H), 2.96-3.00

(m, 1H), 2.77-2.80 (m, 1H),

2.60 (dd, J=5.72,13.18

Hz, 1H), 2.15 (s, 3H), 1.30

(s, 3H)

832 ESIMS m/z

389 ([M+Hr)

1 1-INMR (300 MHz, Me0D

): 68.97 (s, 1H), 8.73 (s,

1H), 8.59 (s, 1H), 8.41 (t, J

=2.10 Hz, 1H), 2.93 (t, J=

6.69 Hz, 1H), 2.83 (dd, J=

8.73, 13.02 Hz, 1H), 2.57

(dd, J= 5.70, 13.05 Hz,

1H), 2.12 (s, 3H), 1.26 (d,

J= 6.75 Hz, 3H)

833 176-178 ESIMS m/z

327 ([M+Hr)

1 11-NMR (400 MHz,

Me0D): 68.74 (s, 1H),

8.59 (d, J= 1.88 Hz, 1H),

8.22 (d, J= 2.36 Hz, 1H),

7.79 (t, J= 2.16 Hz, 1H),

3.98 (s, 3H), 2.86 (t, J=

6.40 Hz, 2H), 2.76-2.80

(m, 2H), 2.17 (s, 1H).

577

17149

834 ESIMS m/z

341 ([M+H])

1 14NMR (400 MHz, Me0D)

:

5812 (s, 1H), 8.57 (d, J

= 1.84 Hz, 1H), 821 (d, J=

2.36 Hz, 1H), 7.76 (t, J=

2.28 Hz, 1H), 3.97 (s, 2H),

2.94-2.99 (m, 1H), 2.85

(dd, J= 8.80, 13.14 Hz,

1H), 2.59 (dd, J= 5.68,

13.14 Hz, 1H), 2.15 (s,

3H), 1.29 (d, J= 6.76 Hz,

3H)

835 ESIMS m/z

311 ([M+H])

I FI NMR (400 MHz,

Me0D): 58.71 (s, 1H),

8.80 (s, 1H), 8.36 (s, 1H),

8.07 (s, 1H), 2.84(t, J=

0.84 Hz, 2H), 2.78 (q, J=

2.28 Hz, 2H), 2.46 (s, 3H),

2.16 (s, 3H)

836

ESIMS

m/z 325

((M+Hr)

1 H NMR (400 MHz,

Me0D): 58.80 (d, J= 2.32

Hz, 1H) 8.70 (d, J= 0.56

Hz, 1H), 8.36 (s, 1H), 8.05

(d, J= 0.64 Hz, 1H), 2.92-

2.99 (m, 1H), 2.85 (dd, J=

8.80, 13.08 Hz, 1H), 2.60

(dd, J= 5.60, 13.14 Hz,

1H), 2.47 (s, 3H), 2.15 (d,

J= 0.60 Hz, 3H), 1.29 (d, J

= 6.76 Hz, 3H)

578

17149

837

I FI NMR (400 MHz, Me0D

): 6 9.00 (d, J= 2.08 Hz,

1H), 8.71 (s, 1H), 8.58 (d,

J= 1.84 Hz, 1H), 8.36(t, J

= 2.04 Hz, 1H), 3.22 (s,

3H), 2.73 (t, J= 7.04 Hz,

2H), 2.54 (t, J= 7.08 Hz,

2H), 2.02 (s, 3H)

I FI NMR (400 MHz, Me0D

): 6 9.01 (d, J= 2.28 Hz,

1H), 8.76 (s, 1H), 8.59 (d,

J= 2.00 Hz, 1H), 8.37 (d, J ESIMS m/z

838 358([M])

= 2.12 Hz, 1H), 3.25 (s,

3H), 2.75-2.86 (m, 2H),

2.42-2.46 (m, 1H), 1.96 (s,

3H), 1.17 (d, J= 6.48 Hz,

3H)

T H NMR (400 MHz, Me0D

839

ESIMS m/z

342

((M+H+1) . )

): 68.70 (d, J= 5.44 Hz,

1H), 8.63(d, J= 1.88 Hz,

1H), 8.28 (d, J= 2.40 Hz,

1H), 7.84(t, J= 2.32 Hz,

1H), 3.99 (s, 3H), 3.25 (s,

3H), 2.72 (t, J= 5.08 Hz,

2H), 2.54 (t, J= 7.00 Hz,

2H), 2.02 (s, 3H)

1 H NMR (400 MHz, Me0D

): 68.74 (s, 1H), 8.62 (d, J

= 2.12 Hz, 1H), 8.27 (d, J=

ESIMS 2.52 Hz, 1H), 7.83(t, J=

840 m/z 355

([M+H])

2.36 Hz, 1H), 3.98 (s, 3H),

3.25 (s, 3H), 2.77 (t, J=

8.28 Hz, 2H), 2.44 (t, J=

7.28 Hz, 1H), 1.95 (s, 3H),

1.16 (d, J= 6.56 Hz, 3H)

579

17149

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.64 (dd, J

= 4.7, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.96 (s, 1H), 7.47 19F NMR

ES I MS m/z (ddd, J= 8.3, 4.7, 0.7 Hz,

(CDCI3) 6 - 841 114), 5.93 (It, J= 53.6, 3.4

425 ([M+H]) 115.32, - Hz, 1H), 3.72(q, J= 7.1

136.89 Hz, 2H), 3.04 (It, J= 16.3,

1.5 Hz, 2H), 2.95 (t, J= 7.0

Hz, 2H), 2.46 (t, J= 7.1

Hz, 2H), 1.17 (t, J= 7.2

Hz, 3H)

'H NMR (CDCI3) 68.92 (d,

J=2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H), 8.01

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.79 (s, 1H), 7.46

ESIMS m/z (ddd, J= 8.3, 4.7, 0.8 Hz,

842 553 ([M+Hr)

1H), 7.40 - 7.34 (m, 6H),

7.25 - 7.19 (m, 6H), 7.19 -

7.12 (m, 3H), 3.64(q, J=

7.2 Hz, 2H), 2.51 (t, J= 7.3

Hz, 2H), 2.03 (t, J= 7.4

Hz, 2H), 1.10 (t, J= 7.2

Hz, 3H)

580

17149

7 H NMR (400 MHz,


= 2.7, 0.7 Hz, 1H), 8.58 (s,

1H), 8.54 (dd, J= 4.8, 1.5

ESIMS Hz, 1H), 7.96 (ddd, J= 8.4,

m/z 525 2.7, 1.5 Hz, 1H), 7.51 - 843

([M+Hr), 523 7.44 (m, 6H), 7.38 (ddd, J

([M-Hr) = 8.3, 4.8, 0.7 Hz, 1H),

7.35- 7.19 (m, 9H), 7.04

(s, 1H), 2.64 (t, J = 7.1 Hz,

2H), 2.10 (t, J= 7.1 Hz,

2H)


6 8.97 (dd, J= 2.7, 0.7 Hz,

1H), 8.64(s, 1H), 8.55 (dd,

J= 4.7,1.4 Hz, 1H),7.99 •

(ddd, J= 8.3, 2.7, 1.5 Hz,

ESIMS m/z 1H), 7.48 (s, 1H),7.40

844 (IR 373 ([M+Hr), (ddd, J= 8.4, 4.8, 0.7 Hz,

371 ([M-Hr) 1H), 2.99 (t, J= 6.9 Hz,

2H), 2.78 - 2.70 (m, 4H),

1.83 (ddq, J= 13.1, 11.3,

7.4 Hz, 1H), 1.56 - 1.49

(m, 1H), 1.12 (dtd, J=

13.3, 7.7, 3.7 Hz, 1H)

581

17149

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.05

ESIMS m/z

(ddd, J= 8.3, 2.6, 1.4 Hz,

1H), 7.96(s, 1H), 7.47 (dd,

J= 8.3, 4.7 Hz, 1H), 3.72 19F NMR

845 (CDCI3) 6 - 421 ([M+Hr) (q, J= 7.2 Hz, 2H), 2.81 (t,

66.03 J= 7.3 Hz, 2H), 2.56 (t, J=

7.1 Hz, 2H), 2.43 (t, J= 7.4

Hz, 2H), 2.27 - 2.09 (m,

2H), 1.88- 1.76 (m, 2H),

1.17(t, J = 7.2 Hz, 3H)

1 HNMR (CDCI3) 6 8.95 (d,

J= 2.3 Hz, 1H), 8.64 (dd, J

= 4.6, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.96 (s, 1H), 7.47

"F NMR

(CDCI3) 6 -

846 ESIMS m/z (ddd, J= 8.4, 4.8, 0.7 Hz, 91.82 (t, J=

411 ((M+Hj+) 1H), 5.77 (II, J= 54.0, 3.2 10.0 Hz), -

Hz, 1H), 3.73(q, J= 7.2 131.92 (t, J=

Hz, 2H), 3.16 (t, J = 6.8 10.1 Hz)

Hz, 2H), 2.57 (t, J= 6.8

Hz, 2H), 1.17 (t, J = 7.2

Hz, 3H)

582

17149

847 ESIMS m/z

479 ([M+H])

1 H NMR (CDCI3) 6 8.97 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.06

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.99 (s, 1H), 7.47 (dd,

J= 8.4, 4.7 Hz, 1H), 4.24-

4.08 (m, 2H), 3.78 - 3.64

(m, 2H), 3.46 (dd, J= 9.9,

4.1 Hz, 1H), 3.06 - 2.78

(m, 3H), 2.55 - 2.32 (m,

3H), 1.24 (t, J= 7.1 Hz,

3H), 1.16(t, J= 7.2 Hz,

3H)

19F NMR

(CDCI3) 6 -

65.29

848 ESIMS Ink

419 ([M+H])

1 H NMR (CDCI3) 68.96 (d,

J= 2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.95 (s, 1H), 7.47 (dd,

J= 8.4, 4.7 Hz, 1H), 5.85 -

5.78(m, 1H), 5.66 (h, J=

1.4 Hz, 1H), 3.72 (q, J=

7.1 Hz, 2H), 3.27 (s, 2H),

2.79 (t, J= 7.3 Hz, 2H),

2.43 (t, J= 7.3 Hz, 2H),

1.17(t, J= 7.2 Hz, 3H)

19F NMR

(CDCI3) 6 -

67.33

849 ESIMS m/z

1 H NMR (CDCI 3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.4, 2.7, 1.5 Hz,

1H), 7.97 (s, 1H), 7.47 (dd,

J= 8.6, 4.8 Hz, 1H), 3.72

(q, J= 7.2 Hz, 2H), 2.85 (t,

J = 7.2 Hz, 2H), 2.75 - 2.65

(m, 2H), 2.45 (t, J= 7.2 Hz,

2H), 2.41 -2.23 (m, 2H),

1.17(t, J=7.2 Hz, 3H)

(CDCI3) 6 -457([M+H])

19F NMR

85.35, -118.30

583

17149

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

ESIMS m/z 1H), 7.96 (s, 1H), 7.47 (dd, ' 9F NMR

850 J= 8.4, 4.8 Hz, 1H), 3.72 (CDCI3) 6 - 443 ([M+H]')

(q, J= 7.2 Hz, 2H), 3.12 (t, 84.46, -117.06

J= 16.9 Hz, 2H), 2.97 (t, J

= 7.0 Hz, 2H), 2.47 (t, J=

7.0 Hz, 2H), 1.17 (t, J= 7.2

Hz, 3H)


68.94 (d, J= 2.3 Hz, 1H),

8.57 (dd, J= 4.7, 1.4 Hz,

1H), 8.02 (ddd, J= 8.3,

(thin film) ESIMS m/z 2.7, 1.5 Hz, 1H), 7.90 (s,

851 1655 373 ([M+H])

1H), 7.43 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.24 (s,

3H), 2.84 (t, J= 7.1 Hz,

2H), 2.69 - 2.61 (m, 2H),

2.47 - 2.41 (m, 2H), 2.41 -

2.32 (m, 2H), 2.28 (s, 3H)


6 8.95 (d, J= 2.4 Hz, 1H),

8.57 (dd, J= 4.7,1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.87 (s,

852 (thin film) ESIMS m/z 1H), 7.43 (ddd, J= 8.3,

1653 387 ([M+H] t ) 4.8, 0.6 Hz, 1H), 3.81 -

3.57 (m, 2H), 2.83 (t, J=

7.2 Hz, 2H), 2.69 - 2.60

(m, 2H), 2.44 - 2.33 (m,

4H), 2.27 (s, 3H), 1.15 (t, J

= 7.2 Hz, 3H)

584

17149


15 8.74(d, J= 1.8 Hz, 1H),

8.43(d, J= 2.5 Hz, 1H),

7.92 (s, 1H), 7.85 (dt, J=

(thin film) ESIMS m/z 9.3, 2.4 Hz, 1H), 3.23 (s,

853 3H), 2.84 (dd, J= 8.9, 5.3 1656 391 ([M+11])

Hz, 2H), 2.71 -2.60 (m,

2H), 2.43 (t, J= 7.1 Hz,

2H), 2.36 (ddd, J= 10.5,

8.2, 5.8 Hz, 2H), 2.27 (s,

3H)

1 H NMR (400 MHz, CDC13)

58.76 (d, J= 1.8 Hz, 1H),

8.43(d, J=2.5 Hz, 1H),

7.89 (s, 1H), 7.86 (dt, J=

(thin film) ESIMS m/z 9.3, 2.4 Hz, 1H), 3.68 (s, 854

1653 405 ([M+H]), 2H), 2.83 (t, J= 7.1 Hz,

2H), 2.69 - 2.60 (m, 2H),

2.43 - 2.32 (m, 4H), 2.27

(s, 3H), 1.15 (t, J = 7.2 Hz,

3H)


5 8.95 (d, J = 2.2 Hz, 1H),

8.57 (dd, J= 4.7, 1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.87 (s,

1H), 7.43 (ddd, J= 8.3,

(thin film) ESIMS m/z 4.8, 0.7 Hz, 1H), 3.69 (brs,

855 1652 381 ([M+Hr)

2H), 2.86 (t, J= 7.2 Hz,

2H), 2.59 (tdd, J= 9.2, 4.7,

2.3 Hz, 2H), 2.41 (t, J= 7.2

Hz 2H), 2.27 (s, 3H), 1.83

- 1.66 (m, 1H), 1.56 - 1.38

(m, 1H), 1.15 (t, J = 7.2 Hz,

3H), 1.03 (dtd, J= 13.2,

7.7, 3.7 Hz, 1H)

585

17149

856 (thin film)

1652

ESIMS m/z

399 (fM+H]+)

I H NMR (400 MHz, CDCI 3)

68.75 (d, J = 1.5 Hz, 1H),

8.43 (d, J= 2.5 Hz, 1H),

7.88 (s, 1H), 7.85 (dt, J=

9.4, 2.4 Hz, 1H), 3.68 (s,

2H), 2.86 (t, J= 7.2 Hz,

2H), 2.59 (dd, J= 7.2, 2.2

Hz, 2H), 2.39 (t, J= 7.2

Hz, 2H), 2.26 (s, 3H), 1.82

- 1.67 (m, 1H), 1.54 - 1.42

(m, 1H), 1.15 (t, J=7.2 Hz,

3H), 1.04 (dtd, J= 13.2,

7.7, 3.7 Hz, 1H)

857

(thin film)

3094, 2974,

2934, 1658

ESIMS m/z

387 ([M+H]+ )

I H NMR (400 MHz, CDCI3)

6 8.95 (dd, J= 2.8, 0.7 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.05 (ddd, J= 8.4,

2.6, 1.5 Hz, 1H), 7.95 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 5.98 (ddt,

J= 17.3, 10.9, 9.5 Hz, 1H),

5.68 (dt, J= 17.3, 2.4 Hz,

1H), 5.47(d, J=10.9 Hz,

1H), 3.72(q, J=7.2 Hz,

2H), 3.09 (t, J= 7.0 Hz,

2H), 2.57 (t, J= 7.0 Hz,

2H), 1.17 (t, J= 7.2 Hz,

3H)

I t NMR (376

MHz, CDCI3) 6

-73.92

586

17149

'H NMR (CDCI3) 5 8.96 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.96 (s, 1H), 7.47 (dd,

J= 8.4, 4.6 Hz, 1H), 4.20 19F NMR ESI MS m/z

858 401 ([M+H])

(dtd, J= 25.3, 7.8, 2.3 Hz,

1H), 3.72(q, J= 7.2 Hz,

(CDCI3) 5 -

87.96, -89.97

2H), 2.82 (t, J= 7.3 Hz,

2H), 2.53 (t, J= 7.2 Hz,

2H), 2.43 (t, J= 7.4 Hz,

211), 2.31 -2.18 (m, 2H),

1.17 (t, J= 7.2 Hz, 3H)

1 H NMR (CDCI3) 58.96

(dd, J= 2.7, 0.7 Hz, 1H),

8.64 (dd, J= 4.8, 1.5 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.97 (s, 19F NMR

ESIMS m/z 1H), 7.47 (ddd, J= 8.3, 859 (CDCI3) 5 -

427 ([M+Hr) 4.7, 0.7 Hz, 1H), 5.34 (q, J 72.34

=6.7 Hz, 1H), 3.73 (q, J =

7.2 Hz, 2H), 3.21 -3.04

(m, 2H), 2.56 (t, J= 6.7 Hz,

2H), 1.18(t, J= 7.2 Hz,

3H)


58.94 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.12 - 7.92 (m, 2H),

(thin film) ESIMS ink 7.47 (ddd, J = 8.3, 4.8, 0.6 860

1661 393 ([M+Hr) Hz, 1H), 3.26 (s, 3H), 2.85

(t, J= 7.2 Hz, 2H), 2.70 -

2.60 (m, 2H), 2.55 - 2.42

(m, 2H), 2.42 -2.27 (m,

2H)

587

17149


6 8.96 (d, J = 2.4 Hz, 1H),

8.64 (dd, J = 4.7, 1.4 Hz,

1H), 8.07 - 8.00 (m, 2H),

(thin film) ESIMS m/z 7.46 (ddd, J = 8.3, 4.8, 0.7 861

1660 423 ([M+Hr) Hz, 1H), 3.85 - 3.61 (m,

2H), 3.23 - 3.08 (m, 1H),

3.03 - 2.76 (m, 3H), 2.74 -

2.52 (m, 4H), 1.18 (t, J =

7.2 Hz, 3H)


68.97 (d, J = 2.5 Hz, 1H),

8.64 (dd, J = 4.7, 1.4 Hz,

1H), 8.09 - 8.00 (m, 2H),

(thin film) ESIMS m/z 7.47 (ddd, J = 8.4, 4.8, 0.7 862

1661 439 ([M+Hr) Hz, 1H), 3.73(q, J = 6.8

Hz, 2H), 3.46 - 3.41 (m,

2H), 3.30- 3.21 (m, 2H),

2.78-2.59 (m, 4H), 1.18 (t,

J = 7.2 Hz, 3H)


68.94 (d, J = 2.3 Hz, 1H),

8.57 (dd, J = 4.7, 1.4 Hz,

1H), 8.02 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.90 (s,

1H), 7.43 (ddd, J = 8.3,

4.8, 0.6 Hz, 1H), 3.27 - (thin film) ESIMS m/z

863 3.21 (m, 3H), 2.86 (t, J = 1655 367 ([M+H]),

7.2 Hz, 2H), 2.59 (ddd, J =

6.9, 3.1, 1.3 Hz, 2H), 2.45

(t, J = 7.1 Hz, 2H), 2.28 (s,

3H), 1.75 (ddq, J = 13.3,

11.3, 7.5 Hz, 1H), 1.53 -

1.41 (m, 1H), 1.04 (dtd, J =

13.1, 7.7, 3.7 Hz, 1H)

588

17149

864 (thin film)

1655

ESIMS m/z

385 ([M+Hr)


t5 8.74(d, J= 1.7 Hz, 1H),

8.43 (d, J= 2.4 Hz, 1H),

7.91 (s, 1H), 7.84 (dt, J=

9.4, 2.4 Hz, 1H), 3.23 (d, J

= 3.9 Hz, 3H), 2.84 (s, 2H),

2.62 - 2.55 (m, 2H), 2.44 (t,

J= 7.2 Hz, 2H), 2.27 (s,

3H), 1.81 - 1.68(m, 1H),

1.53- 1.42(m, 1H), 1.04

(dtd, J= 13.2, 7.7, 3.7 Hz,

1H)

865 ESIMS m/z

412 ([M+Hr)


6 8.96 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.03 (m, 2H), 7.47 (m,

1H), 3.92 (bs, 2H), 3.70 (q,

J= 7.1 Hz, 2H), 3.08 (d, J

= 7.2 Hz, 2H), 3.01 (s, 3H),

1.19(m, 4H), 0.67(m, 2H),

0.44 (m, 2H)

866 (thin film)

1666

ESIMS m/z

426 ([M+H])


69.02 (d, J = 2.5 Hz, 1H),

8.62 (dd, J= 4.8, 1.4 Hz,

1H), 8.16 - 7.90 (m, 2H),

7.44 (ddd, J= 8.3, 4.8, 0.6

Hz, 1H), 4.66(q, J= 7.0

Hz, 1H), 3.94 (bs, 1H),

3.41 (bs, 1H), 3.02 (s, 3H),

2.88 - 2.73 (m, 2H), 1.33

(d, J= 7.1 Hz, 3H), 1.16(t,

J= 7.2 Hz, 3H), 1.07 (ddd,

J= 12.8, 7.7, 4.9 Hz, 1H),

0.69- 0.58 (m, 2H), 0.41 -

0.26 (m, 2H)

589

17149


6 8.97 (d, J= 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.98 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 5.92 (11, J It NMR (376

(thin film) = 55.6, 3.9 Hz, 1H), 3.86 - ESIMS m/z MHz, CDCI3) 6

867 3092, 2976, 544 ((M+Hr)

3.58 (m, 5H), 3.51 (dd, J= -121.40(d, J=

2934, 1657 14.5, 6.4 Hz, 1H), 3.08 (dd, 13.4 Hz)

J= 14.5, 7.7 Hz, 1H), 2.58

(t, J=6.7 Hz, 2H), 2.11 -

1.94(m, 1H), 1.83 (dd, J=

10.5, 7.6 Hz, 1H), 1.45 (t, J

= 7.7 Hz, 1H), 1.29 - 1.20

(m, 1H), 1.16 (t, J= 7.2 Hz,

3H)

1 11 NMR (400 MHz,

CDCI3): 68.87 (s, 1H),

(thin film) ESIMS m/z 8.69 (s, 1H), 8.28 (s, 1H),

868 3091, 2921, 388 8.03 (s, 1H), 3.26 (s, 3H),

1661 ([M+H+1]. ) 2.81 (t, J= 7.20 Hz, 2H),

2.48 (t, J= 7.36 Hz, 2H),

2.09 (s, 3H)

1 H NMR (400 MHz, CDCI3

): 6 8.87 (d, J= 1.60 Hz,

1H), 8.69 (s, 1H), 8.28 (t, J

= 2.00 Hz, 1H), 8.07 (s,

ESIMS m/z 1H), 3.27 (s, 3H), 2.87 (t, J 869

403 ([M+Hr) = 9.12 Hz, 1H), 2.73-2.78

(m, 1H), 2.50 (dd, J= 5.16,

12.62 Hz, 1H), 2.04 (s,

3H), 1.21 (d, J= 3.96 Hz,

3H)

590

17149

870 (thin film)

1690

ESIMS rniz

379 ([M+Hr)


6 8.97 (d, J = 2.4 Hz, 1H),

8.64(s, 1H), 8.56 (dd, J=

4.7, 1.4 Hz, 1H), 7.99 (ddd,

J = 8.3, 2.7, 1.5 Hz, 1H),

7.48 (s, 1H), 7.40 (ddd, J =

8.3, 4.8, 0.6 Hz, 1H), 2.96

(t, J= 6.8 Hz, 2H), 2.76

(ddd, J= 9.3, 7.4, 5.0 Hz,

4H), 2.55 - 2.29 (m, 2H)

871 (thin film)

1718

ESIMS m/z

564 ([M+Hr)


68.95 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.1, 1.7 Hz,

1H), 8.05 (ddd, J = 8.3,

2.7, 1.4 Hz, 1H), 8.01 (s,

1H), 7.47 (dd, J= 8.4, 4.8

Hz, 1H), 3.01 (t, J = 6.8

Hz, 4H), 2.87 (t, J= 7.0

Hz, 4H), 2.72 (ddd, J = 8.3,

7.2, 4.2 Hz, 4H), 2.49 -

2.32 (m, 4H)

872 (thin film)

1594

ESNS

m/z396

([M+Hr)


6 9.54(s, 1H), 8.99(t, J=

3.1 Hz, 2H), 8.59 (dd, J=

4.7, 1.4 Hz, 1H), 8.01 (ddd,

J = 8.3, 2.7, 1.4 Hz, 1H),

7.43 (ddd, J = 8.3, 4.8, 0.6

Hz, 1H), 3.11 (t, J= 3.0

Hz, 4H), 2.86- 2.70 (m,

2H), 2.52 - 2.29 (m, 2H)

591

17149

873

ESIMS ink

489.2

((M+Hr)


6 8.96(d, J= 2.7 Hz, 1H),

8.65 (dd, J = 4.8,1.4 Hz,

1H), 8.05 (ddd, J = 8.4,

2.8, 1.5 Hz, 1H), 7.97 (s,

1H), 7.48 (dd, J = 8.4, 4.7

Hz, 1H), 3.74 (t, J = 7.2

Hz, 2H), 2.84 (t, J = 7.1

Hz, 2H), 2.71 -2.62 (m,

2H), 2.46 (t, J= 7.1 Hz,

2H), 2.43 - 2.29 (m, 2H),

2.27 -2.09 (m, 2H), 1.83

(p, J = 7.4 Hz, 2H)

19F NMR (376

MHz, CDCI3) 6

-66.28, -66.41.

874

ESIMS m/z

503.2

((WM')


68.96 (s, 1H), 8.65 (d, J=

4.7 Hz, 1H), 8.04 (ddd, J=

8.4, 2.7, 1.4 Hz, 1H), 7.95

(s, 1H), 7.47 (dd, J= 8.3,

4.8 Hz, 1H), 3.69 (t, J=6.5

Hz, 2H), 2.84 (t, J= 7.1

Hz, 2H), 2.70 - 2.62 (m,

2H), 2.46 (t, J = 7.2 Hz,

2H), 2.43 - 2.29 (m, 2H),

2.22 - 2.05 (m, 2H), 1.72 -

1.54 (m, 4H)

19F NMR (376

MHz, CDCI3) 6

-66.24, -66.40.

592

17149

875

ES I MS m/z

439 ((hydrate

M+Hr), 421

((keto M+H))

'H NMR (CDCI3) 6 8.98 (d,

J= 2.7 Hz, 0.4H), 8.95 (d,

J= 2.6 Hz, 0.6H), 8.66 -

8.59 (m, 1H), 8.13 - 8.04

(m, 1H), 8.03 (s, 1H), 7.47

(dd, J= 8.3, 4.8 Hz, 1H),

5.20 (br. s, 1H), 3.81 -3.64

(m, 2H), 3.58 (s, 0.8H),

3.02 (t, J= 6.4 Hz, 1.2H),

2.91 (s, 1.2H), 2.84 (t, J=

6.8 Hz, 0.8H), 2.57 - 2.40

(m, 2H), 1.77 (br. s, 1H),

1.23- 1.09 (m, 3H)

19F NMR

(CDCI3) 6 -

76.15 (keto), -

85.24 (hydrate)

876 ESIMS m/z

421 ([M+Hr)


6 8.95(d, J= 2.7 Hz, 1H),

8.63 (dd, J= 4.7, 1.5 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.95 (s,

1H), 7.47 (dd, J= 8.4, 4.7

Hz, 1H), 3.62 (t, J= 7.8

Hz, 2H), 2.84 (t, J= 7.2

Hz, 2H), 2.71 -2.62 (m,

2H), 2.45 (t, J= 7.2 Hz,

2H), 2.36 (dddd, J= 14.9,

12.2, 8.4, 4.9 Hz, 2H), 1.64

-1.51 (m, 2H), 0.93 (t, J=

7.4 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-66.41.

593

17149

877 ESIMS m/z

381 ((M+Hr)

1 H NMR (CDCI3) 58.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.09 -

8.02 (m, 2H), 7.46 (dd, J =

8.3, 4.8 Hz, 1H), 3.72 (q, J

= 7.0 Hz, 2H), 2.81 (t, J =

7.2 Hz, 2H), 2.76 - 2.64

(m, 4H), 2.45 (t, J = 7.2 Hz,

2H), 2.15 (s, 3H), 1.16 (t, J

= 7.2 Hz, 3H)

"C NMR

(CDCI3) 15

206.8, 171.4,

148.6, 140.9,

140.1, 135.7,

126.6, 126.3,

124.1, 123.8,

44.0, 43.4,

34.2, 30.2,

27.6, 25.9,

13.1

878 ESIMS m/z

477 ((M+Hr)

1 H NMR (CDCI3)15 9.02-

8.94 (m, 1H), 8.62 (dd, J =

4.8, 1.5 Hz, 1H), 8.12-

8.02 (m, 2H), 7.92 - 7.83

(m, 2H), 7.50 - 7.39 (m,

3H), 3.71 (q, J= 7.2 Hz,

2H), 3.23 (t, J = 7.1 Hz,

2H), 2.90 - 2.83 (m, 4H),

2.48 (t, J = 7.2 Hz, 2H),

1.16(t, J = 7.2 Hz, 3H)

"C NMR

(CDCI3)15

197.1, 171.4,

148.6, 140.9,

140.1, 139.8,

135.6, 134.8,

129.4, 129.0,

126.6, 126.3,

124.1, 123.9,

44.0, 38.7,

34.3, 27.7,

26.4, 13.1

594

17149

879 (thin film)

1663

ESIMS m/z

453 ([M+H])

1 1-1 NMR (400 MHz, CDCI3)

58.95 (d, J= 2.5 Hz, 1H),

8.68 - 8.59 (m, 1H), 8.08-

8.00 (m, 1H), 7.97 (s, 1H),

7.46 (dd, J=8.2, 4.8 Hz,

1H), 4.53(t, J= 5.7 Hz,

1H), 4.45 - 4.37 (m, 1H),

3.71 (s, 2H), 2.84 (td, J=

7.1, 2.4 Hz, 2H), 2.70-

2.61 (m, 2H), 2.45 (td, J=

7.1, 1.7 Hz, 2H), 2.41 -

2.28(m, 2H), 1.78 (dq, J=

10.4, 6.3, 5.7 Hz, 1H), 1.73

- 1.61 (m, 3H)

"C NMR (101

MHz, CDCI 3) 5

171.47,

148.80,

140.72,

140.04,

135.56, 128.70

(cl. ' ,kr =

277.8), 126.35,

126.32,

124.13,

123.82, 83.58 1

(d, AF = 165.6

Hz), 48.51,

35.64 (q, 2AF = 28.3 Hz),

34.06, 27.57

(d, 2,/CF = 20.2

Hz), 27.40,

24.50 (q, 3Jcp = 3.0 Hz), 23.83

(d, 3JcF = 5.1

Hz); 19F NMR

(376 MHz,

CDCI3) 5 -

66.40 (t, J=

10.4 Hz), -

216.01 - -

220.60(m)

595

17149


6 8.95 (d, J = 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.00 (s,

1H), 7.47 (dd, J= 8.3, 4.7 19F NMR (376

(thin film) ESIMS m/z Hz, 1H), 3.55(d, J= 7.3 880 MHz, CDCI3) 6

1660 433 ([M+H]) Hz, 2H), 2.85 (t, J= 7.2 -66.40.

Hz, 2H), 2.72 - 2.62 (m,

2H), 2.47 (t, J= 7.2 Hz,

2H), 2.44 -2.29 (m, 2H),

0.98 (II, J= 7.7, 4.8 Hz,

1H), 0.56 - 0.46 (m, 2H),

0.25 - 0.16 (m, 2H)


881 (thin film)

2913, 1595

ESIMS m/z

313 ([M+Hr)

59.56 (s, 1H), 9.41 (s,

1H), 9.00 (d,J= 2.4 Hz,

1H), 8.59 (d, J= 3.7 Hz,

1H), 8.01 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.42 (dd,

J = 8.3, 4.7 Hz, 1H),3.16

(t, J= 6.5 Hz, 2H), 3.02 (t,

J= 6.5 Hz, 2H), 2.21 (s,

3H)



6 8.95(d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.95 (s,

1H), 7.47 (dd, J= 8.4, 4.8

1661 424 ((WM . ) Hz, 1H), 4.89 - 4.68 (m,

1H), 3.72(q, J = 7.2 Hz,

2H), 3.12 (t, J= 6.9 Hz,

2H), 2.57 (t, J= 6.9 Hz,

2H), 1.17 (t, J = 7.2 Hz,

3H)

596

17149

883 (thin film)

1661

ESIMS mtz

416 ([M+Hr)


6 8.95 (d, J = 2.5 Hz, 1H),

8.63 (dd, J=4.7,1.4 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.96 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 3.72 (q, J

= 7.1 Hz, 2H), 2.80 (t, J=

7.3 Hz, 2H), 2.74 - 2.60

(m, 4H), 2.42 (t, J= 7.3 Hz,

2H), 2.37 - 2.15 (m, 3H),

1.17(t, J= 7.2 Hz, 3H)

884 (thin film)

1667

ESIMS m/z

435.3

([M+H])


6 8.95(d, J= 2.7 Hz, 1H),

8.63 (dd, J=4.8,1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.93 (s,

1H), 7.47 (ddd, J= 8.4,

4.7, 0.7 Hz, 1H), 3.51 (s,

2H), 2.85 (t, J= 7.2 Hz,

2H), 2.71 -2.60 (m, 2H),

2.47 (t, J= 7.2 Hz, 2H),

2.43 - 2.27 (m, 2H), 1.81

(dt, J= 13.7, 6.9 Hz, 1H),

0.95 (d, J= 6.6 Hz, 6H)

19F NMR (376

MHz, CDCI3) 6

-66.40.

885 ESIMS fit&

313 ([M+H])


58.96 (d, J = 2.5 Hz, 1H),

8.81 (s, 1H), 8.62 (s, 1H),

8.55 (dd, J= 4.7, 1.4 Hz,

1H), 7.99 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.39 (ddd,

J= 8.4, 4.8, 0.7 Hz, 1H),

3.27 (ddd, J= 12.4, 7.5,

6.2 Hz, 1H), 3.13 - 2.95

(m, 3H), 2.69 (s, 3H)

597

17149

886 ESIMS m/z

327 ([M+Hr)


15 8.95-8.94 (m, 1H), 8.80

(bs, 0.35H), 8.71 (bs,

0.65H), 8.637 (s, 0.65H),

8.632 (s, 0.35H), 8.56 -

8.51 (m, 1H), 8.02 - 7.94

(m, 1H), 7.42 - 7.33 (m,

1H), 3.38 - 3.22 (m,

1.65H), 3.17 (dd, J = 13.3,

5.5 Hz, 0.35H), 2.84 (dd, J

= 13.3, 7.3 Hz, 0.35H),

2.75 (dd, J = 12.6, 2.1 Hz,

0.65H), 2.68 (s, 1.05H),

2.67 (s, 1.95H), 1.48 -

1.44 (m, 3H)

887 (thin film)

1669

HRMS-FAB

(m/z) [M+Hr

calcd for

CI7H2ICIF3N4

02S,

437.1020;

found,

437.1043.

1 HNMR (400 MHz,

Chloroform-d)15 8.94 (dd, J

= 2.7, 0.7 Hz, 1H), 8.62

(dd, J = 4.7, 1.4 Hz, 1H),

8.07 - 8.00 (multiple

peaks, 2H), 7.46 (ddd, J = 8.4, 4.8, 0.8 Hz, 1H), 3.83

(br s, 2H), 3.58 (br s, 2H),

3.34 (s, 3H), 2.85 (t, J = 7.2 Hz, 2H), 2.72 - 2.61

(m, 2H), 2.49 (t, J = 7.3 Hz,

2H), 2.45 - 2.26 (m, 2H)

19F NMR (376

MHz, CDCI3) 0

-66.40.

598

17149

IFI NMR (CDCI3) ö 8.99 (d,

J = 2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.06

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 8.03 (s, 1H), 7.46 (dd, 19F NMR

ESIMS ink J= 8.3, 4.8 Hz, 1H), 3.71 888 (CDCI3)15 -

468 ([101-1]+) (q, J = 7.0 Hz, 2H), 3.52 (t, 66.14

J = 6.7 Hz, 2H), 3.20 - 3.07

(m, 2H), 2.91 (s, 3H), 2.67

-2.53 (m, 2H), 2.50 (t, J =

6.6 Hz, 2H), 1.17(t, J = 7.2

Hz, 3H)

'H NMR (CDCI3)25 8.96 (d,

J = 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J = 8.4, 2.6, 1.4 Hz,

1H), 7.96 (s, 1H), 7.47

ESIMS m/z (ddd, J = 8.4, 4.7, 0.8 Hz, 19F NMR

889 403 ([1■4+1-1] +)

1H), 3.72(q, J = 7.2 Hz,

2H), 2.83(t, J = 7.3 Hz,

(CDCI3)25 -

91.57

2H), 2.67 - 2.56 (m, 2H),

2.44 (t, J = 7.3 Hz, 2H),

2.22 - 2.05 (m, 2H), 1.59 (t,

J = 18.5 Hz, 3H), 1.17(t, J

= 7.2 Hz, 3H)

599

17149

890 ESIMS m/z

405 ([M+H]+)

1 H NMR (CDCI3) 6 8.95 (d,

J= 2.6 Hz, 1H), 8.64 (dd, J

= 4.7, 1.4 Hz, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.95 (s, 1H), 7.47 (dd,

J= 8.4, 4.7 Hz, 1H), 6.97

(dq, J= 15.4, 2.0 Hz, 1H),

5.50 (dq, J= 15.4, 6.3 Hz,

1H), 3.73(q, J= 7.2 Hz,

2H), 3.07 (t, J= 7.1 Hz,

2H), 2.52 (t, J= 7.1 Hz,

2H), 1.17 (t, J= 7.2 Hz,

3H)

19F NMR

(CDCI3) 6 -

62.15

891 (thin film)

1670

HRMS—FAB

(m/z) [M+H]

calcd for

C18HI9CIF5N4

OS,

469.0883;

found,

469.0900.


6 8.95 (d, J= 2.6 Hz, 1H),

8.64 (dd, J=4.8,1.4 Hz,

1H), 8.04 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.99 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 4.39 (d, J

= 14.2 Hz, 1H), 3.18(s,

1H), 2.85 (t, J=7.2 Hz,

2H), 2.71 -2.61 (m, 2H),

2.49 (td, J= 7.2, 1.2 Hz,

2H), 2.44 -2.25 (m, 2H),

1.89 (s, 1H), 1.54 - 1.41

(m, 1H), 1.17- 1.03(m,

1H)

600

17149


6 8.96 (d, J = 2.7 Hz, 111),

8.64 (dd, J= 4.8, 1.4 Hz,

HRMS—FAB 1H), 8.05 (ddd, J= 8.3,

(m/z) [M+Hr 2.7, 1.5 Hz, 1H), 7.99 (s,

calcd for 1H), 7.47 (ddd, J= 8.2,

892 (thin film) C171-12,3CIF4N4 4.7, 0.7 Hz, 1H), 4.55 (dt, J

1668 OS, = 47.1, 5.7 Hz, 2H), 3.81 (t,

439.0977; J= 7.3 Hz, 2H), 2.84 (t, J=

found, 7.2 Hz, 2H), 2.71 -2.58

439.0988. (m, 2H), 2.46 (t, J= 7.2 Hz,

2H), 2.44 - 2.27 (m, 2H),

2.01 (dtt, J= 26.1, 7.1, 5.7

Hz, 2H)

I FI NMR (CDCI3) 66.96 (d,

J=2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.07 (s,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.46 (ddd,

ESIMS m/z J= 8.4, 4.7, 0.8 Hz, 1H), 19F NMR

893 421 ([M+H])

3.80 (br. s, 1H), 3.61 (br. s,

1H), 3.41 -3.22 (m, 1H),

(CDCI 3) 6.

