OA17149A - Pesticidal compositions and processes related thereto - Google Patents

Abstract

This document discloses molecules having the formula (I)

Description

PEST1CIDAL COMPOSITIONS AND PROCESSES RELATED THERETO

CROSS REFERENCES TO RELATED APPLICATIONS

Thîs Application claims priority from, and benefit of, U.S. provisional application serial number 61/639,274 - which was filed on April 27, 2012. The entire content of this provisional application ls hereby incorporated by référencé into this Application.

FIELD OF THE DISCLOSURE

This disclosure ls related to the field of processes to produce molécules that are useful as pesticides (e.g., acarlcides, insecticides, molluscicldes, and nematicides), such molécules, and processes of using such molécules 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 ln agriculture. The worid-wlde agricultural losses amount to biilions of U.S. dollars each year.

Termites cause damage to ail 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 importante, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developing résistance to pesticides in current use. Hundreds of pest species are résistant to one or more pesticides. The development of résistance to some of the oider pesticides, such as DDT, the carbamates, and the organophosphates, is well known. But résistance has even developed to some of the newer pesticides.

Therefore, for many reasons, Including the above reasons, a need exists for new pesticides.

DEFINITIONS

The examples given ln the définitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It ls understood that a substituent should comply with chemical bonding rules and steric compatibüity constraints ln relation to the particular molécule to which it ls 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, pentenyl, and hexenyl.

“Alkenyloxy means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

Alkoxy means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, Isobutoxy, and fert-butoxy.

Alkyl means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (Ca)alkyl which represents n-propyl and isopropyl), (C₄)alkyt which represents n-butyl, seo-butyl, isobutyl, and tert-butyl.

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

“Aryl means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and blphenyl.

“(Cj-Cy) where the subscripts “x and “y are integers such as 1, 2, or 3, means the range of carbon atoms for a substituent - for example, (Ci-C^alkyl means methyl, ethyl, n· propyl, isopropyl, n-butyl, sec-butyl, Isobutyl, and tert-butyl, each individualiy.

Cycloalkenyl means a monocyclic or polycyclic, unsaturated (at least one carboncarbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbomenyl, blcyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.

Cycloalkenyloxy means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbomenyloxy, and blcyclo[2.2.2]octenytoxy.

Cycloalkyi means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbomyl, blcycio[2.2.2]octyl, and decahydronaphthyl.

“Cycloalkoxy means a cycloalkyi further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cydopentyloxy, norbomyloxy, and bicyclo[2.2.2]octyloxy.

Halo means fluoro, chloro, bromo, and lodo.

Haloalkoxy” means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.

Haloalkyl means an alkyl further consisting of, from one to the maximum possible number of, Identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

'Heterocyclyl· 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 aromatic heterocyclyls Include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, Imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, Isothiazolyl, isoxazolyl, oxadiazoiyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, qulnoxalinyl, tetrazolyl, thlazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls Include, but are not limited to, piperazlnyl, 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-dihydroisoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl. Additional examples include the following

thietanyl thietanyl-oxide thietanyl-dioxide.

DETAILED DESCRIPTION

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

R6 wherein (a) A Is either

attachment bond

attachment bond (b) R1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted CpCe alkoxy, substituted or unsubstituted C₂-Ce alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted Ce-Caj aryl, substituted or unsubstituted CrCæ heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)₂₁ N(R9)C(=X1)R9, S(O)_nR9, S(O)_nOR9, S(O)nN(R9)2, or R9S(O)_nR9, wherein each said R1, which ls substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, CrCe alkyl, CrCe alkenyl, CrCe haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, C3-C1Q cycloalkyl, C3-C10 cycloalkenyl, C3-C1Q halocydoalkyl, C3-C10 halocycloalkenyl, OR9, S(O)_nOR9, Ce-C2Q aryl, or C1-C2Q heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(c) R2 ls H, F, Cl, Br, I, CN, NO₂₁ substituted or unsubstituted CrCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted CrCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C₁₍) cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted Ce-Caj aryl, substituted or unsubstituted CrCa, heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)₂, N(R9)C(=X1 )R9, SR9, S(O)„OR9, or R9S(O)_nR9, wherein each said R2, which ls substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, C2-C_B haloalkenyloxy, C3-C1Q cycloalkyl, C3-C10 cycloalkenyl, C3-C10 halocydoalkyl, C3-C10 halocydoalkenyl, OR9, S(O)„OR9, Ce-C2o aryl, or C1-C20 heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(d) R3 ls H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C,-Ce alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C3-C10 cydoalkenyl, substituted or unsubstituted Cg-Cîo aryl, substituted or unsubstituted C^Cîo heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)₂, N(R9)C(=X1)R9, SR9, S(O)_nOR9, or R9S(O)_flR9, wherein each said R3, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ Ci-Ce alkyl, CrCe alkenyl, Ci-Ce haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, Ca-Cw cycloalkyl, Ca-C₁₀ cydoalkenyl, C₃-C₁₀ halocydoalkyl, Ca-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, Ce-Cîo aryl, or CrCao heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(e) when A is (1) A1 then A1 is either (a) A11 attachment bond to carbon

Ail where R4 is H, NO₂, substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted C3-C₁₀ cycloalkyl, substituted or unsubstituted Ca-C₁₀ cydoalkenyl, substituted or unsubstituted Ce-Cîo aryl. substituted or unsubstituted C1-C20 heterocyclyl, C(=X1 )R9, C(=X1)OR9, C(=X1)N(R9)₂₁ N(R9h, N(R9)C(=X1)R9, S(O)nOR9, or R9S(O)„R9, wherein each said R4, which ls substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ C_rCe alkyl, CrCe alkenyl, CrCe haloalkyl, Cr Ce haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, Ca-C₁₀ cycloalkyl, C3-C10 cydoalkenyl, C3-C10 halocydoalkyl, C3-C10 halocycloalkenyl, OR9, S(O)_nOR9, Co-Cm aryl, or C1-C20 heterocydyl, (each of which that can be substituted, may optionally be substituted with R9), or (b) A12

attachment bond to nitrogen

A12 where R4 Is a CrCe alkyl, (2) A2 then R4 Is H, F, Cl, Br, i, CN, NO₂, substituted or unsubstituted CrCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted CrCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted CrCw cycloalkyl, substituted or unsubstituted Cj-Cw cycloalkenyl, substituted or unsubstituted Ce-C2o aryl, substituted or unsubstituted C1-C20 heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)₂, N(R9)C(=X1 )R9, SR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said R4, which Is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, CrCe alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C₁₀ cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(O)_nOR9, Ce-C^ aryl, or CrC2o heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(f) R5 Is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted CrCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted CrC₁₀ cycloalkenyl, substituted or unsubstituted Ce-C2o aryl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, SR9, S(O)_nOR9, or R9S(O)„R9, wherein each said R5, which Is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, CrCe alkyl, CrCe alkenyl, CrCe haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, CrC₁₀ cycloalkenyl, CrC₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, or Ce-Cw aryl, (each of which that can be substituted, may optionally be substituted with R9);

(0) (1) when A Is A1 then R6 is R11, substituted or unsubstituted CrCe alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted CrCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Cs-Cîo aryl, substituted or unsubstituted CrC2o heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂₁ N(R9)₂, N(R9)C(=X1)R9, SR9, S(O)_nOR9, R9S(O)_nR9, C_rCe alkyl Ce-C^ aryl (wherein the alkyl and aryl can Independently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9,

R9X2R9, C(=O)(C_rCe alkyl)S(O)n(C_rCe alkyl), C(=O)(CrCe aikyl)C(-O)O(C_rCe alkyl), (CrCe alkyl)OC(=OXCe-C2o aryl). (C_rCe alkyl)OC(=OXCrCe alkyl), CrCe alkyl-(C₃-Ci₀ cyclohaloalkyl), or (C_rCe alkenyl)C(=O)O(CrCe 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, CrCe alkyl, CrCe alkenyl, CrC₆ haloalkyl, C₂Ce haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, C3-C₁₍₎ cycloalkyl, CrCw cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(O)_nOR9, CS-C20 aryl, or C1-C20 heterocyclyl, R9aryl, (each of which that can be substituted, may optionally be substituted with R9).

optionally R6 (except R11) and R8 can be connected ln a cyclic arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, S, or, N, ln the cyclic structure connecting R6 and R8, and (2) when A Is A2 then R6 is R11, H, substituted or unsubstituted CrC_B alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C3-C₁₀ cycloalkenyl, substituted or unsubstituted Ce-Czj aryl, substituted or unsubstituted CrCzo heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)î, N(R9)₂₁ N(R9)C(=X1)R9, SR9, S(O)_nOR9, R9S(O)_nR9, CrCe alkyl Ce-C» aryl (wherein the alkyl and aryl can independently be substituted or unsubstituted), C(=X2)R9, C(-X1)X2R9, R9X2C(=X1)R9, R9X2R9, C(=O)(C_rCe alkyl)S(O)_n(CrCe alkyl), C(=O)(CrCe alkyl)C(=O)O(C_rCe alkyl), (CrCe alkyl)OC(=O)(Ce-C20 aryl). (CrCe alkyl)OC(=O)(Ci-Ce alkyl), CrCe alkyl-(C₃-C₁₀ cyclohaloalkyl), or (C_rCe alkenyl)C(=O)O(C_rCe 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, CrCe alkyl, CrCe alkenyl, CrCe haloalkyl, Cr Ce haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C₃-C₁₀ cycloalkenyl, CrCio halocycloalkyl, CrCio halocycloalkenyl, OR9, S(O)_nOR9, C6-C20 aryl, or C_rC2o heterocyclyl, R9aryl, (each of which that can be substituted, may optionally be substituted with R9).

optionally R6 (except R11) and R8 can be connected ln a cyclic arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, S, or N. In the cyclic structure connecting R6 and R8;

(h) R7 Is O, S, NR9, or NOR9;

(i) R8 is substituted or unsubstituted CpCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted Ce-C2o aryl, substituted or unsubstituted CrC2o heterocyclyl, OR9, OR9S(O)_nR9, C(=X1)R9, C(=X1)OR9, R9C(=X1)OR9, R9X2C(=X1 JR9X2R9,

C(=X1)N(R9)₂₁ N(R9)2, N(R9)(R9S(O)„R9), N(R9)C(=X1 )R9, SR9, S(O)„OR9, R9S(O)„R9, or

R9S(O)_n(NZ)R9, wherein each said R8, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, CpC® haloalkyl, CrCe haloalkenyl, C_rC_B haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, N(R9)S(O)_nR9, oxo, OR9, S(O)nOR9, R9S(O)_nR9, S(O)_nR9, Ce-C» aryl, or Ci-Cm heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9) altematively R8 is R13-S(O)_n-R13 wherein each R13 is independently selected from substituted or unsubstituted CpCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Ce-C^o aryl, substituted or unsubstituted Ci-Cm heterocyclyl, substituted or unsubstituted S(O)_nCi-Ce alkyl, substituted or unsubstituted N(C_rC₆alkyl)₂₁ wherein each said substituted alkyl, substituted alkenyl, 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, NO_2> Ci-Ce alkyl, CrCe alkenyl, Ci-C® haloalkyl, CrCe haloalkenyl, Ci-Ce haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C₁₀ cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OC_rCe alkyl, OCi-C₈ haloalkyl, SfO^CrCealkyl, S(O)_nOCi-Ce alkyl, Ce-C» aryl, or CrC» heterocyclyl, CrCe alkynyl, Ci-Ce alkoxy, N(R9)S(O)_nR9, OR9, N(R9)2, R9OR9, R9N(R9)₂₁ R9C(=X1)R9, R9C(=X1)N(R9)2, N(R9)C(=X1)R9, R9N(R9)C(=X1 )R9, S(O)„OR9, R9C(=X1)OR9, R9OC(=X1)R9, R9S(O)_nR9, S(O)_nR9, oxo, (each of which that can be substituted, may optionally be substituted with R9);

(j) R9 is (each independently) H, CN, substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted CrCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C3-C₁₀ cycloalkenyl, substituted or unsubstituted Ce-C_M aryl, substituted or unsubstituted CpC^ heterocyclyl, substituted or unsubstituted S(O)nCi-Ce alkyl. substituted or unsubstituted NiCpCealkyl)^ wherein each said R9, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ C_rCe alkyl, CrCe alkenyl, C,-C₉ haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C₁₀ cycloalkenyl, C3-C10 halocycloalkyl, C₃-Cio halocycloalkenyl, OCi-C₈ alkyl, OCi-Ce haloalkyl, S(O)_nCi-Cealkyl, S(O)_nOCi-Ce alkyl, Ce-Qa aryl, or CrC» heterocyclyl;

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

(l) X is N or CRm where F^i is H, F, Ci, Br, I, CN, NO₂₁ substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted C₂-C_e alkenyioxy, substituted or unsubstituted C3-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted Ce-Caj aryl, substituted or unsubstituted C1-C20 heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)2, N(R9)C(=X1)R9, SR9, S(O)_nR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said Rni which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ Ct-Ce alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, CrC₁₀ cycloalkenyl, Ca-Cio halocycloalkyl, C3-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, Ce-Czo aryl, or CrCaj heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(m) X1 is (each independently) O or S;

(η) X2 Is (each independently) O, S, =NR9, or =NOR9;

(o) Z is CN, NO₂, C_rCe a1kyt(R9). C(=X1 )N(R9)z;

(p) R11 Is Qi(C=C)R12, wherein Q, is a bond, substituted or unsubstituted C) - Ce alkyl, substituted or unsubstituted C_rCe alkenyl, substituted or unsubstituted CrCe alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted CrCw cycloalkoxy, substituted or unsubstituted CrCealkylORS, substituted or unsubstituted Ct-Ce alkylS(O)_nR9, substituted or unsubstituted C_rCealkytS(O)n(=NR9), substituted or unsubstituted Ct-Ce alkylN(R9) (where (C=C) is attached directly to the N by a bond), substituted or unsubstituted C_rCeaikylN(R9)2, substituted or unsubstituted CrCe alkenyioxy, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted Co-Ce aikylC(=R7)C(j-C6 alkylR9, substituted or unsubstituted Co-Ce alkylC(=R7)OR9, substituted or unsubstituted CrCe alkylOCo-Ce alkylC(=R7)R9₁ substituted or unsubstituted CrCealkylN(R9)(C(=R7)R9), substituted or unsubstituted C_rC_ealkylN(R9)(C(=R7)OR9)₁ substituted or unsubstituted Co-Ce alkyl C(=R7)CoC_e alkylN(R9) (where (CEC) Is attached directly to the N by a bond), substituted or unsubstituted C_o-C_ealkylC(=R7)Co-C_e alkylN(R9)2₍ OR9, S(O)_nR9, N(R9)R9, substituted or unsubstituted CeCzo aryl, substituted or unsubstituted C1-C20 heterocyclyl, wherein each said Q_b which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO_2i CrCe alkyl, CrCe alkenyl, CrCe alkynyl, C,-Ce haloalkyl. Cr Ce haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, SR9, S(O)_nR9, S(O)_nOR9, Ce-C^ aryl, or CrCzo heterocyclyl, R9aryl, C_rCealkylOR9, Ci-CealkylS(O)nR9, (each of which that can be substituted, may optionally be substituted with R9) optionally Q1 and R8 can be connected In a cyclic arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, S, or N, ln the cyclic structure connecting Q1 and R8;

(q) R12 ls Qi (except where Qi is a bond), F, Ci, Br, I, Si(R9)₃ (where each R9 ls Independently selected), or R9; and (r) with the following provisos (1) that R6 and R8 cannot both be C(=O)CH₃, (2) that when A1 is A11 then R6 and R8 together do not form fused ring

Systems, (3) (4) (5) that R6 and R8 are not iinked in a cyciic arrangement with only -CH₂-, that when A is A2 then R5 is not C(=O)OH, that when A is A2 and R6 ls H then R8 is not a -(C_rCe aikyl)-O(substituted aryl), and (6) that when A is A2 then R6 ls not -(C₁aiky1)(substituted aryl).

ln another embodiment of this Invention A ls A1.

ln another embodiment of this invention A is A2.

ln another embodiment of this Invention R1 is H.

ln another embodiment of this invention R2 is H.

ln another embodiment of this invention R3 is selected from H, or substituted or unsubstituted C_rCe alkyl.

ln another embodiment of this invention R3 is selected from H or CH₃.

in another embodiment of the Invention when A is A1 then A1 is A11.

ln another embodiment of the Invention when A ls A1, and A1 ls A11, then R4 is selected from H, or substituted or unsubstituted Cj-Ce alkyl, or substituted or unsubstituted Ce* Croaryl.

in another embodiment of the invention when A ls A1, and A1 is A11 then R4 ls selected from CH₃, CH(CH₃)₂, or phenyl.

ln another embodiment of the invention when A is A1, and A1 ls A12, then R4 is CH₃, ln another embodiment of this Invention when A is A2 then R4 ls selected from H, or substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C₃-Ci₀ cycloalkyl, substituted or unsubstituted Cg-C^o aryl, wherein each said R4, which ls substituted, has one or more substituents selected from F, Cl, Br, or I.

ln another embodiment of this invention when A is A2 then R4 is H or C_rCe alkyl.

ln another embodiment of this invention when A is A2 then R4 is H, CH₃, CH₂CH₃, CH=CH₂, cyclopropyl, CH₂CI, CF₃₁ or phenyl.

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

ln another embodiment of this Invention R5 ls H, F, Cl, Br, I, or substituted or unsubstituted CrCe alkyl, substituted or unsubstituted Cj-Ce alkoxy.

ln another embodiment of this invention R5 is H, OCH₂CH₃, F, Cl, Br, or CH₃.

In another embodiment of this invention, when A is A1 then R6 is substituted or unsubstituted C_rCe alkyl.

In another embodiment of this invention when A ls A2 then R6 is selected from is substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted Ca-C₁₀ cycloalkyl, C(=X1)R9, C(=X1)X2R9, R9X2R9, C(=OXCrCe alkyOSiOMCpCe alkyl), (C_rCe alkylJOC^OXCe-C^ aryl), (C_rCe alkyi)OC(=OXC_rC_e alkyl), or R9X2C(=X1)X2R9.

In another embodiment of this invention when A ls A2 then R6 and R8 are connected In a cyclic arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, S, or, N, In the cyclic structure connecting R6 and R8.

In another embodiment of this Invention R6 ls CrCe alkyl, or CpCe alkyl-phenyl.

In another embodiment of this invention R6 ls H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂, CH₂phenyl, CH₂CH(CH₃)₂, CH₂cyclopropyl, C(=O)CH₂CH₂SCH₃, C(=O)OC(CH₃)3, CH₂CH=CH₂, C(=O)OCH₂CH₃, C(=O)CH(CH₃)CH₂SCH₃, cyclopropyl, CD₃, CH₂OC(=O)phenyl, C(=O)CH₃, C(=O)CH(CH₃)2, CH₂OC(=O)CH(CH3)₂, CH₂OC(=O)CH3, C(=O)pheny!, CHjOCHj, CH₂OQ=O)CH₂OCH₂CH₃, CH₂CH₂OCH₃, CH₂OC(=O)OCH(CH3)₂, CH₂CH₂OCH₂OCH₃. CH₂CH₂OCH₃, CH₂CH₂OC(=O)CH3, CH₂CN.

in another embodiment of this Invention R6 ls methyl or ethyl.

In another embodiment of this invention R7 ls O or S.

In another embodiment of this invention R8 ls selected from substituted or unsubstituted CrCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted Cb-Cm aryl, substituted or unsubstituted CrCw heterocyclyl, R9C(=X1)OR9, SR9, S(O)_nOR9, R9S(O)_nR9, or R9S(O)_n(NZ)R9.

In another embodiment of this invention R8 ls CH(CH3)CH₂SCH₃, CH(CH3)₂, C(CH₃)₂CH₂SCH3, CH₂CH₂SCH₃, CH₂CF₃, CH₂CH₂C(=O)OCH_3i N(H)(CH₂CH₂SCHa), OCH₂CH₂SCH3, CH(CH₂SCH₃)(CH₂phenyl), thiazolyl, oxazolyl, Isothiazolyl, substituted-furanyl, CH₃, C(CH₃)3, phenyl, CH₂CH₂OCH₃, pyridyl, CH₂CH(CH3)SCH₃, OCXCHah, CÎCHj^CHîSCHj, CH(CH3)CH(CH₃)SCH3, CH(CH₃)CF3, CH₂CHrthienyl, CH(CH₃)SCF₃,CH₂CH₂CI, CH₂CH₂CH₂CF_3i CH₂CH₂S(=O)CH₃, CH(CH₃)CH₂S(-O)CH₃, CH₂CH₂S(=O)2CH3, CH(CH₃)CH₂S(=O)₂CH3_> NCHîCHa, N(H)(CH₂CH₂CH₃), C(CH₃)=C(HXCH3), Ν(Η)(ΟΗ₂ΟΗ=ΟΗ₂), CH₂CH(CF₃)SCHa, CH(CF₃)CH₂SCH₃, thietanyl, CH₂CH(CF₃)₂, CH₂CH₂CF(OCF₃)CF3, CH₂CH₂CF(CF3)CFj, CF(CH₃}₂₁ CH(CH3)phenyl-CI, CH(CH₃)pheny!-F, CH(CH3)pheny!-OCF₃, CH₂N(CH3XS(=O)2N(CH3)₂, CH(CH₃)OCH₂CH₂SCH3, CH(CH₃)OCH₂CH₂OCH3, och₃, CH(CH3)SCH₃, CH₂SCH₃, N(H)CH₃, CH(Br)CH₂Br, or CH(CH₃)CH₂SCD₃.

In another more preferred embodiment of this invention R8 ls preferably R13-S(O)_n-R13 wherein each R13 ls Independently selected from substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted 11 or unsubstituted CrCe alkenyloxy, substituted or unsubstituted Qj-Cw cycloalkyl, substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Ce-C» aryl, substituted or unsubstituted Ci-C» heterocydyl, substituted or unsubstituted S(O)_nCrCe alkyl, substituted or unsubstituted NiCrCealkyl^, wherein each said substituted alkyl, substituted alkenyl, substituted alkoxy, substituted alkenyloxy, substituted cycloalkyl, substituted cycloalkenyl, substituted aryl, substituted heterocydyl, has one or more substituents independently selected from F, Cl, Br, I, CN, NO₂₁ C_rCe alkyl, CrCe alkenyl, C_rC_e haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, C3-C10 halocycloalkyl, Qj-Cw halocycloalkenyl, OCrCe alkyl, OCrCe haloalkyl, SfOJnCrCealkyl, S(O)_nOCrCe alkyl, CeC20 aryl, or C1-C20 heterocydyl, CrCe alkynyl, Ci-C_e alkoxy, N(R9)S(O)_nR9, OR9, N(R9)₂, R9OR9, R9N(R9)₂, R9C(=X1)R9, R9C(=X1)N(R9)₂₁ N(R9)C(=X1 )R9, R9N(R9)C(=X1)R9, S(O)_nOR9, R9C(=X1)OR9, R9OC(=X1)R9, R9S(O)_nR9, S(O)„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 CrCe alkyl)S(O)„-(substituted or unsubstituted CrCe alkyl) wherein said substituents on said substituted alkyls are independently selected from F, Cl, Br, I, CN, NO₂₁ CrCe alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, CrCw cycloalkyl, C3-C10 cydoalkenyl, C3-C10 halocycloalkyl, C_rC₁₀ halocycloalkenyl, OCrCe alkyl, OCrCe haloalkyl, S(O)_nC_rCealkyl, S(O)_nOCrCe alkyl, Ce-C^aryl, or Cheterocydyl, CrCe alkynyl, CrCe alkoxy, N(R9)S(O)_nR9, OR9, N(R9)₂, R9OR9, R9N(R9)₂, R9C(=X1)R9, R9C(=X1)N(R9)₂, N(R9)C(=X1)R9, R9N(R9)C(=X1)R9, S(O)_nOR9, R9C(=X1)OR9, R9OC(=X1)R9, R9S(O)_nR9, S(O)_nR9, 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, CH₂CH₂SCH₂CF₃, CH₂SCH₂CF_3i CH2SCHCICF3, CH(CH₂CH₃)SCH₂CF₃₁ CH(CH₃)SCH₂CHF₂, CH(CH₃)SCH₂CH₂F. CH₂CH₂SCH₂CH₂F, CH(CH₃)S(=O)2CH₂CF3. CH(CH₃)S(=O)CH₂CF₃, CH(CH₃)CH₂SCF₃, CH(CH₃)CH₂SCF₃₁CH(CH₃)SCH₂CH₂CF3. and CH₂CH₂SCH₂CH₂CF₃.

In another embodiment of this Invention R8 is (substituted or unsubstituted CrCe alkyl)S(O)ri-(substituted or unsubstituted CrCe alkyl)-(substituted or unsubstituted CrCw cycloalkyl) wherein said substituents on said substituted alkyls and said substituted cycloalkyls are independently selected from F, Cl, Br, I, CN, NO₂, CrCe alkyl, CrCe alkenyl, CrCe haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C_rC_w cycloalkenyl, Qj-Ciq halocycloalkyl, C3-C10 halocycloalkenyl, OCrCe alkyl, OCrCe haloalkyl, S(O)_nCrC_ealkyl, S(O)„OCrCe alkyl, Ce-C» aryl, or CrC™ heterocydyl, CrCe alkynyl, CrCe alkoxy, N(R9)S(O)_nR9, OR9, N(R9)₂, R9OR9, R9N(R9)₂, R9C(=X1)R9, R9C(=X1 )N(R9)₂, N(R9)C(=X1)R9, R9N(R9)C(=X1)R9, S(O)_nOR9, R9C(=X1)OR9, R9OC(=X1)R9, R9S(O)_nR9, S(O)_nR9, oxo, (each of which that can be substituted, may optionally be substituted with R9).

In another embodiment of this invention R8 ls selected from CH(CH₃)CH₂SCH₂(2,2 difluorocyclopropyl), CH₂CH₂SCH₂(2,2 difiuorocyclopropyl), CH₂CH₂S(=O)CH₂(2,2 difluorocyclopropyl), CH₂CH₂S(=O)₂CH₂CH₂(2,2 difluorocyclopropyl), and CH₂CH(CF₃)SCH₂(2,2 difluorocyclopropyl).

In another embodiment of this Invention R8 is (substituted or unsubstituted C_rCe alkyl/ S(O)_n-(substituted or unsubstituted CrCe alkenyl) wherein said substituents on said substituted alkyls and substituted alkenyls are Independently selected from F, Cl, Br, I, CN, NO_2l C_rCe alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, CrCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C_rC₁₀ cydoalkenyl, Cj-Ci₀ halocycloalkyl, C3-C₁₀ halocydoalkenyl, OCrCe alkyl, OCrCe haloalkyl, S(O)_nC_rCealkyl, S(O)„OCrCe alkyl, Cg-C^ aryl, or CrCîo heterocyclyl, CrCe alkynyl, CrCe alkoxy, N(R9)S(O)„R9, OR9, N(R9)₂, R9OR9, R9N(R9)₂, R9C(=X1)R9, R9CÎ=X1)N(R9)2, N(R9)CÎ=X1)R9, R9N(R9)C(=X1)R9, S(O)_nOR9, R9C(=X1)OR9, R9OC(=X1 )R9, R9S(O)„R9, S(O/R9, oxo, (each of which that can be substituted, may optionally be substituted with R9).

In another embodiment of this invention R8 ls selected from CH₂CH₂SCH₂CH=CCI₂, CH2SCH2CH=CCI₂₁ CH(CH3)SCH2CH=CCI₂₁ CH(CH3)SCH=CHF, CH₂CH₂S(=O)CH₂CH₂CF₃. and CH₂CH₂S(=O)₂CH₂CH₂CF₃.

In another embodiment of this Invention X is CR^ where R^ ls H or halo.

In another embodiment of this invention X is CRn, where R„i ls H or F.

In another embodiment of this Invention X1 is O.

In another embodiment of this Invention X2 ls O.

In another embodiment of this invention R11 is substituted or unsubstituted C_rCe alkylC=CR12.

In another embodiment of this invention R11 ls CH₂C=CH.

The molécules of Formula One will generally hâve a molecular mass of about 100 Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass ls from about 120 Daltons to about 900 Daltons, and It ls even more generally preferred if the molecular mass ls from about 140 Daltons to about 600 Daltons.

The following schemes lllustrate approaches to generating aminopyrazoles. In step a of 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 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 amînopyrazole of Formula Va where R5 = H as in step cof Scheme I and as In

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 1
	?	O	i! î Γ
χΑγΑ.		AyA.s *
rîAArj	a) R, N	A 1	rAnArJ, à.
II		ni	IV

Va

Another approach to aminopyrazoles Is illustrated ln 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 Vil, such as methylhydrazine to give a mixture of aminopyrazoles of Formula Vb, wherein R5 and R6 - H, both of whose components were Isolated.

Scheme II

VI

VII

N

Rô

Préparation of aminopyrazoles such as those of Formula Xlla Is demonstrated ln Scheme lll. The compound of Formula X In step a and as in Cristau, Henri-Jean et al. Eur. J.

Org. Chem. 2004, 695-709 can be prepared through the N-arylation of a pyrazole of Formula IX with an approprlate aryl halide of Formula Villa where Q ls bromo ln the presence of a base such as césium carbonate, a copper catalyst such as copper (II) oxide and a ligand such as salïcylaldoxlme in a polar aprotic solvent such as acetonitrile. Compounds of Formula IX, as shown in Scheme lll, wherein R4 - Cl and R5 = H, can be prepared as in Pelcman, B. et al WO

2007/045868 A1. Nitration of the pyrldylpyrazole of Formula X as in step b of Scheme III and as ln 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. Réduction of the nitro functionality of compounds of Formula Xla ln the presence of hydrogen with a catalyst such as 5% Pd/C ln a polar aprotic solvent such as tetrahydrofuran gave the amine of Formula Xlla, as shown In step c in Scheme

III. Réduction 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 éthanol gave the amine of Formula Xlla, wherein

R5 = H, as well as the amine of Formula Xlla, wherein R5 » OEt, as shown in step dof 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 éthanol to give amines of Formula Xlla, wherein

R1, R2, R3, R5 and X are as previously defined R4 = Cl, 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 boronlc acid such as phenylboronlc acid 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 éthanol and toluene to provide cross-coupled pyrazoles of Formula Xlb, as shown in step f of Scheme III.

Scheme lll

Xlb ln step a of Scheme IV, the compounds of Formula Xllb can be treated with triethylorthoformate and an acid such as trifluoroacetic acid. Subséquent addition of a reducing agent such as sodium borohydride in a polar protic solvent such as éthanol gave a compound of Formula XIIla, wherein R6 = methyl.

ln 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 Xllla, wherein R6 = Isopropyl.

In step c of Scheme IV, the compounds of Formula Xllb can be acylated with an acid chioride such as acetyl chioride ln a polar aprotic solvent such as dichloromethane using the conditions described ln Scheme V. Réduction of the amlde with a reducing agent such as lithium aluminum hydride In a polar aprotic solvent such tetrahydrofuran glves compounds of Formula Xllla, wherein R6 = ethyl.

Alternative^, in step dof Scheme IV, the compounds of Formula Xllb can be treated with benzotriazole and an aldéhyde in éthanol followed by réduction using, for example, sodium borohydride, to afford compounds of Formula Xlila. In step e of Scheme IV, the compounds of Formula Xllb can be treated with an aldéhyde such as propionaldéhyde and sodium triacetoxyborohydride in a polar aprotic solvent such as dichloromethane to give compounds of Formula Xi Ha. wherein R6 - propyl. As in step f, acylation of compounds of Formula Xlila 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

Xlila Xllb

la

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./V-dimethylaminopyridine in a polar aprotic solvent such as dichloroethane (DCE) to yield compounds of Formula Ib, wherein R8 is as previously defined. Additionally, when R6 - H the 2° amîde 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 poiar aprotic solvent such as Ν,Ν-dimethylformamide (DMF) to yield the desired compounds of Formula Ib. The acid chiorides used In the acylation reactions herein are either commerdally available or can be syntheslzed by those skilled In the art.

Scheme V

ln step a of Scheme VI and as ln Sammelson et al. Bioorg. Med. Chem. 2004, 12, 33453355, the aminopyrazoles of Formula Vd, whereln 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

N-bromosuccinimide ln a polar aprotlc solvent such as acetonitrile to provîde the R5-substituted pyrazole. In step b, acylation of this compound using the conditions described ln Scheme V affords the compound of Formula le, whereln R1, R2, R3, R4, R5, R6, R8 and X are as previously defined.

ίο

Scheme VI

ln step a of Scheme Vil, ureas and carbamates are made from the aminopyrazoles of Formula Ve. Compounds of Formula Ve, 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 ln step c, respectiveiy, to generate a urea of Formula Id or a carbamate of Formula le, respectiveiy, wherein R9 ls as previously defined.

Scheme VII

Ve

XV

ln step a of Scheme VIII, compounds of Formula Xllc, wherein X, R1, R2, R3, R4 and R5 are as previously defined, can be treated with di-fert-butyi dicarbonate (B0C2O) and a base 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 iodomethane 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) ln a polar aprotic solvent like dichloromethane to give compounds of Formula Xlllb as in step c.

Scheme VIII

XIIc XVIa

^xvn XIHb

In steps a, b andcof Scheme IX, compounds of Formula Xlllc, wherein X, R1, R2, R3, R4, R5 and R6 are as previously defined, can be treated with a compound of Formula XVIII, whereln R8 Is as previously defined and R10 is either OH, OR9 or O(C~O)OR9, to yield compounds of Formula Id. When R10 = OH, compounds of Formula Xlllc can be converted to compounds of Formula Id in the presence of a coupling reagent such as 1-(3dimethy!amlnopropy1)-3-ethy1carbodiimide hydrochloride (EDC-HCI) and a base such as N,Ndimethylaminopyridine (DMAP) in a polar aprotlc solvent such as dlchloroethane (DCE), as shown In step a. When R10 = OR9, compounds of Formula Xlllc can be converted to compounds of Formula Id in the presence of 2,3,4,6,7,8-hexahydro-1H-pyrimldo[1,2a]pyrlmidine in a polar aprotic solvent such as 1,4-dioxane under elevated température, as shown in step b. When R10 = O(C=O)OR9, compounds of Formula Xlllc can be converted to compounds of Formula Id In a polar aprotic solvent such as dichloromethane (DCM), as shown in step c. Acylation of amldes of Formula Id, when R6 = H, with an acid chloride in the presence of a base such as diisopropyl ethylamlne in a polar aprotic solvent such as dichloroethane (DCE) yields Imldes 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 A/,A/-dimethylformamide (DMF) yields alkylated amides of Formula le, as shown in step e. Halogénation of compounds of Formula Id, whereln R1, R2, R3, R4, R6, R8 and X are as previously defined and R5 = H, with a halogen source such as N-bromosucclnlmlde In a polar aprotic solvent such as DCE or a halogen source such as N-chlorosuccinimlde In a polar aprotic solvent such as DCE or acetonitrile or a halogen source such as Selectfiuor® in a mixture of polar aprotic solvents such as acetonitrile and DMF 20 give halogenated pyrazoles of Formula le, wherein R5 = halogen, as shown ln step f of Scheme

IX. Amldes of Formula Id can be converted to thioamides of Formula If ln the presence of a thionating agent such as Lawesson’s reagent ln a polar aprotic solvent such as dichloroethane (DCE), as shown in step g.

Scheme IX

In step a of Scheme X, compounds of Formula XiIid, wherein X, R1, R2, R3, R4, R5 and R6 are as prevlously defined, can be treated with compounds of Formula XIX, wherein R8 ls as prevlously 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, ln 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 ln step b of Scheme X.

Scheme X

XXI

Oxidation of the sulfide to the sulfoxlde or sulfone is accomplished as in Scheme XI where (-S-) 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 poiar protic solvent such as glacial acetic acid to give the sulfoxide of Formula XXIII as in step a of Scheme XI. Altematively, the sulfide of Formula XXlia can be oxidized with an oxidant such as hydrogen peroxide in a poiar protic solvent such as hexafluoroisopropanol to give the sulfoxide of Formula XXili as in 10 step d of Scheme XI. The sulfoxide of Formula XXIII can be further oxidized to the sulfone of Formula XXIV by sodium perborate tetrahydrate in a polar protic solvent such as glacial acetic acid as in step c of Scheme Xi. Altematively, the sulfone of Formula XXIV can be generated in a one-step procedure from the sulfide of Formula XXlia by using the aforementioned conditions with >2 équivalents of sodium perborate tetrahydrate, as in step b of Scheme XI.

Scheme XI

XXIV

Oxidation of the sulfide to the sulfoximine is accompilshed as in Scheme XII where (-S-) can be any sulfide previousiy defîned 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 previousiy defîned, is oxidized as In step a with iodobenzene diacetate in the presence of cyanamide in a polar aprotic solvent such as methylene chioride(DCM)togivethe suifiiimine ofthe Formula XXV.Thesuifiiimine of Formula XXV may be further oxidized to the sulfoximine of Formula XXVI with an oxidant such as metaChioroperoxybenzoic add (“mCPBA’) ln the presence of a base such as potassium carbonate in 10 a protic polar solvent System such as éthanol and water as ln step b of Scheme XII.

XXIIb

XXV

XXVI lodination of the pyrazole of Formula Xb as In step 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 iodinating agent such as lodine 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 Xllle can be prepared from iodopyrazoles of Formula XXVII through cross coupling reactions with an appropriate amine In the presence of a base such as césium carbonate, a copper catalyst such as copper (i) bromide, and a ligand such as 1-(5,6,7,8tetrahydroquinolin-8-yl)ethanone in a polar aprotïc solvent such as DMSO.

ln step a of the Scheme XIV, compounds of the formula XXIX, wherein R4 Is Cl, R5 is H and X' represents CI', can be prepared according to the methods described in Acta. Pharm. Suec. 22,147-156 (1985) byTolf, Bo-Ragnarand 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 be prepared by treating compounds of the Formula XXVIII with hydrogen gas in the presence of a métal catalyst such as 5% Pd on aiumlna and a solution of 50% aqueous HBr in a soivent such as éthanol. Altematively, in step a of Scheme XIV, compounds of the Formula XXIX, wherein R4 is Cl or Br, X'represents Cl· 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 hydrosilane such as triethy! silane in the presence of a métal catalyst such as 5% Pd on alumina and an acid such as HCl or HBr, respectively, ln a solvent such as ethanoi.

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, X^-represents CI or Br' and R5 Is as defined previously, with difert-butyl dicarbonate (Boc₂O) in the presence of a mixture of solvents such as THF and water and a base such as sodium bicarbonate.

ln 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 Cl or Br and R5 Is as defined previously, preferably H, with compounds of the Formula Vlllb, wherein X, R1, R2 and R3 are as defined previously and Q Is lodo, in the presence of a catalytic amount of copper sait such as CuCI₂, a ligand such as an ethane-1,2-diamïne dérivative such as N¹,N²-dimethylethane-1,2-diamine and a base such as K3PO4 in a polar aprotic solvent such as acetonitrile at a suitable température.

ln step c pyrazoles of Formula XXX are coupled with compounds of the Formula Viilb, preferably 3-lodo pyridine, in the presence of a métal catalyst, such as CuCI₂, and a diamine ligand such as N¹ _tN²-dimethylethane-1,2-diamine, and an Inorganic base, such as K3PO4. The reaction is carried out ln a polar aprotic solvent such as acetonitrile. The reaction is conducted at a température 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 Formula Viilb 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 iower 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 such as dichloromethane to give compounds of Formula Xlld, as shown in step d of Scheme XIV.

Scheme XIV

Xlld

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 boronlc ester such as vinylboronic acid plnacol ester or cyclopropylboronlc acid pinacol ester In the presence of a 5 catalyst such as palladium tetrakls, a base such as 2 M aqueous potassium carbonate, and in a mixed solvent system such as éthanol and toluene to provide compounds of Formula XXXII, as shown in step a of Scheme XV.

Scheme XV

XXXI

XXXII

The vlnyl group of compounds of Formula XXXIII, wherein R1

R2, R3, R5, R6, R8 and X are as previously defined, can be reduced ln the presence of hydrogen with a catalyst such as

10% Pd/C ln 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 ln 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. Réduction of the aldéhyde 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 chlorlnating agent such as thionyl chloride in a polar aprotic solvent such as dichioromethane gave compounds of Formula XXXVII, as shown ln step d of Scheme XVI.

Scheme XVI

XXXIII b

XXXV

XXXVI

XXXVII ln step a of Scheme XVII, an □.□-unsaturated acid XXXVIII can be treated with a nucleophile such as sodium thiomethoxide ln a polar protic solvent such as methanol to give acid XXXIX.

Scheme XVII

O SMe

XXXVIII XXXIX

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

A2, R7 is O and R8 is fert-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 Ih, wherein R6 = R11.
	Scheme XVIII
R?		R?
anar,	a	anar,
H
Ig		Ih

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-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride (EDC-HCI), and a base, such as Ν,Ν-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 THF, followed by an alkyl halide R9-Hal to give the compounds of the Formula XLIII.

XLIII

Altematively, ln step a of Scheme XX, compounds of the Formula XL or the corresponding HCl sait, wherein X, R1, R2, R3, R4, R5, and R6 are as previously defined, can be coupled to acids ofthe formulaXLIV,wherein R8 is as previouslydefined, in the presence of a coupling reagent, such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimlde hydrochloride (EDC HCI), and a base, such as Λ/,Ν-dimethylamlnopyridine, 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 b of Scheme XX, compounds of the Formula XLV, 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, ln the presence of a trialkyl silane, such as triethyl silane, in a polar aprotic solvent, such as methyfene 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 X, R1, R2, R3, R4, R5, R6 and R8 are as previously defined, can be treated with a base, such as sodium hydride, ln a polar aprotic solvent such as tetrahydrofuran, or césium 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. Altematively, the modified conditions described by Pustovit and coworkers (Synthesis

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

Scheme XX

XLIV XLV b

XLVII

Altematively, ln step a of the Scheme XXI, compounds of the Formula XL or the corresponding HCl sait, wherein X, R1, 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 soivent such as DMF to yieid compounds of Formula XLIX, where In X, R1, R2, R3, R4, R5, R6 and R9 are as previously defined. In step b of the Scheme XXI, compounds of the Formula XLIX, wherein X, R1, R2, R3, R4, R5, R6 and R9 are as previousiy defined, can be treated with a thio acid sait, such as potassium thioacetate, at an elevated température (about 50 *C) in a solvent, such as DMSO, to give compounds of the Formula L, wherein X, R1, 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 equimolar amount of a base, such as sodium methoxide, prepared from mixing sodium hydride, and methanol, followed by an electrophile (R9- Halo), such as 2-(bromomethy1)-1,1difluorocyclopropane, In a solvent, such as tetrahydrofuran, to give compounds of the Formula Ll.

Scheme XXI

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

R5, R6, and halo are as previously defined, can be treated with an acid chioride of Formula Lll 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 LUI, wherein R8 is either a substituted or unsubstituted alkyl chain. ln step b, compounds of the Formula LUI can be treated with potassium thloacetate to provide compounds of Formula LIV after heating (about 60 ^eC) in a polar aprotic solvent, such as acetone. As indicated ln step c, a one-pot methanolysis/alkylation sequence can be achieved via treatment of compounds of the Formula LIV with one équivalent of a base, such as sodium methoxide (NaOMe) in a polar aprotic solvent, such as tetrahydrofuran (THF). An alkyl sulfonate or alkyl halide, such as 2-iodo-1,1,1-trifluoroethane, can then be added to the reaction mixture to deliver compounds of the Formula LV, wherein R9 ls as previously defined. In step d compounds of the Formula LV may be obtained from compounds of the Formula LUI via treatment with an alkyl thiol such as 2,2,2-trifluoroethanethiol at elevated températures (about 50 *C) in a polar aprotic solvent, such as THF, in the presence of sodium iodide and a base, such as diisopropylethylamine. Altemativeiy, in step f treating compounds of Formula LUI with an alkyl thiol, such as sodium methanethiolate, in a polar aprotic solvent, such as DMSO, at elevated températures (about 50 *C) will afford compounds of Formula LV. As demonstrated ln step e, when compounds of the Formula LIV are treated with two or more équivalents of a base, such as NaOMe, followed by a 1,2,2-trihaloalkyl compound, such as 2-bromo-1,1-difluoroethane, compounds of Formula LVI are obtained.

XL

LIV

LVI

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, ln 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.

Scheme 23

23.1

23.2

23.3

In step a of Scheme 24, compounds of Formula 24.1, where X, R1, R2, R3, R4, R5, R8 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 ls 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 trimethylsllyl trifluoromethanesulfonate and dimethylmethylideneammonium lodide (Eschenmoser*s sait) in a polar aprotic solvent, such as dichloromethane (DCM), to yield compounds of Formula 24.3. ln 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-dimethy1 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 defined.

24.4 24.3

A route to compounds of Formula 25.2 ls 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 as previously defined, are treated with two or more équivalents of a base, such as sodium methoxide, followed by a 1,2-dihaloalkyl compound, such as 1-fluoro-2-iodoethane, ln a solvent, such as tetrahydrofuran (THF), compounds of Formula 25.2, wherein R9 ls as previously defined, are obtained.

Scheme 25

R,'^Sx^_{R1 10} 25.1 25.2

An alternative route to vinyl sulfîdes ls described in step a of Scheme 26. This route utilizes conditions developed by Kao and Lee (Org. Lett. 2011,13, 5204-5207) in which thlols 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(l) oxide, a base, such as potassium hydroxide, and a solvent, such as dioxane, at eievated températures to afford products of Formula 26.2, wherein R9 ls as previously defined.

Scheme 26

ln step a of Scheme 27, an acrylamide of Formula 27.1, wherein X, R1, R2, R3, R4, R5, and R6 are as previousiy defîned, is reacted with a sulfonamide of Formula 27.2, wherein R9 is as previousiy defîned, ln the presence of a base, such as potassium carbonate, at elevated températures 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 aikyî halide, such as 2-bromoacetonitrile, in a polar aprotic solvent, such as tetrahydrofuran (THF), to provide compounds of the Formula 27.4, as demonstrated ln step b.

Scheme 27

27.1

a

27.3

27.2

V N'^S' i

R«

When compounds of the Formula 28.1, wherein X, R1, R2, R3, R4, R5, R6, R8 and halo are as previousiy defîned, are treated with amines of the Formula 28.2, wherein R9 is as previousiy defîned, at elevated températures 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 chioride, such as methanesulfonyl chioride, 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 shown in step b. As demonstrated ln 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 températures 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. Altematively, compounds of Formula 28.3 may be prepared via a two step process as described in steps d 36 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-dimethylaminopropyl)-3-ethylcarbodiÎmide hydrochloride (EDCHCl) and a base such as

N.N-dimethylaminopyridine (DMAP) In a polar aprotic solvent such as dichloroethane (DCE), as shown In step d. The Boc-group can be removed under conditions that are well-known In the art, such as under acldic 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

HO^RÎ^Ny^O^-CH₃ O CH₃

28.7

28.3

RiR₃ ^5 Re

28.4 28.5

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, 8,24332436) to deliver compounds of the Formula 29.2, wherein R9 ls as previously defined. These products may then be subjected to a fluorinating reagent, such as Deoxo-Fluor®, and an

Initiator, such as éthanol, In a polar aprotic solvent, such as dichloromethane (DCM), to deliver compounds of the Formula 29.3, as described in step b.

Scheme 29

29.3

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, ln a solvent, such as THF, to afford an Intermediate aldéhyde of the Formula 30.2. Compounds of the Formula 30.2 can be immediately reacted with a fluorinating reagent, such as Deoxo-Fluor®, ln the presence of an Initiator, such as éthanol, and a solvent, such as tetrahydrofuran (THF), to provide products of the Formula 30.3.

Scheme 30 ,^R2 R4

X-\ 9 OCHj p-// 1 S À · ^Rl Rg OCH₃

R₃ Rs Re

30.1

30.2

O t'a 'Q

ln 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 ln 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 ln step b, ln which a reaction with a thioate sait ln a solvent, such as dimethylformamlde (DMF), provides compounds of the Formula 31.3, wherein W ls aryl 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 équivalent of a base, such as sodium methoxide (NaOMe), in a polar aprotic solvent, such as tetrahydrofuran (THF). A compound of 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

Ra

Ra F

A_.halo κ_β

31.5 ln 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-(fluorosulfonyl)acetate can be heated ln the presence of sodium fluoride to deliver a substituted difluorocyclopropane of the Formula 32.2, as Indicated in step a. ln step b, this product was treated with tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (THF) to afford an intermediate 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.

°^A^^ch2

32.1

32.4

Compounds ofthe Formula 33.1, wherein X, RI, R2, R3, R4, R5, and R6 are as previously defined, where X ls preferably carbon, R1, R2, R3, and R5 are hydrogen and R4 ls 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,Ndimethylaminopyridine (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,Ndimethylaminopyridine, or diisopropylethylamine. The reaction is carried out in a halogenated solvent such as 1,2-dichloroethane or methylene chloride. The reaction is conducted at a température 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.

		Scheme 33
,R2 x~< 'N^ R.-4' j-v	Λ	O + A CI^R8	8	X- Ri—(Z N:	,R2 Vn'J	Λ
^NH
R3 Rs	Rs				R3 R5	Rs
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 treated with an acid of Formula 34.2, wherein R8 is as previously defined, in the presence of Ν,ΛΓ-dicyclohexylcarbodiimide (DCC), and a base, such as N,N-dimethylaminopyridine (DMAP), in a solvent, such as diethyt ether (Et₂O), to yield compounds of Formula 34.3.

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 (DMAP) 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 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

ln 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. ln step b of Scheme 36, oxazolidin10 2-one can be treated with an equlmolar amount of a base, such as sodium hydride followed by compounds of Formula 36.2, in a polar aprotic solvent such as dlmethylformamide (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.

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 bls(trimethylsilyi)amide in a polar aprotic solvent such as THF followed by an acyl chloride such as plvaloyl chloride to yieid 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(trimethylsiiyl)amide in a polar aprotic solvent such as THF followed by an alkyl hallde such as (chioromethylXmethyl)suifane to yieid alkylated ureas of Formula 37.2, wherein R1, R2, R3, R4, R5, R6, R8, and X are as previously defined. In step cof 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(trimethylsiiyl)amide in a polar aprotic solvent such as THF followed by a sulfonyl chloride such as methanesulfonyl chloride to yieid suifonylated ureas of Formula 37.3, wherein R1, R2, R3, R4, R5, R6, R8, and X are as previously defined.

Scheme 37

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 naphthalen-2-ylmethyl 3-(methylthio)propanimidothioate hydrobromide in a polar protic solvent such as éthanol 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.

Scheme 38

38.1 38.2

In step a of the Scheme 39, compounds ofthe 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 te/ï-butoxlde In a polar aprotic solvent such as THF at appropriate températures, to give the corresponding ethers of the Formula 39.3. Altematively, 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 thlols 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.

Scheme 39

39.1

Rg-OH

39.2

39.3

Rg—SH

39.4

ln 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 et.al.

(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 ls not H.

Scheme 40

40.1

Rg ln 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 EDC'HCI 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 ln 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

5 ln 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 triethylamine in an aprotlc solvent such as dichloromethane to give amides of 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 iodomethane in the presence of a base such as potassium fert-butoxide in a solvent such as THF to afford compounds of the Formula 42.3. ln step cof the Scheme 42 amides of the Formula 42.3, wherein X, R1, R2, R3, R4, and 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.

EXAMPLES

The exemples are for Illustration purposes and are not to be construed as limiting the

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

Starting matériels, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seai™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMeft Automated Melting Point System from Stanford Research Systems and are uncorrected. Molécules 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 molécule, the molécule ls named using conventional naming rules. Ail NMR shifts are in ppm (δ) and were recorded at 300,400 or 600 MHz unless otherwise stated. Examples using “room température’ were conducted in climate controiled laboratories with températures ranging from about 20 ’C to about 24 ’C.

Example 1, Step 1: Préparation of 3,3-bis-methylsulfanyl-1-pyridln-3-yl-propenone

To a room-temperature suspension of sodium hydride (NaH, 60% suspension in minerai oll; 4.13 g, 86 mmol) ln dry dimethyl sulfoxide (DMSO, 60 mL) under an atmosphère of nitrogen (N₂) was added 3-acetylpyridine (5.00 g, 41.3 mmol) dropwise over 30 minutes (min). The mixture was stirred for an additional 30 minutes at the same température. Carbon disulfide (CS₂; 3.27 g, 43 mmol) was added dropwise with vigorous stirring followed by iodomethane (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 (EtOH) until the washings were coloriess. The off-whîte solid product was dried under vacuum at 60 ’C to provide 3,3-bis-methylsuifanyl1-pyridin-3-yf-propenone as a brown solid (4.8 g, 51%): ’H NMR (300 MHz, CDCI₃) □ 9.13 (d, J = 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-yl)-3,3-bis(methylthio)prop-2-en-1-one was prepared as described in Example 1, Step 1: mp 150-152 ’C; Ή NMR (400 MHz, CDCI₃) δ 8.93 (t, J= 1.6 Hz, 1H). 8.58(d, J = 2.8 Hz, 1 H),7.94 (ddd, J = 8.9, 2.8,1.7 Hz, 1 H)„ 6.69 (s. 1 H), 2.60 (s. 3H), 2.57 (s, 3H).

Example 1, Step 2: Préparation of (Z)-3-methylamino-3-methylsulfanyi-1-pyrldin-3-ylpropenone o s^x

N

A solution of 3,3-bis-methy!sulfanyl-1-pyridÎn-3-yl-propenone (18.6 g, 82.5 mmol) ln absoluto alcohol (400 mL) under N₂ was treated with methyiamlne hydrochloride (27.86 g, 412 mmol) followed by triethylamine (Et₃N; 58.5 mL, 412 mmol). The mixture was heated to reflux for 3 h, cooled to room température and concentrated under reduced pressure. The solid residue was dissolved in ethyi acetate (EtOAc; 150 mL). The solution was washed with H₂O (2 x 50 mL) and brine (50 mL), dried over Na₂SO4_, concentrated under reduced pressure and purified by silica gel chromatography eluting with 10% EtOAc in petroleum ether to yield (Z)-3methylamino-3-methy!sulfanyl-1-pyridin-3-yl-propenone as a pale yellow solid (8.6 g, 50%): ¹H NMR (300 MHz, CDClj) □ 11.8 (br s, 1 H), 9.06 (s, 1 H); 8.67 (d, J = 3.9 Hz, 1 H), 8.26 (d, J = 8.0 Hz 1 H), 7.46 (dd, J = 7.6, 4.9 Hz 1 H), 5.62 (s, 1 H), 3.10 (d, J = 5.2 Hz, 3H), 2.52 (s, 3H); MS (m/z) 209.2 [M+1].

(Z)-3-(ethylamino)-3(methylthio)-1-(pyridin-3-yl)prop-2-en-1-one was prepared as described in Example 1, Step 2: Ή NMR (400 MHz, CDCI₃) δ 11.81 (bs, 1H), 9.04 (dd, J =2.2, 0.7 Hz, 1 H). 8.64 (dd, J = 4.8,1.7 Hz, 1 H), 8.29 - 7.98 (m, 1 H), 7.35 (ddd, J = 7.9, 4.8, 0.9 Hz, 1 H), 3.45 (q, J = 7.2, 5.6 Hz, 2H), 2.50 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H).

(Z)-3-(cyclopropy!methy!)amino-3(methy!thio)-1-(pyridin-3-yl)prop-2-en-1-onewas prepared as described in Example 1, Step 2:¹H NMR (400 MHz, CDCI₃) δ 9.00 (s, 1H), 9.05 (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, 1 H), 5.62 (s, 1 H), 3.27 (dd. J = 7.0, 5.5 Hz, 2H), 2.50 (s, 3H), 1.20-1.07 (m, 1 H), 0.73 - 0.49 (m, 2H), 0.41 - 0.17 (m, 2H).

Example 1, Step 3: Préparation of methy1-(2-methyl-5-pyridin-3-pyrazoi-3-yi)-amine

A solution of (Z)-3-methy!amino-3-methy!sulfany!-1-pyridin-3-yl-propenone (3.00 g, 14 mmol) and methylhydrazine (729 mg, 15.4 mmol) in absolute EtOH (64 mL) was stirred at reflux for 18 h under N_2> cooled to room température and evaporated under reduced pressure. The residue was dissolved in EtOAc (50 mL), and the organic layer was washed with H₂O (2 x 30 mL) and brine (30 mL), dried over Na₂SO₄, concentrated under reduced pressure and purified using silica gel chromatography eluting with a gradient of 0-1% EtOH in EtOAc to yield two regioisomers in a 1:2 ratio, with the major regloisomer as a brown solid (1.0 g, 27%): ¹H NMR (300 MHz, CDCI₃) □ 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].

1-Ethyl-N-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine was prepared as described In Example 1, Step 3: ESIMS m/z 204 ([M+2H]).

A/-ethyl-1-methy!-3-(pyridin-3-yl)-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-yl)-1H-pyrazol-5-amine was prepared as described In Example 1, Step 3: ESIMS m/z 252 ([M+2H]).

/\A(cyclopropy1methy1)-1-methy1-3-(pyridin-3-y1)-1H-pyrazol-5-amine was prepared as described In Exampie 1, Step 3: ESIMS m/z 230 ([M+2H]).

1-lsopropyl-N-methyl-3-pyridin-3-yl)-1H-pyrazol-5-amine was prepared as described In Example 1, Step 3:¹H NMR (300 MHz, CDCI₃) δ 8.53 (s, 1H), 8.06 - 7.90 (m, 7.2 Hz. 2H),

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/z217 ([M+H]).

3-(5-Fluoropyridin-3-yl)-A/, 1-dimethyl-1H-pyrazol-5-amlnewas prepared as described in Example 1, Step 3: Ή NMR (300 MHz, CDCI3) δ 8.28 (s, 1H), 7.87 (t, J- 1.3 Hz, 1H), 7.60 (m, 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: Préparation of (4-chioro-2-methyl-5-pyrldin-3-yl-2H-pyrazol-3-yl)-methylamlne /

A mixture of methyt-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine (0.35 g, 1.8 mmol) and N-chiorosuccinimide (0.273 g, 2 mmol) was combined Jn acetonitrile (3 mL), stirred at room température for 30 minutes, concentrated under reduced pressure and purified using silica gel chromatography eluting with a gradient of EtOAc In hexanes to yield the title compound as a yellow oil (0.096 g, 23%): IR (thin film) 1581.6 cm’¹; Ή NMR (400 MHz, CDCI₃) □ 9.12 (d, J =

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, 1 H), 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-methy!-5-pyridin-3-yl-2H-pyrazol-3-ylamlne as a green gum (0.046 g, 13%): IR (thin film) 1720.5 cm*¹.; ¹H NMR (CDCI3, 400 MHz) 009.13 (br s, 1H),

8.57 (brs, 1 H). 8.16(dt, J = 8.0, 2.0 Hz, 1H), 7.33(dd, J = 7.8,4.8 Hz, 1 H), 3.76 (s, 3H); ESIMS (m/z) 207.0 [M-1].

Example 3: Préparation of 2,Ν-ΰΙιτΐθΙΐΊγΙ-Ν-(2-ιτΐθ11ιγΙ-5-ργΓ^Ιη-3-γΙ-2Η-ργΓ3ζοΙ-3-γΙ)-3methylsulfanyl-proplonamlde (Compound 1)

To a solution of methyl-(2-methyl-5-pyridin-3-y1-2H-pyrazol-3-yl)-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-methy1sulfany1-propiony1chloride (146 mg, 0.9 mmol) in DCE (1.5 mL). After stirring for 10 minutes (min), a solution of 4-/V,N-dimethy1aminopyridine (DMAP; 107 mg, 0.9 mmol) ln DCE (2 mL) was added dropwise. The ice bath was removed after 30 min, and the mixture was stirred at room température 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 EtOAc In hexane. The product, 2,N-dimethy1-N-(2-methyl-5-pyridin-3-yl-2Hpyrazol-3-yl)-3-methylsulfany1-propionamide, was isolated as a yellow semi-solid (44 mg, 24%): ’H NMR (400 MHz, CDCI₃) □ 9.00 (s, 1H), 8.58 (s, 1H), 8.08 (brd. J = 7.0 Hz, 1 H). 7.35 (br dd, J = 7.3, 4.8 Hz, 1 H), 6.58 (br s, 0.5 H), 6.49 (br s, 0.5 H), 3.89-3.79 (m, 3H), 3.25 (s, 3H), 2.962.80 (m, 1 H), 2.42-2.40 (m, 1 H), 2.02-1.99 (m, 3H), 2.62 (m, 1 H), 1.15 (d, J = 6.0 Hz, 3H); MS (m/z) 305.0 [M+1].

Compounds 2 - 6,9-10,12,18 - 21,24 - 33,477,487, 509, 520, 556-557, 562-568 were made from the appropriate amines ln accordance with the procedures disclosed In Example 3.