66.14

2.67 (td, J= 7.3, 2.2 Hz,

2H), 2.27- 2.08 (m, 2H),

1.87- 1.72(m, 2H), 1.47

(d, J= 6.8 Hz, 3H), 1.17 (t,

J= 7.1 Hz, 3H)

601

17149

894 ESIMS m/z

454 ([M+1-1]*)


6 8.95(d, J= 2.5 Hz, 1H),

8.65 (dd, J= 4.7, 1.4 Hz,

1H), 8.15- 7.89(m, 2H),

7.48 (ddd, J= 8.3, 4.8, 0.6

Hz, 1H), 3.94 (bs, 2H),

3.72 (q, J= 7.2 Hz, 2H),

3.52 - 3.29 (m, 2H), 3.02

(s, 3H), 2.86 -2.60 (m,

2H), 1.19 (t, J = 7.2 Hz,

3H)

895 (thin film)

1680

ESIMS m/z

426 ([M+H])


68.97 (d, J= 2.6 Hz, 1H),

8.68 (dd, J= 4.8, 1.3 Hz,

1H), 8.09 - 7.95 (m, 2H),

7.48 (dd, J=7.8, 4.8 Hz,

1H), 3.94 (bs, 2H), 3.73 (q,

J= 7.4 Hz, 2H), 3.18 (s,

3H), 1.19 (t, J = 7.2 Hz,

3H)

896 (thin film)

1665

ESIMS m/z

419.2

([M+11] + )


68.93 (d, J= 2.7 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

111), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.93 (s,

1H), 7.46 (dd, J= 8.3, 4.7

Hz, 1H), 5.85 (ddt, J=

16.7, 10.1, 6.4 Hz, 1H),

5.26- 5.06 (m, 2H), 4.27

(s, 2H), 2.86 (t, J= 7.2 Hz,

2H), 2.71 -2.61 (m, 2H),

2.49 (t, J= 7.2 Hz, 2H),

2.45 - 2.29 (m, 2H)

It NMR (376

MHz, CDCI3) 6

-66.40.

602

17149

897 (thin film)

1659

HRMS—FAB

(m/z)[M+Hr

calcd for

Ci al-InF3N40

S, 399.1461;

found,

399.1479.

1HNMR (400 MHz, CD03)

6 8.96 — 8.89 (m, 1H), 8.57

(dd, J= 4.8, 1.5 Hz, 1H),

8.02 (ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.84 (s, 1H), 7.42

(ddd, J= 8.4, 4.8, 0.7 Hz,

1H), 5.86 (ddt, J= 16.7,

10.1, 6.4 Hz, 1H), 5.23—

5.09 (m, 2H), 4.23 (s, 2H),

2.84(t, J= 7.1 Hz, 2H),

2.69 — 2.61 (m, 2H), 2.43

(t, J= 7.1 Hz, 2H), 2.40 —

2.31 (m, 2H), 2.26 (s, 3H)

19F NMR (376

MHz, CDCI3) 6

-66.42.

898 (thin film)

1659

ESIMS m/z

423 ([M+H] + )


68.96 (d, J= 2.4 Hz, 1H),

8.63 (bd, J= 3.7 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.96 (s, 1H),

7.47(ddd, J= 8.1, 4.6 Hz,

1H), 4.07 (t, J= 6.9 Hz,

2H), 3.72 (q, J= 7.2 Hz,

2H), 2.87 (t, J= 7.2 Hz,

2H), 2.79 (t, J= 7.0 Hz,

2H), 2.45 (t, J= 7.2 Hz,

2H), 1.17 (t, J = 7.2 Hz,

3H)

899 (thin film)

1675

ESIMS m/z

440 ([M+H] + )


68.96 (d, J= 2.4 Hz, 1H),

8.65 (dd, J= 4.7, 1.4 Hz,

1H), 8.07 - 7.98 (m, 2H),

7.48 (ddd, J= 8.4, 4.8, 0.7

Hz, 1H), 4.11 (q, J= 9.4

Hz, 2H), 3.98 (bs, 2H),

3.71 (q, J= 7.1 Hz, 2H),

3.03(s, 3H), 1.19 (t, J=

7.2 Hz, 3H)

603

17149


HRMS-FAB 6 9.03 - 8.97 (m, 1H), 8.67

(m/z)(M+Hr (dd, J= 4.8, 1.4 Hz, 1H),

calcd for 8.20 (s, 1H), 8.05 (ddd, J= 19F NMR (376

(thin film) C 1 eH15CIF3N5 8.4, 2.7, 1.4 Hz, 1H), 7.49 900 MHz, CDCI3) 6

1684 OS, (ddd, J= 8.3, 4.7, 0.7 Hz, -66.38.

418.0711; 1H), 4.61 (s, 2H), 2.86 (t, J

found, = 7.1 Hz, 2H), 2.79 - 2.60

418.0724. (m, 2H), 2.52 (t, J= 7.1 Hz,

2H), 2.46 -2.26 (m, 2H)

1 FI NMR (CDCI3) 6 8.95 (d,

J= 2.8 Hz, 1H), 8.63 (dd, J

= 4.6, 1.5 Hz, 1H), 8.09 -

8.00 (m, 2H), 7.46 (ddd, J 19F NMR

ESIMS m/z = 8.3, 4.8, 0.7 Hz, 1H), 901 (CDCI3) 6 -

407 ([101-1]+) 3.71 (s, 2H), 3.10 (s, 2H), 66.08

2.74 (t, J= 7.2 Hz, 2H),

2.29 - 2.11 (m, 2H), 1.94 -

1.81 (m, 2H), 1.17(t, J=

7.2 Hz, 3H)


J= 2.0 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H), 8.09 -

7.99 (m, 2H), 7.47 (ddd, J 19F NMR ESIMS m/z

902 393 ([M+Fi])

= 8.3, 4.8, 0.8 Hz, 1H),

3.72 (s, 2H), 3.14 (s, 2H),

(CDCI3) 6 -

66.17

2.90 - 2.81 (m, 2H), 2.54 -

2.37 (m, 2H), 1.18 (t, J=

7.2 Hz, 3H)

604

17149

903 ESIMS m/z

415 ([M+H]+)

1 H NMR (CDCI3) 6 9.00 -

8.93 (m, 1H), 8.63 (dd, J=

4.8, 1.4 Hz, 1H), 8.18 -

8.07 (m, 1H), 8.04 (ddd, J

= 8.3, 2.8, 1.5 Hz, 1H),

7.46 (dd, J= 8.3, 4.7 Hz,

1H), 3.80 (br. s, 1H), 3.60

(br. s, 1H), 3.30 (br. s, 1H),

2.82 - 2.58 (m, 2H), 1.78-

1.61 (m, 2H), 1.56 (ddd, J

= 14.0, 11.1, 6.9 Hz, 1H),

1.47 (d, J= 6.9 Hz, 3H),

1.39 (dddt, J= 12.6, 11.3,

7.7, 3.9 Hz, 1H), 1.17(t, J

= 7.2 Hz, 3H), 0.93 (ddtd, J

= 12.4, 8.6, 7.4, 3.4 Hz,

1H)

19 F NMR

(CDCI3) 6 -

128.06, -

128.47, -

143.57, -

144.01

904 (thin film)

1746, 1709

HRMS—FAB

(m/z) [M+H]+

calcd for

C19 H23 C1F3 N4

035,

479.1126;

found,

479.1139.


6 8.93 (d, J = 2.7 Hz, 1H),

8.59 (dd, J= 4.8, 1.4 Hz,

1H), 8.03 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.91 (s,

1H), 7.43 (dd, J= 8.3, 4.8

Hz, 1H), 3.36 (t, J= 7.2

Hz, 2H), 2.90 (t, J= 7.2

Hz, 2H), 2.81 -2.70 (m,

2H), 2.54 - 2.33 (m, 2H),

1.47 (s, 9H)

19F NMR (376

MHz, CDCI3) 6

-66.39.

605

17149

905 3090, 2931,

1660

ESIMS Ink

437 ([M+Hr),

439

([M+2+H])

'H NMR (400 MHz,


= 2.8 Hz, 1H), 8.64 (dd, J=

4.8, 1.5 Hz, 1H), 8.05 (ddd,

J= 8.3, 2.7, 1.5 Hz, 1H),

7.96 (s, 1H), 7.47 (ddd, J=

8.3, 4.8, 0.8 Hz, 1H), 3.25

(s, 3H), 2.85 (t, J= 7.2 Hz,

2H), 2.70- 2.64 (m, 2H),

2.47 (t, J= 7.2 Hz, 2H),

2.44 -2.29 (m, 2H)

906 (thin film)

1644

ESIMS ink

421 ([M+H])


68.96 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.8, 1.3 Hz,

1H), 8.08-7.96 (m, 2H),

7.46 (dd, J= 8.3, 4.4 Hz,

1H), 3.81 (bd, 2H), 2.95 -

2.83 (m, 1H), 2.73 - 2.48

(m, 4H), 2.42 -2.26 (m,

2H), 1.22 - 1.11 (m, 6H)

907 (thin film)

1658

ESIMS rniz

425 ([M+Hr)

1 1.1 NMR (400 MHz, CDCI3)

6 8.77(d, J= 1.9 Hz, 1H),

8.50 (d, J= 2.5 Hz, 1H),

7.98 (s, 1H), 7.87 (dt, J=

9.1, 2.4 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.84 (t, J=

7.2 Hz, 2H), 2.71 -2.59

(m, 2H), 2.49 - 2.26 (m,

4H), 1.17 (t, J = 7.2 Hz,

3H)

606

17149

1 I-4 NMR (400 MHz, CD03)

15 8.96 (dd, J= 2.7, 0.8 Hz,

1H), 8.63 (dd, J= 4.7, 1.4

Hz, 1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.96 (s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 5.58 (thin film) ESIMS miz

908 1664 418 ([M+H])

(dddd, J= 11.4, 10.8, 7.7,

1.3 Hz, 1H), 3.92 (ddt, J=

13.5, 3.2, 1.0 Hz, 1H), 3.72

(qd, J= 6.9, 4.2 Hz, 2H),

2.88 (td, J=6.9, 3.7 Hz,

2H), 2.47 (t, J= 7.1 Hz,

2H), 1.17 (t, J= 7.2 Hz,

3H)


68.96 (d, J= 2.6 Hz, 1H),

8.64 (dd,J= 4.8, 1.4 Hz,

1H), 8.06 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.97 (s,

1H), 7.47 (dd, J= 8.3, 4.7 (thin film) ESIMS ink

909 Hz, 1H), 3.72 (q, J= 7.2 1782 380 ([M+H]+)

Hz, 2H), 3.64 - 3.51 (m,

1H), 3.51 -3.36 (m, 2H),

3.07 - 2.92 (m, 2H), 2.86 (t,

J= 7.3 Hz, 2H), 2.47 (t, J=

7.3 Hz, 2H), 1.17(t, J= 7.2

Hz, 3H)

607

17149


6 8.95(d, J= 2.6 Hz, 1H),

8.64 (dd, J= 4.8, 1.5 Hz,

1H), 8.06 (ddd, J= 8.3,


2.7, 1.4 Hz, 1H), 7.96 (s,

1H), 7.47 (dd, J= 8.3, 4.7

1721 401 ([M+H]) Hz, 1H), 3.72 (q, J= 7.2

Hz, 2H), 3.31 -3.16 (m,

1H), 3.04 - 2.86 (m, 2H),

2.81 (t, J= 7.3 Hz, 2H),

2.55 - 2.40 (m, 4H), 1.17 (t,

J = 7.2 Hz, 3H)

1 FI NMR (400 MHz,


= 2.8, 0.7 Hz, 1H), 8.63 (dt,

J = 4.8, 1.4 Hz, 1H), 8.06

(ddq, J= 6.8, 2.7, 1.5 Hz,

1H), 7.96 (s, 1H), 7.46 19F NMR (376

911

ESIMS

m/z 431

(ddt, J= 8.5, 5.0, 1.1 Hz,

1H), 3.25 (s, 3H), 2.88 (t, J

MHz, CDCI3) 6

-128.13 (d, J=

([M+Hr), 433 = 7.3 Hz, 2H), 2.61 (ddt, J 157.9 Hz), -

((M+2+Hr) = 6.9, 3.1, 1.2 Hz, 2H),

2.48 (t, J= 7.3 Hz, 2H),

1.75 (dddd, J= 14.8, 11.3,

7.4, 5.8 Hz, 1H), 1.48

142.85(d, J=

156.7 Hz)

(dddd, J= 12.4, 11.2, 7.9,

4.6 Hz, 1H), 1.05 (dtd, J=

13.2, 7.7, 3.7 Hz, 1H)

608

17149

912 ESIMS m/z

393 ([M+H])

'H NMR (CDCI3) 6 8.97 (d,

J=2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.06

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 8.00 (s, 1H), 7.47 (dd,

J=8.4,4.7 Hz, 1H), 3.72

(q, J= 7.2 Hz, 2H), 3.52 -

3.40 (m, 1H), 2.87 (t, J=

7.3 Hz, 2H), 2.58 (dd, J=

18.4, 7.8 Hz, 1H), 2.52 -

2.28 (m, 4H), 2.28 - 2.10

(m, 2H), 2.02- 1.88 (m,

1H), 1.17 (t, J=7.2 Hz,

3H)

"C NMR

(CDCI3) 6

216.5, 171.2,

148.7, 140.9,

140.0, 135.6,

126.3, 126.3,

124.1, 123.8,

45.6, 44.1,

41.0, 37.0,

34.4, 29.8,

26.5, 13.1

913

ESIMS raiz

349 ([M-

2Me0Hr)

1 11 NMR (CDCI3) 68.97 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H), 8.06

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 8.00 (s, 1H), 7.47 (dd,

J= 8.4, 4.8 Hz, 1H), 4.44

(t, J= 5.6 Hz, 1H), 3.72 (q,

J= 7.2 Hz, 2H), 3.30 (s,

6H), 2.82 (t, J= 7.4 Hz,

2H), 2.56 - 2.48 (m, 2H),

2.44 (t, J= 7.3 Hz, 2H),

1.91 - 1.79(m, 2H), 1.16 (t,

J=7.2 Hz, 3H)

"C NMR

(CDCI3) 6

171.4, 148.6,

140.9, 140.0,

135.6, 126.4,

126.3, 124.1,

123.9, 103.2,

53.1, 44.0,

34.3, 32.6,

27.6, 27.5,

13.1

609

17149

914

ESIMS m/z

469

([M+2+Hr),

467 ([M+2-

Fin


58.96 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.96 (d, J

= 3.8 Hz, 1H), 7.47 (ddd, J

= 8.3, 4.7, 0.7 Hz, 1H),

3.72 (q, J= 7.1 Hz, 2H),

2.85 (t, J= 7.2 Hz, 2H),

2.74 - 2.54 (m, 4H), 2.45 (t,

J = 7.3 Hz, 2H), 1.17 (t, J=

7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-44.55

915 (thin film)

1655

ESIMS m/z

437([M+H])


6 9.06 - 8.96 (m, 1H), 8.64

-8.57 (m, 1H), 8.22 - 8.11

(m,1H), 8.09 - 7.98 (m,

1H), 7.47 - 7.39 (m, 1H),

3.54 - 3.05 (m, 4H), 3.02 -

2.74 (m, 2H), 2.67 - 2.48

(m, 3H), 1.33- 1.06 (m,

6H)

916

(thin film)

3092, 2975,

2933, 1659

ESIMS m/z

424 ([M+H])

'H NMR (400 MHz,


= 2.7 Hz, 1H), 8.63 (dd, J=

4.8, 1.5 Hz, 1H), 8.05 (ddd,

J= 8.4, 2.7, 1.5 Hz, 1H),

7.96(s, 1H), 7.47 (dd, J=

8.4, 4.7 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.85(t, J=

7.2 Hz, 2H), 2.75-2.68 (m,

2H), 2.65 - 2.49 (m, 2H),

2.45 (t, J= 7.2 Hz, 2H),

1.17(t, J=7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-51.30

610

17149

917 (thin film)

1659

ESIMS m/z

440 ([M+H])


68.95 (d, J = 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.96 (s,

1H), 7.47 (dd, J= 8.3, 4.7

Hz, 1H), 5.73 (tt, J= 53.9,

2.7 Hz, 1H), 3.72(q, J=

7.2 Hz, 2H), 2.85 (t, J= 7.3

Hz, 2H), 2.74- 2.61 (m,

2H), 2.45 (t, J= 7.3 Hz,

2H), 2.35 - 2.17 (m, 2H),

1.17(t, J=7.2 Hz, 3H)

918

(thin film)

3093, 2973,

2931, 1741,

1658

ESIMS rn/z

387 ([M+Hr)

1 H NMR (400 MHz,


(m, 1H), 8.63 (dd, J= 4.7,

1.4 Hz, 1H), 8.05 (ddd, J=

8.4, 2.7, 1.5 Hz, 1H), 7.95

(s, 1H), 7.47 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 4.31 (dtd,

J= 24.1, 8.3, 1.6 Hz, 1H),

3.72 (q, J= 7.1 Hz, 2H),

3.09 (dt, J= 8.2, 1.6 Hz,

2H), 2.81 (t, J= 7.3 Hz,

2H), 2.44 (t, J= 7.4 Hz,

2H), 1.17(t, J= 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-86.38(d, J=

39.7 Hz), -

89.46 (d, J=

39.7 Hz)

611

17149

I FI NMR (CDCI3) 6 8.96

(dd, J= 2.8, 0.7 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.96 (s, 19F NMR

ESIMS ink 1H), 7.47 (ddd, J= 8.4, 919 (CDC13) 6 -

421 ([M+Hr) 4.8, 0.8 Hz, 1H), 3.72 (q, J 73.06

= 7.2 Hz, 2H), 2.89 - 2.76

(m, 3H), 2.49 - 2.40 (m,

2H), 2.40 - 2.28 (m, 2H),

1.20(d, J= 6.3 Hz, 3H),

1.17(t, J= 7.2 Hz, 3H)

1 11 NMR (CDCI3) 6 8.98 (d,

J=2.7 Hz, 1H), 8.65 (dd, J

= 4.7, 1.4 Hz, 1H), 8.16(s,

1H), 8.05 - 7.96 (m, 1H),

7.46 (ddd, J= 8.3, 4.7, 0.8

Hz, 1H), 4.08 (q, J=7.0 19F NMR ESIMS miz

920 439 ([M+Hr)

Hz, 1H), 3.98 (dd, J= 13.6,

7.0 Hz, 1H), 3.70 - 3.49

(CDCI3) 6 -

65.88

(m, 2H), 3.29 (ddd, J=

13.7, 11.0, 5.6 Hz, 1H),

2.76 - 2.54 (m, 2H), 1.67

(d, J= 7.1 Hz, 3H), 1.22 (t,

J=7.2 Hz, 3H)

612

17149

I FI NMR (CDCI3) 6 9.01 -

8.94 (m, 1H), 8.68 - 8.60

(m, 1H), 8.18 - 8.06 (m,

1H), 8.06 - 7.98 (m, 1H),

7.51 -7.41 (m, 1H), 4.01 - 4a ''F NMR

ESIMS nilz 3.77 (m, 1.8H), 3.65 (br. S. 921 (CDCI3) 6 -

423 ([M+Fin 1.2H), 3.14 (br. s, 0.4H), 65.71, -65.73

3.07 - 2.86 (m, 1H), 2.86 -

2.70 (m, 0.6H), 2.70- 2.44

(m, 2H), 1.46 (br. d, J= 6.8

Hz, 3H), 1.24- 1.12(m,

3H)

I FI NMR (400 MHz,


= 2.7, 0.7 Hz, 1H), 8.64

(dd, J= 4.8, 1.4 Hz, 1H),

8.05 (s, 1H), 8.04 (ddd, J= (thin film)

ESIMS tn/z 2.7, 1.5, 0.7 Hz, 1H), 7.46 922 3091, 2965,

1658 467 ([M+H]) (ddd, J= 8.4, 4.7, 0.7 Hz,

1H), 3.60 (s, 2H), 2.98 (td,

J = 6.8, 1.0 Hz, 2H), 2.87

(td, J= 6.8, 1.0 Hz, 2H),

2.78 - 2.67 (in, 2H), 2.50 -

2.30 (m, 2H), 2.21 (s, 3H)

613

17149

I FINMR (C003) 6 8.95 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.95 (s, 1H), 7.47

(ddd, J= 8.2, 4.8, 0.8 Hz, 19F NMR

ESIMS rn/z 1H), 3.72 (q, J= 7.1 Hz, 923 (CDCI3) 6 -

421 ([M+Hr) 2H), 3.02 (ddd, J= 9.0, 63.70

6.8, 4.4 Hz, 1H), 2.85 (t, J

= 7.0 Hz, 2H), 2.53 - 2.37

(m, 3H), 2.31 -2.13 (m,

1H), 1.36 (d, J= 6.8 Hz,

3H), 1.17 (t, J= 7.2 Hz,

3H)

IFINMR (400 MHz, CDCI3)

6 8.96(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.8,1.4 Hz,

1H), 8.07 (s, 1H), 8.03

(thin film) ESIMS m/z (ddd, J= 8.3, 2.7, 1.4 Hz, 924

1662 409 ([M+Hr) 1H), 7.46 (ddd, J= 8.4,

4.8, 0.6 Hz, 1H), 3.27 (s,

3H), 3.22 - 3.13 (m, 1H),

3.00 - 2.82 (m, 3H), 2.77 -

2.55 (m, 4H)


68.95 (d, J = 2.6 Hz, 1H),

HRMS—FAB 8.64 (dd, J= 4.8, 1.5 Hz,

(m/z)[M+H] 1H), 8.11 (s, 1H), 8.05

(thin film) calcd for (ddd, J= 8.3, 2.7, 1.4 Hz,

19F NMR (376 C18H21CIF3N4 1H), 7.47 (dd, J= 8.3, 4.8

925 3350, 1736, MHz, CDCI3) 6

1668 035, Hz, 1H), 4.27 (br s, 2H),

-66.40. 465.0970; 3.92 (br s, 2H), 2.83 (t, J=

found, 7.2 Hz, 2H), 2.71 -2.57

465.0972 (m, 2H), 2.46 (t, J= 7.1 Hz,

2H), 2.42 - 2.26 (m, 2H),

2.03 (s, 3H)

614

17149

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.6 Hz, 1H), 8.05

(ddd, J= 8.4, 2.8, 1.5 Hz,

1H), 7.97 (s, 1H), 7.47 (dd, 19F NMR

J= 8.3, 4.7 Hz, 1H), 3.72 (CDCI3) 6-

ESIMS m/z (q, J= 7.3 Hz, 2H), 3.32- 89.43 (d, J= 926

415 ((M+Hl+) 3.17(m, 1H), 2.84(t, J= 228.9 Hz), -

7.3 Hz, 2H), 2.61 -2.47 91.14(d, J=

(m, 1H), 2.43(t, J= 7.4 Hz, 228.5 Hz)

2H), 2.32 - 2.11 (m, 2H),

2.11 - 1.89(m, 2H), 1.81 -

1.69 (m, 1H), 1.17 (t, J=

7.2 Hz, 3H)

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.97(s, 1H), 7.47 (dd,

J= 8.4, 4.7 Hz, 1H), 5.90 19 F NMR ESIMS raiz

927 389 (Wl+Hr)

(II, J= 56.5, 4.4 Hz, 1H),

3.72(q, J= 7.2 Hz, 2H),

(CDCI3) 6 -

117.68

2.83 (t, J= 7.2 Hz, 2H),

2.67- 2.56 (m, 2H), 2.44 (t,

J= 7.3 Hz, 2H), 2.10 (lid, J

= 17.0, 7.5, 4.6 Hz, 2H),

1.17 (t, J= 7.2 Hz, 3H)

615

17149

928

(thin film)

3505, 3100,

1671

HRMS-FAB

(m/z)[M+Hr

calcd for

CI7F119CIF3N4

025,

435.0861;

found,

435.0868


6 8.96(d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.10 (s, 1H), 8.04

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 3.26 (s, 1H), 2.95

-2.76 (multiple peaks, 3H),

2.75 - 2.60 (multiple peaks,

3H), 2.60 - 2.45 (multiple

peaks, 4H), 2.46 -2.28 (m,

2H)

19F NMR (376

MHz, CDCI3) 6

-66.43

929 ESIMS m/z

426 ([M+H])

1 11 NMR (CDCI3) 69.02 (d,

J= 2.7 Hz, 1H), 8.62 (dd, J

= 4.8, 1.4 Hz, 1H), 8.13 -

8.04(m, 2H), 7.45 (dd, J=

8.4, 4.8 Hz, 1H), 3.72 (q, J

= 7.1 Hz, 2H), 3.53 (t, J=

6.8 Hz, 2H), 2.93 - 2.82

(m, 5H), 2.51 (t, J= 6.7 Hz,

2H), 1.17 (t, J= 7.2 Hz,

3H), 1.13 - 0.99 (m, 1H),

0.74 - 0.63 (m, 2H), 0.33

(dt, J= 6.2, 4.9 Hz, 2H)

13C NMR

(CDCI3) 6

171.2, 148.6,

140.5, 140.4,

135.7, 127.2,

126.4, 124.0,

123.5, 55.1,

47.3, 43.8,

36.0, 34.1,

13.1, 5.1, 4.8

930 (IR thin film)

1670

HRMS-FAB

(m/z) [M+H]

calcd for

C16H18CIF4N4

OS,

425.0820;

found,

425.0830

I FI NMR (400 MHz, CDC13)

6 8.95 (d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.09 - 7.98 (multiple

peaks, 2H), 7.46 (dd, J=

8.3, 4.8 Hz, 1H), 4.66 (dt, J

= 47.3, 4.8 Hz, 2H), 3.94

(s, 2H), 2.85 (t, J= 7.2 Hz,

2H), 2.73 - 2.59 (m, 2H),

2.51 (t, J= 7.2 Hz, 2H),

2.46 - 2.27 (m, 2H)

"F NMR (376

MHz, CDCI3) 6

-66.42, -

223.86.

616

17149


6 8.93 (dd, J= 2.8, 0.7 Hz,

1H), 8.63 (dd, J= 4.7, 1.4

HRMS-FAB Hz, 1H), 8.10 (s, 1H), 8.04

931 (IR thin film)

(m/z)[M+Hr

calcd for

C-20H2eCIF3N3

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 3.77 (s,

19F NMR (376

MHz, CDCI3) 5 1666 OS, 2H), 2.84(t, J= 7.2 Hz,

-66.42. 476.1493;

found,

476.1498

2H), 2.66 (ddd, J= 8.4,

6.2, 3.8 Hz, 4H), 2.54 (br s,

4H), 2.46 (t, J= 7.2 Hz,

2H), 2.43 - 2.29 (m, 2H),

1.87- 1.56 (multiple

peaks, 4H)


932 ESIMS m/z

6 8.96 (d, J= 2.4 Hz, 111),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.12 - 7.92 (m, 2H),

425 ([M+H]+) 7.47 (ddd, J= 8.3, 4.8, 0.7

Hz, 1H), 3.44 (t, J= 6.7

Hz, 2H), 3.37 - 3.15 (m,

5H), 2.84 - 2.57 (m, 4H)



68.96 (d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.97 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.72 (q, J 933

1659 367 ([M+H]+ ) = 7.2 Hz, 2H), 2.80 (t, J=

7.5 Hz, 2H), 2.45 (dt, J=

15.0, 7.3 Hz, 4H), 1.58 -

1.43 (m, 2H), 1.42 - 1.30

(m, 2H), 1.16 (t, J= 7.2 Hz,

3H), 0.92- 0.75 (t, J= 7.3

Hz, 3H)

617

17149

934 (thin film)

1436, 1360

ESIMS m/z

409 (1M+Hr)


15 8.95(d, J= 2.5 Hz, 11-1),

8.65 (dd, J= 4.8, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.02 (s,

1H), 7.48 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.71 (s,

3H), 3.04 (t, J= 7.4 Hz,

2H), 2.80 (t, J= 7.4 Hz,

2H), 2.69 - 2.57 (m, 2H),

2.44 - 2.26 (m, 2H)

935 (thin film)

1437, 1423

ESIMS m/z

423 ([M+H])

1 14 NMR (400 MHz, CDCI 3 )

08.96 (d, J= 2.3 Hz, 11-1),

8.65 (dd, J=4.8,1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.98 (s,

1H), 7.48 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 4.29 (bs,

2H), 3.03(t, J= 7.4 Hz,

2H), 2.74 (t, J= 7.4 Hz,

2H), 2.68 - 2.58 (m, 2H),

2.42 - 2.27 (m, 2H), 1.28 (t,

J= 7.2 Hz, 3H)

936

(thin film)

2977, 2938,

1663, 1441,

1326

ESIMS m/z

400 ([WM)

I FI NMR (CDCI3)15 9.01 (d,

J=2.7 Hz, 1H), 8.62 (dd, J

= 4.8, 1.4 Hz, 1H), 8.11 -

8.03 (m, 2H), 7.45 (dd, J=

8.2, 4.8 Hz, 1H), 3.80 -

3.64 (m, 2H), 3.50 (t, J=

6.8 Hz, 2H), 2.98 (q, J=

7.4 Hz, 2H), 2.88 (s, 3H),

2.50 (t, J= 6.7 Hz, 2H),

1.33(t, J= 7.4 Hz, 3H),

1.16(t, J= 7.2 Hz, 3H)

618

17149

937

(thin film)

2975, 2935,

1663, 1441,

1332

ESIMS ink

412 ([M+Hr)

I HNMR (CDCI3) 6 9.03 (d,

J = 2.5 Hz, 1H), 8.68 - 8.56

(m, 1H), 8.15 - 8.04 (m,

2H), 7.48 (dd, J = 8.4, 4.8

Hz, 1H), 3.72(d, J = 7.7

Hz, 2H), 3.51 (t, J = 6.8

Hz, 2H), 2.90 (s, 3H), 2.49

(t, J = 6.8 Hz, 2H), 2.28 (tt,

J = 8.0, 4.9 Hz, 1H), 1.23 -

1.09 (m, 5H), 1.02- 0.90

(m, 2H)

938

(thin film)

2978, 1665,

1441, 1385

ESIMS ni/z

440 ([M+H])

1 FI NMR (CDCI3) 6 8.98 (d,

J = 2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J = 8.3, 2.8, 1.5 Hz,

1H), 7.99 (s, 1H), 7.47 (dd,

J = 8.4, 4.7 Hz, 1H), 3.71

(t, J = 7.3 Hz, 4H), 3.06 (d,

J = 1.3 Hz, 3H), 2.53 (t, J =

7.0 Hz, 2H), 1.17 (t, J = 7.2

Hz, 3H)

19F NMR

(CDCI3) 6 -

74.83

939

(thin film)

2977, 1665,

1442, 1323

ESIMS nilz

516 ([M+Hr)

I HNMR (00013) 6 9.03 (d,

J = 2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.12 -

8.04 (m, 2H), 7.88 (d, J =

8.2 Hz, 2H), 7.79 (d, J =

8.4 Hz, 2H), 7.46 (dd, J =

8.4, 4.7 Hz, 1H), 3.72 (q, J

= 7.8 Hz, 2H), 3.35 (t, J =

6.8 Hz, 2H), 2.81 (s, 3H),

2.53 (t, J = 6.7 Hz, 2H),

1.18(t, J = 7.2 Hz, 3H)

19F NMR

(CDCI3) 6 -

63.13

619

17149

'H NMR (CDCI3) 6 9.03 (d,

J=2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.15-

8.05 (m, 2H), 8.01 (dd, J= (thin

7.9, 1.6 Hz, 1H), 7.54- film) 2976,

ESIMS m/z 7.43 (m, 3H), 7.37 (ddd, J 940 2936, 1662,

482 ([M+Hr) = 8.6, 6.9, 1.8 Hz, 1H), • 1487, 1441,

1335 3.71 (q, J= 6.4 Hz, 2H),

3.59 (t, J= 6.9 Hz, 2H),

2.87 (s, 3H), 2.53 (t, J=

7.0 Hz, 2H), 1.17 (t, J=7.2

Hz, 3H)

1 H NMR (CDCI3) 69.02 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.5 Hz, 1H), 8.12 -

8.02 (m, 3H), 7.98 (dt, J=

(thin film) 8.0, 1.5 Hz, 1H), 7.87 (dt, J

= 7.8, 1.4 Hz, 1H), 7.68 (t,

941 2977, 2935,

2234, 1663,

ESIMS m/z

473 ([M+Hr) J= 7.8 Hz, 1H), 7.47 (ddd,

1441, 1344 J = 8.4, 4.7, 0.8 Hz, 1H),

3.72 (q, J= 6.7, 6.1 Hz,

2H), 3.36 (t, J= 6.8 Hz,

2H), 2.82 (s, 3H), 2.53 (s,

2H), 1.18 (t, J= 7.2 Hz,

3H)

620

17149

942

(thin film)

2977, 1664,

1532, 1441,

1351

ESIMS miz

493 ((M+Hr)

I FI NMR (CDCI 3) 6 9.02 (d,

J=2.7 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H), 8.59 (t,

J= 1.9 Hz, 1H), 8.44 (ddd,

J=8.3,2.3,1.1 Hz, 1H),

8.13 - 8.05 (m, 3H), 7.75 (t,

J= 8.0 Hz, 1H), 7.47 (dd, J

= 8.4, 4.8 Hz, 1H), 3.72 (q,

J= 7.1 Hz, 2H), 3.39 (t, J=

6.8 Hz, 2H), 2.86 (s, 3H),

2.54 (t, J= 6.9 Hz, 2H),

1.18 (t, J= 7.2 Hz, 3H)

943

(thin film)

2978, 2937,

1661, 1442,

1331

ESIMS m/z

530 ([M+Hr)

1 H NMR (CDCI3) 6 8.99 (d,

J=2.7 Hz, 1H), 8.62 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J= 8.4, 2.8, 1.5 Hz,

1H), 8.02 (s, 1H), 7.68 -

7.55 (m, 3H), 7.55 - 7.48

(m, 1H), 7.45 (dd, J= 8.4,

4.8 Hz, 1H), 4.27 (s, 2H),

3.80 - 3.62 (m, 2H), 3.31 (t,

J= 6.7 Hz, 2H), 2.73 (s,

3H), 2.41 (t, J= 6.7 Hz,

2H), 1.15 (t, J = 7.2 Hz,

3H)

944

(thin film)

2975, 2934,

1660, 1441,

1396

ESIMS rrVz

452 ([M+H])


J= 2.6 Hz, 1H), 8.60 (dd, J

= 4.7, 1.4 Hz, 1H), 8.14(s,

1H), 8.09 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.48 -

7.40 (m, 2H), 7.38 (d, J=

1.4 Hz, 1H), 3.84 - 3.64

(m, 5H), 3.47 (t, J= 6.9 Hz,

2H), 2.86 (s, 3H), 2.54 (t, J

= 6.1 Hz, 2H), 1.16(t, J=

7.2 Hz, 3H)

621

17149

945

(thin film)

2929, 1662,

1487, 1441

ESIMS m/z

526 ([M+H]')

1 1-I NMR (CDC13) 6 9.02 (d,

J=2.6 Hz, 1H), 8.63 (dd, J

= 4.7, 1.4 Hz, 1H), 8.16 -

8.04 (m, 4H), 8.01 -7.91

(m, 2H), 7.51 -7.42 (m,

1H), 3.79 - 3.64 (m, 2H),

3.37 (t, J= 6.8 Hz, 2H),

3.11 (s, 3H), 2.83 (s, 3H),

2.52 (t, J= 6.9 Hz, 2H),

1.18 (t, J= 7.1 Hz, 3H)

'H NMR (CDCI3) 68.97 (d,

J= 2.7 Hz, 1H), 8.65 (dd, J

= 4.7, 1.4 Hz, 1H), 8.06

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 8.02 (s, 1H), 7.53 - "F NMR

ESIMS m/z 7.43(m, 1H), 7.13 (dq, J= 946 (CDCI3) 5-

437 ([M+Hr) 15.2, 1.8 Hz, 1H), 6.78 (dq, 65.07

J= 15.3, 6.1 Hz, 1H), 3.71

(q, J= 7.2 Hz, 2H), 3.49 (t,

J= 6.7 Hz, 2H), 2.70 (t, J=

6.7 Hz, 2H), 1.17 (t, J = 7.2

Hz, 3H)

1 H NMR (CDCI3) 68.96 (d,

J= 2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.97 (s, 1H), 7.47 (dd,

J= 8.4, 4.7 Hz, 1H), 7.24 19F NMR ESIMS m/z

947 421 ([M-PH] . )

(dq, J= 15.0, 1.9 Hz, 1H),

6.45 (dq, J= 15.0, 6.5 Hz,

(CDCI3) 6 -

63.65

1H), 3.81 -3.60 (m, 2H),

3.35 - 3.22 (m, 1H), 3.18 -

3.02 (m, 1H), 2.72 - 2.52

(m, 2H), 1.16(t, J= 7.2 Hz,

3H)

622

17149

948 (thin film)

1661

ESIMS rniz

490 ([M+Hr)


68.95 (d, J = 2.7 Hz, 1H),

8.63 (dd, J= 4.8,1.5 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.96 (s,

1H), 7.47 (dd, J= 8.3, 4.7

Hz, 1H), 5.73 (tt, J= 53.9,

2.7 Hz, 1H), 3.72 (q, J=

7.2 Hz, 2H), 2.85 (t, J= 7.3

Hz, 2H), 2.74 - 2.61 (m,

2H), 2.45 (t, J= 7.3 Hz,

2H), 2.35 - 2.17 (m, 2H),

1.17(t, J=7.2 Hz, 3H)

949 (thin film)

1660

ESIMS ink

547 ([M+Hr)

'H NMR (400 MHz,


= 2.7 Hz, 1H), 8.63 (dd, J=

4.8, 1.5 Hz, 1H), 8.05 (ddd,

J = 8.3, 2.7, 1.5 Hz, 1H),

7.96 (s, 1H), 7.47 (ddd, J=

8.3, 4.7, 0.8 Hz, 1H), 3.72

(q, J= 7.2 Hz, 2H), 2.81 (t,

J= 7.4 Hz, 2H), 2.56 - 2.47

(m, 2H), 2.43 (t, J= 7.4 Hz,

2H), 2.07 (dq, J = 18.2,

10.1, 8.9 Hz, 2H), 1.70 -

1.64 (m, 4H), 1.17 (t, J =

7.2 Hz, 3H).

623

17149

950 (thin film)

1678

HRMS—FAB

(m/z) [WM

calcd for

C16H 1 7CIF3N4

OS,

443.0726;

found,

443.0732


6 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.65 (dd, J= 4.8, 1.5

Hz, 1H), 8.07- 7.99

(multiple peaks, 2H), 7.47

(ddd, J= 8.3, 4.8, 0.8 Hz,

1H), 6.09 (It, J= 56.2, 4.4

Hz, 1H), 3.98 (br s, 2H),

2.84 (t, J= 7.1 Hz, 2H),

2.73 - 2.63 (m, 2H), 2.52 (t,

J= 7.1 Hz, 2H), 2.45 - 2.29

(m, 2H)

951 3091, 2967,

1658

ESIMS m/z

451 (CM+Hr),

453

([11/41+2+H])

'H NMR (400 MHz,

Chloroform-d) 6 8.96 (s,

1H), 8.64 (dd, J=4.8,1.4

Hz, 1H), 8.07 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.93 (s,

1H), 7.49 (s, 1H), 3.72 (s,

2H), 2.85 (t, J= 7.2 Hz,

2H), 2.71 -2.62 (m, 2H),

2.44 (t, J= 7.3 Hz, 2H),

2.41 -2.29 (m, 2H), 1.24 -

1.12 (m, 3H)

952 (thin film)

1690

HRMS—FAB

(m/z) [WM'

calcd for

C16H15CIF6N4

OS,

461.0632;

found,

461.0637


6 8.96 (dd, J= 2.7, 0.7 Hz,

1H), 8.66 (dd, J= 4.8,1.4

Hz, 1H), 8.08 - 8.00


(ddd,J= 8.3, 4.8, 0.7 Hz,

1H), 3.00 - 2.80 (multiple

peaks, 3H), 2.80 - 2.56


(t, J= 7.1 Hz, 2H), 2.45 -

2.29 (m, 2H)

19F NMR (376

MHz, CDCI3) 6

-66.40, -69.87.