Example 4: Préparation of 1-methyl-1-(2-methyi-5-pyrldln-3-yl-2H-pyrazol-3-yl)-3-(2methylsulfanyl-ethyl)-urea (Compound 7)

To a solution of methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine (150 mg, 0.8 mmol) ln ice-cold DCE (2 mL) under N₂ was added a solution of phosgene ln toluene (20%, 0.43 mL, 0.88 mmol). The Ice bath was removed after 30 min, and the mixture was stirred at room température for 1 h and at reflux for 2 h. The mixture was cooled to room température and then more phosgene (0.86 mL, 1.76 mmol) was added. The mixture was stirred at reflux for 90 min and then cooled ln 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 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-methyl-1-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-(2-methylsulfanyl-ethyl)-urea as a yellow gum (14 mg, 6%): ’H NMR (400 MHz, CDCI₃) □ 8.99 (d. J - 1.5 Hz, 1 H), 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 using 2-(methylthio)ethanol in place of 2-methytthioethylamine.

Example 5: Préparation of 1-methyl-5-(pyridin-3-yl)-1H-pyrazol-3-am!ne and 1-methy!-3(pyridin-3-yl)-1H-pyrazol-5-amine

To éthanol (8.53 mL) was added 3-oxo-3-(pyrîdin-3-yl)propanenitrile (0.82 g, 5.61 mmol) and methylhydrazlne (0.25 g, 5,61 mmol) and stirred at reflux for 2 hours. The reaction was cooled to room température and concentrated to dryness. The crude material was purified by silica gel chromatography by eluting with 0-20% MeOH/dichloromethane to yield two products 1-methyl-5-(pyridin-3-yl)-1H-pyrazol-3-amine (0.060 g; 6.14%): ’H NMR (300 MHz, CDCI₃) □ 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) and 1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine (0.150 g, 15.35%): ’H NMR (300 MHz, CDCI₃) δ 8.88 (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: Préparation of 3-pyrazo!-1-yl-pyrldine

To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml of acetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs₂CO₃ (16.5 g, 0.050 mol), Cu₂O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g, 0.006 mol) under N₂ atmosphère. 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 %): Ή NMR (400 MHz, CDCI₃) □ 8.99 (d, J = 2.8 Hz, 1 H), 8.48 (dd, J = 4.8,1.2 Hz, 1 H), 8.11 - 8.08 (m, 1 H), 7.99 (d, J = 1.2 Hz, 1 H), 7.78 (d, J = 1.2 Hz, 1 H), 7.38 7.35 (m, 1H), 6.53 (t, J= 1.2 Hz, 1H); MS (m/z) 146 [M+1],

3-(3-chloro-1 H-pyrazol-1-yl)pyridine was prepared as ln Example 6, Step 1: mp 98-106 •C; ¹H NMR (400 MHz, CDCI₃) δ 8.93 (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, 1 H), 7.90 (d, J = 2.5 Hz, 1 H), 7.42 (ddd, J = 8.3,4.8, 0.7 Hz, 1 H), 6.46 (d, J = 2.5 Hz, 1H): ¹³C (DMSO-de) 148,142,140,136,131,126,125,108.

2-methy!-3-(3-methyl-1 H-pyrazol-1 -yl)pyridlne was prepared as ln Example 6, Step 1:¹H NMR (400 MHz, CDCI₃) δ 8.53 (d, J = 4.7 Hz, 1 H), 7.67 (d, J = 7.9 Hz, 1 H), 7.54 (t, J = 8.0 Hz, 1 H), 7.27 - 7.19 (m, 1H), 6.27 (d, J- 1.4 Hz, 1H), 2.53 (s, 3H), 2.38 (s. 3H).

3-(3-(Trifluoromethyl)-1 H-pyrazol-1 -yl)pyridine was prepared from the appropriate starting materiais as described ln Example 6, Step 1: mp 59.0-61.0 °C; ’H NMR (400 MHz, CDCI3) δ 9.00 (s, 1 H), 8.70 - 8.59 (m, 1 H), 8.11 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 8.05 - 7.98 (m, 1 H), 7.46 (dd, J = 8.3, 4.8 Hz, 1 H), 6.79 (d, J = 2.4 Hz, 1 H); EIMS m/z 213.

3-Fluoro-5-(3-methyl-1 H-pyrazol-1-yl)pyridine was prepared from the appropriate starting materiais as described ln Example 6, Step 1: mp 70.0-72.0 *C; ’H NMR (400 MHz, CDCI3) δ 8.76 - 8.73 (m, 1 H), 8.37 - 8.33 (m, 1 H), 7.88 - 7.85 (m, 1 H), 7.84 - 7.79 (m, 1 H), 6.34 - 6.29 (m, 1H), 2.37 (s, 3H); EIMS m/z 177.

3-(3-Chloro-1 H-pyrazol-1 -yl)-5-fluoropyridine was prepared from the appropriate starting materiais as described ln Example 6, Step 1: mp 77.0-82.0 ’C; ’H NMR (400 MHz, CDCI₃) δ 8.75 (d, J = 1.8 Hz, 1 H), 8.43 (d, J = 2.3 Hz, 1 H), 7.92 (d, J = 2.6 Hz, 1 H), 7.84 (dt, J = 9.3, 2.4 Hz, 1H), 6.48 (d, J- 2.6 Hz, 1H); EIMS m/z 198.

3-(3-methyl-1 H-pyrazol-1 -yl)pyridine was prepared as described in Example 6, Step 1: ’H NMR (400 MHz, CDCI₃) δ 8.94 (bs, 1H), 8.51 (d, J = 3.9 Hz, 1H), 8.02 (ddd, J- 8.3, 2.6,1.5 Hz, 1 H), 7.90 - 7.79 (m, 1 H), 7.39 (dd, J = 8.2, 5.1 Hz, 1 H), 6.30 (d, J - 2.4 Hz, 1 H), 2.39 (s, 3H).

3-(5-methyl-1 H-pyrazol-1 -yl)pyridine was prepared as in Example 6, Step 1: ’H NMR (400 MHz, CDCI₃) δ 8.77 (d, J = 2.5 Hz, 1 H), 8.65 (dd, J = 4.8, 1.5 Hz, 1 H), 7.84 (ddd, J = 8.2,

2.5,1.5 Hz, 1 H), 7.63 (d, J = 1.6 Hz, 1 H), 7.44 (ddd, J = 8.2, 4.8, 0.7 Hz. 1 H), 6.225 (dd, J = 1.6, 0.7 Hz, 1H), 2.40 (s, 3H).

Example 6, Step 2: Préparation of 3-(4-nltro-pyrazol-1-yl)-pyridlne

NO.

3-Pyrazol-1-yl-pyridine (2 g, 0.032 mol) was dissolved ln concentrated H₂SO₄ (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 H₂SO₄ (30ml, 15 Vol.) was added dropwise over a period of 30 min. Cooling was discontinued and the reaction mixture was stirred

5t at room température ovemight After the reaction was complété, the mixture was poured over crushed ice and neutralized with saturated NaHCOj, filtered, washed with water and dried to fumish the nitro pyrazole as pale yellow solid (1.8 g, 68%): ’H NMR (400 MHz, DMSO-de) □

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,

1H), 7.51 (dd, J = 8.4,4.8 Hz, 1H); MS (m/z} 191 [M+1].

3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 2: mp

139-142 ’C, Ή NMR (400 MHz, CDCI₃) δ 9.01 (d, J = 2.0 Hz, 1 H), 8.73 (d, J = 4.9 Hz, 2H), 8.08 (ddd, J = 8.3,2.5,1.3 Hz, 1 H), 7.52 (dd, J = 8.3,4.8 Hz, 1 H), EIMS m/z 224.

3-(5-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 2:¹H NMR (400 MHz, CDCI₃) δ 8.81 - 8.71 (m, 2H), 8.32 (s, 1 H), 7.83 (ddd, J = 8.2, 2.5,1.6 Hz, 1 H), 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)pyridîne was prepared as In Example 6, Step 2: Ή NMR (400 MHz, d_B-DMSO) δ 14.01 (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); ,’³C 154, 150, 146,135, 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; Ή NMR(400 MHz, CDCI₃) δ 9.01 (d. J= 2.5 Hz, 1 H). 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-Fiuoro-5-(3-methyl-4-nltro-1H-pyrazol-1-yl)pyridine was prepared from the appropriate starting material as described in Example 6, Step 2: mp 90.0-92.0 ’C; ¹H NMR (400 MHz, CDCI3) δ 8.82 (d, J = 2.0 Hz, 1 H), 8.69 (s, 1 H). 8.54 (d, J = 2.5 Hz, 1 H), 7.89 (dt, J = 8.9,2.4 Hz, 1H), 2.66 (s, 3H); EIMS m/z 222.

3-(4-Nitro-3-(trifluoromethyl)-1H-pyrazol-1-yi)pyridine was prepared from the appropriate starting material as described in Example 6, Step 2: mp 121.0-123.0 ’C; ¹H NMR (400 MHz, CDCI3) δ 9.04 (d, J = 2.5 Hz, 1 H), 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-yl)-5-fluoropyridine was prepared from the appropriate starting material as described in Example 6, Step 2: mp 109.5-111.0 ’C; ¹H NMR (400 MHz, CDCI₃) δ 8.83 (d, J = 2.1 Hz, 1 H), 8.75 (s, 1 H), 8.60 (d, J = 2.4 Hz, 1 H), 7.89 (dt, J = 8.6,2.4 Hz, 1H); EIMS m/z 242.

3-(3-Bromo-4-nitro-1H-pyrazol-1-yl)pyridine was prepared from the appropriate starting material as described in Example 6, Step 2: mp 139.0-141.0 ’C; ’H NMR (400 MHz, CDCI₃) δ 9.01 (d, J = 2.5 Hz, 1 H), 8.73 (dd, J = 4.7,1.1 Hz, 1 H), 8.71 (s, 1 H), 8.15 - 8.00 (m, 1 H), 7.52 (dd, J= 8.3, 4.8 Hz, 1H); ESIMS m/z 271 ([M+2]*).

Example 6, Step 3: Préparation of 1-pyrldln-3-yl-1H-pyrazol-4-ylamlne

To a solution of 3-(4-nitro-pyrazo!-1-yl)-pyridine (1.8 g, 0.009 mol) in dry THF (18 mL) was added 5% Pd/C (180 mg) under nitrogen atmosphère. The mixture was then stirred under hydrogen atmosphère until the reaction was complété. The reaction mixture was filtered through a pad of celite, and concentrated to dryness to give an impure dark brown solid (1.76 g): ’H NMR (400 MHz, DMSO-d_e) □ 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, 1 H). 7.54 (d, J = 1.2 Hz, 1 H), 7.45 (d, J = 0.4 Hz, 1 H), 7.38 - 7.35 (m, 1 H), 4.81 (bs 1H); ESIMS (m/z) 161 [M+1].

5-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Example 6, Step 3:’H NMR (400 MHz, CDCI₃) δ 8.74 (d, J = 2.3 Hz, 1 H), 8.63 - 8.50 (m, 1 H), 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): ¹³C (DMSO-d_e) 147,144, 137, 133,130,129,124,123,10; EIMS m/z 174

3-methyl-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as ln Example 6, Step 3: mp 211-215 ’C; Ή NMR (400 MHz, CDCI₃) δ 9.10 - 8.87 (m, 3H). 7.51 (s. 1 H). 3.24 (bs, 2H),

2.29 (s, 3H); ESIMS m/z 176 ([M+H]).

3-chloro-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as in Example 6, Step 3: mp 146-148 ’C; Ή NMR (400 MHz. CDCI₃) δ 9.07 (s. 1 H), 9.02 (s. 2H), 7,52 (s, 1H), 3.45 (s, 2H); ESIMS m/z 196 ([M+H]).

Example 7: Préparation of methyl-(1-pyrldln-3-yl-1H-pyrazol-4-yl)-amlne

Method A:

To a 25 ml round bottom flask containing 1-pyridin-3-yl-1H-pyrazol-4-ylamine (1.76 g, 0.011 mol) in éthanol (26.4 mL) was added benzotriazole (1.31 g, 0.011 mol). The reaction was cooled at 0°C - 10°C and formaldéhyde (0.36 mL, 0.0121 mol) was added slowly and kept for 30 min at this température. The reaction was filtered and concentrated to dryness. The crude material (2.56 g, 0.009 mol) was dissolved ln dry tetrahydrofuran (25.6 mL), cooled to 0°C and sodium borohydride (0.326 g, 0.00882 mol.) was added over 15 min. The reaction was warmed to room température 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 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, de-DMSO) □ 8.92 (d, J = 2.4 Hz, 1 H), 8.47 (dd, J = 4.8,1.6 Hz, 1 H), 8.01 - 7.98 (m, 53

1H), 7.45 (S, 1H), 7.30 (s, 1 H). 7.37 (dd, J = 8.0, 4.4 Hz, 1H), 2.84 (s, 3H); ESIMS m/z 175 «M+1]).

Method B:

1-pyridin-3-yl-1H-pyrazol-4-ylamlne (1.0 g, 6.2 mmol) was dissolved in trlethyl orthoformate (5 mL, 30 mmol) and to that was added trifluoroacetic acid (3-4 drops). The réaction mixture was refluxed at 120*0 for 3 hours and was then concentrated. The crude was dissolved in éthanol (5 ml), cooled to 0*C and treated with sodium borohydride (0.6 g, 15.7 mmol). After warming to room température, the mixture was refluxed for 3 hours. The mixture was concentrated and the residue was suspended between water and diethyl ether. The diethyl 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; ¹H NMR (300 MHz, CDQ₃) δ 8.91 (bs, 1H), 8.46 (d, J = 4.5 Hz, 1 H), 7.99 (d, J = 8.3 Hz, 1 H), 7.43 (s, 1 H), 7.41 (s, 1 H), 7.36 (dd, J = 8.3, 4.7 Hz, 1H), 2.86 (d, J = 12.4 Hz, 3H); ESIMS m/z 175 ([M+1]).

Example 8: Préparation of ethyl-(1-pyrldln-3-yl-1H-pyrazol-4-yl)-amlne

Method A:

To 1-pyridin-3-y!-1H-pyrazol-4-ylamine (0.5 g, 3.12 mmol) in dichloromethane (5 mL) was added acetyl chloride (0.28 g, 3.75 mmol) followed by DMAP (0.57 g, 4.68 mmol) and stirred at room température for 3 hours. The reaction mixture was concentrated and purified by silica gel column chromatography. The recovered material was dissolved in tetrahydrofuran (5 mL) and lithium aluminum hydride (0.23 g, 6.25 mmol) was added and stirred at room température for 12 hours. The reaction was quenched with saturated Na₂SO₄ and filtered through celite. The filtrate was coliected and concentrated to dryness. The crude material was 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 (0.080 g, 14%): ¹H NMR (400 MHz, CDCI₃) δ 8.90 (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).

Method B:

To a solution of tert-butyl ethyl(1-(pyridin-3-y!)-1H-pyrazol-4-yl)carbamate (3.4 g, 11.79 mmol) in dichioromethane (4.54 mL) was added trifluoroacetic acid (9 mL), and the reaction mixture was stirred for 1 hour at room température. Toluene was added and the reaction was concentrated to near dryness. The reaction was poured Into a separatory funnel and carefully 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% MeOH/dichloromethane) to give the desired product as a pale yellow oil (2.10 g, 95%): Ή NMR (400 MHz, CDCI₃) δ 8.90 (dd, J = 1.8, 0.8 Hz, 1 H), 8.51 8.39 (m, 1 H). 7.97 (ddt, J-8.3, 2.7,1.3 Hz, 1 H), 7.41 (d, J = 0.8 Hz, 2H). 7.38 - 7.30 (m, 1 H), 3.21 - 2.93 (m, 2H), 1.34 -1.19 (m, 3H).

3-chloro-N-ethyl-1-(pyridÎn-3-yl)-1H-pyrazol-4-amine was prepared as described In Example 8, Method B: Ή NMR (400 MHz, CDCI₃) δ 8.87 (d, J = 2.5 Hz, 1H), 8.47 (dd, J = 4.7, 1.2 Hz, 1 H), 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), 2.97 (bs, 1H), 1.31 (t, J = 7.1 Hz, 3H).

3-chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazoi-4-amine was prepared as in Example 8, Method B: mp 108-118 C; Ή NMR (400 MHz, CDCI₃) δ 8.88 (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.

N,3-dlmethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as In Example 8, Method B: Ή NMR (400 MHz, CDCI₃) δ 9.03 - 8.73 (m, 1 H). 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-yl)-1H-pyrazol-4-amine was prepared as In Example 8, Method B: Ή NMR (400 MHz, CDCI₃) δ 8.86 (d, J~ 2.5 Hz, 1H), 8.47 (dd, J = 4.7,

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-propyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as ln Example 8, Method B: ’H NMR (400 MHz, CDCI₃) δ 8.86 (d, J = 2.6 Hz, 1 H). 8.47 (dd, J = 4.7, 1.4 Hz, 1 H). 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 Hz, 3H).

1-(5-Fluoropyridin-3-yl)-N,3-dimethyl-1/7-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, CDCI₃) δ 8.67 (s, 1 H), 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+Hf).

N-ethyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described ln Example 8, Method B: mp 85.0-86.0 C; ’H NMR (400 MHz, CDCI₃) δ 8.66 (s, 1H), 8.25 (d, J =2.5 Hz. 1H). 7.72 (dt. J = 10.0,2.3 Hz, 1 H), 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 (ΙΜ+ΗΓ).

3-Methyl-N-propyl-1-(pyrldin-3-yl)-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) δ 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

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-(cyclopropylmethyl)-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amlne was prepared from the appropriate Boc-amine as described In Example 8, Method B: mp 73.0-75.0 ’C; ’H NMR (400 MHz, CDCI3) δ 8.86 (d, J = 2.4 Hz, 1 H), 8.40 (dd, J = 4.7,1.3 Hz, 1 H), 7.94 (ddd. J = 8.3,

2.6.1.5 Hz, 1 H), 7.35 - 7.28 (m, 2H), 2.87 (d, J = 6.9 Hz, 2H). 2.75 (s, 1 H), 2.28 (s, 3H), 1.22 1.05 (m, 1 H), 0.63 - 0.56 (m, 2H), 0.26 (q, J = 4.7 Hz, 2H); ESIMS m/z 229 ([M+H]*).

N-isopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described In Example 8, Method B: IR (thln film) 3303 cm'¹; ’H NMR (400 MHz, CDCI3) δ 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. 1 H), 7.36 - 7.28 (m, 2H), 3.30 (hept, J = 6.3 Hz, 1 H), 2.25 (s, 3H), 1.24 (d, J = 6.3 Hz, 6H); EIMS m/z 216.

5-Ethoxy-1-(5-fluoropyridin-3-yl)-/V,3-dÎmethyl-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described In Example 8, Method B: IR (thin film) 3340 cm’; ’H NMR (400 MHz, CDCI3) δ 8.91 (s. 1 H). 8.31 (d, J = 2.5 Hz. 1 H). 7.88 - 7.80 (m, 1 H), 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/z250.

5-Bromo-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: mp 77.0-79.0 ’C; ’H NMR (400 MHz, CDCI3) δ 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, 1H), 7.51 (s, 1 H). 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-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ’H NMR (400 MHz, CDCI₃) δ 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. 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-/V,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ’H NMR (400 MHz, CDCI₃) δ 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 266 ([M+H]*).

5-Chloro-N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ’H NMR (400 MHz, CDCI₃) δ 8.87 (d, J = 2.3 Hz, 1 H), 8.59 (dd, J = 4.8,1.3 Hz, 1 H), 7.90 (ddd, J = 8.2, 2.6,1.5 Hz, 1 H), 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-fluoropyr1din-3-yl)-N-methyl-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described In Example 8, Method B: mp 117.5-119.0 ’C; ’H NMR (400 MHz, CDCh) δ 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 m/z 227 ([M]*).

3-Chloro-/V-ethyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ¹H NMR (400 MHz, CDCI3) δ

8.70-8.63 (m, 1H), 8.32 (d, J = 2.4 Hz, 1H), 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).

1- (5-Fluoropyridin-3-yl)-N-methyl-3-vinyl-1H-pyrazoi-4-amlne was prepared from the appropriate Boc-amine as described in Example 8, Method B: 105.0-107.0 ’C; ¹H NMR (400 MHz, CDCh) δ 8.72 (s. 1 H), 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+H]*).

3-Cyclopropyl-1-(5-fluoropyridin-3-yl)-/V-methyl-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, CDCI3) δ 8.66 - 8.58 (m, 1 H), 8.23 (d, J = 2.5 Hz, 1 H). 7.75 - 7.68 (m, 1 H), 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+H]*)·

3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Bocamine as described ln Example 8, Method B: mp 137.9-139.9; ’H NMR (400 MHz, CDCI₃) δ 8.84 (d, J = 2.4 Hz, 1 H), 8.50 (dd, J = 4.7,1.4 Hz, 1 H), 7.95 (ddd, J = 8.3,2.7,1.5 Hz, 1 H), 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+H]*).

2- ((3-Chloro-1-(pyridin-3-yl)-1 H-pyrazol-4-yl)amino)acetonitrile was prepared from tertbutyl (3-chloro-1-(pyridin-3-y1)'1/7-pyrazol-4-yl)(cyanomethy1)carbamate as in Example 8, Method B: mp 141-143 ’C; ’H NMR (300 MHz, CDCI3) δ 8.91 (d, J = 2.7 Hz, 1 H), 8.54 (dd, J = 5.1,1.8 Hz, 1 H), 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, 1 H); El MS m/z 235 ([M+1]*).

N-3-dimethyl-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as ln Example 8, Method B: mp 139-143 ’C; Ή NMR (400 MHz, CDCI3) δ 9.02 (s, 2H), 9.00 (s. 1 H). 7.30 (s, 1 H).

2.87 (d, J= 11.5 Hz, 3H). 2.27 (s, 3H); ESIMS m/z 190 ([M+H]).

3- chloro-N-methyl-1-(pyrimidin-5-yl)1-1H-pyrazol-4-amlne was prepared as in Example 8, Method B: mp 111-114 ’C; Ή NMR (400 MHz, CDCI3) δ 9.09 - 9.04 (m, 1 H). 9.02 (s, 2H),

7.30 (s, 1H), 3.14 (bs, 1H), 2.88 (s, 3H); ESIMS m/z 196 ([M+H]).

1-(5-Fluoro-3-pyridyl)-3-methyl-N-(trideuteriomethyl)pyrazol-4-amine was prepared from compound 380 using the procedure as described ln Example 8, method B: mp 146-148 °C; ’H NMR (400 MHz, CDCI3) δ 8.67 (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+H]*); IR (Thîn film) 1599 cm'¹.

3-Chloro-1-(3-pyridyl)-A/-(trideuteriomethyl)pyrazol-4-amine was prepared from compound 381 using the procedure as described in Example 8, method B: mp 104-106 °C; ’H NMR (400 MHz, CDCI3) δ 8.87 (d, J = 1.9 Hz, 1 H), 8.47 (d, J = 4.7 Hz, 1 H), 8.00 - 7.90 (m, 1 H), 7.40 - 7.30 (m, 2H), 3.10 (s, 1 H); ESIMS m/z 212 ([M+H]*); IR (Thin film) 1579 cm'¹.

3-Chloro-N-(cyclopropylmethyl)-1-{pyridin-3-yl)-1 H-pyrazol-4-amlne was prepared from compound 361 using the procedure as described ln Example 8, method B: mp 82-83 °C; ¹H

NMR (400 MHz, CDCI₃) δ 8.86 (d, J = 2.5 Hz, 1 H), 8.47 (dd, J = 4.7,1.3 Hz, 1 H), 7.95 (ddd, J =

8.4, 2.7,1.5 Hz, 1 H), 7.38 - 7.32 (m, 2H), 3.22 (s, 1 H), 2.90 (d, J = 6.9 Hz, 2H), 1.23-1.06 (m,

1H), 0.65 - 0.53 (m, 2H), 0.31 - 0.19 (m. 2H).; ESIMS m/z 249 ([M+H]*):

3-Chloro-/V-propyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from compound 360 using the procedure as described ln Example 8, method B: mp 92-94 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.86 (d, J = 2.6 Hz, 1 H), 8.47 (dd, J = 4.7,1.4 Hz, 1 H), 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 (m. 2H), 1.02 (t, J = 7.4 Hz, 3H); ESIMS m/z 237 ([M+H]*).

3-Chloro-1-(pyridin-3-yl)-N-(4,4,4-trifluorobutyl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described ln Example 8, Method B: IR (thin film) 3416, 3089 cm’¹; ’H NMR (400 MHz, CDCi₃) δ 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 (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-Chioro-1-(pyridin-3-yl)-N-(5,5,5-trifluoropentyl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Exampie 8, Method B; IR (thln film) 3087 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 8.86 (d, J = 2.5 Hz, 1 H), 8.48 (dd, J = 4.7,1.4 Hz, 1 H), 7.96 (ddd, J =

8.3.2.7.1.5 Hz, 1 H), 7.36 (ddd, J = 8.3, 4.8, 0.6 Hz, 1 H), 7.34 (s. 1 H), 3.10 (s, 2H), 3.04 (s, 1 H),

2.30 -1.98 (m, 2H), 1.84 -1.69 (multiple peaks, 4H); ”F NMR (376 MHz, CDCi₃) δ -66.28; ESIMS m/z 320 ([M+2H]*).

3-Chloro-N-(4-fluorobutyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described în Example 8, Method B: mp 82-83 °C; IR (thin film) 3348, 3086 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 8.86 (d, J = 2.5 Hz, 1 H), 8.47 (dd, J = 4.7,1.4 Hz, 1 H), 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); ESIMS m/z 269 ([M+H]*).

3-Chloro-N-lsopropyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thln film) 3318,1583 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 8.86 (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, 1 H), 1.02 (d, J = 6.7 Hz, 6H); ESIMS m/z 251 ([M+H]*).

3-Chloro-N-(2-methoxyethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3364,1485 cm’¹; ’H NMR (400 MHz, CDCI₃) δ 8.86 (dd, J =2.7, 0.7 Hz, 1 H). 8.48 (dd, J = 4.7,1.5 Hz, 1H), 7.96 (ddd, J = 8.4, 2.7,1.5 Hz, 1 H), 7.38 (s, 1 H), 7.38 - 7.34 (m, 1 H), 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]*).

3-Chloro-N-((2,2-difluorocyclopropyl)methyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ’H NMR (400

MHz, CDCh) δ 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, 2H), 2.00-1.84 (m, 1H), 1.55 (m, 1H), 1.26 (s, 1 H), 1.23 -1.11 (m, 1H); ¹⁹F NMR (376 MHz, CDCI₃) δ -128.61 (d, J = 159.5 Hz), -143.58 (d, J = 160.0 Hz); ESIMS m/z 285 ([M+H]*).

3-Chioro-N-(3-fluoropropyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amlne was prepared from the appropriate Boc-amine as described ln Example 8, Method B: iR (thin film) 3359 cm'¹; ’H NMR (400 MHz, CDCh) δ 8.87 (d, J = 2.7 Hz, 1 H), 8.48 (dd, J = 4.7, 1.4 Hz, 1 H), 7.95 (ddd, J = 8.3,

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, 1 H), 2.17 -1.92 (m, 2H); ESIMS m/z 255 ([M+H]*).

N-allyl-3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described ln Example 8, Method B: IR (thin film) 3291 cm'¹; ’H NMR (400 MHz, CDCh) δ 8.85 (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, 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 ([M+H]*).

2- ((3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)amino)ethyl acetate was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3361,1733 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 8.87 (s, 1 H), 8.49 (d, J = 4.7 Hz, 1 H), 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-fluoroethyf)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3369 cm’¹; ’H NMR (400 MHz, CDCh) δ 8.86 (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, 1 H), 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+H]*).

3-Chloro-1-(pyridin-3-yl)-N-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ESIMS m/z 292 ([M+H]*).

3-Chloro-N-(2,2-difluoroethyf)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3295 cm'¹; ’H NMR (400 MHz, CDCh) δ 8.87 (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 (tt, J = 55.9, 4.1 Hz, 1H), 3.69 - 3.26 (multiple peaks, 3H); ’®F NMR (376 MHz, CDCh) δ -122.15; ESIMS m/z 259 ([M+H]*).

3-Chloro-1-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)-1H-pyrazol-4-amîne was prepared from the appropriate Boc-amine as described In Example 8, Method B: IR (thln film) 3309 cm'¹; ¹H

NMR (400 MHz, CDCI₃) δ 8.92-8.85 (m, 1H), 8.52 (dd, 4.8,1.4 Hz, 1H), 7.98 (ddd, J = 8.4,

2.7, 1.5 Hz, 1 H). 7.47 (s, 1H), 7.40 (ddd, J= 8.4,4.8, 0.7 Hz, 1 H). 3.68 (q, J= 8.9 Hz, 2H), 3.49 (s, 1H); ’⁹F NMR (376 MHz, CDCI₃) δ -72.29; ESIMS m/z 277 ([M+H]*).

3-Chloro-N-(2-chloroethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thln film) 3354 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 8.86 (dd, J = 2.7, 0.7 Hz, 1 H). 8.50 (dd, J = 4.8, 1.5 Hz, 1H), 7.96 (ddd, J = 8.3, 2.7,1.4 Hz. 1 H), 7.40 (s, 1 H), 7.37 (ddd, J = 8.5,4.8, 0.8 Hz, 1 H), 3.76 (dd, J = 6.0, 5.4 Hz, 2H), 3.54 (s, 1H), 3.43 (t, J = 5.7 Hz, 2H); ESIMS m/z 257 ([M+H]*).

3-Chloro-1-(pyridin-3-yl)-N-(3_l3,3-trifluoropropyl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thln film) 3366, 3081 cm'¹; ’H NMR (400 MHz, CDCh) δ 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, 2H), 3.22 (t, J = 6.7 Hz, 1H), 2.48 (qt, J = 10.7, 7.0 Hz, 2H); ’⁹F NMR (376 MHz, CDCI₃) δ -64.99; ESIMS m/z 291 ([M+H]*).

N-(but-2-yn-1-yl)-3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3249, 3122 cm'¹; ’H NMR (400 MHz, CDCh) δ 8.89 (dd, J = 2.7, 0.7 Hz, 1H), 8.49 (dd, J= 4.8,1.5 Hz, 1H), 7.98 (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+H]*).

3-Chloro-/V-lsobutyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Exampie 8, Method B: ’H NMR (400 MHz, CDCh) δ 8.86 (d, J= 2.5 Hz, 1 H), 8.47 (dd, J = 4.7,1.3 Hz, 1 H), 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, 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: Préparation of lsopropyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amlne

1-pyridin-3-yl-1H-pyrazol-4-ylamlne (0.6 g, 3.7 mmol) was dissoived in isopropyl acetate (8.5 mL). To the mixture, acetone (0.261 g, 4.5 mmol), trifluoroacetic acid (0.855 g, 7.5 mmol) and sodium triacetoxyborohydride (0.945 g, 4.5 mmol) were added. The reaction was stirred under nitrogen at room température 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

I chromatography (gradient elution of 5% methanol/dichloromethane) to give the title compound as an off white solid (0.35 g, 46%): mp 105 -107 “C; Ή NMR (300 MHz, CDCI₃) δ 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 Hz,6H). ESIMS 214 m/z (M+1).

Example 10: Préparation of propyl-(1«pyridin-3-yl-1H-pyrazol-4-y1-amIne

To 1-pyridin-3-yl-1H-pyrazol-4-ylamine (0.5 g, 3.12 mmol) in dichioromethane (5 mL) was added propionaldéhyde (0.18 g, 3.12 mmol) and sodium triacetoxy borohydride (0.99 g, 4.68 mmol) and stirred at room température for 16 hours. The réaction was taken up in dichioromethane 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% MeOH/Dichloromethane and resubjected in 0-100% ethylacetate/hexanes) to give the title compound as a dark oil (0.05 g, 7%): ¹H NMR (300 MHz, CDCI3) δ 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, 1 H). 7.47 - 7.40 (m, 2H). 7.37 (dd, J = 8.3. 4.7 Hz, 1 H), 3.04 (t, J = 7.1 Hz, 3H), 1.92 -1.46 (m, 2H). 1.03 (t, J = 7.4 Hz, 3H).

Example 11: Préparation of N-methyl-N-(1-pyridin-3-yl-1W-pyrazol-4-yl)-IsobutyramÎde (Compound 42)

A solution of isobutyryt chloride (0.138 g, 1.3 mmol) in dichioroethane (1 mL) was pipetted at a dropwise rate into an ice-cold suspension of methyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine (0.15 g, 0.86 mmol) in dichioroethane (5 mL), stirred for 10 minutes and then treated at a dropwise rate with a solution of 4-/V,N-dimethylaminopyridine (0.11 g, 0.9 mmol) in dichioroethane (1.5 mL). The cooling bath was removed after 30 minutes, stirred under nitrogen at room température for 14 hours, diluted with dichioroethane (40 mL), washed with water (30 mL), brine (10 mL), dried over MgSO₄ and purified by reversed phase column chromatography to give a yellowlsh gum (0.114 g, 54%) ’H NMR (300 MHz, CDCI₃) δ 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 (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]).

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, 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: Préparation of 4,4,4-trlfluoro-2-methyi-N-(1-(pyrldin-3-yl)-1H-pyrazol-4yl)butanamlde (Compound 65)

To a solution of 1-{pyridin-3-yl)-1H-pyrazol-4-amine (0.150 g, 0.93 mmol) in dichloroethane (1.8 mL) was added 4,4₁4-trifluoro-2-methylbutanoic acid (0.14 g, 0.93 mmol) and 4-/V,N-dimethylaminopyridine (0.23 g, 1.87 mmol) followed by 1-{3-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride (0.36 g, 1.87 mmol). The réaction stirred at room température ovemight. The reaction mixture was concentrated and the crude product was purified by silica gel chromatography eluting with 0-5% MeOH/dichloromethane to give a white solid (0.15 g, 55%); mp 140-145’C; ¹H NMR (400 MHz, CDCI₃) δ 9.00 (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, 1 H), 7.40 (ddd, J = 8.3, 4.8, 0.6 Hz, 1 H), 2.92 - 2.61 (m, 2H), 2.32 - 2.05 (m, 1 H), 1.38 (d, J = 6.6 Hz, 3H); ESIMS m/z 300 ([M+2]).

Compounds 53, 58, 62-63, 72,76,80 - 81,107 -108,136-138,147,151 -159,164168,176-179,187-196, 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, 539- 541,544 - 545, 549 - 554, 572 - 577, 578, 579 and 580 were prepared from the appropriate amines In accordance with the procedures disclosed In Example 12. Example 13: Préparation of tert-butyl 1-(pyrldln-3-yl)-1H-pyrazol-4-ylcarbamate (Compound 57)

Method A:

To a solution of 1-{pyridin-3-yl)-1H-pyrazol-4-amine (3 g, 18.73 mmol) In dichloromethane (33.4 mL) was added triethylamine (3.13 mL, 7.68 mmol) and BOC-anhydride (4.5 g, 20.60 mmol). The resulting solution was stirred at room température ovemight. The reaction mixture was partitioned between ethyi 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% ethyi acetate/hexanes to yieid a white solid (2.0 g. 41%); mp 108-112 ’C; ¹H NMR (400 MHz, CDCI₃) δ 9.02 (d, J=2.2 Hz, 1H). 8.51 (t. J= 8.7 Hz, 1H), 8.37 (s, 1 H), 8.30 (s, 1 H), 7.98 (ddd, J = 8.3, 2.4,1.3 Hz, 1 H), 7.68 (s, 1 H), 7.36 (dd, J = 8.2, 4.8 Hz, 1H). 1.52 (s, 9H); ESIMS m/z 261 ([M+1]).

Compounds 64 and 130 were prepared In accordance with the procedures disclosed in Example 13, Method A.

Method B:

To a solution of 1-(pyridin-3-yi)-1H-pyrazol-4-amine (0.1 g, 0.624 mmol) and di-tert-butyl dicarbonate (0.161 mL, 0.693 mmol) 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 température ovemight. The reaction was diluted with water and extracted with ethyi acetate. The combined organic phases were concentrate to give tert-butyl 1 -(pyrldin3-yi)-1H-pyrazol-4-yicarbamate (135 mg, 0.519 mmol, 83 %), for which the analytlcal 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 Exampie 13, Method B. Compound 172 and 317 was also prepared in accordance with the procedures disclosed in Example 17. These compounds, as well as, certain other compounds, were made by alternative methods further illustrating certain embodiments.

Example 14: Préparation of tert-butyl methyl(1-(pyrldln-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 67)

To a solution of tert-butyl 1-(pyridin-3-yi)-1H-pyrazol-4-yicarbamate (1.6 g, 6.15 mmol) in DMF (30.7 mL) at 0’C was added sodium hydride (0.34 g, 8.61 mmol, 60% dispersion In minerai oll) 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 ovemight at room température. Water and ethyi acetate were added and the resulting biphasic mixture was separated. The aqueous layer was extracted one time with ethyi acetate. The combined organic extracts were washed with brine, dried (MgSO₄), filtered and concentrated to dryness. The crude product was purified by silica gel chromatography eluting with 0-35% ethyl acetate/hexanes to yieid a light yellow semi-solid (0.85 g, 50%): IR (KBr) 1703 cm’¹; ¹H NMR(400 MHz, CDCI₃) δ 8.98 (s, 1H), 8.52 (d, J = 3.8 Hz, 1H).

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, 510 511,515,523, and 590 were prepared from the appropriate amldes in accordance with the procedures disclosed in Example 14.

Tert-butyl methyl(3-methyl-1-(pyridin-3-y1)-1H-pyrazol-4-yl)carbamate was prepared as in Example 14: ’H NMR (400 MHz, CDCI₃) δ 8.91 (d, J = 2.5 Hz, 1H), 8.51 (dd, J = 4.7,1.3 Hz, 1 H), 8.00 (ddd, J = 8.3,2.4,1.4 Hz, 1 H), 7.83 (s, 1 H), 7.38 (dd, J = 8.3, 4.7 Hz, 1 H), 3.20 (s, 3H), 2.22 (s, 3H), 1.60-1.30 (m, 9H).

Example 15: Préparation of N-ethyl-N-(1-methyl-3-(pyrldln-3-yl)-1H-pyrazol-5-

To a solution of N-(1-methyl-3-(pyridine-3-yl)-1W-pyrazol-5-yl)isobutyramide (0.08 g, 0.33 mmol) ln DMF (0.66 mL) at 0’C was added sodium hydride (0.016 g, 0.39 mmol, 60% dispersion in minerai oil) in one portion and the suspension was stirred for 30 minutes. The Ice bath was removed and stirred for an additional 30 minutes. Iodoethane (0.06 g, 0.39 mmol) was added In one portion and stirred ovemight at room température. Water and ethyl acetate were added and the resulting blphasic mixture was separated. The aqueous layer was extracted one time with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO<), filtered and concentrated to dryness. The crude product was purified by silica gel chromatography to give the titie compound as a clear oil (27.5 mg, 30%): ’H NMR (300 MHz, CDCIj) δ 9.00 (bs, 1 H), 8.57 (s, 1 H), 8.09 (dd, J = 7.9 Hz, 1 H), 7.34 (dd, 1 H), 6.48 (s, 1 H), 4.00 (m, 1 H), 3.76 (s, 3H), 3.36 (m, 1 H), 2.33 (m, 1 H), 1.17 (t, J = 7.1 Hz, 3H), 1.08 (t, J =6.7 Hz, 6H); ESIMS m/z 273 (M+H).

Compound 22 was prepared ln accordance with the procedures disclosed ln Example 15.

Exemple 16: Préparation of 5-bromo-1H-pyrazol-4-amlne, HBr

Br ^Η^^~^ΝΗ2·^ΗΒΓ

A mixture of 4-nitro-1H-pyrazole (10 g, 88 mmol) and 5% palladium on AI₂O₃ (1 g) ln a mixture of éthanol (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 ethanoi.

The filtrate was concentrated in vacuo to give a white solid. This solid was suspended In 10 mL of éthanol. After swirling the flask for 5 min, diethyl ether was added to complété the crystallization. The solid was filtered. was washed with ether and dried under high vacuum to afford 5-bromo-1H-pyrazol-4-amlne, HBr (18.1 g, 84 % yield) as a white solid: mp 248 ^eC dec;

¹H NMR (400 MHz, DMSO-d_e) δ 11.47 (s, 1H), 10.00 (s, 1H), 7.79 (s, 1H).

Example 17: Préparation of tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 172)

Example 17, Step 1: Préparation of 3-chloro-1H-pyrazol*4*amine hydrochloride

Into a 2 L three-necked round bottom flask affixed with an overhead stirrer, a température probe, an addition funnel, and a nitrogen Inlet were added éthanol (600 mL) and 4nitro-1H-pyrazole (50.6 g, 447 mmol). To this solution was added, In one portion, conc. HCl (368 mL) (note: rapid exotherm from 15 °C to 39 °C) 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 mixture and stirred at room température while triethylsilane (208 g, 1789 mmol) was added drop-wise over 4 h. The reaction, which started to slowly exotherm from 35 °C to 55 °C 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 °C, 50 mmHg) to dryness with the aid of acetonitrile (3 x 350 mL). The resulting yellow solid was suspended In acetonitrile (150 mL) and allowed to stand for 2 h at room température followed by 1 h at 0 oc in the refrigerator. The solids were filtered and washed with acetonitrile (100 mL) to afford the titled compound 3-chloro-1H-pyrazol-4amlne hydrochloride (84 g, 97% yield, 80% purity) as a white solid: mp 190-193 ’C; ¹H NMR (400 MHz, DMSO-d_e) δ 10.46 -10.24 ( bs, 2H), 8.03 (s, 0.54H), 7.75 (s, 0.46H), 5.95 (bs, 1H)); ⁿC-NMR (101 MHz, DMSO) δ 128.24, 125.97, 116.71.

Example 17, Step 2: Préparation of tert-butyl (3-chloro-1H-pyrazol-4-yl)carbamate

Into a 2 L round bottom flask was added 3-chloro-1H-pyrazol-4-amine hydrochloride (100 g, 649 mmol) and THF (500 mL). To this mixture were added di-fert-butyldicarbonate (156 g, 714 mmol) followed by sodium bicarbonate (120 g, 1429 mmol) and water (50.0 ml). The mixture was stirred for 16 h, diluted with water (500 mL) and ethyl acetate (500 mL) and 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 ethyi acetate (2 x 200 mL) and the ethyi acetate extracts were combined, washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and rotary evaporated to give an auburn thïck 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 oc and the solid collected by vacuum filtration and rinsed with hexane (2x10 mL). The sample was air dried to constant mass to afford (3-chloro-1H-pyrazol-4-yl)carbamate (102.97 g, 72% yield, 80% purity) as a light brown solid: mp 137-138 ’C; ¹H NMR (400 MHz, CDC!₃) δ 10.69 (s, 1H), 7.91 (s, 1H), 1.52 (s, 9H).

Example 17, Step 3: Préparation of tert-butyl (3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4yl)carbamate (Compound 172)

To a dry 2 L round bottom flask equipped with mechanical stirrer, nitrogen inlet, thermometer, and reflux condenser was charged the 3-iodopyridine (113.0 g, 551 mmol), (3chloro-1H-pyrazol-4-yl)carbamate (100 g, 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 A/¹,/'/-dimethylethane-1,2-dlamine (101 g,1149 mmol) were added and the mixture was heated to 81 ’C for 4 hours. The mixture was cooled to room température and filtered through a bed of Celite®. The filtrate was transferred to a 4 L Erienmeyer flask equipped with mechanical stirrer and diluted with water untii the total volume was about 4 L. The mixture was stirred for 30 minutes at room température and the resulting solid was collected by vacuum filtration. The solid was washed with water and washed with water and oven dried for several days in vacuo at 40 °C to a constant weight to give tert-butyl (3-chloro-1-(pyridtn-3-yl)-1Hpyrazol-4-yl)carbamate (117.8 g, 87% yield, 80% purity) as a tan solid: mp 140-143 ’C; ¹H NMR (400 MHz, CDCI₃) δ 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 ([Mt-Bu]*), 220 ([M-O-f-Bu]').

Compound 172 was also prepared in accordance with the procedures disclosed in Example 13. Compound 317 was prepared in accordance with the procedures disclosed ln Example 17 from tert-butyl (3-bromo-1H-pyrazol-4-yl)carbamate and also in accordance with the procedures disclosed in Example 13.

Example 18: Préparation of 3-(3-methyl-1H-pyrazol-1-yl)pyridine and 3-(5-methyl-1Hpyrazol-1 -y I ) pyrl di ne

To a solution of 3-methyl-1H-pyrazole (10.99 g, 134 mmol) In N,N-dimethylformamide (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 (10.0 g, 103 mmol) was added, and the reaction was stirred at 100 ’C overnlght. The reaction was cooled to room température 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 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-yl)pyridine (1.0 g, 6%). Analytical data of both products ls consistent with that reported under Example 6, Step 1.

3-(3-Bromo-1H-pyrazol-1-yl)pyridine was prepared from 3-fluoropyridine and 3bromopyrazole, which was made as in W02008130021, as described Example 18: mp 89.5-

92.5 ’C; Ή NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.4 Hz, 1 H), 8.62 - 8.49 (m, 1 H), 8.03 (ddd, J = 8.3,2.7,1.4 Hz, 1H), 7.87 (d, J = 2.5 Hz, 1H). 7.42 (dd, 8.2, 4.7 Hz, 1H), 6.54 (d, J= 2.5 Hz, 1H); ESIMS m/z 224 ([Mf).

Example 19, Préparation of 3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amlne

To a stirred solution of 5-chloro-1H-pyrazol-4-amine, HCl (2 g, 12.99 mmol) and césium carbonate (8.89 g, 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 température and filtered. The solids were washed with copious amount of ethyl acetate. The filtrâtes was washed with brine, dried over anhydrous MgSO< and concentrated in vacuo to give a brown soüd. This solid was dissolved in ethyl acetate and the resulting solution was saturated with hexanes to precipitate 3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine (2.31g, 10.32 mmol, 79 % yield) as a brown solid: Ή NMR (400 MHz, DMSO-d_e) δ 8.89 - 8.82 (m, 1H). 8.45 (d, J =

2.5 Hz, 1 H), 8.07 (d, J= 10.4 Hz, 1H), 7.94 (s, 1H), 4.51 (s, 2H); El MS (m/z) 213 ([M+1]+).

3-Bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine was prepared from the corresponding pyrazole as described in Example 19: mp 164-165 ’C; ’H NMR (400 MHz, CDCI₃) δ 8.65 (d, J = 1.7 Hz, 1 H), 8.36 (d, J = 2.5 Hz, 1 H), 7.76 (dd, J = 5.9, 3.6 Hz, 1 H), 7.48 67 (s, 1 H). 3.22 (s, 2H). ¹³C NMR (101 MHz, CDCIa) δ 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+1J+).

Example 20: Préparation of 1-(5-fluoropyr1dln-3-yl)-3-methy1-1H-pyrazol-4-amlne

To a solution of 3-fluoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine (3.133 g, 14.10 mmol) in éthanol (28.2 ml) was added ethyl acetate until ail of the starting material went into solution. The solution was degassed and 10% palladium on carbon (0.750 g, 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-fiuoropyridtn-3-yl)-3methyl-1H-pyrazol-4-amine (2.000 g, 10.41 mmol, 73.8 %) as a brown solid: mp 136.0-138.0 ’C; ’H NMR (400 MHz, CDCI3) δ 8.67 - 8.59 (m, 1 H), 8.27 (d, J = 2.5 Hz, 1 H), 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-yl)-3-(trifluoromethyl)-1H-pyrazol-4-amine was prepared from the appropriate nitropyrazole as described In Example 20: mp 112.5-115.0’C; ’H NMR (400 MHz, CDCI3) δ 8.89 (d. J = 2.4 Hz, 1 H), 8.57 (dd, J = 4.7, 1.4 Hz, 1 H), 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: Préparation of 3-chloro-1-(pyrIdin-3-yl)-1H-pyrazo1-4-amlne

To 3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine (0.95 g, 4,23 mmol) in acetic acid (8.46 mL), éthanol (8.46 mL) and water (4.23 mLJwas added iron powder (1.18 g, 21.15 mmol) and the reaction was stirred at room température for 30 minutes. To this was added carefully 2 M KOH and extracted with ethyl acetate. The ethyl acetate layers were combined, dried (MgSO₄), filtered and concentrated to dryness. The crude material was purified by silica gel chromatography (0-10% methanol/dichloromethane) to give the desired product as a white solid (0.66 g, 80%): Ή NMR (400 MHz, CDCI3) δ 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-yl)-1H-pyrazol-4-amine was prepared as described in Example 21: ’H NMR (400 MHz, CDCI₃) δ 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.

3-PhenyL1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate nitropyrazole as described ln Example 21: IR (thin film) 3324 cm*¹: ’H NMR (400 MHz, CDCI₃) δ

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

236.

3-Chforo-1-(5-fluoropyridin-3-yl)-1H-pyrazoi-4-amine was prepared from the appropriate nitropyrazole as described ln Example 21: mp 149.0-151.0 ^eC; ’H NMR (400 MHz, CDCI₃) δ 8.65 (d, J = 1.6 Hz, 1 H), 8.35 (d, J = 2.4 Hz, 1 H). 7.75 (dt. J = 9.5, 2.4 Hz, 1 H), 7.51 (s, 1 H), 3.21 (s, 2H): ESIMS m/z 213 ([M]*).

3-Bromo-1-(pyridin-3-yf)-1H-pyrazol-4-amine was prepared from the appropriate nitropyrazole as described In Exampie 21: mp 143.0-146.0 ’C; ’H NMR (400 MHz, CDCI₃) δ 8.85 (d, J= 2.4 Hz, 1H), 8.50 (dd, J = 4.7,1.4 Hz, 1H), 7.96 (ddd, J = 8.3, 2.7,1.5 Hz, 1H), 7.49 (s, 1H), 7.37 (ddd, J= 8.4, 4.7, 0.7 Hz, 1H), 3.21 (s, 2H); ESIMS m/z 241 ([M+2]*).

Example 22: Préparation of tert-butyl (5-methyl-1-(pyridîn-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 281)

To a solution of (E)-tert-butyl 1-(dimethylamino)-3-oxobut-1-en-2-ylcarbamate (0.59 g, 2.58 mmol) ln éthanol (2.5 mL) was added 3-hydrazinylpyridine, 2HCI (0.470 g, 2.58 mmol). The reaction mixture was stirred at ambient température for 16 hours. The reaction mixture was 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*’; ’H NMR (400 MHz, CDCI₃) δ 8.75 (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, 1 H), 7.78 (s, 1 H), 7.43 (ddd, J = 8.1,4.8, 0.6 Hz, 1 H), 6.04 (s, 1H), 2.29 (s, 3H), 1.52 (s, 9H); ESIMS m/z 275 ([M+H]*), 273 ([M-H]').

Example 23: Préparation of tert-butyl 1-(5-fluoropyrldin-3-yi)-3-methyl-1H-pyrazol-4ylcarbamate (Compound 111) and tert-butyl 5-ethoxy-1-(5-fluoropyrldln-3-yl)-3-methyl-1Hpyrazol-4-ylcarbamate (Compound 112)

To a solution of 3-fluoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine (3.133 g, 14.10 mmoi) in éthanol (28.2 mi) was added ethyl acetate until ail of the starting material went into solution. The solution was degassed and 10% palladium on carbon (0.750 g, 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 sotvent was removed under reduced pressure. The residue was dissolved In tetrahydrofuran (32.0 ml) and water (9.61 ml). Di-tertbutyl 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 température ovemight, 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-(5fluoropyrldîn-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (1.673 g, 5.72 mmoi, 41.0 %) as a yellow solid and the tert-butyl 5-ethoxy-1-(5-fluoropyrldin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (0.250 g, 0.74 mmol, 5.2 %) as a brown oil:

Tert-butyl 1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (Compound 111): mp 131.5-133.0 *C; ¹H NMR (400 MHz, CDC1₃) δ 8.75 (s, 1H), 8.32 (d, J = 2.5 Hz, 1 H), 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); ESIMS m/z 293 ([M+H]*).

Tert-butyl 5-ethoxy-1 -(5-fluoropyrldin-3-yl)-3-methyl-1 H-pyrazol-4-ylcarbamate (Compound 112): IR (thln film) 1698 cm'¹; Ή NMR (400 MHz, CDCI₃) δ 8.88 (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 m/z 337 ([M+H]*).

Example 24: Préparation of Bis tert-t-butyl (1-(pyrldin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 595)

To a solution of tert-butyl (1-(pyridin-3-yl)-ïH-pyrazol-4-yl)carbamate (2.00 g, 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 portion and stirred at that température for 30 minutes. To this was then added Boc-Anhydride (1.84 g, 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 température 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 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%): Ή NMR (400 MHz, CDCI₃) δ 9.12 - 8.86 (m, 1 H), 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: Préparation of 3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-amine (Compound 516)

To tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (2 g, 6.79 mmol) ln dichloromethane (6.79 ml) was added trifluoroacetic acid (6.79 ml) and the mixture was left stirring at room température for 2 hours. Toluene (12 mL) was added and the reaction was concentrated to near dryness. The mixture was poured into a separatory funnel containing saturated aqueous sodium bicarbonated and was extracted with dichloromethane. The combined organic layers were concentrated to give 3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-amine (0.954g, 4.90 mmol, 72.2 %) as a white solid: mp 137.9-139.9 ’C: Ή NMR (400 MHz, CDCI₃) δ 8.84 (d, J = 2.4 Hz, 1 H), 8.50 (dd, J = 4.7,1.4 Hz, 1 H), 7.95 (ddd, J - 8.3, 2.7,1.5 Hz, 1 H), 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+H]*).

Example 26: Préparation of N-allyl-1-(5-fluoropyrldin-3-yl)-3-methyl-1H-pyrazol-4-amlne hydrochloride

To a solution of tert-butyl allyl(1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4yljcarbamate (908 mg, 2.73 mmol) in dioxane (5 mL) was added HCl (1M ln ether) (13.65 mL, 13.65 mmol) and the mixture stirred at room température for 48 h. The resulting white solid was filtered, washed with ether and dried under vacuum to give N-allyl-1-(5-fluoropyridin-3-yl)-3methyl-1H-pyrazol-4-amine, HCl (688 mg, 94 % yield) as a white solid: mp 189-190 ’C; ’H NMR (400 MHz, CDCI₃) δ 8.79 - 8.68 (m, 1 H), 8.32 - 8.26 (m, 1 H), 8.23 (s, 1 H), 7.98 - 7.86 (m, 1 H), 5.86 - 5.68 (m, 1 H), 5.28 - 5.17 (m, 1 H), 5.17 - 5.03 (m, 1 H), 3.59 (d, J - 6.2 Hz, 2H), 2.11 (s, 3H): EIMS (m/z) 233 ([M+1 ]+).

N-Allyl-3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was prepared as described in Example 26 from fert-butyl allyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 172-174 ’C; ’H NMR (400 MHz, CDCI₃) δ 9.20 (d, J = 2.5 Hz, 1H), 8.65 (dd, J= 5.3,1.1 Hz, 1H), 8.61 (ddd, J = 8.6, 2.5,1.1 Hz, 1 H), 8.24 (s, 1 H), 7.93 (dd, J = 8.6, 5.3 Hz, 1 H), 3.66 (dt, J = 5.5,1.3 Hz, 2H); EIMS (m/z) 235 ([M+1]+).

N-Allyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was prepared as described in Example 26 from tert-butyl allyl(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl): mp 195-197 ’C; ’H NMR(400MHz, DMSO-d_e) δ 9.12 (d, J= 2.4 Hz, 1H), 8.58(dd, J-5.0, 1.2 Hz, 1H), 8.48(s, 1 H), 8.43 (d, J = 9.7 Hz, 1 H), 7.77 (dd, J = 8.4, 5.0 Hz, 1 H), 6.04 - 5.92 (m, 1 H), 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]+).

3-Bromo-1-(5-fluoropyridin-3-yl)-N-methyl-1H-pyrazol-4-amine, HCl was prepared as described in Example 26 from tert-butyl 3-bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl(methyl)carbamate: mp 167-168 *C; ’H NMR (400 MHz, CDCI₃) δ 8.93 (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).

3-Bromo-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was prepared as described in Example 26 from tert-butyl (3-bromo-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(methyt)carbamate (160 mg, 0.45 mmol) in dioxane (1 mL) was added 4M HCl: mp. 226-228 ’C; ’H NMR (400 MHz, DMSO-c/e) δ 9.26 - 9.06 (d, J = 2.6 Hz, 1 H), 8.69 - 8.54 (m, 1 H), 8.54 - 8.39 (d, J = 8.0 Hz, 1 H), 8.33- 8.14 (s, 1H), 7.90-7.72 (m, 1H), 2.82-2.67 (s, 3H); EIMS (m/z) 253 ([M+1]+), 255 ([M+2H]+).

3-Bromo-N-ethyl-1-(pyridin-3-yl)-1/7-pyrazol-4’amine_l HCl was prepared as described in Example 26 from 3-bromo-A/-ethyb1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl: mp 216-217 ‘C; ’H NMR (400 MHz, DMSO-c/_e) δ 10.66 - 10.05 (s, 3H), 9.28 - 9.20 (d, J = 2.5 Hz, 1 H), 8.74 - 8.67 (m, 1H), 8.67 - 8.56 (m, 3H), 7.96 - 7.84 (m, 1H), 3.21 - 3.14 (m, 2H). 1.29-1.22 (m, 3H): EIMS (m/z) 267 ([M+1 ]+).

3-Chloro-N-(2-methoxyethyl)-1-(pyridin-3-yt)-1H-pyrazol-4-amine_l HCl was prepared as described in Example 26 from tert-butyl (3-chloro-1-(pyridin-3-yi)-1H-pyrazol-4-yl)(2methoxyethyljcarbamate, HCl: mp 157-158 ’C;’H NMR (400 MHz, DMSO) δ 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, 1 H), 3.59 - 3.50 (t, J = 5.8 Hz, 2H). 3.32 - 3.27 (s, 3H), 3.22 - 3.14 (m. 2H); EIMS (m/z) 253 ([M+1]+). Example 27: Préparation of 3-chloro-N-ethyl-1-(pyrldln-3-yl)-1H-pyrazol-4-amlne hydrochloride

Into a 500 mL three-necked round bottom flask equipped with a magnetic stir bar was added a solution of tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-ylXethyl)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 OC. A solution of 4M HCI/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 température for 16 hours. The reaction was diluted with 200 mL of ethyl ether and the solid was filtered and washed with ether and placed in a vacuum oven at 40 oc for 18 hours. The title compound was isolated as a pale yellow solid (18.2 g, 95%): ’H NMR (400 MHz, MeOD) δ 9.52 (d, J = 2.5 Hz, 1H), 9.17 (s, 1H)_t 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, IH), 3.58 (q, J =7.3 Hz, 2H), 1.48 (t, J = 7.3 Hz, 3H): ESIMS m/z 223 ([M+H]*).

3-Chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazole-4-amine, 2HCI was prepared as described In Example 27: ’H NMR (400 MHz, MeOD) δ 9.28 (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. MeOD) δ 141.42,139.58,137.76,134.58,134.11,129.33, 127.55,

122.14,35.62); ESIMS m/z 209 ([M+H]*).

Example 28: Préparation of S^nitro-S-phenyl-IH-pyrazol-l-yOpyrldine

To a suspension of phenylboronlc 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 éthanol (3.31 ml) and 2 M aqueous potassium carbonate (1.492 ml, 2.98 mmol). The solution was degassed by applying vacuum and then purglng with nitrogen (3 times). To the reaction mixture was added paliadium 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 give 3-(4-nitro-3-phenyl-1 H-pyrazol-1-yl)pyridine (499 mg, 1.874 mmol, 80 %) as a yellow solid: mp 144.0-146.0 ’C; ¹H NMR (400 MHz, CDCI3) δ 9.09 (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 m/z 266.

Example 29: Préparation of 5-bromo-1-(pyridin-3-yl)-1H-pyrazol-4-yl(methyl)carbamate (Compound 110)

To tert-butyl methyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (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 réaction was stirred ovemight at 50°C. The reaction was concentrated, diluted with dichloromethane, and washed with water and saturated aqueous sodium thiosulfate. The organic phase was concentrated to give fert-butyl 5-bromo-1-(pyridin-3-yl)-1H-pyrazol-4yl(methyl)carbamate (256 mg, 0.725 mmol, 99 %) as a brown oil: IR (thin film) 1697 cm¹; ’H NMR (400 MHz, CDCI₃) δ 8.89 (s, 1H), 8.68 (d, J= 4.1 Hz, 1H), 7.93 (ddd, J = 8.2,2.5,1.5 Hz,

1H), 7.69 (s, 1Η), 7.46 (dd, J~ 8.1, 4.8 Hz, 1H), 3.22 (s, 3H), 1,44(s, 9H); ESIMS m/z352 ([MΗΓ).

Example 30: Préparation of Bis fert-t-butyl (5-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4yljcarbamate (Compound 109)

To Bis fert-t-butyl (1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (1.30 g, 3.61 mmoi) ln acetonitrile (21.22 mL) was added N-chlorosuccinimide (0.96 g, 7.21 mmol) and the reaction was stirred at 45 ^eC for 48 hours. The reaction was cooled to room température and poured Into water and extracted with dichioromethane. The dichioromethane layers were combined, poured 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 (0.90 g, 63%); mp 109-115 C; ¹H NMR (400 MHz, CDCI₃) δ 8.90 (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+H]*).

Tert-butyl (5-chloro-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(methyl)carbamate was prepared from the appropriate pyrazole in dichioroethane as the solvent as described in Example 30: ESIMS m/z 324 ([M+H]*).

Compounds 110 (see also procedure ln Exampie 29) and 146 were prepared from the appropriate pyrazoles using N-bromosuccinimïde ln accordance with the procedures disclosed ln Example 30.

Tert-butyl 5-bromo-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl(methyl)carbamate was prepared from the appropriate pyrazole ln dichioroethane as described ln Example 30:¹H NMR (400 MHz, CDCI₃) δ 8.88 (d, J = 2.3 Hz. 1 H), 8.69 - 8.60 (m, 1 H), 7.96 - 7.86 (m, 1 H), 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+H]*).

Exampie 31: Préparation of bis fert-butyl (5-fluoro-1-(pyrldin-3-yl)-1H-pyrazoi-4yl)carbamate (Compound 135)

To a solution of bis fert-t-butyl (1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (0.075 g,

0.208 mmol) in DMF (0.416 ml) and acetonitrile (0.416 ml) was added Selecfluor® (0.184 g,

0.520 mmol). The reaction was stirred at room température for one week. The reaction was concentrated, saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organic phases were concentrated and chromatographed (ΟΙ 00% ethyl acetate/hexanes) to give bis tert-butyl (5-fluoro-1-(pyridin-3-y1)-1H-pyrazol-4y1)carbamate (16 mg, 0.042 mmol, 20.32 %) as an off-white solid: ¹H NMR (400 MHz, CDCI3) δ 8.97 (t, J = 2.0 Hz, 1 H), 8.61 (dd, J = 4.8,1.4 Hz, 1 H), 7.99 (ddt, J = 8.3, 2.6,1.3 Hz, 1 H), 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+H]*).

Tert-butyl (5-fluoro-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-y1Xmethy1)carbamate was prepared as described in Example 31 : ’H NMR (400 MHz, CDCI3) δ 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), 1.58 - 1.40 (m, 9H); ESIMS m/z 307 ([M+H]*).

Example 32: Préparation of N-cyclopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine Example 32, Step 1: Préparation of 3-(4-iodo-3-methyl-1H-pyrazol-1-yl)pyridine

To a mixture of 3-(3-methy1-1H-pyrazol-1-yl)pyridine (6.7 g, 42.1 mmol), iodic add (2.96 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 réaction 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 magnésium sulfate, filtered and 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-1Hpyrazol-1-yl)pyridine (11.3 g, 35.7 mmol, 85 %) as a white solid: mp 131 ’C; ’H NMR (400 MHz, CDCI3) δ 8.95 - 8.85 (m, 1 H), 8.52 (dd, J = 4.8,1.4 Hz, 1 H), 8.00 - 7.94 (m, 1 H), 7.91 (s, 1 H), 7.38 (ddd, J = 8.3,4.8, 0.7 Hz, 1H), 2.34 (s, 3H); EIMS m/z 285.

Example 32, Step 2: Préparation of W-cyclopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4amlne

To a solution of 3-(4-lodo-3-methyM H-pyrazol-1 -yîjpyridine (2.0 g, 7.02 mmol) in dimethylsulfoxide (7.02 ml) was added 1-(5,6,7,8-tetrahydroquinolin-8-yl)ethanone (0.246 g, 1.403 mmol), cyclo propana mine (0.486 ml, 7.02 mmol), césium carbonate (6.86 g, 21.05 mmol) and copper(l) 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 acetate/hexanes) to give W-cyclopropyf-3-methyl-1-(pyridin-3-yf)-1H-pyrazol-4-amine (269 mg, 1.255 mmol, 17.90 %) as a yellow solid: mp 104.0-107.0 ^eC; ¹H NMR (400 MHz, CDCh) δ 8.89 (dd, J = 2.7, 0.5 Hz, 1 H), 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, 1 H), 7.33 (ddd, J = 8.3, 4.7, 0.7 Hz, 1 H), 3.42 (s, 1 H), 2.53 - 2.42 (m, 1 H), 2.22 (s, 3H), 0.72 - 0.65 (m, 2H), 0.60 - 0.53 (m, 2H); ESIMS m/z 215 ((M+Hf).

3-Methyl-N-(3-(methylthio)propyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amÎne was prepared as described in Example 32: IR (thin film) 3298 cm'¹; ’H NMR (400 MHz. CDCh) δ 8.87 (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+Hf).

3-Methyl-N-(2-methyl-3-(methylthio)propyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as described in Example 32: IR (thin film) 3325 cm’; ’H NMR (400 MHz, CDCh) δ 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, 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 (s. 3H), 2.12 - 2.02 (m, 1 H), 1.11 (d, J = 6.8 Hz, 3H); EIMS m/z 276.

Exampie 33: Préparation of tert-butyl (3-cyc!opropy!-1-(5-fluoropyridin-3-y!)-1H-pyrazo!-4yl)carbamate (Compound 434) and tert-butyl (1-(5-fluoropyrldin-3-yl)-1H-pyrazol-4yl)carbamate (Compound 489)

To a suspension of 2-cyciopropyl-4_l4,5,5-tetramethyl-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-yl)-1H-pyrazol-4yl)carbamate (1.1 g, 3.08 mmol) followed by éthanol (6.84 ml) and 2 M aqueous potassium carbonate (3.08 mL, 6.16 mmol). The solution was degassed by appiying vacuum and then purging with nitrogen (3 times). To the reaction mixture was added palladium tetrakis (0.178 g, 0.154 mmoi) 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 (3cyclopropy!-1-(5-fluoropyridïn-3-yl)-1H-pyrazol-4-yl)carbamate (705 mg, 2.215 mmol, 71.9 % yield) as a yellow solid and tert-butyl (1-(5-fluoropyridin-3-yl)-1H-pyrazoi-4-yl)carbamate (242 mg, 0.870 mmoi, 28.2 % yleid) as a yellow solid.

tert-Butyl (3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazoi-4-yl)carbamate: mp 156.5-158.0; ’H NMR (400 MHz, CDCI3) δ 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, 1 H), 6.43 (s, 1 H), 1.55 (s. 9H), 1.01 - 0.91 (m, 4H); ESIMS m/z 319 ([M+Hf).

(1-(5-Fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 121.0-123.0 ’C; ’H NMR (300 MHz, CDCI3) δ 8.78 (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 m/z 278 ([M]*).

Compounds 340 and 404 were prepared as described In Example 33.

Example 34: Préparation of tert-butyl (3-ethyi-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl)(methyl)carbamate (Compound 408)

To a N2-purged solution of tert-butyl (1-(5-fluoropyridïn-3-yl)-3-vinyl-1H-pyrazol-4yl)(methyl)carbamate (0.730 g, 2.293 mmol) in methanoi (15.29 mi) 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 température for 60 hours. The reaction gave less than 20% conversion. The reaction mixture was fiitered through celite, concentrated, and redissolved in ethyl acetate (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% complété. 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 fert-butyl (3-ethyl-1-(5fluoropyridin-3-yt)-1H-pyrazol-4-yl)(methyt)carbamate (616 mg, 1.923 mmol, 84 % yield) as yellow oil: IR (thin film) 1692 cm-¹; Ή NMR (300 MHz, CDCIj) δ 8.71 (t, J= 1.4 Hz. 1H), 8,35 (d. J = 2.6 Hz, 1 H), 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: Préparation of N-(1-(5-fluoropyridin-3-yl)-3-formyl-1H-pyrazol-4yl)lsobutyramide (Compound 560)

To a solution of N-(1-(5-fluoropyridin-3-yl)-3-vinyl-1H-pyrazol-4-yt)isobutyramide (0.706 g, 2.57 mmol) In tetrahydrofuran (12.87 ml) and water (12.87 ml) was added osmium tetroxide (0.164 mi, 0.026 mmol), After 10 minutes at room température, sodium periodate (1.101 g, 5.15 mmoi) was added ln portions over 3 minutes and the resulting solution was stirred at room température. 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-yt)-3-formyl1H-pyrazol-4-yt)isobutyramide (626 mg, 2.266 mmol, 88 % yield) as a yellow solid: mp 140.0142.0 C; ’H NMR(300 MHz, CDCIj) δ 10.12 (s. 1H), 9.14(s, 1 H), 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+H]*).

Compound 369 was prepared in accordance with the procedures disclosed in Example 35.

Example 36: Préparation of W-(1-(5-fluoropyrldin-3-yl)-3-(hydroxymethyi)’1H-pyrazol-4yl)isobutyramide (Compound 435) and W-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl)isobutyramlde (Compound 436)

To a solution of N-(1-(5-fluoropyridin-3-yt)-3-formyt-1H-pyrazol-4-yl)isobutyramide (0.315 g, 1.140 mmol) ln methanol (5.70 ml) at 0 *C was added sodium borohydride (0.086 g, 2.280 78 mmol). The reaction was stirred at 0 ’C for 2 hours, and room température for 20 hours. 0.5 M HCl 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% ethy! acetate/hexanes) to give N-(1-(5-fluoropyridin-3-yl)-3(hydroxymethy!)-1H-pyrazol-4-y!)isobutyramide (180 mg, 0.647 mmol, 56.7 %) as a white solid and N-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-y!)isobutyramide (9 mg, 0.036 mmol, 3.18 %) as a white solid.

N-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)isobutyramide: mp 144.0146.0 ’C; ¹H NMR (400 MHz, CDCI₃) δ 8.74 (d, J = 1.1 Hz, 1H), 8.64 (s, 1H), 8.37 - 8.29 (m, 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 ([M+H]*).

N-(1-(5-fluoropyridin-3-y!)-1H-pyrazol-4-y!)isobutyramide: IR (thin film) 1659 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 8.79 (d, J= 1.2 Hz, 1H), 8.60 (s, 1H), 8.38 (d, 2.5 Hz, 1H), 7.81 (dt, J = 9.5, 2.3 Hz, 1 H), 7.68 (s, 1 H), 7.54 (s, 1 H), 2.63 - 2.51 (m. 1 H), 1.28 (d, J = 6.9 Hz, 6H); ESIMS m/z 249 ([M+H]*).

Example 37: Préparation of N-(3-(chloromethyl)-1-(5-fluoropyrldln-3-yl)-1H-pyrazo1-4-

To a solution of A/-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4y1)isobutyramide (0.100 g, 0.359 mmol) in dichloromethane ( 3.59 ml) was added thiony! chloride (0.157 ml, 2.151 mmol). The réaction was stirred at room température 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-(chloromethy!)-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-y!)Îsobutyramide (100 mg, 0.337 mmol, 94 % yieid) as a white solid: mp 172.0-177.0 ’C; ¹H NMR (400 MHz, CDCI₃) δ 8.79 (s, 1 H). 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, 1 H), 1.30 (d, J = 6.9 Hz, 6H); ESIMS m/z 298 ([M+H]*).

Example 38: Préparation of N-(3-ch1oro-1-(pyrldln-3-yI)-1H-pyrazol-4-yi)-A/-ethyi-2methoxyacetamide (Compound 512) (see also Example 11)

To a solution of 3-chloro-/V-ethyl-1-(pyridin-3-yl)-1H-pyrazo1-4-amlne, 2HCI (0.130 g, 0.502 mmol) and in DCM (2.508 ml) was added N-ethyl-N-lsopropylpropan-2-amlne (0.257 ml, 1.505 mmoi) foilowed by 2-methoxyacetyt chloride (0.109 g, 1.003 mmol) and the reaction mixture was stirred at ambient température for 16 hours. The reaction was quenched by the addition of saturated sodium bicarbonate. The organic layer was extracted with DCM. The organic layer was dried over sodium suifate, filtered, concentrated and purified using silica gel chromatography (0-100% ethyl acetate/hexanes) to yield the title compound as a pale yellow oil (0.12 g, 77%): IR (thin film) 3514, 3091, 2978,1676 cm-¹; Ή NMR (400 MHz, CDCI₃) δ 8.96 (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 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 m/z 295 ([M+H]*).

Compounds 71,478,481,483 - 484, and 543 were prepared in accordance with the procedures disciosed in Example 38.

Example 39: Préparation of N43-chloro-1-(5-fluoropyrldln-3-yl)-1H-pyrazol-4-yl)-N-€thyl-2methyl-S-fniethylthlolbutanamide (Compound 182) and (Z)-N-(3-chloro-1-(5-fluoropyrldin3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methylbut-2-enamlde (Compound 183)

To a solution 2-methyl-3-(methylthio)butanoic acid (0.154 g, 1.039 mmol) in dichloromethane (1 mL) at room température was added 1 drop of dimethylformamlde. Oxalyl dichloride (0.178 ml, 2.078 mmol) was added dropwise and the reaction was stirred at room température ovemight. 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-yl)-1H-pyrazol-4-amine (0.100 g, 0.416 mmol) and 4-dimethylaminopyridine (0.254 g, 2.078 mmol) in dichloromethane (1.5 mL) and stirred at room température ovemight. 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-(5fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-(methylthio)butanamide (34 mg, 0.092 mmol, 22.06 %) as a faint yellow oil and (Z)-N-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazo1-4-yl)/V-ethyl-2-methylbut-2-enamide (38 mg, 0.118 mmol, 28.3 % yield) as a yellow oil.

N-(3-chloro-1 -(5-fluoropyridin-3-yl)-1 H-pyrazol-4-yi)-Methyl-2-methyl-3(methylthio)butanamide: IR (thin film) 1633 cm’¹; Ή NMR (400 MHz, CDCI₃) δ 8.79 (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, 1 H), 80

2.59 - 2.33 (m, 1 H), 2.04 (s, 2H), 2.02 (s, 1 H). 1.32 (d, J = 6.7 Hz, 1 H), 1.27 (d, J = 6.2 Hz, 1 H),

1.23 (d, J = 6.9 Hz, 2H), 1.18 - 1.12 (m, 5H); ESIMS m/z 371 ([M]*).

(Z)-A/-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-y1)-N-ethy1-2-methylbut-2-enamide: ’H NMR (400 MHz, CDCI₃) δ 8.73 (d, J= 2.0 Hz, 1 H). 8.46 (d, J= 2.4 Hz, 1H), 7.87 (d, J = 4.9 Hz, 1H), 7.84 (dt, J = 9.2, 2.4 Hz, 1 H). 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); ESIMS m/z 323 ([M]*).

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 ln Example 39.

Example 40: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-N-methyl-2(methylthio)acetamlde (Compound 337)

To an Ice cold solution of 2-(methylthlo)acetic acid (0.092 g, 0.863 mmol) In DCM (2 mL) was added N-ethyl-N-isopropy1propan-2-amine (0.111g, 0.863 mmol) followed by isobutyl 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-yl)-1H-pyrazol-4-amine (0.08 g, 0.383 mmol) in DCM (0.66 mL) and the reaction mixture was stirred at ambient température for 2 hours. The reaction mixture was concentrated and purified using reverse phase C-18 column chromatography (0-100% CH3CN/H2O) to yield the title compound as a pale yellow oil (0.075 g, 66%): ’H NMR (400 MHz. CDCI₃) δ 8.95 (d, J « 2.5 Hz, 1 H), 8.62 (dd. J = 4.8,1.4 Hz, 1 H), 8.13 (s, 1 H), 8.04 (ddd, J = 8.3, 2.7,1.4 Hz, 1 H), 7.50 - 7.43 (m, 1 H), 3.26 (s, 3H), 3.12 (s, 2H), 2.24 (s, 3H); ’³C NMR (101 MHz, CDCI₃) δ 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+Hf).

Compounds 335,336, and 542 were prepared In accordance with the procedures disclosed in Example 40.

Example 41, Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoi-4-yi)-/V-ethyi-2-methyl3-oxobutanamide (Compound 499)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl (259 mg, 1 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 heated In a microwave (CEM Discover) at 150 ’C for 1.5 h, with extemal IR-sensor température monitorlng 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 NH4CI (15 mL), and the organic phase was separated. The aqueous phase was extracted with ethyl acetate (20 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 N-f3-chloro-1-(pyridin-3-yl)-1Hpyrazol-4-yl)-N-ethyl-2-methyl-3-oxobutanamide (37 mg, 11 % yieid, 96% purity) as a colorless oil: ¹H NMR (400 MHz, CDCI₃) δ 9.02 - 8.92 (dd, J = 2.6, 0.8 Hz, 1 H), 8.68 - 8.60 (dd, J = 4.8, 1.5 Hz, 1H), 8.09 - 7.98 (m, 1 H), 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 ([M+1]*), 319 ([M-1]').

Example 42: Préparation of N-(3-chloro-1-(pyrldin-3-y1)-1H-pyrazol-4-yl)-N· ethylcyclopropanecarboxamlde (Compound 538)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine monohydrochloride (0.10 g, 0.0.38 mmol) In dichloroethane (0.75 ml) was added cyclopropanecarboxylic acid (0.03 g, 0.38 mmol) and 4-N,N-dimethylaminopyridine (0.14 g, 1.15 mmol) followed by 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.14 g, 0.77 mmol). The reaction was stirred at room température ovemight. 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 (0.03 g, 25%); mp 111-119 ’C; ¹H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1 H), 8.63 - 8.59 (m, 1 H), 8.06 (ddd, J = 8.3, 2.6,1.4 Hz, 1 H), 8.01 (s, 1 H), 7.46 (dd, J= 8.3, 4.7 Hz, 1 H). 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 wîth the procedures disclosed in Example 42.

Example 43: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)-N-(3-(methylthlo)propanoyl)propanamlde (Compound 407)

S \

To a solution of W-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(methylthio)propanamide (0.216 g, 0.728 mmol) ln DCE (2.91 ml) in a 10 mL vial was added 2-methyl-3(methylthio)propanoyl chloride (0.244 g, 1.601 mmol). The vial was capped and placed in a Biotage Initîator microwave reactor for 3 hours at 100 *C, with extemal IR-sensor température 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 compound as a pale yellow oil (67 mg, 22%): IR (thin film) 2916 and 1714 cm*¹; ’H NMR (300 MHz, CDCI₃) δ 8.96 - 8.92 (d, J = 2.7 Hz, 1 H). 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, 1 H), 3.10 - 2.99 (td, J = 7.2, 3.9 Hz, 2H), 2.96 - 2.86 (dd, J = 13.2, 8.7 Hz, 1 H). 2.86 - 2.79 (t, J =7.3 Hz, 2H), 2.58 - 2.48 (dd, J = 13.1, 5.8 Hz, 1 H), 2.14 - 2.12 (s, 3H), 2.09 - 2.06 (s, 3H), 1.30 - 1.26 (d, J = 6.9 Hz, 3H); ESIMS m/z 413 ((M+Hf).

Compounds 383,410,433,437,451,470, 530 and 531 were prepared ln accordance with the procedures disclosed in Example 43.

Example 44: Préparation of N-[3-chloro-1-(3-pyridyl)pyrazol-4-yl]-2,2-dideuterio-N-ethyl-3methylsulfanyl-propanamlde (Compound 393)

To a 7 mL vial was added 3-chloro-W-ethyl-1-(pyridin-3-yl)-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 ^eC. 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 siowly and stirred at 25 °C ovemight. White precipitate formed during frie reaction. The crude reaction mixture was filtered through a cotton plug and purified by silica gel chromatography (0-100% EtOAc/hexane) to giveA/-[3-chloro-1-(3-pyridyl)pyrazol-4-yl]-2,2-dideuterio-W-ethyl-3methylsulfanyl-propanamide (97 mg, 0.297 mmol, 59.4 % yield) as a colorless oil: ’H NMR (400 MHz, CDClj) δ 8.96 (d, J = 2.4 Hz, 1 H), 8.63 (dd, J = 4.6,0.9 Hz, 1 H). 8.06 (ddd, J = 8.4, 2.7,

1.4 Hz, 1 H), 7.98 (s, 1 H), 7.52 - 7.40 (m, 1 H), 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+H]*); IR (Thin film) 1652 cm*¹.

Compounds 394,396, and 471 - 473 were prepared from the corresponding intermediates and starting materials in accordance with the procedures disclosed in Example

44.

Example 45: Préparation of 1-ethyl-3-(3-methyl-1-(pyridln-3-yl)-1H-pyrazol-4-yl)urea (Compound 145)

To a solution of 3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.1 g, 0.574 mmol) in DCM (5.74 ml) was added ethyl isocyanate (0.041 g, 0.574 mmol) and the reaction mixture was stirred at ambient température for 40 minutes. The reaction mixture had tumed from a clear solution to a suspension with white solid material. The reaction mixture was concentrated and purified using silica gel chromatography (0-20% MeOH/DCM) to yield the title compound as a white solid (0.135 g, 95%): mp 197-200 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.94 (d, J = 2.3 Hz, 1 H), 8.48 - 8.37 (m, 1 H), 8.32 (s, 1 H), 7.94 (d, J = 8.3 Hz, 1 H), 7.52 (br s, 1 H), 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+H]*), 244 ([M-H] ).

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 disclosed in Example 45.

1-(3-Chioro-1-(pyridîn-3-yl)-1H-pyrazoi-4-yl)-3-ethyl-1-mathylthiourea (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 Discover®) with extemal IR-sensor température monitoring from the bottom of the vessel at 120 ’C for 2 hours: white solid; mp 160.0-162.0 ’C; ’H NMR (300 MHz, CDC!₃) δ 8.94 (d, J = 2.6 Hz, 1H), 8.62 (dd, J= 4.8, 1.4 Hz, 1 H), 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); ESIMS m/z 297 ([M+H]*).

Example 46: Préparation of 3-butyl-1-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-1ethylurea (Compound 500)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yi)-1H-pyrazo!-4-amine, 2HCI (0.130 g, 0.502 mmol) in DCE (1.25 ml) was added N-ethyl-N-lsopropylpropane-2-amine (0.21 mL, 1.255 mmol) foliowed by 1-!socyanatobutane (0.109 g, 1.104 mmol) and the reaction mixture was stirred at ambient température for 16 hours. The reaction mixture was concentrated and purified 5 using silica ge! chromatography (0-20% MeOH/DCM) to yield the title compound as a beige solid (0.131 g, 77%): !R (thln film) 3326, 2959, 2931,1648 cm*¹; Ή NMR (400 MHz, CDCI₃) δ 8.95 (s, 1 H). 8.62 (d, J = 4.0 Hz, 1 H), 8.08 - 8.01 (m, 1 H), 7.97 (s, 1 H), 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]*).

Compounds 479 - 480, 501 - 504, 513, 518 and 519 were prepared according to

Example 46.

Example 47: Préparation of 1-(3-chioro»1-(pyridln-3-yl)-1H-pyrazol-4-yl)lmldazolidln-2-one (Compound 374)

Cl O

N

To a solution of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(2-chloroethyl)urea (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 température 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 concentrated. The product was a beige solid which was pure and dîd not need any further purification (63 mg, 72%): mp 167-170 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.96 (d, J= 2.2 Hz, 1 H), 8.56 (dd, J = 4.7,1.4 Hz, 1 H), 8.33 (s, 1 H), 7.99 (ddd, J = 8.3, 2.7,1.4 Hz, 1 H), 7.40 (ddd, J = 8.3, 4.8, 0.7 Hz, 1 H), 5.00 (s, 1 H), 4.14 - 4.07 (m, 2H), 3.68 - 3.58 (m, 2H); ESIMS m/z 264 ([M+H]*).

Compound 349 was prepared in accordance with the procedures disclosed in Example

47.

Exampie 48: Préparation of S-ferf-butyl (3-chioro»1-(pyridln-3-yl)-1H-pyrazol-4yl)(ethyl)carbamothioate (Compound 514)

To a solution of 3-chioro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, 2HCI (0.13 g.

0.502 mmol) ln DCM (2.508 ml) was added AAethyl-N-isopropylpropan-2-amine (0.257 ml, 1.505 mmol) followed by S-tert-butyl carbonochloridothioate (0.153 g, 1.003 mmol). The reaction mixture was stirred at ambient température for 16 hours. The reaction was quenched by the 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; Ή NMR (400 MHz, CDCIj) δ 8.96 (d, J - 2.5 Hz, 1H), 8.60 (dd, J = 4.7,1.4 Hz, 1 H), 8.08 - 8.03 (m, 1 H), 7.97 (s, 1 H), 7.47 - 7.41 (m, 1 H), 3.69 (q, J - 7.2 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 procedures disclosed in Example 48.

Example 49: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl3-(methio)propaneth1oamlde (Compound 364)

To a microwave reaction vessei was added N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)N-ethyl-2-methyl-3-(methio)propanamlde (0.07 g, 0.22 mmol) In dichloroethane (1.87 mL) and Lawesson’s reagent (0.05 g, 0.12 mmol). The vessei was capped and heated in a Biotage Initiator microwave reactor for 15 minutes at 130 ’C, with extemal IR-sensor température monitoring from the side of the vessei. 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 oll (0.33 g, 44%): IR (thin film) 1436 cm*¹; ’H NMR (400 MHz, CDCIa) δ 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]*).

Compounds 372,438 and 548 were prepared in accordance with the procedures disclosed in Example 49.

N-methyl-3-(methylthio)propanethloamide was prepared in accordance with the procedure disclosed in Example 49 and isolated as a clear oil; ’H NMR (400 MHz, CDCI₃) δ 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 ([M+H]*)·

Example 50: Préparation of N-(3-chloro-1*(pyrldin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-4,4,4trifiuoro-3-(methylsulflnyl)butanamlde (Compound 570)

To a 20 mL vial was added N-(3-chloro-1-(pyridin-3-yI)-1H-pyrazol-4-yl)-N-ethyI-4,4,4trifluoro-3-(methy!thio)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 and the solution was stirred at room température. After 3 hours the reaction was quenched with saturated sodium sulfite solution and extracted with EtOAc (3 x 20 mL). The combined organic layers were dried over sodium sulfate, concentrated and purified by chromatography (0-10% MeOH/DCM) to give N-ÎS-chloro-l-Îpyridin-S-ylJ-IH-pyrazoM-ylJ-N-ethyM^^trifluoro-S(methylsulfinyl) butanamlde (76 mg, 0.186 mmol, 89 % yield) as white semi-solid: ¹H NMR (400 MHz, CDCh) δ 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+Hf); IR (Thin film) 1652 cm*¹.

Compound 571 was prepared from the corresponding Intermediates and starting matériels In accordance with the procedures disclosed in Example 50.

Example 51: Préparation of W-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3(methylsulflnyl)propanamide (Compound 362)

To N-(3-chloro-1-(pyridin-3-y!)-1H-pyrazol-4-yl)-N-ethy!-3-(methy!thlo)propanamide (0.08 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 NaHCOj resulting in gas évolution. When the gas évolution had ceased, ethyl acetate was added and the layers were separated. The aqueous layer was extracted twice with ethyl acetate, and ail the organic layers were combined, dried over MgSO₄, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (0-10% methanoi/ dichloromethane) to give the desired product as a clear oil (0.03 g, 40%): IR (thin film) 1655 cm*¹; ¹H NMR (400 MHz, CDCia) δ 8.95 (t, J = 9.2 Hz, 1 H), 8.63 (dd, J = 4.7,1.4 Hz, 1 H), 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, 1 H), 2.94 - 2.81 (m, 1H), 2.74 - 2.62 (m, 2H), 2.59 (s, 3H), 1.25-1.07 (m, 3H); ESIMS m/z 341 ([M+H]*).

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: Préparation of W-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3(methylsulfonyl)propanamide (Compound 363)

To N-(3-chloro-1 -( pyridin-3-yl)-1 H-pyrazol-4-yl)-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 évolution. When the gas évolution had ceased, ethyl acetate was added and the layers were separated. The aqueous layer was extracted twice with ethyl acetate, and ail the organic layers were combined, dried over MgSO₄₁ 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 ciear oil (0.04,47%): (thin film) 1661 cm·¹; Ή NMR (400 MHz, CDCI₃) δ 8.95 (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, 1 H), 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 m/z 357 ([M+H]*).

Compounds 103,104, 219, 329, 331 and 495 were prepared from the appropriate sulfides in accordance with the procedures disclosed In Example 52.

Example 53: Préparation of N-(3-methyl-1-(3-fluoropyridln-5-yl)-1H-pyrazol-4-yl)N-ethyl-2methyl-(3-oxido-D*-sulfanylidenecyanamide)(methyl)propanamide (Compound 250)

To a solution of N-ethyl-N-(H5-fl^uo^roPy^ri^tlin-3-yl)-3-methyl-1H-pyrazol-4-yl)-2-methyl-3(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 température 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 70% mCPBA (0.25 g, 1.13 mmol) in éthanol (4.19 mL) at 0 °C was added a solution of 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 éthanol (4.19 mL) was added ln 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 by silica gel chromatography (0-10% methanol/dichloromethane) to give the desired product as a clear oil (0.16 g, 56%): IR (thin film) 1649 cm*¹; Ή NMR (400 MHz, CDClj) δ 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), 4.323.92 (m, 2H), 3.49 - 3.11 (m, 6H). 2.32 (s, 3H), 1.27 -1.05 (m, 6H); ESIMS m/z 393 ([M+H]*). Example 54: Préparation of N-ethyl-4,4,4-trlfluoro-3-methoxy-N-(3-methyl-1-(pyrldln-3-yl)1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide (Compound 276)

To a solution of N-ethyl-4,4,4-trifluoro-3-hydroxy-N-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-

4-yl)-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. Then iodomethane (0.034 mL, 0.538 mmol) was added and Ice bath was removed and the mixture was stirred at 25 ’C ovemight. Reaction was worked up by slow addition of water and further diluted with 20 mL of water, then extracted with 4x20 mL of EtOAc. The combined organic layers were washed with water, dried over Na₂SO< and concentrated. Silica Gel chromatography (0-100% EtOAc/hexane) gave A/-ethyl-4,4,4-trifluoro-3-methoxy-N-(3-methyl-1(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide (52 mg, 0.123 mmol, 27.3 % yield) as a white solid: mp = 83-86 °C; ’H NMR (400 MHz, CDClj) δ 8.94 (d, J = 2.5 Hz, 1H), 8.59 (dd, J = 4.7,1.3 Hz, 1 H), 8.01 (ddd, J = 8.3, 2.7,1.5 Hz, 1 H), 7.85 (s, 1 H), 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 cm'¹.

Compound 327 was prepared from the corresponding intermediates and starting materials in accordance with the procedures disclosed in Example 54.

Example 55, Step 1: Préparation of N-(2-((fert-butyldlmethy1sl1yl)oxy)ethyl)-N-(3-chloro-1(pyrldin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamlde

A solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)propanamlde (0.150 g, 0.483 mmol) 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)(fert-buty1)dimethylsilane (0.231 g, 0.965 mmol) was added, the ice bath was removed, and the reaction was stirred at room température for 2 hours. The reaction was heated at 65 °C for 1.5 hours and then cooled to room température. 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-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1Hpyrazol-4-yl)-2-methyl-3-(methylthio)propanamlde (0.120g, 0.243 mmol, 50.4 %) as an orange oil: IR (thin film) 1669 cm*¹; ¹H NMR (400 MHz, CDCI₃) δ 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, 1 H), 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 m/z 470 ([M+H]*).

Example 55, Step 2; Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-(2hydroxyethyl)-2-methyl-3-(methylthlo)propanamide (Compound 535)

To a solution of N-(2-((tert-butyldimethylsllyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1Hpyrazol-4-yl)-2-methyl-3-(methylthlo)propanamide (0.180 g, 0.384 mmol) In tetrahydrofuran (1.54 ml) was added tetrabutylammonium fluoride (0.201 g, 0.767 mmol) and the reaction was stirred at room température 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-yl)-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-2methyl-3-(methylthio)propanamlde as a white oll (0.081g, 0.217 mmol, 56.5 %): IR (thin film) 3423,1654 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 9.00 (d, J= 2.5 Hz, 1H), 8.62 (dd. J- 4.7,1.2 Hz, 1H), 8.25 (s, 1 H), 8.07 (ddd, J= 8.3, 2.4,1.3 Hz, 1H), 7.47 (dd, J= 8.3, 4.7 Hz, 1H), 4.473.70 (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]*).

Example 56: Préparation of 2-(N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)propanamldo)ethyl acetate (Compound 547)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-2methyl-3-(methylthio)propanamide (0.045 g, 0.127 mmol) ln dichloromethane (1,27 ml) was added N,N-dimethylpyridin-4-amine (0.023 g, 0.190 mmol) and triethylamine (0.019 g, 0.190 mmol) followed by acetyl chioride (0.015 g, 0.190 mmol). The reaction was stirred at room température ovemight. 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-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)propanamldo)ethyl acetate as a yeliow oil (0.015 g, 0.034 mmol, 26.8 %): IR (thin film) 1739,1669 cm’¹; ¹H NMR (400 MHz, CDCIj) δ 8.97 (d, J =2.3 Hz, 1H), 8.64 (dd, J = 4.7, 1.4 Hz, 1H), 8.15 (s, 1 H), 8.04 (ddd, J= 8.3, 2.7,1.4 Hz, 1H), 7.47 (ddd, J= 8.3, 4.8, 0.7 Hz, 1 H). 4.50 - 3.40 (m, 4H), 2.84 (dd, J = 12.7, 8.9 Hz, 1 H), 2.78 - 2.63 (m, 1 H), 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 m/z 398 ([M+H]*). Example 57: Préparation of 2,2-dldeuterio-3-methylsulfanyl-propanolc acid

To a 100 mL round bottom flask was added 3-(methylthio)propanoic acid (3 g, 24.96 mmol), followed by D₂O (23 mL) and KOD (8.53 mL, 100 mmol) (40% wt solution tn D₂O), the solution was heated to reflux ovemight. NMR showed ca. 95% D at alpha-position. The reaction was cooled down and quenched with concentrated HCl until pH<2. White precipitate appeared ln aqueous layer upon acidifying. Reaction mixture was extracted with 3 x 50 mL EtOAc, the combined organic layers were dried over Na₂SO4, concentrated ln vacuo to almost dryness. 100 mL hexane was added and the solution was concentrated again to give 2,2-dideuterio-3methylsulfanyl-propanoic acid as a coloriess oil (2.539 g, 20.78 mmol, 83%): IR (Thin film) 3430, 1704 cm*¹; ¹H NMR (400 MHz, CDCI3) δ 2.76 (s, 2H), 2.14 (s, 3H); ¹³C NMR (101 MHz, CDCI3) δ 178.28, 38.14-28.55(m), 28.55,15.51; EIMS m/z 122..

2-Deuterlo-2-methyl-3-methylsulfanyl-propanolc acid was prepared as described in Example 57 to afford a coloriess oil (3.62 g, 26.8 mmol, 60.9 %): IR (Thin film) 2975,1701 cm’¹; ¹H NMR (400 MHz, CDCIj) δ 11.39 -10.41 (brs, 1 H). 2.88 - 2.79 (d, J = 13.3 Hz, 1H), 2.61 2.53 (d, J = 13.3 Hz, 1 H), 2.16 - 2.09 (s, 3H), 1.32 -1.25 (s, 3H); ¹³C NMR (101 MHz, CDCIj) δ 181.74, 39.74 - 39.02 (m), 37.16,16.50,16.03; EIMS m/z 135.

Example 58: Préparation of 2-methyl-3-(trideuteriomethylsulfanyl)propanoic acid

To a 50 mL round bottom flask was added 3-mercapto-2-methylpropanolc acid (5 g, 41.6 mmol), followed by MeOH (15 mL), the solution was stirred at 25 ’C. Potassium hydroxide (5.14 g, 92 mmol) was added slowly as the reaction ls exothermlc. Iodomethane-d₃ (6,63 g, 45.8 mmol) was added slowly and then the réaction mixture was heated at 65 ’C ovemight. The reaction was worked up by addition of 2 N HCl until the mixture was acidic. It was then extracted with EtOAc (4x50 mL) and the combined organic layers were dried over Na₂SO₄, concentrated and purified with flash chromatography, eluted with 0-80% EtOAc/hexane to give 2-methyl-3(trldeuteriomethylsulfanyl)propanoic acid (4.534 g, 33.0 mmol, 79 %) as coloriess oll: IR (Thin film) 3446, 1704 cm’’; ’H NMR (400 MHz, CDCI₃) δ 2.84 (dd, J = 13.0, 7.1 Hz, 1 H), 2.80 - 2.66 (m, 1 H), 2.57 (dd, J = 13.0,6.6 Hz, 1 H), 1.30 (d, J = 7.0 Hz, 3H); EIMS m/z 137.

Example 59: Préparation of 2-hydroxy-3-(methylthlo)propanolc acid

O

OH

Sodium methanethiolate (4.50 g, 64.2 mmol) was added at 25 ’C to a solution of 3chloro-2-hydroxypropanolc acid (2 g, 16.06 mmol) in MeOH (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 HCl, extracted with EtOAc (3 x 30 mL), combined organic layers were dried with Na₂SO₄, concentrated to give 2hydraxy-3-(methylthio)propanoic acid as a white solid, (1.898 g, 13.94 mmol, 87 % yield): mp 55-59 °C; IR (Thin film) 2927,1698 cm*’: ’H NMR (400 MHz, CDCI₃) δ 6.33 (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, 1 H), 2.20 (s, 3H); EIMS m/z 136.

Example 60: Préparation of 2-methoxy-3-(methylthio)propanolc acid

O

OMe

SMe

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 mL DMF at 25 °C and stirred for 10 min. Vigorous bubbling was observed upon addition of NaH. Then iodomethane (0.126 mL, 2.020 mmol) was added and the solution was stirred at 25 °C ovemight. The reaction was quenched by addition of 2 N HCl, extracted with 3 x 10 mL of EtOAc, the combined organic layers were washed with water (2 x 20 mL), concentrated and purified by column chromatography, eluted with 0-100% EtOAc/hexane, gave 2-methoxy-3(methylthlo)propanolc acid (126 mg, 0.839 mmol, 45.7 % yield) as coloriess oil: ’H NMR (400 92

MHz, CDCh) δ 9.10 (s, 1H), 4.03 (dd, J = 6.9, 4.4 Hz, 1 H), 3.51 (s, 3H), 2.98-2.93 (m, 1H),

2.86 (dd, 7= 14.1, 6.9 Hz, 1H). 2.21 (s. 3H); EIMS m/z 150.

Example 61: Préparation of 2-(acetylthlomethyl)-3,3,3-trifluoropropanolc acid

O

O

ΗθΤο a 50 mL round bottom flask was added 2-(trifluoromethyl)acrytic 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 ovemight. 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 température. Mixture was purified by vacuum distillation at 2.1-2.5 mm Hg, fraction distilled at 80-85 ’C was mostly thioacetic 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% MeOH/ DCM), to give 2-(acetylthiomethyl)-3₁3,3trifluoropropanoic 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; ’H NMR (400 MHz, CDCh) δ 7.52 (brs, 1H), 3.44 (dt, J ~ 7.5. 3.5 Hz, 2H), 3.20 (dd, J = 14.9,11.1 Hz. 1H), 2.38 (s, 3H); ’³C NMR (101 MHz, CDCh) δ 194.79,171.14, 123.44 (q, 7 = 281.6 Hz), 50.47 (q, 7 = 27.9 Hz), 30.44,24.69 (q, 7 =

2.6 Hz); ”F NMR (376 MHz. CDCh) δ -67.82.

Example 62: Préparation of 3_t3,3-trifluoro-2*(methylthlomethyl)propanolc acid

O

HO

To a solution of 2-(acetylthiomethy!)-3,3,3-trifluoropropanoic acid (649 mg, 3 mmol) in MeOH (5 mL) stîrring 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 cooied down and quenched with 2N HCl until acidic, and the aqueous layer extracted with chloroform (4 x 20 mL). Combined organic layer was dried, concentrated in vacuo, purified with flash chromatography (0-20% MeOH/DCM), to give 3,3,3-trifluoro-2-(methy!thiomethy!)propanoic acid (410 mg, 2.179 mmol, 72.6 % yield) as a light yellow oil: ¹H NMR (400 MHz, CDCh) δ 10.95 (s, 1H), 3.49 - 3.37 (m, 1H), 3.02 (dd. 7 = 13.8, 10.8 Hz, 1H), 2.90 (dd, 7 = 13.8,4.0 Hz, 1H), 2.18 (s, 3H); ¹³C NMR (101 MHz, CDCh) δ 172.04 (q, 7 = 2.8 Hz), 123.55 (q, 7 = 281.2 Hz). 50.89 (q, 7 = 27.5 Hz), 29.62 (q, 7 = 2.3 Hz), 15.85; ¹®F NMR (376 MHz, CDCI₃) δ -67.98.

Example 63: Préparation of 3-(methylthlo)pentanolc acid

HO'

S,S-dimethyl carbonodithloate (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 hydroxlde (3.87 g, 69 mmol) and Water (10 mL)). The réaction mixture was slowly heated to 90°C over a period of 20-30 min. Heating was continued for 3 hours before the reaction was cooled down to 25 °C and quenched slowly with HCl. 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’; Ή NMR (400 MHz. CDCI₃) δ 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, CDCI₃) δ 178.14,43.95, 39.78, 27.04, 12.95, 11.29; EIMS m/z 148.

4-methyl-3-(methy1thio)pentanoic acid was prepared as described In Example 63 and Isolated as a coloriess oil: IR (Thin film) 2960, 1704 cm’¹; ¹H NMR (400 MHz, CDCI₃) δ 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 m/z 162.

^CH₃ O S

HO

3-(Methy1thio)hexanoic acid was prepared according to the procedure described In Example 63 and Isolated as a coloriess oil: IR (thin film) 2921,1705 cm’¹; ¹H NMR (400 MHz, CDCI3) δ 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 1.37 (m, 4H), 0.94 (t. J= 7.2 Hz. 3H); ¹³C NMR (101 MHz, CDCI3) δ 178,19.42.00.40.20, 36.33, 20.05, 13.80.12.86.

3-(Cyclopentylthio)-4,4,4-trifluorobutanoic acid was prepared according to the procedure described in Example 63 and Isolated as a coloriess oil: IR (thin film) 2959,1714 cm'¹; ’H NMR (400 MHz. CDCI₃) δ 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, 3H), 1.53- 1.43 (m, 1 H); EIMS m/z 242.

3-Cyclopropy1-3-(methy1thio)propanoic acid was prepared according to the procedure described in Example 63 and Isolated as a coloriess oil: IR (thin film) 3002,1703 cm'¹; ¹H NMR (400 MHz. CDCI₃) δ 2.73 (dd, J= 7.1, 2.2 Hz, 2H), 2.39 (dt, J= 9.7, 7.1 Hz, 1H), 2.17 (s, 3H).

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); ¹³C NMR (101 MHz, CDCI₃) δ 177.60, 47.18,40.66,16.34, 13.61, 5.30,4.91.

5-Methy1-3-(methy!thlo)hexanoic acid was prepared according to the procedure described ln Example 63 and isolated as a light orange oil: IR (thin film) 2955,1705 cm*¹; ¹H NMR (400 MHz, CDCIj) δ 3.12 - 2.96 (m, 1 H), 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); ¹³C NMR (101 MHz, CDCIj) δ 178.07, 43.35,40.53, 39.99, 25.45,22.91,21.83,12.38.

HO

2-(1 -(Methy1thio)cyclobutyl)acetic acid was prepared according to the procedure described in Example 63 and Isolated as a white crystalline solid: mp 43-46 ’C; IR (thln film) 2955,1691 cm*¹; ¹H NMR (400 MHz, CDCIj) δ 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); ¹³C NMR (101 MHz, CDCIj) δ 176.84, 47.08, 44.08, 33.27,16.00,11.72.

HO

3-(Methylthlo)-3-phenylpropanoic acid was prepared according to the procedure described in Example 63 and isolated as a white solid: mp 75-77 ’C; IR (thln film) 2915,1704 cm’¹; ’H NMR (400 MHz, CDCIj) δ 7.35 - 7.29 (m. 4H), 7.29 - 7.20 (m, 1H), 4.17 (t, J - 7.6 Hz, 1H), 2.93 (dd, J= 7.6, 3.2 Hz, 2H), 1.91 (s, 3H); ¹³C NMR (101 MHz, CDCIj) δ 176.98,140.60, 128.61,127.64,127.56, 46.19, 40.70,14.33.

HO

CF,

3-(Methylthio)-3-(4-(trifluoromethyl)phenyl)propanolc acid was prepared according to the procedure described ln Example 63 and isolated as a white solid: mp 106-108 ’C; IR (thln film)

2924,1708 cm*¹; ¹H NMR (400 MHz, CDCI₃) δ 7.59 (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.

3-(3-Methoxyphenyl)-3-(methylthÎo)propanoic acid was prepared according to the procedure described In Example 63 and Isolated as a white solid: mp 61-63 ’C; IR (thln film) 2921, 1699 cm*¹; ¹H NMR (400 MHz, CDCI₃) δ 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.

3-(Methylthio)-3-(pyridin-3-yl)propanoic acid was prepared according to the procedure described ln Example 63 and isolated as a white semi-solid: IR (thin film) 3349,1547 cm'¹; ¹H NMR (400 MHz, CD₃OD) δ 8.54 (dd, J - 2.3, 0.8 Hz, 1 H). 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, 1 H). 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.

3-(Methylthio)-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; ’H NMR (400 MHz, CD₃OD) δ 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.

Example 64: Préparation of ethyl 1-(hydroxymethyl)cyclopropanecarboxylate

A1M solution of lithium aluminum tri-tert-butoxyhydride ln tetrahydrofuran (70.90 mL, 70.90 mmol) was added to a stirred solution of diethyl cyclopropane-1,1’-<iicarboxylate (6 g, 32.20 mmol) in tetrahydrofuran (129 mL) at 23 ’C. The resulting solution was heated to 65 ’C 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 (MgSO₄), filtered, and concentrated to dryness to give the desired product as a pale yellow oil (4.60, 91 %): ’H NMR (300 MHz, CDCI₃) δ 4.16 (q, J = 7 Hz, 2H), 3.62 (s, 2H), 2.60 (br s, 1 H),

1.22-1.30 (m, 5H), 0.87 (dd, J = 7, 4 Hz, 2H).

Example 65: Préparation of ethyl 1-((methylsulfonyloxy)methyl)cyclopropanecarboxylate

O O

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 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 (6.92 g, 94%): ’H NMR (300 MHz, CDCI₃) δ 4.33 (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, 2H).

Example 66: Préparation of ethyl 1»(methylthlomethyl)cyclopropanecarboxylate

O

Sodium methanethlolate (4.36 g, 62.30 mmol) was added to a stirred solution of ethyl 1((methylsulfonyloxy)methyl) cyclopropanecarboxylate (6.92 g, 31.10 mmol) In N,Ndimethylformamlde (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 combined organic layers were dried (MgSO₄), filtered, and concentrated by rotary évaporation to afford the title compound as a brown oil (5.43 g, 100%): ’H NMR (300 MHz, CDCI₃) δ 4.14 (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).

Exemple 67: Préparation of 1-(methylthlomethy1)cyclopropanecarboxy1ic acid

O

ΌΗ

A 50% solution of sodium hydroxide (12.63 mL, 243 mmol) was added to a stirred solution of ethyl 1-(methylthiomethyl)cyclopropanecarboxylate (5.43 g, 31.20 mmol) In absolute éthanol (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 dichloromethane. The aqueous layer was acidified to ρΗ®«1 with concentrated hydrochloric acid and extracted with dichloromethane. The combined organic layers were dried (Na^SC^), filtered, and concentrated and concentrated to dryness to give the desired product as a light brown oil (2.10 g, 46%): Ή NMR (300 MHz, CDCIj) δ 2.82 (s, 2H)₍ 2.17 (s, 3H), 1.41 (dd, J= 7,4 Hz,

2H), 0.99 (dd, J = 7, 4 Hz, 2H).

Example 68: Préparation of 2,2-dlmethyl-3-(methylthlo)propanoic add

O

OH

2,2-Dimethyl-3-(methylthio)propanoic acid can be prepared as demonstrated in the literature (reference Musker, W. K.; et al. 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-2,2dimethylpropanoic acid (1.0 g, 7.2 mmoi, 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 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 ρΗ=»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 coloriess oil (1.2 g, 99% crude yield). Ή NMR (300 MHz, CDCI₃) δ 2.76 (s, 2H), 2.16 (s, 3H). 1.30 (s, 6H).

Example 69: Préparation of 4,4,4-trif1uoro-3-(methylthlo)butanolc acid

SMe

To a 100 mL round bottom flask was added (E)-4,4,4-trifluorobut-2-enolc 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 mmoi) was added in three portions. Vigorous bubbling was observed, the mixture was stirred at 25 °C ovemight, 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 NaîSO^ concentrated in vacuo and further dried under high vacuum until there was no weight loss to give 4,4,4-trifluoro-3(methylthio)butanoic acid (10.68 g, 56.8 mmol, 99 % yield) as a coloriess oil: ’H NMR (400 MHz, CDCI₃) δ 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, 1 H), 2.65 (dd, J= 16.9, 10.4 Hz, 1H), 2.29 (s, 3H); ¹³C NMR (101 MHz, CDCI₃) δ 175.78 (s), 126.61 (q, J_C-f= 278.8 Hz), 44.99 (q. J_C-f = 30.3Hz), 34.12 (d, J_C-f = 1.7 Hz), 15.95 (s); EIMS m/z 162.

Example 70: Préparation of 3-methyl-3-methylsulfanyl-butyrlc acid

3-methyl-3-methylsulfanyl-butyric acid was made using the procedures disclosed ln J.Chem Soc Perkin 1,1992, 10, 1215-21).

Example 71: Préparation of 3-methylsulfanyl-butyric acid

3-Methylsulfanyl-butyric acid was made using the procedures disclosed In Synthetic Comm.,1W5,15 (7), 623-32.

Example 72: Préparation of tetrahydro-thlophene-3-carboxylic acid

Tetrahydro-thiophene-3-carboxylic acid was made using the procedures disclosed In Heterocycles, 2007, 74, 397-409.

Exampie 73: Préparation of 2-methyl-3-methyisulfanyl-butyric acid

2-Methyl-3-methy1sulfanyl-butyric acid was made as described in J.Chem Soc Perkin 1, 1992, 10,1215-21.

Example 74: Préparation of (1S,2S)-2-(methylthio)cyclopropanecarboxyllc acid (1S,2S)-2-{Methy1thio)cyclopropanecarboxylic acid was made using the procedures disclosed in Synthetic Comm., 2003, 33 (5)’, 801-807.

Example 75: Préparation of 2-(2-(methylthio)ethoxy)propanolc acid

2-(2-{Methy1thio)ethoxy)propanolc acid was made as described in WO 2007/064316 A1.

Example 76: Préparation of 2-((tetrahydrofuran-3-yl)oxy)propanoic acid

O

2-{(Tetrahydrofuran-3-yl)oxy)propanoic acid was made as described In WO 2007/064316 A1.

Example 77: Préparation of tert-Butyl 1-(5-fluoropyrldin-3-yl)-3-methyl-1H-pyrazol-4yl(prop-2-ynyl)carbamate (Compound 601)

To an ice cold solution of tert-butyl 1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4ylcarbamate (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 température and then stirred for additional 3 h at room température. The brown reaction mixture poured Into saturated aqueous NH4CI (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, fiitered, 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 give the title compound as a light yellow solid (1103 mg, 81%); mp 81-82 ’C; ’H NMR (400 MHz, CDCIj) δ 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 ([M]*).

Compounds 596 and 606 were prepared In accordance with the procedure disclosed In Example 77 from the corresponding amine.

Example 78; Préparation of 1-(5-f1uoropyrldln-3-yl)-3-methyl-N-(prop-2-ynyl)-1H-pyrazol-4amlne, hydrochloride

To a solution of tert-butyl 1-(5-fluoropyrldin-3-yl)-3-methyl-1H-pyrazol-4-yl(prop-2ynyl)carbamate (1.03 g, 3.11 mmol) In dioxane (5 mL) was added 4M HCl (3.9 mL, 15.5 mmol) Indioxane. The mixture was stirred at room température 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 white solid (741 mg, 89%): mp 167-168 ’C; Ή NMR (400 MHz, DMSO d_e) δ 8.92 - 8.85 (m,

H), 8.42 (d, J - 2.5 Hz, 1 H), 8.15 (s, 1 H), 8.12 - 8.02 (m, 1 H), 3.85 (d, J = 2.5 Hz, 2H), 3.27 3.19 (m, 1 H). 2.22 (s, 3H); ESIMS m/z 230.4 ([M]*).

3-Chloro-N-(prop-2-ynyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amlne, hydrochloride was prepared in accordance with the procedure disclosed in Example 78 from (Compound 606): mp 180-182 ’C; ’H NMR (400 MHz, CDCI₃) δ 9.22 (d, J= 2.5 Hz, 1H), 8.67 (dd, J= 5.3, 1.0 Hz, 1 H), 8.64 (ddd, J = 8.6, 2.6, 1.2 Hz, 1 H), 8.32 (s, 1 H), 7.96 (dd, J = 8.6, 5.3 Hz, 1 H), 3.81 (d, J = 2.4 Hz, 2H), 3.15 (t, J = 2.4 Hz, 1 H); ESIMS m/z 234 ([M+2]*).

3-Methyl-/V-(prop-2-yn-1 -yl)-1 -(pyridin-3-yl)-1 H-pyrazoi-4-amine, hydrochloride was prepared ln accordance with the procedure disclosed in Example 78 from Compound 596: mp 161-163 °C; ’H NMR (400 MHz, DMSO-d_e) δ 8.46 (s, 1H), 8.05 (s, 0H), 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 ([M]+).

Example 79: Préparation of N-(1’(5-Fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-yl)-3’ (methylthio)-N-(prop-2-ynyl)propanamide (Compound 605)

To a stirred solution of 1-(5-fluoropyridin-3-yl)-3-methyl-M-(prop-2’yn’1-yl)-1H-pyrazol-4amine, HCl (100 mg, 0.38 mmoi) and N,N-dimethylpyrldin-4-amine (115 mg, 0.94 mmol) in CH2CI2 (2 mL) was added 2-methyl-3-(methylthio)propanoyl chloride (69 mg, 0.45 mmoi) and the mixture stirred at room température for 24 h. The mixture was concentrated in vacuo to give a brown oil, which was purified on silica gel eluting with mixtures of ethyi acetate and hexanes to give the titie compound as a colorless oil (80 mg, 61%): ’H NMR (400 MHz, CDCI3) δ 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, 1 H). 4.49 (s, 1H), 2.88 (dd, J = 12.8, 9.4 Hz. 1 H), 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); 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: Préparation of N-(3-Chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)-4,4,4-trifluoro-3(methylthio)-N-(prop-2-yn-1-yl)butanamlde (Compound 613)

I01

To a 7 mL vial was added 3-chloro-N-(prop-2-yn-1-y!)-1-(pyridin-3-yl)-1H-pyrazol-4amine (140 mg, 0.6 mmol), N,N-dimethylpyridin-4-amine (249 mg, 2.040 mmol), N1((ethy!imino)methy!ene)-N3,N3-dimethylpropane-1,3-dÎarnlne hydrochloride (276 mg, 1.440 mmol) followed by 4,4,4-trifluoro-3-(methylthio)butanoic acid (158 mg, 0.840 mmol) and DCE (1.2 mL). The solution was stirred at 25 °C for 18 hours, the crude réaction mixture was concentrated and purified with silica gel chromatography (0-100% EtOAc/hexane) to give the title compound as a brown oil (237 mg, 0.588 mmol, 98%): (IR thin film) 1674 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 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. 1 H). 2.29 (d, J = 2.5 Hz, 4H); ESIMS m/z 403 ([M+H]*).

Compounds 597, 604, 609, 614-616 were prepared in accordance with the procedure disclosed ln Example 80.

Example 81: Préparation of 3-Chloro-N-(prop-2-ynyl)-1-(pyrldin-3-yl)-1H-pyrazol-4-amlne

Cl

To a solution of fert-butyl (3-chloro-1-(pyridîn-3-yl)-1H-pyrazol-4-yl)(prop-2-yn-1yljcarbamate (2.2 g, 6.61 mmol) ln dichloromethane (8.3 ml) was added 2,2,2-trifluoroacetic acid (12.06 g, 106 mmol) and the reaction mixture was stirred at ambient température for 1 hour. The reaction was quenched by the addition of saturated sodium bicarbonate. The organic 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%): ’H NMR (400 MHz, CDCl₃) δ 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, 1 H), 3.90 (s, 2H), 3.38 (s, 1 H), 2.44 - 2.09 (m, 1 H); ESIMS m/z 233 ([M+H]*).

Example 82: Préparation of /V-(3-Chloro-1-(pyrIdln-3-yl)-1H-pyrazol-4-yl)-2-(methylthlo)-N(prop-2-yn-1-yl)propanamlde (Compound 611)

To a solution of 2-(methylthio)propanoic acid (0.36 g, 3.00 mmol) in dichloromethane (3 mL) was added oxaly! dichloride (0.29 ml, 3.31 mmol) followed by one drop of N.Ndimethylformamide. The reaction mixture was stirred for 30 minutes before ail solvent was evaporated. The resulting residue was dissolved in dichloromethane (2 mL) and it was added to 102 a pre-stirred solution of 3-chloro-N-(prop-2-yn-1-yl)-1-(pyridin-3-yl)-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 température for 16 hours. The reaction mixture was concentrated and the residue was purified using silica gel chromatography (0-100% ethyl acetate/hexanes) to afford the title compound as a yellow oil (432 mg, 1.23 mmol, 85%): Ή NMR (400 MHz, CDCI₃) δ 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); ’³CNMR(101 MHz, CDCI₃) δ 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, 16.42,11.07; ESIMS m/z 335 ([M+H]*).

Compound 612 was prepared in accordance with the procedure disclosed in Example 82.

Exampie 83: Préparation of N-(3-Chloro-1-(pyridin’3«yl)-1H-pyrazol-4-yl)-2(methylsulfinyl)-N-(prop-2-yn-1-yl)propanamide (Compound 617)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-(methylthio)-A/-(prop-2-yn1-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 température. The reaction was complété after 1 hour. The reaction was quenched with 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 gei chromatography (0-20% methanol/dichloromethane) to afford the title compound as an off-white foam (82 mg, 0.21 mmol, 78 %): ’H NMR (400 MHz, CDCI₃) δ 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, 1 H), 4.88 (br s, 1 H), 4.14 (br s, 1 H). 2.64 (s, 1,2H), 2.55 (s, 1.8H), 2.33 - 2.27 (m, 1 H), 1.47 (d, J = 6.8 Hz, 3H); ’³C NMR (101 MHz, CDCI₃) δ 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+H]*).

Example 84: Préparation of W-(3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2(methylsulfonyl)-N-(prop-2-yn-1-yl)propanamide (Compound 618)

103

To a solution of N-(3-chloro-1-(pyiidin-3-yl)-1H-pyrazol-4-yl)-2-(methylthlo)-/V-(prop-2-yn1-yl)propanamlde (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 vlal was heated to 65 ’C for 2 hours. The reaction mixture was cooled to ambient température 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% methanol/dichloromethane) to afford the title compound as a yellow foam (84 mg, 0.21 mmol, 73%): ’H NMR (400 MHz, CDCI₃) δ 9,00 (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, 1 H), 3.01 (s, 3H), 2.34 - 2.29 (m, 1H), 1.67 (d, J = 7.0 Hz, 3H); ¹³C NMR (101 MHz, CDCI₃) δ 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+H]*).

104

Example 85: Préparation of N-(3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl·

3*(trityithio)propanamide

To a solution of N,N-dimethylpyridin-4-amine (2.60 g, 21.31 mmol), 2-methyl-3(tritylthio)propanoic acid (4.41 g, 12.18 mmol) (prepared according to Ondetti, Miguel Angel et.a/. DE 2703828) and N1-((ethylimino)methytene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (2.36 g, 15.22 mmol) In CH₂CI₂ (20 mL) was added 3-chloro-N-ethyt-1-(pyridin-3ylJ-1H-pyrazol-4-amine, 2HCI (3.0 g, 10 mmol). The mixture was stirred at 0 ’C for 2 hours, then at room température for additional 48 hours. The mixture was diluted with ethyl acetate (100 mL) and saturated aqueous NH₄CI. The organic phase was separated, washed with brine, dried over MgSO₄ 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 molécule as a pink solid (2.97 g, 51 %): mp 64-66 °C; ’H NMR (400 MHz, CDCI₃) δ 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 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 m/z 568 (ΙΜ+ΗΓ).