624

17149

953 (thin film)

1671

HRMS-FAB

(m/z) (M+H].

calcd for

C16H 1 8C12F3N

40S,

441.0525;

found,

441.0537


58.97 (d, J= 2.7 Hz, 1H),

8.65 (dd, J= 4.8, 1.4 Hz,

1H), 8.10 (s, 1H), 8.06

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.48 (ddd, J= 8.2,

4.8, 0.7 Hz, 1H), 3.98 (br s,

2H), 3.73 (br s, 2H), 2.84

(t, J= 7.2 Hz, 2H), 2.72 -

2.61 (m, 2H), 2.49 (t, J=

7.2 Hz, 2H), 2.45 - 2.28

(m, 2H)

19F NMR (376

MHz, CDCI3) 6

-66.39.

954 (thin film)

1672

HRMS-FAB

(m/z) [WM+

calcd for

C I7H 14CIF4N4

OS,

475.0789;

found,

475.0795


6 8.96 (dd, J=2.7, 0.7 Hz,

1H), 8.65 (dd, J= 4.8, 1.5

Hz, 1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.99 (s,

1H), 7.48 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 4.01 -

3.83 (m, 2H), 2.84 (t, J=

7.1 Hz, 2H), 2.73 - 2.59

(m, 2H), 2.60 - 2.41

(multiple peaks, 4H), 2.42 -

2.27 (m, 2H)

19F NMR (376

MHz, CDCI3) 6

-64.93, -66.40

625

17149

I li NMR (400 MHz, CDCI3)

6 8.95 (dd, J= 2.8, 0.7 Hz,

1H), 8.57 (dd, J= 4.8, 1.5

Hz, 1H), 8.51 (s, 1H), 8.00

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.41 (ddd, J= 8.3,

(thin film) ESIMS m/z 4.7, 0.7 Hz, 1H), 4.15 - 955

1689 324 ([M+1-1] + ) 3.90 (m, 2H), 3.08 (dd, J=

13.1, 3.9 Hz, 1H), 2.88 (td,

J=8.9,3.9 Hz, 1H), 2.72

(dd, J= 13.1, 8.8 Hz, 1H),

2.47 (dddd, J= 12.9, 8.8,

7.5, 3.2 Hz, 1H), 2.18 (s,

3H), 2.16 - 2.06 (m, 1H)

T N NMR (400 MHz, CDCI3)

68.91 (dt, J= 2.2, 1.0 Hz,

1H), 8.54 (dd, J= 4.7,1.4

Hz, 1H), 8.45 (d, J= 1.0

Hz, 1H), 7.97 (ddt, J= 8.3,

2.4, 1.1 Hz, 1H), 7.45 -

(thin film) ESIMS ink 7.35 (m, 1H), 4.10 - 3.90 956

1690 340 (NMI') (m, 2H), 3.29 (td, J= 13.1,

4.1 Hz, 1H), 3.24 - 3.07

(m, 1H), 2.79 (ddd, J=

13.1, 9.2, 8.3 Hz, 1H), 2.68

- 2.65 (m, 3H), 2.66 - 2.59

(m, 1H), 2.20 - 2.06 (m,

1H)

626

17149

957 3091, 2967,

1654

ESIMS m/z

x467

((M+Hr), 469

([M+2+H])

I FI NMR (400 MHz,


= 2.8, 0.7 Hz, 1H), 8.64

(dd. J= 4.8, 1.4 Hz, 1H),

8.06 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 8.00(s, 1H), 7.46

(ddd, J= 8.4, 4.8, 0.8 Hz,

1H), 3.72 (m, 2H), 3.25 -

3.09 (m, 1H), 3.02 - 2.81

(m, 3H), 2.68 (m, 1H), 2.66

- 2.53 (m, 3H), 1.18 (t, J=

7.2 Hz, 3H)

958 (thin film)

1671

HRMS—FAB

(m/z) [WM'

calcd for

C181-113CIF3N4

OS,

431.0915;

found,

431.0925


5 8.95 (d, J= 2.8 Hz, 1H),

8.64 (dd, J= 4.8,1.5 Hz,

1H), 8.11 -8.03 (multiple

peaks, 2H), 7.47 (ddd, J=

8.3, 4.7, 0.7 Hz, 1H), 4.41

(s, 2H), 2.85 (t, J= 7.3 Hz,

2H), 2.72 - 2.62 (m, 2H),

2.48 (t, J= 7.3 Hz, 2H),

2.44 - 2.28 (m, 2H), 1.80 (t,

J= 2.4 Hz, 3H)

19F NMR (376

MHz, CDCI3) 5

-66.40.

959 (thin film)

1660

ESIMS m/z

469 ([11/44+Hr)


58.94 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.90 (s,

1H), 7.55 (s, 1H), 7.51 -

7.34 (m, 4H), 3.74-3.69 (m,

4H), 2.74 (t, J= 7.3 Hz,

2H), 2.37 (t, J= 7.3 Hz,

2H), 1.15 (t, J= 7.2 Hz,

3H)

627

17149

960 (thin film)

1659

ESIMS m/z

469 ([M+Hr)


ö 8.95 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.91 (s,

1H), 7.54 (d, J= 8.0 Hz,

2H), 7.47 (dd, J= 8.0, 4.4

Hz, 1H), 7.40(d, J=8.0

Hz, 2H), 3.76 - 3.65 (m,

4H), 2.72 (t, J= 7.3 Hz,

2H), 2.38 (t, J= 7.3 Hz,

2H), 1.15(t, J=7.2 Hz,

3H)

961 (thin film)

1660

ESIMS m/z

470 ([M+H])

1 HNMR (400 MHz, CDCI3)

O 8.95(d, J= 2.5 Hz, 1H),

8.63 (m, 2H), 8.04 (ddd, J

= 8.3, 2.7, 1.4 Hz,1H), 7.90

(s, 1H), 7.54 (d, J= 8.0 Hz,

1H), 7.47 (dd, J= 8.0, 4.4

Hz, 1H), 7.40(d, J= 8.0

Hz, 1H), 3.76 - 3.65 (m,

4H), 2.73 (t, J= 7.3 Hz,

2H), 2.38 (t, J= 7.3 Hz,

2H), 1.15 (t, J = 7.2 Hz,

3H)

628

17149


69.01 -8.90 (m, 1H), 8.63

(dd, J= 4.8, 1.4 Hz, 1H),

8.06 (ddd, J = 8.3, 2.7, 1.5

Hz, 1H), 7.97 (s, 1H), 7.47

(thin film) ESIMS tn/z

(ddd, J = 8.3, 4.7, 0.8 Hz,

1H), 4.78 (dd, J = 7.7, 6.2 962

1690 382 (CM+Hr) Hz, 2H), 4.36 (t, J = 6.1

Hz, 2H), 3.72 (q, J = 7.2

Hz, 2H), 3.15 (tt, J = 7.8,

6.0 Hz, 1H), 2.90 - 2.73

(m, 4H), 2.42 (t, J = 7.3 Hz,

2H), 1.17 (t, J = 7.2 Hz,

3H)

'H NMR (400 MHz, CDCI 3) '

963 (thin film) ESIMS miz

6 8.96 (d, J = 2.7 Hz, 1H),

8.64 (dd, J= 4.9, 1.5 Hz,

1H), 8.05 (ddd, J = 8.3,

2.7, 1.5 Hz, 1H), 7.96 (s,

1H), 7.47 (ddd, J= 8.5,

1661 508 ([M+H]) 4.8, 0.8 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.86 (t, J =

7.2 Hz, 2H), 2.80 - 2.63

(m, 2H), 2.45 (t, J = 7.3 Hz,

2H), 2.42 - 2.26 (m, 2H),

1.17 (t. J = 7.2 Hz, 3H)

629

17149

964 ESIMS m/z

437 ([M+Hr)

'H NMR (CDCI3) 6 8.97 (d,

J=2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.4 Hz, 1H), 8.09 -

7.99 (m, 2H), 7.46 (dd, J=

8.4, 4.8 Hz, 1H), 3.83 -

3.60 (m, 2H), 3.25 - 2.91

(m, 2H), 2.90 - 2.57 (m,

4H), 2.21 (II, J= 15.1, 10.1

Hz, 1H), 1.43 (d, J= 6.9

Hz, 1.67H), 1.40 (d, J= 6.9

Hz, 1.33H), 1.18 (t, J= 7.2

Hz, 3H)

19F NMR

(CDCI3) 6 -

62.92, -63.40

965 ESIMS m/z

468 ((M+Hr)

1 H NMR (400 MHz,


= 2.7 Hz, 1H), 8.64 (dd, J=

4.7, 1.4 Hz, 1H), 8.06 (ddd,

J = 8.3, 2.7, 1.5 Hz, 1H),

8.016 (s, 1H), 7.47 (ddd, J

= 8.4, 4.8, 0.8 Hz, 1H),

3.72 (q, J= 7.5 Hz, 2H),

3.45 - 3.37 (m, 2H), 3.32 (t,

J= 7.1 Hz, 2H), 2.90 (s,

3H), 2.67 (t, J= 7.1 Hz,

2H), 2.51 -2.35 (m, 2H),

1.17(t, J= 7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-65.30 (d, J=

12.7 Hz)

630

17149

966 (thin film)

1662

ESIMS m/z

558 ([M+H])


15 8.95 (dd, J= 2.7, 0.8 Hz,

1H), 8.63 (dd, J=4.8,1.4

Hz, 1H), 8.05 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.96 (s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.86 (t, J=

7.2 Hz, 2H), 2.75 - 2.62

(m, 2H), 2.45 (t, J= 7.2 Hz,

2H), 2.43 - 2.27 (m, 2H),

1.17(t, J=7.2 Hz, 3H)

967 (thin film)

1661

ESIMS m/z

519 ([M+H])

1 1-I NMR (400 MHz, CDCI3)

58.96 (dd, J= 2.6, 0.8 Hz,

1H), 8.63 (dd, J=4.7,1.4

Hz, 1H), 8.05 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.96 (s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.86 (t, J=

7.3 Hz, 2H), 2.77 - 2.69

(m, 2H), 2.45 (t, J= 7.3 Hz,

2H), 2.43 - 2.30 (m, 2H),

1.17(t, J=7.2 Hz, 3H)

968 (thin film)

3105, 1706

HRMS—FAB

(m/z) [WM'

calcd for

C14H12CIN40

25,

341.0834;

found,

341.0835


5 8.93 (d, J = 2.6 Hz, 1H),

8.59 (dd, J= 4.8, 1.5 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.94 (s,

1H), 7.43 (dd, J=8.3,4.8

Hz, 1H), 4.27 (br s, 2H),

3.67 (q, J= 7.2 Hz, 2H),

2.69 (br s, 2H), 2.07 (br s,

3H), 1.20 (t, J= 7.1 Hz,

3H)

631

17149

969 (thin film)

1437, 1424

ESIMS rn/z

439 ([M+Hr)


08.98 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.10 - 8.02 (m, 2H),

7.47 (ddd, J= 8.3, 4.8, 0.7

Hz, 1H), 4.28 (bs, 2H),

3.54 (bs, 1H), 3.10 - 2.81

(m, 5H), 2.67 - 2.52 (m,

2H), 1.29 (t, J= 7.2 Hz,

3H)

970 (thin film)

3106, 1707

HRMS-FAB

(m/z) [M+Hr

calcd for

C13HI7CIF3N4

02S,

409.0707;

found,

409.0716


6 8.92(d, J= 2.7 Hz, 1H),

8.59 (dd, J= 4.9, 1.3 Hz,

1H), 8.03 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.92 (s,

1H), 7.43 (dd, J= 8.4, 4.7

Hz, 1E1). 4.51 -4.15


3.57 (m, 2H), 3.28 - 3.07

(m, 1H), 3.00 (d, J= 9.5

Hz, 1H), 2.85 (br s, 1H),

1.20 (t, J= 7.1 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-66.64

971 ESIMS (raiz

407 ([M+H])

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.7, 1.5 Hz, 1H), 8.05

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.96 (s, 1H), 7.46 (dd,

J= 8.3, 4.7 Hz, 1H), 3.70

(q, J= 7.2 Hz, 2H), 3.04 (q,

J= 10.0 Hz, 2H), 2.68 (t, J

= 7.0 Hz, 2H), 2.27 (t, J=

7.0 Hz, 2H), 1.94 (p, J=

7.0 Hz, 2H), 1.16 (t, J = 7.2

Hz, 3H)

"F NMR

(CDCI3) 6 -

66.39

632

17149

972 (thin film)

1708

HRMS-FAB

(m/z) [M+Fi]'

calcd for

C141-115CIF3N4

025,

395.0551;

found,

395.0546


6 8.93 (d, J= 2.7 Hz, 1H),

8.59 (dd, J= 4.8, 1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 795_

7.83 (m, 1H), 7.44 (dd, J=

8.3, 4.7 Hz, 1H), 4.51 -

4.24 (m, 2H), 3.67 (q, J=

7.2 Hz, 2H), 3.33 - 3.00

(m, 2H), 1.20(t, J= 7.1 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

41.14

973 (thin film)

1661

ESIMS ink

455 ([M+Hi+)


6 8.88(d, J= 2.5 Hz, 1H),

8.62 (dd, J= 4.7, 1.3 Hz,

1H), 7.97 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.82 (s,

1H), 7.50 - 7.40 (m, 3H),

7.36 - 7.32 (d, J= 5.2 Hz,

2H), 3.71 (q, J= 7.1 Hz,

2H), 3.27 (t, J= 7.3 Hz,

2H), 2.50 (t, J= 7.3 Hz,

2H), 1.16(t, J= 7.2 Hz,

3H)

974 (thin film)

3321, 1650

.

HRMS-FAB

(m/z)[M+11] +

calcd for

CI5H 18CIF3N5

OS,

408.0867;

found,

408.0881

I FI NMR (400 MHz, COCI3)

6 8.95 (dd, J= 2.6, 0.7 Hz,

1H), 8.63 (dd, J= 4.7, 1.4

Hz, 1H), 8.04 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.98 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 4.77 (t, J

= 6.0 Hz, 1H), 3.68 (q, J=

7.1 Hz, 2H), 3.42(q, J=

6.3 Hz, 2H), 3.08 (q, J=

9.9 Hz, 2H), 2.85 - 2.74

(m, 2H), 1.16(t, J= 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-66.54

633

17149

'H NMR (400 MHz,


= 2.7, 0.7 Hz, 1H), 8.64

(dd, J= 4.7, 1.4 Hz, 1H),

8.17 - 7.85 (m, 2H), 7.46

(thin film) ESIMS m/z (ddd, J= 8.4, 4.8, 0.8 Hz, 975

1662 374 ([M+Hr) 1H), 3.73 (qd, J= 6.8, 3.7

Hz, 2H), 3.19 (dt, J= 13.0,

7.6 Hz, 1H), 3.08 - 2.84

(m, 3H), 2.76 - 2.50 (m,

4H), 1.18(t, J=7.2 Hz,

3H).

1 11 NMR (400 MHz, CDCI 3)

6 8.97 (dd, J= 2.8, 0.7 Hz,

1H), 8.63 (dd,J=4.8,1.4

Hz, 1H), 8.09 - 7.98 (m,


976 4.7, 0.8 Hz, 1H), 3.82 - 1660 535 ([M+Hr)

3.61 (m, 2H), 3.18 (dt, J=

13.0, 7.6 Hz, 1H), 3.07 -

2.85 (m, 3H), 2.76 - 2.49

(m, 4H), 1.18 (t, J= 7.2 Hz,

3H)


HRMS-FAB 68.93 (d, J= 2.7 Hz, 1H),

(m/z)[M+Hr 8.65 - 8.55 (m, 1H), 8.02

calcd for (ddd, J= 8.3, 2.8, 1.5 Hz, 19F NMR (376

(thin film) C1511 17C1F3N4 1H), 7.90 (s, 1H), 7.44 (dd, 977 MHz, CDCI3) 6

1708 025, J= 8.4, 4.7 Hz, 1H), 4.41 - -39.33

409.0707; 4.03 (m, 2H), 3.77 - 3.59

found, (m, 2H), 3.57 - 3.38 (m,

409.0708 1H), 1.59- 1.28 (m, 3H),

1.29- 1.13(m, 3H)

634

17149

1 H NMR (CDCI3) 6 8.98

(dd, J= 2.7, 0.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 8.00 (s, 19F NMR

ESIMS rn/z 1H), 7.46 (ddd, J= 8.3, 978 (CDCI3) 6 -

468 ([M+H]') 4.7, 0.8 Hz, 1H), 3.72 (q, J 65.23

= 7.1 Hz, 2H), 3.50 (t, J=

6.5 Hz, 2H), 3.47 - 3.40

(m, 2H), 2.85 (s, 3H), 2.62

-2.41 (m, 4H), 1.17 (t, J=

7.2 Hz, 3H)


6 8.97 (dd, J= 2.7, 0.7 Hz,

HRMS-FAB 1H), 8.63 (dd, J= 4.8, 1.4

(m/z)[M+H)* Hz, 1H), 8.05 (ddd, J= 8.3,

calcd for 2.7, 1.5 Hz, 1H), 8.01 (s, 19F NMR (376

(thin film) CI 7H 19CIF3N4 1H), 7.46 (ddd, J= 8.4, 979 MHz, CDCI3) 6

1666 02S, 4.8, 0.8 Hz, 1H), 3.70 (q, J -66.58.

435.0864; = 7.2 Hz, 2H), 3.09 - 2.98

found, (m, 2H), 2.92 (t, J= 6.6 Hz,

435.0877 2H), 2.50 (t, J= 6.6 Hz,

2H), 2.44 - 2.28 (m, 2H),

1.15(t, J= 7.2 Hz, 3H)

'El NMR (400 MHz, CDCI3)

6 8.99 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J= 4.8,1.4

Hz, 1H), 8.15 - 7.96 (m,


980 4.8, 0.8 Hz, 1H), 3.71 (q, J 1661 383 ([M+1-1] . )

= 7.2 Hz, 2H), 2.83 (t, J=

7.2 Hz, 2H), 2.74- 2.60

(m, 4H), 2.45 (t, J= 7.3 Hz,

2H), 2.38 (s, 6H), 1.16 (t, J

= 7.2 Hz, 3H)

635

17149

981 ESIMS m/z

405 ((kl+Hr)

'H NMR (CDCI3) 6 8.97

(dd, J= 2.7, 0.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.09 - 8.00 (m, 2H),

7.46 (ddd, J= 8.3, 4.8, 0.8

Hz, 1H), 6.02 (11, J= 56.1,

3.9 Hz, 1H), 3.85 - 3.62

(m, 2H), 3.24 - 3.08 (m,

1H), 2.98 - 2.76 (m, 3H),

2.76 -2.60 (m, 2H), 2.46 -

2.24 (m, 2H), 1.18 (t, J=

7.2 Hz, 3H)

19F NMR

(CDCI3) 6 -

112.36 - -

121.41 (m)

982 (thin film)

3084, 1672

HRMS-FAB

(m/z) [M+Hr

calcd for

CI7H13CIF6N4

02S,

491.0738;

found,

491.0750


6 8.97 (dd, J= 2.7, 0.7 Hz,

1H), 8.65 (dd, J= 4.8, 1.5

Hz, 1H), 8.07 (s, 1H), 8.04

(ddd, J= 8.4, 2.7, 1.5 Hz,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.91 (br s,

2H), 3.16 (dt, J= 14.3, 7.4

Hz, 1H), 3.01 -2.79


(s, 2H), 2.67 - 2.54 (m,

2H), 2.49 (dt, J= 10.5, 7.4

Hz, 2H)

19F NMR (376

MHz, CDCI3) 6

-64.96, -65.82.

636

17149

983 (thin film)

1659

ESIMS m/z

470 ([M+Fi])


6 8.96(d, J= 2.5 Hz, 1H),

8.68 - 8.61 (m, 2H), 8.06

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.98 (bs, 1H), 7.59 (s,

1H), 7.47 (dd, J= 8.3, 4.7

Hz, 1H), 7.35 (d, J= 5.0

Hz, 1H), 3.87 (s, 2H), 3.70

(q, J= 7.1 Hz, 2H), 2.81 (t,

J= 7.3 Hz, 2H), 2.44 (t, J=

7.3 Hz, 2H), 1.15(t, J=7.2

Hz, 3H)

984

(thin film)

3321, 3085,

1656

HRMS-FAB

(m/z) [WM'

calcd for

C1el1eCIF3N3

OS,

394.0711;

found,

394.0718


6 8.95(d, J= 2.7 Hz, 1H),

8.64 (dd, J=4.8,1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.8, 1.5 Hz, 1H), 7.97 (s,

1H), 7.50 - 7.41 (m, 1H),

4.97 (t, J = 6.5 Hz, 1H),

4.50 (d, J= 6.6 Hz, 2H),

3.69 (q, J= 7.1 Hz, 2H),

3.35(q, J= 10.2 Hz, 2H),

1.17(t, J= 7.2 Hz, 3H)

19F NMR (376

MHz, CDa 3) 6

-66.62.

637

17149

1 H NMR (CDCI3) 6 8.93

(dd, J= 2.7, 0.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.02 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.85 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 7.33 - ulF NMR

ESIMS ink 7.25 (m, 2H), 7.25 - 7.15 985 (CDCI3) 6 -

497 ([M+1-1] .) (m, 3H), 3.70 (q, J= 7.6 63.14

Hz, 2H), 3.17 - 3.06 (m,

1H), 2.97 (dd, J= 14.1, 6.3

Hz, 1H), 2.88 (dd, J= 14.1,

7.8 Hz, 1H), 2.84- 2.70

(m, 2H), 2.46 - 2.30 (m,

4H), 1.15 (t, J = 7.2 Hz,

3H)

'H NMR (CDCI3) 6 9.02 -

8.90 (m, 1H), 8.63 (dd, J=

4.8, 1.4 Hz, 1H), 8.11 (s,

1H), 8.03 (ddd, J= 8.3,

ESIMS m/z 2.7, 1.5 Hz, 1H), 7.47 (ddd, 19F NMR

986 393 ([M+H])

J= 8.3, 4.8, 0.8 Hz, 1H),

3.43 (q, J=6.8 Hz, 1H),

(CDCI3) 6 -

66.19

3.26 (s, 3H), 2.80 (t, J=

8.0 Hz, 2H), 2.46 - 2.23

(m, 2H), 1.49 (d, J= 6.9

Hz, 3H)

638

IA

17149

987 ESIMS m/z

407 ([M+H])

1 H NMR (CDCI3) 5 9.00 -

8.90 (m, 1H), 8.63 (dd, J =

4.8, 1.4 Hz, 1H), 8.12 (s,

1H), 8.04 (ddd, J = 8.3,

2.8, 1.5 Hz, 1H), 7.47 (ddd,

J = 8.3, 4.8, 0.8 Hz, 1H),

3.41 (q, J = 7.6, 7.2 Hz,

1H), 3.25 (s, 3H), 2.75 -

2.59 (m, 2H), 2.27 - 2.11

(m, 2H), 1.86- 1.73 (m,

2H), 1.47(d, J = 6.9 Hz,

3H)

19F NMR

(CDCI3)15 -

66.16

988 (thin film)

3315, 1719

HRMS-FAB

(m/z)

[M+Na]

calcd for

C 1 21-112CIF3N5

Na02S,

472.0792;

found,

472.0812


59.01 -8.92 (m, 1H), 8.89

(s, 1H), 8.62 (dd, J= 4.8,

1.5 Hz, 1H), 8.09 - 7.98


(ddd, J = 8.4, 4.8, 0.8 Hz,

1H), 3.38 (qd, J = 7 .3, 5.4

Hz, 2H), 2.81 (t, J = 6.8

Hz, 2H), 2.71 -2.65 (m,

2H), 2.62 (t, J = 6.8 Hz,

2H), 2.47 - 2.27 (m, 2H),

1.24 (t, J = 7.3 Hz, 3H)

19F NMR (376

MHz, CDCI3) /5

-66.39

989 (thin film)

1660

HRMS-FAB

(m/z)[M+Hr

calcd for

CI3H14CIF3N5

OS,

380.0554;

found,

380.0557


5 8.98 - 8.91 (m, 1H), 8.64

(dd, J = 4.8, 1.5 Hz, 1H),

8.04 (ddd, J = 8.3, 2.7, 1.5

Hz, 1H), 7.97 (s, 1H), 7.47

(ddd, J = 8.4, 4.8, 0.8 Hz,

1H), 5.08 (m, 1H), 4.72

(dd, J = 6.8, 1.0 Hz, 2H),

3.83 - 3.61 (m, 2H), 1.18 (t,

J = 7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 5

-40.06

639

17149

990 (thin film)

3305, 1655

HRMS-FAB

(m/z) [M+11].

calm! for

C15H 18C1F3N5

OS,

408.0867;

found,

408.0873


6 8.95 (dd, J= 2.8, 0.8 Hz,

1H), 8.64 (dd, J= 4.7,1.4

Hz, 1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.98 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 4.77 (t, J

= 6.4 Hz, 1H), 4.44(d, J=

6.4 Hz, 2H), 3.69 (q, J=

7.1 Hz, 2H), 2.91 -2.72

(m, 2H), 2.60 - 2.38 (m,

2H), 1.17 (t, J = 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-66.26

991 ESIMS m/z

457 01+11].)

'H NMR (400 MHz, CDCI3 )

6 8.89 (d, J = 2.5 Hz, 1H),

8.62 (dd, J= 4.7, 1.4 Hz,

1H), 8.39(d, J= 5.5 Hz,

1H), 8.04- 7.95 (m, 2H),

7.88 (s, 1H), 7.47 - 7.42

(m, 1H). 3.73 (q, J=7.2

Hz, 2H), 3.49 (t, J= 6.8

Hz, 2H), 2.69 (t, J= 6.8

Hz, 2H), 1.17 (t, J= 7.2

Hz, 3H)

992 ESIMS m/z

425 ([M+Hr)

I FI NMR (CDCI3) 08.97

(dd, J= 2.7, 0.8 Hz, 1H),

8.65 (dd, J= 4.8, 1.5 Hz,

1H), 8.20 (s, 1H), 8.00

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 4.15 (q, J

=7.1 Hz, 1H), 3.72 - 3.55

(m, 1H), 3.34 (s, 3H), 3.33

-3.22 (m, 1H), 2.78 - 2.53

(m, 2H), 1.67 (d, J= 7.1

Hz, 3H)

' 9F NMR

(CDCI3) 6 -

65.85

640

17149

'H NMR (CDCI3) 6 9.02 -

8.93 (m, 1H), 8.69 - 8.60

(m, 1H), 8.18 (s, 0.5H),

8.15 (s, 0.5H), 8.07 - 7.96

(m, 1H), 7.53 - 7.41 (m, "F NMR

ESIMS Ink 1H), 4.03(q, J= 6.9 Hz, 993 (CDCI3) 6 -

409 ([M+Hr) 1H), 3.33 (s, 1.5H), 3.31 65.73

(s, 1.5H), 3.26 -3.09 (m,

0.5H), 3.09 - 2.87 (m, 1H),

2.87 - 2.72 (m, 0.5H), 2.70

-2.45 (m, 2H), 1.46 (d, J=

6.9 Hz, 3H);

'H NMR (CDCI3) 68.97

(dd, J= 2.6, 0.8 Hz, 1H),

8.64 (dd, J= 4.8,1.5 Hz,

1H), 8.21 (s, 1H), 8.00

' (ddd, J= 8.3, 2.7, 1.5 Hz,

ES I MS m/z 1H), 7.45 (ddd, J= 8.3, "F NMR

994 4.8, 0.8 Hz, 1H), 4.11 (q, J (CDCI3) 6 - 439 ([M+Hr)

= 7.1 Hz, 1H), 3.47 (dt, J= 66.44

14.3, 7.5 Hz, 1H), 3.33 (s,

3H), 3.24 - 3.07 (m, 1H),

2.42 - 2.23 (m, 2H), 2.22 -

2.11 (m, 2H), 1.64 (d, J=

7.1 Hz, 3H)

641

17149

1 H NMR (CDCI3) 6 9.03 -

8.93 (m, 1H), 8.70 - 8.61

(m, 111), 8.19 (s, 0.5H),

8.16 (s, 0.5H), 8.07 - 7.95

(m, 1H),7.51 - 7.40 (m,

ESIMS m/z 1H), 4.08- 3.90(m, 1H), 19F NMR

995 423 ([M+Hr)

3.32 (s, 1.5H), 3.30 (s, (CDCI3) 6-

1.5H), 3.06 - 2.90 (m, 66.14

0.5H), 2.90 - 2.74 (m, 1H),

2.64 (dt, J= 13.6, 7.2 Hz,

0.5H), 2.40 - 2.20 (m, 2H),

2.16- 1.96 (m, 2H), 1.51 -

1.35 (m, 3H)


69.01 -8.90 (m, 1H), 8.63 HRMS-FAB

(m/z) [WM' (dd, J = 4.8, 1.4 Hz, 1H),

calcd for 8.04 (ddd, J= 8.4, 2.7, 1.5

Hz, 1H), 7.98 (s, 1H), 7.46 19F NMR (376

996 (thin film)

3325, 1651

CI4H16CIF3N5

OS, (ddd, J = 8.3, 4.8, 0.8 Hz, MHz, CDCI3) 6

394.0711; 1H), 4.81 (t, J = 6.0 Hz, -40.58

found, 1H), 3.68 (q, J = 7.1 Hz,

394.0723 2H), 3.48 (q, J = 6.3 Hz,

2H), 3.11 -2.97 (m, 2H),

1.16 (t, J= 7.1 Hz, 3H)

642

1

17149

997 (thin film)

3314, 1644

HRMS-FAB

(m/z) [M+Hr

calcd for

CI3H 1 8C1F3N3

OS,

408.0867;

found,

408.0884


6 8.96 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J=4.7,1.4

Hz, 1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.97 (s,

1H), 7.46 (ddd, J= 8.4,

4.8, 0.7 Hz, 1H), 4.37 (d, J

= 7.7 Hz, 1H), 4.17 (p, J=

6.4 Hz, 1H), 3.77 - 3.57

(in, 2H), 3.16 - 2.99 (m,

2H), 1.20 (d, J= 6.8 Hz,

3H), 1.15 (t, J= 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-40.72

998 (thin film)

1657

ESIMS m/z

407 ([M+Hr)

1 1.1 NMR (400 MHz, CDCI 3 )

6 8.95 (d, J= 2.4 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.89(s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.6 Hz, 1H), 7.21 (dd,

J= 4.9, 3.0 Hz, 1H), 7.06

(dd, J = 1.9, 1.0 Hz, 1H),

7.01 (dd, J= 5.0, 1.2 Hz,

1H), 3.78 - 3.59 (m, 4H),

2.75 (t, J= 7.4 Hz, 2H),

2.34 (t, J= 7.4 Hz, 2H),

1.15(t, J = 7.2 Hz, 3H)

643

17149

999

(thin film)

3321, 3083,

1649

HRMS-FAB

(m/z) [WM+

calcd for

CI6H20CIF3N5

OS,

422.1024;

found,

422.1027


6 8.95 (dd, J= 2.8, 0.7 Hz,

1H), 8.62 (dd, J= 4.7, 1.4

Hz, 1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.98 (s,

1H), 7.46 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 4.82 (t, J

= 5.8 Hz, 1H), 3.68(q, J=

7.1 Hz, 2H), 3.40 (td, J=

6.6, 5.8 Hz, 2H), 2.76 -

2.58 (multiple peaks, 4H),

2.46- 2.25(m, 2H), 1.16 (t,

J= 7.2 Hz, 3H)

19F NMR (376

MHz, CDCI 3) 6

-66.30

1000 (thin film)

1710

HRMS-FAB

(m/z) NM].

calcd for

C151-112C1F3N,

025,

409.0707;

found,

409.0718


69.01 -8.86 (m, 1H), 8.59

(dd, J= 4.9, 1.4 Hz, 1H),

8.02 (ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.88 (s, 1H), 7.43

(dd, J= 8.3, 4.7 Hz, 1H),

4.21 (br s, 2H), 3.66 (q, J=

7.1 Hz, 2H), 2.85 (br s,

2H), 1.99 (br s, 2H), 1.20

(t, J= 7.1 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-41.32

644

17149

1 H NMR (400 MHz,


= 2.6, 0.8 Hz, 1H), 8.64

(dd, J= 4.8, 1.4 Hz, 1H),

8.05 (ddd, J= 8.4, 2.7, 1.5

Hz, 1H), 7.94 (s, 1H), 7.47 1 t NMR (376

ESIMS m/z (ddd, J= 8.3, 4.8, 0.8 Hz, 1001 MHz, CDCI3)

435 ([M+H]) 1H), 4.07(p, J= 5.9 Hz, 55-63.69

1H), 3.70 (q, J= 7.1 Hz,

2H), 2.84 - 2.69 (m, 1H),

2.67 (d, J= 5.5 Hz, 1H),

2.64 - 2.48 (m, 2H), 2.30

(s, 3H), 1.16(t, J= 7.2 Hz,

3H)


6 9.00 - 8.92 (m, 1H), 8.63

(dd, J= 4.7, 1.4 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.97 (s, 1H), 7.47 (thin film) ESIMS m/z

1002 1656 374 ([M+Hr)

(ddd, J= 8.4, 4.8, 0.8 Hz,

1H), 3.72(q, J= 7.2 Hz,

2H), 3.66- 3.57 (m, 2H),

2.91 -2.79 (m, 4H), 2.45 (t,

J= 7.3 Hz, 2H), 1.17 (t,J=

7.2 Hz, 3H)

645

17149


6 8.97 (dd, J= 2.8, 0.8 Hz,

1H), 8.63 (dd, J= 4.8, 1.4

Hz, 1H), 8.11 - 7.99 (m,

2H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 4.02 - (thin film) ESIMS m/z

1003 3.85 (m, 2H), 3.80- 3.58 1658 390 ([M+H])

(m, 2H), 3.19 (dt, J= 13.2,

7.6 Hz, 1H), 3.14 - 3.07

(m, 2H), 2.96 (dt, J= 12.9,

6.3 Hz, 1H), 2.70 (td, J=

7.3, 3.4 Hz, 2H), 1.18 (t, J

= 7.2 Hz, 3H)


6 8.97 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J= 4.8, 1.5

Hz, 1H), 8.09 - 7.99 (m,

2H), 7.46 (ddd, J= 8.4,

(thin film) ESIMS m/z 4.7, 0.8 Hz, 1H), 6.62 (dd,

1004 J=16.4, 9.8 Hz, 1H), 6.10 1662 354 ([M+H])

-5.91 (m, 2H), 3.71 (qd, J

= 7.0, 2.8 Hz, 2H), 3.22 (dt,

J=13.5, 7.4 Hz, 1H), 2.90

(dt, J= 13.3, 6.3 Hz, 1H),

2.71 -2.50 (m, 2H), 1.16 (t,

J= 7.2 Hz, 3H)

646

17149

1005 ESIMS m/z

484 ([M+H])

'H NMR (400 MHz,


= 2.7 Hz, 1H), 8.64 (dd, J=

4.8, 1.5 Hz, 1H), 8.59 -

8.50 (m, 2H), 8.04 (ddd, J

= 8.3, 2.8, 1.5 Hz, 1H),

7.47 (ddd, J= 8.3, 4.8, 0.7

Hz, 1H), 7.81 (s, 1H) 7.26

(m, 2H), 3.96 - 3.58 (m,

4H), 3.33 (t, J= 6.7 Hz,

1H), 2.60 - 2.24 (m, 4H),

1.17(t, J= 7.2 Hz, 3H)

"F NMR (376

MHz, CDCI3) 6

-63.42

1006 ESIMS m/z

482 ([WM1

1 H NMR (CDCI3) 6 8.98 (d,

J= 2.7 Hz, 1H), 8.62 (dd, J

= 4.7, 1.4 Hz, 1H), 8.05

(ddd, J= 8.3, 2.8, 1.4 Hz,

1H), 8.01 (s, 1H), 7.46 (dd,

J= 8.4, 4.8 Hz, 1H), 3.71

(q, J= 7.0 Hz, 2H), 3.49 (t,

J=6.9 Hz, 2H), 3.24 (I, J=

7.2 Hz, 2H), 2.83 (s, 3H),

2.53 (t, J= 6.8 Hz, 2H),

2.24 - 2.01 (m, 2H), 1.91 -

1.77 (m, 2H), 1.16 (t, J=

7.2 Hz, 3H)

"F NMR

(CDCI3) 6 -

66.09

ESIMS m/z

400 (IM+Hr)

1 H NMR (CDC13) 59.01

(dd, J=2.7, 0.7 Hz, 1H),

8.61 (dd, J= 4.7, 1.5 Hz,

1H), 8.13 - 8.02 (m, 2H),

7.45 (ddd, J= 8.3, 4.8, 0.8

Hz, 1H), 3.71 (q, J= 7.1

Hz, 2H), 3.50 - 3.43 (m,

2H), 3.27 (q, J= 7.1 Hz,

2H), 2.82 (s, 3H), 2.52 (t, J

= 6.9 Hz, 2H), 1.22- 1.12

(m, 6H)

"C NMR

(CDCI3) 6

171.2, 148.6,

140.4, 140.4,

135.7, 127.2,

126.4, 124.0,

123.4, 44.2,

43.8, 43.8,

37.9, 34.6,

13.9, 13.1

647

17149


6 8.96 (dd, J= 2.7, 0.7 Hz,

1H), 8.75(d, J= 2.0 Hz,

1H), 8.63 (dd, J= 4.8, 1.5

Hz, 1H), 8.05 (ddd, J= 8.4,

1008 ESIMS m/z

2.7, 1.5 Hz, 1H), 8.04(s,

1H), 7.46 (ddd, J= 8.3, 19F NMR (376

MHz, CDCI3) 5 490 ((WM +) 4.8, 0.8 Hz, 1H), 7.25 -

-63.45 7.23 (m, 1H), 4.03 - 3.90

(m, 2H), 3.73 (m, 2H), 3.46

(p, J= 6.5 Hz, 1H), 2.55 (d,

J= 6.8 Hz, 2H), 2.52 - 2.39

(m, 2H), 1.16 (t, J= 7.1 Hz,

3H)

I FI NMR (400 MHz,


(m, 1H), 8.63 (dd, J= 4.8,

1.4 Hz, 1H), 8.05 (ddd, J=

8.3, 2.7, 1.4 Hz, 1H), 7.97


(s, 1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.72 (q, J 1009

1660 388 ((M+Hr) = 7.2 Hz, 2H), 3.62(t, J=

6.2 Hz, 2H), 2.82 (dd, J=

7.7, 7.0 Hz, 2H), 2.64 (t, J

= 7.0 Hz, 2H), 2.44 (t, J=

7.3 Hz, 2H), 2.08 - 1.95

(m, 2H), 1.17 (t, J = 7.2 Hz,

3H).