Example 86: Préparation of N-(3-chloro-1-(pyr1dln-3-yl)-1M-pyrazo1-4-y1)-N-methyl-3(tritylthio)propanamlde

To a solution of 3-chloro-N-methy1-1-(pyridin-3-yt)-1H-pyrazol-4-amine, HCl (1.5 g, 6.12 mmol) ln CH₂CI₂ (10 mL) were added 3-(tritylthio)propanolc acid (2.35 g, 6.73 mmol) (prepared according to Ondetti, Miguel Angel et.a/. DE 2703828). N,N-dimethylpyridin-4-amine (0.82 g, 6.73 mmol) and N1-((ethytimino)methytene)-N3,N3-dimethytpropane-1,3-diamine, HCl (1.76 g, 9.18 mmol), and the mixture was stirred at room température for 16 h. The mixture was diluted with CH₂CI₂ (100 mL) and water (50 mL) and the organic phase separated. The aqueous phase was extracted with ethyl acetate and the comblned organic phase was washed with brine, dried 105 over MgSO₄ and concentrated in vacuo to give the titie molécule as a white powder (1.95 g,

59%): mp 62-64’C; Ή NMR (400 MHz, CDCIj) δ 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+H]*).

Example 87: Préparation of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazo1-4-yl)-3-mercapto-Nmethylpropanamlde

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y1)-N-methyl-3(tritylthio)propanamide (1.300 g, 2.411 mmol) in CH₂CI₂ (6.14 g, 72.3 mmol) were added triethylsilane (1.402 g, 12.06 mmol) followed by 2,2,2-trifluoroacetic acid (2.75 g, 24.11 mmol) at room température. The mixture was stirred for 1 hour and quenched with saturated aqueous NaHCOj. The mixture was diluted with CH₂CI₂ and the organic phase was separated. The aqueous phase was extracted with CH₂CI₂ and the organic phases were combined, washed with brine dried over anhydrous MgSO₄ and concentrated in vacuo to give a light yellow oil. This oil was purified on silica gel eluting with ethyl acetate and hexanes to give the titie molécule as a colorless oil (701 mg, 93 %): IR (thln film) 3094,2980,1657, 1582 cm'¹; Ή NMR (400 MHz, CDCIj) δ 8.95 (d, J = 2.6 Hz, 1 H), 8.63 (s, 1 H), 8.06 (s, 1 H), 8.04 - 7.96 (m, 1 H), 7.52 - 7,42 (m, 1H), 3.26 (s, 3H), 2.85 - 2.73 (m, 2H), 2.56 - 2.48 (m, 2H).

The following molécules were made in accordance with the procedures disclosed ln

Example 87:

N-(3-ch1oro-1-(pyridln-3-y1)-1H-pyrazol-4-y1)-N-ethy1-3-mercatopropanamlde

The titie molécule was isolated as a light brown gum (902 mg, 64 %): IR (thin film) 3086, 2980, 2936, 2548,1657 cm*¹; ¹H NMR (400 MHz, CDCIj) δ 8.96 (dd, J = 2.7, 0.7 Hz, 1H), 8.63 (dd, J = 4.8, 1.5 Hz, 1 H). 8.06 (ddd, J = 8.3,2.7,1.4 Hz, 1 H), 7.97 (s, 1 H), 7.47 (ddd, J = 8.4, 4.7, 0.8 Hz, 1 H). 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-H]').

N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-Methyl-3-mercapto-2-methylpropanamide

106

The title molécule was Isolated as a coloriess oil which solidified upon standing: mp 9496 ’C; ¹H NMR (400 MHz, CDCI₃) δ 8.97 (dd, J =2.7, 0.7 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1 H), 8.05 (ddd, J = 8.3, 2.7,1.5 Hz, 1H), 8.02 (s, 1 H). 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); ESIMS m/z 325 ([M+H]*).

Example 88: Préparation of 3-(((2,2-difluorocyclopropyl)methyl)thlo)propanoic acid

HO

Powdered potassium hydroxide (423 mg, 7.54 mmol) and 2-{bromomethyi)-1,1difluorocyclopropane (657 mg, 3.84 mmoi) were sequentially added to a stirred solution of 3mercaptopropanoic acid (400 mg, 3.77 mmol) in methanol (2 mL) at room température. The resulting white suspension was stirred at 65 ’C for 3 h and quenched with 1N aqueous HCl and diluted with 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 molécule as a coloriess oil (652 mg, 84%): IR (KBr thin film) 3025,2927, 2665, 2569,1696 cm·¹; Ή NMR (400 MHz, CDCIj) δ 2.85 (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 ([M-H]).

The following molécules were made In accordance with the procedures disclosed In Example 88:

4-(((2,2-Difluorocyclopropyi)methy1)thio)butanoic acid: ¹H NMR (400 MHz, CDCI3) δ 11.31 (s, 1 H), 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 (101 MHz, CDCI3) δ 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); ^1SF NMR (376 MHz, CDCIj) δ-128.12 (d, J =

156.8 Hz), -142.77 (d, J = 156.7 Hz).

4-((2,2,2-Trifluoroethyl)thio)butanoic acid: ¹H NMR (400 MHz, DMSO-d_e) δ 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). Example 89: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-3-(((2,2difIuorocyclopropyl)methyl)thlo)-N-ethylpropanamide (Molécule 626)

107

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3mercatopropanamide (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 température for 10 min followed by addition of 2-(bromomethyl)-1,1-difluorocyclopropane (60 mg, 0.35 mmol). The mixture was stirred at room température 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 chromatography eluting with mixtures of ethyl acetate and hexanes to give the title moiecule as a colorless gum (101 mg, 78%): IR (thin film) 3092, 2975,2931, 1659,1584 cm*¹; ’H NMR (400 MHz, CDCh) δ 8.99-8.90 (m, 1H), 8.63 (dd, 7= 4.8,1.5 Hz. 1H), 8.05 (ddd, 7= 8.3, 2.7,1.5 Hz, 1H), 7.96 (s, 1H), 7.47 (ddd, 7= 8.3, 4.7, 0.7 Hz, 1H), 3.72 (q, 7= 7.2 Hz, 2H), 2.87 (t, 7 =

7.3 Hz, 2H), 2.63 -2.55 (m, 2H), 2.46 (t, 7= 7.3 Hz, 2H), 1.76 (ddq, 7= 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, 7= 7.2 Hz. 3H), 1.04 (dtd, 7= 13.2, 7.6, 3.7 Hz, 1H); ESIMS m/z 400 ([M+H]*).

Molécules 624, 625, 629,633,643 653 in Table 1 were made in accordance with the procedures disclosed in Example 89.

Example 90: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(((2,2dlfluorocyclopropy1)methy!)suifinyi)-N-ethy!propanamlde (Moiecule 627)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(((2,2difluorocyclopropyl)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 stirred at 50 *C for 1 hour. The mixture was cooied to room température, 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 MgSO< and concentrated in vacuo to give a coforiess oil. This oil was purified on silica gel eluting with methanol and CH₂CI₂ (0-10% gradient) to give

108 the title molécule as a coloriess gum (91 mg, 88%): IR (thin film) 3448, 3092, 2976, 2933,1659,

1585,1440,1012 cm*¹; ’H NMR(400 MHz. CDCI₃) δ 8.97 (d. 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. 1 H), 3.00 - 2.79 (m, 3H), 2.69 (m, 2H). 2.13 -1.85 (m. 1 H),

1.77-1.62 (m. 1H), 1.41-1.21 (m, 1H), 1.18 (t, J= 7.2 Hz. 3H); ESIMS m/z 417 ([M+H]*).

Molécules 622,630,645 ln Table 1 were made In accordance with the procedures disclosed ln Example 90.

Example 91: Préparation of N-(3-chloro-1-(pyridln-3-yi)-1H-pyrazol-4-yl)-3-(((2,2-difluoro cyclopropyl)methyl)suifonyl)-N-ethylpropanamlde (Molécule 628)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y1)-3-(((2,2difluorocyclopropyl)methyl)thlo)-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 température, quenched with saturated aqueous sodium bicarbonate and then diluted with ethyi acetate. The organic phase was separated and the aqueous phase was extracted with ethyi 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 ethyi acetate and hexanes to give the title molécule as a coloriess gum (90 mg, 83%): IR (thin film) 3104, 2980,2934,1662,1486, 1460 cm·’; Ή NMR (400 MHz, CDCI₃) δ 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. 1 H), 3.11 - 3.00 (m. 1 H), 2.72 (t, J - 6.9 Hz, 2H), 2.13 - 1.96 (m, 1 H). 1.73 (tdd, J= 11.5, 8.3, 5.4 Hz, 1H), 1.45 (ddt, J= 16.1, 8.0, 3.8 Hz, 1 H), 1.18 (t, J= 7.2 Hz, 3H); ESIMS m/z 433 ([M+H]*).

Molécules 623,631,644 ln Table 1 were made In accordance with the procedures disclosed ln Example 91.

Example 92: Préparation of N-(3-chloro-1-(pyridin-3-yi)-1H-pyrazol-4-yl)-N(cyclopropylmethyl)-3-(((2,2-difluorocyclopropyl)methyi)thio)propanamid (Molécule 632)

109

To a solution of 3-chloro-N-(cyclopropylmethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine (108 mg, 0.43 mmol), N,N-dimethylpyridin-4-amine (53mg, 0.43 mmol) and 3-(((2,2difluorocyclopropyl)methyl)thîo)propanoic acid (85 mg, 0.43 mmol) in DMF (5 mL) was added N1-((ethylimino)methylene)-/V3,N3-dimethylpropane-1,3-diamine hydrochloride (101 mg, 0.65 mmol). The resulting brown-yellow mixture was stirred at ambient température 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 molécule as a coloriess oîl (120 mg, 61 %): IR (thin film) 3089, 3005, 2923,1660 1584 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 8.95 (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 m/z 427 ([M+H]*).

Molécule 646 in Table 1 was made In accordance with the procedures disclosed In Example 92.

Example 93: Préparation of (E)-N-(3-chloro-1-(pyridIn-3-yI)-1H-pyrazoi-4-yl)-N-ethyl-4,4,4trlfluorobut-2-enamlde

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, 2HCI (1.0 g, 3.38 mmol), N,N-dimethylpyridin-4-amîne (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-((ethylimîno)methylene)-N3,N3dimethylpropane-1,3-diamlne, HCl (973 mg, 5.07 mmol). The resulting brown-yellow mixture was stirred at ambient température for 2 hours. The mixture was diluted with saturated aqueous NH₄CI and ethyl acetate and saturated with NaCl. The organic phase was separated and the aqueous phase extracted with ethyl; acetate (22 x 5050 mL). The combined organic phase was dried over MgSO₄, filtered and concentrated in vacuo to give the title molécule as a light brown gum (901 mg, 73%): IR (thin film) 3093, 2978, 2937,1681,1649,1585,1114 cm'¹; Ή NMR (400 MHz. CDCIj) δ 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, 1 H). 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 m/z 345 ([M+H]*). Example 94: Préparation of S-(4-((3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)(ethyl)amIno)-

1,1,1-trifluoro-4-oxobutan-2-yl) ethanethloate liO

To a solution of (E)-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-4,4_l4-

trifluorobut-2-enamide (465 mg, 1.349 mmol) In dry DMSO (5 mL) was added potassium ethanethloacetate (616 mg, 5.40 mmol). The mixture was stirred at 50 ’C for 96 hours under 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 MgSO₄₁ 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 molécule as a brown gum (265 mg, 44%); IR (thin film) 3099, 2976, 2936,1708,1666,1585,1102 cm*¹; ¹H NMR (400 MHz,

CDCIj) δ 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, 1 H), 2.53 (dd, J- 16.6, 9.4 Hz, 1H), 2.41 (s, 3H), 1.16 (t, 7.2 Hz, 3H); ESIMS m/z421 ([M+H]*).

Example 95: Préparation of W-(3-chioro-1*(pyrldln-3-yl)-1H-pyrazol-4-yl)-3-(((2,2difluorocyclopropyl)methyl)thlo)-N-ethyl-4,4,4-trif1uorobutanamlde (Molécule 634)

To a solution of methanol (21.1 mg, 0.66 mmol) ln 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 température and S-(4-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-

1,1,1-trifluoro-4-oxobutan-2-yl) ethanethioate (266 mg, 0.63 mmol) ln THF (1 mL) was added. After stirring for 30 minutes, 2-(bromomethyl)-1,1-difluorocydopropane (130 mg, 0,76 mmol) was added. The mixture was stirred at room température 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 acetate extracts were dried over MgSO₄, filtered and concentrated in vacuo to give a colorless oil. Purification on silica gel eluting with ethyl acetate and hexanes gave the title molécule as a brown oil (89 mg, 30% yield): iR (thin film) 3097,2978, 2937 1664,1440 cm*¹; ¹H NMR (400 MHz, CDCIj) δ 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

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); ESIMS m/z 469 ([M+H]*).

112

Example 96: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-2((cyclopropylmethyl)thlo)-N-ethylpropanamlde (Molécule 621)

To a solution of methanol (9.99 mg, 0.312 mmol) ln THF (1 mL) was added sodium hydride (12.4 mg, 0.31 mmol, 60% oil suspension). The mixture was stirred at room température for 10 minutes and added S-(1-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-1oxopropan-2-yl) 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) 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 molécule as a colorless gum (31 mg, 30%): IR (thin film) 3081,2972, 2930, 2871, 1655, 1438 cm'¹; ¹H NMR (400 MHz, CDCIj) δ 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, 1 H), 7.50 - 7.40 (m, 1 H), 3.81 (bs, 1 H), 3.59 (bs, 1 H), 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 m/z 365 ([M+H]*). Molécule 651 ln Table 1 was made ln accordance with the procedures disclosed in 20 Example 96.

Example 97: Préparation of N-(3-chloro-1-(pyrldln-3-yl)’1H-pyrazol-4-yl)-3((cyc!opropylmethyl)thlo)-N-ethylpropanamide (Molécule 619)

To a solution of methanol (9.99 mg, 0.31 mmol) In DMSO (1 mL) was added sodium hydride (12.4 mg, 0.31 mmol). The mixture was stirred at room température for 10 minutes and added a solution of S-(3-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-3-oxopropyl) 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 an additional 30 minutes. The mixture was diluted with saturated aqueous NH₄CI and ethyl acetate and the organic phase separated. The aqueous phase was extracted with ethyl acetate and the

113 combined organic phase was washed with brine, dried over MgSO< 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 molécule as a colorless gum (33 mg, 31%): IR (thin film) 3080, 2978, 2930,1660,1584 cm*¹; ¹H NMR (400 MHz, CDCI₃) δ 8.95 (d, J = 2.8 Hz, 1H), 8.63 (dd, J = 4.7,1.5 Hz, 1 H), 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, 1 H), 0.60 - 0.34 (m, 2H), 0.24 - 0.09 (m, 2H); ESIMS m/z 365 ([M+H]*).

Example 98: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-2((cyclopropylmethyl)thio)-N-ethylacetamide (Molécule 620)

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 température for 10 minutes and cooied to 0-5 'C and added a solution of S-(2-((3-chloro-1-{pyridin-3-yl)-1H-pyrazol-4yl)(ethyl)amino)-2-oxoethyl) ethanethioate (100 mg, 0.29 mmol). After stirring the mixture for 30 min, (bromomethyi)cyclopropane (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 MgSO< and concentrated In vacuo to give an oily residue. This residue was purified on silica gel eluting with ethyl acetate and hexanes to give the title molécule as a colorless gum (38 mg, 37%): IR (thin film) 3080,2975, 2931,1657,1584 cm·¹; ¹H NMR (400 MHz, CDCI₃) δ 8.96 (dd, J = 2.7, 0.7 Hz, 1 H), 8.63 (dd, J = 4.8,1.4 Hz, 1 H), 8.08 (s, 1 H), 8.04 (ddd, J = 8.4,

2.8,1.5 Hz, 1 H), 7.46 (ddd, J = 8.4, 4.7, 0.8 Hz, 1 H), 3.6 (bs, 1 H), 3.17 (s, 1 H), 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 (m, 3H), 0.24 (dd, J = 4.8,1.4 Hz, 2H); ESIMS m/z 351 ([M+H]*).

Molécule 650 in Table 1 was made In accordance with the procedures disclosed in Example 98.

Example 99: Préparation of N-(3-chloro-1-(pyridln-3-yl)-1 H-pyrazol-4-y 1)-3-((3,3dichloroallyl)thio)-N-methylpropanamide (Molécule 649)

114 ci

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-3-mercapto-Nmethylpropanamide (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 température for 10 min and cooled to 0-5 *C. 1,1,3Trichloroprop-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 give the title molécule as a colorless gum (60 mg, 43.9 %): IR (thin film) 3078, 2926,1659, 1583,1458,1437, 803 cm*¹; ¹H NMR (400 MHz, CDClj) δ 8.94 (dd, J= 2.7,0.7 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1 H), 8.04 (ddd, J = 8.3,2.7,1.4 Hz, 1H), 7.98 (s, 1 H), 7.47 (ddd, J = 8.3, 4.7, 0.7 Hz, 1 H), 5.30 (s, 1 H), 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 m/z 406 ([M+2]*), 403.7 ([M-1]').

Example 100: Préparation of 2-ch!oro-N-(3-ch!oro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-Nethylpropanamlde

To a solution of 3-chloro-N-ethy1-1-(pyridin-3-yl)-1H-pyrazol-4-amine (1.0 g, 4.49 mmol) ln 1,2-dichloroethane (44.9 ml) at 0 ’Cwere added diisopropylethylamine (0.941 ml, 5.39 mmol) and 2-chloropropanoyl chloride (0.436 ml, 4.49 mmol), sequentially. The reaction was allowed to warm to ambient température and was stirred for 1.5 hr. The reaction was quenched with the addition of aqueous NaHCOj and the layers were quickly separated. The aqueous layer was extracted with CH₂CI₂ (3 x 50 mL) and the combined organics were dried over Na₂SO₄, filtered and concentrated ln vacuo. The crude residue was purified via flash chromatography (30 to 100% EtOAc/Hex) to give the title molécule as a white solid (1.301 g, 93%): mp 94-105 ^eC; ¹H NMR (400 MHz, CDClj) δ 8.97 (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 m/z 313 ([M+H]*).

The following molécules were made in accordance with the procedures disclosed in Example 100:

115

2-chloro-N-(3-chloro-1*(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethylbutanamlde

Mp 95-103 ’C; ’H NMR (400 MHz, CDCIj) δ 8.98 (d, J =2.6 Hz, 1 H), 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, 1 H), 1.19 (t, J = 7.2 Hz, 3H), 0.97 (t, J = 7.3 Hz, 3H); ESIMS m/z 327 ([M+H]*).

2-chloro-N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethylacetamlde (Compound Y2007)

Duo to observed décomposition when left at ambient températures ovemight, the title molécule was immediateiy used in subséquent reactions: ’H NMR (400 MHz, CDCIj) δ 8.96 (d, J= 2.6 Hz, IH), 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, 1 H), 3.93 (s, 2H), 3.79 - 3.68 (bs, 2H), 1.19 (t, J = 7.2 Hz, 3H).

N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-2-((1-chloro-2,2,2-trlfluoroethyl)thlo)-Nethylacetamlde (Molécule 638)

Supporting analytical data for the title molécule can be found in Table 2.

Example 101: Préparation of S-(1-((3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)(ethyl)amlno)1-oxopropan-2-yl) ethanethloate (Molécule 685)

To a solution of 2-chloro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-Nethylpropanamide (1.0 g, 3.19 mmol) in acetone (6.39 ml) was added potassium ethanethloate (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 EtOAc (20 mL). The layers were separated and aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic extract was dried over anhydrous Na₂SOi, filtered and concentrated in vacuo.

116

The crude residue was purified (flash chromatography, 20 to 100% EtOAc/Hex) to give the title molécule as a brown, highly viscous oll (1.07g, 90%).

The following molécules were made in accordance with the procedures disclosed in

Example 101:

S-(1-((3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)(ethyl)amlno)-1-oxobutan-2-yl) ethanethloate

Mp 116-122 ’C; ¹H NMR (400 MHz, CDCI₃) δ 8.97 (d, J~ 2.6 Hz, 1H), 8.63 (dd, J = 4.8,

1.5 Hz, 1 H), 8.13 - 7.99 (m, 2H), 7.46 (dd, J = 8.3, 4.7 Hz, 1 H), 4.14 (t, J = 7.3 Hz, 1 H), 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); ESIMS m/z 367 (]M+H]*).

S-(2-((3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-2-oxoethyl) ethanethloate (Molécule 694)

Mp 117-124 ‘C; ¹H NMR (400 MHz, CDCI₃) δ 8.98 (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: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-((2,2,220 trlfluoroethyl)thlo)propanamlde (Molécule 635)

To a dry round-bottom flask under N₂ were added sodium hydride (0.018 g, 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 température until cessation of hydrogen évolution was observed (-45 min). The reaction was then cooled at 0 ’C and S-(1-((3-chloro-1 -<pyridin-3-yl)-1 H-pyrazol-4yl)(ethyl)amino)-1-oxopropan-2-yl) ethanethioate (0.150 g, 0.425 mmol) in THF (2.1 mL) was added. The reaction was warmed to ambient température and stirred for 30 min. The réaction 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 température and stirred ovemight. The

117 reaction was diluted in EtOAc (20 mL) and quenched with H₂O (5 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3x10 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% CH₂CI₂/EtOAc) to give the title molecuie as an opaque, viscous oil (43 mg, 25%): IR (thln film) 1657 cm'¹; ’H NMR (400 MHz, CDCh) δ 8.96 (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); ”F NMR (376 MHz, CDCI₃) δ -66.16; ESIMS m/z 393 ([M+H]*).

Molécules 637, 639-642, and 652 ln Table 1 were made in accordance with the procedures disclosed in Example 102.

Exampie 103: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazoi-4-yl)-N-ethyl-2-((2fluorovinyl)thlo)propanamide (Molecuie 654)

To a dry round-bottom flask under N₂ were added a 60% dispersion of NaH in minerai 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 température until cessation of hydrogen évolution was observed (-45 min). The reaction was then cooled at 0 ’C and S-(1-((3-chloro-1-(pyridin-3-yl)1H-pyrazoî-4-yl)(ethyl)amino)-1-oxopropan-2-y!) ethanethioate (0.150 g, 0.425 mmol) ln THF (2.1 mL) was added. Reaction was warmed to room température 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. Réaction was warmed to room température and stirred ovemight. LCMS analysis Indicated presence of two products, the major corresponding to the desired élimination product and the minor corresponding to the Initial alkylation. Therefore, the réaction was cooled to 0 ’C and transferred to a vial containing additional NaOMe (freshly prepared by mlxlng NaH (5.86 mg, 0.147 mmol) and MeOH (5.93 pL, 0.147 mmol) in THF (0.73 mL) at 0 ’C. After stirring an additional 18h, reaction was diluted in EtOAc (5 mL) and quenched with H₂O (5 mL). Aqueous layer was extracted with EtOAc (3x10 mL) and the combined organic extracts were dried over Na₂SO₄, filtered, and concentrated in vacuo to give a yellow oil. The crude residue was purified via flash chromatography (25-80% EtOAc/Hex) to give an Inséparable mixture of olefin isomers (-3:2, E7Z) as an opaque, viscous oil (15 mg, 10%): IR (thin film) 3091, 1656 cm ’; Ή NMR (400 MHz, CDCI₃) δ 8.97 (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,

118

H), 3.72 - 3,47 (m, 1 H), 3.47 - 3.20 (m, 1 H), 1.50 (d, J = 6.9 Hz, 1.2H), 1.42 (d, J= 6.8 Hz,

1.8H), 1.17 (m, 3H); ESIMS m/z 355 ([M+H]*).

Example 104: Préparation of N-(3-ch!oro-1-(pyridin-3-yl)-1H-pyrazo!-4-y!)-N-ethy!-3-( (2,2,2trifluoroethy!)thio)propanamlde (Molécule 636)

To a solution of 3-ch!oro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazo!-4-yl)-Nethylpropanamide (100 mg, 0.32 mmol) in THF (0.3 mL) was added sodium lodide (4.7 mg, 0.032 mmol), 2,2,2-trifluoroethanethlol (148 mg, 1.3 mmol), and N,N-di-iso-propylethylamlne (222 pl, 1.277 mmol). The réaction mixture was heated ovemight at 50 ’C, diluted with DCM 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 molécule as a coiortess oil (109 mg, 83%): Ή NMR (400 MHz, CDCI₃) δ 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); ^1BF NMR (376 MHz, CDCI₃) δ -66.56 (s); ESIMS m/z 393 ([M+H]*),

Example 105: Préparation of N-(3-chloro-1-(pyridln-3-yl)-1H-pyrazo!-4-y!)-N,2-dimethy!-3((trifluoromethyi)thio)propanamlde (Molecuie 647)

To a solution of 2-methyl-3-((trifluoromethyl)thlo)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 température for 1 hour (gas évolution was observed). The réaction mixture was concentrated and the crude acid chloride was dissolved in DCM (0.3 mL) which was subsequentiy added to a pre-stirred solution of 3-chloro-N-methy1-1-(pyridin-3-yl)-1H-pyrazol-4amine 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 ovemight at room température.. The reaction mixture was diluted with saturated NaHCO₃ and extracted with DCM. The organic layer was dried over Na₂SO<, filtered and concentrated. The crude material was purified via flash chromatography eluting with 0-100% EtOAc/hexanes to give the title molecuie as a yellow oil (93 mg, 65.7%): IR (thln film) 1654 cm*¹; ¹H NMR (400 MHz, CDCI₃) δ 8.96 (d, J = 2.6 Hz, 1 H), 8.64 (dd, J = 4.7,1.3

119

Hz, 1 H), 8.08 - 8.00 (m, 1 H), 7.98 (d, J = 8.3 Hz. 1 H), 7.51 - 7.44 (m, 1 H), 4.07 - 3.36 (m, 2H),

3.25 - 3.11 (m, 1 H), 2.94 - 2.77 (m, 2H), 1.22 - 1.15 (m, 6H); ESIMS m/z 394 ([M+H])*).

Molécule 648 in Table 1 was made In accordance with the procedures disclosed In

Example 105

Example 106: Préparation of N-methyl-M-(1-methyl-3-(pyrldin-3-yl)-1H-pyrazol-5-yl)-3((3,3,3-trifluoropropyl)thio)propanamlde (Compound 1011)

CH₃

A solution of 3-((3,3,3-trifluoropropyl)thlo)propanolc acid (75 mg, 0.372 mmoi), DMAP (110 mg, 0.903 mmol), and /V,1-dimethy!-3-(pyridin-3-yl)-1H-pyrazo1-5-amine (50 mg, 0.266 mmol) in dry diethy! ether (886 pL) was cooled to 0 *C under N₂. N,N'-Dicyciohexylcarbodiimide (DCC) (132 mg, 0.638 mmol) was added and the reaction was warmed up to room température under N₂, then stirred at room température overnight. The reaction mixture was fiitered 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/EtOAc afforded the title compound as a clear oil (64 mg, 61%).

Example 107: Préparation of tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(2hydroxyethyljcarbamate (Compound Y2151)

OH

To a solution of 2-((tert-butoxycarbonyl)(3-chloro-1-(pyridin-3-y!)-1H-pyrazol-4y!)amino)ethyl acetate (841 mg, 2.21 mmol) In MeOH (7.3 mL) was added potassium carbonate (305 mg, 2.21 mmoi). The reaction was stirred at room température overnight. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2x10 mL). The organic layer was washed with saturated aqueous NaHCO₃ (10 mL), dried over MgSO₄ and concentrated. Et₂O was added and the resulting precipitate was collected by filtration to afford the titie compound as a white solid (249 mg, 32%).

Example 108: Préparation of 2-((fert-butoxycarbonyi)(3-chioro-1-(pyridin-3-yi)-1H-pyrazoi4-yl)amino)ethyl methanesulfonate

120

To a solution of tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-ylX2hydroxyethyljcarbamate (574 mg, 1.69 mmol) in dry CH₂CI₂ (4.0 mL), triethylamine (260 μΙ, 1.86 mmol) was added under N₂. Methanesulfonyl chloride (145 μΙ, 1.864 mmol) was added dropwise and the réaction was stirred at room température for 4 h. After the reaction was deemed complété by LCMS, the reaction mixture was diluted with CH₂CI₂ (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/EtOAc afforded the title compound as a coloriess liquid (330 mg, 44%): ¹H NMR (400 MHz. CDCI₃) δ 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 m/z 417 ([M+H]*).

Example 109: Préparation of tert-butyl (3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)(2(pyrrolldin-1-yl)ethyl)carbamate (Compound Y2152)

To a solution of 2-((tert-butoxycarbonyl)(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4yl)amino)ethyl methanesulfonate (129 mg, 0.309 mmol) In dry DMF (884 μΙ), triethylamine (51.8 μΙ, 0.371 mmol) and pyrrolidine (37.5 μί, 0.449 mmol) was added under N₂. The reaction was then heated at 80 ’C under N₂ ovemight. After the reaction was deemed complété by LCMS, the reaction mixture was diluted with water (10 mL) and saturated aqueous NaHCO₃ (5 mL), then extracted with EtOAc (3x10 mL). The organic layer was dried over MgSO* and concentrated under reduced pressure. Purification by silica gel chromatography by eluting with 0-50% CH₂CI₂/MeOH afforded the title compound as an off-white solid (65 mg, 51%).

Exemple 110: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-(oxlran-2ylmethyl)-3-((3,3,3-trlfluoropropyl)thio)propanamide (Compound 928)

121

F

F

A solution of /V-(3-chioro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3trifluoropropyl)thio)propanamlde (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 minerai oil) 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 température and stirred ovemight under N₂. The reaction mixture was quenched with water (15 mL) and extracted with EtOAc (3x10 mL). The organic layer was dried over MgSO₄ and concentrated under reduced pressure. Purification by silica gel chromatography by eluting with 0-90% hexane/EtOAc afforded the title compound as an yellow oil (28 mg, 21%).

Exampie 111: Préparation of W-(3-chloro-1*(pyridin-3-yl)-1H-pyrazol-4-yl)-N(ethylcarbamoyl)-3-((3,3,3-trifluoropropyl)thio)propanamide (Compound 988)

F

F

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3trifluoropropyl)thio)propanamide (106 mg, 0.280 mmol) in dry CH₂CI₂ (1.8 mL), isocyanatoethane (44.3 pi, 0.560 mmol) was added. The reaction mixture was stirred at room température ovemight then refluxed for 2 h. The solvent was switched to THF and another portion of isocyanatoethane (44.3 pi, 0.560 mmol) was added and refluxed for additional 2 h. Toluene (1.9 mL) was added along with another portion of isocyanatoethane (44.3 pl, 0.560 mmol) and the reaction was refluxed ovemight. 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 Biotage® Initiator microwave reactor for total of 9 h at 120 ’C, then for 8 h at 125 ’C, with extemal IR-sensor température 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% CH₂CI₂/MeOH and a subséquent

122 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

Example 112: Préparation of 4-((3-chloro«1«(pyrldin-3-yl)-1H-pyrazol-4-yl)(ethyl)amlno)-4oxobutanolc acid (Compound Y2187)

ln a 100 mL round bottom flask (RBF), 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4amine (500 mg, 2.25 mmol), DMAP (27.4 mg, 0.225 mmol), triethylamine (0.469 mL, 3.37 mmoi), 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 ovemight. The reaction mixture was concentrated and purified by silica gel chromatography by eluting with 0-15% CH₂CI₂/MeOH to afford the title compound as an off-white solid (635 mg, 86%).

Example 113: Préparation of S-(3,3,3-trifluoropropyl) 4-((3-chloro*1-(pyridln-3-yi)-1H· pyrazol-4-yl)(ethyl)amlno)-4-oxobutanethloate (Compound 979)

A solution of 4-((3-chloro-1-(pyridin-3-yl)-1H-pyrazo1-4-yl)(ethyl)amino)-4-oxobutanoic acid (100 mg, 0.310 mmol), 3,3,3-trifluoropropane-1-thiol (42.0 pi, 0.387 mmol), and DMAP (3.79 mg, 0.031 mmol) in dry CH₂CI₂ (620 μΙ) was cooled to 0 ’C. DCC (63.9 mg, 0.310 mmol) was added and the reaction was warmed up to room température under N₂, then stirred ovemight. The reaction mixture was filtered using additional CH₂Cl₂ (1 mL) to remove saits and concentrated under reduced pressure. Purification by silica gel flash column chromatography eluting with 10-90% hexanes/EtOAc afforded the title compound as a slightly yellow clear viscous semi-solid (83 mg, 60%). Reference: J. Am. Chem. Soc., 2009,131,14604-14605. Example 114: Préparation of 3,3,3-trifIuoropropyl 4-((3-chioro*1-(pyridln-3-yl)-1H-pyrazol4-yl) (ethyi )a ml no)-4-oxobutanoate (Compound Y2154)

A solution of 4-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-4-oxobutanoic acid (101 mg, 0.313 mmol), sodium bicarbonate (526 mg, 6.26 mmol), and 3-bromo-1,1,1trifluoropropane (66.6 μΙ, 0.626 mmoi) in DMF (1565 μΙ) was stirred at room température under N₂ ovemight. The reaction was quenched with water (15mL) and extracted with CH₂CI₂ (3x10 124 mL). The organic layer was dried and concentrated under reduced pressure. Purification by silica gel chromatography by eluting with 0-100% hexanes/EtOAc afforded the title compound as a clear oil (36 mg, 26%). Reference: Syn. Commun., 2008,38, 54-71.

Example 115: Préparation of 2-((2,2,2-trifluoroethyi)thlo)ethyl (3-chloro-1-(pyridln-3-yl)1H-pyrazol-4-yl)(ethyl)carbamate (Compound 970) .CI h₃c

A solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (170 mg, 0.763 mmol) In dichloroethane (2 mL)was cooled to 0 ’C. Under N₂₁ 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) was added ln one portion. The ice bath was removed and the mixture was stirred at room température for 5 minutes and at 80 ’C for 50 min. The mixture was cooled to room température and then 2-((2,2,2-trifluoroethyl)thio)ethanol (251 mg, 1.57 mmol) was added with CH₂CI₂ (0.5 mL) followed by another portion of N,N-dimethylpyridin-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 CH₂CI₂ (10 mL) and saturated aqueous NH₄CI (10 mL). The organic layer was separated, dried, and concentrated. Purification by silica gel chromatography by eluting with 0-100% hexanes/EtOAc and a subséquent purification eluting with 0-100% water/acetonitrile afforded the title compound as a cloudy white oil (33 mg, 10%).

Exampie 116: Préparation of 1-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yi)-1-ethyi-3-(((3,3,3trif1uoropropyi)thio)methyl)urea (Compound 990) .Cl ch₃

To a solution of 2-((3,3,3-trifluoropropyl)thio)acetic acid (696 mg, 3.70 mmol) ln CH₂CI₂ (7.40 mL), oxalyl chloride (1.619 mL, 18.49 mmol) was added along with a drop of DMF at room température. Once DMF was added, gas évolution was observed and continued for about 30 min. The reaction mixture was stirred at room température for total of 1 h then the solvent was removed under reduced pressure. Acetone (18.50 mL) 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 réaction mixture was diluted with water (15 mL) and stirred at room température for 5 min. Dichloromethane (10 mL) was added and the organic layer was separated, dried, and

125 concentrated under reduced pressure to afford 2-i(3,3,3-trifluoropropy!)thïo)acety1 azide as dark brown-green oil. Dry CH₂CI₂ (4193 pl) was added to the crude azide and refluxed for 2 h. The reaction was cooled to room température and 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4amine (140 mg, 0.629 mmol) was added. The reaction was stirred ovemight at room température. The reaction was concentrate under reduced pressure and purified by silica gel chromatography by eluting with 0-10% CH₂CI₂/MeOH to afford titie compound as a light brown solid (179 mg, 68%). Référencé: J. Org. Chem., 2003, 68, 9453-9455.

Exemple 117: Préparation of 3-(3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)-5(hydroxymethyl)oxazoiidin-2-one (Compound Y2148)

OH

To a solution of tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(oxiran-2ylmethyl)carbamate (321 mg, 0.915 mmol) in dry CH₂CI₂ (915 pL), trifluoroacetic acid (915 pL) was added under N₂. The reaction mixture was stirred at room température for 90 min under N2. The reaction mixture was diluted with toluene (10 mL) and concentrated under reduced pressure to almost dryness. EtOAc (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 EtOAc (3x5 mL), dried over MgSO₄, and concentrated under reduced pressure to afford the titie compound as a white foam (134 mg, 47%).

Example 118: Préparation of W-((3-chloro-1-(pyrldin-3-yi)-1H-pyrazol-4yl)(ethyl)carbamoyl)-4-methoxybenzamide (Compound Y2189) .Cl

A solution of 4-methoxybenzamide (61.1 mg, 0.404 mmol) and oxalyl chloride (44.2 pl, 0.505 mmol) ln DCE (1684 pl) was refluxed for 15 h under N₂. The reaction was cooled to room température and 3-chloro-/V-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (75 mg, 0.337 mmol) was added and stirred ovemight at room température. The reaction mixture was diluted with saturated aqueous NaHCOj (5 mL) and CH2CI2 (3 mL). The phases were separated and the aqueous layer was washed with CH₂CI₂ (2x3 mL). The combined organic layer was dried and concentrated. Purification by silica gel chromatography elutlng with 15-100% hexanes/EtOAc

126 afforded the title compound as white solid (107 mg, 78%). Reference: J. Org. Chem., 1963, 73,

1805.

Example 119: Préparation of 1-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-1-ethylurea (Compound Y2186)

A solution of N-((3-chloro-1-(pyridin-3-yl)-1H-pyrazoi-4-y!)(ethyl)carbamoy!)benzamide (300 mg, 0.811 mmol) in dry MeOH (2028 μΙ) and 2 N aqueous NaOH (811 μΙ, 1.62 mmol) was heated at 65 ’C for 3 h. The reaction mixture was cooied to room température and neutralized with 2 N aqueous HCl and concentrated under reduced pressure which produced yellow precipltate. The precipitate was collected by filtration, washed with hexanes (3 mL), and dried under vacuum to afford the title compound (109 mg, 48%).

Example 120: Préparation of N-ethyl-N-(3-methyl-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-4oxobutanamlde (Compound Y2185)

A solution of N-(3-chloro-1-(pyridin-3-yi)-1H-pyrazol-4-yl)-N-ethyi-4-hydroxybutanamlde (41 mg, 0.133 mmol) ln dry CH₂CI₂ (1328 μ!) was cooied to 0 ’C ln 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 température and stirred for 5 h. LCMS indicated no product formation so another portion of Dess-Martin periodinane (64.8 mg, 0.153 mmol) was added and stirred at room température ovemight. The reaction mixture was diluted with saturated aqueous NaHCÛ3 (5 mL) and extracted with CH₂CI₂ (3x5 mL). The organic layer was dried, concentrated, and purified by silica gel chromatography eluting with 0-50% CH₂Ci₂/MeOH to afford the title compound as clear oil (21 mg, 46%).

Example 121: Préparation of 1,1,1-trifluoro-7,7-dimethoxyheptan-4-o!

in an oven dried vial with a stir bar, magnésium (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 l₂ and heated

127 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 lodine color dîsappeared. The reaction mixture was refluxed for 1 h under N₂ to give a cloudy colorless solution, ln a separate oven dried round bottom flask, 4,4,4-trifluorobutanal (208 pL,

1.983 mmol) was added with dry THF (10 mL, 0.2M) and cooled to 0 ’C. Room température

Grignard reagent was added drop wise over 8 min and stirred at 0 ’C for 30 min. The réaction was warmed up to room température and stirred for 1.5 h. The reaction was quenched with saturated aqueous NH₄CI (15 mL) and extracted with CH₂CI₂ (3x15 mL). The organic layer was dried, concentrated, and purified by silica gel chromatography eluting with 0-10% CH₂CI₂/MeOH to afford the title product as 85% pure clear semi-solid (372 mg, 69%): IR (thin film) 3442 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 4.39 (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, 1 H); ”F NMR (376 MHz, CDCI₃) δ -66.37; HRMS-FAB (m/z) [M+Naf calcd for C^HvFjNaOj, 253.1022; found,

253.1025.

128

Example 122: Préparation of 7,7,7-trlfluoro-4-oxoheptanolc acid

Lf ?

o

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 HCl (8079 pL, 8.08 mmol) was added at room température. The reaction mixture was stirred for 1 h then diluted with water (10 mL) and Et₂O (10 mL). The organic layer was separated and the aqueous layer was washed with Et₂O (2x10 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 mL) and glacial acetic acid (0.5 mL). Then KMnO₄ (766 mg, 4.85 mmol) dissolved In water (10 mL) was added to the stirring solution drop wise and stirred at room température for 2.5 h. GCMS analysis showed incomplète conversion so more KMnO₄ (510 mg) was added and the reaction was left stirring ovemight at room température. The reaction was diluted with AcOH (15 mL; 2 mL glacial AcOH in 13 mL water) and CH₂CI₂ (10 mL). The organic layer was separated and the aqueous layer was extracted with CH₂CI₂ (2x10 mL). The combined organic layer was washed with water (15 mL), dried, and concentrated. Purification by silica gel chromatography eluting with 0-10% CH₂CI₂/MeOH afforded the title compound as white solid (66 mg, 15%): IR (thin film) 1715 cm’¹; ¹H NMR (400 MHz, CDCIj) δ 2.81 - 2,72 (multiple peaks, 4H), 2.69 (ddd, J= 6.8, 5.5, 1.2 Hz, 2H), 2.50 - 2.35 (m, 2H), 1.59 (br s, 1H); ¹⁹F NMR (376 MHz, CDCI₃) δ -66.66.

Exampie 123: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yi)-N-ethyl-7,7,7trifluoro-4-oxoheptanamlde (Compound Y2188)

H₃C

A solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amlne (62 mg, 0.278 mmol), 7,7,7-trifluoro-4-oxoheptanolc acid (66.2 mg, 0.334 mmol), and DMAP (51.0 mg, 0.418 mmol) in dry Et₂O (928 pL) was cooled to 0 ’C in an Ice bath under N₂. DCC (138 mg, 0.668 mmol) was added and the reaction was warmed up to room température slowiy. The reaction was stirred under N₂ ovemight at room température. A white precipitate was filtered off with Et₂O (1 mL) and the fiitrate was concentrated. Purification by silica gel chromatography eluting with 0-75% hexanes/EtOAc afforded the title product as brown viscous oil (59 mg, 50%).

Example 124: Préparation of N-(3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2hydroxypropanamlde

129

To a solution of 1-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y1)(ethyl)amlno)-1-oxopropan2-yl acetate (2.4 g, 7.1 mmol) in methanol (8.9 mL) and tetrahydrofuran (8.9 mL) was added 2M lithium hydroxlde (7.1 mL, 14.2 mmol). The reaction mixture was stirred for 2 hours at 25 ’C. The reaction mixture pH was then made neutral by the addition of a 2M HCl. The mixture was extracted with ethyl acetate, and the organic portions were combined, dried over MgSO₄₁ filtered and concentrated in vacuo to afford the title compound as a white soiid (1.85 g, 88%); mp 137138 *C; ¹H NMR (400 MHz, DMSO) δ 9.08 (d, J~ 2.5 Hz, 1 H). 8.98 (s. 1 H). 8.58 (dd, J = 4.7, 1.1 Hz, 1 H), 8.23 (ddd, J = 8.4, 2.6,1.3 Hz, 1 H), 7.59 (dd, J = 8.3,4.7 Hz, 1 H), 4.97 (d, J - 7.6 Hz, 1 H), 4.08 (m, 1 H), 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 m/z 295.6 ([M+H]*).

Example 125:1-((3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yi)(ethyl)amlno)-1-oxopropan-2-yl methanesulfonate (Compound Y2008)

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazo1-4-yl)-N-ethyl-2hydroxypropanamide (100 mg, 0.34 mmoi) 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 CH₂CI₂, and washed with water. The phases were separated, dried, concentrated In vacuo and purified by silica gel chromatography eluting with 0-70% acetone In hexanes to afford the titie compound as a light yellow oil (88 mg, 70%): IR (thin film) 2980, 2936,1676 cm'¹; ’H NMR (400 MHz, CDCh) δ 9.00 (d, J = 2.5 Hz, 1 H), 8.64 (dd, J = 4.8,1.4 Hz, 1 H), 8.12 (s, 1 H), 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 ([M+H]*).

Exemple 126: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-3-((3,3difluorocyclobutyl)thlo)-N-ethylpropanamlde (Compound 910)

130

N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethy!-3-((3oxocyclobutyl)thlo)propanamlde (100 mg, 0.264 mmol) was dissolved In CH₂CI₂ (2 mL) and stirred at 0 ’C. Deoxofluor® (0.083 mL, 0.449 mmol) and EtOH (2.312 μΙ, 0.040 mmol) was 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 équivalent of Deoxofluor® (50 μί) and another 2.5 μί of EtOH was added. The réaction was worked up by slow addition of NaHCOj solution and stirred for 30 min at 25 ’C. The mixture was diluted with water (20 mL) and extracted with CH₂CI₂ (3 x 20 mL). The combined organic layer was washed with 0.01 M HCl, dried over Na₂SO₄ and purified with silica gel chromatography (0-100% EtOAc/hexane) to give the titie compound as a light yellow oll(19mg, 18%).

Example 127: Préparation of N-(3-ch!oro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N>ethyl-3(vlnylsulflnyl)propanamlde (Compound 1004)

To a 7 mL vial was added N-(3-chloro-1-(pyridÎn-3-yl)-1H-pyrazol-4-y!)-N-ethyl-3mercaptopropanamide (0.050 g, 0.161 mmol), 1,2-dibromoethane (0.907 g, 4.83 mmol) followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0,024 g, 0.161 mmol). The solution was stirred at 25 ’C ovemight, 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 hours, then worked up with sodium sulfite solution and extracted with CH₂Cl₂. The crude reaction mixture was purified by silica gel chromatography (0-10% MeOH/CH₂CI₂) to give the title compound as a brown oil (33 mg, 58%).

Example 128: Préparation of 3-(A/-carbamoy!-S-methy!sulfon!mldoyl)-N-(3-chloro-1(pyridln-3-yl)-1H-pyrazol-4-yl)-N-ethylpropanamlde (Compound Y2099)

I3I

h₃c

N-[3-chloro-1-(3-pyridy1)pyrazol-4-y1]-3-{Mcyano-S-methy1-sulfonimldoyl)-N-ethylpropanamide (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 added slowly until the aqueous layer was neutral. The aqueous layer was extracted with CH₂CI₂ and the combined organic layers were dried over Na₂SO₄ and concentrated. The crude reaction mixture was purified by silica gel chromatography (0-10% MeOH/CH₂CI₂) to give the title compound as white solid (135 mg, 40%).

Example 129: Préparation of 4-chloro-N-(3-chloro-1-(pyr!din-3-y!)-1H-pyrazol-410 yl)butanamlde (Compound Y2166)

To a solution of 3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine (1.34 g, 6,69 mmol) in CH₂CI₂ (11 mL) cooled to 0 ’C was added triethylamine (1.439 mL, 10.33 mmol) and 4chlorobutanoyl chioride (0.971 g, 6.89 mmol). The solution was allowed to slowly warm to 25 ’C 15 and stirred for 1 h. The reaction was diluted with water (20 mL) and extracted with CH₂CI₂ (3 x mL). The combined organic layers were dried, concentrated and purified with chromatography (0-100% EtOAc/hexane) to give the title compound as white solid (1.87 g, 91%).

132

Example 130: Préparation of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)pyrrolldin-2-one (Compound Y2167)

A solution of 4-chloro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)butanamide (1.82 g, 6.08 mmol) ln THF (50 mL) was cooled to 0 ’C. NaH (0.280 g, 7.00 mmoi) 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 CH₂CI₂ (3 x 20 mL). The combined organic layers were dried, concentrated and purified with silica gel chromatography (0-10% MeOH/CH₂CI₂) to give the title compound as yellow solid (1.70 g, 96%).

Example 131: Préparation of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3· methylenepyrrolldln-2-one (Compound Y2168)

A solution of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)pynOlidin-2-one (1600 mg. 6.09 mmol) ln CH₂CI₂ (15 mL) was cooied to 0 ’C. Triethylamine (1.273 mL, 9.14 mmol) and 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 sait (dimethylmethylideneammonium iodideX1465 mg, 7.92 mmol) was then added and the solution was allowed to warm to 25 ’C and stir ovemight. The solution was diluted with CH₂CI₂ (30 mL) and 1N HCl (30 mL) was added and the mixture was stirred for 10 min before It was neutralized with NaOH solution to pH =12. The mixture was extracted with CH₂Ci₂, and the combined organic layers were dried, concentrated and purified with silica gel chromatography (0-10% MeOH/CH₂CI₂) to give the title compound as light yellow solid (866 mg, 52 %).

133

Exampie 132: Préparation of 1-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl}-3((methylthlo)methyl)pyrrolidin-2-one (Compound 955)

N

1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-methylenepyrrolidin-2-one (400 mg, 1.46 mmol) was dissoived in THF (6 mL). Potassium hydroxide (384 mg, 5.82 mmol) dissoived in water (1 mL) was added to the mixture, followed by S,S-dimethyl carbonodithioate (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 CH₂CI₂ (3 x 20 mL). The combined organic layers were dried and concentrated, and the crude mixture was purified by silica gel chromatography (0-10% MeOH/CH₂CI₂) to give the title compound as white solid (385 mg, 82%).

Example 133: Préparation of methyl 2-cyclobutylldeneacetate

O,

MeO

To a 250 mL round bottom flask was added methyl 2(triphenylphosphoranylidene)acetate (12.04 g, 36 mmol) and benzene (90 mL). Cyclobutanone (5.05 g, 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 fiitered off and the solution was concentrated and purified by silica gel chromatography to give the title compound as a coloriess oil (3.22 g, 71%): IR (thln film) 1714 cm'¹; ’H NMR (400 MHz, CDC13) δ 5.60 (t, J = 2.3 Hz, 1 H). 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 (tt, J= 11.4, 5.8 Hz, 2H); ’³C NMR (101 MHz, CDCI3) δ 167.92, 166.95,111.93, 50.79, 33.71, 32.32,17.62.

Example 134: Préparation of 2-cyclobutylldeneacetic acid

HO

To a solution of methyl 2-cyclobutylideneacetate (100 mg, 0.793 mmol) In MeOH (1.00 mL) stirring at RT was added 2N LiOH solution (prepared from lithium hydroxide hydrate (100 mg, 2.378 mmol) and water (1 mL)). The mixture was stirred at 25 ’C overnight, then it was worked up by addition of 2N HCl and extracted with CH₂CI₂. The combined organic layer was dried to give a white solid, which was purified by silica gel chromatography (0-70% EtOAc/hexane) to give the title compound as a white solid (20 mg, 23%): IR (thin film) 2923, 1647 cm*’: ’H NMR (400 MHz, CDCl₃) δ 10.89 (s, 1H), 5.60 (dd, J= 4.3, 2.1 Hz. 1H), 3.38 - 3.02

134 (m, 2H), 2.97 - 2.71 (m. 2H). 2.10 (dq, J = 15.9, 8.0 Hz, 2H); ¹³C NMR (101 MHz, CDCI₃) δ

172.35,171.33,112.13, 34.10, 32.58.17.56.

Example 135: Préparation of 3-((3,3,3-trlf1uoropropyl)thlo)propanolc acid

3-Mercaptopropanoic acid (3.2 g, 30.1 mmol) was dissolved ln MeOH (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 (6.14 g, 34.7 mmol). The solution was then stirred at 65 ’C for 3 h and then the reaction was quenched with 1N HCl until the pH of the solution was acldic. The mixture was extracted with CH₂CI₂ (3 x 30 mL) and the combined organic phases were dried, concentrated and purified by silica gel chromatography (0-50% EtOAc/hexane) to give the title compound as colorless oil mixed with some white suspension (5.5 g, 90%): IR (thin film) 2936,1708 cm·’; Ή NMR (300 MHz, CDCI₃) δ 2.86 - 2.78 (m, 2H). 2.78 - 2.58 (m, 4H), 2.52 - 2,25 (m, 2H); EIMS m/z 202.

Example 136: Préparation of N-[3-chloro-1-(3-pyrldyl)pyrazol-4-ylJ-3-[3-[[3-chloro-1-(3pyrldyl)pyrazo1-4-y1]-methyl-amlno]-3-oxo-propy1]sulfanyl-N-ethyl-2-methyl-propanamide (Compound 790)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3mercatopropanamlde (100 mg, 0.308 mmol) and 3-chloro-N-(3-chloro-1-(pyridin-3-yl)-1Hpyrazol-4yl)-N-methylpropanamide (100 mg, 0.334 mmol) in DMF (1 mL) was added sodium hydride (60% dispersion ln oil, 15 mg, 0,375 mmol). The mixture was stirred at room température for 18 h and diluted with water and CH₂Cl₂. The organic phase was separated, dried over Na₂SO₄, filtered and concentrated ln vacuo to give an orange oil. This oll was purified by chromatography eluting with mixtures of methanol and methyiene chloride to give the title compound as a yellow oil (120 mg, 66%).

Example 137: Préparation of N-(3-chloro-1-(pyridin-3-yl)-ÏH-pyrazol-4-yl)-3-((2-((3-chloro1-(pyridin-3-y1)-1H-pyrazol-4-yl)(methyl)amino)-2-oxoethy1)thlo)-N-ethylpropanamlde (Compound 789)

135

To a solution of N-(3-chloro-1-(pyridin-3-yl)-ïH-pyrazol-4-y1)-N-ethyl-3mercaptopropanamida (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-chioro-N-(3-chloro-1-(pyridin-3-yl)-1A7pyrazol-4-y1)-/V-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 Et₂O. To the organic phase was added ammonia in MeOH (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 eluting with mixtures of methanol and CH₂CI₂ to give the title molecuie as an orange oil (120 mg, 66%).

Example 138: Préparation of tert-butyl ((1R,4S)-4-((3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4yl)(methyl)carbamoyl)cyclopent-2-en-1-yl)carbamate

Cl

ch₃

A solution of 3-chloro-N-methy1-1-(pyridin-3-yl)-1H-pyrazol-4-amine (200 mg, 0.96 mmol) in THF (10 mL) was cooled to -78 ’C. Lithium bis(trimethy1sily1)amide (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-carboxytate (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 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%): ’H NMR (400 MHz, CDCIj) δ 9.01 - 8.93 (d, J = 2.8 Hz, 1 H), 8.66 - 8.60 (m, 1 H), 8.11 - 8.02 (m, 2H), 7.52 - 7.42 (m. 1 H), 5.93 - 5.85 (m, 1 H), 5.72 - 5.66 (m, 1 H), 5.53 - 5.44 (d, J = 9.5 Hz, 1 H), 4.80 - 4.67 (m, 1 H), 3.58 - 3.47 (m, 1 H). 3.30 - 3.21 (s, 3H), 2.35 - 2.22 (m, 1H), 1.90 -1.80 (m, 1H), 1.51 -1.34 (s, 9H); ’³C NMR (101 MHz, CDCI₃) δ 175.26, 155.23, 148.70, 140.31, 140.00,135.61,135.18,

136

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+H]*, 416 ([M-H]*).

Example 139: Préparation (1S,4R)-4-amino-N-(3-chloro-1-(pyridin-3-yi)-1H-pyrazol-4-yl)-Nmethyicyclopent-2-enecarboxamide 2,2,2-trlfluoroacetate

Cl

OH

To a solution of tert-buty! ((1R,4S)-4-((3-chlorO’1-(pyridin-3-y1)-1H-pyrazol-4yl)(methyl)carbamoyl)cyclopent-2-en-1-yl)carbamate (130 mg, 0.31 mmol) in CH₂CI₂ (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 the title compound as a clear oil (130 mg, 94%): ’H NMR (400 MHz, CD₃OD) δ 9.02 (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, 1 H),

7.63 (ddd, J = 8.4, 5.0, 0.7 Hz, 1 H), 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, CDCIj) δ 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

Example 140: Préparation of (1S,4R)-N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-Nmethyl-4-(methylsulfonamldo)cyclopent-2-enecarboxamlde (Compound Y2054)

Cl

To a solution of (1S,4/?)-4-amino-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-Nmethylcyclopent-2-enecarboxamide 2,2,2-trifluoroacetate (541 mg, 1.25 mmol) dissolved in CH2CI2 (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 purified by silica gel chromatography utilizlng methanol and CH2CI2 resulting in the Isolation of the title compound as a white foam (319 mg, 64%).

Exemple 141: Préparation of (1S,3R)-N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-Nmethyl-3-(methylsulfonamldo)cyclopentanecarboxamlde (Compound Y2092)

Cl

A solution of (1/?,4S)-4-amino-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y!)-Nmethylcyclopent-2-enecarboxamide 2,2,2-trifluoroacetate (60 mg, 0.15 mmol) in methanol (1.5 mL) was passed through an H-Cube® continuous flow hydrogenator equipped with a 10% Pd/C cartridge (full H₂,25 ’C, 1 mL/min flow rate). The resulting solution was concentrated and purified by silica gel chromatography utilizing methanol and CH2CI2 as a mobile phase to provide the title compound as white solid (16 mg, 24%).

Example 142: Préparation of N-(3-chloro-1-(pyrIdin-3-yI)-1H-pyrazol-4-y])-3-(1H-tetrazoi-5y])-N-ethylpropanamide (Compound Y2178)

To a solution of N-(3-chloro-1-(pyridin-3-y!)-1H-pyrazol-4-yl)-3-cyano-Nethylpropanamide (0.176 g, 0.579 mmol) in toluene (5.79 mL) at ambient température and

138 under N₂ were added azidotrimethylsllane (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 température for 24 h at which point UPLC-MS analysis indicated nearly complété conversion to a product of the desired mass. The reaction was cooled, diluted (slowly) in MeOH (20 mL) and concentrated in vacuo to afford a dark brown oil. The residue was absorbed onto Celite and purified via reverse phase flash chromatography (0 to 100% CHjCN/H₂O) to afford the desired product as a pale brown glassy solid (49 mg, 24%).

Example 143: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3trifluoro-2-methylpropyl)thio)propanamlde (Compound 919)

CI h₃c

To a solution of A/-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((2(trifluoromethyl)allyi)thio)propanamide (0.056 g, 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 (0.110 g, 1.337 mmol). The réaction 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 équivalents of both the hydrazide and sodium acetate were added. The reaction was again heated to 90 ’C and stirred for an additional 2 h. UPLC-MS indicated only minor amount of starting material remaining. Therefore, an additional 5 équivalents 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 EtOAc (10 mL) and washed with water (2x5 mL) and brine (1x5 mL). The organic layer was dried over Na₂SO₄, filtered and concentrated in vacuo to afford a yellow oil. The crude residue was purified via normal phase flash chromatography (0 to 100% EtOAc/CH₂CI₂) to afford the desired product as a pale yellow oil (46 mg, 79%).

139

Example 144: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2(vinyithio)propanamide (Compound 787)

To a dry round bottom flask under N₂ were added sodium hydride (0.043 g, 1.063 mmol, 5 60% dispersion In minerai oil) and THF (2.126 mL), followed by methanol (0.086 mL, 2.126 mmol). The reaction was allowed to stir at ambient température until cessation of gas évolution was observed (-45 min). The réaction was then cooled to 0 ’C and S-(1-((3-chloro-1-(pyridin-3yl)-1H-pyrazol-4-yl)(ethyl)amino)-1-oxopropan-2-yl) ethanethloate (0.150 g, 0.425 mmol) in THF (2.126 mL) was added. The reaction was warmed to ambient température and stirred for 30 min. 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 réaction was warmed to ambient température and stirred ovemight. The reaction was diluted in EtOAc (5 mL) and quenched with H₂O (1 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3x10 mL). The combined organic extracts were dried over Na₂SO₄, filtered and concentrated in vacuo to give a brown oil.

The crude residue was purified via flash chromatography (25-80% EtOAc/Hexanes) to give the desired product as an opaque oil (29 mg, 20%).

Example 145: Préparation of (E)-N-(3-chloro-1-(pyrid1n-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3((3₍3,3-trifluoroprop-1-en-1-yi)thlo)propanamlde (Compound 890)

To an oven-dried microwave vial under N₂ were added dioxane (0.241 mL), Cu₂O (3.45 mg, 0.024 mmol), KOH (0.0I54 g, 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-yl)-1H-pyrazo1-4-yl)-N-ethyl-3mercaptopropanamlde (0.150 g, 0.483 mmol), sequentially. The reaction was capped and placed on a Biotage® Initiator microwave reactor for 3 h at 110 ’C, with extemal IR-sensor température monitoring from the side of the vessel. During this time, the reaction mixture went from a thlck, yellow mixture to a black mixture. The heterogeneous mixture was cooled to room température and diluted with EtOAc (20 mL). The mixture was filtered through a pad of Celite (EtOAc wash) and the filtrate was concentrated in vacuo to give an dark brown oll, The crude residue was purified via normal phase flash chromatography (0 to 100% EtOAc/CH₂CI₂) to

140 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.