648

17149

1010 (thin film)

1661

ESIMS m/z

404 ([M+H])

IFI NMR (400 MHz, CDCI 3 )

6 8.97 (dd, J= 2.8, 0.7 Hz,

1H), 8.63 (dd, J= 4.7, 1.4

Hz, 1H), 8.09 - 8.00 (m,

2H), 7.46 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.82 -

3.60 (m, 4H), 3.24 - 3.08

(m, 1H), 2.96 - 2.86 (m,

2H), 2.81 (dt, J= 13.1, 7.1

Hz, 1H), 2.69 (q, J= 7.3,

6.7 Hz, 2H), 2.27 (dtd, J=

7.8, 6.8, 5.6 Hz, 2H), 1.17

(t, J= 7.2 Hz, 3H)

1011 (thin film)

1677

HRMS-FAB

(m/z) (WM+

calcd for

C1 61-12,3F3N40

S, 373.1304;

found,

373.1312


6 9.05 - 8.94 (m, 1H), 8.58

(dd, J= 4.8, 1.7 Hz, 1H),

8.14 - 8.00 (m, 1H), 7.35

(ddd, J= 8.0, 4.8, 0.9 Hz,

1H), 6.49 (s, 1H), 3.80 (s,

3H), 3.25 (s, 3H), 2.84 (s,

2H), 2.71 -2.60 (m, 2H),

2.59 - 2.17 (m, 4H)

19F NMR (376

MHz, CDCI3) 6

-66.41

1012 ESIMS m/z

327 ([M+Fi])

1 11 NMR (CDCI3) 6 9.02 -

8.94 (m, 1H), 8.68 - 8.59

(m, 1H), 8.22 (s, 0.45H),

8.19 (s, 0.55H), 8.08 - 7.96

(m, 1H), 7.51 -7.40 (m,

1H), 4.03 (br. s, 0.45H),

3.95 (q, J= 6.8 Hz, 0.55H),

3.33 (s, 1.35H), 3.30 (s,

1.65H), 2.65 (s, 1.35H),

2.55 (s, 1.65H), 1.44 (d, J

= 6.8 Hz, 1.65H), 1.38 (d, J

= 6.2 Hz, 1.35H)

13C NMR

(CDCI3) 6

168.8, 148.9,

148.7, 140.4,

140.3, 139.7,

135.6, 135.5,

126.5, 126.4,

124.6, 124.1,

124.0, 58.6,

37.6, 37.5,

34.8

649

17149

1013 (thin film)

1674

HRMS-FAB

(m/z) (M+Fir

calcd for

C19H24F3N40

S, 413.1617;

found,

413.1637


69.00 (d, J= 2.4 Hz, 1H),

8.58 (dd, J= 4.8, 1.7 Hz,

1H), 8.09 (dt, J= 7.9, 1.9

Hz, 1H), 7.35 (ddd, J= 8.0,

4.8, 0.9 Hz, 1H), 6.52 (s,

1H), 3.83 (s, 3H), 3.57 (qd,

J= 13.8, 7.3 Hz, 211), 2.99

- 2.73 (m, 2H), 2.73 - 2.56

(m, 2H), 2.55 - 2.15


0.89 (m, 1H), 0.62 - 0.40

(m, 2H), 0.35 - 0.08 (m,

2H)

. a ''F NMR (376

MHz, CDCI3) 6

-66.41.

1014 ESIMS m/z

487 ([M+Hr)

'H NMR (CDCI3) 69.00

(dd, J= 2.8, 0.8 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.08 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.01 (s,

1H), 7.55(t, J= 1.1 Hz,

1H), 7.47 (ddd, J= 8.3,

4.7, 0.8 Hz, 1H), 7.06 (t, J

= 1.1 Hz, 1H), 7.01 (d, J=

1.3 Hz, 1H), 4.22 (dd, J=

14.5, 5.2 Hz, 1H), 4.11 -

4.02 (m, 1H), 3.81 -3.61

(m, 2H), 3.32 - 3.19 (m,

1H), 2.79 (dt, J= 13.4, 6.8

Hz, 1H), 2.69 (dt, J= 13.1,

6.5 Hz, 1H), 2.52 - 2.39

(m, 1H), 2.39 - 2.23 (m,

3H), 1.16 (t, J = 7.2 Hz,

3H)

19F NMR

(CDCI3) 6 -

63.20

650

17149

1015

(thin film)

3096, 2976,

1660

ESIMS m/z

783 ([M+Hj+)

I FI NMR (400 MHz,


= 2.4 Hz, 1H), 9.01 —8.97

(m, 1H), 8.63 (m, 2H), 8.12

(s, 1H), 8.12 — 8.04 (m,

3H), 7.46(m, 2H), 3.80—

3.61 (m, 4H), 3.53 — 3.36

(m, 2H), 2.75 — 2.41 (m,

8H), 1.14 (m, 6H)

19F NMR (376

MHz, CDCI3) 6

-63.32, -63.21

1016

(thin film)

3094, 2977,

2934, 1662

ESNS m/z

407 ([M+1-1] . )

IFI NMR (400 MHz,

Chloroform-cf) 6 8.96 (dd, J

= 2.7, 0.7 Hz, 1H), 8.64

(dd, J = 4.7, 1.5 Hz, 1H),

8.05 (ddd, J = 8.3, 2.7, 1.5

Hz, 1H), 7.96 (s, 1H), 7.47

(ddd, J = 8.4, 4.8, 0.8 Hz,

1H), 3.73 (d, J = 7.1 Hz,

2H), 3.44 - 3.25 (m, 1H),

2.53 (m, 2H), 2.51 -2.43

(m, 2H), 2.13 (s, 3H), 1.17

(t, J = 7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-63.50

651

17149

1017 (thin film)

1673

HRMS-FAB

(m/z) EM+Hr

calcd for

C2oH23F2N40

S, 407.1712;

found,

407.1711


6 9.10 - 8.93 (m, 1H), 8.57

(dd, J= 4.8, 1.7 Hz, 1H),

8.09 (dt, J=7.9,2.0 Hz,

1H), 7.35 (ddd, J= 7.9,

4.8, 0.9 Hz, 1H), 6.51 (s,

1H), 3.83 (s, 3H), 3.56 (dp,

J= 13.8, 7.0 Hz, 2H), 3.02

-2.74 (m, 2H), 2.59 (dq, J

= 7.3, 1.4 Hz, 2H), 2.47

(dtd, J= 16.4, 6.8, 4.6 Hz,

1H), 2.34 - 2.17 (m, 1H),

1.74 (ddq, J= 13.3, 11.3,

7.4 Hz, 1H), 1.57 - 1.38

(m, 1H), 1.02 (dddd, J=

17.4, 12.4, 7.7, 3.3 Hz,

2H), 0.62 - 0.45 (m, 2H),

0.33 - 0.12 (m, 2H)

19F NMR (376

MHz, CDCI3) 6

-128.15 (dd, J

=158.9 Hz,

7.5 Hz), -

142.78 (dd, J=

157.3, 7.5 Hz)

1018 (thin film)

1660

ESIMS m/z

415 ((WM')


68.94 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.88 (s,

1H), 7.49 - 7.43 (m, 1H),

7.17 - 7.02 (m, 4H), 3.69

(q, J= 7.1 Hz, 2H), 3.64(s,

2H), 2.73 (t, J= 7.4 Hz,

2H), 2.36 (t, J= 7.4 Hz,

2H), 2.29 (s, 3H), 1.14 (t, J

= 7.2 Hz, 3H)

652

17149

1019 (thin film)

1661

ESIMS m/z

485 ([M+Hr)


68.95 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.08 - 8.04 (ddd, J=

8.3, 2.7, 1.4 Hz, 1H), 7.89

(s, 1H), 7.47 (dd, J= 8.3,

4.2 Hz, 1H), 7.31 -7.27

(m, 1H), 7.23 - 7.13 (m,

2H), 7.04 (d, J= 8.1 Hz,

1H), 3.75 - 3.63 (m, 4H),

2.74 (t, J= 7.3 Hz, 2H),

2.35 (t, J= 7.3 Hz, 2H),

1.15(t, J= 7.2 Hz, 3H)

1020 (thin film)

3424, 1672

HRMS—FAB

(m/z)(M+Hr

calcd for

C16H23F2N40

35,

413.1453;

found,

413.1463


6 9.05 - 8.93 (m, 1H), 8.58

(dd, J= 4.9, 1.7 Hz, 1H),

8.09 (dt, J= 7.9, 2.0 Hz,

1H), 7.35 (ddd, J= 7.9,

4.8, 0.9 Hz, 1H), 6.52 (s,

1H), 4.17 - 3.96 (m, 1H),

3.82 (s, 3H), 3.48 (q, J=

7.0 Hz, 1H), 3.44 — 3.24


(s, 1H), 2.81 -2.62 (m,

1H), 2.59 - 2.42 (m, 1H),

2.09 - 1.94 (m, 1H), 1.73

(tdd, J= 11.5, 8.3, 5.4 Hz,

1H), 1.52- 1.32(m, 1H),

1.20(t, J= 7.2 Hz, 3H)

I t NMR (376

MHz, CDCI3) 6

-130.35 (dd, J

= 159.2, 11.8

Hz), -141.01

(dd, J= 159.1,

20.0 Hz)

rr

653

17149

1021 (thin film)

1661

ESIMS

m/z 485

([M+H])


68.95 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.91 (s,

1H), 7.49- 7.44 (m, 1H),

7.30 (d, J= 8.7 Hz, 2H),

7.12 (d, J= 7.9 Hz, 2H),

3.76- 3.59 (m, 4H), 2.73 (t,

J=7.4 Hz, 2H), 2.37 (t, J=

7.4 Hz, 2H), 1.15 (t, J= 7.2

Hz, 3H)

1022 (thin film)

1661

ESIMS m/z

483 ((M+Hr)


68.94 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.87 (s,

1H), 7.58 - 7.33 (m, 5H),

3.97 (q, J= 7.0 Hz, 1H),

3.68 (q, J= 7.6, 7.0 Hz,

2H), 2.70 - 2.54 (m, 2H),

2.32 - 2.23 (m, 2H), 1.54

(d, J= 7.1 Hz, 3H), 1.15(t,

J= 7.2 Hz, 3H).

1023 (thin film)

1661

ESIMS m/z

483 ((M+H]+ )


68.94 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.87 (s,

1H), 7.58 - 7.33 (m, 5H),

3.97(q, J= 7.0 Hz, 1H),

3.68 (q, J= 7.6, 7.0 Hz,

2H), 2.70 - 2.54 (m, 2H),

2.32 - 2.23 (m, 2H), 1.54

(d, J= 7.1 Hz, 3H), 1.15(t,

J = 7.2 Hz, 3H)

654

17149

1024 (thin film)

1652

ESIMS a* 501 ([M+H])

I HNMR (400 MHz, CDCI3 )

15 8.95 (d, J= 2.5 Hz, 1H),

8.59 (dd, J= 4.7, 1.4 Hz,

1H), 8.01 -7.94 (m, 2H),

7.37 (dd, J= 8.4, 4.8 Hz,

1H), 7.02 (bs, 1H), 6.88 (s,

2H), 3.67 (q, J= 7.1 Hz,

2H), 2.91 -2.83 (m, 4H),

2.66 (t, J= 6.7 Hz, 2H),

2.49 (t, J= 6.7 Hz, 2H),

2.25 (s, 3H), 2.20 (s, 6H),

1.12 (t, J=7.2 Hz, 3H)

1025 (thin film)

1660

ESIMS m/z

429 ([M+1-1] . )

1 FINMR (400 MHz, CDCI 3)

68.92 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.01 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.88 (s,

1H), 7.48- 7.42(m, 1H),

7.31 -7.26 (m, 2H), 7.22 -

7.14(m, 3H), 3.70 (q, J=

7.1 Hz, 2H), 2.91 (dq, J= 13.9, 7.0 Hz, 1H), 2.79 -

2.71 (m, 3H), 2.70 - 2.61

(m, 1H), 2.38 (t, J = 7.4 Hz,

2H), 1.32 (d, J= 6.9 Hz,

3H), 1.15 (t, J = 7.2 Hz,

3H)

655

17149

1026 (thin film)

1660

ESIMS ink

415 ([M+Hr)

I H NMR (400 MHz, CDCI3)

6 8.93(d, J= 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.02 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.91 (s,

1H), 7.45 (ddd, J= 8.4,

4.8, 0.6 Hz, 1H), 7.31 -

7.23(m, 2H), 7.22 - 7.13

(m, 3H), 3.72 (q, J= 7.2

Hz, 2H), 2.89- 2.80 (m,

4H), 2.78 - 2.69 (m, 2H),

2.43 (t, J= 7.4 Hz, 2H),

1.16(t, J= 7.2 Hz, 3H)

1027 (thin film)

1662

ESIMS rn/z

429 ([M+Hr)


68.99 (d, J= 2.4 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.07 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.01 (s,

1H), 7.91 -7.87 (m, 2H),

7.60 - 7.51 (m, 1H), 7.49 -

7.39 (m, 3H), 3.78 (s, 2H),

3.69(q, J= 7.1 Hz, 2H),

2.87 (t, J= 7.2 Hz, 2H),

2.48 (t, J= 7.1 Hz, 2H),

1.13 (t, J= 7.2 Hz, 3H)

1028 (thin film)

1660

ESIMS m/z

423 ([M+H])


6 8.98 (s, 1H), 8.65 (s,

1H), 8.10 - 7.98 (m, 2H),

7.47 (dd, J=8.4,4.5 Hz,

1H), 3.81 -3.63 (m, 2H),

3.17 (dt, J= 13.0, 7.6 Hz,

1H), 3.02 - 2.79 (m, 3H),

2.75 - 2.42 (m, 4H), 1.18 (t,

J= 7.2 Hz, 3H) (several

aromatic protons

broadened into singlet)

1

656

17149


59.01 (s, 1H), 8.68 (s,

1H), 8.05(d, J= 11.9 Hz,

2H), 7.51 (d, J= 12.6 Hz,

1H), 3.73 (qd, J=6.8,3.6

1029 (thin film) ESIMS m/z Hz, 2H), 3.18 (dt, J= 13.2,

1660 423 ([M+Hr) 7.6 Hz, 1H), 3.04 - 2.79

(m, 3H), 2.76 - 2.46 (m,

4H), 1.18 (t, J=7.2 Hz,

3H) (several aromatic

protons broadened into

singlet)


6 8.95 (dd, J= 2.8, 0.8 Hz,

1H), 8.63 (dd, J=4.8,1.4


Hz, 1H), 8.05 (ddd, J= 8.3,

2.8, 1.5 Hz, 1H), 7.96 (s,

1H), 7.46 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.72 (q, J 1030

1660 382 ((M+Hr) = 7.2 Hz, 2H), 2.81 (dd, J=

8.0, 7.0 Hz, 2H), 2.56 -

2.35 (m, 4H), 1.69- 1.55

(m, 1H), 1.49 - 1.37 (m,

2H), 1.16(t, J= 7.2 Hz,

3H), 0.86 (d, J= 6.6 Hz,

6H)

657

17149


6 8.95 (dd, J = 2.8, 0.8 Hz,

1H), 8.63 (dd, J = 4.8, 1.5

Hz, 1H), 8.05 (ddd, J= 8.4,

2.8, 1.5 Hz, 1H), 7.97 (s,

1H), 7.47 (ddd, J = 8.3,

4.8, 0.8 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.82 (dd, J = (thin film) ESIMS m/z

1031 7.9, 7.0 Hz, 2H), 2.62 - 1660 380 ([M+Hr)

2.51 (m, 2H), 2.44 (dd, J=

7.9, 7.0 Hz, 2H), 1.44 (q, J

=7.1 Hz, 2H), 1.16 (t, J =

7.2 Hz, 3H), 0.72 (dddd, J

= 11.9, 8.0, 6.9, 2.8 Hz,

1H), 0.45 - 0.36 (m, 2H),

0.02 (dt, J = 6.0, 4.4 Hz,

2H)


6 8.96 (dd, J = 2.9, 0.8 Hz,

1H), 8.63 (dd, J= 4.8, 1.5

Hz, 1H), 8.05 (ddd, J = 8.3,

2.7, 1.5 Hz, 1H), 7.97 (s,

1H), 7.47 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.72 (q, J

(thin film) ESIMS m/z = 7.2 Hz, 2H), 2.91 -2.75 1032

1661 416 ([M+H]) (m, 2H), 2.57 (t, J = 7.3 Hz,

2H), 2.44 (dd, J = 7.7, 7.0

Hz, 2H), 1.77- 1.67 (m,

2H), 1.62- 1.52(m, 1H),

1.39 (dddd, J = 12.6, 11.3,

7.6, 4.1 Hz, 1H), 1.17 (t, J

= 7.2 Hz, 3H), 0.93 (dtd, J

= 13.0, 7.5, 3.5 Hz, 1H)

658

17149

1033 (thin film)

1662

ESIMS m/z

457 ([M+H])

'H NMR (400 MHz,


(m, 1H), 8.61 (dd, J = 4.7,

1.4 Hz, 1H), 8.50 - 8.40

(m, 1H), 7.96 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.86, (s,

1H), 7.43 (ddd, J = 8.3,

4.8, 0.8 Hz, 1H), 7.32 (dt, J

= 1.6, 0.8 Hz, 1H), 7.12 -

7.02 (m, 1H), 3.73 (q, J =

7.2 Hz, 2H), 3.47 (t, J= 7.0

Hz, 2H), 2.63 (t, J = 7.0

Hz, 2H), 1.17 (t, J = 7.2

Hz, 3H).


6 8.97 -8.88 (m, 1H), 8.67

(d, J= 2.2 Hz, 1H), 8.65 -

8.60 (m, 2H), 8.02 (ddd, J

= 8.3.2.7. 1.5 Hz, 1H),

1034 (thin film) ESIMS m/z 7.91 (s, 1H), 7.81 (td, J=

1662 457 ([M+Hr) 2.1, 0.9 Hz, 1H), 7.46 (ddd,

J= 8.3, 4.8, 0.8 Hz, 1H),

3.72 (q, J= 7.2 Hz, 2H),

3.30 (t, J= 7.2 Hz, 2H),

2.51 (t, J= 7.2 Hz, 2H),

1.16 (t, J= 7.2 Hz, 3H)

659

17149


68.92 (d, J= 2.7 Hz, 1H),

8.67 - 8.58 (m, 1H), 8.46

(d, J= 5.3 Hz, 1H), 8.00


(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.91 (s, 1H), 7.50 - 1035

1662 457 ([M+Hr) 7.40 (m, 2H), 7.25 (dd, J=

5.3, 1.8 Hz, 1H), 3.74 (q, J

= 7.2 Hz, 2H), 3.34 (t, J=

7.3 Hz, 2H), 2.56 (t, J= 7.3

Hz, 2H), 1.18 (t, J= 7.2

Hz, 3H)


6 8.87 (dd, J= 2.8, 0.8 Hz,

1H), 8.61 (dd, J = 4.8, 1.4


Hz, 1H), 8.56 - 8.47 (m,

1H), 7.99 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.89(s,

1H), 7.59 (ddd, J= 8.7,

1659 457 ([M+H]i 2.4, 0.8 Hz, 1H), 7.44 (ddd,

J= 8.3, 4.8, 0.8 Hz, 1H),

7.24 - 7.17 (m, 1H), 3.73

(q, J= 7.2 Hz, 2H), 3.46 (t,

J=7.0 Hz, 2H), 2.64 (t, J=

7.0 Hz, 2H), 1.17(t, J= 7.2

Hz, 3H)

660

17149

1037 (thin film)

1662

ESIMS rniz

484 ([M+1-1] . )


6 8.94 (dd, J= 2.7, 0.8 Hz,

1H), 8.62 (dd, J=4.8,1.4

Hz, 1H), 8.03 (ddd, J= 8.3,

2.8, 1.5 Hz, 1H), 7.95 (s,

1H), 7.68 - 7.54 (m, 1H),

7.52 -7.41 (m, 2H), 7.35 -

7.28 (m, 2H), 3.72 (q, J=

7.2 Hz, 2H), 3.11 -2.97

(m, 2H), 2.88 (t, J= 7.3 Hz,

2H), 2.75 - 2.64 (m, 2H),

2.46 (t, J= 7.3 Hz, 2H),

1.16(t, J=7.2 Hz, 3H)

1038 (thin film)

1662

ESIMS Rik

484 ([1‘4+Hr)

'H NMR (400 MHz, 0001 3)

69.01 -8.88 (m, 1H), 8.63

(dd, J = 4.8, 1.5 Hz, 1H),

8.03 (ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.94 (s, 1H), 7.49

- 7.42 (m, 3H), 7.42 - 7.34

(m, 2H), 3.72(q, J= 7.2

Hz, 2H), 2.93 (dd, J= 8.8,

6.6 Hz, 2H), 2.85 (t, J= 7.3

Hz, 2H), 2.81 -2.71 (m,

2H), 2.44 (t, J= 7.3 Hz,

2H), 1.16 (t, J = 7.2 Hz,

3H)

661

17149


6 8.94 (dd, J= 2.6, 0.8 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.03 (ddd, J= 8.4,

2.8, 1.5 Hz, 1H), 7.94 (s,

1H), 7.60 - 7.49 (m, 2H),

7.46 (ddd, J= 8.3, 4.8, 0.8 (thin film) ESIMS m/z

1039 1662 484 (fiVI+Hr)

Hz, 1H), 7.31 -7.27 (m,

2H), 3.72 (q, J= 7.2 Hz,

2H), 2.92 (dd, J= 8.8, 6.6

Hz, 2H), 2.85 (t, J= 7.4

Hz, 2H), 2.80 - 2.71 (m,

2H), 2.44 (t, J= 7.4 Hz,

• 2H), 1.16 (t, J= 7.2 Hz,

3H)


6 8.95 (dd, J= 2.7, 0.8 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.05 (ddd, J= 8.4,

2.8, 1.5 Hz, 1H), 7.96 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.72 (q, J (thin ESIMS m/z

1040 film)1660 408 ([M+H]. )

= 7.1 Hz, 2H), 2.81 (dd, J=

8.0, 7.0 Hz, 2H), 2.54 -

2.35 (m, 4H), 1.86- 1.67

(m, 4H), 1.58 - 1.51 (m,

3H), 1.48 (dtd, J= 7.7, 3.2,

1.8 Hz, 2H), 1.16(t, J= 7.2

Hz, 3H), 1.04 (ddt, J=

11.8, 9.3, 7.4 Hz, 2H)

662

17149

1041 (thin film)

1661

ESIMS m/z

384 ([M+Hr)


6 9.03 - 8.93 (m, 1H), 8.63

(dd, J= 4.8, 1.4 Hz, 1H),

8.05 (ddd, J= 8.4, 2.7, 1.5

Hz, 1H), 7.98 (s, 1H), 7.47

(ddd, J= 8.4, 4.8, 0.8 Hz,

1H), 3.72 (q, J= 7.2 Hz,

2H), 3.42 (t, J= 6.1 Hz,

2H), 3.30 (s, 3H), 2.81 (dd,

J= 7.8, 7.0 Hz, 2H), 2.55

(t, J= 7.3 Hz, 2H), 2.44 (t,

J= 7.4 Hz, 2H), 1.81 (tt, J

= 7.1, 6.1 Hz, 2H), 1.16(t,

J= 7.2 Hz, 3H)

1042 (thin film)

1656

ESIMS m/z

404 ([M+Hr)


6 9.04 - 8.94 (m, 1H), 8.63

(dd, J= 4.7, 1.4 Hz, 1H),

8.06 (ddd, J= 8.4, 2.7, 1.5

Hz, 1H), 8.03(s, 1H), 7.46

(ddd, J= 8.3, 4.8, 0.8 Hz,

1H), 3.90(d, J= 0.9 Hz,

2H), 3.72 (q, J= 7.2 Hz,

2H), 3.12 (t, J=6.6 Hz,

2H), 2.98 (s, 3H), 2.57 (t, J

= 6.6 Hz, 2H), 1.17 (t, J =

7.2 Hz, 3H)

663

17149


6 8.99 (dd, J= 2.7, 0.8 Hz,

1H), 8.61 (dd, J= 4.8, 1.5

Hz, 1H), 8.08- 8.03 (m,

2H), 7.92- 7.88 (m, 2H),

7.70 - 7.64 (m, 1H), 7.59 - (thin film) ESIMS m/z

1043 7.53 (m, 2H), 7.44 (ddd, J 1658 465 ([MOM +)

= 8.4, 4.8, 0.8 Hz, 1H),

4.02 (s, 2H), 3.73 (q, J=

7.1 Hz, 2H), 3.04 (t, J= 6.7

Hz, 2H), 2.58 (t, J= 6.7

Hz, 2H), 1.17 (t, J= 7.2

Hz, 3H)


6 9.02 - 8.94 (m, 1H), 8.63

(dd, J= 4.7, 1.4 Hz, 1H),

8.07 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.99 (s, 1H), 7.91

-7.86 (m, 2H), 7.70 - 7.65

(thin film) ESIMS iniz (m, 1H), 7.61 -7.55 (m, 1044

1660 480 (CM+Hr) 2H), 7.46 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.70 (q, J

= 7.2 Hz, 2H), 3.37 - 3.27

(m, 2H), 2.82 - 2.73 (m,

4H), 2.41 (t, J= 7.1 Hz,

2H), 1.15(t, J= 7.2 Hz,

3H)

664

17149

'H NMR (400 MHz,


= 2.7, 0.8 Hz, 1H), 8.63

(dd, J= 4.8,1.4 Hz, 1H),

8.06 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.99 (s, 1H), 7.95

(thin film) ESIMS m/z - 7.87 (m, 2H), 7.46 (ddd, J 1045

1660 498 ([M+H]) = 8.3, 4.8, 0.8 Hz, 1H),

7.28 - 7.23 (m, 2H), 3.70

(q, J= 7.2 Hz, 2H), 3.36 -

3.27 (m, 2H), 2.82 - 2.74

(m, 4H), 2.41 (t, J= 7.1 Hz,

2H), 1.15(t, J= 7.2 Hz,

3H).


6 8.98 (dd, J= 2.8, 0.8 Hz,

1H), 8.63 (dd, J= 4.8, 1.5

Hz, 1H), 8.06 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.02 (s,


1046 4.8, 0.8 Hz, 1H), 3.72 (q, J 1657 418 ([M+H])

= 7.2 Hz, 2H), 3.32 - 3.24

(m, 2H), 2.97 (t, J= 0.6 Hz,

3H), 2.95 - 2.90 (m, 2H),

2.86 (t, J= 6.9 Hz, 2H),

2.48 (t, J= 6.9 Hz, 2H),

1.17(t, J= 7.2 Hz, 3H)

665

17149

1047 (thin film)

1661

ESIMS m/z

432 ([101-1]*)


5 8.92 (dd, J= 2.7, 0.8 Hz,

1H), 8.62 (dd, J= 4.7, 1.5

Hz, 1H), 8.01 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.89 (s,

1H), 7.44 (ddd, J= 8.3,

4.7, 0.8 Hz, 1H), 7.30 -

7.23 (m, 2H), 6.97 - 6.91

(m, 1H), 6.89 - 6.84 (m,

2H), 4.11 (t, J= 6.6 Hz,

2H), 3.71 (q, J= 7.2 Hz,

2H), 2.94 (t, J= 7.3 Hz,

2H), 2.87 (t, J= 6.6 Hz,

2H), 2.48 (t, J= 7.3 Hz,

2H), 1.16 (t, J = 7.2 Hz,

3H)

1048 (thin film)

1661

ESIMS m/z

419 ([M+H])


59.01 -8.91 (m, 1H), 8.63

(dd, J= 4.8, 1.4 Hz, 1H),

8.04 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.93 (s, 1H), 7.47

(ddd, J= 8.3, 4.8, 0.8 Hz,

1H), 6.62(t, J= 2.1 Hz,

2H),6.11 (t, J= 2.1 Hz,

2H), 3.97 (t, J= 6.7 Hz,

2H), 3.71 (q, J= 7.2 Hz,

2H), 2.80 (t, J= 7.3 Hz,

2H), 2.41 (td, J= 7.2, 2.2

Hz, 4H), 2.00 (p, J= 6.9

Hz, 2H), 1.16 (t, J= 7.2

Hz, 3H)

666

17149


6 8.94 (dd, J= 2.7, 0.8 Hz,

1H), 8.63 (dd, J= 4.7, 1.5

Hz, 1H), 8.02 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.94 (s,

1H), 7.45 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 6.77 (d, J

(thin film) ESIMS m/z = 8.7 Hz, 1H), 6.73 - 6.68 1049

1662 476 ([M+Hr) (m, 2H), 3.86 (s, 3H), 3.84

(s, 3H), 3.72 (q, J= 7.2 Hz,

2H), 2.85 (dd, J= 7.8, 7.0

Hz, 2H), 2.82 - 2.77 (m,

2H), 2.72 (ddd, J= 8.3,

6.9, 2.2 Hz, 2H), 2.44 (dd,

J=7.7,7.1 Hz, 2H), 1.16

(t, J= 7.2 Hz, 3H)


6 8.98 (dd, J= 2.7, 0.8 Hz,

1H), 8.63 (dd, J=4.8,1.4

Hz, 1H), 8.07 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.99 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 6.89 (d, J (thin film) ESIMS m/z

1050 = 1.3 Hz, 1H), 6.85(d, J= 1660 420 ([M+H] + )

1.4 Hz, 1H), 4.03(t, J=7.0

Hz, 2H), 3.71 (q, J= 7.2

Hz, 2H), 2.82 (t, J= 7.0

Hz, 2H), 2.76 (t, J= 7.0

Hz, 2H), 2.40- 2.35 (m,

5H), 1.16 (t, J = 7.2 Hz,

3H)

667

17149

1051 (thin film)

1663

ESIMS m/z

471 ([M+H])


II 8.96 (dd, J= 2.7, 0.8 Hz,

1H), 8.62 (dd, J= 4.8, 1.4

Hz, 1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.02 (s,

1H), 7.82 (td, J= 7.8, 0.8

Hz, 1H), 7.59(d, J= 7.9

Hz, 1H), 7.52 (dd, J= 7.8,

1.0 Hz, 1H), 7.46 (ddd, J=

8.4, 4.7, 0.8 Hz, 1H), 3.82

(s, 2H), 3.70 (q, J= 7.2 Hz,

2H), 2.77 (t, J= 7.3 Hz,

2H), 2.46 (t, J= 7.3 Hz,

2H), 1.15(t, J= 7.2 Hz,

3H)

1052 (thin film)

1661

.

ESIMS m/z

549 ([M+H)+ )

1 1-1 NMR (400 MHz,

Chloroform-d) 5 8.99 (dt, J

= 1.7, 0.9 Hz, 1H), 8.96 (d,

J= 2.7 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.26 -

8.18 (m, 2H), 8.06 (ddd, J

= 8.4, 2.8, 1.5 Hz, 1H),

7.99 (s, 1H), 7.46 (ddd, J=

8.3, 4.8, 0.8 Hz, 1H), 3.70

(ddd, J = 8.1, 6.7, 4.9 Hz,

4H), 2.94 - 2.86 (m, 2H),

2.82 (t, J = 7.1 Hz, 2H),

2.43 (t, J = 7.1 Hz, 2H),

1.16(t, J= 7.2 Hz, 3H).

668

17149

1 H NMR (CDCI 3) 6 8.95

(dd, J= 2.7, 0.8 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.04 (add. J= 8.4,

2.7, 1.5 Hz, 1H), 7.95 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.72 (q, J 19F NMR ESIMS m/z

1053 = 7.1 Hz, 2H), 2.95 - 2.72 (CDCI3) 6 - 463 ([M+H1+)

(m, 3H), 2.56 - 2.37 (m, 63.40

3H), 2.37 - 2.21 (m, 1H),

1.82 (dp, J= 13.3, 6.7 Hz,

1H), 1.55 - 1.36 (m, 2H),

1.16(t, J= 7.2 Hz, 3H),

0.89 (d, J= 6.7 Hz, 3H),

0.86 (d, J= 6.5 Hz, 3H)

1 FINMR (400 MHz, CDCI 3)

6 9.06 - 8.93 (m, 1H), 8.58

(dd, J= 4.8, 1.7 Hz, 1H),

HRMS-FAB 8.09 (dt, J= 7.9, 2.0 Hz,

(m/z) [M+H] 1H), 7.35 (ddd, J= 7.9,

(thin film) calcd for 4.8, 0.9 Hz, 1H), 6.49 (s, 19F NMR (376

1054 1673

Ci7FInF3N40 1H), 4.11 - 3.97(m, 1H), MHz, CDCI3) 6

S, 387.1461; 3.79 (s, 3H), 3.49 - 3.30 -66.60

found, (m, 1H), 2.83 (dt, J= 10.2,

387.1468 6.8 Hz, 2H), 2.72 - 2.58

(m, 2H), 2.53 - 2.16


(t, J= 7.2 Hz, 3H)

669

17149

1055 ESIMS rniz

435 ([M+H])

'H NMR (CDCI3) 6 8.96 (d,

J= 2.8 Hz, 1H), 8.64 (d, J

= 5.3 Hz, 1H), 8.05 (ddd, J

= 8.4, 2.7, 1.4 Hz, 1H),

7.95 (s, 1H), 7.47 (dd, J =

8.4, 4.6 Hz, 1H), 3.72 (q, J

= 7.2 Hz, 2H), 2.91 -2.74

(m, 3H), 2.54 - 2.24 (m,

4H), 1.84- 1.67(m, 1H),

1.67- 1.59(m, 1H), 1.17(t,

J = 7.2 Hz, 3H), 0.99 (t, J =

7.3 Hz, 3H)

19F NMR

(CDCI3) 6-

63.70

1056 (thin film)

3455, 1673

HRMS—FAB

(m/z) [WM+

calcd for

C121-122F3N40

25,

403.1410;

found,

403.1428

IF1 NMR (400 MHz, CDCt 3)

6 8.99 (s, 1H), 8.58 (dd, J

= 4.9, 1.7 Hz, 1H), 8.16 -

8.02 (m, 1H), 7.35 (ddd, J

= 8.0, 4.8, 0.9 Hz, 1H),

6.52 (d, J = 8.6 Hz, 1H),

4.20 - 3.96 (m, 1H), 3.82

(d, J = 4.9 Hz, 3H), 3.52-

3.32 (m, 1H), 3.29 - 3.03

(m, 1H), 3.03 - 2.80



1.20 (t, J = 7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-65.83

670

17149

1057 (thin film)

3548, 1674

HRMS-FAB

(m/z)

(M+Nar

calcd for

CI7H2I F3N4N

a03S,

441.1179;

found,

441.1180

1 1-I NMR (400 MHz, CDCI 3)

5 9.06 - 8.92 (m, 1H), 8.58

(dd, J= 4.9, 1.6 Hz, 1H),

8.10 (dt, J= 7.9, 1.9 Hz,

1H), 7.36 (ddd, J= 7.9,

4.9, 0.9 Hz, 1H), 6.52 (s,

1H), 4.18 - 4.00 (m, 1H),

3.82 (s, 3H), 3.60 - 3.47

(m, 1H), 3.47 - 3.19



2.60 - 2.43 (m, 1H), 1.20 (t,

J= 7.2 Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-65.94

1058 (thin film)

1675

HRMS-FAB

(m/z) [WM

calcd for

C I7H2I F2N40

S, 367.1399;

found,

367.1401


58.99 (dd, J= 2.3, 0.9 Hz,

1H), 8.57 (dd, J=4.8,1.7

Hz, 1H), 8.07 (dt, J= 7.9,

1.9 Hz, 1H), 7.35 (ddd, J=

7.8, 4.8, 0.9 Hz, 1H), 6.49

(s, 1H), 3.80 (s, 3H), 3.25

(s, 3H), 2.97 - 2.78 (m,

2H), 2.59 (ddd, J= 7.4,

2.3, 1.2 Hz, 2H), 2.41 (d, J

= 59.4 Hz, 2H), 1.74 (ddq,

J=13.1,11.1, 7.4 Hz, 1H),

1.57 - 1.39 (m, 1H),1.03

(dtd, J= 13.2, 7.6, 3.7 Hz,

1H)

19F NMR (376

MHz, CDCI3) 6

-128.19 (d, J=

156.9 Hz), -

142.74 (d, J=

157.7 Hz)

671

17149

IFI NMR (400 MHz,


(m, 1H), 8.63 (dd, J= 4.8,

1.5 Hz, 1H), 8.15 - 8.01

(thin film) (m, 2H), 7.47 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.75 (ddq, 19F NMR (376

1059 3098, 2976,

2935, 2250,

ESIMS m/z

446 ([M+H]) J= 21.1, 13.6, 7.0 Hz, 2H), MHz, CDCI3) 6

1660 3.44 (p, J= 6.8 Hz, 1H), -63.59

2.96 - 2.80 (m, 2H), 2.72

(td, J= 7.4, 6.4 Hz, 2H),

2.59 - 2.55 (m, 2H), 2.55 -

2.43 (m, 2H), 1.30- 1.09

(m, 3H)


6 9.00 (dd, J= 2.3, 0.8 Hz,

1H), 8.57 (dd, J= 4.9, 1.7

Hz, 1H), 8.09 (dt, J= 8.0,

2.0 Hz, 1H), 7.35 (ddd, J= HRMS—FAB

8.0, 4.8, 0.9 Hz, 1H), 6.48 19F NMR (376 (m/z) [M+Hr

calcd for (s, 1H), 4.11 -3.95 (m, MHz, CDCI3) 6

(thin film) 1H), 3.79 (s, 3H), 3.47- -128.16 (d, J= 1060 CI8H23F2N40

3422, 1671 3.33 (m, 1H), 2.97 - 2.76 156.9 Hz), - 8,381.1555;

found, (m, 2H), 2.59 (dt, J= 7.8,

1.6 Hz, 2H), 2.54 - 2.36

142.76 (d, J=

157.0 Hz) 381.1550

(m, 1H), 2.35 - 2.17 (m,

1H), 1.84 - 1.68 (m, 1H),

1.55 - 1.41 (m, 1H), 1.19 (t,

J= 7.3 Hz, 3H), 1.03 (dtd,

J=13.1, 7.7, 3.6 Hz, 1H)

672

17149


68.99 (s, 1H), 8.57 (dd, J

= 4.8, 1.6 Hz, 1H), 8.09 (d,

HRMS—FAB J= 8.0 Hz, 1H), 7.35 (ddd,

(m/z) [WM J= 7.9, 4.9, 0.9 Hz, 1H), "F NMR (376

calcd for 6.52(d, J= 11.4 Hz, 1H), MHz, CDCI3) 6

(thin film) C18H23F21140 4.13 - 3.95 (m, 1H), 3.82 -124.54-- 1061

3445, 1672 25, (d, J= 7.7 Hz, 3H), 3.47- 133.44 (m), -

397.1504; 3.33 (m, 1H), 3.29 - 2.32 136.13 - -

found, (multiple peaks, 6H), 2.17- 147.71 (m)

397.1510 1.85(m, 1H), 1.79 - 1.62

(m, 1H), 1.39- 1.24(m,

1H), 1.20(t, J=7.2 Hz,

3H)


6 8.94 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.90 (s,

1062 (thin film) ESIMS m/z 1H), 7.66 - 7.54 (m, 2H),

1662 469 (iM+Hr) 7.53 - 7.42 (m, 2H), 7.34 -

7.25 m, 1H), 3.85 (s, 2H),

3.70 (q, J= 7.1 Hz, 2H),

2.80 (t, J= 7.3 Hz, 2H),

2.40 (t, J= 7.4 Hz, 2H),

1.15 (t, J = 7.2 Hz, 3H)

673

17149


68.89 (d, J = 2.6 Hz, 1H),

8.60 (dd, J= 4.7, 1.4 Hz,

1H), 8.07 (s, 1H), 7.98


(ddd, J= 8.3.2.7, 1.5 Hz,

1H), 7.46 - 7.40 (m, 1H),

2959, 1660 397 ((M+Hr) 3.62 (q, J= 7.1 Hz, 2H),

3.33 (s, 3H), 2.74 (d, J=

6.7 Hz, 2H), 1.72- 1.60

(m, 1H), 1.31 (t, J = 7.1 Hz,

3H), 0.84 (d, J= 6.7 Hz,

6H)



6 8.90 (d, J = 2.5 Hz, 1H),

8.59 (dd, J= 4.7, 1.4 Hz,

1H), 8.00 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.87 (s,

2975, 1650 341 ([M+Hr) 1H), 7.47 - 7.38 (m, 1H),

4.35 (s, 2H), 3.32 (q, J=

7.1 Hz, 2H), 3.13 (s, 3H),

2.16 (s, 3H), 0.96 (t, J=

7.1 Hz, 3H)


6 8.98 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 (m, 2H), 7.48

Y2000 ESIMS m/z (ddd, J= 8.3, 4.8, 0.5 Hz,

313 ([M+H]') 1H), 4.28 (dd, J= 12.7, 6.3

Hz, 1H), 3.73(d, J= 77.1

Hz, 2H), 3.36 (m, 3H), 1.64

(d, J= 6.6 Hz, 3H), 1.19(t,

J=7.2 Hz, 3H)

674

17149


68.95 (d, J= 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.2 Hz,

1H), 8.03 (ddd, J= 8.3, 19F NMR (376

2.7, 1.4 Hz, 1H), 7.97 (s, Y2001 MHz, CDCI3) 6

1H), 7.47 (dd, J= 8.3, 4.7

Hz, 1H), 4.22 (d, J=6.1 -74.00 (s)

Hz, 1H), 3.75 (m, 4H), 1.35

(d, J= 6.6 Hz, 3H), 1.18(t,

J= 7.2 Hz, 3H)


6 8.96 (d, J= 2.4 Hz, 1H),

8.69 - 8.58 (m, 1H), 8.11 -

8.01 (m, 1H), 7.97 (s, 1H),

(thin film) ESIMS tn/z 7.48 (dd, J= 8.3, 4.7 Hz, Y2002

1485 337 ([M+Hr) 1H), 3.72 (bs, 2H), 3.11 -

2.93 (m, 2H), 2.92 - 2.81

(m, 2H), 2.80 - 2.68 (m,

1H), 2.31 -2.09 (m, 2H),

1.21- 1.10(m, 3H)

1 H NMR (400 MHz,

DMSO-d5) 59.08 (d, J=

2.5 Hz, 1H), 8.98 (s, 1H),

8.58 (dd, J= 4.7, 1.1 Hz,

ESIMS nilz 1H), 8.23 (ddd, J= 8.4,

2.6, 1.3 Hz, 1H), 7.59 (dd, Y2003 295.6

J=8.3,4.7 Hz, 1H), 4.97 ([M+H])

(d, J= 7.6 Hz, 1H), 4.08

(m, 1H), 3.57 (d, J= 50.6

Hz, 2H), 1.10(d, J=6.5

Hz, 3H), 1.07 (t, J = 7.1

Hz, 3H)

675

17149

Y2004 (thin film)

1695

ESIMS m/z

365 ([M+H])


6 8.78 (d, J = 2.5 Hz, 1H),

8.47 (dd, J= 4.7, 1.4 Hz,

1H), 7.91 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.67 -

7.38 (m, 1H), 7.37 - 7.28

(m, 4H), 7.27 - 7.22 (m,

2H), 4.69 (s, 2H), 2.09 (s,

3H), 1.46 (s, 9H)

Y2005 (thin film)

2971, 1702

ESIMS m/z

335 ([M+H])


68.95 (s, 1H), 8.56 (d, J=

4.3 Hz, 1H), 7.98 (d, J=

7.1 Hz, 1H), 7.41 (dd, J=

7.5, 4.7 Hz, 1H), 3.60 -

3.29 (m, 2H), 2.21 (s, 3H),

1.63- 1.48 (m, 5H), 1.42

(s, 6H), 0.95 - 0.89 (m, 3H)

Y2006

ESIMS m/z

366 ([M+14] + ),

363 (EM-Hr)


68.93 (d, J= 2.5 Hz, 1H),

8.64 (m, 1H), 8.07 (s, 1H),

8.03 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.47 (dd, J= 8.3,

4.8 Hz, 1H), 3.37 (s, 3H)

19F NMR (376

MHz, CDCI3) 6

-55.44 (s)

Y2007 ESIMS m/z

299 ([M+H])


69.21 (s, 1H), 8.97 (d, J=

2.6 Hz, 1H), 8.70 - 8.61

(m, 1H), 8.07 (s, 1H), 7.53

-7.41 (m, 1H), 4.07 - 3.90

(m, 2H), 3.73 (s, 2H), 1.22

-1.11 (m, 3H)

676

17149


59.00 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.8,1.4 Hz,

1H), 8.12 (s, 1H), 8.02

Y2008

(thin film)

2980, 2936,

1676

ESIMS m/z

373.6

([M+H])

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 5.17 (q, J

= 6.7 Hz, 1H), 3.71 (m,

2H), 3.13 (s, 3H), 1.50 (d,

J = 6.7 Hz, 3H), 1.19 (t, J=

7.2 Hz, 3H)

73C NMR (101

1 H NMR (300 MHz, CDC° MHz, CDCI3) 5

6 8.92 (d, J = 2.6 Hz, 1H), 171.74,

8.61 (dd, J= 4.8, 1.4 Hz, 148.59,

1H), 8.05 - 8.00 (m, 1H), 140.21,

ESIMS m/z 7.99 (s, 1H), 7.44 (dd, J= 140.01,

Y2009 309 ([M+H]')

8.4, 4.8 Hz, 1H), 3.86 (dq,

J= 11.9, 6.1 Hz, 1H), 3.31

135.70,

126.33,

(s, 3H), 3.24 (s, 3H), 2.52 126.23,

(dd, J= 15.2, 7.3 Hz, 1H), 125.94,

2.23 - 2.08 (m, 1H), 1.14 124.10, 74.22,

(d, J= 6.2 Hz, 3H) 56.52, 40.64,

36.80, 19.18


6 8.90 (d, J = 2.5 Hz, 1H),

8.49 (dd, J = 4.7, 1.3 Hz,

1H), 7.97 (dd, J = 8.3, 1.0 ESIMS m/z

Y2010 Hz, 1H), 7.56 (s, 1H), 7.38 251 ((M+Hr)

(dd, J = 8.3, 4.7 Hz, 1H),

5.16 (s, 1H), 2.94 (s, 3H),

1.91 (s, 3H)

677

17149

Y2011

(thin film)

3440, 2923,

1663

ESIMS m/z

251 ([M+Hr)


6 8.94(d, J= 2.6 Hz, 1H),

8.62 (dd, J= 4.7,1.3 Hz,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.97 (s,

1H), 7.46 (dd, J= 8.3, 4.7

Hz, 1H), 3.24 (s, 3H), 1.99

(s, 3H)

Y2012

ESIMS

m/z 294

([M+H])


68.91 (d, J)= 2.4 Hz, 1H),

8.58 (dd, J= 4.7, 1.4 Hz,

1H), 8.02 - 7.97 (m, 1H),

7.88 (s, 1H), 7.46 - 7.39

(m, 1H), 3.27 - 3.19 (m,

2H), 3.12 (s, 3H), 2.70 (s,

3H), 1.06 - 0.99 (m, 3H)

13C NMR (101

MHz, CDCI3) 6

161.77,

148.14,

139.79,

139.18,

135.83,

128.72,

125.92,

124.03,

123.71, 44.87,

39.41, 35.26,

12.33

Y2013

_

ESIMS m/z

299.6

([M+H])

1 H, NMR (400 MHz, CDCI 3)

6 8.96 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.14 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.5 Hz, 1H), 4.35 (q, J

= 6.6 Hz, 1H), 3.29 (s, 3H),

1.65 (d, J= 6.6 Hz, 3H)

13C NMR (101

MHz, CDCI3) 6

169.97 (s),

148.84 (s),

140.22

(s),140.17,

135.61 (s),

126.44(s),

124.44(s),

124.13 (s),

49.46 (s),

37.57 (s),

29.20, 20.89

(s)

678

17149

Y2014 (thin film)

1677

ESIMS m/z

277 ([M+H]s )


58.96 (s, 1H), 8.66 (d, J=

4.2 Hz, 1H), 8.12 (s, 1H),

8.03 (ddd, J= 8.4, 2.7, 1.4

Hz, 1H), 7.48 (dd, J= 8.3,

4.7 Hz, 1H), 3.37 (s, 2H),

3.30 (s, 3H)

Y2015 (thin film)

1671

ESIMS m/z

290 ((M+Hr)


58.97 (d, J= 2.6 Hz, 1H),

8.66 (dd, J= 4.8, 1.4 Hz,

1H), 8.10 (s, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.48 (ddd, J= 8.4,

4.8, 0.5 Hz, 1H), 3.74 (q, J

= 7.1 Hz, 2H), 3.35 (s, 2H),

1.20 (t, J= 7.2 Hz, 3H)

Y2016 (thin film)

1674

ESIMS m/z

291 ([M+Hr)


58.98 (s, 1H), 8.65 (d, J=

4.2 Hz, 1H), 8.21 (s, 1H),

8.02 (ddd, J= 8.3, 2.6, 1.4

Hz, 1H), 7.47 (dd, J= 8.3,

4.7 Hz, 1H), 3.51 (dd, J=

13.9, 6.9 Hz, 1H), 3.30 (s,

3H), 1.53 (d, J= 7.1 Hz,

3H)

Y2017 (thin film)

2962, 1674

ESIMS m/z

305 ([M+H] . )


58.92 (d, J).= 1.8 Hz, 1H),

8.58 (d, J= 4.0 Hz, 1H),

8.10(s, 1H), 7.96 (ddd, J =

8.3, 2.4, 1.3 Hz, 1H), 7.40

(dd, J= 8.3, 4.7 Hz, 1H),

3.91 - 3.48 (m, 2H), 3.37

(s, 1H), 1.45 (d, J= 7.1 Hz,

311), 1.13 (t, J= 7.2 Hz,

3H)

679

17149

Y2018 (thin film)

1673

ESIMS m/z

331 ([M+Hr)

'H NMR (400 MHz, CDC1 3)

6 8.98 (s, 1H), 8.64 (dd, J

= 4.7, 1.3 Hz, 1H), 8.20(s,

1H), 8.02 (d, J= 7.8 Hz,

1H), 7.46 (dd, J= 8.2, 4.7

Hz, 1H), 3.80 - 3.23 (m,

3H), 1.52 (d, J= 7.1 Hz,

3H), 1.08 - 0.90 (m, 1H),

0.61 - 0.41 (m, 2H), 0.20

(q, J= 4.9 Hz, 2H)

Y2019 (thin film)

3091, 1657

ESIMS m/z

295 ([M-Hr)


6 8.95 (d, J= 2.6 Hz, 1H),

8.63 (s, 1H), 8.06 (s, 1H),

8.04 - 7.96 (m, 1H), 7.52 -

7.42 (m, 1H), 3.26 (s, 3H),

2.85 - 2.73 (m, 2H), 2.56 -

2.48 (m, 2H), 1.70(m, 1H)

Y2021

(thin film)

3109, 2934,

1682

ESIMS m/z

333.4([M+Hr

)


6 8.93 (d, J= 2.6 Hz, 1H),

8.62 (dd, J= 4.7, 1.2 Hz,

1H), 8.04 (m, 2H), 7.45

(dd, J= 8.3, 4.8 Hz, 1H),

3.33 (s, 3H), 2.25 (s, 3H)

680

17149

Y2022 (thin film)

2975, 1664

ESIMS

ink 346

((WM')


68.91 (d, J= 2.6 Hz, 1H),

8.62 (dd, J= 4.8, 1.3 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.67 (s,

1H), 7.45 (dd, J=8.3,4.8

Hz, 1H), 7.26 - 7.24 (m,

1H), 6.28 (dd, J=3.1,1.9

Hz, 1H), 6.00 (d, J=2.8

Hz, 1H), 3.71 (dd, J= 13.9,

7.0 Hz, 2H), 2.98 (t, J= 7.4

Hz, 2H), 2.47 (t, J= 7.5

Hz, 2H), 1.15 (t, J= 7.2

Hz, 3H)

Y2023 (thin film)

2975, 1663

ESIMS m/z

346 ([11/41+1-1] + )


68.90 (d, J = 2.5 Hz, 1H),

8.62 (dd, J= 4.7, 1.4 Hz,

1H), 8.01 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.56 (s,

1H), 7.49(d, J= 1.6 Hz,

1H), 7.48- 7.42 (m, 2H),

6.23 (t, J= 2.1 Hz, 1H),

4.48 (t, J= 6.4 Hz, 2H),

3.67 (dd, J= 13.8, 7.0 Hz,

2H), 2.71 (t, J= 5.8 Hz,

2H), 1.10(t, J=7.2 Hz,

3H)

681

17149


S 8.87(d, J= 2.6 Hz, 1H),

8.61 (dd, J= 4.8, 1.4 Hz,

1H), 8.00 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.54 (d, J

= 1.6 Hz, 1H), 7.45 (dd, J=

8.5, 4.6 Hz, 1H), 7.41 (d, J

Y2024 (thin film) ESIMS mix = 2.1 Hz, 1H), 7.09(s, 1H),

2975, 1658 360 ([M+Hr) 6.28 (t, J= 2.0 Hz, 1H),

4.42 (dd, J= 13.3, 10.7 Hz,

1H), 4.07 (dd, J=13.4, 4.2

Hz, 1H), 3.95 (s, 1H), 3.27

(s, 1H), 3.21- 3.10(m,

1H), 1.16 (d, J= 6.9 Hz,

3H), 1.01 (t, J= 7.2 Hz,

3H)


58.80 (s, 1H), 8.60 (dd, J

= 4.7, 1.3 Hz, 1H), 7.96 (d,

J = 8.3 Hz, 1H), 7.44 (dd, J

= 8.3, 4.7 Hz, 1H), 7.18 (d,

J= 4.8 Hz, 1H), 7.04 - 6.95

(thin film) ESIMS m/z (m, 1H), 6.78 (d, J= 3.3 Y2025

2973, 1658 376 ([M+Hr) Hz, 1H), 6.51 (s, 1H), 3.89

(s, 1H), 3.38 (s, 1H), 3.23

(dd, J= 14.0, 10.4 Hz, 1H),

2.75 (dd, J= 14.0, 4.0 Hz,

1H), 2.72 - 2.62 (m, 1H),

1.20 (d, J= 6.6 Hz, 3H),

1.08 (t, J= 7.2 Hz, 3H)

682

17149


15 8.89 (d, J= 2.5 Hz, 1H),

8.62 (dd, J=4.8,1.4 Hz,

1H), 8.00 (ddd, J= 8.3,

Y2026 (thin film) ESIMS miz 2.7, 1.5 Hz, 1H), 7.62 (s,

1663 332 ([M+H]) 1H), 7.51 -7.42 (m, 3H),

6.24 (t, J= 2.1 Hz, 1H),

4.48 (t, J= 6.4 Hz, 2H),

3.21 (s, 3H), 2.76 (t, J=

6.4 Hz, 2H)


t5 8.86(d, J= 2.6 Hz, 1H),

8.61 (dd, J= 4.8, 1.3 Hz,

1H), 7.99 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.54 (d, J

= 1.6 Hz, 1H), 7.45 (dd, J=

(thin film) ESIMS rniz 8.3, 4.8 Hz, 1H), 7.41 (d, J Y2027

2975, 1663 346 ([11/44+1-1r) = 2.2 Hz, 1H), 7.18 (s, 1H),

6.28(t, J= 2.0 Hz, 1H),

4.44 (dd, J= 13.4, 10.4 Hz,

1H), 4.07 (dd, J= 13.4, 4.2

Hz, 1H), 3.31 -3.20 (m,

1H), 3.16 (s, 3H), 1.16 (d,

J= 6.9 Hz, 3H)


(thin film) ESIMS rniz

5 8.79(d, J= 2.5 Hz, 1H),

8.60 (dd, J= 4.8, 1.4 Hz,

1H), 8.01 -7.92 (m, 1H),

7.43 (dd, J= 8.3, 4.5 Hz,

1H), 7.18 (dd, J= 5.1, 1.0 Y2028

2971, 1658 362 ([M+Hr) Hz, 1H), 6.99 (dd, J= 5.0,

3.4 Hz, 1H), 6.92 - 6.51

(m, 2H), 3.24 (dd, J= 15.0,

11.2 Hz, 1H), 3.18(s, 3H),

2.81 -2.71 (m, 2H), 1.20

(d, J= 6.5 Hz, 3H)

683

17149

Y2029 ESIMS m/z

359 ([M+Hr)


68.99 (s, 1H), 8.63 (d, J=

4.1 Hz, 1H), 8.12 - 8.06

(m, 2H), 7.50 - 7.43 (m,

3H), 7.41 -7.36 (m, 3H),

3.75(q, J= 6.9 Hz, 2H),

1.21 (t, J= 7.2 Hz, 3H)


68.95 (bs, 1H), 8.61 (d, J

= 4.4 Hz, 1H), 8.05 (ddd, J

ESIMS m/z

= 8.3, 2.7, 1.4 Hz, 1H),

7.98 (s, 1H), 7.44 (dd, J= Y2030

325 ([M+Hr) 8.3, 4.8 Hz, 1H), 3.73 (q, J

= 7.2 Hz, 2H), 3.58 (dt, J=

13.7, 6.9 Hz, 1H), 1.30 (d,

J= 6.9 Hz, 6H), 1.19 (t, J=

7.2 Hz, 3H)


ESIMS m/z

68.96 (d, J= 2.6 Hz, 1H),

8.61 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.00 (s,

1H), 7.45 (dd, J= 8.3, 4.8 Y2031

339 ([M+H]) Hz, 1H), 3.74 (q, J= 7.2

Hz, 2H), 2.79 (d, J= 6.7

Hz, 2H), 1.81 (dp, J= 13.2,

6.6 Hz, 1H), 1.19(t, J=7.2

Hz, 3H), 0.95 (d, J= 6.7

Hz, 6H)

684

17149

Y2032 ESIMS m/z

322 ([M+H])

1 H NMR (400 MHz,

DMSO-d6) 511.38 (s, 1H),

9.0 (s, 1H), 8.98(d, J= 1.4

Hz, 1H), 8.51 (d, J= 2.5

Hz, 1H), 8.23 - 8.16 (m,

1H), 4.55 - 4.37 (m, 2H),

4.35 - 4.17 (m, 2H), 2.24

(s, 3H)

Y2033 ESIMS m/z

307 ([1v1+H]*)

1 1-1 NMR (400 MHz, CDCI3)

6 8.95 (d, J= 2.6 Hz, 1H),

8.61 (dd, J= 4.7, 1.4 Hz,

1H), 8.11 (s, 1H), 8.02

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.44 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.21 (s,

3H), 2.78 (t, J= 6.3 Hz,

2H), 2.41 (t, J= 6.3 Hz,

2H), 2.18 (s, 3H)

Y2034 ESIMS m/z

304 ([M+Hr)

I FI NMR (400 MHz,

DMSO-d6) 611.39 (s, 1H),

9.05(d, J=2.5 Hz, 1H),

8.95 (s, 1H), 8.60 - 8.37

(m, 1H), 8.19 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.52 (m,

1H), 4.47 (m, 2H), 4.34 -

4.17 (m, 2H), 2.24 (s, 3H)

Y2035

ESIMS

m/z318([M+

H])

'H NMR (400 MHz,

DMSO-d6) 69.06 (d, J=

2.5 Hz, 1H), 8.47 (dd, J=

4.7, 1.4 Hz, 1H), 8.35 (s,

1H), 8.19 (d, J= 7.9 Hz,

1H), 7.51 (ddd, J= 8.4,

4.7, 0.6 Hz, 1H), 4.47 (t, J

= 7.7 Hz, 2H), 4.13 (bs,

2H), 2.48 (s, 3H), 2.21 (s,

3H)

685

17149

Y2036 (thin film)

1669

ESIMS m/z

320 ([M+H])


6 8.95 (d, J= 2.6 Hz, 1H),

8.65 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 - 8.02 (m, 2H),

7.48 (ddd, J= 8.3, 4.8, 0.5

Hz, 1H), 3.29 (s, 3H), 3.10

(q, J= 9.9 Hz, 2H)

Y2037 (thin film)

1667

ESIMS m/z

333 ([M+Hr)


08.97 (d, J = 2.5 Hz, 1H),

8.65 (dd, J= 4.7, 1.2 Hz,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 8.01 (s,

1H), 7.48 (dd, J= 8.3, 4.7

Hz, 1H), 3.85 - 3.56 (m,

2H), 3.06(q, J= 10.0 Hz,

2H), 1.19 (t, J= 7.2 Hz,

3H)

Y2038 (thin film)

1674

ESIMS m/z

360 ([M+Hr)


5 8.96 (d, J= 2.5 Hz, 1H),

8.65 (dd, J= 4.7, 1.3 Hz,

1H), 8.10 - 8.00 (m, 2H),

7.48 (ddd, J= 8.3, 4.8, 0.5

Hz, 1H), 3.57 (s, 2H), 3.09

(q, J= 9.9 Hz, 2H), 0.98

(qdd, J= 7.4, 4.8, 2.6 Hz,

1H), 0.52 (dd, J= 7.9, 0.9

Hz, 2H), 0.22 (q, J= 4.9

Hz, 2H)

686

17149

Y2039 (thin film)

1671

ESIMS m/z

406 ((M+H])


6 8.93 (d, J= 2.5 Hz, 1H),

8.58 (dd, J= 4.7, 1.3 Hz,

1H), 8.02 (d, J= 7.5 Hz,

1H), 7.90 (s, 1H), 7.43 (dd,

J=8.3,4.7 Hz, 1H), 3.65

(t, J= 7.1 Hz, 2H), 2.26 -

2.10 (m, 2H), 1.91 -1.75

(m, 2H), 1.45 (s, 9H)

Y2040 (thin film)

1698

ESIMS mix

340 ([M+1-1]+ )


68.92 (d, J= 2.5 Hz, 1H),

8.57 (dd, J=4.7,1.3 Hz,

1H), 8.02(d, J= 8.3 Hz,

1H), 7.89 (s, 1H), 7.42 (dd,

J=8.3,4.7 Hz, 1H), 4.53

(t, J= 5.8 Hz, 1H), 4.41 (t,

J= 5.6 Hz, 1H), 3.61 (t, J=

7.1 Hz, 2H), 1.85 - 1.74

(m, 1H), 1.74 - 1.65 (m,

3H), 1.44 (s, 9H)

Y2041 ESIMS m/z

263 ([M+Fi])


6 8.84 (d, J = 2.7 Hz, 1H),

8.47 (dd, J= 4.7, 1.4 Hz,

1H), 7.93 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.64 (s,

1H), 7.35 (dd, J= 8.3, 4.8

Hz, 1H), 4.60 (s, 2H), 1.51

(m, 1H), 1.04 (m, 2H), 0.89

(m, 2H)

687

17149


15 8.95(d, J= 2.5 Hz, 1H),

8.62 (d, J = 3.9 Hz, 1H),

8.08 - 8.00 (m, 2H), 7.45 ESIMS rn/z

Y2042 277 ([1‘4+1-1r)

(dd, J = 8.3, 4.7 Hz, 1H),

3.26 (s, 3H), 1.54- 1.49

(m, 1H), 1.10 - 0.97 (m,

2H), 0.73 (dd, J= 7.5, 3.1

Hz, 2H)


El 8.96(d, J = 2.5 Hz, 1H),

8.66 - 8.40 (m, 1H), 8.10 -

7.92 (m, 2H), 7.45 (dd, J =

(thin film) ESIMS m/z 8.2, 4.7 Hz, 1H), 3.55 (s, Y2043

1650 317 ([M+Hr) 2H), 1.48 (td, J= 8.0, 4.0

Hz, 1H), 1.09 - 0.92 (m,

3H), 0.72 (d, J = 4.9 Hz,

2H), 0.53 - 0.43 (m, 2H),

0.22 - 0.14 (m, 2H)


68.96 (d, J = 2.5 Hz, 1H),

8.62 (d, J = 4.7 Hz, 1H),

8.14 - 7.94 (m, 2H), 7.45 (thin film) ESIMS m/z

Y2044 1649 291 ([M+Hr)

(dd, J = 8.2, 4.8 Hz, 1H),

3.24 (s, 3H), 1.41 (d, J=

6.2 Hz, 1H), 1.30 - 1.15

(m, 2H), 102 (d, J = 6.0 Hz,

3H), 0.56 (bs, 1H)

688

17149


6 8.97 (d, J= 2.5 Hz, 1H),

8.61 (m, 1H), 8.07 (ddd,J

= 8.4, 2.6, 1.4 Hz, 1H),

8.03 (s, 1H), 7.46 (dd, J=

(thin film) ESIMS m/z 8.3, 4.7 Hz, 1H), 3.54 (s, Y2045

1646 332 ([M+Hr) 1H), 1.41 (m, 1H), 1.29 -

1.19 (m, 2H), 1.20 - 1.11

(m, 2H), 1.02(d, J= 6.0

Hz, 3H), 0.55 (bs, 1H),

1 0.48 (d, J= 7.2 Hz, 2H),

0.19(d, J= 4.8 Hz, 2H)


68.95 (d, J= 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.03 (dd, J= 2.7, 1.5

Hz, 1H), 8.02 (s, 1H),7.46 (thin film) ESIMS m/z

Y2046 1670 314 ([M+H])

(dd, J=8.3, 4.8 Hz, 1H),

3.31 (s, 3H), 2.32 (ddd, J=

13.2, 10.6, 7.9 Hz, 1H),

2.26 - 2.13 (m, 1H), 1.63

(ddt, J= 13.4, 6.8, 3.8 Hz,

1H)

689

17149


68.97 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.8, 1.3 Hz,

1H), 8.05 (dd, J= 2.7, 1.4

Hz, 1H), 8.03 (s, 1H), 7.47

(dd, J= 8.3, 4.8 Hz, 1H),

(thin film) ESIMS m/z 3.77 (dd, J= 13.7, 7.0 Hz, Y2047

1665 353 ([M+Hr) 1H), 3.44 (dd, J= 14.0, 7.3

Hz, 1H), 2.38 - 2.11 (m,

2H), 1.63 (ddd, J= 10.9,

7.1, 4.4 Hz, 1H), 1.06 -

0.92 (m, 1H), 0.56 - 0.45

(m, 2H), 0.21 (td, J= 4.9,

3.0 Hz, 2H)


6 8.94(d, J= 2.6 Hz, 1H),

8.62 (dd, J = 4.8,1.4 Hz,

ESIMS m/z 1H), 8.05 - 7.98 (m, 2H), Y2048

297 ([M+1-11 +) 7.46 (dd, J= 8.3, 4.7 Hz,

1H), 5.66 (s, 1H), 3.72 -

3.59 (m, 5H), 1.17 (t, J=

7.2 Hz, 3H)

IFI NMR (300 MHz, CDCI 3 )

69.05 (d, J = 2.6 Hz, 1H),

8.91 (s, 1H), 8.59 - 8.48


(m, 1H), 8.13 - 8.04 (m,

Y2049 3050, 2931,

1583 325 ([M+H]t )

1H), 7.40 (dd, J= 8.4, 4.8

Hz, 1H), 3.81 (q, J= 7.2

Hz, 2H), 3.73 (s, 3H), 2.95

(q, J= 14.1, 7.0 Hz, 2H),

1.44- 1.28 (m, 6H)

690

17149

Y2050 ESIMS m/z

280 ([M+H])

I HNMR (400 MHz,

Acetone-de) 59.10 (d, J=

2.6 Hz, 1H), 8.72 (s, 1H),

8.59 (dd, J= 4.7, 1.3 Hz,

1H), 8.22 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.56 (m,

1H), 3.65(d, J= 7.1 Hz,

2H), 2.15(q, J= 7.4 Hz,

2H), 1.11 (t, J= 7.2 Hz,

3H), 1.00 (t, J= 7.4 Hz,

3H)

Y2051 (thin film)

1679

ESIMS m/z

420 ([M+Hr)


5 8.92 (d, J = 2.5 Hz, 1H),

8.58 (dd, J= 4.7, 1.2 Hz,

1H), 8.02(d, J= 7.4 Hz,

1H), 7.87 (s, 1H), 7.42 (dd,

J=8.3,4.7 Hz, 1H), 3.60

(t, J= 6.7 Hz, 2H), 2.23 -

2.06 (m, 2H), 1.65- 1.60

(m, 4H), 1.44 (s, 9H)

Y2052 ESIMS m/z

325 ([M+H])


5 8.97 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J=4.8,1.5

Hz, 1H), 8.05 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.02 (s,

1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.85 (m,

1H), 3.60 (m, 1H), 2.91

(ddd, J= 13.2, 9.4, 8.1 Hz,

1H), 2.41 (ddd, J= 13.2,

9.2, 4.9 Hz, 1H), 1.49 (dd,

J = 9.2, 8.2 Hz, 1H), 1.18

(t, J= 7.2 Hz, 3H), 1.14(d,

J= 6.7 Hz, 3H) (note: SH

proton was not seen in I FI

NMR)

691

17149


6 9.06 (d, J= 2.7 Hz, 1H),

' 3C NMR (101

MHz, CDCI3) 6

8.61 (dd, J= 4.7, 1.4 Hz, 175.06,

1H), 8.44 (s, 1H), 8.13 148.34,

(ddd, J= 8.3.2.7. 1.5 Hz, 139.87,

1H), 7.50 (dd, J= 8.4, 4.8 139.77,

ESIMS m/z Hz, 1H), 6.38 (d, J= 9.7 135.60,

Y2053 394 ([M-Hr)

Hz, 1H), 5.96 (dt, J= 5.7,

2.1 Hz, 1H), 5.84 (ddd, J=

134.26,

132.41,

5.5, 2.5, 1.2 Hz, 1H), 4.53- 126.88,

4.42 (m, 1H), 3.69 - 3.58 126.29,

(m, 1H), 3.26 (s, 3H), 3.00 125.25,

(s, 3H), 2.34 (dt, J= 13.6, 124.18, 58.77,

8.1 Hz, 1H), 2.09 - 1.99 47.25, 41.66,

(m, 1H) 37.52, 35.86

1 11 NMR (400 MHz, CDCI 3 ) 13C NMR (101

68.99 (d, J= 2.6 Hz, 1H), MHz, CDCI3) 6

8.63 (dt, J= 4.8, 2.4 Hz, 175.08,

1H), 8.22 - 8.16 (m, 1H), 148.73,

8.07 (ddd, J= 8.3, 2.7, 1.5 140.11,

Hz, 1H), 7.47 (ddd, J = 7.4, 140.01,

ESIMS m/z 4.8, 2.2 Hz, 1H), 6.04- 135.58,

Y2054 394 ([M-Hr)

5.91 (m, 2H), 5.80 (dd, J=

5.6, 2.5 Hz, 1H), 4.54-

134.53,

132.36,

4.44 (m, 1H), 3.58 (dt, J= 126.36,

6.4, 2.1 Hz, 1H), 3.25 (d, J 126.17,

= 2.7 Hz, 3H), 2.99 (d, J= 125.53,

2.6 Hz, 3H), 2.26 (dt, J= 124.17, 58.73,

13.7, 8.0 Hz, 1H), 2.09- 47.33, 41.89,

2.00 (m, 1H) 37.67, 35.84

692

17149

1 11 NMR (400 MHz, CDCI 3 )

6 8.93 (d, J= 2.6 Hz, 1H),

8.59(d, J= 3.7 Hz, 1H),

(thin film) ESIMS m/z 8.02(d, J= 8.2 Hz, 1H), Y2055

1702 392 ([M+Hr) 7.89 (s, 1H), 7.43 (dd, J=

8.1, 4.8 Hz, 1H), 3.82 (br s,

2H), 2.47 (br s, 2H), 1.48

(s, 9H)


68.96 (bd, 1H), 8.61 (s,

1H), 8.54 (dd, J=4.7,1.4

Hz, 1H), 7.97 (ddd, J= 8.3,

ESIMS m/z 2.7, 1.4 Hz, 1H), 7.39 (ddd, Y2056

263 ([M+Hr) J= 8.4, 4.7, 0.7 Hz, 1H),

7.33(s, 1H), 1.67 - 1.59

(m, 1H), 1.13 (dt, J=6.6,

4.0 Hz, 2H), 0.94 (td, J=

7.1, 4.1 Hz, 2H)

'H NMR (400 MHz, CDC1 3 )

6 8.97 (d, J= 2.4 Hz, 1H),

8.61 (d, J= 3.6 Hz, 1H),

(thin film) ESIMS m/z 8.09 — 8.00 (m, 2H), 7.45 Y2057

1666 307 ([M+H]) (dd, J= 8.4, 4.7 Hz, 1H),

3.44 (s, 3H), 1.58 — 1.52

(m, 3H), 1.13 — 1.05 (m,

2H), 0.85 — 0.75 (m, 2H)

1 11 NMR (400 MHz, CDC13)

68.91 (d, J= 2.6 Hz, 1H),

8.61 (bd, 1H), 8.10 — 7.99

(thin film) ESIMS m/z (m, 4H), 7.63 — 7.55 (m, Y2058

1678 397 ([M+Hr) 1H), 7.50 — 7.38 (m, 3H),

5.89 (bs, 2H) 1.67— 1.46

(m, 1H), 1.20 — 1.04 (m,

2H), 0.91 —0.73 (m, 2H)

693

17149


6 8.95 (d, J= 2.4 Hz, 1H),

8.63 (d, J= 4.7 Hz, 1H),

8.10 (s, 1H), 8.04 (m, 1H),

(thin film) ESIMS m/z 7.46 (dd, J= 8.3, 4.8 Hz, Y2059

1679 379 ([M+Hr) 1H), 5.70 (s, 2H), 4.13 (s,

2H), 3.60 (bd, 2H), 1.31 —

1.18(m, 4H), 1.16 — 1.06

(m, 2H), 0.85 — 0.76 (m,

2H)


68.95 (s, 1H), 8.62 (d, J=

4.3 Hz, 1H), 8.09 — 7.98

ESIMS m/z (m, 2H), 7.45 (dd, J= 8.2, Y2060

305 ([1\141-1]) 4.7 Hz, 1H), 2.53 (s, 3H),

1.97 — 1.87 (m, 1H), 1.23 —

1.12 (m, 2H), 1.00 — 0.85

(m, 2H)

1 11 NMR (400 MHz, CDCI 3 )

68.95 (bs, 1H), 8.61 (d, J

= 4.2 Hz, 1H), 8.08 — 7.95

(m, 2H), 7.45 (dd, J= 8.3,

Y2061 4.7 Hz, 1H), 3.51 —3.31

(m, 1H), 2.01 —1.87 (m,

1H), 1.23 (d, J=6.8 Hz,

6H), 1.20 — 1.15 (m, 2H),

0.98 — 0.92 (m, 2H)


68.94 (s, 1H), 8.63 (d, J=

(thin film) ESIMS m/z 4.3 Hz, 1H), 7.99 (d, J= Y2062

2978, 1709 328 ([M+H)) 7.8 Hz, 1H), 7.47 (dd, J=

8.0, 4.8 Hz, 1H), 3.20 (s,

3H), 1.59- 1.40 (m, 9H)

694

17149

Y2063 (thin film)

2977, 1706

ESIMS m/z

325 ([M+H])


58.80 (s, 1H), 8.43 (d, J=

1.9 Hz, 1H), 7.79 (d, J=

8.8 Hz, 1H), 3.18 (s, 3H),

2.23 (s, 3H), 1.63- 1.37

(m, 9H)

Y2064 (thin film)

1646

ESIMS m/z

387 ((M+Hr)


58.87 (d, J = 2.5 Hz, 1H),

8.61 (dd, J= 4.8, 1.4 Hz,

1H), 7.96 (ddd, J= 8.3,

2.5, 1.4 Hz, 1H), 7.84(s,

1H), 7.44 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 5.68 (bs,

1H), 4.01 (s, 3H), 3.86 (q,

J= 7.1 Hz, 2H), 1.27 (t, J =

7.1 Hz, 3H), 1.13 (s, 9H)

Y2065 (thin film)

1655

ESIMS m/z

321 ([M+H]. )


5 8.95 (d, J= 2.5 Hz, 1H),

8.64(d, J= 3.8 Hz, 1H),

8.07 (d, J= 8.4 Hz, 1H),

7.98 (s, 1H), 7.47 (dd, J=

8.2, 4.7 Hz, 1H), 3.95 (d, J

= 9.2 Hz, 2H), 3.31 -3.16

(m, 5 H), 2.62 - 2.47 (m,

1H), 1.93 (qd, J= 12.3, 4.5

Hz, 2H), 1.55- 1.52 (m,

2H)

695

17149


6 8.95 (d, J= 2.6 Hz, 1H),

8.63 (dd, J= 4.7, 1.2 Hz,

1H), 8.15- 8.00(m, 1H),

7.95 (s, 1H), 7.47 (dd, J= (thin film) ESIMS m/z

Y2066 1657 335 ([M+Hr)

8.3, 4.8 Hz, 1H), 3.91 (dd,

J= 11.0, 3.5 Hz, 2H), 3.41

(t, J= 10.8 Hz, 2H), 3.23

(s, 3H), 2.11 (bs, 3H), 1.63

(d, J = 12.8 Hz, 2H), 1.20

(m, 2H)

1 11 NMR (400 MHz, CDCI 3)

6 8.88 (t, J=1.9 Hz, 1H),

8.54 (dd, J=4.7,1.3 Hz,

(thin film) ESIMS m/z 1H), 7.94 - 7.86 (m, 1H), Y2067

2978, 1705 383 ((WM+ ) 7.42 - 7.35 (m, 1H), 7.35 -

7.20 (m, 5H), 4.69 (s, 2H),

2.04- 1.90(m, 3H), 1.63 -

1.37 (m, 9H)