Exemple 146: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3(methylsuifonamldo)propanamlde (Compound Y2145)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylacry1amlde (0.538 g, .1.944 mmol) in DMF (19.44 mL) at ambient température were added K₂CO₃ (0.672 g, 4.86 mmol) and methanesulfonamide (0.277 g, 2.92 mmol). The reaction was fltted with a reflux condenser and heated to 80 ’C. After stirring for 1 h, the reaction was cooled to ambient température and diluted in EtOAc (50 mL) and water (50 mL). The layers were mixed vigorously for 2 min and then separated. The aqueous phase was extracted with EtOAc (3 x 50 mL) and the combined organic extracts were washed with brine (3 x 100 mL), dried over Na₂SO₄, filtered and concentrated ln vacuo to afford a clear oil. The crude residue was purified via normal phase flash chromatography (0 to 30% MeOH/EtOAc) to afford the desired product as a clear semlsolid (524 mg, 69%).

Example 147: Préparation of N-(3-chloro«1-(pyrldln-3-yi)-1H-pyrazol-4-yi)-3-(N· (cyanomethyl)methylsulfonamido)-A/-methylpropanamlde (Compound 803)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1W-pyrazol-4-yl)-/V-methyl-3(methylsulfonamido)propanamide (0.085 g, 0.238 mmol) In THF (2.376 mL) at 0 ’C was added NaH (9.98 mg, 0.249 mmol, 60% dispersion In minerai 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 température and was stirred for 1h. The reaction was quenched with the addition of water (5 mL) and was diluted ln EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (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% MeOH/CH₂CI₂) to give the desired product as a pale yellow foam (86 mg, 87%).

141

Example 148: Préparation of N-(3’Chloro-1-(pyrIdin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3’ trifluoropropyl)amlno)propanamlde

F

To a microwave vial were added MeOH (2.0 mL), 3,3,3-trifluoropropan-l-amlne (0.386 g, 3.42 mmol) and 3-chioro-N-(3-chioro-1-(pyridin-3-yl)-1H-pyrazoi-4-yi)-N-ethylpropanamide (0.107 g, 0.342 mmol), sequentlally. The reaction was capped and placed In a Biotage® Initiator microwave reactor for 3 h at 100 ’C, with extemai IR-sensor température monitoring from the side of the vessei. After cooling, the reaction was concentrated in vacuo and purified via normal phase flash chromatography (0 to 15% MeOH/EtOAc) to afford the desired product as an opaque viscous oll (127 mg, 94%): ’H NMR (400 MHz, CDCi₃) δ 8.94 (dd, J = 2,8, 0.7 Hz, 1H), 8.63 (dd, J- 4.7,1.5 Hz, 1 H), 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. 1 H), 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); ’⁹F NMR (376 MHz. CDCI₃) δ -65.13; ESIMS m/z 390 ([M+H]*).

N-(3-chioro-1-(pyridin-3-yl)-1H-pyrazol-4-yi)-N-ethyl-3-(methylamino)propanamide was prepared as ln Exampie 148: ’H NMR (400 MHz, CDCI₃) δ 9.01 (d, J= 2.6 Hz, 1H), 8.61 (dd, J = 4.8,1.4 Hz. 1 H), 8.23 (s. 1 H). 8.06 (ddd, J = 8.3, 2.7,1.4 Hz. 1 H), 7.45 (dd. J = 8.3, 4.8 Hz, 1 H), 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); ’³C NMR (101 MHz. CDCI₃) δ 172.1,148.6,140.8,140.1,135.6,126.6,126.3, 124.1,123.8, 47.1,43.8, 36.1. 33.5,13.1; ESIMS m/z 308 ([M+H]*).

N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-A/-ethyl-3-((4,4_l4trifluorobuty1)amino)propanamlde was prepared as in Example 148: ’H NMR (400 MHz, CDCI₃) δ 9.04 (d, J = 2.7 Hz, 1 H), 8.61 (dd. J = 4.7,1.5 Hz, 1 H), 8.36 (s, 1 H). 8.08 (ddd, J = 8.4, 2.8.

1.5 Hz, 1 H). 7.45 (ddd, J = 8.4, 4.8, 0.7 Hz, 1 H), 3.69 (q, J = 7.2 Hz, 2H). 3.18 (t, J = 6.0 Hz, 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). 2.141.98 (m, 2H), 1.16 (t, J = 7.2 Hz. 3H); ’⁹F NMR (376 MHz, CDCI₃) δ -66.03; ESIMS m/z 404 ([M+H]*).

N-(3-chioro-1-(pyridin-3-yl)-1 H-pyrazol-4-yl)-N-ethyl-3-(ethylamino)propanamide was prepared as In Exampie 148: Ή NMR (400 MHz, CDCI₃) δ 9.05 (s, 1H), 8.61 (s, 1H), 8.41 (dd, J = 7.6, 2.1 Hz. 1 H). 8.09 (dd, J = 8.3,1.4 Hz, 1 H), 7.44 (dd. J = 8.4,4.8 Hz. 1 H), 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 (m, 3H); ’³C NMR (101 MHz, CDCI₃) δ 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+H]*).

N-t3-chloro-1 -( pyrîdï n-3-yl )-1 H-pyrazol-4-yl)-N-ethyl-3-(pheny1amIno)propanamide was prepared as ln Example 148: ’H NMR (400 MHz, CDCI₃) δ 8.81 (d, J =2.7 Hz, 1 H), 8.60 (dd, J = 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, 1 H), 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: Préparation of N-(3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(N(3,3,3-trlfluoropropyl)methylsulfonamldo)propanamide (Compound 978)

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1/-/-pyrazol-4-y1)-N-ethy1-3-((3,3,3trifluoropropyl)amino)propanamide (0.085 g, 0.218 mmol) in CH2CI2 (2.181 mL) at ambient température and under N₂ were added dilsopropylethyiamine (0.152 mL, 0.872 mmol) and methanesulfonyl chloride (0.025 mL, 0.327 mmol). The reaction was allowed to stir ovemight after which the reaction was diluted in CH2CI2 (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% EtOAc/CH₂Cl2) to afford the desired product as a pale yellow, viscous oil (78 mg, 73%).

143

Example 150: Préparation of N-tS-chloro-l-Îpyrldln-S-ylJ-IH-pyrazol^ylJ-N-ethyl-StmethyltSAd-trifluoropropyOamlnoJpropanamide (Compound Y2146)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3(methylamino)propanamide (0.139 g, 0.452 mmol) ln DMF (4.52 mL) at amblent température were added K₂CO₃ (0.125 g, 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 ovemight. UPLCMS analysis Indicated the presence of unreacted starting material. Therefore, an additional 3 équivalents of 3-bromo-1,1,1-trifluoropropane were added and reaction was left to stir at 70 ’C for 3h. UPLC-MS analysis indicated complété consumption of starting material and conversion to product of the desired mass. The reaction was cooled, diluted in EtOAc (20 mL) and filtered through a pad of Celite. The filtrate was then washed with half-saturated brine (3 x 20 mL), dried over Na₂SO₄, filtered and concentrated in vacuo. The crude residue was purified via normal phase flash chromatography (0 to 15% MeOH/CH₂CI₂) to afford the desired product as a clear oil (84 mg, 44%).

Example 151: Préparation of N-(3-chloro-1-(pyr1din-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3oxobutyl)thlo)propanam1de (Compound 877)

To a solution of but-3-en-2-one (0.040 mL, 0.444 mmol) in water (0.370 mL) and dioxane (0.370 mL) was added N-(3-chloro-1-(pyridin-3-yl)-1/-/-pyrazol-4-yl)-N-ethyl-3mercaptopropanamide (0.115 g, 0.370 mmol) at ambient température. The reaction was allowed to stir for 1 h at which point the reaction was diluted in CH₂CI₂ and the mixture was stirred vigorously for 1 h. The mixture was then passed through a phase separator and the remalning aqueous phase was washed with CH₂CI₂ (3x5 mL). The combined organic extracts were concentrated in vacuo to provide the desired product as an orange oii that was analytically pure by ¹H 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: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3dif!uorobutyl)thlo)-N-ethylpropanamide (Compound 889)

144

ch₃

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3oxobutyl)thio)propanamlde (0.184 g, 0.483 mmol) in CH₂CI₂ (4.83 mL) at 0 ‘C was added Deoxo-Fluor® (0.534 mL, 2.90 mmol) followed by EtOH (0.017 mL, 0.290 mmol). The reaction was stirred at ambient température for 48 h during which time the solution went from pale yellow to dark brown. The reaction was diluted ln CH₂CI₂ (10 mL) and quenched with the careful addition of NaHCO^^) (5 mL). The layers were separated and the aqueous phase was extracted with CH₂CI₂ (3 x 10 mL). 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% EtOAc/CH₂CI₂) to afford the desired product as a paie yellow oil (43 mg, 21%).

Example 153: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3dlf1uoropropyl)thlo)-N-ethylpropanamlde (Compound 927)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3dimethoxypropyl)thio)-N-ethylpropanamide (0.307 g, 0.743 mmol) in THF (7.43 mL) was added a 1.0M aqueous solution of HCl (7.43 mL, 7.43 mmol). The reaction was allowed to stir at ambient température for 1 h at which point TLC/UPLC-MS analysis indlcated complété hydrolysis to the desired aldéhyde product had occurred. The mixture was diluted in EtOAc (20 mL) and water (10 mL). The layers were mixed, separated, and the aqueous layer was extracted with EtOAc (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 vacuo. The crude product was dried via azeotropic distillation from toluene (3 x 10 mL) and then placed under N₂. To the flask was added CH₂CI₂ (7.44 mL) and the solution was cooled to 0 ’C. Deoxo-Fluor® (0.686 mL, 3.72 mmol) and EtOH (4,34 pl, 0.074 mmol) were added and the reaction was warmed to ambient température. After 18 h, the reaction was diluted in CH₂CI₂ (10 mL) and quenched with the careful addition of NaHCO^aq) (5 mL), The layers were separated and the aqueous phase was extracted with CH₂CI₂ (3x10 mL). The combined organic extracts were dried over Na₂SO₄, filtered and concentrated in vacuo. The

145 crude material was purified via normal phase flash chromatography (0 to 100% EtOAc/CH₂CI₂) to afford the desired product as a pale yellow oil (151 mg, 50%).

Example 154: Préparation of 1,1,1-trlfluoro-3-lodo-5-methylhexane

CH₃

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, trifluoroiodomethane (0.873 g, 4.46 mmol) (approximate) was condensed Into the reaction vessel. After warming to ambient température, the reaction was stirred for 2.5 h. Prior to removing the cap, the reaction was vented with a needle and substantial gas évolution was observed. The reaction was then diluted In water (5 mL) and the mixture was extracted with Et₂O (3 x 20 mL) and the combined extracts were dried over MgSOi, filtered and concentrated in vacuo to afford a clear oii (740 mg, 80%). Crude ’H NMR analysis Indicated desired product to be of -90% purity. Product was therefore used In subséquent reactions without further purification: ’H NMR (400 MHz, CDClj) δ 4.25 - 4.06 (m. 1H), 2.94 (dqd, J= 15.5,10.6, 6.1 Hz, 1 H), 2.77 (dqd. J = 15.5,10.0, 7.5 Hz, 1 H), 1.92 -1.74 (m, 2H), 1.45 -1.28 (m. 1 H), 0.98 (d. J =

6.5 Hz, 3H), 0.87 (d, J - 6.5 Hz, 3H); ’®F NMR (376 MHz, CDCb) δ -63.63. Reference: Ignatowska, J.; Dmowski, W. J. Fluor. Chem., 2007, 128, 997-1006.

(4_i4_t4-trifluoro-2-iodobutyl)benzene was prepared as in Example 154: ’H NMR (400 MHz. CDCI₃) δ 7.41 - 7.27 (m, 3H), 7.23 - 7.16 (m, 2H), 4.33 (dq. J-8.2, 6.7 Hz, 1 H). 3.31 3.15 (m, 2H), 2.96 - 2.72 (m. 2H); ”F NMR (376 MHz, CDCI₃) δ -63.63; EIMS m/z 314.

1-(4,4,4-trifluoro-2-iodobutyl)-1W-imidazole was prepared as In Example 154: ’H NMR (400 MHz, CDCI₃) δ 7.61 (t, J- 1.1 Hz, 1H), 7.12 (t, J - 1.1 Hz, 1H), 7.00 (t, J - 1.4 Hz, 1H), 4.46 - 4.31 (m, 3H), 2.88 - 2.66 (m, 2H); ’⁹F NMR (376 MHz, CDCb) δ -63.57; EIMS m/z 304.

1,1,1-trifluoro-3-lodopentane was prepared as In Example 154: ’H NMR (400 MHz, CDCb) δ 4.20 (tdd, J = 7.9, 6.2,4.4 Hz, 1 H), 3.01 - 2.84 (m, 1 H), 2.84 - 2.69 (m, 1 H), 1.84 -1.74 (m, 2H), 1.06 (t, J - 7.1 Hz, 3H); ’⁹F NMR (376 MHz, CDCb) δ -64.06; EIMS m/z 252. Example 155: Préparation of S-(1,1,1-trifluoro-5-methylhexan-3-yl) benzothloate

146

To a solution of 1,1,1-trifluoro-3-iodo-5-methylhexane (0.047 g, 0.168 mmol) in DMF (1.678 mL) at ambient température was added potassium benzothioate (0.035 g, 0.201 mmol). The reaction was allowed to stir for 18 h at which point the reaction was diluted in water (3 mL) and EtOAc (5 mL). The layers were mixed and then separated. The aqueous layer was extracted with EtOAc (3x5 mL) and the combined organic extracts were washed with water (1 x 10 mL) and half saturated brine (2 x 10 mL), dried over Na₂SO₄, fiitered and concentrated in vacuo. Residue was purified via flash chromatography (0 to 30% EtOAc/Hexanes) to afford the desired product as a clear oil (37 mg, 68%): ’H NMR (400 MHz, CDCI₃) δ 7.99 - 7.92 (m, 2H), 7.62 - 7.55 (m, 1 H), 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): ”F NMR (376 MHz, CDCI₃) δ -62.89.

S-(4_i4_i4-trifluoro-1-phenylbutan-2-yl) benzothioate was prepared as in Example 155: ’H NMR (400 MHz, CDCI₃) δ 7.97 - 7.89 (m, 2H), 7.58 (ddt, J = 7.9,6.9,1.3 Hz, 1H), 7.49 - 7.41 (m, 2H). 7.39 - 7.26 (m, 5H), 4.29 - 4.15 (m, 1 H), 3.11 (d, J = 7.2 Hz, 2H), 2.54 (qd, J = 10.6,6.6 Hz, 2H); ”F NMR (376 MHz, CDCI3) δ -62.86; EIMS m/z 324.

S-(4_i4_i4-trifluoro-1-(1 H-imidazol-1 -yt)butan-2-yl) benzothioate was prepared as in Example 155: ’H NMR (400 MHz, CDCI₃) δ 7.98 - 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, 3H), 2.64 - 2.39 (m. 2H); ’⁹F NMR (376 MHz, CDCI₃) δ -62.98; EIMS m/z 314.

S-(1,1,1-trifluoropentan-3-yl) benzothioate was prepared as in Example 155: ’H NMR (400 MHz, CDCI₃) δ 8.02 - 7.91 (m, 2H), 7.64 - 7.55 (m, 1H), 7.51 - 7.40 (m, 2H), 4.06 - 3.90 (m, 1 H), 2.70 - 2.41 (m, 2H), 2.02 - 1.86 (m, 1 H). 1.86 -1.71 (m, 1 H), 1.05 (t, J = 7.3 Hz, 3H); ’⁹F NMR (376 MHz, CDCI₃) δ -63.32; EIMS m/z 262.

Example 156: Préparation of W-(3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((1,1,1trifluoro-5-methylhexan-3-yi)th1o)propanamlde (Compound 1053)

CH₃

147

To a suspension of NaH (60% in minerai oil, 0.012 g, 0.300 mmol) in THF (2.86 mL) at ambient température and under N₂ was added MeOH (0.058 mL, 1.429 mmol). The reaction became homogenous and gas évolution 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-yl) benzothloate (0.083 g, 0.286 mmol) In THF (2 mL) was added slowly. The reaction was warmed to ambient température, stirred for 45 min, and then retumed to 0 ’C. To the reaction was added a solution of 3-chloro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylpropanamide (0.090 g, 0.286 mmol) in THF (2 mL). The reaction was warmed to ambient température and stined for 18 h. The réaction was diluted in EtOAc (20 mL) and water (10 mL). The layers were mixed and then separated. The aqueous layer was extracted with EtOAc (3 x 20 mL) and the combined organic extracts were dried over Na₂SO₄₁ filtered and concentrated in vacuo. The crude residue was purified via normal phase flash chromatography (0 to 100% EtOAc/CH₂CI₂) to afford the desired product as a pale yeliow oil (63 mg, 45%).

Example 157: Préparation of fert-butyl(2-(2,2-dîfluorocyc1opropyl)ethoxy)dipheny1s1lane

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-butyl)diphenylsilane (3.6 g, 11.59 mmol) and sodium fluoride (7.30 mg, 0.174 mmol) (For préparation of starting olefin, see: Waser, J.; Gaspar, B.; Nambu, H.; Carreira, E. M. J. Am. Chem. Soc. 2006, 128, 11693-11712). To the closed addition funnel was added trimethylsilyi 2,2-difluoro-2-(fluorosulfonyl)acetate (4.57 mL, 23.19 mmol). The réaction 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 complété, the reaction was allowed to continue stirring at 120 ’C for 30 min. The reaction was cooled to ambient température, diluted in CH₂CI₂ (50 mL) and washed with NaHCO^q) (2 x 50 mL). The organic phase was separated, dried over Na₂SO₄, filtered and concentrated in vacuo to provide a brown oil. The crude residue was purified via normal phase flash chromatography (0 to 15% CH₂CI₂/Hexanes) to provide the desired product as a clear oîl (3.07 g, 73%): ’H NMR (400 MHz, CDCIj) δ 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, 1 H), 1.73 -1.55 (m, 2H), 1.42-1.27 (m. 1 H), 1.06 (s. 9H), 0.94 - 0.81 (m, 1 H); ’⁹F NMR (376 MHz, CDCIj) δ -128.54 (d, J = 156.2 Hz), -143.96 (d, J= 155.5 Hz); ’³C NMR (101 MHz, CDCIj) δ 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).

148

Example 158: Préparation of 2-(2,2-difluorocyclopropyl)ethyi 4-methylbenzenesulfonate

To a solution of tert-butyl(2-(2,2-difluorocyclopropyl)ethoxy)diphenylsilane (0.386 g, 1.071 mmol) ln THF (10.71 mLJatO’Cwas added a 1.0M solution ofTBAF (3.21 mL, 3.21 mmol) in THF. The reaction was warmed to ambient température and stirred for 3 h. The réaction was quenched with the addition of NH₄CI₍,_q) (1 mL) and the mixture was partitloned between water (15 mL) and EtOAc (15 mL). The layers were mixed well and then separated. The aqueous layer was extracted with EtOAc (3 x 20 mL) and the combined organic extracts were dried over Na₂SO₄, filtered and concentrated in vacuo. The crude residue was then taken up in CH2CI2 (7.15 mL). To the solution were then added pyridine (0.434 mL, 5.36 mmol) and ptoluenesulfonyl chloride (0.614 g, 3.22 mmol). The réaction was stirred at ambient température for 48 h at which point the reaction was partitioned between CH2CI2 (50 mL) and water (25 mL). The layers were separated and the organic layer was washed with 1N HCI₍,_q) (20 mL), water (20 mL) and brine (20 mL). The organic layer was then dried over Na2SO₄, filtered and concentrated ln vacuo. The crude residue was purified via normal phase flash chromatography (0 to 50% EtOAc/Hexanes) to afford the desired product as a clear oil (142 mg, 46%, 2 steps): ’H NMR (400 MHz, CDCI3) δ 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, 1 H), 1.81 -1.69 (m, 1 H), 1.63 -1.48 (m, 1 H). 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) δ 145.0,132.9,129.9,

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); ”F NMR (376 MHz, CDCI₃) δ -129.09 (d, J = 157.8 Hz), -144.18 (d, J = 158.1 Hz).

Example 159: Préparation of N-(3-ch1oro-1*(pyridin-3-yl)-1H-pyrazol-4-yl)-Nmethylacrylamide (Compound Y2098)

To a solution of 3-chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.526 g, 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 mmoi). The reaction was allowed to warm to ambient température and was stirred for 1 h. The reaction was quenched with the addition of NaHCOa(_tq) and was diluted with CH₂CI₂. The layers were separated and the aqueous layer was extracted with CH₂CI₂. The combined organic extracts were dried over Na₂SO₄, filtered and

149 concentrated in vacuo. The crude product was purified via flash chromatography (0 to 10%

MeOH/CH₂CI₂) to give the desired product as an orange solid (634 mg, 91%).

Example 160: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1 H-pyrazol-4-yl)-N-ethyl-3-((3,3,3trlfluoropropyl)thio)propanamlde (Compound 653)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (10 g, 44.9 mmoi) ln CH₂CI₂ (100 mL) at 0 ’C and under N₂ were added pyridine (5.45 mL, 67.4 mmol), 4dimethylaminopyridine (DMAP) (2.74 g, 22.45 mmol), and 3-((3,3,3trifluoropropyl)thio)propanoyl chloride (9.91 g, 44.9 mmol), sequentially. The reaction was warmed to ambient température 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 CH₂CI₂ (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% EtOAc/CH₂Cl2) to afford the desired product as a pale yellow solid (17.21 g, 89%).

Example 161: Préparation of N-(1-(5-fluoropyrldln-3-yl)-3-methyl-1H-pyrazol-4-yi)-2oxooxazolldine-3-carbothioamlde (Compound Y2032)

To a solution of 1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine (0.10 g, 0.52 mmol) and triethylamine (0.24 mL, 1.71 mmol) ln 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 ln 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 IN HCl and extracted with diethyl ether. The ether layers were combined, washed with water and half saturated aqueous sodium bicarbonate, dried (MgSO₄), filtered and concentrated to dryness to give the desired isothiocyanate (0.12 g, 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 (0.03 g, 0.61 mmol, 60% dispersion in minerai oil) in one portion and the suspension was stirred for 20 minutes. The reaction mixture was cooled to 0 C and 3-fluoro-5150 (4-lsothiocyanato-3-methyl-1H-pyrazol-1-yl)pyridine (0.12 g, 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, 16%).

Example 162: Préparation of 3-(4-lsothiocyanato-3-methyl-1H-pyrazol-1-yl)pyridlne

To a solution of 3-methy1-1-(pyridin-3-y1)-1H-pyrazol-4-amine (0.50 g, 2.87 mmol) and triethylamlne (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-methy1benzene-1-sulfonyl chloride (0.60 g, 0.3.16 mmoi) 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 HCl and extracted with diethyl ether. The ether layers were combined, washed with water and half saturated aqueous NaHCO₃₁ dried (MgSO₄), filtered and concentrated to dryness. The crude material was purified by silica gel chromatography eluting with 0-100% ethyl acetate/hexanes to give the desired product as a light yellow solid (0.48 g, 78%): ¹H NMR (400 MHz, CDCI₃) δ 8.89 (d, J = 2.6 Hz, 1H), 8.56 (dd, j = 4.7,1.4 Hz, 1 H), 7.96 (ddd, J = 8.3, 2.7,1.5 Hz, 1 H), 7.89 (s, 1 H), 7.40 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 2.40 (s, 3H); ESIMS m/z218 ([M+H]*).

Example 163: Préparation of N-(3-methyl-1-(pyridln-2-yl)-1H-pyrazol-4-yl)-2oxooxazolidine-3-carbothiamlde (Compound Y2034)

To a solution of oxazolîdin-2-one (0.06 g, 0.66 mmol) dissolved in dry DMF (2.2 mL) was added sodium hydride (0.03 g, 0.67 mmol, 60% dispersion in minerai oil) in one portion and the suspension was stirred for 20 minutes. The reaction mixture was cooled to 0 ’C and 3-(4lsothiocyanato-3-methyl-1H-pyrazol-1-yl)pyridine (0.12 g, 0.56 mmol) was added in one portion

151

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 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: Préparation of methyl N-(3-methyl-1«(pyrldin-3-yl)-1H-pyrazol-4-yl)-2oxooxazolldine-3-carblmldothioate (Compound Y2035)

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 minerai oil) In one portion and the suspension was stirred for 20 minutes. The reaction mixture was cooled to 0 ’C and 3-(4isothiocyanato-3-methyl-1H-pyrazol-1-yl)pyridine (0.12 g, 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 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/ChkClî to give the desired product as a light yellow solid (0.14 g, 82%). Example 165: Préparation of N-acety!-N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4yl)cyclopropanecarboxamlde (Compound Y2060)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)cyclopropanecarboxamide (0.15 g, 0.57 mmol) In dichloroethane (2.5 mL) was added diisopropylethylamlne (0.12 mL, 0.68 mmol) followed by acetyl chloride (0.54 g, 0.68 mmol) and the reaction was stirred at room température ovemight Saturated aqueous NaHCOj was added and the mixture was extracted with CH2CI2. 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

Example 166: Préparation of S-methyl (3-chloro-5-(methylthlo)-1-(pyrldln-3-yl)-1H-pyrazol4-yl)(ethyl)carbamothloate (Compound Y2076)

To a solution of THF (1.35 mL) and diisopropylethylamine (0.07 mL, 0.40 mmol) was added 2.5M n-butyllithlum (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-yl)-1H-pyrazol-4-yl)(ethyl)carbamothloate (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 (0.04 g, 0.37 mmol) and the reaction was stirred for additional 20 minutes. The reaction was poured Into water and extracted with ethyl acetate. The ethyl acetate layers were combined, dried (MgSO₄), filtered and concentrated to dryness. The crude product was purified by silica gel chromatography eluting with 0-100% ethyl acetate/hexanes to give the desired product as a clear oil (53 mg, 46%).

Example 167: Préparation of N-(3-chioro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(3,3,3trifluoropropyl)thlo)propanamlde (Compound 653)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-/V-ethyl-3mercaptopropanamlde (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 minerai oil) In one portion and the reaction was stirred for 10 minutes. To this was added 3-bromo-1,1,1trifluoropropane (0.06 g, 0.35 mmol) In one portion in a minimum amount of dry DMF and the reaction was stirred at room température for 2 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layers were combined 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 clear oil (83 mg, 63%). Example 168: Préparation of tert-butyl (2-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4yl)(ethyl)amino)-2-oxoethyl)(methy!)carbamate

I53

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.40 9,1.79 mmol) in dichloroethane (3.59 mL) was added 2-((tert-butoxycarbonyl)(methyl)amino)acetÎc acid (0.37 g, 1.97 mmol). 4-N,N-dimethylaminopyridine (0.24 9,1.97 mmol) and 1-{3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.51 g, 2.69 mmol) and the reaction was stirred ovemight at room température. The reaction mixture was concentrated to dryness and the crude product was purified by silica 9e! 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'¹; Ή NMR (400 MHz, CDCI₃) δ 8.96 (d, J = 2.4 Hz, 1H), 8.63 (dd, J = 5.3 Hz, 1H), 8.11

- 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 m/z 394 ((M+H)*).

The following molécules were made in accordance with the procedures disclosed in Example 168:

fert-Butyl (2-{(3-chloro-1 -<pyridin-3-yl)-1H-pyrazol-4-yl)(methy!)amino)-2oxoethyl)(methyl)carbamate: ’H NMR (400 MHz, CDCI₃) δ 8.95 (d, 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 (2-((3-chloro-1 -(pyridin-3-yl )-1 H-pyrazol-4-yl)(cyclopropylmethyl)amino)-2oxoethyl)(methyl)carbamate; IR (thin film) 1675 cm’; ¹H NMR (400 MHz, CDCI₃) δ 8.95 (bs, 1 H), 8.63 (dd, J = 5.1 Hz, 1 H), 8.17 - 7.88 (m, 2H), 7.54 - 7.36 (m, 1 H), 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 m/z 420 ((M+H]*).

Example 169: Préparation of N-(3-chloro-1-pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2(methylamlno)acetamide

To a solution of tert-butyl (2-((3-chloro-1-{pyridin-3-yl)-1H-pyrazol-4-yl)(ethy!)amino)-2oxoethyl)(methyl)carbamate (0.57 g, 1.44 mmol) in CH2CI2 (1.44 mL) was added trifluoroacetic 154 acid (1,44 mL) and the reaction was stirred at room température 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 CH₂C!₂. The CH₂CI₂ layers were combined and concentrated to dryness. The crude product was purified by silica gel chromatography eluting with 0-15% methanol/CH₂CI₂ to give the desired product as a yellow otl (0.31 g, 73%): IR (thin film) 1666 cm·¹; ’H NMR (400 MHz, CDCI₃) δ 8.98 (d, 7= 2.6 Hz, 1H), 8.63 (dd, 7 = 4.7,1.3 Hz, 1 H), 8.06 (m, 2H), 7.47 (dd, 7 = 8.3,4.8 Hz, 1 H), 3.72 (q, 7 = 7.1 Hz, 2H), 3.30 (S, 2H), 2.48 (s, 3H), 1.17 (t, 7= 7.2 Hz, 3H); ESIMS m/z 294 ([M+H]*).

The following compounds were made in accordance with the procedures disclosed in Example 169:

N-(3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-methyl-2-(methylamino)acetamlde: IR (thin film) 1666 cm'’; ’H NMR (400 MHz, CDCI₃) δ 8.96 (d, 7= 2.6 Hz, 1H), 8.64 (dd, 7= 4.8,1.3 Hz. 1H), 8.11 - 7.94 (m, 2H), 7.47 (dd. 7 = 8.4, 4.4 Hz. 1H). 3.30 (s, 2H), 3.27 (s, 3H), 2.47(s, 3H); ESIMS m/z 280 ([M+H]*).

N-(3-Ch!oro-1 -(pyridin-3-yl >1 H-pyrazo!-4-yl)-N-(cyc!opropylmethyl)-2(methylamino)acetamide: IR (thin film) 1667 cm'¹; ’H NMR (400 MHz, CDCI3) δ 8.98 (d, 7= 2.6 Hz. 1H), 8.63 (dd, 7 = 4.7.1.3 Hz, 1 H). 8.11 (s, 1H), 8.06 (ddd, 7 = 8.3. 2.7,1.4 Hz. 1H), 7.47 (dd. 7= 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]*).

Example 170: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-(Nmethylmethylsulfonamido)acetamide (Compound 800)

To a solution of N-(3-chloro-1-(pyridin-3-y!)-1 H-pyrazo!-4-yl)-N-ethyf-2(methylamino)acetamlde (0.10 g, 0.34 mmol) ln CH₂CI₂ (0.68 mL) was added methanesuifonyl chloride (0.06 g, 0.51 mmol) followed by diisopropylethylamine (0.12 mL, 0.68 mmol) and the reaction was stirred ovemight at room température. The reaction mixture was poured into saturated aqueous NaHCO₃ and extracted with CH₂CI₂. The CH₂CI₂ layers were combined and concentrated to dryness. The crude product was purified by silica gel chromatography eluting with 50-100% ethyl acetate/hexanes to give the desired product as a white semi-solid (81 mg, 64%).

Example 171: Préparation of N-(3-chloΓO-1-(pyΓidin-3-yl)-1Hpyrazol-4-yl)-Λ^ethyl·3-((3_t3,3trifluoropropyl)sulflnyl)propanamide (Compound 861)

155

Method A: To N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3,3,3trifluoropropyl)thlo)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 hour. The reaction mixture was carefully poured Into a separatory funnel containing saturated aqueous NaHCO₃ resulting in gas évolution. When the gas évolution had ceased, ethyl acetate was added and the iayers 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 with 0-5% methanol/ CH₂CI₂ to give the desired product as a dark oil (60 mg, 33%).

Method B: To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-/V-ethyl-3((3,3,3-trifluoropropyl)thlo)propanamide (500 mg, 1.229 mmol) in hexafluoroisopropanol (5 mL) stirring at room température was added 30% hydrogen peroxide (523 mg, 4.92 mmol). The solution was stirred at room température for 15 min. It was quenched with saturated sodium sulfite solution and extracted with CH₂CI₂. Silica gel chromatography (0-10% MeOH/CH₂CI₂) gave the title compound as white semi-solid (495 mg, 95%).

Example 172: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2(methylamlno)propanamide

2-chloro-N<3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-/\/-ethylpropanamide (0.51 g, 1.62 mmol) and methylamine (4.05 mL, 32.6 mmol, 33% In éthanol) were placed in a 25 mL vial on a Biotage® Inltiator microwave reactor for 45 minutes at 100 ’C, with extemal IR-sensor température monitoring from the side of the vessel. The reaction was concentrated to dryness and purified by silica gel chromatography (0-10% methanol/CH₂CI₂ to give the desired product as a yellow solid (0.21 g, 43%): ¹H NMR (400 MHz, CDCI₃) δ 8.96 (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, 1 H), 3.93 - 3.57 (m, 2H), 3.25 - 3.11 (m, 1 H), 2.34 (s, 3H). 1.21 -1.17 (m, 6H).

156

The following compound was made in accordance with the procedures disclosed in

Example 172:

N-(3-chioro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(methylamlno)propanamide

Ή NMR (400 MHz, Acetone) δ 9.12 (dd, 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) m/z 308.4 ([M+H]*); IR (KBr thin film) 3055, 2971, 2773,1656 cm’¹.

Example 173: Préparation of N-(3-chioro-1-(pyridin-3-yi)-1H-pyrazol-4-yi)-N-ethyl-2-(210 methoxyethoxy)acetamide (Compound Y2195)

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-chioro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazoi-4-yl)-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 température and was stirred ovemight (ca 16 h), at which point the reaction was deemed complété 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 (SIO₂,100-200 mesh; eluting with 0 to 20% methanol in CH₂CI₂) to afford the title compound as a tan solid (0.045 g, 20%).

Example 174: Préparation of N-((3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4yl)(methyl)carbamoyl)-N-ethylplvaiamlde (Compound Y2082)

157

To a solution of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-ethyl-1-methylurea (0.075 g, 0.268 mmol) in THF (2.68 mL) at -78 ^eC was added 1 M lithium bis(trimethylsîlyl)amide (LIHMDS) (0.282 mL, 0.282 mmol) ln 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 min and room température for 30 min. Brine was added and the reaction was extracted with EtOAc. The combined organic phases were concentrated and purified by flash chromatography (0-15% MeOH/CH₂CI₂) to give the title compound as a yellow oil (54 mg, 55%): IR (thin film) 2969,1681 cm'¹; ¹H NMR (400 MHz, CDClj) δ 8.93 (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); ESIMS m/z 365 ([M+H]*).

Example 175: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-3(methylthio)propanlmidamlde (Compound 706)

To a solution of 3-chloro-1*(pyridin-3-yl)-1H-pyrazoi-4-amine (0.058 g, 0.297 mmol) in EtOH (0.992 mL) was added naphthalen-2-ylmethyl 3-(methylthio)propanimidothioate hydrobromide (0.106 g, 0.297 mmol). The reaction was stirred at 0 ’C for 1 hour. The solvent was removed under reduced pressure and water and Et₂O were added. The phases were separated and the aqueous phase was concentrated to give a crude mixture. The residue was dissolved ln MeOH (1 mL) and MP-carbonate (0.281 g, 0.892 mmol) was added. The reaction was stirred at room température for 1 hour. The reaction was filtered, concentrated and purified by flash chromatography (0-15% MeOH/hexanes) to give the title compound as light brown solid (32 mg, 31 %): mp 137 ’C; ¹H NMR (300 MHz, CDClj) δ 8.86 (d, J = 2.6 Hz, 1H), 8.49 (dd, J = 4.8, 1.2 Hz, 1 H), 7.95 (ddd, J = 8.3, 2.5,1.3 Hz, 1 H), 7.68 (s, 1 H). 7.37 (dd, J = 8.3, 4.8 Hz, 1 H), 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: Préparation of naphthalen-2-ylmethyl 3-(methylthlo)propanlmidothloate hydrobromide

158

HBr

NH sAz^S^

To a solution of 3-(methytthio)propanethioamlde (0.062 g, 0.458 mmol) ln CHCI₃ (1.146 mL) was added 2-(bromomethyl)naphtha!ene (0.101 g, 0.458 mmol). The mixture was heated at reflux for 1.5 hours. The reaction was cooled to room température, Et₂O was added and a precipitate formed. The solvent was removed under reduced pressure. Et₂O 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%): ¹H NMR (300 MHz, DMSO-de) δ 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-methyl-3-(methyIthlo)propanimidothioate hydrobromide was prepared in accordance with the procedure disclosed in Exemple 176 and isolated as an offwhite semi-solid; ¹H NMR (400 MHz, DMSO-d_e) δ 8.08 (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):

ESIMS m/z 290 ([M+H]*).

Naphthalen-2-yImethyI N-methyfethanimidothioate hydrobromide was prepared ln accordance with the procedure disclosed in Example 176 and isoiated as a white solid; ¹H NMR (400 MHz, DMSO-d_e) δ 8.02 (s, 1 H), 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+H]*).

Naphthalen-2-yimethyl ethanimidothioate hydrobromide was prepared as described ln

Shearer, B. G. et al. Tetrahedron Letters 1997, 35,179-182.

Naphthalen-2-ylmethyl cyclopropanecarbimldothioate hydrobromide was prepared in accordance with the procedure disclosed in Example 176 and isolated as a yellow soiid; ’H NMR (400 MHz, DMSO-d_e) δ 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, 1 H), 1.46 - 1.37 (m, 2H), 1.36-1.29 (m, 2H); ESIMS m/z 242 ([M+H]*).

Example 177: Préparation of ethyl N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-N'-ethyl-Nmethylcarbamlmidothloate (Compound Y2049)

159

N^^CH3

JLs⁷™’ N

CH₃

To a solution of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y1}-3-ethyl-1-methy1thiourea (0,085 g, 0.287 mmol) In éthanol (1.916 mL) In a microwave vial was added iodoethane (0.028 mL, 0.345 mmol). The reaction was heated in a microwave (CEM Discover®) with extemal IRsensor température monitoring from the bottom of the vessel at 80 *C for 6 hours. The reaction was concentrated and purified by flash chromatography (0-100% EtOAc/Hexanes) to give the title compound as a yellow oii (56 mg, 57%): iR (thîn film) 3050,2931, 1583 cm'¹; ’H NMR (300 MHz, CDCIj) δ 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, 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); ESIMS m/z 325 ([M+H]*).

Example 178: Préparation of N-(3-chloro-1*(pyridln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(W· methyl-N-(3,3,3-trlfluoropropyl)suifamoyl)propanamide (Compound 965)

To a stirred solution of A/-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-y!)-N-ethyl-3mercaptopropanamlde (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-2,5dione (258 mg, 1.93 mmol) in portions over 3 min. After stirring for 1 hour, 3,3,3-trifluoro-N· methyipropan-1-amine (82 mg, 0.64 mmol) was added and the reaction was stirred for additional 14 hours at room température. The mixture was filtered and concentrated in vacuo to give a brown residue. Purification of thls residue on silica gel eluting with CH2CI2 and methanol afforded the title compound as an off-white gum (71 mg, 22%).

Example 179: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((1-chloro-

2,2,2-trlfluoroethyl)thio)-N-ethylpropanamlde (Compound 859)

160

To a suspension of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3mercaptopropanamîde (0.100 g, 0.322 mmol), sodium dithionite (0.070 g, 0.338 mmol) and sodium bicarbonate (0.028 g, 0.338 mmol) In DMSO (3.22 mL) at 40 ’C was added 2-bromo-2chloro-1,1,1-trifluoroethane (0.079 g, 0.402 mmol) dropwise. The reaction was stirred at the same température for 3 h after which the reaction was cooled, poured Into water (10 mL) and extracted with EtOAc (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% EtOAc/CH₂CI₂) to afford the desired product as a clear, viscous oil (111 mg, 77%). (Reference: Pustovit, étal., Synthesîs, 2010, 7,1159-1165).

Example 180: Préparation of N-(3-chloro-1-(pyrldin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-((3(mesitylamino)-3-oxopropyl)thio)propanamlde (Compound 1024)

CH₃

To a stirred solution of N-(3-chloto-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3mercaptopropanamide (0.20 g, 0.64 mmol) In acetonîtrile (2.1 mL) was added 3-bromo-Nmesitylpropanamlde (0.17 g, 0.64 mmol) and césium carbonate (0.23 g, 0.70 mmol) and the reaction was stirred ovemight at room température. The reaction was loaded directly onto celite and placed ln a vacuum oven ovemight at 25 ^eC. The crude product was purified by silica gel chromatography eluting with 0-75% ethyl acetate/hexanes to give the desired product as a white semi-solid (226 mg, 53%).

Example 181: Préparation of two enantlomers of N-(3-chloro-1-(pyridln-3-yl)-1H-pyrazol-4yl)-N-ethyi-3-((3,3,3-trifluoropropyl)sulfinyl)propanamIde (Compounds 1028 and 1029)

CF₃

161

The two enantiomers of the title molecuie were separated by chiral HPLC using a RegisCell™ 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 mL/min at ambient température. Under these conditions compound 1028 was collected at a rétention time of 6.0 min and possessed an optical rotation of [DId³⁰ - +25.9 (c 0.27% In CDCI₃). Compound 1029 was collected at a rétention time of 7.5 min and possessed an optical rotation of [OJd³⁰ = -27.4 (c 0.27% in CDCI3). Characterization data for these molécules are listed in Table 2.

Example 182: Préparation of /V-(3-chloro-1-(pyridin-3-yi)-1H-pyrazol-4-yl)-4,4,4-trifluoro-Nmethyl-3-(methylsulfonyl)butanamide (Compound 714)

To a 20 mL vial was added N-(3-chioro-1-(pyridÎn-3-y1)-1/-/-pyrazol-4’yl)-4,4,4-trifluoro-Nmethyl-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 température for 3 hours. The reaction was quenched by the addition of sodium sulfite solution, extracted with DCM and concentrated. Purification with silica gel chromatography (0-100% EtOAc/hexane) afforded N(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-4,4,4-trifluoro-N-methyl-3-(methylsulfonyl)butanamide as a white solid (25 mg, 18%).

Exemple 183: Préparation of enantiomers of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)· N-ethyl-2-methyl-3-(methy1suifinyl)propanamlde (Compounds 804-807)

The four stereolsomers 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 température. Under these conditions compound 804 was collected at a rétention time of 8.4 minutes and possessed an optical rotation of [Dfo³⁰ - -43.8 (c 0.5% in CDCI₃). Compound 805 was collected at a rétention time of 11.9 minutes and possessed an optical rotation of [djo³⁰ +48.2 (c 0.5% In CDCI3). Compound 806 was collected at a rétention time of 16.4 minutes and possessed an optical

162 rotation of [□ Jd³⁰ = +113.4 (c 0.5% ln CDCI₃). Compound 807 was collected at a rétention time of 20.6 minutes and possessed an optical rotation of (nlo³⁰ = -93.0 (c 0.5% in CDCI₃).

Characterizatîon data for these molécules are listed ln Table 2.

Example 184: Préparation of 3-((3,3,3-trif1uoropropyl)thlo)propanoyl chloride

O

CiXk/'-’-.g/'x/CFj

A dry 5 L round bottom flask equipped with magnetic stirrer, nitrogen inlet, reflux condenser, and thermometer, was charged with 3-((3,3,3-trifluoropropy1)thio)propanoic acid (188 g, 883 mmol) ln dîchloromethane (3 L). Thionyi chloride (525 g, 321 mL, 4.42 mot) was then added dropwise over 50 minutes. The reaction mixture was heated to reflux (36 °C) for two hours, then cooled to ambient température. 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) δ 3.20 (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); ”F NMR (376 MHz, CDCI₃) δ -66.42, -66.43, -66.44, -66.44.

Example 185: Préparation of 3-chioro-1-(5-chloropyridin-3-yl)-1H-pyrazol-4-amlne

Cl

To a solution of tert-butyl (3-chloro-1H-pyrazol-4-yl) carbamate (5 g, 22.97 mmol) in a mixture of DMF-H₂O (9:1) (40 mL) was added copper iodide (0.13 g, 0.69 mmol, 0.03 eq), césium carbonate (14.97 g, 45.9 mmol), 8-hydroxy quinoline (0.33 g, 2.30 mmol) and 3-bromo-

5-chloropyridine (5.29 g, 27.5 mmol). The mixture was heated at 140 *C under nitrogen for 11 hours. The reaction mixture was cooled to room température, quenched with ammonium hydroxide (15 mL), filtered through celite and the filtrate was extracted with ethyi acetate (3 x 50 mL). The combined organic layer was washed with brine (1 x 50 mL) dried over anhydrous Na₂SO₄₁ filtered, and evaporated to dryness under reduced pressure. The crude product was purified on silica gel using 0-100% ethyi acetate in hexane as eluent to give the title compound as dark brown amorphous solid (1.35 g, 26%): ’H NMR (400 MHz, DMSO-cf_e) δ 8-93 (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]*).

The following molécules were made in accordance with the procedures disclosed in Example 185:

1-(5-Bromopyridin-3-yl)-3-chloro-1H-pyrazol-4-amine: ESIMS m/z 274 ([M+H]*).

163

3-Chloro-1-(5-methoxypyridin-3-yl)-1H-pyrazol-4-amlne: ESIMS m/z 225 ([M+H]*).

3-Chloro-1-(5-methylpyridin-3-yl)-1H-pyrazol-4-amine: ’H NMR (400 MHz, DMSO-d_e,

D₂O): δ 8.68 (s, 1H), 8.27 (s, 1H), 7.86 (d, J = 5.64 Hz, 2H), 2.34 (s, 3H); ESIMS m/z 209 ([M+H]*).

Example 186: Préparation of tert-butyl (3-chloro-1-(5-chloropyrldln-3-yl)-1H-pyrazol-4yl)carbamate

To a solution of amine 3-chloro-1-(5-chloropyridin-3-yl)-1H-pyrazol-4-amlne (1.00 g, 4.4 mmol) and triethylamine (666 mg, 6.6 mmol) In dry THF (10 mL) was added dl-tert-butyl dicarbonate anhydride (960 mg, 4.62 mmol) over 30 minutes and the reaction was allowed to stir at room température 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%):

ESIMS m/z 330 ([M+H]*).

The following molécules were made in accordance with the procedures disclosed in Example 186:

tert-Butyl (1-(5-bromopyridin-3-yl)-3-chloro-1H-pyrazol-4-yl)carbamate: ESIMS m/z 372 ([M+H]*).

tert-Butyl (3-chloro-1 -(5-methylpyridin-3-yl)-1 H-pyrazol-4-yl)carbamate: ESIMS m/z 309 ([M+H]*).

Example 187: Préparation of tert-butyl (3-chloro-1-(5-chloropyridln-3-yl)-1H-pyrazol-4y!)(methy!)carbamate

To a solution of tert-butyl (3-chloro-1-(5-chloropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (501 mg, 1.5 mmol) In dry THF (10 mL) was added potassium tert-butoxide (1.5 mL, 1 M

164 solution in THF) and the réaction 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 température. 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 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 ([M+H]*).

The following molécules were made In accordance with the procedures disclosed in Example 187:

tert-Butyl (1-(5-bromopyridin-3-yl)-3-chloro-1H-pyrazol-4-yl)(methyl)carbamate: ESiMS m/z 387 ([M+H]*).

fert-Butyl (3-chloro-1-(5-methylpyridin-3-yl)-1 H-pyrazol-4-yl)(methyl)carbamate: ESIMS m/z 265 ([M-f-Bu]*).

Example 188: Préparation of 3-chloro-1-(5-chloropyrldln-3-yl)-N-methyl-1H-pyrazol-4amlne

Cl

fert-Butyl (3-chloro-1-(5-chloropyridin-3-yl)-1H-pyrazol-4-yl)(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 dloxane (5 mL, 4 M) was added dropwise, and the mixture was stirred for 2 hours, then concentrated under reduced pressure. The residue was diluted with CH₂CI₂ (50 mL), and the solution washed with aqueous sodium bicarbonate, water (10 mL) and brine (10 mL). The organic layer was dried over Na₂SO_4l and concentrated under reduced pressure to give the title compound (148 mg, 61%): ESMS m/z 244 ([M+H]*).

The following molécule was made In accordance with the procedures disclosed in Example 188:

1-(5-Bromopyridin-3-yl)-3-chloro-N-methyl-1H-pyrazoi-4-amlne: ESIMS m/z 289 ([M+Hf).

Example 189: Préparation of N-(3-chloro-1-(5-methoxypyrldln-3-yl)-1H-pyrazol-4-yl)-2,2,2· trifluoroacetamlde

165

Cl ο

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) ln dry dichloromethane (10 mL) was added trifluoroacetic anhydride (1.0 eq) dropwise at 0 ^eC. The reaction mixture was slowly warmed to room température 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 m/z 321 ([M+H]*).

Example 190: Préparation of N-(3-chloro-1-(5-methoxypyrldin-3-yl)-1H-pyrazol-4-yl)-2,2,2trlfluoro-N-methylacetamlde

Cl O

To a solution of N-(3-chloro-1-(5-methoxypyridin-3-y1)-1H-pyrazol-4-yl)-2,2,2trifluoroacetamide (700 mg, 2.18 mmol) in dry THF (10 mL) was added potassium tert-butoxide (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 température. The réaction 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 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): ESIMS m/z 335 ([M+H]*). Example 191: Préparation of 3-chloro-1-(5-methoxypyridln-3-yl)-N-methyl-1H-pyrazol-4amlne

Cl

166

To a suspension of A/-(3-chloro-1-(5-methoxypyridin-3-yl)-1H-pyrazol-4-yl)-2,2,2-trifluoroN-methylacetamide (410 mg, 1.23 mmol) In methanoi (10 mL) was added K₂CO₃ (254 mg, 1.8 mmol) and the mixture stirred at room température for 4 hours. The reaction was concentrated under reduced pressure and the residue suspended In dichloromethane (50 mL), and washed 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 m/z 239 ([M+H]*).

Example 192: Préparation of dlethyl(2-((3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4yl)(ethyl)amlno)-2-oxoethyi)phosphonate '3

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amlne (2.00 g, 8.98 mmol), 2-(diethoxyphosphoryl)acetic acid (1.94 mg, 9.88 mmol) and N,N-dimethylpyridin-4amlne (2.20 g, 17.96 mmol) In dry DMF (10 mL) was added N’-((ethy!imino)methylene)-W^J,N^adimethylpropane-1,3-diamine hydrochloride (2.58 g, 13.47 mmol), and the mixture was stirred at 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 NH₄CI, 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 CH2CI2 and methanoi to give the title compound as a brown solid (2.62 g, 69%): mp 46-48 *C; ’H NMR (400 MHz, CDCI₃) δ 9.00 (dd, J = 2.7, 0.7 Hz, 1 H), 8.62 (dd, J = 4.7,1.4 Hz, 1 H), 8.35 (s, 1 H), 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 m/z 401 [(M+H)*] 399 [(M-H)î Example 193: Préparation of (E)-N-(3-chloro-1*(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-5,5,5trlfluoropent-2-enamlde (Compound Y2177)

167

To a solution of diethyl (2-((3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)amino)-2oxoethyljphosphonate (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 was stirred for 1 hour. The mixture was then warmed to room température and stirred at room température for 2 hours. Additional NaH (30 mg, 0.75 mmol, 60% wt. oil suspension) was added and the mixture stirred at room température for 0.5 h. The mixture was diluted with water and ethyl acetate and the organic phase separated, washed with brine, dried over MgSO< and concentrated in vacuo to give a brown oily residue. This residue was purified on silica gel eluting with CH2CI2 and methanol to give the title compound as a light yellow gum (230 mg, 51%).

Example 194: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3dif1uoroailyl)thio)-/V-ethylpropanamide (Compound 918)

To a solution of 3-((3-bromo-3,3-difluoropropyl)thio)-A/-(3-chloro-1-(pyridin-3-yl)-1Hpyrazol-4-yl)-N-ethylpropanamid6 (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 mln in a Biotage® Initiator microwave reactor with extemal IR-sensor température monitoring from the side of the vessel. The mixture was diluted with ethyl acetate and then washed with saturated aqueous ammonium chloride and brine, dried over MgSO4 and concentrated In vacuo to give a brown gum. This gum was purified on silica gei eluting with methylene chloride and methanol to give the title compound as a light yellow oil (76 mg, 92%). Example 195: Préparation of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-ethyl-1,3dlmethylurea (Compound Y2012)

168

To a solution of 3-chloro-/\/-methy1-1-{pyridÎn-3-y1)-1H-pyrazol-4-amine (0.100 g, 0.48 mmol) in CH2CI2 (1.9 ml) was added N-ethy1-/\/-isopropy1propan-2-amine (0.21 ml, 1.20 mmol) followed by ethy1(methyl)carbamic chloride (0.117 g, 0.959 mmol) and the réaction mixture was stined at ambient température for 2 hours. The reaction was quenched by the addition of saturated sodium bicarbonate. The aqueous layer was extracted with CH2CI2. 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: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethy1-2-(2,2,2trlfluoroethoxy)propanamlde (Compound Y2001)

H₃C

To a solution of 2,2,2-trifiuoroethanol (128 mg, 1.3 mmol) in DMF (1.3 mL) was added sodium hydride (51.1 mg, 1.3 mmol). The reaction mixture was stined for 30 min until the mixture became clear and no H₂ évolution was observed. To this solution was added 2-chloroN-{3-chloro-1-<pyridin-3-y1)-1H-pyrazol-4-yl)-N-ethy1propanamide (200 mg, 0.64 mmol) and the reaction mixture was stirred at 50 ’C ovemight. The reaction mixture was diluted with CH₂CI₂ and washed with water, the phases were separated with a Biotage® 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%).

Example 197: Préparation of N-(3-chloro-1-(pyrldln-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2((methylthlo)methoxy)propanamide (Compound Y2199)

To a solution of N-(3-chloro-1-(pyridin-3-y1)-1H-pyrazol-4-y1)-N-ethy1-2hydroxypropanamide (100 mg, 0.34 mmol) In THF (1.1 mL) was added sodium hydride (60% in minerai oil, 33.9 mg, 0.85 mmol). The mixture was stirred for 15 min and then (chloromethyl)(methy1)sulfane (33.6 pL, 0.41 mmol) was added. After stirring at ambient temp ovemight the réaction mixture was diluted with CH₂CI₂ and washed with water. The phases were separated and dried with a Biotage® Phases Separator® and concentrated in vacuo. The

169 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: Préparation of N-(3-chloro-1-(pyrldin-3-yl)’1H-pyrazol-4-yl)-2,2-difluoro-Nmethyl-2-(methylthlo)acetamide (Compound Y2021)

CH₃F F

To a solution of 2-bromo-N-(3-chloro-1-(pyridin-3-y1)-1W-pyrazol-4-yl)-2,2-difluoro-Nmethylacetamide (250 mg, 0.684 mmol) in DMSO (2.3 mL) was added methanethiol, sodium sait (96 mg, 1.37 mmol). The reaction mixture was heated to 50 ’C for 3h and then diluted with water and extracted with CH₂CI₂. The organic phases were dried with MgSO₄, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 080% acetone In hexanes to afford the titled compound as a red oil (188 mg, 83%).

Example 199: Préparation of 3-chloro-N-ethyl-1*(pyrldin-3-yl)-1H-pyrazol-4-amlne

To a 100 mL round bottom flask charged with 3-chloro-N-ethyl-1-(pyridin-3-y1)-1H· pyrazol-4-amine-bls HCl sait (2 g, 6.77 mmol) was added DCM (20 mL) and the suspension was stirred at room température. To this suspension was added saturated NaHCO₃ solution slowiy 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 compound as an off-white solid (1.41 g, 94%). Analytical data of 3-chloro-N-ethy1-1-(pyridin-3yl)-1H-pyrazol-4-amine can be found in Example 8.

Example A: Bioassays on Green Peach Aphid (“GPA) (Myzus persicae) (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 acts as 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, Iettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many omamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed résistance to many pesticides.

Certain molécules disclosed ln this document were tested against GPA using procedures described ln the following example, ln the reporting of the results, ‘Table 3: GPA

170 (MYZUPE) and sweetpotato whltefly-crawler (BEMITA) Rating Table’ was used (See Table

Section).

Cabbage seedlings grown ln 3-lnch 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 stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment Test compounds (2 mg) were dissolved ln 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 ln H₂O 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 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 aphlds per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W.S. Abbott, A Method of Computing the 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 aphlds on solvent check plants and Y = No. of live aphids on treated plants

The results are indicated in the table entitled Table 4. Biological Data for GPA (MYZUPE) and sweetpotato whltefly-crawler (BEMITA)'* (See Table Section). Example B: Insecticidal test for sweetpotato whltefly-crawler (Bemlsla tabac!) (BEMITA) In foliar spray assay

Cotton plants grown in 3-inch pots, with 1 smail (3-5 cm) true ieaf, were used as test 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. Aduits were blown off leaves using a hand-held Devilbiss sprayer (23 psi). Plants with egg infestation (100-300 eggs per plant) were placed ln 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 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 ln H₂O to obtain a test solution at 200 ppm. A hand-held Deviibiss 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 ln a holding room for 8-9 days at approximately 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 correction formula and presented In Table 4. Biological Data for GPA (MYZUPE) and sweetpotato whltefly-crawler (BEMITA)” (see column BEMITA):

Corrected % Control = 100 * (X - Y) / X where X = No. of live nymphs on solvent check plants

Y = No. of live nymphs on treated plants

PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, SOLVATES, ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND RADIONUCLIDES

Molécules 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, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartane, 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. Examples of preferred cations include sodium, potassium, and magnésium.

Molécules of Formula One may be formulated into sait dérivatives. By way of a nonlimiting example, a sait dérivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a sait. A free base may be regenerated by treating the sait with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (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 dimethyiamine sait..

Molécules 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 are often referred to as solvatés. However, It Is particulariy désirable to form stable hydrates with water as the solvent.

Molécules of Formula One may be made into ester dérivatives. These ester dérivatives can then be applied ln the same manner as the invention disclosed in this document is applied.

Molécules of Formula One may be made as various crystal polymorphe. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same moiecule can hâve vastly different physical properties and biological performances.

Molécules of Formula One may be made with different isotopes. Of particular importance are molécules having ?H (also known as deuterium) in place of ¹H.

Molécules of Formula One may be made with different radionuclides. Of particular importance are molécules having ¹³C or ¹⁴C.

STEREOISOMERS

172

Molécules of Formula One may exist as one or more stereoisomers. Thus, certain moiecules 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 stereoisomers may be obtained by known sélective synthetic procedures, by conventional synthetic procedures using resoived starting materials, or by conventional resolution procedures. Certain moiecules disciosed in this document can exist as two or more isomers. The various Isomers include géométrie isomers, diastereomers, and enantiomers. Thus, the moiecules disciosed in this document include géométrie isomers, racemic mixtures, individual stereoisomers, and opticaliy active mixtures. It will be appreciated by those skilled ln the art that one Isomer may be more active than the others. The structures disciosed ln the présent disclosure are drawn in only one géométrie form for clarity, but are Intended to represent aii géométrie forms of the molécule.