6 8.98 (d, J= 2.5 Hz, 11-1),

8.63 (dd, J= 4.8, 1.4 Hz,

(thin film) ESIMS m/z 1H), 8.06 - 7.79 (m, 2H), Y2068

1656 385 ((M+Hr) 7.45 (ddd, J= 8.3, 4.8, 0.6

Hz, 1H), 6.24 - 5.96 (m,

1H), 4.14 (s, 3H), 3.44 (s,

3H)

696

17149

Y2069 ESIMS rn/z

345 ([lvt+Hr)

1 1-1NMR (400 MHz, CDCI3)

08.86 (d, J = 2.4 Hz, 1H),

8.59 (dd, J= 4.7, 1.4 Hz,

1H), 8.00 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.89 (s,

1H), 7.42 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 6.92 (s,

1H), 4.04 (q, J=7.3 Hz,

2H), 3.37 (s, 3H), 2.52 (s,

3H), 1.36 (t, J= 7.3 Hz,

3H)

Y2070 (thin film)

1638

ESIMS ink

345 (IM+Hr)


si5 8.83(d, J= 2.6 Hz, 1H),

8.58 (dd, J= 4.8, 1.4 Hz,

1H), 7.97 - 7.88 (m, 1H),

7.76 (s, 1H), 7.41 (dd, J=

8.0, 4.5 Hz, 1H), 3.65 (s,

3H), 3.38 (s, 3H), 2.25 (s,

3H), 2.17 (s, 3H)

Y2071

(thin film)

3093, 2978,

1681, 1649

ESIMS

ink 345

([M+H])


6 8.97 (d, J= 2.7 Hz, 1H),

8.65 (dd, J=4.9,1.4 Hz,

1H), 8.07 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.99 (s,

1H), 7.48 (dd, J= 8.3, 4.8

Hz, 1H), 6.84 (dq, J= 15.4,

6.8 Hz, 1H), 6.60 - 6.44

(m, 1H), 3.80 (q, J= 7.2

Hz, 2H), 1.22 (t, J= 7.2

Hz, 3H)

697

17149

Y2072

(thin film)

3098, 2977,

1675

ESIMS m/z

381 ([M+Hr),

379 ([m-fin


6 8.96 (d, J= 2.7 Hz, 1H),

8.65 (dd, J= 4.8, 1.5 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 2H), 7.48 (ddd,

J= 8.3, 4.7, 0.8 Hz, 1H),

4.42 (m, 1H), 3.79 (m, 2H),

3.21 (m, 1H), 2.66 (m, 1H),

1.20 (t, J= 7.2 Hz, 3H)

Y2073 (thin film)

2139, 1656

ESIMS m/z

366 ([M+H])


8 9.05 (d, J = 2.6 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.27 (s, 1H), 8.09

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 3.74 (qd,

J= 13.5, 6.8 Hz, 2H), 3.37

(td, J= 12.4, 4.6 Hz, 1H),

3.23 - 3.05 (m, 1H), 2.96 -

2.86 (m, 1H), 2.82 (s, 3H),

2.67 (dt, J= 16.3, 3.9 Hz,

1H), 1.19 (t, J= 7.2 Hz,

3H)

Y2074

(thin film)

2977, 1688,

1649

ESIMS m/z

419 ((M+Hr)


6 8.76 (d, J= 2.5 Hz, 1H),

8.57 (dd, J= 4.7, 1.2 Hz,

1H), 7.86 (ddd, J= 8.3,

2.4, 1.4 Hz, 1H), 7.52(s,

1H), 7.42 - 7.32 (m, 5H),

3.77 (q, J= 7.0 Hz, 2H),

3.18 (s, 3H), 1.31 (t, J=

7.1 Hz, 3H)

698

17149

Y2075 (thin film)

1652

ESIMS m/z

297 ([1■441]. )


15 8.95(d, J= 2.6 Hz, 1H),

8.62 (dd, J= 4.7, 1.3 Hz,

1H), 8.05 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 8.00(s,

1H), 7.45 (dd, J= 8.3, 4.8

Hz, 1H), 3.75(q, J= 7.2

Hz, 2H), 2.30 (s, 3H), 1.20

(t, J= 7.2 Hz, 3H)

Y2076 (thin film)

1660

ESIMS m/z

343 (CM+Hr)

I HNMR (400 MHz, CDCI 3)

O 8.98 (d, J = 2.3 Hz, 1H),

8.70 (dd, J= 4.8, 1.3 Hz,

1H), 8.03(d, J= 8.3 Hz,

1H), 7.48 (dd, J= 8.2, 4.8

Hz, 1H), 3.80 (ddq, J=

109.5, 14.2, 7.3 Hz, 2H),

2.32 (s, 3H), 2.22 (s, 3H),

1.22 (t, J= 7.2 Hz, 3H)

Y2077 ESIMS rniz

327 ([M+H])

T H NMR (CDCI3) •5 8.98 (d,

J= 2.6 Hz, 1H), 8.64 (dd, J

= 4.8, 1.4 Hz, 1H), 8.08 (s,

1H), 8.05 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.47 (dd,

J= 8.3, 4.7 Hz, 1H), 3.99

(m, 1H), 3.86 (br s, 1H),

3.60 (br s, 1H), 2.13 (dt, J

= 14.6, 7.3 Hz, 1H), 1.91

(dt, J= 14.5, 7.3 Hz, 1H),

1.19 (t, J= 7.2 Hz, 3H),

0.97 (t, J= 7.3 Hz, 3H)

699

17149

Y2078 ESNS m/z

235 ([M+H])


t5 8.77 (d, J = 1.1 Hz, 1H),

8.52(s, 1H), 8.35(d, J=

2.5 Hz, 1H), 7.78 (dt, J=

9.7, 2.3 Hz, 1H), 6.91 (s,

1H), 2.33 (s, 3H), 2.23 (s,

3H)

Y2079

(thin film)

2981, 2253,

1687

ESIMS m/z

421 ([M+H]+ )


158.99 (d, J= 2.5 Hz, 1H),

8.61 (dd, J= 4.7, 1.3 Hz,

1H), 8.32 (s, 1H), 8.01

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.95 - 7.88 (m, 2H),

7.67 - 7.58 (m, 1H), 7.58 -

7.50 (m, 2H), 7.44 (ddd, J

= 8.3, 4.8, 0.4 Hz, 1H),

3.43 (s, 3H), 3.16 (q, .1=

7.2 Hz, 2H), 1.05 (t, J= 7.2

Hz, 3H)

Y2080 (thin film)

2928, 1654

ESIMS m/z

325 ([M+Hr)


6 8.59(d, J= 1.6 Hz, 1H),

8.39 (d, J= 2.5 Hz, 1H),

7.75 (dt, J= 9.4, 2.4 Hz,

1H), 7.48 (s, 1H), 7.35 -

7.28 (m, 3H), 7.25 - 7.19

(m, 2H), 4.79 (s, 2H), 2.03

(s, 3H), 1.96 (s, 3H)

700

17149

Y2081 (thin film)

2979, 1678

ESIMS rn/z

353 ([M+1-11+)


58.90 (d, J= 2.6 Hz, 1H),

8.59 (dd, J= 4.7, 1.4 Hz,

1H), 8.01 (s, 1H), 7.99

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.46 - 7.40 (m, 1H),

4.12(q, J= 7.1 Hz, 2H),

3.57 (q, J= 7.1 Hz, 2H),

3.33 (s, 3H), 1.25 (t, J=

7.1 Hz, 3H), 1.21 (t, J= 7.1

Hz, 3H)

Y2082 (thin film)

2969, 1681

ESIMS ink

365 ([M+1-11+ )


58.93 (d, J = 2.5 Hz, 1H),

8.61 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 (s, 1H), 8.00

(ddd, J= 8.3, 2.6, 1.4 Hz,

1H), 7.44 (dd, J=8.3, 4.7

Hz, 1H), 3.58 (q, J= 7.0

Hz, 2H), 3.35 (s, 3H), 1.25

- 1.13 (m, 12H)

Y2083 (thin film)

2926, 1601

ESIMS m/z

341 ([M+H]+ )


58.57 (d, J= 1.8 Hz, 1H),

8.40 (d, J= 2.5 Hz, 1H),

7.74 (dt, J= 9.3, 2.4 Hz,

1H), 7.44 (s, 1H), 7.36 -

7.29 (m, 5H), 5.51 (s, 2H),

2.50 (s, 3H), 2.03 (s, 3H)

Y2084

(thin film)

2981, 2257,

1683

ESIMS nilz

359 ([M+H] +)


6 8.96 (d, J = 2.6 Hz, 1H),

8.61 (dd, J= 4.7, 1.4 Hz,

1H), 8.19 (s, 1H), 7.97

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.49 - 7.40 (m, 1H),

3.41 -3.33 (m, 5H), 3.17

(s, 3H), 1.19 (t, J=7.2 Hz,

3H)

701

17149

Y2085 (thin film)

2189, 1659

ESIMS m/z

382 ([M+H])


6 9.00 (d, J = 2.7 Hz, 1H),

8.64 (dd, J= 4.8, 1.4 Hz,

1H), 8.12 (s, 1H), 8.06

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.47 (dd, J= 8.3, 4.7

Hz, 1H), 3.85 - 3.65 (m,

4H), 3.35 (s, 3H), 2.84 (t, J

= 6.3 Hz, 2H), 1.19 (t, J =

7.2 Hz, 3H)

Y2088

(thin film)

2981, 2255,

1687

ES I MS m/z

385 ([M+Hr)


68.94 (d, J= 2.7 Hz, 1H),

8.58 (dd, J= 4.7, 1.4 Hz,

1H), 8.18 (s, 1H), 7.94

(ddd, J= 8.3, 2.6, 1.4 Hz,

1H), 7.40 (dd, J= 8.3, 4.7

Hz, 1H), 3.43 - 3.31 (m,

5H), 2.88 - 2.77 (m, 1H),

1.29 - 1.21 (m, 2H), 1.17(t,

J=7.2 Hz, 3H), 1.13 - 1.03

(m, 2H)

Y2089

(thin film)

1981, 2254,

1688

ESIMS m/z

461 ([M+H])

I li NMR (300 MHz, CDCI3)

68.97 (d, J = 2.6 Hz, 1H),

8.61 (dd, J= 4.8, 1.2 Hz,

1H), 8.22 (s, 1H), 7.99

(ddd, J= 8.4, 2.7, 1.5 Hz,

1H), 7.52 (d, J=4.2 Hz,

1H), 7.47 - 7.40 (m, 1H),

6.95 (d, J= 4.1 Hz, 1H),

3.40 (s, 3H), 3.27 (q, J=

7.2 Hz, 2H), 1.08 (t, J= 7.2

Hz, 3H)

702

17149

Y2090 (thin film)

3965,1656

ESIMS m/z

350 ([M+H])

"Fl NMR (400 MHz,

Chloroform-0 a 8.95 (d, J

= 2.6 Hz, 1H), 8.63 (dd, J=

4.8, 1.4 Hz, 1H), 8.05 (ddd,

J= 8.3, 2.8, 1.5 Hz, 1H),

7.97(s, 1H), 7.47 (dd, J=

8.3, 4.8 Hz, 1H), 3.71 (t, J

= 4.7 Hz, 6H), 3.00 (s, 2H),

2.48 (t, J= 4.6 Hz, 4H),

1.17(t, J = 7.2 Hz, 3H)

Y2091 (thin film)

3098, 1664

ESIMS

m/z 331

([M+Hr), 329

([M-Hr)

1 11 NMR (400 MHz,

Chloroform-cf) a 8.95 (d, J

= 2.6 Hz, 1H), 8.66 (dd, J=

4.8, 1.5 Hz, 1H), 8.02 (ddd,

J= 8.3, 2.7, 1.5 Hz, 1H),

7.81 (s, 1H), 7.48 (dd, J=

8.3, 4.7 Hz, 1H), 7.34 (d, J

= 1.0 Hz, 1H), 7.06 (t, J=

1.0 Hz, 1H), 6.88 (t, J = 1.3

Hz, 1H), 4.58 (s, 2H), 3.74

(q, J= 7.2 Hz, 2H), 1.19(t,

J= 7.2 Hz, 3H)

Y2092

(thin film)

3232, 3106,

2968, 294Z

2870, 2251,

1651, 1585


15 8.97 (d, J= 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.08 - 8.03 (m, 2H),

7.47 (dd, J= 8.4, 4.7 Hz,

1H), 6.14 (d, J= 8.4 Hz,

1H), 3.98 - 3.89 (m, 1H),

3.25 (s, 3H), 2.97 (m, 4H),

2.00- 1.72 (m, 6H)

' 3C NMR (101

MHz, CDCI3) a

178.38,

148.74,

140.25,

140.00,

135.59,

126.31,

125.90,

125.76,

124.16, 55.39,

41.55, 39.47,

37.49, 37.46,

34.86, 29.08

703

17149

Y2093

(thin film)

3086, 2980,

2936, 2548,

1657

ESIMS m/z

309 ([M-Hr)

'H NMR (400 MHz,


= 2.7, 0.7 Hz, 1H), 8.63

(dd, J= 4.8, 1.5 Hz, 1H),

8.06 (ddd, J= 8.3, 2.7, 1.4

Hz, 1H), 7.97 (s, 1H), 7.47

(ddd, J= 8.4, 4.7, 0.8 Hz,

1H), 3.72(q, J= 7.1 Hz,

2H), 2.79 (dt, J= 8.5, 6.8

Hz, 2H), 2.49 (1, J= 6.7

Hz, 2H), 1.67 (t, J= 8.4

Hz, 1H), 1.17 (t, J= 7.2

Hz, 3H)

Y2094

(thin film)

3082, 2983,

1649, 1486,

1291

ESIMS m/z

265 ([M+H])

1 FI NMR (CDCI3) 6 9.00 -

8.91 (m, 1H), 8.63 (dd, J=

4.8, 1.5 Hz, 1H), 8.06 (ddd,

J= 8.3, 2.7, 1.4 Hz, 1H),

7.95 (s, 1H), 7.46 (ddd, J=

8.3, 4.7, 0.7 Hz, 1H), 3.70

(q, J= 7.2 Hz, 2H), 1.97(s,

3H), 1.16(t, J=7.2 Hz,

3H)

Y2097 ESIMS m/z

299 ((WM+ )

I HNMR (CDCI3) 6 8.96 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.14-

7.93 (m, 2H), 7.47 (dd, J=

8.4, 4.6 Hz, 1H), 3.80 (t, J

= 6.7 Hz, 2H), 3.27(s, 3H),

2.68 (t, J= 6.6 Hz, 2H)

13C NMR

(CDCI3) 6

170.4, 148.7,

140.2, 140.1,

135.6, 126.4,

126.1, 125.3,

124.1, 39.8,

37.1, 36.4

704

17149

Y2098 ESIMS m/z

263 ([M+H])

'H NMR (CDCI3) 5 8.95 (d,

J=2.6 Hz, 1H), 8.62 (dd, J

= 4.8, 1.4 Hz, 1H), 8.04

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.98 (s, 1H), 7.46 (dd,

J= 8.4, 4.7 Hz, 1H), 6.44

(dd, J= 16.8, 2.0 Hz, 1H),

6.24 (dd, J=16.8,10.3 Hz,

1H), 5.65 (dd, J= 10.4, 1.9

Hz, 1H), 3.32 (s, 3H)

Y2099 (thin film)

3333, 1656

ESIMS m/z

82 (IM+H-

H2011

I FINMR (400 MHz,

Methanol-d4) 5 9.07 (d, J=

2.7 Hz, 1H), 8.74 - 8.65

(m, 1H), 8.58 (dd, J= 4.8,

1.4 Hz, 1H), 8.28 (ddd, J=

8.4.2.7, 1.4 Hz, 1H), 7.63

(dd, J= 8.4, 4.8 Hz, 1H),

3.85- 3.66 (m, 4H), 3.26

(s, 3H), 2.78 (dq, J= 14.1,

7.2 Hz, 2H), 1.19 (t, J = 7.2

Hz, 3H)

Y2102 ESIMS m/z

358 ([M+Hr)

1 H NMR (CDCI3) 58.96 (d,

J= 2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05 (s,

1H), 8.03 (ddd, J= 8.4,

2.8, 1.5 Hz, 1H), 7.46 (dd,

J= 8.5, 4.8 Hz, 1H), 5.25

(t,J=6.4 Hz, 1H), 3.43-

3.30 (m, 2H), 3.25 (s, 3H),

2.96(s, 3H), 2.50(t, J=

5.5 Hz, 2H)

„ ''C NMR

(CDCI3) 5

169.6, 146.3,

137.7, 137.5,

133.1, 123.9,

123.7, 122.6,

121.6, 37.8,

36.7, 34.5,

31.9

705

17149

Y2104 (thin film)

2139, 1655

ESIMS m/z

366 ([M+Hr)

'H NMR (400 MHz,


= 2.7 Hz, 1H), 8.67 (s, 1H),

8.60 (dd, J = 4.8, 1.4 Hz,

1H), 8.17 (ddd, J = 8.3,

2.7, 1.5 Hz, 1H), 7.43 (ddd,

J = 8.4, 4.8, 0.8 Hz, 1H),

3.46 - 3.33 (m, 2H), 3.29

(s, 3H), 2.90 - 2.82 (m,

1H), 2.79 (s, 3H), 1.23 (d,

J=6.4 Hz, 3H).

Y2105 (thin film)

2139, 1654

ESIMS m/z

366 ([M+Hr)


69.11 (d, J= 2.5 Hz, 1H),

8.61 (dd, J= 4.8, 1.4 Hz,

1H), 8.43 (s, 1H), 8.13

(ddd,J= 8.3, 2.7, 1.4 Hz,

1H), 7.44 (ddd, J=8.3,

4.8, 0.6 Hz, 1H), 3.54 (dd,

J= 13.1, 4.6 Hz, 1H),3.30

(dd, J= 10.1, 5.3 Hz, 1H),

3.27 (s, 3H), 2.99 (dd, J=

13.1, 8.5 Hz, 1H), 2.82 (s,

3H), 1.28 (d, J= 6.9 Hz,

3H)

Y2106 ESIMS m/z

280 ([M+Hr)

'H NMR (CDCI 3) 68.91 (d,

J= 2.7 Hz, 1H), 8.58 (dd,J

= 4.7, 1.4 Hz, 1H), 8.09 -

7.95(m, 2H), 7.44 (dd, J=

8.3, 4.7 Hz, 1H), 4.64 (q, J

= 4.6 Hz, 1H), 3.67 (q, J =

7.2 Hz, 2H), 2.78 (d,J=

4.7 Hz, 3H), 1.15 (t, J=7.1

Hz, 3H)

13C NMR

(CDCI3) 6

157.1, 148.4,

141.5.139.8,

135.6, 127.1,

126.0, 124.1,

123.2.43.8,

27.5, 13.9

706

17149

1 11 NMR (400 MHz, CDCI 3 )

68.85 (d, J= 2.6 Hz, 1H),

8.62 (dd, J=4.7,1.3 Hz,

1H), 7.99 (ddd, J= 8.3,


2.7, 1.4 Hz, 1H), 7.62 (s,

1H), 7.45 (dd, J= 8.3, 4.8 Y2107

2926, 1663 348 ([M+1-1]') Hz, 1H), 7.18 (dd, J= 5.2,

1.1 Hz, 1H), 6.91 (dd, J=

5.1, 3.5 Hz, 1H), 6.77 (dd,

J=3.4,0.9 Hz, 1H), 3.73

(m, 4H), 1.16 (t, J= 7.2 Hz,

3H)


(thin film) ESNS m/z

6 8.82(d, J= 2.5 Hz, 1H),

8.61 (dd, J = 4.7, 1.4 Hz,

1H), 7.96 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.48 (s,

1H), 7.44 (dd, J= 8.5, 4.6 Y2108

2973, 1658 348 ([M+Hr) Hz, 1H), 7.24 (dd, J= 4.9,

3.0 Hz, 1H), 6.91 (dd, J=

2.8, 1.0 Hz, 1H), 6.87 (dd,

J= 4.9, 1.1 Hz, 1H),3.70

(m, 2H), 3.56 (s, 2H), 1.15

(t, J= 7.2 Hz, 3H)


Y2109 (thin film) ESIMS m/z

6 8.93 (d, J= 2.6 Hz, 1H),

8.62 (dd, J= 4.8, 1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.96 (s,

2972, 1659 377 ([M+H]) 1H), 7.45 (dd, J= 8.3, 4.7

Hz, 1H), 3.73 (m, 2H), 3.59

(s, 2H), 2.53 (s, 3H), 2.26

(s, 3H), 1.16 (t, J= 7.2 Hz,

3H)

707

17149

Y2110 (thin film)

2975, 1667

ESIMS m/z

347 ([M+H])


15 8.95 (d, J= 2.6 Hz, 11-1),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.02 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.90(s,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 6.04 (s, 1H), 3.74

(m, 2H), 3.68 (s, 2H), 2.23

(s, 3H), 1.18 (t, J= 7.2 Hz,

3H)

Y2111 (thin film)

2974, 1660

ESIMS m/z

343 ([M+H])


/5 8.85(d, J= 2.5 Hz, 1H),

8.61 (dd, J= 4.7, 1.4 Hz,

1H), 8.49 (m, 1H), 7.99

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.83 (s, 11-9, 7.60 (td,

J= 7.7, 1.8 Hz, 1H), 7.44

(ddd, J= 8.3, 4.7, 0.5 Hz,

1H), 7.24 (d, J= 7.8 Hz,

111), 7.15 (ddd, J= 7.4,

4.9, 0.8 Hz, 1H), 3.75 (m,

4H), 1.17 (t, J= 7.2 Hz,

3H)

Y2112 (thin film)

2975, 1659

ESIMS m/z

442 ([M+H])


08.90 (d, J = 2.6 Hz, 1H),

8.64 (dd, J= 4.7, 1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.86 (s,

1H), 7.66 (d, J = 7.6 Hz,

1H), 7.46 (m, 2H), 7.37 (m,

1H), 7.32 (td, J=7.6,1.5

Hz, 1H), 3.82 (s, 2H), 3.72

(m, 211), 1.18(t, J= 7.2 Hz,

3H)

708

17149

Y2113 (thin film)

2190, 658

ESNS m/z

382 ((M+Hr)

I li NMR (400 MHz, CDCI 3)

69.08 (d, J = 2.5 Hz, 1H),

8.63 (dd, J= 4.7, 1.3 Hz,

1H), 8.29 (s, 1H), 8.06

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.48 - 7.38 (m, 1H),

4.17 (dd, J= 14.3, 10.3 Hz,

1H), 3.49 (dd, J= 8.0, 4.7

Hz, 1H), 3.32 (s, 3H), 3.29

(s, 3H), 3.20 (dd, J= 14.3,

2.7 Hz, 1H), 1.25(d, J=

7.1 Hz, 3H)

Y2114 (thin film)

2190, 1660

ESIMS m/z

382 ([M+H])


6 9.04 (d, J = 2.6 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.14(s, 1H), 8.04

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 4.10 (dd,

J = 14.0, 11.2 Hz, 1H),

3.55- 3.40 (m, 1H), 3.35

(dd, J= 14.1, 2.7 Hz, 1H),

3.31 (s, 3H), 3.28 (s, 3H),

1.24 (d, J= 7.1 Hz, 3H)

Y2115

(thin film)

3092, 2923,

1654, 1625,

1486, 1437,

1353

ESIMS m/z

277 ([M+H])

1 FINMR (CDCI3) 6 8.91 (d,

J= 2.7 Hz, 1H), 8.60 (dd, J

= 4.8, 1.4 Hz, 1H), 8.02

(ddd, J= 8.3, 2.6, 1.4 Hz,

1H), 7.91 (s, 1H), 7.44

(ddd, J= 8.4, 4.8, 0.8 Hz,

1H), 5.15 (s, 2H), 3.30 (s,

3H), 1.89 (s, 3H)

709

17149

Y2116

(thin film)

3068, 2977,

2932, 2143,

1653, 1440

ESIMS ink

365 ([M+H])

'H NMR (CDCI3) 6 9.11 (s,

0.5H), 9.07 (s, 0.5H), 8.63

(td, J= 5.2, 1.4 Hz, 1H),

8.58 (br s, 0.5H), 8.27 (br

s, 0.5H), 8.20 - 8.13 (m,

0.5H), 8.11 (ddd, J= 8.3,

2.7, 1.4 Hz, 0.5H), 7.49 -

7.41 (m, 1H), 4.22 (d, J=

8.1 Hz, 1H), 4.01 (br s,

0.5H), 3.91 -3.63 (m, 1H),

3.62 - 3.48 (m, 0.5H), 2.90

(s, 1.5H), 2.81 (s, 1.5H),

1.57 (d, J= 6.9 Hz, 3H),

1.28- 1.19(m, 3H)

Y2117 ESIMS m/z

381 ((M+H]+ )

IFI NMR (CDCI3) 6 9.09 (d,

J= 2.7 Hz, 1H), 8.68 - 8.57

(m, 2H), 8.06 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.44 (dd,

J=8.4,4.7 Hz, 1H), 4.45

(q, J= 7.0 Hz, 1H),3.98

(dq, J= 14.1, 7.2 Hz, 1H),

3.54 (dq, J= 14.2, 7.1 Hz,

1H), 3.36 (s, 3H), 1.78 (d,

J= 7.0 Hz, 3H), 1.24 (t, J=

7.2 Hz, 3H)

.. "C NMR

(CDCI3) 6

165.5, 148.9,

140.8, 139.9,

135.4, 128.8,

126.4, 124.0,

121.4, 112.1,

62.3, 45.2,

36.8, 13.4,

12.6

Y2118 (thin film)

1676,

ESIMS m/z

333 ([M+H])


6 8.95(d, J= 2.6 Hz, 1H),

8.65 (dd, J= 4.7, 1.3 Hz,

1H), 8.04 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 8.00(s,

1H), 7.65 (s, 2H), 7.52 -

7.39 (m, 1H), 5.15 (s, 2H),

3.75 (q, J= 7.2 Hz, 2H),

1.19(t, J= 7.2 Hz, 3H)

710

17149

Y2119 (thin film)

1655

ESIMS m/z

346 ([M+H])


58.95 (d, J = 2.4 Hz, 1H),

8.62 (dd, J= 4.8, 1.4 Hz,

1H), 8.00 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.69 (s,

1H), 7.52 - 7.43 (m, 2H),

7.05 (t, J= 1.0 Hz, 1H),

6.89 (t, J = 1.2 Hz, 1H),

4.31 (s, 2H), 3.68 (d, J=

6.7 Hz, 2H), 2.56 (t, J= 6.2

Hz, 2H), 1.13 (t, J = 7.2

Hz, 3H)

Y2120 (thin film)

1682

ESNS m/z

333 ((M+Hr)


59.02 (d, J= 2.5 Hz, 1H),

8.65 (dd, J= 4.8, 1.4 Hz,

1H), 8.26 (s, 1H), 8.08

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.74(d, J= 1.0 Hz,

1H), 7.70(d, J= 0.9 Hz,

1H), 7.48 (ddd, J= 8.3,

4.8, 0.6 Hz, 1H), 5.09 (s,

2H), 3.74 (q, J= 7.0 Hz,

2H), 1.17(t, J= 7.2 Hz,

3H)

Y2121 (thin film)

1679,

ESIMS m/z

333 ([M+Fi])

1 H NMR (400 MHz,


= 2.7, 0.8 Hz, 1H), 8.62

(dd, J = 4.8, 1.4 Hz, 1H),

7.99 (ddd, J= 8.4, 2.8, 1.5

Hz, 1H), 7.52 - 7.41 (m,

3H), 7.06 (t, J = 1.1 Hz,

1H), 6.89 (t, J = 1.3 Hz,

1H), 4.32 (t, J = 6.2 Hz,

2H), 3.22 (s, 3H), 2.60 (t, J

= 6.2 Hz, 2H).

711

17149

Y2122 (thin film)

1676

ESIMS m/z

333 ([M+Hr)

'H NMR (400 MHz, CD03)

6 8.99 (d, J = 2.6 Hz, 1H),

8.67 (dd, J= 4.7, 1.4 Hz,

1H), 8.55 (s, 1H), 8.15 (s,

1H), 8.07 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 7.49 (ddd,

J= 8.3, 4.8, 0.6 Hz, 1H),

5.37 (s, 2H), 3.76 (q, J=

7.2 Hz, 2H), 1.21 (t, J= 7.2

Hz, 3H)

Y2123 (thin film)

1658

ESIMS m/z

348 ([M+Hr)


6 8.96 (d, J= 2.6 Hz, 1H),

8.79(s, 1H), 8.64 (dd, J=

4.8, 1.4 Hz, 1H), 8.03 (ddd,

J= 8.3, 2.7, 1.4 Hz, 1H),

7.89 (s, 1H), 7.47 (ddd, J=

8.3, 4.8, 0.6 Hz, 1H), 4.75

(t, J= 5.7 Hz, 2H), 3.66 (q,

J= 7.2 Hz, 2H), 2.86 - 2.71

(m, 2H), 1.12 (t, J= 7.2 Hz,

3H)

Y2124

'H NMR (400 MHz,

DMSO-d6): 09.75 (s, 1H),

9.03 (d, J= 2.32 Hz, 1H),

8.94 (s, 1H), 8.58 (d, J=

2.08 Hz, 1H), 8.41 (t, J=

2.20 Hz, 1H), 2.73-2.80

(m, 1H), 1.10 (d, J= 6.80

Hz, 6H)

Y2125 ESIMS m/z

353 ([M+H])

'H NMR (400 MHz,

DMSO-d6): 6 10.05 (s, 1H),

9.03 (s, 1H), 8.95 (s, 1H),

8.58 (d, J= 2.08 Hz, 1H),

8.43 (t, J= 2.20 Hz, 1H),

2.69-2.73 (m, 2H), 2.55-

2.63 (m, 2H)

712

17149

Y2126 ESIMS m/z

396 am-fin

1 H NMR (400 MHz,

Me0D): 6 8.99 (d, J= 2.24

Hz, 1H), 8.77(d, J= 9.16

Hz, 1H), 8.61 (d, J= 1.92

Hz, 1H), 8.44 (t, J= 2.08

Hz, 1H), 2.76-2.79 (m, 2H),

2.56-2.68 (m, 2H) (note:

NH proton Is not seen)

Y2127

1 FINMR (400 MHz,

DMSO-d6): 69.73 (s, 1H)

8.91 (s, 1H), 8.69 (s, 1H),

8.30 (s, 1H), 7.80 (s, 1H),

3.93 (s, 3H), 2.74-2.79 (m,

1H), 1.11 (d, J = 6.80 Hz,

6H)

Y2128

ESIMS

m/z 349

([M+H])

I FINMR (400 MHz,

Me0D): 68.82 (s, 1H),

8.70 (d, J=2.04 Hz, 1H),

8.32 (d, J= 2.52 Hz, 1H),

8.02 (t, J= 2.32 Hz, 1H),

4.04 (s, 3H), 2.78 (t, J=

8.04 Hz, 2H), 2.59-2.65

(m, 2H)

Y2129

ESIMS

m/z 277 ([M-

HD

'H NMR (400 MHz,

DMSO-d6): 69.71 (s, 1H),

8.83 (m, 2H), 8.37 (d, J=

1.04 Hz, 1H), 8.06 (s, 1H),

2.73-2.79 (m, 1H), 2.37 (s,

3H), 1.10(d, J= 6.80 Hz,

6H)

Y2130 ESIMS m/z

331 ([M-Hr)

'H NMR (400 MHz,

DMSO-d6): 6 10.02 (s,

1H), 8.84 (m, 2H), 8.37 (s,

1H), 8.07 (s, 1H), 2.37 (s,

3H), 2.72 (t, J= 6.76 Hz,

2H), 2.55-2.69 (m, 2H)

713

17149

Y2131 ESIMS m/z

313 ([M+H])

'H NMR (400 MHz,

DMSO-d6): 69.04 (m, 2H),

8.66 (s, 1H), 8.42 (s, 1H),

3.10 (s, 3H), 2.57-2.61 (m,

1H), 0.97(d, J= 6.64 Hz,

6H)

Y2132 ESIMS m/z

367 ((M+Hr)

'H NMR (400 MHz,

Me0D): 69.00 (d, J= 2.12

Hz, 1H), 8.71 (s, 1H), 8.59

(d, J= 1.96 Hz, 1H), 8.37

(t, J= 2.24 Hz, 1H), 3.25

(s, 3H), 2.51 (q, J= 5.20

Hz, 4H)

Y2133 ESIMS m/z

357 ([M+H])

1 H NMR (400 MHz,

CDCI3): 68.87 (s, 1H),

8.68 (s, 1H), 8.27 (s, 1H),

8.00 (s, 1H), 3.23 (s, 3H),

2.57-2.64 (m, 1H), 1.10 (d,

J= 6.72 Hz, 6H)

Y2134 ESIMS m/z

411 ([M+Hr)

I FI NMR (400 MHz,

CDCI3): 68.87 (s, 1H),

8.69 (s, 1H), 8.28 (t, J=

2.08 Hz, 1H), 8.00 (s, 1H),

3.26 (s, 3H), 2.48-2.56 (m,

2H), 2.41 (t, J= 7.28 Hz,

2H)

Y2135 ESIMS m/z

309 ([M+H])

I ll NMR(400 MHz, DMS0-

de ): 6 9.03(s, 1H), 8.66(d,

J= 2.08 Hz, 1H), 8.31 (d, J

= 2.52 Hz, 1H), 7.78 (t, J=

2.28 Hz, 1H), 3.92 (s, 3H),

3.09 (s, 3H), 2.54-2.58 (m,

1H), 0.84 (d, J= 6.96 Hz,

6H)

714

17149

Y2136 ESIMS m/z

363 ([M+H]+)

'H NMR (400 MHz,

Me0D): 58.70 (s, 1H),

8.62(d, J= 2.08 Hz, 1H),

8.28 (d, J = 2.52 Hz, 1H),

7.84 (t, J= 2.32 Hz, 1H),

3.25 (s, 3H), 3.99 (s, 3H),

2.47-2.58 (m, 4H)

Y2137 ESIMS m/z

293 ([M+Hr)

1 11 NMR (400 MHz,

Me0D): 58.84 (d, J = 1.92

Hz, 1H), 8.71 (s, 1H), 8.42

(s, 1H), 8.11 (s, 1H), 3.22

(s, 3H), 2.66-2.72 (m, 1H),

2.49 (s, 3H), 1.08 (d, J =

6.72 Hz, 6H)

Y2138

ESIMS m/z

348

([M+1+Fin

I FI NMR (400 MHz,

Me0D): 6 8.83 (s, 1H),

8.65 (s, 1H), 8.42 (s, 1H),

8.11 (s, 1H), 3.24 (s, 3H),

2.48-2.51 (m, 7H)

Y2139

ESIMS m/z

283 ([M+H] + ),

281 ([M-Hr)

IFI NMR (400 MHz,


= 2.7, 0.7 Hz, 1H), 8.65 (s,

1H), 8.56 (dd, J= 4.8, 1.5

Hz, 1H), 7.99 (ddd, J = 8.4,

2.7, 1.5 Hz, 1H), 7.40 (ddd,

J — 8.4, 4.8, 0.8 Hz, 1H),

7.32 (s, 1H), 2.98 - 2.88

(m, 2H), 2.82 - 2.74 (m,

2H), 1.72 (t, J = 8.4 Hz,

1H)

Y2140 ESIMS nilz

356 ([Mr)

I FI NMR (400 MHz,

CDCI3): 68.87 (s, 1H),

8.68 (s, 1H), 8.27 (s, 1H),

8.00 (s, 1H), 3.23 (s, 3H),

2.57-2.64(m, 1H), 1.10(d,

J = 6.72 Hz, 6H)

715

17149

ESIMS m/z

I ll NMR (400 MHz,

CDCI3): 68.87 (s, 1H),

8.69 (s, 1H), 8.28 (t, J=

Y2141 411 2.08 Hz, 1H), 8.00(s, 1H),

([M+2+Hr) 3.26 (s, 3H), 2.48-2.56 (m,

2H), 2.41 (t, J= 7.28 Hz,

2H)


J=2.6 Hz, 1H), 8.62 (dd, J "C NMR

= 4.8, 1.4 Hz, 1H), 8.05 (CDCI3) 6

(ddd, J= 8.3, 2.7, 1.5 Hz, 165.8, 148.6,

1H), 7.96 (s, 1H), 7.46 (dd, 141.2, 140.0,

ESIMS m/z J= 8.4, 4.7 Hz, 1H), 6.44 Y2142 135.6, 129.0,

277 ([M+Hr) (dd, J= 16.8, 2.0 Hz, 1H), 127.6, 126.3,

6.18 (dd, J= 16.7, 10.3 Hz, 126.3, 124.1,

1H), 5.63 (dd, J= 10.3, 1.9 123.8, 44.1,

Hz, 1H), 3.78(q, J=7.2 13.0

Hz, 2H), 1.20 (t, J= 7.2

Hz, 3H)


6 8.97 (d, J= 2.5 Hz, 1H),

8.63 (dt, J = 4.7,1.6 Hz,

1H), 8.06 (ddd, J= 8.3,

3.9, 2.5 Hz, 1H), 7.95 (s,

1H), 7.52 - 7.38 (m, 1H),

6.50 (d, J= 9.2 Hz, 0.7H),

(thin film) ESIMS m/z 5.50 (d, J= 8.5 Hz, 0.3H), Y2143

1649 413 ((WM') 3.90 - 3.53 (m, 2H), 2.37

(dd, J= 8.5, 5.3 Hz, 0.4H),

1.90- 1.81 (m, 0.6H), 1.62

(d, J= 8.4 Hz, 0.6H), 1.39 -

1.34 (m, 0.4H), 1.29 (s,

1.5H), 1.28 (s, 1.5H), 1.17-

1.13 (m, 3H), 1.09 (s,

1.5H), 1.02 (s, 1.5H)

716

17149

(thin film) ESIMS rniz


6 8.92(d, J = 2.7 Hz, 1H),

8.65 - 8.51 (m, 1H), 8.02

(d, J = 8.3 Hz, 1H), 7.90 (s,

Y2144 355.3 1H), 7.42 (dd, J= 8.4, 4.8 1704

(1M+Hr) Hz, 1H), 4.54 (dt, J = 47.0,

5.7 Hz, 2H), 3.72 (t, J = 7.1

Hz, 2H), 2.00 (dp, J= 26.1,

6.3 Hz, 2H), 1.44 (s, 9H)

1 H NMR (CDC13) 68.97

(dd, J = 2.7, 0.7 Hz, 1H), "C NMR

8.63 (dd, J = 4.8, 1.5 Hz, (CDC13) 6

1H), 8.08 - 7.99 (m, 2H), 171.6, 148.8,

ESIMS tniz 7.46 (ddd, J= 8.3, 4.8, 0.7 140.7, 140.2,

Y2145 372 (1M+H1)

Hz, 1H), 5.26 (t, J = 6.5

Hz, 1H), 3.71 (q, J = 7.2

135.6, 126.6,

126.4, 124.1,

Hz, 2H), 3.41 -3.30 (m, 123.3, 44.0,

2H), 2.96 (s, 3H), 2.47 (dd, 40.2, 39.2,

J = 6.2, 4.8 Hz, 2H), 1.17 34.6, 13.1

(1, J = 7.2 Hz, 3H)

'H NMR (COCI3) 68.95 (d,

J = 2.6 Hz, 1H), 8.63 (dd, J

= 4.8, 1.5 Hz, 1H), 8.05

(ddd, J = 8.3, 2.7, 1.5 Hz,

ESIMS m/z 1H), 7.95(s, 1H), 7.47 (dd, "F NMR

Y2146 J = 8.3, 4.7 Hz, 1H), 3.71 (CDCI3) 6 - 404 (1M+Hr)