COMBINATIONS

Moiecules of Formula One may also be used In combination (such as, in a compositionai mixture, or a simultaneous or sequentiai application) with one or more compounds having acaricidal, aigicidal, avicidal, bactericidal, fungicidal, herbicidal, Insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties. Additionally, the moiecules of Formula One may also be used ln combination (such as, in a compositionai mixture, or a simultaneous or sequentiai application) with compounds that are antifeedants, bird repellents, chemosterilants, 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 Moiecules of Formula One are - (3ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1methytcyclopropene, 1-naphthol, 2-(octylthlo)ethanol, 2,3,5-tri-lodobenzolc acid, 2,3,6-TBA, 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-ethylhexy1, 2,4,5-T-3-butoxypropy1, 2,4,5-TB, 2,4,5-Tbutometyl, 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-triethytammonium, 2,4,5-T-trolamîne,

2.4- D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethy1hexy1, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DBsodium, 2,4-D-butotyi, 2,4-D-butyl, 2,4-D-diethytammonium, 2,4-D-dimethylammonIum, 2,4-Ddiolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium,

2.4- D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-Dmeptyi, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium,

2.4- D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2hydroxypropyl)ammonium, 2,4-D-trolamlne, 2iP, 2-methoxyethylmercury chloride, 2phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassîum, 4-CPA173 sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8phenylmercurioxyquinoline, abamectin, absclsic acid, ACC, acephate, acequinocyl, acetamlprid, acethion, acetochlor, acetophos, acetoproie, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrîn, acroleln, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zlnc, alachlor, alanycarb, albendazole, aldlcarb, aldimorph, aldoxycarb, aldrin, allethrin, allicln, allidochlor, allosamidin, alloxydim, alloxydimsodium, allyl alcohol, allyxycarb, alorac, a/pha-cypermethrin, a/pha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amlcarthiazol, amtdithion, amidoflumet, amldosulfuron, aminocarb, amlnocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2hydroxypropyljammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraqulnone, antu, apholate, aramite, arsenous oxide, asomate, as pi ri n, asulam, asulam-potassium, asulam15 sodium, athldathion, atraton, atrazine, aureofungln, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenldin, azamethlphos, azimsulfuron, azinphos-ethyl, azinphosmethyl, aziprotryne, azithiram, azobenzene, azocyciotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonlum, benazolîn-ethyl, benazoiln-potasslum, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanll, benomyl, benoxacor, benoxafos, benqulnox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodlum, benthlavalicarb, benthiavalicarbisopropyl, benthiazole, bentranil, benzadox, benzadox-ammontum, benzalkonium chloride, benzamacril, benzamacril-lsobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamlc acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthlazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, befa-cyfluthrin, befa-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxlao, bioallethrin, bioethanomethrln, blopermethrin, bloresmethrln, blphenyl, blsazir, blsmerthiazol, blspyribac, bispyribac-sodium, blstrifluron, bitertanol, bithionol, blxafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brasslnolide, brasslnolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithlum, bromacii-sodium, bromadiolone, bromethalin, bromethrin, bromfenvînfos, bromoacetamlde, bromobonil, bromobutide, bromocyclen, bromoDDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, bumlnafos, buplrimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathlofos, 174 butenachlor, butethrin, buthîdazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxlm, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxln, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chlorambenmethylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonlum, 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, 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, chlorthalmonomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin il, 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-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, ctoransulam-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, crimldine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide,

175 cyclethrin, cycloate, cycloheximlde, cycloprate, cycloprothrin, cyclosulfamuron, cycloxydîm, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymlazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazîne, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, cf-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephionO, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, dfanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicambadimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorpropethylammonium, dichlorprop-lsoctyl, dlchlorprop-methyl, dichlorprop-P, dichlorprop-P-2ethylhexyl, dichlorprop-P-dimethylammonlum, dichlorprop-potassîum, dlchlorprop-sodium, dlchlorvos, dichlozoline, diclobutrazol, dîclocymet, 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, difethialone, diflovldazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodlum, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimeplperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dîmethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dlmethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dïnoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinosebsodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dlpropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, dispariure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithlanon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC176 potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicln hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothaldiammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxîconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, eriujixlancaoan, esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl anaphthaleneacetate, 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, 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, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpicîonil, fenplrithrin, fenpropathrin, fenpropldin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothlon, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthlon-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fîpronil, flamprop, flamprop-îsopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazonesodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetii, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyrethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazln, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol177 butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyrmeptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacetmethyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldéhyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamtne, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrln, furametpyr, furathiocarb, furcarbanil, furconazole, furconazofe-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, glbberellic acid, gibberellins, gliftor, glufosinate, glufoslnate-ammonium, glufosinate-P, glufosInate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosatediammonlum, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosatemonoammonium, glyphosate-potassium, gfyphosate-sesquisodium, glyphosate-trimeslum, glyphosine, gossyplure, grandfure, griseofulvin, guazatine, guazatine acétates, halacrinate, halfenprox, halofenoztde, hafosafen, hafosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, hafoxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachforophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythlazox, HHDN, holosulf, huancalwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, Imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, Imazamethabenz-methyl, fmazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, Imazapyrisopropylammonium, imazaquin, Imazaquin-ammonium, Imazaquin-methyl, imazaquin-sodîum, imazethapyr, imazethapyr-ammonium, Imazosulfuron, imibenconazole, imlcyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, Inezin, iodobonil, lodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, lofensulfuron, lofensulfuronsodium, ioxynîl, ioxynll octanoate, ioxynil-lithium, ioxynil-sodium, Ipazine, ipconazole, ipfencarbazone, iprobenfbs, iprodione, iprovalicarb, iprymidam, ipsdlenol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, Isolan, Isomethiozin, isonoruron, isopolinate, Isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaiedione, Isoxaben, Isoxachlortole, isoxadifen, Isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectîn, izopamfos, japonilure, japothrins, jasmoiin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jlaxiangjunzhi, jiecaowan, jiecaoxl, jodfenphos, juvénile hormone I, juvénile hormone II, juvénile hormone III, kadethrin, karbutilate, karetazan,

178 karetazan-potasslum, kasugamycin, kasugamycln hydrochloride, kejunlin, kelevan, ketospïradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kulcaoxl, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, loopiure, lufenuron, ivdingjunzhi, Ivxiancaolin, lythidathion, MAA, malathion, maleic hydrazlde, malonoben, maitodextrin, ΜΑΜΑ, mancopper, mancozeb, mandipropamld, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPAbutyl, MCPA-dimethytammonium, MCPA-diolamine, MCPA-ethyl, MCPA-lsobutyl, MCPA-isoctyl, MCPA-lsopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPAthioethyl, MCPA-trolamlne, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecopropdimethylammonium, mecoprop-diolamlne, mecoprop-ethadyl, mecoprop-isoctyl, mecopropmethyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-Pisobutyl, mecoprop-potasslum, mecoprop-P-potasslum, mecoprop-sodium, mecoprop-trolamlne, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyrdiethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomolc acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfoian, mepiquat, mepiquat chioride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chioride, mercuric oxide, mercurous chioride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumlzone, metalaxyl, metalaxyi-M, metaldehyde, metam, metam-ammonlum, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxoion, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazoie, methfuroxam, methldathlon, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl aphoiate, methyl bromide, methyl eugenoi, methyl lodide, methyl Isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chioride, methylmercury benzoate, methylmercury dicyandiamlde, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metomlnostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsuifovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mleshuan, miibemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosuitap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscaiure, myciobutanil, myclozolin, N-(ethylmercury)-p-toiuenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamlde, naphthalic anhydride, naphthoxyacetic acids, naproanilide,

179 napropamlde, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamldeolamlne, nicosulfuron, nicotine, nifluridide, nlpyraclofen, nïtenpyram, nithlazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nltrofluorfen, nitrostyrene, nitrothal-lsopropyl, norbormide, norflurazon, nomicotine, noruron, novaturon, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobln, oryzatin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dlmolamine, oxapyrazonsodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinlc acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfiuorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, paradichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathlon, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluldone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury dérivative of pyrocatechol, phenylmercury nitrate, phenylmercury sallcylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycln, phosmet, phosnlchlor, phosphamldon, phosphîne, phosphocarb, phosphores, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, plcloram-lsoctyl, picloram-methyl, picloram-olamine, plcloram-potassium, picloramtriethylammonlum, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, plperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, plproctanyl, piproctanyl bromide, piprotal, plrimetaphos, pirimlcarb, pirimioxyphos, plrimiphos-ethyl, ptrlmiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp’-DDT, prallethrin, precocene 1, precocene II, precocene lll, pretilachlor, primldophos, primlsulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calclum, prohydrojasmon, promacyt, promecarb, prometon, prometryn, promurit, propachlor, propamldine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, proptconazole, proplneb, proplsochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proqulnazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride,

180 prathioconazole, prothiofos, prothoate, protrifenbute, proxan, prOxan-SOdlUW, pryDêChlOÎ, pydanon, pymetaine, pyracatboM. pyractafos, pyracW.p^dostaoWn wtaJWt» pyraflufen-ethyl, parole. _Pyramal.

pyrazolynate, pyrazophos, pyrazosulfuron. pyrazosuifuron-ethyi, pyrazothion, _Pyrnz_Oxyf_en. pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-lsopropyl, pyribambenz-propyf, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanii, pyrimldifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetoi sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazoie, qulnmerac, quinoclamine, quinonamid, quinothlon, quinoxyfen, quintiofos, quintozene, quizalofop, qulzalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingdîng, rabenzazoie, rafoxanide, rebemlde, resmethrin, rhodethanil, rhodoiaponin-lli, ribavirln, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, salsentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolîn, sethoxydim, shuangjiaancaoün, siduron, sigiure, silafluofen, silatrane, silica gel, silthiofam, simazîne, simeconazoie, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosiiicate, sodium naphthenate, sodium orthophenylphenoxlde, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiciofen, spiromesifen, s pi rote trama t, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfîram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryi fluoride, sulglycapin, sulprofos, sultropen, swep, fau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCAsodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthluron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasui, thallium sulfate, thenylchior, theta-cypermethrin, thiabendazole, thlacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thlobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxaiate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal,

181 thlometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thlosemicarbazide, thiosultap, thlosultap-diammonium, thiosultap-disodium, thlosultap-monosodium, thiotepa, thiram, thuringlensln, tiadinil, tiaojiean, tlocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, trlazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonlum, tricyclazole, tridemorph, trldiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyt, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, unlconazole, unlconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vemolate, vinclozolin, warfarin, warfarin-potassium, warfarinsodium, xlaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xytytcarb, yishijing, zarilamld, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, a-ecdysone, amultistriatin, and α-naphthaleneacetic acid. For more information consult the Compendium of Pesticide Common Names located at http://www.alanwood.net/pesticides/index.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 éditions.

BIOPESTICIDES

Molécules 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 biopesticides. The term “biopesticide 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 forgrape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents hâve also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringlensls, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetia pesticides. Biological Insecticides include products based on: I

1. entomopathogenic fungl (e.g. Metarhizium anisopliae);I

2. entomopathogenic nematodes (e.g. Stelnemema feltiae); andI

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).I

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Other examples of entomopathogenic organisais include, but are not limited to, bacuioviruses, bacteria and other prokaryotic organlsms, fungi, protozoa and Microsproridia. Biologicaliy derived insecticides include, but not limited to, rotenone, veratridine, as well as mlcroblal toxins; Insect tolérant or résistant plant varieties; and organisme modified by recombinant DNA technology to either produce insecticides or to convey an insect résistant property to the genetically modified organism. ln one embodiment, the molécules of Formula One may be used with one or more biopesticides in the area of seed treatments and soi! 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 of Biocontrol Agents (formeriy the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Famham, Surrey UK.

OTHER ACTIVE COMPOUNDS

Molécules of Formula One may also be used in combination (such as in a compositionai mixture, or a simultaneous or sequential application) with one or more of the following:

1. 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1 -azaspiro[4,5]dec-3-en-2-one;

2. 3-Î4-chloro-2,4-dimethyl[1 ,r-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2one;

3· 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone·,

4. 4-[[(6-chioro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;

5. 3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1_l2,2,2-tetrafluoro-1(trifluoromethyl)ethyl]phenyl]-1,2-benzenedlcarboxamide;

6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;

7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;

8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;

9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesuifonamide;

10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesuifonamide;

11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N’methyl-benzenesulfonamide;

12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;

13. 3-(difluoromethyl)-N-[2-(3,3-dÎmethylbutyl)phenyl]-1-methyl-1 H-pyrazoie-4-carboxamide;

14. N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-p-tolyl) hydrazone;

15. N-ethyl-2,2-dichloro-1 -methylcyclopropane-carboxamide-2-(2,6-dichloro-a,a,a-trifluoro-ptolyl) hydrazone nicotine;

16. 0-((E-)-[2-(4-chioro-phenyl)-2-cyano-1-(2’trifluoromethylphenyl)-vinyl]} S-methyl thiocarbonate;

17. (E)-N1-[(2<hloro-1,3-thiazol-5-ylrnethyl)]-N2-cyano-N1-methylacetamidine;

18. 1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2a]pyridin-5-ol;

183

19. 4-[4-chloropheny1-(2-butyltdine-hydrazono)methy1)]pheny1 mesylate; and

20. N-Ethy1-2,2-dichloro-1-methy1cyclopropanecarboxamide-2-(2,6-dichloroa/pha,a(pha,a(pha-trifluoro-p-tolyl)hydrazone.

SYNERGISTIC MIXTURES

Molecuies 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 molecuies 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 antagonlst; GABA and glutamate-gated chloride channel agonist; acétylcholine receptor agonist; acétylcholine receptor antagonlst; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acétylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Generally, weight ratios of the molecuies of Formula One in a synergistic mixture with another compound are from about 10:1 to about 1:10, in another 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 appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formuiated into, for example, baits, concentrated émulsions, dusts, emulsifiable concentrâtes, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrâtes, suspoemulslons, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra 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 CropUfe International (2002).

Pesticides are applied most often as aqueous suspensions or émulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrâtes, 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 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,

184

F naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-lonlc surfactants such as ethylene oxide adducts of alkyl phénols.

Emulsifiable concentrâtes 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 ls either a water miscible solvent or a mixture of water-immlscible organic solvent and emulsifiers. Usefui organic solvents Include aromatlcs, especially xylenes and petroleum fractions, especially the hlgh-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 dérivatives, aliphatic ketones such as cyclohexanone, and complex 10 alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrâtes are seiected from conventional anionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoiuble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by fmeiy grinding the pesticide and vigorousiy mixing it Into a carrier 15 comprised of water and surfactants. Ingrédients, such as inorganic salts and synthetic or naturel gums may also be added, to increase the denslty 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 homogenizlng it in an impiement such as a sand mill, bail mill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that are particuiariy usefui for 20 applications to the soit. 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 maklng 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 ln 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 foiiage application with a dust blower machine.

It ls equaliy practicai to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oiis, which are widely used in agricultural chemistry.

Pesticides can also be applied ln the form of an aérosol composition, ln such compositions the pesticide is dissolved or dispersed ln a carrier, which is a pressure-generating propellant mixture. The aérosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.

185

Pesticide baits are formed when the pesticide Is mixed with food or an attractant or both.

When the pests eat the bait they aiso 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 hâve a relatively high vapor pressure and hence can exlst as a gas in sufficient concentrations to kill pests In soit or enclosed spaces. The toxicity of the fumlgant ls 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 cutlcle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or In spécial chambers.

Pesticides can be mlcroencapsulated 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 govem the speed with which the active Ingrédient within is released, which In tum, affects the residual performance, speed of action, and odor of the product.

Oii solution concentrâtes are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usuaiiy 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 increaslng the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better pénétration of crevices, and better adhesion to greasy surfaces.

Another embodiment is an oil-in-water émulsion, wherein the émulsion comprises oily globules which are each provided with a iamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which Is agricuiturally active, and Is indivldually coated with a monoiamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilie 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, 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 Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

OTHER FORMULATION COMPONENTS

186

Generally, when the molécules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components inciude, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, pénétrants, buffers, sequestering agents, drift réduction agents, compatibllity agents, anti-foam 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 pénétration 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 powders In water to make concentrâtes for soluble liqulds or suspension concentrâtes; and during mixing of a product with water In a spray tank to reduce the wetting time of wettable powders and to improve the pénétration 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 phénol ethoxylates; and aliphatic alcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface of partides and helps to preserve the state of dispersion of the partides and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the partides redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrâtes and water-dispersible granules. Surfactants that are used as dispersing agents hâve the abilîty to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of partides. 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 suspension concentrâtes, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldéhyde condensâtes. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionlcs such as alkylarylethylene oxide condensâtes and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrâtes. In recent years, new types of very high molecular weight polymeric surfactants hâve been deveioped as dispersing agents. These hâve very long hydrophobie ’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 longterm stability to suspension concentrâtes because the hydrophobie backbones hâve many anchoring points onto the particle surfaces. Exemples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldéhyde condensâtes; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.

187

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 emulslfier blends contain alkyiphenoi or aliphatic alcohol with twelve or more ethyiene oxide units and the oil-soluble calcium sait of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB) values from 8 to 18 will normally provide good stable émulsions. Emulsion stability can sometimes be improved by the addition of a smali amount of an EO-PO block copolymer surfactant.

A solubilizing agent is a surfactant which will form micelies in water at concentrations above the criticai micelle concentration. The micelies are then able to dissolve or solubilize water-insoiubie matériels inside the hydrophobie part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyi oleate esters.

Surfactants are sometimes used, either alone or with other additives such as minerai or 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 dépend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyi ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation Is a material added to the pesticide to give a product of the required strength. Carriers are usuaily materiais with high absorptive capacities, while diluents are usually materiais 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 concentrâtes, oil-lnwater émulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granuiar formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffine. 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 useful as cosoivents 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 concentrâtes, émulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent séparation and settling of the dispersed particles or droplets. Thickening, gelling, and anti-settling agents generally fall into two categories, namely water-insoiubie particulates and water-soluble polymers. It is possible to produce suspension concentrate

188 formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonîte, magnésium alumlnum silicate, and attapulgite. Watersoluble polysaccharides hâve been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are naturel extracts of seeds and seaweeds or are synthetic dérivatives 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 antl-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settiing agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Therefore préservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium sait; sorbic acid and Its sodium or potassium salts; benzoic acid and Its sodium sait; p-hydroxybenzoic acid sodium sait; methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations to foam during mixing operations ln production and ln 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 nonsilicones. Silicones are usually aqueous émulsions of dimethyl polysiloxane, while the nonsilicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. ln 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 biodégradable and generally derived from naturel and/or sustainable sources, e.g. plant and animal sources. Spécifie 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 Academie Publishers. Also see Insecticides ln Agriculture and Environment - Retrospects and Prospects by A.S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

PESTS ln general, the molécules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.

189

In another embodiment, the molécules of Formula One may be used to control pests In the Phyla Nematoda and/or Arthropode.

In another embodiment, the molécules of Formula One may be used to control pests in the Subphyla Chellcerata, Myrlapoda, and/or Hexapoda.

In another embodiment, the molécules of Formula One may be used to control pests In the Classes of Arachnlda, Symphyla, and/or Insecte.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Anoplura. A non-exhaustive list of particular généra Includes, but ls not limited to, Haematoplnus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A 10 non-exhaustive list of particular species Includes, but is not limited to, Haematoplnus asinl, Haematoplnus suis, Linognathus setosus, Linognathus ovîllus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.

In another embodiment, the molécules of Formula One may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular généra Includes, but ls not limited to, 15 Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia 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., Rhlzotrogus spp., Rhynchites spp.,

Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species Includes, but ls not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis,

Ceutorhynchus napl, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nénuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus,

Liogenys suturalis, Ussorhoptrus oryzophllus, Maecolaspls Joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinocéros, Oryzaephilus mercator, Oryzaephlius surinamensis, Ouléma melanopus, Ouléma oryzae, Phyllophaga cuyabana, Popilliajaponica, Prostephanus truncatus, Rhyzopertha dominica,, Sitona lineatus, Sitophilus granarlus, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.

190 ln another embodiment, the molécules of Formula One may be used to control pests of the Order Dermaptera.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Blattarla. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanlca, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.

ln another embodiment, the molécules of Formula One may be used to control pests of the Order Diptera. A non-exhaustive list of particular généra includes, but ls not limited to, Aedes spp„ Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Daslneura spp., Délia spp., Drosophila spp., Fannla spp., Hylemyia spp., Uriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species Includes, but ls not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera Invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Délia platura, Fannia canicularis, Fannia scalaris, Gasterophilus Intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Uriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

ln another embodiment, the molécules of Formula One may be used to control pests of the Order Hemlptera. A non-exhaustive list of particular généra includes, but ls not Ümited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Phifaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopafosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Trlatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but ls not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solanl, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagl, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphls noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus héros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striateflus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,

191

Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarlum, Macrosiphum rosae. Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum. Midis longicornis, Myzus persicae, Nephotettix cindipes, Neurocolpus longlrostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria zlziphi, Peregrinus maldis, Phylloxéra vitifoliae, Physokermes plceae,, Phytocoris califomicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus pemiciosus, Rhopalosiphum maidis, Rhopalosiphum padl, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.

ln another embodiment, the moiecules of Formula One may be used to control pests of the Order Hymen optera. A non-exhaustive list of particular généra Includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Po/fstes spp., Solenopsis spp., Vespula spp., and 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 Invlcta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.

ln another embodiment, the moiecules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular généra includes, but ls not limited to, Coptotermes spp., Comitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procomitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species Includes, but ls not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassel, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensls, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginlcus.

ln another embodiment, the moiecules of Formula One may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular généra Includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptiiia spp., Chilo 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., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia 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,

192

Amyelols transitella, Anacamptodes defectaria, Anarsla lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographe gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha crame relia, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Dama diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignoseilus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erlonota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta Indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis alblcosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unlpuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia Interpunctella, Piutella xylostella, Polychrosls viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia Includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera erîdania, Thecla basllides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pyrina.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular généra Includes, but is not limited to, Anaticola spp., Bovicola spp., Cheloplstes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramîneus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular généra inciudes, 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 australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited

193 to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canls, Ctenocephalides felis, and Pulex Irritans.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular généra inciudes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. inciudes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella Williams!. Heliothrips haemorrholdalis, Rhipiphorothrips cruentatus, Scirtothrips citrl, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensls, Thrips nigropilosus, Thrips orlentalis, Thrips tabac!.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Thysanura. A non-exhaustive list of particular généra inciudes, but is not limited to, Lepisma spp. and Thermobia spp.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Acarina. A non-exhaustive list of particular généra inciudes, but is not limited to, Acarus 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 inciudes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassl, Aculus schlechtendal!, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citrl, Panonychus ulml, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus. Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.

In another embodiment, the molécules of Formula One may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. Inciudes, but is not limited to, Scutigerella Immaculata.

In another embodiment, the molécules of Formula One may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular généra inciudes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive iist of particular sp. inciudes, but Is not limited to, Dirofilaria Immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis.

For additional information consult ‘Handbook of Pest Control - The Behavior, Life History, and Control of Household Pests’ by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

APPLICATIONS

194

Molécules 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 prefened, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more prefened.

The area to which a molécule 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 omamental plants, are growing; where domesticated animais are residing; the Interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used ln building (such as impregnated wood), and the soit around buildings. Particular crop areas to use a molécule of Formula One Include areas where apples, com, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuabie crops are growing or the seeds thereof are going to be planted. It Is also advantageous to use ammonium sulfate with a molécule of Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity, or both, are reduced ln an area. This can corne about when: pest populations are repulsed from an area; when pests are incapacitated ln 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 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 iocus is generally a non-human area.

The molécules of Formula One may be used in mixtures, appiied simultaneously or sequentially, aione or with other compounds to enhance plant vigor (e.g. to grow a better root System, to better withstand stressful growing conditions). Such other compounds are, for exampie, compounds that modulate plant ethylene receptors, most notably 1methylcyclopropene (also known as 1-MCP). Furthermore, such molécules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuabie agricultural commodities. Such times include the early planting season when pest pressure is usually low.

The molécules of Formula One can be applied to the foliar and fruiting portions of plants to control pests. The molécules wili either corne ln 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 moiecuies of Formula One can also be applied to the soit, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molécule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.

195

Generally, with baits, the baits are placed In the ground where, for example, termites can corne Into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, orslant surface) where, for example, ants, termites, cockroaches, and flies, can corne Into contact with, and/or be attracted to, the bait. Baits can comprise a molécule of Formula One.

The molécules of Formula One can be encapsulated inslde, 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, repeated applications of the molécules of Formula One may be désirable to controi newly emerged larvae.

Systemic movement of pesticides ln plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molécules of Formula One to a different portion of the plant. For example, control of foliar-feeding insects can be achleved 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 ail types of seeds, Including those from which plants genetically modified to express specialized traits will germinate. Représentative examples Include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide résistance, such as Roundup Ready seed, or those with stacked foreign genes expressing insecticidal toxins, herbicide résistance, nutrition-enhancement, drought résistance, or any other bénéficiai traits. Furthermore, such seed treatments with the molécules 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, which can lead to higher yields at harvest time. Generally, about 1 gram of the molécules 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.

It should be readily apparent that the molécules 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 résistance, or those with stacked foreign genes expressing insecticidal toxins, herbicide résistance, nutrition-enhancement, or any other bénéficiai traits.

The molécules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sectoror in the field of non-human animal keeping. The molécules of Formula One are applied, such as by oral administration in the form of, for

196 example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parentéral administration in the form of, for example, an Injection.

The molecuies of Formula One may also be employed advantageously In livestock 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 animais. Suitable formulations are administered orally to the animais with the drinking water or feed. The dosages and formulations that are suitable dépend on the species.

The molecuies of Formula One may aiso be used for controlling parasitic worms, especially of the intestine, in the animais listed above.

The molecuies 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.

Pests around the world hâve been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The molecuies of Formula One may also be used on such new invasive species to control them in such new environment.

The molecuies of Formula One may aiso be used in an area where plants, such as crops, are growing (e.g. pre-plantlng, 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 molecuies 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 yieid of a plant (e.g. increased biomass and/or increased content of valuable ingrédients), improving the vigor of a piant (e.g. Improved piant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingrédients), and improving the tolérance to ablotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy évaluation processes by various govemmental authorities (local, régional, state, national, and International). Voluminous data requirements are specified by regulatory authorities and must be addressed through data génération 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 Wtde Web. These govemmental authorities then review such data and If a détermination of safety Is concluded, provide the potential user or seller with product registration approval. Thereafter, In that locality where the product registration Is granted and supported, such user or seller may use or sell such pesticide.

197

A molécule according to Formula One can be tested to détermine its efficacy against pests. Furthermore, mode of action studies can be conducted to détermine if said moiecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.

The headings ln 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

Compound No.	Appear ance	Structure
1	yellow gum	CH3 N-/ fl zCH3 fl < CH CHj CHs
2	yellow solid	zCH’o _ »-*t V X CH CH’ CHa
3	yellow gum	ch3 N-/ fl sZCH3 < X 'ch CH*

198

4	yellow oil	ch3 îvv-n CH,
5	yellow oil	zCH’o v CH,
6	yellow gum	CH, \ VL /^/^CH3 CH,
7	yellow gum	CH, }Ï-N/ V »3 <N=^ CH,

199

8	yellow gum	zCHjo ΓΥ<λΓο CH,
9	beige gum	zCH3o cl CHî
10	colories s gum	zCH’o ÎYr * Ir CH>
12	colories s glass	ch3 NZ 3° <NY I 'ch, ch’

200

18	Brown oil	HjC \-N X CH CH’ CHj
19	Yellow oil	HjC n
20	Yellow oil	H3C V~zCHj \ CH CH’ <-h3
21	Yellow oil	HjC \-N V/^s/CH3 CHj

201

22	clear oll	z ch3 q CH N-< V_/CH3 f| Ί /—ch3 < Λ HjC rr
23	clear oll	ZCH’ A CH, fC W CHj Îl T /
24
25		cy H)^nv>O

202

26		Cll3 rv ΙΙ,Α' Λλ° f |l h>c HjC II jC
27		HjC ~\3Γ H3C
28		n.. h3c ~y-N h3c
29		rv_/> i 1 ν-8/Λ h3c ~\^-n h3c

203

30		113e HjC
31		S ΪΓ^ é,1p
32	Gold syrup	ch3 CH>
33	Brown solid	0 N=\ 7^CH3 M

204

34	Off white solid	cy Y
35	Off white solid	o CH, W-CH’ σΝ>
36	Off white solid
37	White solid	cy

205

38	Off white solid	H3C—o U
39	White solid	H,C—S -v> ? σ
40	Pale yellow solid	σ!>·
41	Brown thick mass	CT ryy

206

42	Pale yellow seml solid	o ch3 a ch·
43	Pale yellow solid
44	White solid	H3c—s η X' σ·>', rr
45	Brown thîck mass	0 CH, W-CH’ CH’ CX o.,

207

46	Pale yellow thick mass	H3C /--CH3 ,1 />— H /CH’ k JJ o CHj
47	Pale yellow thick mass	HjC N^=\ --CHj a‘;> br / h3c—s
48	Pale green thick mass	HjC—, σ^ν· HjC—S
49	Pale yeilow solid	0 nsa y-cH3 σ'·'

208

50	Brown thick mass	H3C—» xt /Z N CH3 A JJ O ch3 br
51	Pale yellow thick mass	H3C—s nX,
52	tan solid	o __ Q “
53	White Solid	N V/~S/CHl H H3C CH3 (7 br

209

54	Clear Oil	ch3 r\ °K~ =Η, C
55	White Semi Solid	-γ VT CH, O Y N
56	Brown Solid	~ Y-
57	White Solid	HîÇ CHj n ΚΛ“QN>“

210

58	Clear Oil	/CHi /CH’ H CHj U N
59	White Solid	CHj o ^CHj
60	White Solid	CH1 o rC H O rr
61	Light Yellow Solid	CH, n Z CH»

211

62	Clear Oil	-K-V1''· σ0 ^br
63	Light Yellow Solid	ry bl·*' ch, U
64	White Solid	hjC CHj K-yXo br
65	White Solid	o ~Â/F ch, O ^br

212

66	White Semi Solid	s-ch3 vP a N
67	Yellow Semi Solid	H3C. CH3 ,X-CH3 Λ-θ J <«, N
68	Clear Oil	h3c ch3 Cl Ov V-CH3
69	Dark Brown Oil	P /S Q- e», br

2I3

70	Viscous Pale Yeliow Oil	Cl Q sJyF CH3 F Q “
71	White Solid	rC ν~α Pi ) v h’c
72	White Seml Solid	ch3 rrN>N> CH3 v «’c
73	White Semi Solid	CH3 o Q », N

214

74	Clear Oil
75	White Semi Solid	PHjq s/CHj CH, Q ™, N
76	Clear Oil	ch3 CHjq ÇH2_s Z ch> N
77	White Solid	Cl o rC K“‘ CH, U

215

78	White Solid	Cl o /CH> U TT
79	White Solid	ci o s/CH> ch, (J N
80	White Solid	CH, sz ci o \ / V__/^CH3 ch, C
81	White Solid	r( nr

2I6

82	White Solid	IJ
83	White Solid	ÆF><s/CH) H CHj
84	White Solid	rÿk· H CH 3 (J
85	Off- White Solid	r^yV-ii

217

86	Yellow Solid	H3C CH,
87	Yellow Solid	f· î V’ rC χ<Λ“· u l
88	White Solid	'c», Q e«,
89	White Solid	rYN^>-H3 «’c

218

90	Clear Oil	;Z'R- σ
91	Faint Yellow Oil	F F )Gq Z3 KR’ Q br
92	Faint Yellow Oil	F F X 0 j»CH3 ch3 C “· N
93	White Solid	Γ’!/»’ V H’c

219

94	Ciear Oil	CHj /1¾ z~s ch3
95	Ciear Oil
96	Yellow Solid	CH ~ /CH3 HjC
97	Yellow Oil	ch z—s/CHî CH3 h’c

220

98	Yellow Oil
99	Yellow Solid	σΝ> br
100	Clear Oil	)=4 Z CH= σ .^z“' N
101	Clear Oil	CH, CH 7 TH3 0 y--S σ »Γ ^bT

221

102	Clear Oil	zch3 XXθ'
103	Clear Oil	zch3 σ .Γ N
104	Faint Yellow Oil	,ch3 XK” σ .2 N
105	Off- White Solid	ch3 o zCH3 N

222

106	Faint Yellow Oil	σΝ>“·
107	White Solid	CHj o K<CH’ CHj (a ^ch3
108	Clear Oil	/Hj s Cl CHjC \ CH3 U
109	Yellow Solid	v‘MH y=\ ’ Cl 0 y~CH3 h3c

223

110	Brown Oil	h3c ch3 K<ZCH3 ί I L CHs
111	Yellow Solid	cHj o H’ VH> U o
112	Brown Oil	F». « V· CHj
113	Yellow Oil	n CHj N^\ χχ-5 Il 1 k CH’

224

114	Brown Oil	ΓΜ HjS /CHî .CHj o. V rt CHj
115	Light Brown Solid	HjC CHj rC k^·
116	Yeilow Soiid	HjC CHj Pb o J V ’
117	Yellow Oil	r\ K</Hl CHj Il i À CHj

225

118	Brown Oil	ΟΠ - c“·
119	Brown Oil	CHj 0 z CH3 Tn N Z CHj
120	Brown Oil	CHj o CH3 ’YYi CHj
121	Off- White Solid	CHj Q /CHj CHj xj TT

226

122	Faint Yellow Solid	kc’ CH, O e,„
123	Clear Oil	rC v~s'
124	Yellow Solid	CH3 o /Η3 Ά CH, y H.C
125	White Solid	N=Z WH’ CH, 1NJ »’c

227

126	Yellow Oil	CHj0 /CHj H CH, CX ^CH,
127	Yellow Oil	CH,q CH, ex ^CH,
128	Néon Yellow Oil	CH, o /H, îA. yz5 en “· br
129	Néon Yellow Oil	PHj 0 nA W'5

228

130	Pink Solid
131	Red Oil	rC VY’ YH1 br
132	Yeliow Oil	CHj o /H3 στ - br
133	Yeliow Oil	α o zCH> d-K ça

229

230

138	Yellow Oil	\ F
139	Faint Yellow Oil	CHj o /H, στ“ îr
140	Faint Yellow	rC CrT
141	Light Yellow Solid	h3c ch3 CH, O y— CH, or x 1Ψ

231

142	Clear Oil	P o /c3 \ CHj H>C
143	Colorie ss Oil	ch3 ο K
144	Colorie ss Oil	CH, / 3 CH3 O i--S ch3 σ
145	White Solid	rqyrn· Q

232

146	Gray Oil	ββ:'· N
147	Colorie ss Oil	ς j N
148	White Solid	njh’WH3 ^>CCH) cy N
149	Yellow Solid	h3c ch3 JU' FOO K, br

r

233

234

235

158	Clear Oil	σ X)
159	Clear Oil	ch’F < H3C N
160	White Solid	P q /= x^r N
161	Brown Oil	V“

236

162	Light Brown Solid	/ \\ CH3
163	White Solid	P 0 C H 3 y H’c
164	White Solid	P o V/’ vo N
165	White Solid	ΓΗ « yCH3 z ’yv-·' Q

237

166	Yellow Oil	r-u CH, rrN>N> H3C
167	Grey Oil	N
168	Falnt Purple Oil	y.P4' WX «aC
169	White Solid	CHO ?—CH3

238

170	White Solid	CH3 o i---/ σ «y N
171	White Solid	ch3 CHj o --/ N
172	White Solid	rC fj'
173	White Solid	P o rC H TX 0H· N

239

174	Clear Oil	P q C ““ N
175	White Solid	P o Fxv^Y^O’'~N\ ch, TT Cl
176	Yellow Oil	P 0 ZCH’ U pz-s 'YY^ch,
177	White Solid	P o H’V/H1 XX

240

178	Yellow Oil	,C1 <λ F. \ rr
179	White Solid	Λ CH, XX N
180	Yellow Solid	Cl 0 ~Zf H’C
181	Faint Yellow Oil	Cl Ο Yp CHl

241

182	Faint Yellow Oil	P o 'A ΥγΟ'-'Ρ™, 3C
183	Yellow Oil	/' Vj-H CH, IL. HjC N
184	Colorie ss Oil	CH3 fT
185	White Solid	CHj ÇHj 0 y--S fT

242

186	White Solid	CHO, CH3 vV^“· ΐζ JJ Xch2
187	Yellow Solid	/»>o r Λ CHj F IL.,^ «.C
188	Yellow Oil	PH3 o __/ XX '
189	Yellow Oil	ch3 o ch3 s/chî c= V «x

243

190	Yellow Oil	ÇHjo y^CHj RT
191	Yellow Oil
192	Yellow Oil	„„ HîÇ CH, PH3 0 \__s/ 3 Vb
193	Yellow Solid	Pb o __7 -, F ''tr

244

194	White Solid	yCH> Λ fwAN' Yj br
195	White Solid	/CHî?\ /s^cn3 O ....
196	Tan Solid	\\ zCIÎ3 U “
197	White Solid	CH, qT “

245

246

202	White Semi Solid	Cl n r< H ' CH, U H,?
203	Yellow Oil	H,C pu q ’
204	Yellow Oil	H 3 C CH, Cl o 3 V / 3 ?r
205	Yellow Oil	AND Enantiomer P 0 ρ/π < h3c N

247

206	Yellow Oil	H’c
207	White Solid	°^_/F rr^> CH5 < H3c
208	White Solid	Cl n A H ’ \CHj Q ?r
209	Yellow Oll	,CI °^/H3 Q^’CH’

248

210	Yellow Oil	P 0 /«’ U VZ~S Q CK, N
211	Yellow Oil	ci o __g/CH3 cA'“· N
212	Yellow Oil	P 0 /»> Q- c». N
213	Yellow Oil	p V/-A J N σ - N

249

214	Yellow Oil	p - Λ CH, N
215	Clear Oil	CH, rw f Çh3O j—s r* J, z) N 'CH, vZ
216	Cream Colored Solid
217	Clear Oil	JCHj YK’ N CHj

250

218	Clear Oil	CHj CHjO t--S
219	Clear Oil	ch3 στη*Yy .2
220	Yeliow Oil	ξ F ch30 /~^/î wy
221	White Solid	γυ X2 σΛ> br

251

222	White Solid	__Z4’1 CHp /—> U
223	White Solid	rC XACH’ V
224	Colorie ss Oil	,CH3o Y CH3 σ “
225	Light Yellow Oil	CHJ0 zCH3

252

226	White Solid	CH, n ^d-Zo Q-
227	White Solid	F F fAZ /CH;)O /F Q NT
228	Colorie ss Oil	F F /CHj o _\/^F Cl,)
229	Colorie ss Oil

253

230	Colorie ss Oil	Cr “ TT
231	Colorie ss Oil	CH, P CH'
232	White Solid
233	White Solid	F /F ch3O n C-X ΓΎ CH3 CH3

254

255

238

Colorie ss Oil

239

Colorie ss Oil

240

White

Solid

256

242	Colorie ss Oil	F /CHjO\ /-Va F γ br
243	Colorie ss Oil	/β
244	White Solid	CH, n K r<MCHj CHj «,0
245	White Solid	CH> .c

257

246	Colorie ss Oil
247	White Solid	ch3O ΓΥ^> < Λ HjC
248	Colorie ss Oil	CHîn < y HjC bT
249	White Solid	CH, n σ

258

250	Clear Oil	ch3O A/”’ , χχ?- H’C
251	Brown Oil	Or br
252	Off White Solid	Br 0 Z CH3 N=Z X^~S 17 br
253	Off White Solid	ch3 Br 0 y--S N CHj χγ”>Β N

259

260

258	Brown Oil	Cl o J W X~ CH, N=< /-O7 Qz S,,,.
259	White Solid	Ύ YHîV>s'CH’ W-n H3C
260	Colorie ss Oil	ch30 ch3 HjC
261	White Solid

261

262	White Solid	fA/F ^/CH3A c J —N F σΌ
263	Colorie ss Oil	F V yCHÎO bT
264	Colorie ss Oil	F °\ z-~A/\?~F γΆ f >T
265	White Solid	CH,n c J \\ F\zCH3 'YY'Q^’J ch3 Ύ J A

262

266	Coiode SS Seml- Solid	ί-γχ-Χ CH> H,C
267	Colorie ss Oïl	XX- < X HjC
268	White Solid	F~xC pHjO Ο-ΛνΧ X .)
269	White Solid	Ibc

263

270	White Solid	CH,n
271	Colorie ss Oil	E Μ //-N YL ✓ a br F
272	White Solid	PHjO r xi —N ργγΝ^ ) JT CHî h’c
273	Colorie ss Oil	XA CH, U h/ N

264

274	Colorie ss Oil	CH, Çi 'hc
275	White Solid	vA'O 0 CH)
276	White Solid	__f H’ __h3c H3C F N F
277	Brown Amorph ous Solid	zch3 Br O y—S ï Z>— Z CHj fXjA ch’

265

278	White Solid	yCHP\ /—CH3 XM- ΓΥ 3
279	White Solid	ch3 CHp y--' / H Q· e». >r
280	White Solid	CX v
281	Orange Foam	CH3 H J£Nh3 HA_Λ X

266

282	Colorie ss Oil	zch3 X
283	Colorie ss Oil	/η3 Cl 0 /— s bT
284	Colorie ss Oil	Cl O. CH, Q. J Xch2 N
285	Clear Oil	ch3 zch3

267

286	Yelîow Oil	Y1Vz's^F rVr^> < HjC N
287	Yellow Oil	ch3 /h, ch 3
288	Yellow Oil	ch3 zch3 /--/ S σΑ CH3
289	Dark Yellow Oil	ch3 /η3 ch3

268

290	Yellow Oil	ch3 ch3 σ x; ch3
291	Clear Oil	h3c Cl œ3c—A-CH3
292	Tan Solid
293	Clear Oil	fl 0'^0?'''''

269

294	Yellow Oil	CHj
295	White Semi- Solid	CHj
296	Colorie ss Oli
297	White Solid	Br 0 j—CHj U h U N

270

298	White Solid	ch3 Br 0 y---f H U rr
299	White Solid	_/Hî Br 0 y---'J
300	White Solid	ci O. /—CH, c
301	White Solid	CH3 Cl 0 y---' H Q c, NT

271

302	White Solid	_/H2 Cl Ov y---'J Q c’
303	Colorie ss Oil	Xk· αχ N 3
304	Light Yellow Oil	Cl o ch3 H3C
305	White Solid

272

306	Grey Solid	a.)
307	Colorie ss Oil	Cl n
308	Colorie ss Oil	CH, ÎJ H,/ bT
309	Colorie ss Oil	^rr f

273

310	Light Yellow SemlSolid	CH, (J h/ N
311	Colorie ss Oil
312	White Solid	Cl o J. Λ—N XR-R
313	Light Yellow Solid

274

314	Faint Yellow Oil	Phj o /CHî Νχ p~s N
315	Faint Yellow Oil	CHj o /Hj N
316	Faint Yellow Solid	,CH3 0 CH, (J i> N
317	White Solid	K vF. Q N

275

318	Brown Solid	CH, Cl O ,----' ALy» U N
319	Brown Solid	__/Hi Cl 0 y--y
320	Yellow Solid	Cl O% /—ch3 σ.> br
321	Yellow Solid	ch3 Cl 0 j—f σΑ N

276

277

326	Colorie ss Oil	h3ç ci ο V bT
327	White Solid	/Hj \\ΗΐΟχ xAw N
328	White Foam	ch3 .et C> y—s; ° CH’ a c-
329	White Foam	ch3 P y— N^=\ / \ θ / /)— N ch, σ

278

332

Clear

Yellow

Oil

279

334	Light Brown Solid	Cl Ov /—CH,
335	White Solid	rC °K'cn· Q “
336	White Solid	P o . /CH1 Q br
337	Pale Yellow Oil	ci n rCX~CH’ U 3

280

338	Clear Oil	ΓΥ' Γ < H3c br
339	Clear Oil	F F Cl O _V σ .Γ
340	White Solid	Hli^ h3c ch3 ^2 / ~CH3
341	Yeîlow Oil	,CH’O ’V br

281

342	Yellow Oil	cï-i CH, br
343	Yellow Oil	br
344	Yellow Oil	PHjO __/ br
345	Yellow Solid	Cl ov ch3 fY CH3

282

346	White Solid	rCX ox N
347	Pale Yellow Oil	V/~S' s/C’ >Î.NX »>c
348	Brown Solid	/Cl U
349	Beige Solid	ch3 o Q-X

283

350	Colorie ss Oil	CH, / 3 Br O y--S Yjn 'CH) Ar
351	White Solid	'A'' ‘
352	Yellow Solid	5 -/Y ^br
353	Yellow Oil	·, -c·

284

354	Yellow Oil	H’S 0 ,C> C H 3 XJ CHî N
355	Yellow Solid	CH·
356	Yellow Oil	7 Z-'”
357	Yellow Oil	wA.

285

358	Off- White Solid
359	Off White Solid	I z>—N ^^0 VjCH)
360	White Solid	q μ/™en CH3
361	Tan Soiid	HîÇ CH, X >X“·

286

362	Clear Oil	γί CH, Ci o y 3 σ .2
363	Clear Oil	ri 9v CH, C' q V 3 cFF N
364	Yellow Oil	P S «Z™’ J HjC
365	Yellow Oil	7' W-/H) ch3

287

366	Yellow Oil	rC Ύ’°“' cyy ch3
367	Clear Oil	p o zCH’ CrN>vT ch3
368	White Solid	Cl ~ /CHj /c Q - Y c/x H’c
369	Light Brown Oil	5 ?\ H’kCH1 rk Av™’ U CH’

288

370	Colorie ss Gum	H3C CHj Xr CHj
371	Colorie ss Gum	CHj Br O *.....S ï _Δ Vf” Vhi στ
372	Yellow Oil	Cl s zCH> V H>c
373	White Solid	HjC CHj en N

289

374	Belge Solid	Cl o V=\ /-N H y
375	White Solid	ÇH3 0 j—CHj NA_V“ h U
376	White Solid	CHj ÇHj 0 / f TJ N
377	White Solid	ÇH X1 FïT N

290

378	White Solid	z CH3O IL h3c
379	White Solid	ci o cXX'.....
380	White Solid	/«, a H VHl X-γ CHl v /-°
381	White Solid	A xXσ

291

382	Clear Oil	F F rrN^> H,C
383	Pale Yellow Oit	P O Ç -.-χ0 \h,
384	Colorie ss Oit	AA bT
385	White Solid	/CH V ^CHj rGp o 1 ^bT

292

386	White Solid	CH. ÇHj o --/ N
387	White Solid	ÇH.o Z’ 'ïY
388	White Solid	N-/CH’V/~Br ΎΤ =- ’ N
389	Colorie ss Oil	z ch3 0 A~D Yxc \ CH, H,C

293

390	Off- White Solid	CHÎO 'T-d r(>-Cs Cil, V A
391	Colorie ss Oil	p . X CH, Q- .... br
392	Colorie ss Oil	C. V ζΆ-Ά- ch> U br
393	Colorie ss Oil	a o zCH> Y

294

394	Colorie ss Oil	IL
395	Pink Solid	/Cl VT-* Q “
396	Colorie ss Oil	Q “ bT
397	Colorie ss Oil	f>o nA >_<~S ^bT

295

398	White Solid	CH CHj CHjo / ΥΎ c’
399	White Solid	CH, CH, U br
400	Yellow Oil	CHj /CHj CH j
401	Yellow Oil	CH3 /H 3 σψ CHj

296

402	Yellow Oil	CHj zCHj Γ* Λ—x V CHî U CHj
403	Yellow Oil	CH, /H, Q ç HjC
404	Yellow Solid	Hî\\ ' H_X' H CH, 1
405	Colorie ss Oil	P o /CH’ σ

297

406	Colorie ss Oil	^R
407	Pale Yellow Oil	P o (Χρ s\ ch3
408	Yellow Oil	H,C
409	White Solid	U

298

410	Orange Oil	o ch3
411	Beige Solid	ÇH, 0 ,--CH, br
412	White Solid	ch3 ch3 o —/
413	White Solid	ch3O _2

299

414	Yellow Oil	η ΗΛ CHj Y Q N
415	Off- White Solid	Y d- CH3
416	Yellow Oil	h3c ) ZCHî r<^s o br
417	Yellow Oil	h3c ) q /ch3 rb-C 'fj'

300

418	Yellow Solid	H3C
419	Yellow Oil	H3C m r \ H’\ ,CH3 N ÿ R .—N\ X x
420	Yellow Oil	J? ys7-'c,‘ χΗ,
421	Light Yellow Oil	Η3ξ χΧ^ XX

301

422	Light Yellow Oil
423	Light Yeilow Oil	0 ciij o z__y~CHj 'i/o
424	Tan Solid	XT'O
425	Colorie ss Oil

302

303

430	Light Yellow Oil	X
431	White Solid	XX·
432	Yellow Oil	Cl o rC XX N
433	Yellow Oil	P o zUXl. C J QT <xCHi tX

304

434	White Solid	> HjC CHj Xï
435	White Solid	0 “·
436	White Solid	XX
437	Yellow Oil	Cl 0 /CHj Çr »V“· CHj

305

438	Yellow Oil	CH, Q C», N
439	White Solid	CH3 o rXX
440	White Solid	ÇHÎ O zCH3 rLM vy-X,
441	Yellow Solid	F», °> î e N

306

442	White Solid	,ch3 o L> br
443	White Solid	PH,OK ___ xX t ^bT
444	Brown Solid	M CHi
445	Brown Solid	/Cl O CHj {·=( V/s V CH1

307

446	Yellow Solid
447	Dark Oil	ή zc,,J
448	Brown Solid	Ar ÎX'N'^'\h, CH3
449	Tan Solid	/cl °, r<

308

450	White Oil	AA “ .V' CHj
451	Yellow Oil	rC0X~s/CH’ u W ^CHj
452	Colorie ss Oil	Br q /«> ΓΥ-Λ'/'5 /Y// \ Q N
453	White Solid	Λ °\ /Hî CHj Q N

309

454	White Solid	Jh' I λ—N CHj rf
455	Colorie ss Gum
456	Yellow Oil	Cl o a N
457	White Oil	Q V 0<+-cH,

310

311

462	White Solid	ch3 .ΓΚ
463	White Solid	ch3 Q .Γ ’
464	Colorie ss Gum	F F Cr
465	White Solid	J V/CH3 ï î\^ch3 Q N

312

466	White Solid	AND Enantiomer CHj Br Ο .......S
467	Colorie ss Gum	H3C zCH3
468	Light Yellow Solid	Br 0. S—CH,
469	White Solid	Br 0 S-CH, CHa Q

3I3

470	Light Yeliow Oil	rC R~/Hj Q
471	Light Yeliow Oil
472	Light Yeliow Oil	YY
473	Light Purple Solid	CHJO /»> yAA N

314

474	Yellow ou	Cr v- CHj
475	Light Yellow Oil	Cl O y^LnA/xs-ch’ i L & A CHj
476	White Solid	Br 0 S-CH, T'A— t? 'CH, Q “
477	Offwhite Solid	/CHA n-n v—ch, îi i CH3

315

478	Clear Oil	0 < HjC N
479	Beige Solid	Cl S /—ch3 ozr xr
480	White Solid	S. /—ch3 Λ N
481	Light Yellow Oil	Cl Cl °\ /--- σΝΥ

316

483

Clear

Viscous

Oil

317

486	Off White Solid	ri .CH3 br
487	Offwhite Gum	XVP· Jv N\ H’é Ιι ίΓ CHî At
488	Light Yellow Solid	Η,ς CHj d 0 V-CH, cXT N 0 / HjC
489	Yellow Solid	o HVH1 \\ /-CHj

318

490	Light Yellow Oil	br
491	Light Yellow Oil	\ F σ bT
492	White Solid	Ci oK ch3 nr
493	Light Orange Oil	yV ^bT

319

320

498	Light Yellow Oil	J W‘ N o / h3c
499	Colorie ss Oil	h3c Cl 0 /==° / ch3 N
500	Beige Solid	y--CH, Cl O y---' c&y
501	White Solid	eu, r-l σ -·>

32I

502	Thick Yellow Oil	CHj br
503	Belge Solid	H3C CH3
504	Beige Solid	HjC CHj bT
505	Colorie ss Gum	Br O ™ /--S Χ^ΡΝ·Χ3<2 F—/ 'CH, O F F br

322

506	Clear Colorie ss Oil
507	Clear Colorie ss Oil	CH, ci o J σΡ<:
508	Clear Colorie ss Oil	J'
509	Pale Yellow Gum	CH3O ί| CHî chî 'tr

323

510	Yellow Oil	Cl o zCHî σ H... HjC
511	White Oil	XX σχζ o— ch3
512	Pale Yellow Oil	ci o X X°~CH’ «3C
513	Thick Clear Oil	/—CH3 XX crX) X

324

514

White

Solid

516

Dark

Brown

Oil

517

White

Solid

325

518	White Solid	s-ch3 bT
519	White Solid	s-ch3 Cl OK /----' abb N
520	Brown Gum	h3c / R\ /CH’ 1 /—N\ CHj il CH3
521	Beige Solid	Cl o fX. Y^S CH3 Q f

326

522	White Solid	ci O eu. u x
523	Yellow Solid	i> H>YH> r( ^°XcH) Q' C·,
524	Light Brown Solid	P 0 ΓΎ H’c h’c
525	Faint Yellow Solid	z q /Hj A y~^s U br

327

526	Faint Yellow Solid	F q /CHî CH, XX
527	Yellow Oil	ch, XX “ xr
528	Light Brown Oil	Av wA
529	Faint Yellow Solid	rZ A'/'

328

530	Clear Oil	ci o __/F \ CHj
531	Yellow Oil	F F Cl o / F —N σ Y λ cilj
532	White Solid	ci o Yr· CH, O < N \ h3cz
533	Orange Oil	ρΐ o rC σΝγ N \ O / h3c

329

534	Red Oil	Cl n rf αχ
535	White Oil	σΧ· N oh
536	White Solid	Ιχ. H3c iX
537	Clear Oil	F F /CI ° αχ

330

538	White Solid	/C1 rA
539	Clear Oil	P Cl /H, Æm aA
540	Clear Oil	rm' rr >
541	Light Yellow Oil	(^Hj A (T N o HjC

331

542	Colorie ss Oil	P 0 ___/CH3 C J chî N
543	White Solid	n CH, ( J CHJ N
544	White Solid	ci o CH, U br
545	White Fluffy Solid	Pi o rtKCH’ (J N

332

546

Brown

Solid

O

54Θ

WhiteYellow

Oil

333

334

554	Colorie ss Oil	P F\zCHj A
555	Yellow Oil	α o F\/f A
556	Pale Yellow Gum	h3c CH3 ch3
557	Pale Yellow Gum	h3c y_cH3 ch3 — \ /CH3 L 0 ch3 A

335

558	Faint Yellow Oil	P o -AS σΌ ' N
559	Faînt Yeliow Oil	P o r—f bT
560	Yellow Solid	U CHj o br
561	White Solid	γγΑΧ“· ^br

336

563

Pale Yellow

Gum

564

Pale

Yellow

Gum

337

566	Pale Yellow Gum	ch3 XF ^br
567	Off- white Solid	CH3 o N-H X ZCHj CHj CH’
568	Pale Yellow Gum	CHj O f jrS“-*V_s CHj XCHj
569	Colorie ss Oil	OF

338

570	White Seml- Solid	F F Ci o, V zch3 3
571	White Seml- Solid	ci q ch3 e/W H3C
572	Colorie ss Oil	F P θ\ C j
573	Colorie ss Oil	F P o —‘F cAv“ '

339

340

578	Colorie ss Oil	Br O CHj —H '—S CHj CHj O HîC rr
579	Colorie ss Oil	AK .Z
580	Colorie ss Oil	Cl O CHj ifY^K >“CH> H 1 ch3 h3c
581	Colorie ss Solid	σζ N

341

582	Clear Oil	ri b< bT
583	Brown Oil	k HjC
584	Dark Yellow Oil	σΥ ^bT
585	White Solid	P 0 (X?

342

586	Yellow Solid	/Ο ο ΗΛ < H3c bT
587	Purple Solid	ri A P 0 z <ïi r PpA H)C
588	Dark Yellow Oil	σΝ>“·· bT
589	Colorie ss Solid	h3c P1 o \ V H’c

343

590	Brown Solid	H,C CH, Cl 0 V-ch3
591	Light Yellow Solid	CH, ci o / nA / CHj ab
592	Brown Oil	cXc~ N
593	Brown Oil	C' Q Jt ---N Q «...

344

345

598	Colorie ss Oil	/«h CHj O y--s
599	Colorie ss Oil	eu. / 3 CHj 0 y--S \01,3 O -c N
600	White Solid	TW· Yn,, V^CH U N
601	Yellow Solid	HjC Cil, CHP ^C», YT -CH
602	Colorie ss Oil	/Hj rCHS

346

603	Light Brown Solid	CH
604	Brown Gum	v_/—V
605	Light Brown Oil	/H, /K XL
606	Light Brown Oil	Η Π-. QO-v_,
607	Colorie ss Oil	CH 3

347

608	Colorie ss Oil	,CHj
609	Colorie ss Oil	V a ov i—X
610	Yellow Solid	Cl o ch3
611	Yellow Oil	ζγΜΠ c·
612	Beige Solid	ax

348

613	Brown Oil
614	Colorie ss Oil	P O, \ZCH, Q -c
615	Colorie ss Oil	CT -c N
616	White Solid	hjC_/ch’ P Ο Λ /H, σ0? HC
617	Off- White Foam	στ;

349

618	Yellow Foam	r-OT Yh, cr j
619	Colorie ss Oil	N
620	Colorie ss Gum	A As A N
621	Colorie ss Gum	A (ΓΓ N
622	Colorie ss Oil	P 0 py < ô v
623	Colorie ss Gum	ci 0 n=< I JA
624	Colorie ss Gum	N

350

625	Colorie ss Oil	x4'
626	White Solid	N
627	Colorie ss Gum	py < ô
628	Colorie ss Gum	pyNX< pA ^bF
629	Colorie ss Oil	N
630	Colorie ss Oil
631	Colorie ss Oil	XVx qX ppF ^bF

351

632	Colorie ss Oil	σ </
633	Colorie ss Gum	F Cl 0
634	Brown Oil
635	Clear Oil	F F e CI 0 s2 (Y? N
636	Colorie ss Oll	F F Y V-Y Cn” N
637	Pale Yellow, Viscous Oil	F F ev7' N
638	Viscous Brown Oil.	F F q-Z

352

639	Pale Yellow, Viscous Oil	v C! 0 S->F Cf > N
640	Opaqu e Viscous Oil.	cio s-/-13 a > N
641	Opaqu a. Viscous Oil.	a o S^-F ΓΤ ; N
642	Opaqu e, Viscous Oil.	F F Çlo s-RF ΓΤ N
643	Oil	N
644	White Semi- Solid.	___. N^ZC1 o 0 0 F fui I s' J?
645	White semisolid.	CI ,—x >W o 0 F /Λ-κ A jt s AF W '-Si aYs-R;f
646	White Solid	•CH-Z' i J N

353

647	Yeliow Oil	F F ci 0 y~F N
648	Yeliow Oil	F F p o y-F N
649	Colorie ss Oil	Cl N
650	Colorie ss Gum	nA χΧ'Άι N
651	Colorie ss Gum	ci ,cl Q s~y^<, N
652	Opaqu e Viscous Oil.
653	Oil	A N

354

654

Opaqu e Viscous Oil.

Cl 0 ΓΧ ? N

Table 1: Continued

Compound No.	Appearance	Structure	Prepared as in Example:
655	Colorless Oil	Cl 0 CH, CH, >-CH, ILN«I H,C	51
656	Light Brown Gum	Cl 0 CH, |fV ) >-CH, U J H,C H,C	51
657	Colorless Gum	Cl 0 CH, CH, 0’ )-CH, L J H,C N	52

355

658	Colorless Oil	,αθ zV’ ) N iLnJ h3c h3c' Vh3	149
659	Faint Yellow Solid	7 l^.^o3 0	35
660	Yellow Oil	o 7 O CH, ΎΛ/^0 CH? J η ch3 3 kJT	35
661	Clear Oil	C«3 Cl ο ) ch3	11
662	Clear Oil	ch3 N< V fY^XcH, V H3C 5	11

356

663	Clear Oil	ch3 ÇrA··	11
664	Clear Oil	ch3 ci o \ N=<_ y-S N Λν σ χ F	11
665	Clear Oil	ch3 Cl o \ ch3 Q 4 F	11
666	Clear Oil	Fy p nA°AS CrNA Ιψ H,C	12
667	White Solid	H3CAyCH3 çX N CH3	12

357

668	White Solid	H3C^CH3 Cl 0 Λ ch3 nZka CÔ	12
669	White Solid	ci oH3CÎhJch3 Q “	12
670	White Solid	c, o^ch, ÇQ	12
671	Colorless Gum	(J CH,CH,	106
672	Colorless Gum	nA^sX) Πι fcH> N	106

358

673	Colorless Gum	7CI O nA A JL J 0 Ί > ch 3 V h3c	106
674	Colorless Gum	Cr N	106
675	Light Brown Gum	yÿ-iys; i J CH, CH, 5 N	101
676	Light Brown Gum	/CI 0 N==\ A JL Jl (J CHjCHjO kiT	51
677	Colorless Oil	P 0 Çr Ό rr	101

359

678	White Foam	Cl 0 OfK ffA Q N	106
679	Coloriess Oiî	z-ch3 JW CT CHs N	12
680	Coloriess OU	z-ch3 Cl 0 \ ch3 N< K>S' (YV N 3	12
681	Coloriess Oit	z-ch3 Cl 0 \ CH, n< μ/s' 3 . N rN ÇQ	12
682	Coloriess Oit	Cl 0 L CHj Qn>'ch3 N	12

360

683	Coloriess Oil	Il J H,C N 3	12
684	Coloriess Oil	α o \ <.,ch3 A As A	12
685	Tan Solid	ci 0 AAo N, CH3 y h3c	101
686	Coloriess Oil	«A' A? N ch3	12
687	White Solid	F F Cl o k CH3 /^,νΖ-ν 0 Cr CHj N	50

361

688	Light Yellow Oil	H3C Ach3 Cl o V ch3 Cr ch’ N	12
689	Light Brown Oil	h3c Ach3 Cl 0 V CH3 3 ___ ri >-N Çr V	12
690	Colorless Oil	H,C Ach3 Cl 0 V CH3 NssZ >>S· 3 j. ri σ	12
691	White Solid	F F CI'C^F N< K/5 Q CH> N	89
692	Light Brown Oil	P ο ο jX^ri^-NyJis-z^S^CH 3 ΓΎ Ιψ H,C	101

362

693	Light Brown Oil	F F ci-cTF y/-s _ Λ Λ·Ν ιίΎ > V H,C	89
694	Tan Solid	p ο c zCHj ΓτΝ^> V h3c	101
695	Light Brown Oil	h3c P 0 _ç^CH N< N ΟΤ > V H,C	89
696	Falnt Yellow Oil	Cl NCH’ CH> N=C N Γ7 H N	175
697	Beige Solid	N< Vf™3	39

363

698	White Solid	Çr «,	12
699	White Solid	H	12
700	White Solid	fp_J Ï.NJ H3C—'	12
701	White Solid	ντΉ“· N z^~N σ <?	12
702	Pale Yellow Oil	N< O-CH, PfNj-O-CH,	51

364

703	White Foam	ci o °t_H N=C ( ‘0 3	52
704	Orange Oil	Cl o S-ru N< K/S CHî \-CH3 V h3c	39
705	Clear Thick Oil	C' O %_CH N< ^CH’ |<!YN'F,j ''CHj V HjC	51
706	Light Brown Solid	H C! N C», n=( N Z^“N Q H N	175
707	Light Brown Oil	h3c Cl O o^CH3 N< KZ'5 Cr fcH’ N	97

365

708	Colorless Gum	N Λ-Ν ÇrV	97
709	Colorless Gum	N< «JC	97
710	Colorless Gum	CH Cl 0 c/ N< „ _ N Z-N CHj if>r > ψ «JC	97
711	Colorless Gum	C! O c/===\ Ψ H3C F f	97
712	Colorless Oil	Cl 2. CH, ,C12 N-Ÿ 3 n=V ^~< 'ô irvNj-N CH, h,c	149

366

713	Colorless Oil	,C1 θ3φ·°Η3 X V b ch3 V h3c	149
714	White Solid	F F ci ο V CHa N< X Q CH)	182
715	White Solid	CH, p o 5-V N ,Λ-Ν F ûr H N	12
716	Colorless Clear Gum	oy Cl ο >ν~ρ x KS~S N À-N (7 x N	97
717	Colorless Gum	Cl O o,CH3 \ CH3 3 Μ X	97

367

718	Coloriess Gum	ΫΛ'Ζ-ί:''' (JY	97
719	Coloriess Gum	ci o /— N=( JU/'SV-S , N ÀN ΓΥ UN=J h3c	97
720	Coloriess Gum	,cl °. s~P _ N ^-N CHj ΓΥ > ILnJ h,c	97
721	Coloriess Gum	O Çl 0 gl·®7 ^5-NK<CHJCH> lNJ h3c	97
722	Coloriess Gum	Cl o c/=\ ^.!W<	97

368

723	Colorless Gum	Cl Cl θ g F p Z F ly h,c	97
724	Clear Oil	O-CH, P o s' CH, U H,?	102
725	Clear Oil	HC P 0 s' CH, V H,C	102
726	Clear Oil	NST ,°o s' · Cil, Çr »,c>	102
727	Clear Oil	h3c ci θ s U H?	102

369

728	Clear Oil	S-CH, C'Q ? CH, H,C	102
729	Clear Oil	Cl o S-/^CH3 ^yN^-NfcH, CH3 M H,C	102
730	Clear Oil	ch3 cio s^° nA qY	102 |
731	Brown Oil	/' <> s-Z Pr^N> h3c	102
732	Clear Oil	Yp^CH1 CrN^~N> V H,C	102

370

733	Clear Oil	CH, < 0 Cl O K' 0 _ N X~N ιίΎ > V h3c	102
734	Clear Oil	h3c 0 [fY ' V h3c	102
735	Brown Oil	c, JW P^.nJ-n HNJ h3c	102
736	Clear Oil	zN f N >A~N ifv > HjC	102
737	Clear Oil	CH3 ρ^>·Ν V h3c	102

371

738	Clear Oil	CH, ifYNA V H,C	102
739	Clear Oil	/—CH, Ao 3 γύν^ν> H3C	102
740	Pink Solid	ci o QN>tCH Cf ° br	42
741	Coloriess Gum	.CH Cl O e/Z ψ h3c	97
742	Coloriess Gum	iYCH3 Cl ο sAn nZ Av -,ΝΖ’ί CH3 U h3c	97

372

743	Light Brown Oil	CH, s' 3 Cl 0 L F X-X' σχ s' ch3	11
744	Light Yellow Oil	Λ N Λ“Ν (? ,{ FjZ F	12
745	Light Yellow Oil	ch, X F	11
746	Light Yellow Oil	X“· Çrp F	12
747	Light Yellow Oil	H,C ru, ex F	12

373

748	Colorless Oil	H3C Cl o cAch3 Q--Q	97
749	Light Yeliow Oii	n< va™3 CHj Q ? F	12
750	Light Yellow Oil	Cl o CHj Q ? F	11
751	Brown Solid	F F F-ï* Cl o \ CH, ry ° bT	50
752	Light Yellow Oil	Cl A3 S ch, N< A N A~N oy F	11

374

753	Colorless Gum	O P 0 _Z=N N=< KZ~s Çr c„,	89
754	Colorless Gum	•nv Cl 0 N< K/~S F Q CH’ N	89
755	Light Yellow Oil	/C1 2X S-CHj bH >-< 3 ch3 ® f F	12
756	Light Yellow Oil	γ£Χ“·	12
757	Light Yellow Oil	σ A	12

375

758	Light Yellow OU	yC1 % S-CH3 ch3 C? X	12
759	Light Yellow Oil	JVfs'CH1 CHj Q X	11
760	Colorless Gum	,cl O s-^ Çr ».	101
761	Colorless Gum	ch3 Cr fcH’ N	101
762	Colorless Gum	ci H3C P 0 S-V|CHj Çr ™·	101

376

763	Ciear Oil	S-CH, Cl o _/ 3 Çr Ό	12
764	Coloriess Oil	Cl n CH, lU î. Lch3 _ ri A-AX^S^CHj Cr fcH> N	101
765	Amorphous Solid	P 0 CHj (7 CHj o N	91
766	Coloriess Amorphous Solid	ci o ÇH3 N< ï iCH3 fj CHj O N	91
767	Coloriess Amorphous Solid	Br οψ AnAA-ch, (J CHj 0 N	91

377

768	Light Yellow Oil	çrp fXf	12
769	Off-White Solid	N< CH, i? i	12
770	Light Yellow Oil	,C|O z-/”3 N=<_ λ-Ρ ch, fZ‘f	11
771	Light Yellow Oil	0 Cl O V CH3 Νχ V>s· 3 _ N XN Çr	12
772	Light Yellow Oil	O Cl o V ch3 n< 3 CT V N 3	12

378

773	Light Yellow Oil	0 Cl ο Ά CH, N-< 3 _ N À-N CQ	12
774	Light Yellow Oil	N< V~S'CH’ F	12
775	Light Yeilow Oii	Cl 0 _s·™3 N =4 _ N ,Λ-Ν Çr J F	12
776	Light Yellow Oil	,cl 0 _.s-CHj Çr ? F	12
777	White Soiid	H3C^CH3 Cl o V .CH3 N< >_/-? N θ Cr fcH’ N	50

379

778	White Semi- Soîid	H3C-yCH3 Cl o V CH, W N θ Γτ > V », C	50
779	Tan Solid	Cl 0 s-zCH’ h3c	101
780	Light Yellow Oil	F F Cl cSCCH> nX / Π CHî N	12
781	Light Yellow Oil	f F F Q CH ci o ys-CH> n< y—/ N Λ-Ν Γϊ > Ιψ h3c	12
782	White Solid	F F Cl o V CH, n< 3 rr H N	50

380

783	Yelîow Oit	N< CH, ILnJ H,C	89
784	Clear Colorless Oil	CH, H-N*· H,C	89
785	Clear Colorless Oil	CH, CCH’ CH, H,C	89
786	Clear Colorless Oil	AA ^n^-n ch, H,C	89
787	Opaque Viscous Oil	PI _ CH, Cl q s-^ 2 nX >-( ^yNy-N CH, Q h,?	144

381

788	White Solid	CI O s_yCH» n<	101
789	Orange Oil	rCH3 kbT	137
790	Pale Yellow Oil	0 θ Y-N |l J i CH, HjC S Ν'* H3X	136 i
791	Light Yellow Oil	q Cl O L CH, NsZ 3 ΓΤ ch’ N	12
792	Light Yellow Oil	q Cl o V CH, N< ___ N Λ-Ν ÇQ	12

382

793	Light Yellow Oil	O Cl o \ CH, (U P* 3 CF	12
794	Light Yellow Oil	h3ç o σ ci ο Ά ch, Cr CHs N	12
795	Light Yellow Oil	h3ç O çs Cl 0 F11: nX Rs ~ N 1ψ H,c	12
796	Light Yellow Oil	H,C ’b O Cl o Y CH, N< Λ N zZ N cF	12
797	Yellow Solid	<γΗ, Cl o F-CH3 N< t. J H3C N	89

383

798	Colorless Gum	ch3 o^n-(-ch \ CH3 ci ο ψ H,C	89
799	Oil	ci ο οχ	89
800	White Seml Solid	H,C O pu Cl 0 3 n-^ch. Ύ h3c	170
801	White Solid	_- H3C 0 pu P ° N-'S C 3 VYJ-' ό q cH3	170
802	White Seml Solid	Cl o3UCH> N< >-/ l Λ N 4?* N Q X	170

384

803	Pale Yellow Foam	ry zX'V- v ch3 y	147
804	Colorless Gummy Liquid	Cl 0 /''S N=4 y~\ X° N	183
805	Colorless Gummy Liquid	Cl O /-*S. \ Xo N	183
806	Colorless Gummy Liquid	AA q >	183
807	Colorless Gummy Liquid	ci o z^s. cr^ N	183

385

808	Brown Solid	ci oH’ci, °	149
809	White Solid	ci οΗ^ .9 nX K/a ch3 CH? Cr ch> iX	149
810	White Solid	ci oHî<L .9 Α-ΝΧ<'’ XF ^IX F	149
811	Yellow Oil	H,C o F\ CI O 3 tr *· )—, pXîX	149
812	Light Yellow Semi-solid	Q NX°yXX Cr cHs iX	12

386

813	Light Yellow Seml-Solid	Q N Pr > V H3C	12
814	Light Yellow Seml-Solid	ô	12
815	Pale Orange Foam	CI JW 0 0 Q-nAVch3 hJ ch>	51
816	Pale Orange Solid	w CH>	52
817	Brown Gum	Cl 0 l<S'N'^ ) ST LJ Hjc kCHj N 0	94

387

818	Opaque, Viscous Oil	φΑχγ X F	102
819	Pale Yellow, Viscous Oil	N Cl h2 bX I H3(T	102
820	Opaque, Viscous Oil	N CI N Η,(Ζ CH>	102
821	Opaque, Viscous Oil	XT Cl FF Q-4NtX X J η3Χ	102
822	Opaque, Viscous Oil	XT Cl h3ct	102

388

68ε

ZOU	rHD^ fA>cH N D D M	l!0 snoosiA ©nbedo	Z28
zou	a Y» J 0 |>N	l!0 snoosiA Μ0||θλ	928
96	0 ΥΗ 'Κ^'Α*ϊ>Ο D	HO snoosiA ‘anbedo	S28
20 l·	tH3 Y» r-YK-o JJ 13	HO snoosiA ‘enbedo	V28
6H	'H? YH 0 0 o I3	iu||j anbedo	£28

828	Pale Yeliow Oil	H3C^ F^F	102
829	Opaque, Viscous Oil	--- N-' y F h3c?	12
830	White Solid	ch3 Cl O y-S V	11
831	Off White Solid	s-CHj H 5 I J	11
832	Off White Solid	B; h çh3 A-nY'AY N=/ *N^x θ w Cl	11

390

833	Off White Solid	HïCV H O-n/vnvXxS'ch3 N==/ 0 Cl	11
834	Off White Solid	H3C'V\ N=fC1o Q-nAnjç-s,ch3 H CH3	11
835	Off White Solid	H3Cv xt .Cl N H	11
836	Off White Solid	H3C .. Cl H CHj	11
837	Yellow Liquid	Cl N C1 ÇZ^vXnÀ^s-CHj ch3	79

391

838	Yellow Liquid	Cl N Cl ch3ch3	79
839	Yellow Liquid	N=\ ° N\îs7. ΝΑ^χ-χ s„ C H 3 H3C-0 CH3	79
840	Brown Gummy	h3c-o ci ch3ch3	79
841	Pale Yellow, Viscous Oil	FF H 3 CT	89
842	White Solid	KT Cl 4 # ry-XCAO o	12

392

843	White Solid	ci o A-ZT Q N	42
844	White Solid	F Cl O F CrN>H	42
845	Colorless Oil	P^XÎ-n-11---F hP f	89
846	Opaque, Viscous Oil	Ο-Χνχ- h.c-1 ’	89
847	Clear, Viscous Oil	H3C r—\ N=rfC1 ο F h3c^	89

393

848	White Solid	«y c»3	89
849	Clear, Viscous Oil	J F * H3C' '	89
850	Opaque Film	J FF HjCT	89
851	Light Yellow Oil	Çr e».	12
852	Light Yellow Oil	N Λ-Ν Pr > V HjC	12

394

853	Light Yellow Oil	'ΐτ l' N	12
854	Light Yellow Oil	F F ÇH3O --Λψ N:À F N VQ	12
855	Light Yellow Oil	ΓγΝ^~Ν> V H,C	12
856	Light Yellow Oil	ILn«I h3c	12
857	Brown Oil	c 0 jACHî N< ûr ch’	89

395

858	Opaque, Viscous Oil	N Cl --- h3c^ f	89
859	Clear, Viscous Oil	XJ CI r-x JW 0 Cl Q-CL f	179
860	Yellow Oil	F F ci 0 WF N< V~S Cr CHj X	12
861	Dark Oil	F F Cl 0 W^F ιΤΎ > V H,c	171
862	Yellow Oil	f.f ci o 9./W-F QX>	91

396

863	Light Yellow Oil	F, F JTV’N' Cr ch’ N	12
864	Yellow Oil	CH3n F F Ï7 cH= N	12
865	White Solid	H,C 0 CS '0 Cf Ά V H3C	170
866	Clear Yellow 011	,cl °?W-x7 n=\ z-( '0 ^N>N ch, y H,C	170
867	Brown Oil	tX Cl 0 SA/ AXC ô (fM N	149

397

868	Liquid	o V X ch3	11
869	Pale Brown Solid	ch3ch3	11
870	White Solid	F F ,C1 V z-s'—k,; rr 11 N	12
871	Yellow Oil	<y\ x	12
872	White Solid	J4 N<VS CrN>îi N	49

398

873	Viscous Clear Oil	V F L	12
874	Clear Viscous Oil	F-}- F F	12
875	White Foam	J HO OH H3C7	89
876	White Cloudy Viscous Oil	^ch3	12
877	Orange Oil	M C1 r—A Nftf O 0 H3C^	151

399

878	White Solid	M A	89
879	Cloudy White Viscous Oil	F	12
880	Ciear Yellow Viscous Oil	çyAAA·/ V	12
881	Ught Yellow Solid	A As'c 3 _ n /An Cr H N	49
882	Brown Oil	C. 0 Ά N=z _ ώ Z-N ίΆ V H3C	89

400

883	Light Yellow Oil	ΓγΆ H,C	89
884	Yellow Viscous Oil	'yCH, CH,	12
885	White Solid	Cl o c.CHJ Qn>h N	51
886	White Solid	Cl 0 CH> n< ch,°	51
887	Yellow Viscous OU	°'CH,	12

40!

888	Clear, Viscous Oil	H3A CH, F	149
889	Pale Yellow Oil	Μ Λ1 N Nas/ O FF h3c^	152
890	Pale Yellow Oil	0-nXV.s^Ja h3c^	145
891	Yellow Viscous Oil	y’	12
892	Light Yellow Viscous Oil	^F	12

402

893	Clear Oil	h3c^ CHa	102
894	White Solid	ξ f „ H,C O_ %F ,a ηΡ & h3c	170
895	Clear Oil	F p h3c o \Z p n=\ y-7 b ÇrF	170
896	Yellow Viscous Oil	S ch2	106
897	Light Orange Viscous Oil	ch2	106

403

898	Clear Oil	f f N< V~S F «•J »3C	89
899	Pink Seml Solid	H,C O F\ F ,CI A /Ύ HP 'o F ρτΝΆ L*1 ”3C	170
900	Clear Viscous Oil	OXUA	106
901	Clear Oil	HjC^	102
902	Pale Orange Oil	HjA F	102

404

903	Clear Oil	H,f C»3	102
904	White Solid	ΑλΑ: X. h3c^ch3	106
905	Light Brown Oil	U Or fcH’ N	79
906	Clear Coloriess Oil	F F Y-F Cl o _s^ A. /VA ch, U H,C>	89
907	Clear Oil	F F /-F N<* V-^S V h3c	11

405

908	Light Yellow Oil	Cl o Pr V H3C	89
909	Light Yellow Oil	O o iU >-/s . ώ >N Çr Û	89
910	Light Orange Oil	C. o A nX >_7~s - N /”N lil > Ψ h3c	126
911		F Br O ^_cZ*x/”F yy fcH> NX	42
912	Clear Oil	çy<xNvsx5° h3c^	151

406

913	Clear Oil	XT Cl r-Λ. JW o OCHj h3c^	89
914	Light Yellow Oil	kBr Cl o /->-/ F N< Q CHs N	89
915	Clear Yellow Oil	F F WF ci o n=Z KC’b CH3 H3C	51
916	Coloriess Gum	F ΓΊ Cl o Cr w N	89
917	Light Yellow Oil	ff Cl o --->V n< >_^s b N À'N ιΓΎ > Ιψ h3c	89

407

918	Light Yellow OU	F dF Cl 0 /-S IL #l «je N	194
919	Pale Yellow Oil	H3Z CH>	143
920	White Solid	Η,Ζ CH> F	52
921	Tacky, coloriess solid	Kl ,CI iw 0 0 h3Z ch> f	51
922	Coloriess Oil	V Cl 0 zAf N< CX 0 S-CHj	43

408

923	Clear Oil	X! Cl 0 CH,F _ —'-xgxO'Cp h,Y	89
924	Clear Coloriess Oil	F F C1 o N Λ·*4 Çr c'	51
925	Viscous Slïghtly Yeliow Oil	ΟγΟ CH,	106
926	Pale Yeliow Oil	(yXUAF H,cr	152
927	Pale Yeliow Oil	h3c^	153

409

928	Yellow Viscous OU		110
929	Clear Oil	>rJ iH>	149
930	Yellow Viscous Oil	S F	106
931	Slightly Yellow Oil	S ô	106
932	White Solid	,cl Cr CHj br	91

410

933	Clear Oil	/CH3 pl o /—s _ N S-™ V H.C	89
934	Clear Yellow Oil	Jp-s ûr CHj N	49
935	Clear Yellow Oil	F F >XF ci s </— çr”X	49
936	Pale Red Oil	M >Cl r~X JW 0 0 0 O~nxAnA^nX^ch3 N—' | I «Y CH,	149
937	Opaque Film	M Cl Z—\ .N=Y 0 0 0 H3CT CH3	149

4ll

938	Opaque Film	h,P ch=f	149
939	Clear Oil	—cSp H,P CH, LCyF F	149
940	Clear Oil	H,CJ ZcAJ	149
941	Clear OU	αΗνχ-χ Hp ch, M	149
942	Clear Oil	X, cl JW ο ΟΟ O H,P έ«3 Μ	149

412

943	Clear Oil	hY ch> f	149
944	Opaque Oil	h3/ ch3n«/	149
945	White Solid	o-Xxxk H Y LAs-CH3 O O	149
946	Clear Glass	Y OO H3<r	52
947	Clear Glass	XT ,C' A-NJX J? Lf h3<X 0	51

413

948	Yellow Oil	fF f Cl o Λ-f F _ N Λν Pr x V H,C	89
949	Coloriess Oil	Br p . N ^~N çX	89
950	Yellow Oil	V F	106
951	Light Yellow Oil	F F Br O /—S νΛ X Pr’O' > LJ H>c N	79
952	Orange Oil	F	106

414

953	Yellow Oil	Cl	106
954	Yellow Oil	F^F	106
955	White Solid	ci o Cr u N	132
956	White Solid	xi-ènr·	50
957	Colorless Oil	F F J' Br O /—S > IL J h3c N	51

415

958	White Solid	,,σ	106
959	Yellow Oil	F F _ N Z“N ÇrV	89
960	Clear Yellow Oil	N< HjC	89
961	Clear Yellow Oil	ci o N< N F _ N Z“N ΓΤ V h3c	89
962	Colorless Oil	prN^~N> H,C	89

416

963	Light Yellow Oit	1F V P o zJA N zAN ψ H,C	89
964	Opaque Oil	M ,C1 N=Z 0 CH, F p Q-nAa^sa>ff A °	51
965	Off White Gum	H,Ç F CI 0 On Af F f M AN, 0 ίΥΌ ILn<J HjC	178
966	Coloriess Oil	„ ,yf;· >-Z^s Ff N ^~N ΓΎ > HjC	89
967	Coloriess Oil	F F n α ο Λ N=< F F N À-N ΓΎ > H3C	89

417

968	Clear Viscous Oil	^CH3	115
969	Clear Yellow Oil	F F Cl S Çr A	51
970	Cloudy White Oil	^CH,	115
971	Opaque Viscous Oil	Q-aXnâ___ h3c^	12
972	Light Yellow Clear Viscous Oil	''CH, F	115

418

973	Clear Colorless Oil	pv U-N»1 H,C	12
974	Off-White Solid	k ch3	115
975	Colorless Oil	c, o 7^’ ex > V H,C	50
976	Colorless Oil	F>LBr ci o nX FF Pr > V h3c	50
977	Slightly Orange Clear Viscous Oil	ο-τΑψ kCH, CH, F	115

419

978	Pale Yellow, Viscous Oil		149
979	Slightly Yellow Clear Viscous Semi-Solid	X, ° F	113
980	Colorless Oil	H,Ç Cl 0 /-~Z'CH3 _ ώ J>~N	89
981	Opaque, Viscous Oil	,N=fCI 0 F N— I n X 0	51
982	Clear Viscous Oil	è 6 F^F	83

420

983	Dark Orange Oil	en N> F Ï-A h3c	89
984	Light Yellow Solid	h3c^ f	116
985	Coloriess Oil	ÇrCjXu HaC^	156
986	Coloriess Oil	CH3CH3 F r	102
987	Clear Oil	ch3ch3	102

421

988	White Solid	nF Η,Χ	111
989	Light Brown Solid	'N=/ h 3<r	116
990	Light Brown Solid	HjC'J	116
991	Yellow Oil	Cl 0 F nX 'V CrN>N> V HjC	89
992	White Solid	Xî C1 Z—N .Ns=f o O O GAnAV^ CHjCH, F . .	52

422

993	White Solid	M zCI /7-^. JW o O Owyx CH3CH3 F	51
994	White Solid	ch3ch3	52
995	White Solid	Λ ch3ch3	51
996	Light Yellow Semi-Solid	h3c^ f	116
997	Light Yellow Seml-Solid	CH’F	116

423

998	Yellow Oil	Çr'v	89
999	Light Yellow Viscous Oil	O'An-^n--sW'F Η3σ^ F	116
1000	Clear Oil	^ch3	115
1001	Coloriess Gum	F F Ü ci ο Y-s >-CH3 iT*rN<r > U h3c	89
1002	Coloriess Oil	Cl o ζ-Ά1 n< N zAn Pr > V h3c	180

424

1003	White SemlSolid	Cl o z-CI _ ύ ° ΓΎ > h3c	50
1004	Brown Oil	CI θ Nsz ^fCH_ w ° ιΡτΝΆ H,C	127
1005	Light Yellow Gum	F F Cl o ÇpO n<P Il J h3c N	89
1006	Opaque, Viscous Oil	M >CI ο ο ο Ç/”N^nx11s^z ,'n'^ch3	149
1007	Orange, Viscous Oil	KT Cl -—X Nftf O O O Ç/nAnAx~nach H, J A,	149

425

1008	Light Yellow Gum	c ojZ AA IL J h3 c N	89
1009	Light Yellow Oil	Cl 0 Z^cl PT 'J) h3c	89
1010	Coloriess Oil	Cl 0 A KS'iS ___ M N θ ιΓΎ > h3c	50
1011	Clear Oil	F F XF 'CHj^ 7n-n Λ JL Λ-ν (Xj / CHj	106
1012	Coloriess, Tacky SemlSolid	xr Cl ,-rx NsZ o O CH3CH3	51

426

1013	Yeliow Viscous Oil/Seml Solid	F F n-n fT y N	106
1014	Orange Oil	O-YAw; HjC^	156
1015	Light Brown Gum	F F y-F F -N. ( F-é-FCHj f H P θ >-s ) < />1/^ NA_xf s Ό vn U «ae N	136
1016	Light Yeliow Oit	F F tF™, Ά > ÇJ	136
1017	Yeliow Oil	- n-n'CHo’ V	106

427

1018	Clear Colorless Oil	,CI O. ΓΎ > ILnJ h3c	89
1019	Yellow Oil	çr Û '	89
1020	Clear Viscous Oil	F p επ,ο n-n Λ JL Pj^ ^CHj	84
1021	Yellow Oil	? μΧΥ1 çA	89
1022	Yellow Oil	H;)C\ /=\ F jy-m γτνΑν> ψ HjC	89

428

1023	Clear Colorless Semi Solid	F «.0 /-N n< °>v-s V HjC	180
1024	White Semi Solid	CH, h8c-0 >-n ch3 ILn^J h3c	180
1025	Clear Colorless Oil	p Cl O , NJp-S CH, _ Λ Cr > V H,C	180
1026	Clear Colorless Oil	Cl o N< Pt > H,C	180
1027	Orange Oil	P Cl o N< V~S ° N Λ·ν rr V «.c	180

429

1028	White Solid	cf3 Cl 0 /—s <+>· σ N	181
1029	White Seml- Solid	^J=F3 Cl O /**S N=Z_ 0 (-)- — N N	181
-------F------ 1030	Colorless Oil	h3c Cl 0 Z-Jz-CH, ___ N >-N cr > V «JC	180
1031	Colorless Oil	ci O n< ___ M /-N |CY V h3c	180
1032	Colorless Oil	F c X k/V-s N XN pp» ILn«J h3c	180

430

1033	Off-Whlte Solid	pT? F . ώ A-N ÇrO	180
1034	Colorless Oil	CO £>V N< F , ώ A-N Çr Ό	180
1035	Colorless Oil	a „ N< F . N /-N ιΓΎ > V H3C	180
1036	Yellow Oil	Cl 0 A/ N< N AN Xi?	180
1037	Colorless Oil	o Cl 0 A \ F N< /F N Λ-Ν ιΓΎ V HJC	180

431

1038	Coloriess Oil	« » _ N Λ“ν ιΤΎ > V H3C	180
1039	Coloriess Oil	V & Cl 0 NesZ N ΓΎ > V h3c	180
1040	Coloriess OU	Cl 0 .—'J Ψ h3c	180
1041	Coloriess Oil	ch3 Cl o Z*° n< _ N S** Γί> h3c	180
1042	Coloriess Oil	Cl O Z-<CH3 N< ΓΎ > V h3c	180

432

1043	Light Yellow Oil	Cl ο N< âT° N iTt > ILn^ h3c	180
1044	Colorless Oil	ci 0 N -Λ~Ν Pr > jC	180
1045	Colorless Oil	PfN^N> V HJC	180
1046	Colorless Oil	O>p Cl o Z^ CI,3 NsX N y~N ÇrO	180
1047	Colorless Oil	N< 'βΤ'5''' ΓΎ > h3c	180

433

1048	Light Yellow Oil	Cl 0 ΓΎ ILn<J h3c	180
1049	Coloriess Oil	H3C-qH3C Cl o _ N >-N ρχ> h,c	180
1050	Light Yellow Oil	Fn ci o z—N+: N< CH, N À-N ÇrZ	180
1051	Coloriess Oil	çX >’	180
1052	Coloriess Oil	ZV-XC^f' F çX	180

434

1053	Pale Yellow Oil	ch3 Hjtr	156
1054	Light Yellow Oil	^br	106
1055	Pale Orange Oil		156
1056	Clear Really Viscous Oil	F. F PM JL·^ ° ^cHj ^bl·	83
1057	Clear/White Viscous Seml-Solid	F F o _XF CH3o X'/--- NX ^bl	84

435

1058	Clear Semi- Solîd	pH,o n'N cHj	106
1059	Light Yellow Gum	FF N CA?	89
1060	Yellow Viscous Oil	Λ /An ^CH3 ^br	106
1061	Clear Viscous Oil	n-N A7^ 'n Λ JL	83
1062	Orange Oil	j?*, M H3C	89

436

1063	Yellow Solid	cio °izYH’ K>NCH>	174
1064	Faint Yellow Oil	N<	174
Y2000	Colorless Solid	p Cl ^,νΧ-N CH, V H,C	100
« Y2001	White Solid	F F ,C1 Q b N=( >-( Ιί^γ-ΝΧ-Ν. CH, H,C	196
Y2002	Gummy White Solid	Cl 0 ÇQ	12

437

Y2003	White Solid	,CI °« °H ,/χ·Ν-/Α CHj M H3C	124
Y2004	Yellow Oil	n<>-oXch’	11
Y2005	Yellow Oil	n< \/ch3 çn? N ch3	31
Y2006	Yellow Oil	,CI° Br Çr '»	100
Y2007	Light Yellow Gum	,CI 0 V<nA^ci ρχΎ ψ HjC	100

438

Y2008	Light Yellow Oil	Ά H,C	125
Y2009	White Solid	Cl N=A —< Cr ch’ N	12
Y2010	Faint Yellow Solid	,ch3 Cl N N==\ ^ch3 N A~NH θ' N	175
Y2011	White Solid	H Cl N N«®( AcH3 Cr ch’ N	175
Y2012	Yellow Oil	CIO /—CH, n=< y-N qn>HCHj C»3 N	195

439

Y2013	Brown Solid	P cl (γΧχ	100
Y2014	Yellow Solid	ci o X1 y-/ (7 CHj N	12
Y2015	Light Yellow Solid	Cl o nX_ yS N z^~N Pr > V h3c	12
Y2016	Light Yellow Semi-Solid	ci o X y/	12
Y2017	Light Yellow Semi-Solid	Cl o nX_ ych3 h3c	12

440

Y2018	Light Yellow Oil	Cl 0 N=(_ CHj Q j	12
Y2019	Coloriess Oil	Cl 0 Q “	87
Y2021	Light Brown Oil	ci S’cs Ci fcHî N	198
Y2022	Yellow Oil	(A	42
Y2023	Yellow Oil	w v-o ΓγΝ ' V H>c	42

441

Y2024	Off-White Solid	CH3 1-jX HjC	42
Y2025	Yellow Oil	C! O - A CHa V h3c	42
Y2026	Off-White Semlsolid	en ·-> br	42
Y2027	Off-White Solid	xy>HCH3CH3 ^br	42
Y2028	Light Brown Semisolid	Cl 0 —Λ bT	42

442

Y2029	Yellow Oil	V1 H’c	11
Y2030	White Solid	,C1 o 3 )_ch3 N=\ >-S 3 ιΤγ A Ü-Z HjC	11
Y2031	White Solid	CIO ,-/¾ rA> V HjC	11
Y2032	White Solid	/cha 1 fAÀu ΎΎ H N	163
Y2033	Brown Solid	Cl 0 __/CH3 AiA^0 Cr CHî A	40

443

Y2034	White Solid	CHS ? N=( ^-N ? Cr H N	163
Y2035	Light Yellow Solid	CH, CHjS ? ûr bT	164
Y2036	White Solid	ci o vL N=C >—Τ·ρ Cr CH’ N	12
Y2037	White Solid	Cl Ο V Çr~Y	12
Y2038	Colorless Oil	ci O vL N A~N θ' <?	12

444

Y2039	White Solid	h3c ch, ci o J nX >-o^CH3 N Q ? N F \ F-V F	14
Y2040	White Solid	h3c CH, ci o J nX λ-ο^ CI’3 σ J F	14
Y2041	Light Brown Solid	Cl HN N Z/~NH θ' N	175
Y2042	White Solid	ci o ûr ch’ N	12
Y2043	Clear Oil	Cl o Ae (Y n N	12

445

Y2044	Yellow Oil	Cl o ch3 QN>NcHj N	12
Y2045	Clear Oil	Cl 0 CH, N=T λ-<ϊ ^bT	12
Y2046	Yellow Oil	,CI 0 UF n< hX (7 CHî br	12
Y2047	Clear Oil	Cl 0 L_F n< H Cr hj br	12
Y2048	White Solid	Cl ν'*™’ ΖχΛΧ/ ri Cr ch> N	45

446

Y2049	Yellow Oil	Cl n^C»3 Cr CHj N	177
Y2050	Yellow Solid	P’ CHj n4 y-/ 3 _ N fV > V H3C	11
Y2051	White Solid	ci oH3<\Îch σ ? Λρ	14
Y2052	White Solid	,C1 o Çr Û γ.	87
Y2053	Salmon Colored Foam	Cl nX CHj aWt N	140

447

Y2054	White Foam	Cl nA ch3	140
Y2055	Light Yeliow Oil	- N P - fXf	14
Y2056	White Solid	Cl O Ατό CT '« ^bT	11
Y2057	Yeliow Oil	ci o Çrp	14
Y2058	Yeliow Oil	Cl o nX_ >-<j PjR ” Jo	14

448

Y2059	Yellow Oil	Cl O ιίΎ o CHj	14
Y2060	White Solid	Cl 0 Q <?-CHj N	14
Y2061	White Solid	Μ Ah,	14
Y2062	Falnt Orange Oil	ci oHjCvCH’ N< lo^CH, Cr v ch> N	31
Y2063	Faint Yellow Oil	CH0 H3CvCH’ N< %/CH’ T7 v CHj N	31

449

Y2064	White Semi Solid	Cl o Jk^H3 nX >_/Y^ch3 N'N f η >h3c Hac 3	11
Y2065	Yellow Seml Solid	ci θ >r	11
Y2066	Yellow Oil	ûr ch’ NT	11
Y2067	Clear Oil	CH3oH3Cv5H3 nX XoXcH> çrTyj	31
Y2068	Yellow Oii	z.. H3C Çl O	11

450

Y2069	White Solid	Cf «3C H,C 3 br	11
Y2070	Yellow Oil	H,C 01 0 L Ns\ Pr h3c chj	11
Y2071	Light Brown Gum	Cl 0 pÿW U H>c	42
Y2072	Brown Gum	Pr*^TMF M «3e	42
Y2073	White Seml- Solid	Cl θ z-S'CH3 ___ N ./ XX > X “-N*1 H,C	53

451

Y2074	Yellow Oil	fV CH3 kCH3	174
Y2075	Clear Oil	nZ W”3 ΓγΝ>Ν> Ύ h3c	11
Y2076	Clear Oil	7CI .CH3 na y-s 3 on—3 N H3C'	166
Y2077	White Solid	7C1 Q Cl h3c	100
Y2078	White Solid	CH30 N=\ XcHj 77 N	11

452

Y2079	Yellow Oil	n 0 Cl ο A H Ό fyN An u <ch3	174
Y2080	Yellow Oil	ch30 N=K /·—CH3 y	14
Y2081	Yellow Oil	_ O N< >-N 0 ’ fY CHj 3 N	174
Y2082	Yellow Oil	Cl O °ft CHj N< Κν££Η3 ΓΥ CH3<CH’ N	174
Y2083	Off-White Solid	ch3S n=\ yCH3	49

453

Y2084	White Solid	r> ° Cl O °Â< U Pns~ch’ <CH’	174
Y2085	White SemlSolld	x °xc,,! N=Y J-' N prN>N> J X H,C	53
Y2088	Yellow Solid	η θ Cl o °X' rvN^NbH3 <CH’	174
Y2089	Dark Yellow Oil	Cl 0 ^f/S'v'CI N< M~V CH3	174
Y2090	Brown Gum	X PrN^~ > H J H,C N	148

454

Y2091	Light Brown Gum	Cl ο N<_ M h’c	148
Y2092	White Solid	Cl nX ch3	141
Y2093	Light Brown Solid	Cl 0 PrN^” > ψ «ae	87
Y2094	Opaque, Waxy Solid	Cl 0 N=\ >-CH3 N Λ-Ν ÇrÛ	159
Y2097	Opaque, Viscous Oil	ch3	100

455

Y2098	Bright Yellow Solid	N Cl (yaxcH, ch3	159
Y2099	White Solid	Cl 0 Rnhi ipr > 0 V h3c	128
Y2102	Coloriess, Viscous Oil	\ ,N;=/CI O 0 0 c Vn \ X 'V' ch3 m	146
Y2104	Light Yellow Semi-Soiid	,C1 ° Y1 ί'Λ-'n—=N br	53
Y2105	Light Yellow Semi-Soiid	F V/-™’ il—N ΓΤ CHs br	53

456

Y2106	White Solid	M XCI ____ n (TV-nŒ JL W ™ h3cJ ch>	45
Y2107	Faint Yeliow Oil		42
Y2108	Yellow Oil	Cl 0 O N=C J-' ΓΎ > V H,C	42
Y2109	Yellow Oil	CH, o n<V=<CHj pyN^”> ü.n; h3c	42
Y2110	Yellow Oil	□o °>ycH3 ÇrO	42

457

Y2111	Yellow Oil		425
Y2112	Falnt Yellow Oil	çô 'Λ	42
Y2113	White Semi- Solid	xnp kbr	53
Y2114	White Solid	Ci ç. V’ n=V JK ν-ξν St	53
Y2115	Pale Orange Oil	/TA -N=<CI° Q-nXn-Vh’ ch3ch2	159

458

Y2116	White Foam	N=VCI 0 Η,Α CH3	53
Y2117	White Solid	XT CI _-x NaZ ο O N—=N o-Av», Η,Ρ CH’	53
Y2118	White Solid	p Vp NA A-' - N Çr~X	12
Y2119	Coloriess Oil	γτν^> h3c	12
Y2120	White Solid	N**\ P Q N j NA A^ N Λν Γτ > >ÎNJ H,C	12

459

Y2121	White Solid	P1 o N. ÇrX	12
Y2122	White Solid	nA Cl 0 ïr « N< VN*N N z/~N ΓΎ V h3c	12
Y2123	Colorless Oil	P 0 N pr Ύ H,C	12
Y2124	White Solid	Cl CH3 Ύ J 0 ch3	11
Y2125	Off White Solid	Cl ;h. Ή o \-cf3 N	11

460

Y2126	Off White Solid	l J n	11
Y2127	Yellow Solid	H3C“O H CH3 O-naYNXJ'ch3 N=/ xF 0 w Cl	11
Y2128	Off White Solid	br	11
Y2129	Ash White Solid	H’c>=\ H=<CI0 O'N'^'n-\ch’ H ch3	11
Y2130	Yellow Solid	H3C. N « H gF F	11

46!

Y2131	Dark Brown Solid	CH3 ci °Ach3 w Cl	79
Y2132	Off White Solid	Cl cl CHj P	79
Y2133	Brown Solid	Cl O CH, 7 >-N CH3 CHj J A	79
Y2134	Off White Solid	‘Au CH3	79
Y2135	Off White Solid	XI Cl N=\ .NA 0 h3c-o ch3ch3	79

462

Y2136	Brown Liquid	M Cl N=\ .N=< 0 H3C-t> CH3 F	79
Y2137	Brown Solid	N=\ O Ο'ν>ΑνΑγ€η3 h3c ch3ch3	79
Y2138	Brown solid	HjC xt Cl ZXA; CH3 F	79
Y2139	White Solid	Cl O A >~^SH .AA C J N	87
Y2140	Off White Solid	Cl Xî ° yN· CHj CH3 Br	79

463

Y2141	Off White Solid	Cl NT 0 >=N· /=N F CH3 Br	79
Y2142	White Solid	O-nAnÂ^ch2 H3cr	159
Y2143	Clear Hard Oil	ci o z=iCI PT > ch, Ύ H,C	12
Y2144	White Solid	NT Y' z-N NsZ o CH, W N 0 CH3	14
Y2145	Clear SemiSolid	R o 0 0 ryNANA^Nx n^7 j N CHs h3c^	146

464

Y2146	Clear Oll	H,^	150
Y2147	Viscous Clear Light Yellow Oil	XI C1 jr-X .N=f 0 ÇH, ΓΜ J II tek \=/ p	14
Y2148	Light Yellow Solid	XI Cl οΑθ OH	117
Y2149	Slightly Yellow Clear Oil	--x N^/C1 0 CH, ÇpJpAïh OyO CH,	14
Y2150	Clear Oil	F F QO	53

465

Y2151	Clear Viscous Oil	OH	107
Y2152	Off-White Solid	,__k N--/Cl o CH, ô	109
Y2153	Clear Light Yellow Oil	____ Nsa/01 O CH, Q-n,XnaoX™, F	14
Y2154	Clear Viscous Oil	''CH, ° F	114
Y2155	Light Brown Oil	Q-<Xna0^f f ^ch3	115

466

Y2156	Light Brown Oil		115
Y2157	Light Yellow Oil	qAW* L CH, CH, 3	115
Y2158	White Solid	^ch3	115
Y2159	Light Pink Viscous Oil	^ch3	115
Y2160	White Foamy Solid	kCH, F	115

467

Y2161	Light Yellow Oil	___ Nycl o CH, V F	14
Y2162	Clear Yellow Oil	N=^CI 0 CHj ψ F	14
Y2163	Clear Yellow Oil	,Ν=ζα0 ÇH3 Q-nAnAoÀch3 Cl	14
Y2164	Clear Oil	k CH, F CHj	115
Y2165	White Solid	Lch, f	115

468

Y2166	White Solid	Cl o X1 N=C Cr H N	129
Y2167	Yellow Solid	Cl O Cr u n	130
Y2168	Light Yellow Solid	CA&'· N	131
Y2169	Light Brown Solid	«X	14
Y2170	Light Yellow Clear Oil	kCH, F	115

469

Y2171	Light Yellow Oil	CrN> br	12
Y2172	White Solid	Cl 0 n^n NssÇ ûr ch> br	12
Y2173	Colorless Oil	CrN> fc”> br	12
Y2174	Colorless Oil	Qn> ch3 br	12
Y2175	Off-White Solid	η-*Λ U	45

470

Y2176	White Solid	j A h3Y	42
Y2177	Light Yellow Gum	A	193
Y2178	Pale Brown, Glassy Solid	M A W ^Αζγ H,CJ MN-N	142
Y2179	Light Yellow Oil	A	87
Y2180	Pale Yellow, Viscous Oil	M Cl 0 OO --- -r ό	149

471

Y2181	White Solid		42
Y2182	Clear Oil	CHf“^	42
Y2184	Light Yellow Solid	A î___	45
Y2185	Clear Oil	h3(T	120
Y2186	Off-White Solid	a \=/ H3cr	119

472

Y2187	Light Brown Soiid	_ NVC1 o kHj 0	112
Y2188	Brown Viscous Oil	Χη3 0	123
Y2189	White Soiid	z-x .¾° 0 0 O-VfaVi hZ Wh>	118
Y2190	Off-White Soiid	H 3 CT FZ^q^F	118
Y2191	White Solid	xr CI /-x Na/ OOF Ο-ΛλΑΑ-’ .p H A*, F	118

473

Y2192	White Solid	M >C1 Nsf 0 0 H 3 C Cl	118
Y2193	Slightly Yellow Solid	NI >Cl /--N Nssf 0 0 HjCr x^'^ch3	118
Y2194	White Solid	NT >C1 r-κ .N=Y OOF	118
Y2195	Tan Solid	N=iC1 0 ^%-N^-n-JI^0'-xxœCH3 HjC	173
Y2196	White Solid	Cl n SAy-”·^ Q A	12

474

Y2197	Yellow Oil	sX H,c	173
Y2198	Yellow Oil	jt « J<F C J h J CH1 N H3C	173
Y2199	Off White Solid	ly hjC	197
Y2200	White Solid	rN P o L? Cr c,b N	12
Y2201	White Solid	rN P o P N< V N /N ¢7	12

Table 2: Compound number and analytlcal data

475

Compound No.	MP (’C)	IR (cm’1)	MASS	HNMR	NMR
596	73-75		ESIMS m/z 312 [M+1]+	1H NMR (300 MHz, DMSO-de) δ 9.04 (d, J = 2.4 Hz, 1H), 8.60 (s, 1H), 8.49 (dd. J = 4.7, 1.4 Hz, 1 H), 8.17 (ddd, J =8.4, 2.7, 1.4 Hz, 1H), 7.52 (ddd, J = 8.4, 4.7, 0.6 Hz, 1 H), 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+H]*)	1H NMR (400 MHz, CDCh) δ 8.97 (d, J2.5 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).	’3C NMR (101 MHz, CDCh) 6 192.20, 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

598			ESIMS m/z 315 ([M+H]*)	Ή NMR (400 MHz, CDCI3) δ 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, 1 H), 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) δ 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 ([MSMe+H]*)	’H NMR (400 MHz, CDCI3) δ 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), 7.487.38 (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(6, 3H), 2.24 (s, 1H), 2.01 (S, 3H), 1.14 (d, J = 6.7 Hz, 3H).

477

600	89-90		ESIMS m/z 283 ([M+H]*)	’H NMR (400 MHz, CDCI3)5 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, 1 H), 7.43 (dd, J =8.3, 4.8 Hz, 1H), 4.43 (s, 1H), 2.60 (dt, J= 13.5, 6.8 Hz, 1 H), 2.29 (s, 3H), 2.23 (t, J =2.5 Hz, 1H), 1.08 (d, J = 6.7 Hz, 6H).	13C NMR (101 MHz, CDCI3) δ 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 ([ΜΗ]*)	H NMR (400 MHz, CDCI3)C8.73 (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

602			ESIMS m/z 347 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 1 H), 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,1 H), 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-H]*)	’H NMR (400 MHz, CDCIj) δ 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

604			ESIMS m/z 353 ([M]*)	’HNMR (400 MHz, CDCI3) δ 8.77 (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).	,3CNMR(101 MHz, CDCI3) δ 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]*)	’HNMR (400 MHz, CDCI3) δ 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

606			ESIMS m/z 276 ([M-tBuf)	’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), 8.057.92 (m, 1 H), 7.42 (dd, J = 8.3, 4.8 Hz, 1H), 4.36 (s, 2H), 2.29 (t, J = 2.4 Hz. 1 H), 1.46 (s. 9H).	uCNMR(101 MHz, CDCI3) δ 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]*)	’H NMR (400 MHz, CDCIj) δ 8.96 (d, J = 2.5 Hz, 1H), 8.64 (dd. J = 4.7,1.3 Hz, 1H). 8.12 (s, 1 H). 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).	UC NMR (101 MHz, CDCIj) δ 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

608			ESIMS m/z 349 ([M+Hf)	’H NMR (400 MHz, CDCI3)ô8.97 (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).	13CNMR(101 MHz, CDClj) δ 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+H]*)	’H NMR (400 MHz, CDCI3)ô8.97 (d, J2.5 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).	’3CNMR(101 MHz, CDCI3) 6170.10, 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

610	98-99		ESIMS m/z 303 ([M+H]*)	'H NMR (400 MHz, CDCI3)5 8.96 (d. J = 2.6 Hz, 1H), 8.63 (dd, J = 4.7,1.2 Hz, 1H), 8.09 (s, 1H), 8.06 (ddd, J = 8.3, 2.7,1.5 Hz, 1 H), 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).
611			ESIMS m/z 335 ([M+H]*)	’H NMR (400 MHz, CDCI3)5 8.97 (d, J = 2.5 Hz, 1 H), 8.668.60 (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), 2.302.24 (m. 1H), 2.09 (s, 3H), 1.46 (d, J =6.9 Hz, 3H).	,3C NMR (101 MHz, CDCI3) δ 171.30, 148.66, 140.71, 140.18, 135.71, 127.87, 126.35, 124.11, 122.12, 78.53, 72.92, 53.39, 37.97,16.42, 11.07.

483

612	65-68		ESIMS m/z 321 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.96 (S, 1H), 8.63 (d, J =4.2 Hz, 1H), 8.21 (s, 1H), 8.09 -8.00(m, 1H), 7.507.43 (m, 1H), 4.53 (br s, 2H), 3.12 (s, 2H), 2.28 (t, J= 2.5 Hz, 1H), 2.23 (s,3H).	13CNMR(101 MHz, CDCIj) δ 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]*)	’H NMR (400 MHz, CDCIj) δ 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

614		(IR thin film) 1671	ESIMS m/z 353 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J2.5 Hz, 1H), 8.64 (dd, J = 4.7,1.4 Hz, 1H), 8.12 (s, 1 H), 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 m/z 407 ([M+H]*)	’H NMR (400 MHz, CDCIa) δ 8.97 (d, J = 2.5 Hz, 1 H), 8.65 (dd, J = 4.7,1.2 Hz, 1H), 8.13 (s, 1 H), 8.07 (ddd, J = 8.3, 2.7,1.5 Hz, 1H), 7.48 (dd, J =8.3, 4.7 Hz, 1 H), 4.47 (s, 2H), 2.58-2.39 (m, 4H), 2.29 (t, J =2.5 Hz, 1H).

485

616		(IR thin film) 1662	ESIMS m/z 377 «M+H]*)	’H NMR (400 MHz, CDCI3) δ 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- 4.10 (m, 2H), 3.06 (ddd, J = 7.7, 6.2, 4.3 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).
617			ESIMS m/z 351 ([M+H]*)	’H NMR (400 MHz, CDCI3)Ô8.98 (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, 1H), 4.88 (br s, 1H), 4.14(brs, 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).	’3CNMR(101 MHz, CDO3) δ 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.

486

618			ESIMS m/z 367 ([M+H]*)	’H NMR (400 MHz, CDCh) δ 9.00 (s, 1H), 8.65 (s, 1H), 8.29 (s, 1H), 8.03 (d, J = 8.0 Hz, 1 H), 7.54-7.39 (m, 1H), 4.89 (d, J = 16.9 Hz, 1 H), 4.204.08 (m, 1H), 4.073.92 (m, 1H), 3.01 (s, 3H), 2.34-2.29 (m, 1H), 1.67 (d, J = 7.0 Hz, 3H).	13C NMR (101 MHz, CDCh) δ 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.
619		(thin film) 3080, 2978, 2930, 1660, 1584	ESIMS m/z 365 ([M+H]*)	ΊΗ NMR (400 MHz, CDCh) δ 8.95 (d, J = 2.8 Hz, 1H), 8.63 (dd, J = 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, 1 H), 0.600.34 (m, 2H), 0.240.09 (m, 2H)

487

620		(thin film) 3080, 2975, 2931, 1657, 1584	ESIMS m/z 351 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (dd, J = 2.7, 0.7 Hz,1H), 8.63 (dd, J =4.8,1.4 Hz, 1H), 8.08 (s, 1 H), 8.04 (ddd. J = 8.4, 2.8,1.5 Hz, 1H). 7.46 (ddd, J = 8.4.4.7, 0.8 Hz, 1 H), 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 =4.8,1.4 Hz, 2H)
621		(thin film) 3081, 2972, 2930, 2871, 1655, 1438	ESIMS m/z 365 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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), 2.582.41 (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

622		(thin film) 3420, 3080, 2975, 1660, 1584	ESIMS m/z 381 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 9.02 - 8.90 (m, 1H), 8.63 (dd, J = 4.8,1.4 Hz, 1 H), 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+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 1 H), 3.773.69 (m, 2H), 3.42 (t, J = 7.2 Hz, 2H), 3.172.91 (m, 2H), 2,72 (t, J = 7.1 Hz, 2H). 1.301.12 (m, 1H), 1.12 (m, 3H), 0.82-0.70 (m, 2H), 0.44 (dt, J =6.3, 4.9 Hz, 2H)

489

624

(thin film) 3082, 2974, 2933, 1655, 1584

ESIMS m/z 379 ([M+H]*)

’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.8 Hz, 1 H). 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, 1 H), 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

625

(thin film) 3091, 2974, 2933, 2875, 1655, 1584

ESIMS m/z 414 ([M+H]*)

’H NMR (400 MHz, CDCI3)ô8.96 (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, 1 H), 1.211.11 (m, 6H), 1.02 (ddq, J =16.7, 8.0, 3.9 Hz, 1H)

491

626	60-61	(thln film) 3092, 2975, 2931, 1659, 1584	ESIMS m/z 400 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 1 H), 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), 2.632.55 (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		(thln film) 3448, 3092, 2976, 2933, 1659, 1585, 1440, 1012	ESIMS m/z 417 ([M+H]*)	’HNMR (400 MHz, CDCh) δ 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

628		(thln film) 3104, 2980, 2934, 1662, 1486, 1460	ESIMS m/z 433 ([M+H]*)	’H NMR (400 MHz, CDCIa) δ 9.00 - 8.90 (m, 1H), 8.64 (dd, J = 4.7,1.4 Hz, 1H), 8.098.00 (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), 3.113.00 (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]*)	’H NMR (400 MHz, CDClj) δ 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

630		(thin film) 3439, 2992, 1662, 1584, 1013	ESIMS m/z 403 ([M+H]*), 401 ([M-H]’)	^NMR (400 MHz, CDCIj) δ 8.96 (d, J = 2.7 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1H), 8.07 (d, J =1.8 Hz, 1H), 8.03 (ddd, J =8.3, 2.7,1.4 Hz, 1 H), 7.46 (ddd, J =8.3, 4.8, 0.7 Hz, 1H), 3.30 (s, 3H), 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)
631		(thin film) 3584, 3104, 2929, 1662, 1584	ESIMS m/z 419 ([M+H]*). 417 ([M-H]')	’H NMR (400 MHz, CDCIj) δ 8.96 (d, J = 2.6 Hz, 1 H), 8.64 (dd, J = 4.8,1.5 Hz, 1H), 8.04 (m, 2H), 7.47 (ddd, J =8.3, 4.8,0.8 Hz, 1H), 3.43 (t,J = 6.9 Hz, 2H), 3.37- 3.28 (m, 1H), 3.27 (s, 3H), 3.13-3.00 (m, 1 H), 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

632		(thin film) 3089, 3005, 2923, 1660 1584	ESIMS m/z 427 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (d, J = 2.6 Hz, 1 H), 8.63 (dd, J = 4.8,1.5 Hz, 1H), 8.05 (ddd, J =8.3, 2.7, 1.5 Hz, 1 H), 7.99 (s, 1 H), 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)
633		(thin film) 3298, 3097, 2923, 1668, 1584	ESIMS m/z 411 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 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 Hz, 1H), 7.47 (dd, J = 8.4, 4.8 Hz, 1H), 4.47 (s, 2H), 2.88 (t. J =7.2 Hz, 2H), 2.61 (ddd. J = 6.6, 5.1,2.3 Hz, 2H), 2.51 (t, J = 7.3 Hz. 2H), 2.27 (t, J =2.5 Hz, 1H), 1.83-1.67 (m, 1 H), 1.54-1.40 (m, 1H), 1.05(dtd, J = 13.3,7.7, 3.7 Hz, 1H)

495

634		(thin film) 3097, 2978, 2937 1664, 1440	ESIMS m/z 469 ([M+Hf)	’H NMR (400 MHz, CDClj) δ 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, 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, 1 H), 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]*)	’H NMR (400 MHz, CDClj) δ 8.97 (d, J = 2.6 Hz, 1H), 8.70- 8.52 (m, 1H), 8.087.99 (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

636			ESIMS m/z 393 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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 ([M+H]*)	’H NMR (400 MHz, CDCI3)Ô8.95 (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 ([M+H]*)	’HNMR(400 MHz, CDCI3)Ô8.96 (d, J = 2.7 Hz, 1 H), 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

639		(KBr) 1657	ESIMS m/z 407 ([M+H]*)	'H NMR (400 MHz, CDCIj) δ 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, 1 H), 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] *)	’H NMR (400 MHz, CDCIj) δ 8.97 (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

641		(KBr) 1656	ESIMS m/z 357 ([M+H] *)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J- 2.8 Hz, 1H),8.63(dd, J = 4.7,1.4 Hz, 1H), 8.11 (s, 1 H), 8.04 (ddd, J =8.3, 2.7,1.5 Hz, 1 H), 7.46 (dd, J =8.4, 4.7 Hz, 1H), 4.48 (dt, J = 47.1,6.4 Hz, 2H), 3.84 (br. s, 1 H), 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] +)	’HNMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.6 Hz, 1H), 8.64 (dd.J = 4.8,1.4 Hz, 1H), 8.11 (s, 1 H), 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 (m, 1H), 3.37- 3.13 (m. 5H), 1.48 (d, J = 6.9 Hz, 3H)

499

643		(thin film) 1657	ESIMS m/z 359 ([M+2H]*),	’H NMR (400 MHz, CDCI3)5 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 = 8.3,4.8 Hz, 1H), 4.53 (dt, J = 47.1,6.4 Hz, 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, 1 H), 2.46 (t, J =7.3 Hz, 2H), 1.17 (t, J =7.2 Hz, 3H)
644		(KBr) 1652, 1322, 1141	ESIMS m/z 425 ([M+H]*)	’H NMR (400 MHz, CDCI3)6 8.99 (d, J = 2.7 Hz, 1H), 8.71- 8.59 (m, 1H), 8.18 (s, 1H), 8.06 - 7.94 (m, 1H), 7.46 (dd, J = 8.4, 4.7 Hz, 1H), 4.25 (dq, J = 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

645

(KBr) 1653, 1079

ESIMS m/z 409 ([M+H] *)

’H NMR (400 MHz, CDCI3) δ 8.99 (d, J = 2.5 Hz, 1H), 8.66 (dd, J = 4.8,1.4 Hz, 0.55H), 8.62 (dd, 7 = 4.8,1.4 Hz, 0.45H), 8.17 (S, 0.45H), 8.11 (s, 0.55H), 8.05 (ddd, 7 = 8.3, 2.9,1.5 Hz, 0.55H), 7.99 (ddd, 7 = 8.4, 2.8, 1.5 Hz, 0.45H), 7.48 (dd, 7 = 8.4, 4.7 Hz, 0.55H), 7.44 (dd, 7 =8.4,4.8 Hz, 0.45H), 4.25 (br. s, 0.45H), 4.07 (q, 7=6.7 Hz, 0.55H), 4.02 - 3.75 (m. 1.45H), 3.75-3.33 (m, 2H), 3.18 (dq, 7 = 14.4,10.1 Hz, 0.55H), 1.54 (d, 7=6.8 Hz, 3H), 1.20 (dt, 7=14.2, 7.2 Hz, 3H)

501

646	111.Ο- 113.5		ESIMS m/z 366 ([M+H]*)	’HTlMR (400 MHz, CDCIj) δ 8.97 (d, J = 2.6 Hz, 1Η), 8.64 (d, J = 4.9 Hz, 1H), 8.56 (dd, J = 4.7,1.4 Hz, 1H), 7.99 (ddd, J =8.4, 2.7, 1.4 Hz, 1 H), 7.56 (s, 1H), 7.41 (ddd, J = 8.3, 4.8, 0.6 Hz, 1 H), 3.22 (ddd, J =14.0, 8.9, 0.6 Hz, 1H), 3.04 (dd, J =14.1, 5.5 Hz, 1H), 2.98-2.75 (m, 1H), 1.40 (d, J =6.9 Hz, 3H)
647		(thin film) 1659	ESIMS m/z 380 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.94 (d, J = 2.6 Hz, 1H), 8.63 (dd.J = 4.7, 1.3 Hz, 1H), 8.06 - 7.98 (m, 2H), 7.47 (dd, J = 8.3, 4.8 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

648		(thin film) 1657	ESIMS m/z 394 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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+2HD 403.7([M- H])	’H NMR (400 MHz, CDCIj) δ 8.94 (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, 1 H), 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	ESIMS m/z 406 ([M+2HD	’H NMR’(4Ô0 MHz, CDCIj) δ 8.95 (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

651		(thin film) 3081, 2972, 2930, 1655, 1584, 1485, 802	ESIMS m/z 417.1 ([M+H]*)	’H NMR (400 MHz, CDCh) δ 8.98 (d, J- 2.6 Hz, 1H), 8.63 (dd, J = 4.7, 1.5 Hz, 1H), 8.11 (s, 1H), 8.05 (ddd, J =8.3, 2.7, 1.5 Hz, 1H), 7.47 (ddd, J =8.3, 4.8, 0.8 Hz, 1H), 6.02 (s, 1H), 3.79 (d, J14.1 Hz, 2H), 3.50 (bs, 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)
652			ESIMS m/z 407 ([M+H] +)	’H NMR (400 MHz, CDClj) δ 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, 1H),7.47(dd, J = 8.3, 4.8 Hz, 1H), 3.79 (d, J = 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