(q, J = 7.1 Hz, 2H), 2.72 (1, 65.19

J = 7.1 Hz, 2H), 2.64 - 2.53

(m, 2H), 2.38 - 2.21 (m,

4H), 2.17 (s, 3H), 1.16 (1, J

= 7.2 Hz, 3H)

717

17149

Y2147 (thin film)

3575, 1703

HRMS—FAB

(m/z) [WM

calcd for

Ci6H2OCIN40

3, 351.1218;

found,

351.1237


6 8.94 (d, J= 2.7 Hz, 1H),

8.57 (dd, J= 4.8, 1.5 Hz,

1H), 8.12 - 7.89 (multiple

peaks, 2H), 7.41 (dd, J=

8.4, 4.7 Hz, 1H), 4.04 (d, J

= 14.8 Hz, 1H), 3.42 (br s,

1H), 3.27 (s, 1H), 2.89 -

2.80(m, 1H), 2.57 (dd, J=

4.7, 2.6 Hz, 1H), 1.45 (s,

9H)

Y2148 (thin film)

3122, 1752

HRMS—FAB

(m/z)(M+Hr

calcd for

C12H 12CIN40

3, 295.0592;

found,

295.0600


6 9.02 - 8.93 (m, 1H), 8.56

(dd, J= 4.8, 1.5 Hz, 1H),

8.45 (s, 1H), 8.03 (ddd, J=

8.3, 2.7, 1.4 Hz, 1H), 7.42

(ddd, J= 8.3, 4.8, 0.7 Hz,

1H), 4.82 (dddd, J= 8.9,

6.9, 4.0, 3.0 Hz, 1H), 4.28

(t, J= 8.8 Hz, 1H), 4.11

(dd, J= 8.7, 6.8 Hz, 1H),

4.02 (dd, J= 12.8, 3.0 Hz,

1H), 3.78 (dd, J= 12.7, 4.0

Hz, 1H), 3.49(s, 1H)

13C NMR (101

MHz, CDCI3) 6

155.84,

148.05,

139.96,

135.80,

134.93,

126.25,

124.04,

122.92,

119.95, 74.51,

62.61, 46.65

Y2149

(thin film)

3583, 1739,

1704

HRMS—FAB

(m/z) [WM+

calcd for

C17linCIN40

4, 381.1324;

found,

381.1331


08.93 (d, J= 2.7 Hz, 1H),

8.58 (dd, J= 4.8, 1.4 Hz,

1H), 8.02 (d, J= 8.1 Hz,

1H), 7.96 (s, 1H), 7.43 (dd,

J= 8.3, 4.7 Hz, 1H), 4.25

(t, J= 5.4 Hz, 2H), 3.83 (t,

Jr 5.4 Hz, 2H), 2.03 (s,

3H), 1.42 (s, 9H)

718

17149

Y2150 (thin film)

1660

ESIMS m/z

463 ([M+H])


5 9.00 (d, J= 2.5 Hz, 1H),

8.65 (dd, J= 4.8, 1.4 Hz,

1H), 8.10 - 8.04 (m, 2H),

7.48 (ddd, J= 8.4, 4.8, 0.7

Hz, 1H), 3.89 - 3.59 (m,

6H), 2.93 - 2.76 (m, 4H),

1.19(t, J= 7.2 Hz, 3H)

Y2151 (thin film)

3394, 1695

HRMS—FAB

(m/z) [WM

calcd for

CI3H2OCIN40

3, 339.1218;

found,

339.1227

1 11NMR (400 MHz, CDCI3)

68.92 (d, J= 2.8 Hz, 1H),

8.57 (dd, J= 4.8, 1.5 Hz,

1H), 8.08 - 7.89 (multiple

peaks, 2H), 7.42 (dd, J=

8.3, 4.7 Hz, 1H), 3.83 (q, J

= 5.1 Hz, 2H), 3.73 (dd, J=

5.7, 4.6 Hz, 2H), 2.48 (s,

1H), 1.45 (s, 9H)

Y2152 (thin film)

3351, 1694

HRMS—FAB

(m/z) [M+H]'

calcd for

C13H2714502,

392.1848;

found,

392.1850


68.91 (d, J= 2.6 Hz, 1H),

8.57 (dd, J= 4.7, 1.4 Hz,

1H), 8.02 (multiple peaks,

J= 7.2 Hz, 2H), 7.42 (dd, J

= 8.3, 4.8 Hz, 1H), 3.71 (t,

J= 7.2 Hz, 2H), 2.71 (s,

1H), 2.58 (multiple peaks,

5H), 1.83 (s, 3H), 1.78

(multiple peaks, J= 3.3 Hz,

4H), 1.64- 1.30 (multiple

peaks, 6H)

719

17149

Y2153 (thin film)

1704

HRMS—FAB

(m/z) [WM '

calcd for

C151419CIFN,

2,

341.1175;

found,

341.1178


58.93 (d, J= 2.7 Hz, 1H),

8.57 (dd, J= 4.8, 1.4 Hz,

1H), 8.01 (dt, J= 8.6, 1.7

Hz, 1H), 7.93 (s, 1H), 7.42

(dd, J= 8.4, 4.7 Hz, 1H),

4.70 (br s, 1H), 4.58 (br s,

1H), 3.84 (dt, J= 26.3, 4.8

Hz, 2H), 1.44 (s, 9H)

Y2154 (thin film)

1740, 1667

HRMS—FAB

(m/z) [WM

calcd for

C121-112CIF3N4

3,

419.1092;

found,

419.1098


58.96 (d, J= 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.05 (ddd, J = 8.3,

2.7, 1.4 Hz, 1H), 8.02 (s,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 4.30(t, J= 6.4

Hz, 2H), 3.71 (q, J= 7.1

Hz, 2H), 2.66 (t, J= 6.5

Hz, 2H), 2.57 - 2.39


(t, J= 7.2 Hz, 3H)

I9F NMR (376

MHz, CDCI3) 5

-66.02

Y2155 (thin film)

1707

HRMS—FAB

(m/z) [WM'

calcd for

Ci4HisCIF3N4

02,

363.0830;

found,

383.0842


5 8.92 (d, J= 2.7 Hz, 1H),

8.59 (dd, J= 4.8, 1.5 Hz,

1H), 8.02 (ddd, J= 8.4,

2.7, 1.5 Hz, 1H), 7.86(s,

1H), 7.43 (dd, J= 8.4, 4.7

Hz, 1H), 4.37 (d, J= 43.7

Hz, 2H), 3.67 (q, J= 7.1

Hz, 2H), 2.49 (d, J= 45.5

Hz, 2H), 1.20 (t, J= 7.2

Hz, 3H)

19F NMR (376

MHz, CDCI3) 5

-64.89

720

17149

Y2156 (thin film)

1709

HRMS—FAB

(m/z) [M+1-1] +

calcd for

Ci5HI1CIF3N4

02,

377.0987;

found,

377.0997


58.93 (d, J = 2.6 Hz, 1H),

8.59 (dd, J= 4.8, 1.5 Hz,

1H), 8.03 (ddd, J= 8.4,

2.7, 1.4 Hz, 1H), 7.89 (s,

1H), 7.44 (dd, J= 8.4, 4.8

Hz, 1H), 4.17 (br s, 2H),

3.66 (q, J= 7.1 Hz, 2H),

2.40- 1.75 (multiple peaks,

4H), 1.20 (t, J= 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-64.89

Y2157 (thin film)

1647

HRMS—FAB

(m/z) [WM'

calcd for

C I 5HI8CIF3N3

0, 376.1146;

found,

376.1155


6 9.04 - 8.80 (m, 1H), 8.60

(d, J= 5.0 Hz, 1H), 8.00

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.83 (s, 1H), 7.44 (dd,

J=8.3,4.7 Hz, 1H), 3.54

(q, J= 7.1 Hz, 2H), 3.50 -

3.42 (m, 2H), 2.67 (s, 3H),

2.45- 2.25(m, 2H), 1.18 (t,

J = 7.0 Hz, 3H)

19F NMR (376

MHz, CDC13) 6

-65.22

Y2158 (thin film)

3332, 1650

HRMS—FAB

(m/z) [WM'

calcd for

Cl4H16CIF3N3

0, 362.0990;

found,

362.0996

1 1-I NMR (400 MHz, CDCI3)

6 8.94 (d, J = 2.7 Hz, 1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.95(s,

1H), 7.46 (dd, J= 8.3, 4.8

Hz, 1H), 4.65 (t, J= 6.0

Hz, 1H), 3.68 (q, J= 7.1

Hz, 2H), 3.47 (q, J= 6.3

Hz, 2H), 2.36 (qt, J= 10.9,

6.4 Hz, 2H), 1.16 (t, J= 7.1

Hz, 3H)

19F NMR (376

MHz, CDCI3) 6

-64.96.

721

17149

Y2159 (thin film)

1664

HRMS-FAB

(m/z) [WM+

calcd for

Ci4H13FCI3N4

OS,

379.0602;

found,

379.0612

I I-1 NMR (400 MHz, CDCI3)

58.95 (d,J=2.7Hz,1H),

8.63 (dd, J= 4.8, 1.4 Hz,

1H), 8.06 (ddd, J= 8.3,

2.8, 1.5 Hz, 1H), 8.01 (s,

1H), 7.46 (dd, J= 8.4, 4.7

Hz, 1H), 3.75 (q, J= 7.2

Hz, 2H), 3.00 (dd, J= 9.3,

6.3 Hz, 2H), 2.53 - 2.35

(m, 2H), 1.20(t, J= 7.2 Hz,

3H)

I9F NMR (376

MHz, CDCI3) 5

-66.45.

Y2160 (thin film)

3335, 1650

HRMS-FAB

(m/z)(M+Hr

Gala! for

C I5H 1 8CIF3N3

0,376.1146;

found,

376.1155


15 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J=4.8,1.4

Hz, 1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.97 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.7 Hz, 1H), 4.49 (t, J

= 6.0 Hz, 1H), 3.68(q, J=

7.2 Hz, 2H), 3.28 (q, J=

6.7 Hz, 2H), 2.25 - 2.02

(m, 2H), 1.83- 1.67 (m,

2H), 1.16 (t, J = 7.1 Hz,

3H)

I9F NMR (376

MHz, CDCI3) 5

-66.15

Y2161 (thin film)

1708

HRMS-FAB

(m/z) [M+1-1]+

caicd for

C131-11801F2N4

02,

359.1081;

found,

359.1085


•5 8.93(d, J= 2.7 Hz, 1H),

8.58 (dd, J= 4.8, 1.4 Hz,

1H), 8.01 (dt, J= 8.2, 2.1

Hz, 1H), 7.92 (s, 1H), 7.43

(dd, J= 8.3, 4.7 Hz, 1H),

6.07 (t, J= 56.1 Hz, 1H),

3.84 (dt, J=13.5, 7.3 Hz,

2H), 1.61 -1.32 (m, 9H)

I9F NMR (376

MHz, CDCI3) 5

-122.47

722

17149

Y2162 (thin film)

1716

HRMS—FAB

(m/z)[M+Hr

calcd for

0151-112CIF3N4

02,

377.0987;

found,

377.0991

I FI NMR (400 MHz, CDC13)

58.93 (d, J= 2.7 Hz, 1H),

8.59 (dd, J= 4.6, 1.4 Hz,

1H), 8.01 (d, J= 8.5 Hz,

1H), 7.95 (s, 1H), 7.49 -

7.37 (m, 1H), 4.17 (q, J=

8.6 Hz, 2H), 1.54 (s, 3H),

1.43 (s, 6H)

. n ''F NMR (376

MHz, CDCI3) 6

-70.99

Y2163 (thin film)

1701

HRMS—FAB

(m/z) [WM'

calcd for

C151-119C12N4

02,

357.0880;

found,

357.0885


58.93 (d, J= 2.6 Hz, 1H),

8.58 (dd, J= 4.8, 1.5 Hz,

1H), 8.07 - 7.99 (m, 1H),

7.97 (s, 1H), 7.43 (dd, J=

8.4, 4.8 Hz, 1H), 3.88 (t, J

= 6.2 Hz, 2H), 3.70 (s, 2H),

1.62- 1.32(m, 9H)

Y2164 (thin film)

3334, 1650

HRMS—FAB

(m/z) [WM

calcd for

C141-116CIF3N5

0,362.0990;

found,

362.0993


58.91 (d, J= 2.6 Hz, 1H),

8.60 (dd, J= 4.8, 1.4 Hz,

1H), 7.97 (ddd, J= 8.3,

2.6, 1.4 Hz, 1H), 7.77 (s,

1H), 7.44 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 3.99 (q, J

= 9.2 Hz, 2H), 3.57 (q, J=

7.1 Hz, 2H), 2.72 (br s,

3H), 1.20 (t, J= 7.1 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-70.24

723

17149

Y2165 (thin film)

3302, 1661

HRMS-FAB

(m/z)[M+Hr

calcd for

C1 31-114CIF3N3

0,348.0833;

found,

348.0838

1 11 NMR (400 MHz, CDCI 3)

IS 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.63 (dd, J= 4.8, 1.5

Hz, 1H), 8.04 (ddd, J= 8.3,

2.7, 1.5 Hz, 1H), 8.00 (s,

1H), 7.46 (ddd, J= 8.4,

4.7, 0.7 Hz, 1H), 4.75 (t, J

= 6.5 Hz, 1H), 3.88 (qd, J=

9.1, 6.5 Hz, 2H), 3.71 (q, J

=7.2 Hz, 2H), 1.17 (t, J =

7.2 Hz, 3H)

19F NMR (376

MHz, CDC13)45

-73.10

Y2166 (thin film)

1686

ESIMS m/z

300 ([M+Hr)


si5 8.97 (dd, J= 2.6, 0.8 Hz,

1H), 8.63 (s, 1H), 8.55 (dd,

J = 4.8, 1.5 Hz, 1H),7.99

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.40 (ddd, J= 8.3,

4.7, 0.8 Hz, 1H), 7.24 (s,

1H), 3.68 (t, J= 6.1 Hz,

2H), 2.66 (t, J= 7.1 Hz,

2H), 2.23 (ddd, J= 7.6,

6.3, 1.1 Hz, 2H)

Y2167 (thin film)

1675

ESIMS m/z

264 ([M+H])


15 8.96 (dd, J= 2.7, 0.8 Hz,

1H), 8.57 (dd, J=4.8,1.4

Hz, 1H), 8.49 (s, 1H), 8.00

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.41 (ddd, J= 8.4,

4.7, 0.7 Hz, 1H), 4.10 -

3.97 (m, 2H), 2.57 (dd, J=

8.6, 7.7 Hz, 2H), 2.23 (tt, J

= 7.8, 6.9 Hz, 2H)

724

17149

Y2168 (thin film)

1691

ESIMS m/z

276 ([M+Hr)


6 8.97 (dd, J= 2.8, 0.7 Hz,

1H), 8.67 (s, 1H), 8.58 (dd,

J= 4.7, 1.4 Hz, 1H),8.01

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.42 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 6.15 (td, J

= 2.8, 0.6 Hz, 1H), 5.54 -

5.45 (m, 1H), 4.10 (dd, J=

7.3, 6.4 Hz, 2H), 2.96 (ddt,

J=7.5,6.5,2.7 Hz, 2H)

Y2169 (thin film)

1704

HRMS-FAB

(m/z) [M+1-1] +

calcd for

C17F120CIN40

2, 347.1269;

found,

347.1282


6 8.93 (dd, J= 2.8, 0.7 Hz,

1H), 8.58 (dd, J=4.8,1.5

Hz, 1H), 8.10 - 8.00 (m,

2H), 7.42 (dd, J= 8.4, 4.7

Hz, 1H), 4.30(q, J=2.4

Hz, 2H), 1.82 (t, J= 2.4

Hz, 3H), 1.46 (s, 9H)

Y2170 (thin film)

1677

HRMS-FAB

(m/z) [M+H]

calcd for

CI3H13CIF3N4

OS,

365.0445;

found,

365.0450


6 8.97 (dd, J= 2.7, 0.7 Hz,

1H), 8.64 (dd, J= 4.8, 1.4

Hz, 1H), 8.10 - 8.01


(ddd, J= 8.3, 4.7, 0.7 Hz,

1H), 3.78 (q, J= 7.2 Hz,

2H), 3.61 (q, J= 9.9 Hz,

2H), 1.22 (t, J= 7.2 Hz,

3H)

"F NMR (376

MHz, CDCI3) 6

-66.63

725

17149


•5 8.94 (dd, J= 2.7, 0.8 Hz,

1H), 8.62 (dd, J= 4.8,1.4

Hz, 1H), 7.99 (ddd, J= 8.4,

(thin film) ESIMS m/z 2.8, 1.5 Hz, 1H), 7.52 - Y2171

1659 332 ([M+H]) 7.41 (m, 3H), 7.06 (t, J=

1.1 Hz, 1H), 6.89(t, J= 1.3

Hz, 1H), 4.32 (t, J= 6.2

Hz, 2H), 3.22 (s, 3H), 2.60

(t, J= 6.2 Hz, 2H)


08.99 (dd, J= 2.7, 0.8 Hz,

1H), 8.66 (dd, J=4.8,1.4

Hz, 1H), 8.15 (s, 1H),8.05

Y2172 (thin film) ESIMS m/z (ddd, J= 8.3, 2.7, 1.4 Hz,

1683 319 (IM4-Hr) 1H), 7.77 (d, J= 1.1 Hz,

1H), 7.73(d, J= 1.1 Hz,

1H), 7.48 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 5.11 (s,

2H), 3.31 (s, 3H)


0 8.92 (dd, J= 2.8, 0.7 Hz,

1H), 8.63 (dd, J= 4.8,1.4

Hz, 1H), 8.19 (s, 1H), 8.01

Y2173 (thin film) ESIMS m/z (ddd, J= 8.3.2.7, 1.5 Hz,

1660 333 ([M+Hr) 1H), 7.91 (s, 1H), 7.86 (s,

1H), 7.46 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 4.51 (t, J

= 6.1 Hz, 2H), 3.21 (s, 3H),

2.76 (t, J= 6.1 Hz, 2H)

726

17149

Y2174 (thin film)

1660

ESIMS ink

333 ([M+H])

'H NMR (400 MHz, CD03)

6 8.95 (d, J = 2.7 Hz, 1H),

8.80 (s, 1H), 8.64 (dd, J=

4.8, 1.5 Hz, 1H), 8.01 (ddd,

J= 8.3, 2.7, 1.4 Hz, 1H),

7.93 (s, 1H), 7.47 (ddd, J=

8.4, 4.8, 0.8 Hz, 1H), 4.94 -

4.56 (m, 2H), 3.21 (s, 3H),

2.84 (dd, J= 6.3, 5.1 Hz,

2H)

Y2175 (thin film)

3325, 1651

HRMS-FAB

(m/z)1M+Fli +

calcd for

C I 8H 1 9CIN50,

356.1273;

found,

356.1276


68.91 (dd, J= 2.7, 0.7 Hz,

1H), 8.60 (dd, J=4.8,1.5

Hz, 1H), 8.01 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.95 (s,

1H), 7.43 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 7.35 -


4.71 (t, J= 5.8 Hz, 1H),

4.42 (d, J= 5.7 Hz, 2H),

3.72 (q, J= 7.2 Hz, 2H),

1.18 (t, J= 7.1 Hz, 3H)

Y2176 ESIMS m/z

304 ((Whi])

I li NMR (CDCI3) 6 8.97 (d,

J=2.7 Hz, 1H), 8.65 (dd, J

= 4.8, 1.4 Hz, 1H), 8.05

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 8.01 (s, 1H), 7.48

(ddd, J= 8.4, 4.8, 0.7 Hz,

1H), 3.73(q, J=7.2 Hz,

2H), 2.67(t, J= 7.1 Hz,

2H), 2.52 (t, J= 7.2 Hz,

2H), 1.18 (t, J = 7.2 Hz,

3H)

727

17149

Y2177

ESIMS m/z

359 ([M+H]),

358 ((M-H])

'H NMR (400 MHz,


(m, 1H), 8.63 (dd, J= 4.7,

1.5 Hz, 1H), 8.05 (ddd, J=

8.3, 2.7, 1.4 Hz, 1H), 7.95

(s, 1H), 7.47 (ddd, J= 8.3,

4.8, 0.8 Hz, 1H), 6.85 (dt, J

= 14.9, 7.3 Hz, 1H), 6.06

(d, J= 15.3 Hz, 1H), 3.78

(q, J= 7.1 Hz, 2H), 2.99 -

2.77 (m, 2H), 1.20 (t, J=

7.2 Hz, 3H)

Y2178

ESIMS m/z

374 ([M+Hr),

345 um-Hr)

'H NMR (Me0H-d4) 69.04

(dd, J= 2.7, 0.7 Hz, 1H),

8.54 (dd, J= 4.9, 1.4 Hz,

1H), 8.38 (s, 1H), 8.24

(ddd, J= 8.4, 2.7, 1.4 Hz,

1H), 7.59 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 3.68 (q, J

= 7.4 Hz, 2H), 3.35 (s, 1H),

3.17 - 3.02 (m, 2H), 2.72-

2.53(m, 2H), 1.15(t, J=

7.2 Hz, 3H)

13C NMR

(Me0H-d4) 6

174.5, 162.1,

148.8, 141.5,

141.0, 137.7,

129.8, 128.,

125.8, 124.7,

45.1, 34.0,

22.0, 13.2

Y2179

(thin film)

3096, 2976,

1660

ESIMS m/z

393 ([M+Hr),

391 (EM-Hr)

I FI NMR (400 MHz,


= 2.7, 0.7 Hz, 1H), 8.64

(dd, J= 4.8, 1.5 Hz, 1H),

8.05 (ddd, J= 8.3, 2.7, 1.5

Hz, 1H), 7.96 (s, 1H), 7.47

(ddd, J= 8.3, 4.8, .8 Hz,

1H), 3.72(q, J= 7.2 Hz,

2H), 3.58(h, J= 7.1 Hz,

1H), 2.71 -2.40 (in, 4H),

2.37 - 2.24 (m, 1H), 1.18(t,

J=7.2 Hz, 3H)

728

17149

Y2180 ES I MS at&

448 ([M+Hr)

1 H NMR (CDC13) 6 8.95

(dd, J= 2.7, 0.7 Hz, 1H),

8.62 (dd, J= 4.8, 1.4 Hz,

1H), 8.04 (ddd,J= 8.3,

2.7, 1.5 Hz, 1H), 7.91 (s,

1H), 7.46 (ddd, J= 8.3,

4.7, 0.8 Hz, 1H), 7.41 -

7.34 (m, 2H), 7.34 - 7.24

(m, 3H), 3.99(t, J= 7.1 Hz,

2H), 3.65(q, J= 7.1 Hz,

2H), 2.90 (s, 3H), 2.46 (t, J

=7.1 Hz, 2H), 1.12 (t, J =

7.2 Hz, 3H)

13C NMR

(CDCI3) 6

170.5, 148.6,

140.6, 140.2,

139.3, 135.6,

129.5 (2 C),

128.4(2 C),

128.2, 126.7,

126.4, 124.1,

123.5, 47.8,

43.8, 37.1,

33.8, 13.0

Y2181 ES I MS ink

534 ([M-PH])

'H NMR (COCI3) 6 8.70 -

8.56 (m, 2H), 7.80 (ddd, J

= 8.3, 2.7, 1.5 Hz, 1H),

7.43 (ddd, J= 8.3, 4.7, 0.8

Hz, 1H), 7.40 - 7.24 (m,

5H), 7.19 (dq, J= 5.8, 2.6,

1.5 Hz, 10H), 6.99 - 6.85

(m, 1H), 3.95 (ddd, J=

14.3, 10.2, 6.1 Hz, 1H),

3.48 (dq, J= 13.2, 6.8, 6.3

Hz, 1H), 2.62 - 2.42 (m,

1H), 1.62 (dd, J= 5.8, 2.9

Hz, 1H), 1.22 (d, J = 1.5

Hz, 1H), 1.19(t, J=7.1

Hz, 3H)

729

17149

Y2182 ESIMS m/z

355 ([p4M]• )

1 H NMR (CDCI3) 58.95 (d,

J= 2.3 Hz, 1H), 8.62 (dd, J

= 4.8, 1.4 Hz, 1H), 8.19 (s,

1H), 8.04 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.51 -

7.41 (m, 1H), 3.30 (br. s,

3H), 1.46 (br s, 2H), 1.16

(br s, 2H)

"C NMR

(CDCI3) 6

168.6, 148.6,

140.2, 139.0,

135.8, 126.4,

124.9, 124.7,

124.1, 33.5,

26.4, 16.5(2

C)

Y2184

(thin film)

3657, 1727,

1666

HRMS-FAB

(m/z) [M+H]

calcd for

C181-117C1N50

2, 370.1065;

found,

370.1066


6 8.98 - 8.90 (m, 1H), 8.62

(dd, J= 4.7, 1.4 Hz, 1H),

8.08(s, 1H), 8.02 (ddd, J=

8.4, 2.7, 1.4 Hz, 1H), 7.69 -


7.56 - 7.48 (m, 1H), 7.49 -


3.77 (q, J= 7.2 Hz, 2H),

1.25(t, J= 7.2 Hz, 3H)

Y2185

ESIMS m/z

309

([M+Nar)


59.82 (d, J= 0.7 Hz, 1H),

8.97 (d, J=2.6 Hz, 1H),

8.63 (dd, J= 4.8, 1.5 Hz,

1H), 8.07 - 8.03 (multiple

peaks, 2H), 7.46 (dd, J=

8.3, 4.8 Hz, 1H), 3.70 (q, J

= 7.1 Hz, 2H), 2.82 (d, J=

6.3 Hz, 2H), 2.45 (t, J= 6.3

Hz, 2H), 1.16 (t, J= 7.2

Hz, 3H)

730

17149

Y2186

(thin film)

3424, 3274,

3152, 3080,

1658, 1602.

1588

HRMS-FAB

(m/z)(M+Hr

calcd for

C11Ht3CIN50,

266.0803;

found,

266.0804


68.89 (d, J= 2.6 Hz, 1H),

8.54 (dd, J= 4.8, 1.4 Hz,

1H), 8.06 (s, 1H), 8.03

(ddd, J= 8.3, 2.7, 1.5 Hz,

1H), 7.48 - 7.39 (m, 1H),

3.61 (q, J= 7.2 Hz, 2H),

2.70(s, 2H), 1.12(t, J=

7.2 Hz, 3H)

Y2187

(thin film)

3487, 1720,

1660

HRMS—FAB

(m/z) [WM'

caicd for

C14H1eC1N40

3, 323.0905;

found,

323.0906

'FiNMR (400 MHz, CDCI 3)

69.00 (s, 1H), 8.59 (d, J=

4.8 Hz, 1H), 8.15 (ddd, J=

8.4, 2.6, 1.4 Hz, 1H), 8.12

(s, 1H), 7.49 (dd, J= 8.4,

4.8 Hz, 1H), 3.72 (q, J=

7.2 Hz, 2H), 3.49 (s, 1H),

2.72 (d, J= 10.6 Hz, 2H),

2.47 (t, J= 6.4 Hz, 2H),

1.16(t, J=7.2 Hz, 3H)

Y2188 (thin film)

1721, 1665

HRMS-FAB

(m/z) [M+Hr

calcd for

C12H 19CIF3N4

02,

403.1143;

found,

403.1149


6 8.97 (d, J = 2.7 Hz, 1H),

8.63 (dd, J= 4.7, 1.4 Hz,

1H), 8.10 - 8.01 (multiple


8.3, 4.8, 0.7 Hz, 1H), 3.68

(q, J= 7.2 Hz, 2H), 2.84-


2.51 -2.34 (multiple peaks,

4H), 1.15 (t, J = 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) 6

-66.60

731

17149

Y2189

(thin film)

3246, 3095,

1728, 1667

HRMS-FAB

(m/z) [M+H]

calcd for

C1 91-113CIN30

3, 400.1171;

found,

400.1173


5 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.62 (dd, J= 4.7, 1.5

Hz, 1H), 8.09 (s, 1H), 8.02

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.67 - 7.55 (multiple


8.3, 4.8, 0.8 Hz, 1H), 6.92 -

6.82 (m, 2H), 3.83(s, 3H),

3.76 (q, J= 7.2 Hz, 2H),

1.24 (t, J= 7.2 Hz, 3H)

Y2190

(thin film)

3097, 1730,

1672

HRMS-FAB

(m/z) [WM'

calcd for

CI3H18CIF3N3

03,

454.0888;

found,

454.0892


15 8.98 - 8.92 (m, 1H), 8.63

(dd, J = 4.8, 1.4 Hz, 1H),

8.09 (s, 1H), 8.03 (ddd, J=

8.3, 2.7, 1.4 Hz, 1H), 7.75-

7.67 (m, 2H), 7.67 - 7.60

(m, 1H), 7.46 (ddd, J= 8.4,

4.8, 0.8 Hz, 1H), 7.31 -

7.19(m, 2H), 3.75(q, J=

7.2 Hz, 2H), 1.24(t, J= 7.2

Hz, 3H)

I9F NMR (376

MHz, CDCI3) 5

-57.66.

Y2191

(thin film)

3245, 3104,

1716, 1681

HRMS-FAB

(m/z)(M+Hr

calcd for

C181112CIF3N3

02,

460.0594;

found,

460.0597

I FINMR (400 MHz, CDCI 3)

5 8.98 - 8.91 (m, 1H), 8.67

(dd, J= 4.8, 1.5 Hz, 1H),

8.10 - 8.02 (multiple peaks,

2H), 7.97 (s, 1H), 7.49

(ddd, J= 8.3, 4.8, 0.7 Hz,

1H), 3.71 -3.59 (m, 2H),

1.19 (t, J= 7.2 Hz, 3H)

732

17149

Y2192

(thin film)

3096, 1737,

1677

HRMS-FAB

(m/z) [M+Hr

calcd for

C1814 15C13N5

02,

438.0286;

found,

438.0291


15 8.95 (dd, J= 2.7, 0.7 Hz,

1H), 8.66 (dd, J= 4.8, 1.5

Hz, 1H), 8.09 - 8.00


(s, 1H), 7.51 -7.43


(dd, J= 8.6, 2.4 Hz, 1H),

7.30 (dd, J= 8.6, 0.5 Hz,

1H), 3.77 - 3.60 (m, 2H),

1.19(t, J= 7.2 Hz, 3H)

Y2193

(thin film)

3246, 3096,

1729, 1670

HRMS-FAB

(m/z) [WM'

calcd for

C19H19C1N50

2, 384.1222;

found,

384.1227


08.95 (s, 1H), 8.62 (d, J=

4.8 Hz, 1H), 8.10 (s, 1H),

8.02 (ddd, J= 8.4, 2.7, 1.4

Hz, 1H), 7.68 (s, 1H), 7.57

-7.49 (m, 2H), 7.45 (dd, J

= 8.4, 4.8 Hz, 1H), 7.24 -

7.16(m, 2H), 3.76 (q, J=

7.2 Hz, 2H), 2.37 (s, 3H),

1.24 (t, J= 7.2 Hz, 3H)

Y2194

(thin film)

3247, 3095,

1741, 1677

HRMS-FAB

(m/z)[M+1-1] +

calcd for

C i8H16CIFN5

02,

388.0971;

found,

388.0974


68.98 (d, J= 2.7 Hz, 1H),

8.66 (dd, J= 4.7, 1.4 Hz,

1H),8.41 (d, J= 14.4 Hz,

1H), 8.10 - 8.05 (multiple

peaks, 2H), 8.02 (td, J=

7.9, 1.9 Hz, 1H), 7.54-


7.31 -7.21 (m, 1H), 7.02

(ddd, J= 12.3, 8.3, 1.1 Hz,

1H), 3.77 (q, J= 7.1 Hz,

2H), 1.24 (t, J= 7.2 Hz,

3H)

19F NMR (376

MHz, CDCI3) •E•

-114.79

733

17149

Y2195

ESIMS m/z

340 ([M+1].),

398 ([M-Hr)

1 H NMR (CDCI3) 6 8.96 (d,

J= 2.5 Hz, 1H), 8.62 (dd, J

= 4.7, 1.2 Hz, 1H), 8.11 —

7.96 (m, 2H), 7.45 (dd, J=

8.3, 4.7 Hz, 1H), 3.99 (s,

2H), 3.72 (q, J= 7.2 Hz,

2H), 3.65 (dd, J= 5.5, 3.3

Hz, 2H), 3.55 (dd, J= 5.5,

3.4 Hz, 2H), 3.35 (s, 3H),

1.17 (1, J=7.2 Hz, 3H)

Y2196

ESIMS

m/z 336

([M+H]')

1 H NMR (CDCI3) 68.95 (d,

J = 2.5 Hz, 1H), 8.63 (d, J

= 4.6 Hz, 1H), 8.04 (ddd, J

= 8.3, 2.6, 1.4 Hz, 1H),

7.99(s, 1H), 7.46 (dd, J=

8.3, 4.7 Hz, 1H), 3.96 (s,

2H), 3.71 (q, J= 7.1 Hz,

2H), 3.33 (d, J= 7.0 Hz,

2H), 1.17(t, J= 7.2 Hz,

3H), 1.10 — 0.94 (m, 1H),

0.60 — 0.36 (m, 2H), 0.25 —

0.11 (m, 2H)

Y2197

(thin film)

2934, 1676,

1459

ESIMS

m/z 365

([M+2Hr)

1 H NMR (CDCI3) 68.95 (s,

1H), 8.64 (s, 1H), 8.04 (d,

J= 8.2 Hz, 1H), 7.98 (s,

1H), 7.47 (dd, J=7.7,4.6

Hz, 1H), 4.10(s, 2H), 3.99

(q, J= 8.7 Hz, 2H), 3.72 (q,

J= 7.1 Hz, 2H), 1.18 (t,J=

7.2 Hz, 3H)

734

17149

Y2198

(thin film)

2923, 1679,

1459

ESIMS

m/z 378

(IM 4+111

1 H NMR (CDCI3) 6 8.94 (d,

J= 2.5 Hz, 1H), 8.64 (dd, J

= 4.7, 1.2 Hz, 1H), 8.03

(ddd, J= 8.3, 2.7, 1.4 Hz,

1H), 7.97 (s, 1H), 7.47 (dd,

J= 8.3, 4.7 Hz, 1H), 4.13

(dd, J= 39.8, 14.9 Hz, 2H),

3.94 (dt, J= 12.9, 6.4 Hz,

1H), 3.71 (q, J= 7.1 Hz,

2H), 1.40(d, J= 6.5 Hz,

3H), 1.18 (t, J = 7.2 Hz,

3H)

Y2199

ESIMS m/z

355.7

((M+Hr),

353.4 ([M-H]-

)


68.98 (d, J = 2.5 Hz, 1H),

8.64 (dd, J= 4.7, 1.3 Hz,

1H), 8.06 (m, 2H), 7.47

(dd, J= 8.3, 4.7 Hz, 1H),

4.62 (dd, J= 52.7, 11.8 Hz,

2H), 4.40 (q, J= 6.6 Hz,

1H), 3.62 (m, 2H), 2.11 (s,

3H), 1.33(d, J= 6.6 Hz,

3H), 1.17(t, J= 7.2 Hz,

3H)

Y2200 (thin film)

1669

ESIMS m/z

318 ([M+H])


68.94 (d, J= 2.6 Hz, 1H),

8.65 (dd, J= 4.7, 1.3 Hz,

1H), 8.02 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.87(s,

1H), 7.53 - 7.44 (m, 1H),

7.35 (s, 1H), 7.07 (s, 1H),

6.89 (s, 1H), 4.61 (s, 2H),

3.28 (s, 3H)

735

17149

Y2201 (thin film)

1675

ESIMS m/z

358 ([M+H])

T H NMR (400 MHz, CDCI 3)

68.95 (d, J= 2.6 Hz, 1H),

8.65 (dd, J= 4.7, 1.4 Hz,

1H), 8.03 (ddd, J= 8.3,

2.7, 1.4 Hz, 1H), 7.84(s,

1H), 7.48 (ddd, J= 8.3,

4.8, 0.4 Hz, 1H), 7.35 (s,

1H), 7.06 (s, 1H), 6.89 (s,

1H), 4.60 (s, 2H), 3.56 (d,

J= 5.5 Hz, 2H), 0.98 (qdd,

J= 7.4, 4.8, 2.6 Hz, 1H),

0.59 - 0.44 (m, 2H), 0.21

(q, J= 4.9 Hz 2H)

Table 3: CPA (MYZUPE) and sweetpotato whitefly-crawier (BEMITA) Rating Table

% Control (or Mortality) Rating

80-100 A

More than 0— Less than 80 B

Not Tested C

No activity noticed in this bioassay D

Table 4. Biological Data for CPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA)

Corn-

pound

No.

MYZUPE

% Ctrl @

200 ppm

BEMITA %

Ctrl @ 200

ppm

596 A A

597 A B

598 A B

599 A B

600 A B

601 A A

602 A A

736

17149

603 A A

604 A A

605 A A

606 A A

607 A A

608 A A

609 A A

610 A A

611 A A

612 A A

613 A A

614 A A

615 B A

616 C C

617 C C

618 C C

619 A A

620 A A

621 A A

622 A A

623 A A

624 A A

625 A A

626 A A

627 A C

628 A A

629 A C

630 A A

631 A A

632 C C

633 C C

634 C C

635 A A

636 A A

637 A A

737

17149

638 A A

639 A A

640 A A

641 A A

642 A A

643 A C

644 A A

645 A A

646 A B

647 A A

648 A A

649 A A

650 A A

651 A A

652 C C

653 A C

654 B B

655 A A

656 A A

657 A A

658 A A

659 B A

660 B B

661 A B

662 A A

663 A B

664 A A

665 A A

666 B A

667 A A

668 A A

669 A A

670 A A

671 A A

672 A A

738

17149

673 A A

674 A A

675 A A

676 A A

677 A A

678 B A

679 A B

680 A A

681 A A

682 A B

683 A A

684 A B

685 A B

686 A A

687 A A

688 A A

689 A A

690 A A

691 B A

692 A A

693 B A

694 A A

695 A A

696 B A

697 B A

698 B A

699 A A

700 B A

701 B A

702 A A

703 A A

704 A A

A A

706 A A

707 A A

739

17149

708 A A

709 D A

710 A A

711 A B

712 A A

713 A A

714 A A

715 A A

716 A A

717 A A

718 B A

719 A A

720 A A

721 B B

722 A B

723 A A

724 A A

725 A A

726 A A

727 A A

728 A A

729 A B

730 A A

731 B A

732 A A

733 C A

734 A A

735 B A

736 A A

737 A A

738 A A

739 B A

740 B B

741 A A

742 A A

740

17149

743 A A

744 A A

745 A A

746 A A

747 A B

748 A A

749 A A

750 A A

751 A A

752 A A

753 D A

754 B A

755 A A

756 A A

757 B A

758 A A

759 A A

760 A A

761 D A

762 A A

763 A A

764 A A

765 A A

766 A A

767 A A

768 A A

769 A B

770 A A

771 A A

772 A A

773 A A

774 A A

775 A A

776 A A

777 A A

741

17149

778 A A

779 A A

780 A A

781 A A

782 A B

783 A A

784 A A

785 A A

786 A B

787 A B

788 B A

789 B A

790 B A

791 B A

792 A A

793 B A

794 B A

795 B A

796 D B

797 B A

798 A A

799 A A

800 A A

801 A A

802 A A

803 A A

804 A A

805 A A

806 A A

807 A B

808 A A

809 A A

810 A A

811 D A

812 B A

742

17149

813 A A

814 B A

815 A A

816 A A

817 A A

818 A A

819 A B

820 A B

821 A A

822 A A

823 B A

824 A A

825 A A

826 A A

827 B A

828 A A

829 A A

830 B B

831 A B

832 A B

833 B B

834 B B

835 B B

836 A B

837 A A

838 A A

839 B D

840 B B

841 A A

842 B A

843 B D

844 A B

845 A A

846 A A

847 B A

743

17149

848 A A

849 A A

850 B A

851 A A

852 A A

853 A A

854 A A

855 A A

856 A A

857 A A

858 A A

859 A A

860 A A

861 A A

862 A A

863 A A

864 A A

865 A B

866 A A

867 B A

868 B A

869 A A

870 A B

871 A B

872 A A

873 A A

874 A A

875 B B

876 A B

877 B A

878 B A

879 A A

880 A A

881 A A

882 B A

744

17149

883 A A

884 A A

885 A A

886 A A

887 A A

888 B A

889 A A

890 B A

891 A A

892 A A

893 A A

894 A A

895 A A

896 B A

897 A A

898 A A

899 A A

900 A A

901 A A

902 A A

903 A A

904 A A

905 A A

906 A A

907 A A

908 A A

909 B A

910 A A

911 A A

912 B A

913 A A

914 A A

915 A A

916 A A

917 A A

745

17149

918 A A

919 A A

920 A A

921 A A

922 A A

923 A A

924 A A

925 A A

926 A A

927 A A

928 B A

929 A A

930 A A

931 A A

932 A A

933 A A

934 A A

935 A A

936 A A

937 A A

938 B A

939 B A

940 B A

941 B A

942 B A

943 B A

944 A A

945 B A

946 B A

947 B A

948 A A

949 A D

950 A A

951 A A

952 A A

746

17149

953 A A

954 A A

955 A A

956 A A

957 A A

958 A A

959 A A

960 A A

961 A A

962 A A

963 A A

964 A A

965 A A

966 A A

967 A A

968 A A

969 A A

970 A A

971 A A

972 B A

973 A A

974 A A

975 B A

976 A A

977 A A

978 A A

979 D A

980 B A

981 A A

982 A A

983 A A

984 B A

985 B A

986 A A

987 A A

747

17149

988 A A

989 A A

990 B A

991 B A

992 A A

993 A A

994 A B

995 A A

996 A A

997 A A

998 A A

999 A A

1000 B A

1001 B A

1002 A A

1003 A A

1004 B A

1005 B A

1006 B A

1007 A A

1008 A A

1009 A A

1010 B A

1011 A A

1012 A A

1013 A A

1014 B A

1015 B A

1016 A A

1017 B A

1018 A A

1019 A A

1020 B A

1021 A A

1022 A A

748

17149

1023 B A

1024 B A

1025 A A

1026 A A

1027 A A

1028 A A

1029 A A

1030 A A

1031 A A

1032 A A

1033 A A

1034 A A

1035 A A

1036 A A

1037 A A

1038 A A

1039 A A

1040 A A

1041 A A

1042 A A

1043 A A

1044 A A

1045 B A

1046 A A

1047 A A

1048 A A

1049 B A

1050 B A

1051 A A

1052 B A

1053 A A

1054 A A

1055 A A

1056 A A

1057 A A

749

17149

V a 9ZOZA

a a LZOZA

V a 9ZOZA

a a GZOZA

a V 4ZOZA

V a EZOZA

V a ZZOZA

a V LZOZA

V a 6 lOZA

a V 9 LOZA

a V L WV.

V V 9 LOZA

V V 9 LOZA

a v p LOZA

V V E LOZA

V V ZLOZA

0 0 L LOZA

a a 0 LOZA

V V 600ZA

a V 900ZA

V a LOOZA

a a 900A

a a GOOZA

V a 400ZA

V V E0OZA

V V ZOOZA

8 a LOOZA

V V 000ZA

0 V V90 L

V V £901.

V V Z901.

V V I. 90 L

V V 0901

V V 6501

V 9 8901

17149

15L

a a E9OZA

a a Z9OZA

V V 1903A

V V 090A

V V 6SOZA

V V 990ZA

V V LGOZA

a V 950A

0 0 950ZA

V a VGOZA

V a Mt).

a V NOZA

V a t GOZA

V V 050ZA

V a 6VOZA

V a 9VOZA

V V LVOZA

V V 9VOZA

V V 5VOZA

V V ttOZA

V V EVOZA

V V EMMA

0 0 LVOZA

V a OVOZA

v a 6EOZA

V V 9EOZA

V V LEOZA

V V 9EOZA

U a 5EOZA

V V VEOZA

V a EEOZA

U a ZEOZA

V V lEOZA

U a OEOZA

V a 6ZOZA

17149

Y2064 B A

Y2065 A A

Y2066 B A

Y2067 B D

Y2068 B A

Y2069 A A

Y2070 A A

Y2071 B A

Y2072 A A

Y2073 A A

Y2074 B A

Y2075 B A

Y2076 B B

Y2077 A A

Y2078 A B

Y2079 A A

Y2080 D A

Y2081 A A

Y2082 A A

Y2083 B A

Y2084 B A

Y2085 A A

Y2088 A A

Y2089 A A

Y2090 A A

Y2091 B A

Y2092 A C

Y2093 B A

Y2094 A A

Y2097 C C

Y2098 B A

Y2099 B A

Y2102 A A

Y2104 A A

Y2105 A A

752

17149

Y2106 A A

Y2107 A A

Y2108 B A

Y2109 B A

Y2110 A A

Y2111 B A

Y2112 B A

Y2113 A A

Y2114 A A

Y2115 B B

Y2116 A A

Y2117 A D

Y2118 A A

Y2119 B A

Y2120 A A

Y2121 A A

Y2122 A B

Y2123 A A

Y2124 B B

Y2125 B B

Y2126 B B

Y2127 D B

Y2128 B B

Y2129 A B

Y2130 B B

Y2131 B A

Y2132 B B

Y2133 B B

Y2134 B B

Y2135 B B

Y2136 B B

Y2137 B D

Y2138 B C

Y2139 B D

Y2140 B B

753

17149

Y2141 B B

Y2142 B A

Y2143 B A

Y2144 C C

Y2145 C C

Y2146 A A

Y2147 C C

Y2148 B B

Y2149 A A

Y2150 A A

Y2151 B C

Y2152 C C

Y2153 A A

Y2154 B A

Y2155 A A

Y2156 A A

Y2157 A A

Y2158 A A

Y2159 A A

Y2160 A C

Y2161 C C

Y2162 C C

Y2163 C C

Y2164 A A

Y2165 A A

Y2166 A B

Y2167 C C

Y2168 A B

Y2169 C C

Y2170 B A

Y2171 B A

Y2172 A A

Y2173 A A

Y2174 A A

Y2175 A A

754

17149

Y2176 A A

Y2177 A A

Y2178 D B

Y2179 B A

Y2180 B A

Y2181 C C

Y2182 C C

Y2184 A A

Y2185 C C

Y2186 C C

Y2187 D B

Y2188 B A

Y2189 B A

Y2190 B A

Y2191 B B

Y2192 B B

Y2193 B A

Y2194 A A

Y2195 B A

Y2196 B A

Y2197 B A

Y2198 A A

Y2199 A A

Y2200 B A

Y2201 B A

755

17149

attachment bond

R4

R1 N R3 R5

Al or

R4

attachment bond

A2

WE CLAIM

1. A composition comprising a molecule according to

'Formula One"

A N R8

I R6

5

wherein

(a) A is either

(b) R1 is H, F, CI, Br, I, CM, NO2, substituted or unsubstituted CI-C6 alkyl, substituted

or unsubstituted C2-C6 alkenyi, substituted or unsubstituted C I -Cis alkoxy, substituted or

10 unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted %C u, cycloaikyl, substituted or

unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Ce-C20 aryl, substituted or

unsubstituted C 1 -C20 heterocyclyi, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(=X1)R9, S(0)R9, S(0),OR9, S(0)N(R9) 2, or R9S(0)nR9,


15 selected from F, CI, Br, I, Chi, NO2, CI-C6 alkyl, OrC6 aikenyl, CI-C6 haloalkyl, C2-05

haloalkenyl, C I-C6 haloaIkyloxy, C2-C6 haloalkenythxy, 03-C10 cycloalkyl, C3-C10 cycloalkenyi,

CrCio halocycloalkyl, C3-C 1 0 halocycloalkenyl, OR9, S(0),OR9, C6-C20 aryl, or C 1 -C20

heterocyclyi, (each of which that can be substituted, may optionally be substituted with R9);

(c) R2 is H, F, Cl, Br, I, CN, NO2, substituted or unsubstituted CI-C6 alkyl, substituted

20 or unsubstituted CrC6 alkenyi, substituted or unsubstituted C 1 -C6 aikoxy, substituted or

unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-00 cycloalkyl, substituted or

756

17149

R4

N



R5

unsubstituted C3-C, 0 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

unsubstituted CI-C20 heterocyclyl, OR9, C(=X1)R9, C(=X1 )0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(X1)R9, SR9, S(0)0R9, or R9S(0) nR9,

wherein each said R2, which Is substituted, has one or more substituents

5 selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, C2-C6

haloalkenyl, Ci-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-Clo cycloalkenyl,

C3-C1 0 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)0R9, C6-C20 aryl, or Creco


(d) R3 Is H, F, CI, Br, I, CN, NO2, substituted or unsubstituted CI-C6 alkyl, substituted

10 or unsubstituted C-rCe alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted or

unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or

unsubstituted CrC10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

unsubstituted C 1-C20 heterocyclyl, 0R9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9)2,

N(R9)C(X1)R9, SR9, S(0)0R9, or R9S(0) nR9,


selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, CrCe alkenyi, C1-C6 haloalkyl, CrCe

haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-Cio cycloalkenyl,

C3-C 10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)0R9, C6-C20 aryl, or C1-C2o


20 (e) when A Is

(1) Al then Al Is either

(a) All

All

where R4 Is H, NO2, substituted or unsubstituted CI-Cs alkyl,

25 substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C1-C6 alkoxy, substituted

or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted CrC10 cycloalkenyl, substituted

or unsubstituted C6-C20 aryl, substituted or unsubstituted CI-C20 heterocyclyl, C(X1)R9,

C(=X1)0R9, C(=X1)N(R9)2, N(R9h, N(R9)C(=X1)R9, S(0)0R9, or R9S(0)„R9,

wherein each said R4, which Is substituted, has one or more

30 substituents selected from F, CI, Br, I, CN, NO2, CI-Co alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, Cr

Ce haloalkenyl, C 1 -C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C 1 0 cycloalkyl, 03-C10 cycloalkenyl,

C3-C1 0 halocycloalkyl, C3-C1 0 halocycloalkenyi, OR9, S(0)0R9, C6-C20 aryl, or C1 -C20

757

17149

heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9), or

(b) Al2



Al2

where R4 Is a C I-C6 alkyl,

5

(2) A2 then R4 Is H, F, Cl, Br, I, CN, NO2, substituted or unsubstituted C 1-C6

alkyl, substituted or unsubstituted C-C alkenyl, substituted or unsubstituted C 1 -C6 alkoxy,

substituted or unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl,

substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Ce-C20 aryl,

10 substituted or unsubstituted CI-C20 heterocyclyl, OR9, C(X1)R9, C(X1)0R9, C(X1)N(R9)2,

N(R9)2, N(R9)C(=X1)R9, SR9, S(0)0R9, or R9S(0) nR9,

wherein each said R4, which Is substituted, has one or more substituents

selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, CrC6 alkenyl, C I -C6 haloalkyl, CrCe

haloalkenyl, C1-C6 haloalkyloxy, CrC6 haloalkenyloxy, CrC1 0 cycloalkyl, C3-C10 cycloalkenyl,

15 C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)0R9, C6-C-20 aryl, or C1-C2o


(f) R5 Is H, F, Cl, Br, I, CN, NO2, substituted or unsubstituted C 1 -C6 alkyl, substituted

or unsubstituted CrC6 alkenyl, substituted or unsubstituted C 1 -C6 alkoxy, substituted or

unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C 3-C 10 cycloalkyl, substituted or

20

unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, OR9, C(=X1)R9,

C(=X1)0R9, C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, SR9, S(0)0R9, or R9S(0) nR9,


selected from F, CI, Br, I, CN, NO2, C1-C6 alkyl, CrC6 alkenyl, CI-C6 haloalkyl, Cree

haloalkenyl, CI -C6 haloalkyloxy, CrC6 haloalkenyloxy, C3-C 1 0 cycloalkyl, C3-C10 cycloalkenyl,

25

C3-C1 0 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(0)„0R9, or C5-C20 aryl, (each of which

that can be substituted, may optionally be substituted with R9);

(g)

(1) when A Is Al then R6 Is R1 1, substituted or unsubstituted C1-C6 alkyl,

substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C 1 -C6 alkoxy, substituted

30 or unsubstituted C2-C6 alkenyloxy, substituted or unsubstituted C3-C 1 0 cycloalkyl, substituted or


758

17149

unsubstituted CI-C2oheterocyclyl, 0R9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9) 2 , N(R9)2,

N(R9)C(=X1)R9, SR9, S(0),OR9, R9S(0),R9, CI-Ce alkyl C8-e#20 aryl (wherein the alkyl and aryl

can Independently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9,

R9X2R9, C(=OXCI-Co alky9S(0)n(CrCe IAA. C(=0)(Ci-05 alkyl)C(=0)0(CI-Co alkyl). (CrCe

5 alky1)0C(=0)(Ce-C2o aryl), (CrCe alkY1 )0C(=OXCI -C6 alkYI). C 1 -05 alkyl-(Co-Cio cyclohaloalkYI).

or (C1-C6 alkeny9C(=0)0(Ci-C6 alkyl), or R9X2C(=X1)X2R9,

wherein each said R6 (except R11), which Is substituted, has one or more

substituents selected from F, Cl, Br, I, CN, NO2, C 1 -C6 alkyl, C2-Ce alkenyl, CI-Co haloalkyl, Cr

Ce haloalkenyl, CI -C6 haloalkyloxy, CrC6 haloalkenyloxy, C3-C10 cycloalkyl, C 3-C1 0 cycloalkenyl,

10 C3-C 10 halocycloalkyl, C3-C10 halocycloalkenyl, 0R9, S(0)0R9, Ce-C20 aryl, or C 1-020


R9),

optionally R6 (except R11) and R8 can be connected in a cyclic


15 from 0, S, or, N, in the cyclic structure connecting R6 and R8, and

(2) when A Is A2 then R6 Is R11, H, substituted or unsubstituted CI-C6 alkyl,

substituted or unsubstituted 02-C6 alkenyl, substituted or unsubstituted C 1 -C6 alkoxy, substituted

or unsubstituted 02-C6 alkenyloxy, substituted or unsubstituted C3-C 10 cycloalkyl, substituted or

unsubstituted CrClo cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

20 unsubstituted CI-C2oheterocyclyl, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)2, N(R9) 2 ,

N(R9)C(=X1)R9, SR9, S(0)0R9, R9S(0) nR9, C1-05 alkyl Ce-C20 aryl (wherein the alkyl and aryl

can Independently be substituted or unsubstituted), C(X2)R9, C(=X1)X2R9, R9X2C(=X1)R9,

R9X2R9, C(=OXCI-Ce aNYOS(0)n(CI-Ce alkYI). C(=0)(C1-C6 alky9C(=0)0(C1-Ce alkyl). (CrCe

alky1)0C(=0)(C6-C20 aryl), (C 1 -C6 alkyl)0C(=OXCI-Ce alkyl), Ci-05 alkyl-(Co-Cio cyclohaloalkY1).

25 or (C1-C6 alkeny)C(=0)0(C1-C6 alkyl), or R9X2C(=X1)X2R9,

wherein each said R6 (except R11), which is substituted, has one or more

substituents selected from F. Cl, Br, I, CN, NO2, CI-Ce alkyl, CrC6 alkenyl, CI-05 haloalkyl. Cr

Ce haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, CrClo cycloalkyl, C3-C 1 0 cycloalkenyl,

CrClo halocycloalkyl, CrClo halocycloalkenyl, OR9, S(0)0R9, C5-C20 aryl, or C1-C2o

30 heterocyclyl, R9aryl, (each of which that can be substituted, may optionally be substituted with

R9),

optionally R6 (except R11) and R8 can be connected in a cyclic


from 0, S, or N, in the cyclic structure connecting R6 and R8;

35 (h) R7 is 0, S, NR9, or NOR9;

(i) R8 is substituted or unsubstituted C I-C6 alkyl, substituted or unsubstituted CrC6

alkenyl, substituted or unsubstituted CI-C6 alkoxy, substituted or unsubstituted CrC6

759

17149

alkenyloxy, substituted or unsubstituted Ce-C10 cycloalkyl, substituted or unsubstituted C 3-C1 0

cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-Cm

heterocyclyl, OR9, OR9S(0)nR9, C(=X1)R9, C(=X1)0R9, R9C(=X1)0R9, R9X2C(=X1)R9X2R9,

C(=X1)N(R9)2, N(R9)2, N(R9)(R9S(0),129), N(R9)C(=X1)R9, SR9, S(0),OR9, R9S(0),R9, or

5 R9S(0),(NZ)R9,


selected from F, Cl, Br, I, CN, NO 2, C1 -C6 alkyl, CrC6 alkenyl, C i-C6 haloalkyl, CarC6

haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, CrCie cycloalkyl, C3-C10 cycloalkenyl,

C3-C1 0 halocycloalkyl, C3-C1 0 halocycloalkenyl, N(R9)S(0)R9, oxo, OR9, S(0)0R9,

10

R9S(0)nR9, S(C)R9, C6-C20 aryl, or C1-C20 heterocyclyl, (each of which that can be substituted,

may optionally be substituted with R9);

0) R9 is (each independently) H, CN, substituted or unsubstituted C 1 -C6 alkyl,

substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C 1-03 alkoxy, substituted

or unsubstituted CrC6 alkenyloxy, substituted or unsubstituted %C10 cycloalkyl, substituted or

15 unsubstituted Ce-C10 cycloalkenyl, substituted or unsubstituted C6-C20 aryl, substituted or

unsubstituted C 1 -Cm heterocyclyl, substituted or unsubstituted S(0)nC1-C6 alkyl, substituted or

unsubstituted N(C 1-C6a1ky92.


selected from F. CI, Br, I, CN, NO2, C1-C6 alkyl, %Cs alkenyl, C 1 -C6 haloalkyl, C2-C6

20 haloalkenyl, C1-C6 haloalkyloxy, CrCe haloalkenyloxy, CrCie cycloalkyl, C 3-C1 0 cycloalkenyl,

C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OC I-C6 alkyl, OC I-C6 haloalkyl, S(0),C1-C6alkyl,

S(0),OCI-C6 alkyl, C6-C20 aryl, or C I -C20heterocycly1;

(k) n is 0, 1, or 2;

(I) X Is N or CRni where Rni is H. F, Cl, Br, I, CN, NO2, substituted or unsubstituted

25 C1-C6 alkyl, substituted or unsubstituted CrC6 alkenyl, substituted or unsubstituted C 1 -C6

alkoxy, substituted or unsubstituted CrC6 alkenyloxy, substituted or unsubstituted C 3-C1 0

cycloalkyl, substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted C6-C20

aryl, substituted or unsubstituted C 1-Cmheterocyclyl, OR9, C(=X1)R9, C(=X1)0R9,

C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, SR9, S(0)R9, S(0)0R9, or R9S(0) nR9,

30

wherein each said R„, which is substituted, has one or more substituents

selected from F, Cl, Br, I, CN, NO2, CI-C6 alkyl, CrC6 alkenyl, C1-C6 haloalkyl, CrCe

haloalkenyl, C 1 -C6 haloalkyloxy, C2-C6 haloalkenyloxy, CrC10 cycloalkyl, C3-C10 cycloalkenyl,

Ce-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(C)0R9, C6-C20 aryl, or C1-C2o

heterocyclyi, (each of which that can be substituted, may optionally be substituted with R9);

35 (m) X1 is (each independently) 0 or S;

(n) X2 Is (each independently) 0, 5, =NR9, or =NOR9;

(o) Z is CN, NO2, C 1 -C6 alkyl(R9), C(=X1)N(R9)2;

760

17149

(p) R11 is 0 I (CEC)R12, wherein Q 1 Is a bond, substituted or unsubstituted CI – Cts

alkyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl,

substituted or unsubstituted C 3-C1 0 cycloalkyl, substituted or unsubstituted C2-C10 cycloalkoxy,

substituted or unsubstituted C I-05 alkylOR9, substituted or unsubstituted C I-C6 alkylS(0)nR9,

5 substituted or unsubstituted C I-05 alkylS(0)n(=NR9), substituted or unsubstituted C 1-C6

alkylN(R9) (where (CEC) Is attached directly to the N by a bond), substituted or unsubstituted

C I -Ce alkylN(R9)2, substituted or unsubstituted GrC6 alkenyloxy, substituted or unsubstituted

C3-C1 0 cycloalkenyl, substituted or unsubstituted C o-C6 alkylC(=R7)Co-C6 alkylR9, substituted or

unsubstituted C0-C6 alkylC(=R7)0R9, substituted or unsubstituted C 1 -C6 alkyl0C0-C6

10 alkylC(=R7)R9, substituted or unsubstituted C I-05alkylN(R9)(C(=R7)R9), substituted or

unsubstituted C I-C6 alkylN(R9)(C(=R7)0R9), substituted or unsubstituted Co-C6 alkyl C(=R7)C0-

Cs alkylN(R9) (where (CEC) Is attached directly to the N by a bond), substituted or unsubstituted

C0-C6alkylC(=R7)CrC6 alkylN(R9)2, OR9, S(0)R9, N(R9)R9, substituted or unsubstituted Cr C20 aryl, substituted or unsubstituted C I-C2o heterocyclyl,

15 wherein each said C1 1 , which is substituted, has one or more substituents

selected from F, CI, Br, I, CN, NO2, C 1 -C6 alkyl, C2-C6 alkenyl, CrCo alkynyl, C1-C6 haloalkyl, Cr

Ce haloalkenyl, C1-C6 haloalkyloxy, C2-C6 haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl,

CrCio halocycloalkyl, C3-C10 halocycloalkenyl, OR9, SR9, S(0)R9, S(0)0R9, C5-C20 aryl, or

CI-C2oheterocyclyl, R9aryl, C 1 -03alkylOR9, C I -C6alkylS(0)nR9, (each of which that can be

20 substituted, may optionally be substituted with R9)

optionally Q 1 and R8 can be connected in a cyclic arrangement, where optionally

such arrangement can have one or more heteroatoms selected from 0, S, or N, In the cyclic

structure connecting Oland R8;

(q) R12 Is 0 1 (except where 011s a bond), F, CI, Br, I, Si(R9)3(where each R9 is

25 Independently selected), or R9;

wherein said molecule is selected from

Y2000

CI 0 CI IS)—( N /S • i

1 CH3

H3C

761

17149

Z9L

E ND

j N /

c 0-4 N P p-4 Of 3 HD DEN w

■ GOOZA

.

N—c1S EP"( \bruin HD DEN ---

POOZA

D c H c H 0 (N/ 1.1

HO 0 13

EOM.

(DELI

041—cliti S 0 0

N. ZOOZA

D c H

E H 3 csi ...r1s1 )=--4

0 0 10

J--2 AZ'

1.00ZA

17149

Y2006

CI ---4 ,--S

Br N 0

1■1j- N F F b 11 3

Y2007 \

CI 0 NS. Jc,ci 14 / N

H3C)

Y2008

CI 0 Hcf0 N-

14 Nx CH?

H3C1

Y2009

CI 0113C C11 3 N -

b H 3

Y2010

,CH3 CI N

N i -CH3 i

N NH

763

17149

Y2011 ■

C ,-CH 3

/ N ‘CH 3

Y2012

CI 0 rCH3 V-5_ ,-- N

N / N CH 3 b H 3

Y2013 ■.

CI 0 CI 1■1-5„h< N / -;_. C 1 H

Y2014 ■

CI 0_

;

#,N VS_ I sh t N / -__

cH3

Y2015 ■.

CI 0 / N

1$5._ N / 1%1‘

/ H,C

' .

764

17149

Y2016 ■

CI 0

IS -- w, CH / II_ 3

cH 3 -

Y2017

CI N-- 14 / l`t CH 3

1 H 3 C

Y2018 ■

d o N- IV / CH3

Y2019 \

Cl 0

illiiii-NA SH bi3

Y2021

H C CI 0 3 • S

tz1-5 N,--(i.F

1%1 f 4rii .... . .3

765

17149

Y2022

\ I Ni.-S-N\

1 H 3 C

Y2023 ■

CI 0 N-=( ,--7-1%0N

-N 14 >

H 3 C

Y2024 CH3

CI 0 N.. 1‘1=-( ,--(N\=-1 Aft'Ix

1 H 3 C

Y2025

CI 13 \

lisIli-Nx CH3 1

C H3

i

Y2026

CI 0 l‘k N-5 ,---rt) A , N

bli 3

766

17149

Y2027 ■

CI 0 N.. 1‘1( ,—( 1%ksei T:IN,_ CH 1

CH3 -

Y2028

CI 0 \

/:%111-5- N._ C 11 A

Y2029

\

CI 0 * TS-5 ,-S N / Nk

i H 3 C

Y2030

H 3 C

) 11 3 C

Y2031

Cil 3 Cl

) H 3 C

767

17149

Y2032

cil 7 N3 ,—.Nrto ' / N ‘,....I

■ H

Y2033

CI 0

kr- 11 C H3

C H3

0

Y2034

■

0

CH3s iL )\-- N. y

N ‘....., H

Y2035 A

C H 3

/ 0

CH3s q

Y2036

0 0 N —

F F

1■I / 11, CH3

768

17149

69L.

N i

N NH 0

N

I

lVOZA

i

1 nt—c , o--i -N

'Ho"( , 0 ID

E ND D`H

ovoa

N-2 0—‘ —N

E HD-7( E HD O C H° 13

6COZA

?

—N 0 13

d

9COZA

DH (N%

(

N—c 1,1'1V —N

I 0 0

LEM

17149

Y2042 ■

C'0 N( N,—<1

N b H 3

Y2043

C'0 N -k.)---.1 N „if L..<1

Y2044

C o

/ N b H3

CH 3

Y2045 ■

d o N- IV /

CH 3

Y2046

CI 0 N- 14 / N

b H3

770

17149

ILL

f --N HD-(0

i f 0 - HD D-H

ID

LGOZA

0 C H

( c ■ N,1$

E HD 0 10

GOV.

C UD 1 k-0 ■

C H 0,./S-i rm C N ID HD,/

6POZA

C H D l$

S --N c

E N ID

SPO ZA

/ Il -- 14

0 ID

LVOZA

17149

Y2052 ■

CI

1■1

N -5" , SH

) CH3 H 3 C

Y2053

CI NS

N_ CH

/1 / loa.

- R 0

0

23

Y2054 ■

CI N- CH 3 14 / N

. .0

0 SC)

CH 3

Y2055

H3C CH 0

3

CI 3 V ... r-CH

NISS-1 1̀' °

..F..

F 11

Y2056

CI (3 N- ---1 14 / N,

11

772

17149

Y 2057 \

C'0 tzl--5.)-1 N ) H 3 C-0

Y2058 •-,

No

C'0

/ N )

0

*

Y2059 N

CI 0 TZ1-51-1

o/ (0

0 ( CH 3

Y2060

CI 0 ili15.11-1

.--C H 3 0

Y2061 ■,

II I

C' 0 N 14 C

CH 3

773

17149

Y2062

c 011 3Cy5 H 3

V ... 13 CH 3

N / it CH3

F

Y2063

C H0113 Cy_C H3 N ,... 0 C H 3

N F.rtf /

b H3 F

Y2064

CI 0 C ItsH

3

V CH 3

N ... "- T`it N'N

H3 C/ H36

Y2065

CI o N1

\ b H3

Y2066 0 CI 0,5)

NVS— N, ■ C H3

774

17149

SLL

DEH A UNA

Chi_c1 ■

d ti -N i 0 13

EHO O EN O E H

-N NI, 0 0

0 H

OLOZA

N %

E H D D E N ? E H Ci.,

e‘N ---( its1-2 N-."--1

0 0

6903A

(JD / 1 \

,1 c 3-14

ID

9903A

110 .3

EHD-K0-1( N

c r 0-H3 E HD 0 - H

L9OZA

17149

912

,D H S

C H ■ 9LOZA D -Th N / lii

-- N H 0 0 ID

D E H ( c .S--i N HD 0 3

SLOZA

13 C HD CHO

N --c 1;1 4 0 ID

0

VLOZA

0 C H ,N < fi 1.1-cl

.S 0 ID C HD

ELM.

D C H ■ ZLOZA

(N-91 a ---N I

ID 0 ID

17149

Y2077

CI /3 a

NVi-Isth-C H3 \ l H 3 C

Y2078

CH3 0

N / N NH

Y2079

n 0 CI 0 N *

)\--N / N N

CH3 bH3

Y2080

CH30 N ,---CH3 / N

•

Y2081

0

CI coit ;La ne-C H

N/ Nie, L CH

L. H 3 3

777

17149

Y2082 ■

CI 0

N-3_ .2, / N ks. CH3 " ' 1- kA-1 3 CH 3

Y2083

CH3 S

i N

lik

Y2084

I %.N*

n 0 CI 0 '-'*,!!...

N ..... N,0 CH3

i N LCH3 bH3

Y2085 ■

q c11 3

ci o. ris.

N-5

14 , N d

) N / H 3 C

I ■ N-

Y2088

0 a 0 1;11

i N t_CH3 N bH3

778

17149

Y2089

r" ■, N

n 0 CI 0 N S CI

. N ru ....n 3

‘CH3

Y2090 CI

ci H3 C

Y2091

tsc CI 0 VNJ

Y2092

CI C H3 0

N-5,4 / N ‘0.1.“,C H 3 ■

1 1...C)

0 0

Y2093

CI 0

N ,...."-SH

S_ N /

■ " > H 3 C

779

17149

081.

H ENO c1-10

,SN r FIN,

10 ZOLZA

z 0 (

DH

r S E • n 0 0

HO 0

660A

E H ? ,■.-14

z143 11 C 0 13

/ 860ZA

H3 13%. -NrN ,..•‘

0,

,,

/1=14 ID

/

L6OZA

e ri,

14— 2 0 0

V6OZA

17149

Y2104

CI 0 .CH3 S

— N — NiSi— N C Os/

‘CH 3 -

Y2105 N..

.CH3

CI 0 S

is,

NI:4-S- N,_ CH 1 — CH3 -

N

Y2106 01 0

\ NA.NH

n31/4.

Y2107 N--

S N CI op

4 / N >

H 3 C

Y2108

CI 0 N-- 14 N

> H 3 C

781

17149

Y2109

y\11 3

NS CI •D

N- CH 3

H3C)

Y2110

0* CH3 CI 0

N- /4 / N

) H 3 C

Y2111

■.

CI 0 N- 14 / N

H3C)

Y2112

CI 0 *

S N

H3C

F_K

> FF

Y2113 ,.

0 CH CI 0 tk 3

N- .14-1‘1 TZ, / N cH 3

cH 3

782

17149

Y2114

0 0 9013

--r-N

ti-NICH3CH:k -

Y2115

‘ `

CI Piz"( 0 \,,e.kNrC H 3

61 11 3 CH 2

Y2116

\

N N- a 0 N

iy, N CH 3 ti fj CH3 nr...

Y2117

CI

"-aN NAy' S‘CH 3

H3C) CH 3

Y2118

1•1") CI 0 isq . N

ti:S_J--/

/ H 3 C

783

17149

Y2119

N .0( ,---7—tr —N

H3C)

Y2120

rrN\

CI 0 ja IS-57,—/ N / sk

H3e

Y2121

CI 0 N Nr-t4 ,---r itil 14 j—N

I-13C)

Y2122 •%,

N br \ CI 0 k e ff

I■15_ IN H3C

/

Y2123

CI 0 N

H3C)

784

17149

Y2124 Cl.,.r.,..( 1%1 0... )

N'

CI

N5_ H CH • / N 3

--( 0 CH3

Y 2125

CI

N-Sil 14 i N

CL(f •[)\—CF3 i N'

Y2126

k ) NI'

CI 0, j—CF3 N-5_ N / 11

Y2127 H3C-0

\ ' H CI 113

tkyNICCH3 'Nck 0

CI

Y2128

CI

-N \ N

'CH 3 F3C

785

17149

Y2129 H C CI

0 NiL(CH3 H CH3

Y2130

H C Ne_

14 ..„,

Cl 0

N F H

Y2131

CH 3

CI Oyitta3 N \ r■y 'CH 3

eN1/4 CI

Y2132

CI N..,

bit n

N‘aa - N oH 3

Y2133 Br li. )

N'

CI 0 CH 3

4, I '. CH 3

786

17149

Y2134

Br CI

N .v.A. As......„.. N N CF3

CH 3

Y2135 \

H 3 C-0

Pir.-.(CI

0 ‘....-A- NAT,CH 3

61-1 3 CH 3

Y2136 i

H 3 C-0

(CI

0

NA-".....)<FF CH 3 F

Y2137

/

H3C

INT r.:(CI

0 ...NANAsyC H 3

tH3CH3

Y2138

Ii C / \

, CI

a H 3 F F

787

17149

Y2139

CI 0 ,...."-SH

I■1- --, N

■ N • H

Y2140

0 CI

N. H 3 C IAN

)t--N

CH 3 :6H 3

\ -

Br

Y2141

CI 0

F aH 3

\ /

Br

Y2142

CI

\ N

0 CH2

Y2143

CI 0

N / N ■ ) H 3 C

CI

CI CH 3

CH 3

788

17149

Y2144

A .I<CH 3 N 0 CH3

F

Y2145 / \

CI 0 0„0

NiL .N :Si,CH3

H30)

H

Y2146

pirz(CI 0 F

F \--A NIA N.VIC F

H3C ) CH 3

Y2147

Isl‘ .. CI0 CH_3

N 0 CH

L\V 3

Y2148

CI

OH

/

789

17149

Y2149

/ CI

Prze 0 CH/ v...sk A ,IcCH 3

N 0 CH 3

CI OtO

CH 3

Y2150

■

F F

0 riLF CI 0 .., ii.;" ,..../-014 NJ-14‘ --3/4--N

H3C/

Y2151

CI0 CH3

1/4.A. A )cCH 3 N 0 CH 3

OH

Y2152

CI y-1,3

N 0 CH 3

A \__/

Y2153

/ CI Ny_ A0 713143

\--A N eC CH 3

Li F

790

17149

Y2154

lc CI 0 F

• NiC-7.%Ir°1„F

0 F LCH3

Y2155

CI 0 F ..\...A A .............je

N 0 F L CH3

Y2156

CI N:_t 9 F

‘-lA NAOleF

LC H3 F

Y2157

\ CI

0 F

N N F 6/1 3

cH 3

Y2158

CI 0 F ...,./. A .71c F

N N F L r, ti .....3

791

17149

Y2159

Plz-fCI

0 F ...,.. .A. ..............)< F

N S F

LCH 3

Y2160

Isizr.,,C1 0 F

\--ANAN F

LCH3 F

/

Y2161

\ , C C

II— 1 5cHnin

Ln 3

y F

Y2162

/ pieCI 0 c}1 3

...4111- 0)CCCH1133 F

F

Y2163

/ pteCI 0 cH3

--s-AriNAO)CCCH1133

CI

792

17149

Y2164

Isii. CI

jo ..., F F

NA

Wi' L a H 3 F CH 3

Y2165

CI 0 F F

NA

N'''t Lf, u F ,..,.. 3

Y2166

CI CI 0,..y._ j NS_ 74 / N

H

Y2167

CI 0

1■1-

Y2168

CI 0

N.S.. CH 2

isr

793

17149

Y2169

C H3 /

Nia 0

N 0 CH 3

Y2170

CI 0

N rThr

LCH3 F

Y2171

CI 0 Nr...."-1

-5. 14 N / N.

CH 3

Y2172

i Art CI 0 k N

N:::( ,—/ N

TZ1-N. CH 3

Y2173

CI o N, NS_ ,--7-N\:_-1N /4 / li

CH 3

794

17149

Y2174 ■

CI iscX.

N .._ CH3

Y2175

CI 0

NAN * L

C H3

Y2176

phga 0

\'''.k NiC• N

H 3 C)

Y2177

■

F F F

CI 0

N-. ;, / N IN )

11 3 C

Y2178 / \

CI 0

N)L-CN N ,

H3C) HN-I4

795

17149

Y2179

F F

CI 0

N§-N\1■1

■ . H 3 C

F

SH

Y2180

CI

N

H 3 C ) NAZ CH 3 *

Y2181 N

410

Y2182

/ CI

0

N aH 3

Y2184

/ CI

\rA NAN

H 3 C)

*

796

17149

Y2185

PI:.-1C1

0 /

•NiL.,,...0..0

H 3 C)

Y2186

CI 0

/ \---NA

N H2

) H3 CI

Y2187

CI 0

Q-XN#LTh( OH 0 LCH3

Y2188

Pir-f CI

0 F

0 L. C H 3

Y2189 /

H 3 C)

CI 0

N N 0

H ir o'CH3

797

17149

Y2190 CI

Nze 0 0 (}-N......

H ci

A

11 * F _3 _ 0 F

Y2191

CI Isli.—.( 0 0 ‘...A NAN it

) H H 3 C F ..

F

Y2192 1 \

CI NINly, 0 0

•-•"Nd1/4 N

H3C) H CI

* CI

Y2193 / N-..:(0 0 0

14\ANA

N ) H

H 3 C

0 CH3

Y2194 \

CI 0

.VANAN ) H

0

H 3 C

798

17149

Y2195 \

CI

0-CH3 ,

H 3 C

Y2196

CI X--i...NYLo a,

" r)

Y2197

C 0 F

/ Nji"%.' 0J<F F ur

,,) I Ia

Y2198

C F F

/ N 0yk F

H3C) CH3

Y2199

CI 0 n N-

,..a..cm.

14 / N, CH 3 S-CH3 H3C

i

I

799

17149

Y2200

N

CI 0 1:72

1■15_ 1\fr N / • -,_

CH 3

Y2201

1%1 CI 0 NI i

NS. ,---/—

d■

2. A composition according to claim 1 further comprising:

(a) one or more compounds having acaricidal, algicidal, avicidal, bactericidal,

fungicidal, herbicidal, Insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties;

5 or

(b) one or more compounds that are antifeedants, bird repellents, chemosterilants,

herbicide safeners, insect attractants, Insect repellents, mammal repellents, mating disrupters,

plant activators, plant growth regulators, or synergists; or

(c) both (a) and (b).

10

3. A composition according to claims 1 or 2 further comprising an agriculturally acceptable

carrier.

4. A process comprising applying a composition according to claims 1, 2, or 3, to an area to

15 control a pest, In an amount sufficient to control such pest.

5. A process according to claim 4 wherein said pest Is selected from beetles, earwigs,

cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths,

butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks,

20 nematodes, and symphylans.

800

17149

N° 17149 - Organisation Africaine de la Propriété Intellectuelle

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Transcript of N° 17149 - Organisation Africaine de la Propriété Intellectuelle