653		(thin film) 1659	ESIMS m/z 409 ([M+2HD	’H NMR (400 MHz, CDCI3)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), 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+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (m, 1H), 8.64 (dd, J= 4.7,1.4 Hz, 1H), 8.13 (S, 0.4H), 8.04 (m, 1.6H), 7.547.41 (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, 1H), 3.72 - 3.47 (m, 1H), 3.473.20 (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

655	(thin film) 3432, 2969, 2932, 1659	ESIMS m/z 369 ((M+H]*)	’H NMR (DMSO-de) δ 9.04 (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, 1 H), 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 D	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 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), 1.221.10 (m,6H)

506

657	(thïn film) 2977, 2935, 1662,1583.	ESIMS m/z 385 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 9.01 (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), 3.423.35 (m, 1H), 3.27 (s, 3H), 3.14-3.04 (m, 1H), 2.782.71 (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]*)	’H NMR (400 MHz, CDCI3) 5 9.01 (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, 1 H), 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(1, J =6.8 Hz, 2H), 1.16 (t, J =7.2 Hz, 3H)	”CNMR(101 MHz, CDCI3) 5 171.17 (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

659		ESIMS m/z 355 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 10.11 (s, 1 H), 8.91 (d, J = 1.8 Hz, 1H), 8.58 (d, J = 2.4 Hz, 1 H), 8.24 (s, 1 H), 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)
660	(thin film) 2932, 1697, 1657,1600	ESIMS m/z 369 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 10.13 (d, J=0.7 Hz, 1H), 8.93 (d, J= 1.9 Hz, 1H), 8.57 (d, J =2.5 Hz, 1H), 8.36 (s, 1H),7.95(dt, J = 8.9, 2.3 Hz, 1H), 3.83 (dd, 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=7.0Hz, 3H)
661	(IR thin film) 1658	ESIMS m/z 367 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J =2.5 Hz, 1H), 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, 1 H), ,3.95 -3.71 (bs, 1H), 3.31-3.10 (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

662	(thin film) 1657	ESIMS m/z 339 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 9.04-8.90 (m, 1H), 8.64 (d, J=4.1 Hz, 1H), 8.128.00 (m, 1H), 7.92 (s, 1H), 7.51-7.41 (m, 1H), 5.04 (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)
663	(thin film) 1652	ESIMS m/z 353 ([M+H]*)	1H NMR (400 MHz, CDCIj) δ 8.97 (d, J =2.4 Hz, 1H), 8.66-8.55 (m, 1H), 8.087.99 (m, 1H), 7.99-7.90 (s, 0.7H), 7.88 (s, 0.3H), 7.50-7.39 (m, 1H). 5.154.94 (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)
664	(thin film) 1664	ESIMS m/z 387 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (d, J = 2.5 Hz, 1H), 8.67-8.61 (m, 1H). 8.088.01 (m, 1H), 8.00 (s, 1H), 7.50-7.42 (m, 1H). 4.39 (d, J =14.2 Hz, 1H), 3.18 (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

665	(thin film) 1667	ESIMS m/z 401 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 8.96 (d, J =2.8 Hz. 1H). 8.64 (d, J =4.3 Hz, 1H), 8.12- 7.95 (m, 2H), 7.51 - 7.40 (m. 1H), 4.40 (bs, 1H), 3.16-2.91 (bs, 1H), 2.91 -2.59 (m, 2H), 2.562.37 (m, 1H), 2.03 (s, 2H), 2.01 (s, 1H), 1.55-1.44 (m, 1H). 1.29-1.06 (m, 5H).
666	(thin film) 1665	ESIMS m/z 447 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.96 (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 (m. 1H), 3.94-3.62 (m, 3H), 3.45-3.28 (m, 1H), 2.69-2.55 (m, 1H), 2.482.34 (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

667	(thin film) 1638,	ESIMS m/z 382 ([M+H]*)	’HNMR (400 MHz, CDCIj) 6 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, 1 H), 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, 1 H), 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]*)	’H NMR (400 MHz, CDCIj)” δ 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, 1 H), 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

669	(thin film) 1650	ESIMS m/z 340 ([M+H]* )	’H NMR (400 MHz, CDCIj) 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), 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]*)	’H NMR (400 MHz, CDCIj) 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]*)	’H NMR (400 MHz, CDCIj) 6 8.68 - 8.52 (m, 2H), 7.76 (d, J =8.0 Hz, 1 H), 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

672	(thin film) 3058,1636, 1568	ESIMS m/z 371 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.96 - 8.92 (m, 0.6H), 8.90 (d, J = 2.6 Hz, 0.4H), 8.67-8.60 (m, 1H), 8.068.04 (m, 0.4H), 8.02 (d,7 = 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, 7=10.1 Hz, 0.4H), 5.93 (d, 7= 10.0 Hz, 0.6H), 5.74 (d, 7=14.8 Hz, 0.6H), 5.65 (d, 7=15.0 Hz, 0.4H), 3.34 (s, 1.8H), 3.27 (s, 1.2H)
673	(thin film) 3057, 2973, 2932,1708	ESIMS m/z 401 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.87 (d, 7 = 2.6 Hz, 1H), 8.60 (d, 7=4.8 Hz, 1H), 8.52-8.44 (m, 1H), 8.007.91 (m, 1H), 7.34 (s, 1H), 7.17-7.08 (m, 5H), 3.283.16 (m,1H), 3.16-3.06 (m. 2H), 2.95 (dd, 7= 13.8, 5.0 Hz, 1H), 2.85 (m, 1H), 1.22 (d, 7 = 6.7 Hz, 3H), 1.18-1.10(m, 3H)
674	(thin film) 3058,2974, 1632,1567	ESIMS m/z 385 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (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, 7 = 9.9 Hz, 0.7H), 5.65 (d, 7 = 15.0 Hz, 0.3H), 3.81 (m, 1.4H), 3.73 (m, 0.6H), 1.23 (t,7 = 7.1 Hz, 2.1 H), 1.181.13 (m, 0.9H)

513

675	(thin film) 3057, 2960, 1663	ESIMS m/z 339 ([M+H]*)	’HNMR(400MHz, CDCI3) 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 m/z 404 ([M+H]*)	’HNMR(400 MHz, CDCI3) 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 m/z 373 ([M+H]*)	’HNMR (400 MHz, CDCI3) 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, IH). 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

678		ESIMS m/z 540 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.91 (d, J = 2.7 Hz, 1H), 8.67-8.61 (m, 1H), 8.067.96 (m, 1 H), 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)
679	(thin film) 1658	ESIMS m/z 354 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 8.02 (s, 1H), 7.47 (ddd, J =8.3, 4.8,0.4 Hz, 1 H), 3.26 (s, 3H). 3.15-3.06 (m, 1 H). 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)
680	(thin film) 1584	ESIMS m/z 368 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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. 1 H), 7.49 - 7.43 (m, 1H), 3.73 (qd, J =13.5, 6.7 Hz, 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

681	(thin film) 1657	ESIMS m/z 394 ([M+H]*)	’H NMR (400 MHz, CDClj) 5 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, 1 H), 8.02 (s, 1H), 7.47 (ddd, J =8.3, 4.8, 0.5 Hz, 1 H), 3.56 (s, 2H), 3.19-3.06 (m, 1H). 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)
682	(thin film) 1659	ESIMS m/z 352 ([M+H]*)	’H NMR (400 MHz, CDClj) 5 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 (s, 3H), 2.68 - 2.43 (m, 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, 1 H), 0.28 (dt, J =14.5,4.8 Hz, 1H)

516

683	(thin film) 1656	ESIMS m/z 366 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (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), 8.00 (s, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.863.63 (m, 2H), 2.64-2.43 (m,3H), 2.13 (S, 3H), 1,18 (t, J =7.2 Hz, 3H), 0.91 0.72 (m, 1 H), 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)
684	(thin film) 1656,	ESIMS m/z 392 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 2H), 2.61 - 2.47 (m, 3H), 2.13 (s, 3H), 0.99 (tt, 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), 0.560.44 (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

685		ESIMS m/z 353 ([M+H]*)	’H NMR (400 MHz, CDCI3) 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), 4.334.21 (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]*)	’H 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, 1 H), 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), 0.690.57 (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

687	(thin film) 1667	ESIMS m/z 396 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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), 4.344.17 (m, 1 H), 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+H]*)	’H NMR (400 MHz, CDCI3) δ 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

689	(thin film) 1657	ESIMS m/z 382 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 1 H), 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), 3.233.04 (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 m/z 408 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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

691		ESIMS m/z 477 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.87 (d, J =2.6 Hz, 1H), 8.63-8.57 (m, 1H>, 8.498.42 (m, 1H), 8.02-7.95 (m, 1H), 7.91 (s, 1H), 7.65 (d, J =2.0 Hz, 1H), 7.487.40 (m, 1H), 3.53-3.46 (m, 2H), 3.27 (s, 3H), 2.69 -2.60(m, 2H)
692		ESIMS m/z 353 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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), 2.482.41 (m, 2H), 2.28 (s, 3H), 1.21 -1.10 (m, 3H)
693	(thîn film) 3057, 2967, 1661	ESIMS m/z 491 ([M+H]*)	’H 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, 1 H), 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

694		ESIMS m/z 339 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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&363 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.89 (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, 1 H), 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

697		ESIMS m/z 325 ([M+H]*)	’H NMR (300 MHz, CDClj) δ 8.84 (d, J = 2.6 Hz, 1H), 8.48 (dd, J =4.7,1.1 Hz, 1H), 8.12 (s, 1 H), 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+H]*)	’H NMR (400 MHz, CDClj) δ 8.95 (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), 2.192.11 (m, 3H), 1.93 (s, 3H), 1.93 -1.86 (m. 1H)
699	(thin film) 1658	ESIMS m/z 366 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 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

700	(thin film) 1658,	ESIMS m/z 340 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (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, 1H), 7.46 (ddd, J = 8.3, 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)
701	(thîn film) 1658	ESIMS m/z392 ([M+H]*)	’H NMR (400 MHz, CDCIj)’ δ 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), 8.02 (s, 1H), 7.46 (dd, J =8.4, 4.7 Hz, 1H), 3.55 (s, 2H), 2.62 (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

702	(thin film) 1655,1584.	ESIMS m/z 341 ([M+H]*’	’H NMR (400 MHz, CDCI3) δ 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), 4.01 (brs, 0.5H), 3.80 (dd, J = 11.3, 3.1 Hz, 0.5H), 3.33 (d, J =12.4 Hz, 3H). 2.66 (S, 1.5H), 2.55 (s, I. 5H) 2.06 (ddd, J =13.0, II. 3, 7.2 Hz, 0.5H), 1.84 (brs, 0.5H), 1.73(brs, 0.5H), 1.51 (brs, 0.5H), 1.01 (td, J = 7.3, 3.9 Hz, 3H)
703	(thin film) 1659,1585.	ESIMS m/z 357 ([M+H]*’	’H NMR (400 MHz, CDCI3) δ 8.98 (d, J =2.5 Hz, 1H), 8.66-8.60 (m, 1H), 8.28 (s, 1 H), 7.99 (ddd, J =8.3, 2.6,1.4 Hz, 1H), 7.45 (dd, J = 8.3, 4.8 Hz, 1H), 3.91 (dd, J =11.5, 3.1 Hz, 1H), 3.35 (s, 3H), 3.00 (s, 3H), 2.17 (td, */= 12.1,11.5, 7.2 Hz, 1H), 2.10-1.99 (m, 1H), 1.00 (t, J =7.4 Hz, 3H)

525

704	(thin film) 1655, 1585.	ESIMS m/z 339 ([M+H]*)	’H NMR (300 MHz, CDCI3) δ 8.93 (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 (brs, 1H), 3.51 (brs, 1H), 2.89(brs, 1H), 2.00 (s, 3H), 2.00- 1.84 (m, 1H), 1.60 (dq, J = 13.7,7.7, 7.3 Hz, 1 H), 1.16 -1.08 (m, 3H), 0.88 (t, J = 7.3 Hz, 3H)
705	(thin film) 1657, 1585.	ESIMS m/z 355 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.99 (d, J =5.4 Hz, 1H), 866-8.59 (m, 1H), 8.25 (brs, 0.5H), 8.17(brs, 0.5H), 8.06-7.97 (m, 1H), 7.45 (td, 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 (brs, 1H), 2.64 (S, 1.5H), 2.53 (s, 1.5H), 2.12-2.02 (m, 0.5H), 1.83 (brs, 0.5H), 1.69(brs, 0.5H), 1.46 (brs,0.5H), 1.22 - 1.17 (m, 3H), 1.02 (t, J = 7.3 Hz, 3H)
706		ESIMS m/z 297 ([M+H]*)	’HNMR (300 MHz, CDCI3) δ 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, 1 H), 7.68 (s, 1H), 7.37 (dd, */= 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

707	(thin film) 3093, 2958, 1661	ESIMS m/z 339 ([M+H]*), 337.4 ([M-H]’ )	’H NMR (400 MHz, CDCh) δ 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, 2.7, 1.4 Hz, 1H), 7.98 (s, IH), 7.46 (ddd, J = 8.3, 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 (t, J =7.5 Hz, 2H), 1.23 (d, J =6.7 Hz, 6H)
708	(thin film) 3088, 2958, 1661	ESIMS m/z 415 ([M+H]*)	’H NMR (400 MHz, CDCh) 5 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, 1 H), 7.82 (s, 1H), 7.47 (ddd. J =8.3, 4.7, 0.7 Hz, 1H). 7.327.20 (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

709	(thin film) 2967,1661	ESIMS m/z 339.66 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (dd, J = 2.7, 0.7 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1H), 8.07 (s, 1 H), 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 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.95 (d, J = 2.7 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1 H), 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 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.96 (dd, J = 2.7, 0.7 Hz, 1H), 8.62 (dd, J = 4.8,1.5 Hz, 1H), 8.14 (s, 1 H), 8.03 (ddd, J =8.3, 2.7,1.5 Hz, 1 H), 7.61 (ddd, J = 8.1, 7.5, 0.8 Hz, 1 H), 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

712	(thin film) 3391,2894, 2675, 2496, 1666	ESIMS m/z 386.5 ([M+H]*)	’HNMR (400 MHz, CDCIj) δ 9.00 (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, 1 H), 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, 3 H)
713	(thin film) 3101,2934, 1671	ESIMS m/z 415 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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+H]*)	’HNMR(400 MHz, CDCI3) δ 8.97 (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, 1 H), 3.30 (s, 3H), 3.19-3.08 (m, 4H), 2.59 (dd, J= 17.1, 3.6 Hz, 1H)

529

715	(thin film) 1658	ESIMS m/z 365 ([M+H]*)	1H NMR (400 MHz, CDCIj) 5 8.98 (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), 7.487.37 (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	ESIMS m/z 457.0 ([M+H]*), 455.5 ([Μ-ΗΓ )	’H NMR (400 MHz, CDCIj) δ 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+H]*)	'H NMR (400 MHz, CDCIj) 5 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

718	(thin film) 3091,2976, 1663	ESIMS m/z 476.9 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 1 H). 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 ([M+H]*)	’H NMR (400 MHz. CDCI3) 6 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

720	(thin film) 3087, 2969, 2927,1658	ESIMS m/z 401 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.88 (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, 1 H), 7.81 (bs, 1H), 7.45 (ddd, J = 8.4, 4.8, 0.8 Hz, 1H), 7.247.15 (m,5H), 4.20 (q, J = 7.1 Hz, 1H), 3.70 (bm, 2H), 2.93 (d, J =14.4 Hz, IH), 2.84 (d, J = 14.3 Hz, 1H), 1.56 (d, J =7.3 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H)
721	(thin film) 3068, 2969, 1655	ESIMS m/z 415 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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, 1 H), 7.30 (m, 3.45H), 7.20-7.10 (m, 1H), 7.03 (dd, J =8.3, 7.1 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

722	(thin film) 3091, 2976, 2932,1659	ESIMS m/z 456 ([M+H]*), 454.4 ([Μ-H]' )	’H NMR (400 MHz, CDCI3) δ 8.79 (d, 7 = 2.7 Hz, 1H), 8.58 (dd, 7 =4.7,1.4 Hz, 1H), 8.30 (S, 1H), 7.94 (ddd, 7 =8.3, 2.7,1.4 Hz, 1H), 7.57 (t, 7=7.8 Hz, 1H), 7.41 (ddd, 7 = 8.4, 4.7, 0.8 Hz, 1H), 7.31 (d, 7 = 8.1 Hz, 1H), 7.24 (s, 1 H), 4.79 (q, 7 = 7.0 Hz. 1H), 3.80 (m, 1H), 3.51 (m. 1H), 1.50 (d, 7 =7.1 Hz, 3H), 1.14 (t, 7=7.2 Hz, 3H)
723	(thin film) 3091,2976, 2933,1659	ESIMS m/z 489 ([Μ-H])	’H NMR (400 MHz, CDCI3) δ 8.67 (s, 1 H), 8.58 (dd, 7 = 4.8,1.4 Hz, 1H), 8.21 (s, 1H), 7.86 (s, 2H), 7.61 (d, 7 = 2.0 Hz, 1 H), 7.39 (dd, 7 = 8.4, 4.7 Hz, 1H), 4.87 (d, 7=6.9 Hz, 1H), 3.74 (s, 2H), 1.57 (d, 7 = 8Hz, 3H), 1.18 (t, 7 = 7.2 Hz, 3H)
724	(thin film) 1661	ESIMS m/z 369 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (bs, 1H), 8.63 (d, J = 4.3 Hz, 1H), 8.15 (s, 1H), 8.05 (ddd, 7 =8.3, 2.6,1.4 Hz, 1H), 7.46 (dd, 7=8.3, 4.7 Hz, 1H), 3.80 (bs, 1H), 3.60 (bs, 1H), 3.48 (t, 7 = 6.4 Hz, 2H), 3.41 - 3.30 (m, 1H), 3.29 (s, 3H), 2.78 (td. 7= 6.4, 1.2 Hz, 2H), 1.44 (d, 7 =7.1 Hz3H), 1.11 (t, 7= 7.2 Hz, 3H)

533

725		ESIMS m/z 350 ([M+2H]*)	’H NMR (400 MHz, CDCI3) δ 8.97(d, J = 2.6 Hz, 1H), 8.63 (dd. J = 4.7,1.3 Hz, 1H), 8.12 (s, 1H), 8.04 (ddd, J = 8.3, 2.7,1.5 Hz. 1 H), 7.46 (dd, J =8.3, 4.8 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)
726	(thin film) 1654	ESIMS m/z 365 ([M+2HD	’HNMR (400 MHz, CDClj) δ 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 (dd, J =8.3,4.7 Hz, 1H), 3.94-3.51 (m, 2H), 3.36 (bs, 1H), 2.97 (dt, J =13.3, 6.6 Hz. 1H), 2.84 (dt, J = 13.6, 6.9 Hz. 1H), 3.042.90 (m. 1H), 2.66-2.53 (m, 1H), 1.52 (d, J=7.1 Hz, 3H), 1.19 (t, J = 7.2 Hz, 3H)
727	(thin film) 1655	ESIMS m/z 354 ([Μ+2ΗΓ)	’HNMR(400MHz, CDClj) δ 8.96 (d, J = 2.2 Hz, 1H), 8.62 (d, J =4.6 Hz, 1H), 8.13 (s, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.46 (dd, J = 8.3, 4.8 Hz, 1H), 3.903.47 (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

728	(thin film) 1655	ESIMS m/z 385 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 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, 1 H), 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, 1 H), 2.88-2.79 (m, 2H), 2.67-2.58 (m, 2H), 2.10 (S, 3H), 1.491.45 (m, 3H), 1.17 (t, J = 7.2, 2.6 Hz, 3H)
729	(thin film) 1656	ESIMS m/z 381 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 8.96 (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

730	(thin film) 1658	ESIMS m/z 355 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.3 Hz, 1H), 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]*)	’H NMR (400 MHz, CDC!3) 5 8.96 (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	ESIMS m/z 340 ([M+2H]*)	’H NMR (400 MHz, CDCI3) 5 8.96 (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, 1 H), 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

733	(thin film) 1658	ESIMS m/z 397 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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 m/z 369 ([M+H]*)	’H NMR (400 MHz, CDCI3) 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 m/z 349 ([M+H]*)	’H NMR (400 MHz, CDCIj) 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

736	(thin film) 1657	ESIMS m/z 364 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 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 Hz, 1H), 3.73 (q, J =7.1 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)
737	(thin film) 1657	ESIMS m/z 353 ([M+H]*)	Ή NMR (400 MHz, CDCIj) 6 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 = 8.3, 4.8 Hz, 1H), 3.72 (q, J = 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)
738		ESIMS m/z 381 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.95 (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 = 8.4, 4.7 Hz, 1H), 3.71 (q, J = 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

739	(thin film) 1659	ESIMS m/z 410 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ9.00 (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, 1 H), 4.204.05 (m, 2H), 3.72 (dd, J = 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)
740	(thin film) 3065, 2973, 2931, 1656	ESIMS m/z 568 ([M+H]*)	’H NMR (400 MHz, CDCl'aT 6 8.89 (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, J =8.4, 4.7 Hz, 1H), 7.34- 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, 11.9, 5.2 Hz, 1H), 1.14 (t, J =7.1 Hz. 3H), 0.95 (d, J =6.8 Hz, 3H)
741	(thin film) 3392. 3090. 2974, 1654	ESIMS m/z 363 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 8.96 (t, J = 2.7 Hz, 1H), 8.71-8.56 (m, 1H), 8.17 7.94 (m. 2H), 7.52 - 7.38 (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

742	(thin film) 3091, 2971, 2926,1654	ESIMS m/z 423 ([M+H]*)	’HNMR (400 MHz, Chloroform-d) δ 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 (ddd, J = 8.2, 4.7, 0.8 Hz, 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)
743	(thin film) 1716	ESIMS m/z 469 ([M+H+1]*)	’H NMR (400 MHz, CDCI3) δ 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, 1H), 7.47 (ddd, J =8.4, 4.8, 0.6 Hz, 1H), 3.78- 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

744	(thin film) 1670	ESIMS m/z 476 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 7.48 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.893.66 (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)
745	(thin film) 1662	ESIMS m/z 422 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (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, 1 H), 7.47 (ddd, J =8.3, 4.8,0.5 Hz, 1H), 4.15- 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), 1.901.74 (m, 2H), 1.16 (d, J = 6.7 Hz, 3H)

541

746	(thin film) 1668	ESIMS m/z 440 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz, 1H), 8.64 (dd, J= 4.8,1.4 Hz, 1 H), 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]*)	’HNMR (400 MHz, CDCI3) 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, 1 H), 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

748	(thin film) 3091,2966, 2927,1659	ESIMS m/z 353 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 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, 1 H), 7.96 (s, 1H). 7.47 (ddd, J = 8.2, 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)
749	(thin film) 1659	ESIMS m/z 372 ([M+H]*)	’H NMR (400 MHz, CDCIj) 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, 1H), 7.51-7.43 (m, 1H), 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

750	(thin film) 1658,	ESIMS m/z 386 ([M+H]*)	’H NMR (400 MHz, CDCh) 0 8.96 (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, 1 H), 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		’H NMR (400 MHz, CDCh) δ 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, 1 H), 7.47 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 4.35-4.15 (m, 1 H), 3.29 (s, 3H), 3.01 (dd, J =17.2, 7.0 Hz, 1H), 2.75-2.56 (m, 4H)	”F NMR (376 MHz, CDCh) δ -63.15.

544

752	(thin film) 1663	ESIMS m/z 422 ([M+H]*)	’H NMR (400 MHz, CDClj) 0 8.96 (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), 3.873.61 (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)
753	(thin film) 3092, 2935, 1662	ESIMS m/z 443 ([M+H]*)	1H NMR (400 MHz, Chloroform-d) 0 8.90 - 8.81 (m, 1H), 8.65 (d, J =5.0 Hz, 1H), 8.61 (dd, J =4.7, 1.4 Hz, 1 H), 7.97 (ddd, J = 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)
754	(thin film) 3091,2934, 1661	ESIMS m/z 443 ([M+H]*)	’H NMR (400MHz, Chloroform-d) δ 8.93 (d, J = 1.1 Hz, 1H), 8.90 (dd, J = 2.7. 0.7 Hz, 1 H), 8.62 (dd, J = 4.8,1.4 Hz. 1H), 8.027.97 (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, 1 H), 3.52 (t, J = 6.9 Hz, 2H), 3.27 (s, 3H), 2.67 (t, J = 6.9 Hz, 2H)

545

755	(thin film) 1662	ESIMS m/z 408 ((M+Hf)	’H NMR (400 MHz, CDCh) δ 8.96 (s, 1 H), 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, 4.7 Hz, 1H), 4.05-3.43 (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)
756	(thin film) 1672	ESIMS m/z 490 ([M+Hf)	’H NMR (400 MHz, CDCh) δ 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 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), 1.691.62 (m,4H)
757	(thin film) 1661	ESIMS m/z 436 ([M+H]*)	1H NMR (400 MHz, CDCh) δ 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), 3.81 - 3.58 (m, 2H), 3.31 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

758	(thin film) 1660	ESIMS m/z 422 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.95 (d, J =2.6 Hz, 1H), 8.63 (dd, J =4.7,1.3 Hz, 1 H), 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+H]*)	’H NMR (400 MHz, CDCIj) 6 8.96 (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

760	(thin film) 3095,2920, 1659	ESIMS m/z 394 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.85 (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+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.85 (dd, J = 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	ESIMS m/z 436 ([M]*)	’H NMR (400 MHz, Chloroform-d) δ 8.83 (dd, J = 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, 1 H), 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

763	(thin film) 1656	ESIMS m/z 339 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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 m/z 338 ([M- Me]*)	’HNMR (400 MHz, Chloroform-d) δ 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, 1 H), 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+H]*)	’H NMR (400 MHz, CDCIj) δ 8.96 (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), 3.143.02 (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

766	(thin film) 3105,2971, 1657	ESIMS m/z 369 ([M+H]*)	’H NMR (400 MH^ CDCIj) 6 8.96 (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, 1 H), 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+H]*)	’H NMR (400 MHz, CDCIj) 6 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+H]*)	*H NMR (400 MHz, CDCIj) 6 8.97 (d, J = 2.6 Hz, 1H), 8.66 (dd, J =4.7,1.3 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7,1.4 Hz, 1 H), 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, 1H), 2.29 (s, 3H)

550

769	(thin film) 1657	ESIMS m/z 394 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.7,1.3 Hz, 1H), 8.15 (s, 1H), 8.03 (ddd, J =8.3, 2.7,1.5 Hz, 1H), 7.52-7.42 (m, 1H), 4.14-3.61 (m, 2H), 3.343.21 (m, 1H), 2.64-2.34 (m, 2H), 2.08 (s, 3H), 1.44 (d, J =6.9 Hz, 3H)
770	(thin film) 1666	ESIMS m/z 408 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.96 (d, J = 2.5 Hz, 1H), 8.65 (dd, J =4.7,1.2 Hz, 1H), 8.04 (ddd, J =8.3, 2.8,1.5 Hz, 2H), 7.47 (dd. J = 8.4, 4.7 Hz, 1H), 4.143.65 (m, 2H), 2.84 (dd, J = 12.7, 9.1 Hz. 1H), 2.772.64 (m, 1H), 2.64-2.39 (m, 3H), 2.02 (s, 3H), 1.16 (d, J = 6.7 Hz, 3H)
771	(thin film) 1661,	ESIMS m/z 388 ([M+H]*)	’HNMR (400 MHz, CDCI3) 5 8.89 (d, J = 2.5 Hz, 1H), 8.63 (dd, J =4.7,1.3 Hz, 1H), 8.03 (ddd, J = 8.3, 2.7,1.4 Hz, 1H), 7.47 (dd, 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

772	(thin film) 1659	ESIMS m/z 402 ([M+H]*)	’HNMR(400 MHz, CDClj) δ 8.89 (s, 1 H), 8.63 (dd, J = 4.7,1.2 Hz, 1H). 8.03 (ddd, J =8.3, 2.5,1.4 Hz, 1H), 7.47 (dd, J = 8.3, 4.8 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)
773	(thin film) 1659	ESIMS m/z 428 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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 7.26 (m, 6H), 4.33 (dd, J = 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).
774	(thin film) 1664	ESIMS m/z 408 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.96 (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, 1H), 7.48 (dd, J =8.4, 4.8 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

775	(thin film) 1661	ESIMS m/z 372 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.7 Hz, 1H), 8.63 (dd, 7=4.8,1.5 Hz, 1H), 8.05 (ddd, 7=8.3, 2.6,1.4 Hz, 1H), 7.98 (s, 1H). 7.47 (dd, 7 =8.4, 4.8 Hz, 1H), 4.54 (t. 7 =5.7 Hz, 1H), 4.42 (t, 7 =5.4 Hz, 1H), 3.79-3.61 (m, 2H), 2.79 (t, 7 = 7.3 Hz, 2H), 2.46 (t, 7 = 7.3 Hz, 2H), 2.07 (s, 3H), 1.831.74 (m, 1 H), 1.74-1.66 (m. 3H)
776	(thin film) 1662	ESIMS m/z 422 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.95 (d, 7 = 2.7 Hz, 1 H), 8.64 (dd,7 = 4.8,1.4 Hz, 1 H), 8.05 (ddd, 7 = 8.3, 2.7,1.5 Hz, 1H), 7.96 (s, 1H), 7.47 (dd, 7 = 8.3, 4.7 Hz, 1 H), 3.69 (t, 7 = 6.6 Hz, 2H), 2.79 (t, 7 = 7.3 Hz, 2H), 2.46 (t, 7 = 7.3 Hz, 2H), 2.13 (dtd, 7 = 10.8, 7.8, 3.9 Hz, 2H), 2.07 (s, 3H), 1.66-1.62 (m, 4H).

553

777	(thin film) 1660	ESIMS m/z 384([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.6 Hz, 1H), 8.62 (dd, J= 4.8,1.5 Hz, 1H), 8.16 (s, 1H), 8.11 - 7.98 (m, 1H), 7.45 (dd, J = 8.3,4.8 Hz, 1H), 3.37- 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)
778	(thin film) 1654	ESIMS m/z 384 ([M+H]*)	’HNMR (400 MHz, Chloroform-d) δ 9.02 - 8.91 (m, 1H), 8.63 (ddd, J = 8.3, 4.7,1.4 Hz, 1H>, 8.12 (s, 1 H), 8.09-7.98 (m, 1H), 7.45 (dt, J = 8.6, 4.4 Hz, 1H), 3.89-3.56 (m, 2H). 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

779		ESIMS m/z 367 ([M+H]*)	1H NMR (CDClj) δ 8.97 (d, J = 2.6 Hz. 1H). 8.63 (dd, J = 4.8, 1.5 Hz, 1H), 8.137.99 (m, 2H), 7.46 (dd, J = 8.3, 4.7 Hz, 1H), 4.14 (t, J = 7.3Hz. 1 H), 3,85(brs. 1H), 3.57 (brs, 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]*)	Tî NMR (4ÔÔ MHz? Chloroform-d) δ 8.94 (d, J = 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

781	(thin film) 1661	ESIMS m/z 470 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 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 ([M+H]*)	’HNMR (400 MHz, DMSO-de) δ 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, 1 H), 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

783	(thin film) 1654	ESIMS m/z 414 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.94 (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, 1 H), 7.92 (s, 1H), 7.45 (dd, J = 8.3, 4.7 Hz, 1H), 7.28-7.10 (m, 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)
784	(thin film) 1654	ESIMS m/z 378 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 9.00 (d, J =2.5 Hz, 1H), 8.63 (dd, J =4.7,1.3 Hz, 1H), 8.12 (s, 1H), 8.05 (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)
785	(thin film) 1656	ESIMS m/z 395 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.96 (d, J = 2.7 Hz, 1H). 8.65-8.54 (m, 1H), 8.107.94 (m, 2H), 7.46 (dd, J = 8.3, 4.8 Hz, 1H), 3.96- 3.46 (bd, J =95.1 Hz, 2H), 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

786	(thin film) 1727,1657	ESIMS m/z 425 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 9.01 (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, 1H). 7.43 (dd, J = 8.3, 4.8 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 4.00 - 3.42 (bd, 2H), 2.97-2.82 (m, 1H), 2.78-2.63 (m,3H), 2.622.43 (m, 3H), 1.25 (t, J = 7.1 Hz. 3H), 1.21-1.10 (m, 6H)
787	(thin film) 3091, 2973, 2929,1656, 1584, 1485, 1438,1250, 944	ESIMS m/z 337 ([M+H]*)	’H NMR (CDCI3) 5 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, 2.7,1.5 Hz, 1H), 7.46 (dd, J =8.4, 4.7 Hz, 1H), 6.44 (dd, J =16.8, 9.9 Hz, 1H), 5.29 (d, J =5.5 Hz, 1H), 5.26 (d, J =1.5 Hz, 1H), 3.83 (s. 1H), 3.60 (s, 1 H), 3.42 (q, J = 6.8 Hz, 1H), 1.51 (d, J = 6.8 Hz. 3H), 1.17 (t. J = 7.1 Hz. 3H)
788		ESIMS m/z 339 ([M+H]*)	’H NMR (CDCI3) 5 8.98 (dd, J =2.7,0.7 Hz, 1 H), 8.63 (dd, J =4.8,1.5 Hz, 1H), 8.16 (s, 1 H), 8.05 (ddd, J =8.3,2.7, 1.5 Hz, 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

			’H NMR (400 MHz, CDCIj)	nC NMR (101 MHz, CDCIj) 6 171.25, 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,
789		ESIMS m/z	2.7,1.5 Hz, 1H), 8.04 (ddd,	135.66,
	559 ([M+H]*)	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

790		ESIMS m/z 587 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 7 = 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), 2.842.65 (m, 4H), 2.57-2.38 (m, 3H), 1.16 (t, J = 7.1 Hz, 3H), 1.11 (d, J= 6.5 Hz, 3H)	’3C NMR (ÏÔ1 MHz, CDCI3) δ 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 m/z 389 ([M+H]*)	’H NMR (400 MHz, CDChf 6 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, <7=7.9,2.0 Hz, 1H), 7.48 (dd, <7 = 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, <7 = 15.8, 7.3 Hz, 2H), 1.92 (s, 3H)

560

792

(thin film) 1656

ESIMS m/z 403 ([M+H]*)

’H NMR (400 MHz, Chloroform-d) δ 8.97 (dd, J = 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 = 15.6 Hz, 1 H), 7.63 (dt, J = 7.9,2.0 Hz. 1H), 7.537.45 (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

793	(thin film) 1658	ESIMS m/z 429 ([M+H]*)	’H NMR (400 MHz. Chloroform-d) δ 8.96 (d, J = 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 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)
794	(thin film) 1662	ESIMS m/z 418 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.90 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1H), 8.02 (ddd, J =8.3, 2.7,1.5 Hz, 1H), 7.46 (dd, J = 8.4, 4.8 Hz, 1H), 7.21 (t, J =7.9 Hz, 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

795	(thin film) 1659	ESIMS m/z 432 ([M+H]*)	“’H NMR (4ÔÔ MHz? Chloroform-d) δ 8.90 (d, J = 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+H]*)	’H NMR (400 MHz, CDCI3) δ 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

797	(thin film)	ESIMS m/z 382 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 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]*)	’H NMR (400 MHz, Chloroform-d) δ 9.06 - 8.89 (m. 1H), 8.63 (dd, J = 4.8, 1.5 Hz, 1H), 8.07 (ddd, J = 8.3,2.7.1.4 Hz, 1 H), 7.99 (s, 1 H), 7.46 (ddd, J =8.3, 4.7, 0.8 Hz, 1H), 6.55 (bs, 1 H), 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

799	(thîn film) 1658	ESIMS m/z 380 ([M+2HD	’H NMR (400 MHz, CDCI3) 6 8.97 (d, J =2.6 Hz, 1H), 8.63 (dd, J= 4.7,1.4 Hz, 1H), 8.06 (ddd, J =8.3, 2.7,1.4 Hz, 1 H), 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	(thîn film) 1673	ESIMS m/z 372 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 8.96 (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, IH), 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	(thîn film) 1671	ESIMS m/z 358 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 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

802	(thin film) 1667	ESIMS m/z 398 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.95 (d, J = 2.5 Hz, 1H), 8.64 (dd, 7=4.8,1.4 Hz, 1H), 8.04 (m, 2H), 7.47 (dd, 7=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)
803		ESIMS m/z 397 ([M+H]*)	’H NMR (CDCI3) δ 8.96 (d, 7 = 2.7 Hz, 1H), 8.62 (dd,7 = 4.8,1.4 Hz, 1 H), 8.05 (s, 1H). 8.02 (ddd, 7 = 8.3, 2.7,1.5 Hz, 1H), 7.45 (dd, 7 = 8.4, 4.7 Hz, 1H), 4.44 (s, 2H), 3.57 (t, 7= 5.8 Hz, 2H), 3.26 (s, 3H), 3.00 (s, 3H), 2.63 (t, 7= 5.8 Hz, 2H)	UC NMR (CDCI3) δ 171.3,148.7, 140.2,139.9, 135.6.126.4, 124.9,124.1, 115.4, 67.1, 44.6, 37.5, 37.3, 37.1, 34.4.
804	(thin film) 1650	ESIMS m/z 356 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 9.04 (d, 7 = 2.7 Hz, 1 H), 8.60 (dd,7 = 4.8. 1.5 Hz, 1H), 8.24 (s, 1H), 8.02 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.41 (dd, 7 = 8.3, 4.7 Hz. 1H), 4.12 (s. 1H). 3.37 (s, 1H), 3.28 - 3.10 (m, 2H). 2.60 (s, 3H), 2.57 (d, 7 = 2.9 Hz, 1H) 1.22 (d, 7 = 6.6 Hz, 3H), 1.18 (t, 7 = 7.2 Hz, 3H).

566

805	(thin film) 1650	ESIMS m/z 356 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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]*)	’H NMR (400 MHz, CDCI3) 5 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, 1 H), 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)

567

807	(thin film) 1650	ESIMS m/z 356 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 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+H]*)	1H NMR (400 MHz, CDCI3) δ 9.00 (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 (tt, 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 ([M+H]*)	’H NMR (400 MHz. CDCI3) δ 9.00 (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 =8.1,4.8 Hz. 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

810		ESIMS m/z 469 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.99 (d, J = 2.3 Hz, 1H), 8.63 (d, J =4.6 Hz, 1H), 8.08 (s, 1H), 8.01 (m, IH), 7.44 (dd, J =8.3, 4.8 Hz, 1H), 4.75 (q, J = 7.1 Hz, IH), 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)	WF NMR (376 MHz, CDCIj) 6 -66.12 (s)
811		ESIMS m/z 487 ([M+H]*)	1H NMR (400 MHz, CDCIj) 6 9.02 (d, J = 2.2 Hz, 1 H). 8.62 (d, J =3.8 Hz, 1H), 8.18 (s, 1H), 8.04 (ddd, J = 8.3, 2.6,1.4 Hz, 1 H), 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)	”F NMR (376 MHz, CDCIj) 6 -106.12 (s)
812	(thin film) 1660	ESIMS m/z 389 ([M+H]*)	’HNMR (400 MHz, CDCIj) 6 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), 7.267.15 (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

813	(thin film) 1657	ESIMS m/z 403 ([M+H]*)	’H NMR (400 MHz, CDClj) 5 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]*)	’H NMR (400 MHz. CDClj) 5 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

815	(thin film) 3447, 3072, 2975, 2933. 1652,1485, 1439,1035	ESIMS m/z 341 ([M+H]*)	’H NMR (CDClj) δ 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), 4.183.91 (m, 1H), 3.87 (q, J = 6.8 Hz, 1 H), 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+H]*)	’H NMR (CDClj) δ 8.98 (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, 1 H), 7.45 (ddd, J = 8.3, 4.7,0.7 Hz, 1H), 4.05-3.91 (m. 2H), 3.603.47 (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+H]*)	’H NMR (400 MHz, Chloroform-d) δ 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, 1 H), 7.53 -7.42(m, 1H). 4.78 (pd. J = 9.0, 4.4 Hz. 1H), 3.903.54 (m, 2H), 2.76 (dd, J = 16.6,4.4 Hz. 1H), 2.53 (dd, J =16.6, 9.4 Hz, 1 H), 2.41 (s, 3H). 1.16 (t, J =7.2 Hz, 3H)

571

818		ESIMS m/z 375 ([M+H]*)	’H NMR (CDCI3) δ 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), 7.96 (s, 1H), 7.47 (dd, J =8.5, 4.7 Hz, 1H), 5.86 (tt, J =56.6, 4.4 Hz, 1H), 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)	19F NMR (CDCIj) δ 113.24
819		ESIMS m/z 351 ([M+H]*)	’HNMR (CDCIj) δ 8.96 (d, J = 2.8 Hz, 1H), 8.62 (dd, J = 4.7, 1.5 Hz, 1H), 8.11 (s, 1H), 8.04 (ddd, J = 8.3, 2.7,1.5 Hz, 1H), 7.46 (dd, J =8.4, 4.8 Hz, 1H), 5.80 (ddt, J= 16.9,10.1,6.6 Hz, 1H), 5.11 -4.99 (m, 2H), 3.84-3.59 (m, 2H), 3.12 (s, 2H), 2.74 (t, J = 7.4 Hz, 2H), 2.41 - 2.29 (m, 2H), 1.17 (t, J = 7.2 Hz, 3H)	13C NMR (CDCIj) δ 169.7.148.6, 140.6, 140.1, 136.4, 135.6, 127.3,126.3, 124.1, 123.4, 116.2,44.0, 33.5, 33.3, 31.8,13.0

572

820		ESIMS m/z 365 ([M+H]*)	’H NMR (CDCh) δ 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)	’3C NMR (CDCI3) δ 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 ([M+H]*)	’H NMR (CDCI3) δ 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), 3.843.61 (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)	’®F NMR (CDCI3) δ 128.02 (d, J = 156.7 Hz),142.82 (d, J = 156.6 Hz)

573

822		ESIMS m/z 371 ([M+Hf)	’H NMR (CDCIj) δ 8.96 (d, J = 2.6 Hz, 1 H), 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 (dt, J = 47.2, 5.7 Hz, 2H), 3.72 (q, J =7.2 Hz, 2H), 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)	’9F NMR (CDCIj) δ 16.20
823		ESIMS m/z 398 ([M+Hf)	’H NMR (CDCIj) δ 9.02 (d, J = 2.7 Hz, 1H), 8.62 (dd, J = 4.8,1.5 Hz, 1H), 8.12 8.03 (m, 2H), 7.45 (dd, J = 8.4, 4.7 Hz, 1H), 6.41 (dd, J =16.6, 9.9 Hz, 1H), 6.19 (d, J =16.6 Hz, 1H), 5.99 (d, J = 9.9 Hz. 1H), 3.72 (q, J = 7.2 Hz, 2H), 3.38 (t, J = 6.7 Hz, 2H), 2.82 (s. 3H), 2.51 (t, J = 6.7 Hz, 2H), 1.17 (t, J =7.2 Hz, 3H)	’3C NMR (CDCIj) δ 171.0,148.6, 140.5,140.4, 135.7,132.2, 128.0,127.2, 126.4.124.1, 123.5.47.1, 43.9, 36.3, 34.1,13.1

574

824		ESIMS m/z 401 ([M+H]*)	’H NMR (CDCIj) δ 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)	”F NMR (CDCIj) δ - 127.81, - 128.23
825		ESIMS m/z 367 ([M+H]*)	’H NMR (CDCIj) δ 9.00 (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)	13C NMR (CDCIj) δ 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 ([M+H]*)	’H NMR (CDCIj) δ 8.96 (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, J = 7.2 Hz, 3H)	19F NMR (CDCIj) δ 103.97 (dd, J = 85.8, 32.6 Hz), -122.37-124.03 (m), - 174.73-- 176.48 (m)

575

827		ESIMS m/z 587 ([M+H]*)	’H NMR (CDClj) δ 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, 1 H), 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)	13C NMR (CDClj) δ 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 ([M+H]*)	’HNMR (CDClj) δ 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 (CDClj) δ 66.96
829		ESIMS m/z 415 ([M+H]*)	’H NMR (CDClj) δ 8.96 (d, J = 2.7 Hz, 1H), 8.63 (dd, J = 4.8,1.4 Hz, 1 H), 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, 1 H), 3.70 (q, J =7.2 Hz, 2H), 2.652.50 (m, 4H). 2.28 (t, J = 6.9 Hz, 2H), 1.99-1.86 (m,2H), 1.83-1.65 (m, 1 H), 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)	19F NMR (CDClj) δ 128.06 (d, J = 157.2 Hz),142.88 (d. J = 156.8 Hz)

576

830			’HNMR(400 MHz, DMSO-d6): δ 9.93 (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]*)	’HNMR(400 MHz, MeOD~ ): δ 8.95 (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+H]*)	’HNMR (300 MHz, MeOD ):δ8.97 (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+H]*)	’H-NMR(400 MHz, MeOD): δ 8.74 (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, 1 H), 3.98 (s. 3H), 2.86 (t, J = 6.40 Hz. 2H), 2.76-2.80 (m, 2H),2.17(s, 1H).

577

834		ESIMS m/z 341 ([M+H]*)	’HNMR (400 MHz, MeOD) :5 8.72 (s, 1H), 8.57 (d, J = 1.84 Hz, 1H), 8.21 (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]*)	’H NMR (400 MHz, MeOD): δ 8.71 (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^325 ([M+H]*)	’H NMR (400 MHz, MeOD): δ 8.80 (d, J = 2.32 Hz, 1 H) 8.70 (d, J =0.56 Hz, 1H), 8.36 (s, 1H), 8.05 (d, J =0.64 Hz, 1H), 2.922.99 (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

837			’HNMR (400 MHz, MeOD ): δ 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)
838		ESIMS m/z 358([M]*)	’H NMR (400 MHz, MeOD ): δ 9.01 (d, J =2.28 Hz, 1H), 8.76 (s, 1H), 8.59 (d, J =2.00 Hz, 1H), 8.37 (d, J = 2.12 Hz, 1H), 3.25 (s, 3H), 2.75-2.86 (m, 2H), 2.42-2.46 (m, 1 H), 1.96 (s, 3H), 1.17 (d, J =6.48 Hz, 3H)
839		ESIMS m/z 342 ([M+H+1]*)	’H NMR (400 MHz, MeOD ): δ 8.70 (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)
840		ESIMS m/z 355 ([M+H]*)	’H NMR (400 MHz, MeOD ): δ 8.74 (s, 1H), 8.62 (d, J = 2.12 Hz, 1 H), 8.27 (d, J = 2.52 Hz, 1H), 7.83 (t, J = 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, 1 H), 1.95 (s, 3H), 1.16 (d, J =6.56 Hz, 3H)

579

841		ESIMS m/z 425 ([M+H]*)	’H NMR (CDCI3) 0 8.96 (d, J = 2.7 Hz, 1 H), 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 (ddd, J =8.3,4.7, 0.7 Hz, 1H), 5.93 (tt, J =53.6, 3.4 Hz, 1H), 3.72 (q, J =7.1 Hz, 2H), 3.04 (tt, 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)	’9F NMR (CDCI3) δ - 115.32,- 136.89
842		ESIMS m/z 553 ([M+H]*)	’H NMR (CDCh) δ 8.92 (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, 1 H). 7.79 (S, 1H). 7.46 (ddd, J = 8.3. 4.7,0.8 Hz, 1H), 7.40 - 7.34 (m, 6H), 7.25-7.19 (m, 6H). 7.197.12 (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

843		ESIMS m/z 525 ([M+H]*), 523 ([M-H]-)	’H NMR (400 MHz, Chloroform-d) δ 8.94 (dd, J = 2.7, 0.7 Hz, 1H), 8.58 (s, 1H). 8.54 (dd, J = 4.8, 1.5 Hz, 1 H). 7.96 (ddd. J = 8.4, 2.7,1.5 Hz. 1H). 7.51 7.44 (m, 6H), 7.38 (ddd, J = 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)
844	(IR	ESIMS m/z 373 ([M+H]*), 371 ([M-H]')	’H NMR (400 MHz, CDCIj) 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, 1 H). 7.48 (s, 1H), 7.40 (ddd, J =8.4, 4.8,0.7 Hz, 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

845		ESIMS m/z 421 ([M+H]*)	’H NMR (CDCI3) δ 8.96 (d, J =2.7 Hz, 1H), 8.63 (dd, J = 4.7,1.4 Hz, 1 H), 8.05 (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 (q, J = 7.2 Hz, 2H). 2.81 (t, 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)	’9F NMR (CDCI3) δ 66.03
846		ESIMS m/z 411 ([M+H]*)	’H NMR (CDCI3) δ 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 (ddd, J =8.4,4.8, 0.7 Hz, 1H), 5.77 (tt. J = 54.0, 3.2 Hz, 1H), 3.73 (q. J = 7.2 Hz, 2H), 3.16 (t, J =6.8 Hz, 2H), 2.57 (t, J = 6.8 Hz, 2H), 1.17 (t, J =7.2 Hz, 3H)	’9F NMR (CDCI3) δ 91.82 (t, J = 10.0 Hz),131.92 (t, J = 10.1 Hz)

582

847		ESIMS m/z 479 ([M+H]*)	Ή NMR (CDCI3) δ 8.97 (d. J =2.6 Hz, 1H), 8.63 (dd,7 = 4.8,1.5 Hz, 1 H), 8.06 (ddd, 7=8.3, 2.7,1.5 Hz, 1H), 7.99 (s, 1H), 7.47 (dd, 7=8.4, 4.7 Hz, 1H), 4.244.08 (m, 2H), 3.78 - 3.64 (m, 2H), 3.46 (dd, 7= 9.9, 4.1 Hz, 1H), 3.06-2.78 (m, 3H), 2.55 - 2.32 (m, 3H), 1.24 (t, 7 =7.1 Hz, 3H), 1.16 (t, 7 = 7.2 Hz, 3H)	’®F NMR (CDCI3) δ 65.29
848		ESIMS m/z 419 ([M+H]*)	’H NMR (CDCI3) δ 8.96 (d, 7 = 2.7 Hz, 1H), 8.64 (dd, J = 4.8,1.4 Hz, 1H), 8.05 (ddd, 7=8.3, 2.7,1.5 Hz, 1H), 7.95 (s, 1 H), 7.47 (dd, 7=8.4,4.7 Hz, 1 H), 5.85- 5.78 (m, 1 H), 5.66 (h. 7 = 1.4 Hz, 1H), 3.72 (q, 7 = 7.1 Hz, 2H). 3.27 (s, 2H), 2.79 (t, 7=7.3 Hz, 2H), 2.43 (t, 7 = 7.3 Hz, 2H), 1.17 (t, 7= 7.2 Hz, 3H)	”F NMR (CDCI3) δ 67.33
849		ESIMS m/z 457([M+H]*)	’H NMR (CDCI3) δ 8.96 (d, 7 = 2.7 Hz, 1H), 8.63 (dd,7 = 4.8, 1.5 Hz, 1H). 8.05 (ddd, 7= 8.4,2.7,1.5 Hz, 1H), 7.97 (s, 1H), 7.47 (dd, 7 = 8.6, 4.8 Hz, 1H), 3.72 (q, 7=7.2 Hz, 2H), 2.85 (t, 7=7.2 Hz, 2H), 2.75-2.65 (m, 2H), 2.45 (t, 7=7.2 Hz, 2H), 2.41 - 2.23 (m, 2H), 1.17 (t, 7=7.2 Hz, 3H)	’9F NMR (CDCI3) δ 85.35, -118.30

583

850		ESIMS m/z 443 ([M+H]*)	’H NMR (CDCI3) δ 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, 1 H), 7.96 (s, 1H), 7.47 (dd, J =8.4, 4.8 Hz, 1H), 3.72 (q, J =7.2 Hz, 2H), 3.12 (t, 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)	19F NMR (CDCI3) δ 84.46, -117.06
851	(thin film) 1655	ESIMS m/z 373 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.94 (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, 1 H), 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)
852	(thin film) 1653	ESIMS m/z 387 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 1H), 7.43 (ddd, J =8.3, 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

853	(thin film) 1656	ESIMS m/z 391 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.74 (d, 7=1.8 Hz, 1H), 8.43 (d, 7 = 2.5 Hz, 1H), 7.92 (s, 1H), 7.85 (dt, 7 = 9.3, 2.4 Hz, 1H), 3.23 (s, 3H), 2.84 (dd, 7= 8.9, 5.3 Hz, 2H), 2.71 - 2.60 (m, 2H), 2.43 (t, 7 = 7.1 Hz, 2H). 2.36 (ddd, 7= 10.5, 8.2, 5.8 Hz, 2H), 2.27 (s, 3H)
854	(thin film) 1653	ESIMS m/z 405 ([M+H]*),	’H NMR (400 MHz, CDCi3) δ 8.76 (d, 7=1.8 Hz, 1H), 8.43 (d, 7=2.5 Hz, 1H), 7.89 (s. 1 H), 7.86 (dt, 79.3,2.4 Hz, 1H), 3.68 (s, 2H). 2.83 (t, 7 = 7.1 Hz, 2H), 2.69 - 2.60 (m, 2H), 2.43-2.32 (m,4H), 2.27 (s. 3H), 1.15 (t, 7= 7.2 Hz, 3H)
855	(thin film) 1652	ESIMS m/z 381 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.2 Hz, 1H), 8.57 (dd, 7=4.7,1.4 Hz, 1H), 8.03 (ddd, 7 = 8.3, 2.7,1.4 Hz, 1H), 7.87 (s, 1 H), 7.43 (ddd, 7 =8.3, 4.8, 0.7 Hz, 1H), 3.69 (brs, 2H), 2.86 (t,7=7.2 Hz, 2H), 2.59 (tdd, 7=9.2, 4.7, 2.3 Hz, 2H), 2.41 (t,7=7.2 Hz, 2H), 2.27 (s, 3H), 1.83 -1.66 (m, 1 H), 1.56-1.38 (m. 1H). 1.15 (t, 7= 7.2 Hz, 3H), 1.03 (dtd, 7= 13.2, 7.7, 3.7 Hz, 1H)

585

F

856	(thin film) 1652	ESIMS m/z 399 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.75 (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+Hf)	’H NMR (400 MHz, CDCI3) 5 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, 1 H). 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, 1 H), 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)	19F NMR (376 MHz, CDCI3) 5 -73.92

586

858		ESIMS m/z 401 ([M+H]*)	’H NMR (CDCI3) δ 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, 1 H), 4.20 (dtd, J =25.3, 7.8,2.3 Hz, 1H), 3.72 (q, J = 7.2 Hz, 2H), 2.82 (t, J = 7.3 Hz, 2H), 2.53 (t, J = 7.2 Hz, 2H), 2.43 (t, J = 7.4 Hz, 2H), 2.31 -2.18 (m,2H), 1.17 (t, J = 7.2 Hz, 3H)	19F NMR (CDCI3) δ 87.96, -89.97
859		ESIMS m/z 427 ([M+H]*)	’H NMR(CDCh) δ 8.96 (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, 1H), 7.47 (ddd, J = 8.3, 4.7, 0.7 Hz, 1H), 5.34 (q, J = 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)	19F NMR (CDCI3) δ 72.34
860	(thin film) 1661	ESIMS m/z 393 ([M+H]*)	’H NMR (400 MHz, CDChT δ 8.94 (d, J =2.5 Hz, 1H), 8.63 (dd, J =4.7,1.4 Hz, 1H), 8.12-7.92 (m, 2H), 7.47 (ddd, J = 8.3,4.8, 0.6 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

861	(thin film) 1660	ESIMS m/z 423 ([M+H]*)	’HNMR (400 MHz, CDClj) 5 8.96 (d, J = 2.4 Hz, 1H), 8.64 (dd, J = 4.7,1.4 Hz, 1H), 8.07-8.00 (m,2H), 7.46 (ddd, J = 8.3, 4.8,0.7 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)
862	(thin film) 1661	ESIMS m/z 439 ([M+H]*)	’H NMR (400 MHz, CDClj) 5 8.97 (d, J = 2.5 Hz, 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), 3.73 (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)
863	(thin film) 1655	ESIMS m/z 367 ([M+H]*),	’HNMR (400 MHz, CDClj) 5 8.94 (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, 1 H), 7.90 (s, 1 H), 7.43 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.27- 3.21 (m, 3H), 2.86 (t, J = 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

864	(thin film) 1655	ESIMS m/z 385 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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+H]*)	’H NMR (400 MHz, CDCIj) δ 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]*)	’H NMR (400 MHz, CDCIj) δ 9.02 (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

867	(thin film) 3092, 2976, 2934, 1657	ESIMS m/z 544 ([M+H]*)	’H NMR (400 MHz, CDCIj) 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, 1 H), 7.98 (s, 1H), 7.46 (ddd, J = 8.3, 4.8, 0.8 Hz, 1 H), 5.92 (tt, J = 55.6, 3.9 Hz, 1H), 3.863.58 (m, 5H), 3.51 (dd, J = 14.5,6.4 Hz, 1H), 3.08 (dd, 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, 1 H), 1.45 (t, J = 7.7 Hz, 1H), 1.29-1.20 (m, 1H), 1.16 (t, J =7.2 Hz, 3H)	19F NMR (376 MHz, CDCIj) 6 -121.40 (d, J = 13.4 Hz)
868	(thin film) 3091, 2921, 1661	ESIMS m/z 388 ([M+H+1]*)	’H NMR (400 MHz, CDCIj): 6 8.87 (s, 1H), 8.69 (s, 1 H), 8.28 (s, 1H), 8.03 (s, 1H), 3.26 (s, 3H), 2.81 (t, J = 7.20 Hz, 2H), 2.48 (t, J = 7.36 Hz, 2H), 2.09 (s, 3H)
869		ESIMS m/z 403 ([M+H]*)	’H NMR (400 MHz, CDCIj ):6 8.87 (d, J =1.60 Hz, 1H), 8.69 (S, 1H), 8.28 (t, J = 2.00 Hz, 1H), 8.07 (s, 1H), 3.27 (s, 3H), 2.87 (t, J = 9.12 Hz, 1 H), 2.73-2.78 (m, 1H), 2.50 (dd, J = 5.16, 12.62 Hz, 1 H), 2.04 (s, 3H), 1.21 (d, J =3.96 Hz, 3H)

590

870	(thin film) 1690	ESIMS m/z 379 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.97 (d, J = 2.4 Hz, 1H), 8.64 (s, 1 H), 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+H]*)	’H NMR (400 MHz, CDClj) δ 8.95 (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	ESIMS m/z396 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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

873		ESIMS m/z 489.2 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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 = 7Λ 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)	’9F NMR (376 MHz, CDCh) δ -66.28,-66.41.
874		ESIMS m/z 503.2 ([M+H]*)	’HNMR (400 MHz, CDCh) δ 8.96 (s, 1 H), 8.65 (d, J = 4.7 Hz, 1H), 8.04 (ddd, J = 8.4, 2.7,1.4 Hz, 1 H), 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, CDCh) δ -66.24, -66.40.

592

875		ESIMS m/z 439 ([hydrate M+Hf), 421 ([keto M+Hf)	Ή NMR (CDCIa) δ 8.98 (d, J = 2.7 Hz, 0.4H), 8.95 (d, J = 2.6 Hz, 0.6H), 8.668.59 (m, 1H), 8.13-8.04 (m, 1H), 8.03 (s, 1 H), 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)	”F NMR (CDCIa) δ 76.15 (keto), 85.24 (hydrate)
876		ESIMS m/z 421 ([M+Hf)	’H NMR (400 MHz, CDCIa) 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, 1 H), 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)	”F NMR (376 MHz, CDClj) δ -66.41.

593

877		ESIMS m/z 381 ([M+H]*)	’H NMR (CDCIj) δ 8.98 (d, J = 2.7 Hz, 1H), 8.63 (dd, J = 4.8,1.5 Hz, 1H), 8.098.02 (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)	’3C NMR (CDCI3) δ 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+H]*)	’H NMR (CDCI3) δ 9.02 8.94 (m, 1H), 8.62 (dd, J = 4.8,1.5 Hz, 1 H), 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)	’3C NMR (CDCI3) δ 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

879

(thin film) 1663

ESi MS m/z 453 ([M+H]*)

’H NMR (400 MHz, CDCIj) 5 8.95 (d, J =2.5 Hz, IH), 8.68-8.59 (m, 1H), 8.088.00 (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, 1 H), 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, 1 H). 1.73 -1.61 (m, 3H)

13CNMR(101 MHz, CDCIj) 5 171.47, 148.80, 140.72, 140.04, 135.56, 128.70 (q.1Jcf = 277.8), 126.35, 126.32, 124.13, 123.82, 83.58 (d, ’JCf= 165.6 Hz), 48.51, 35.64 (q, 2JCf = 28.3 Hz), 34.06,27.57 (d, 2JCf = 20.2 Hz), 27.40, 24.50 (q, 3Jcf = 3.0 Hz), 23.83 (d, 3Jcf = 5.1 Hz); ”F NMR (376 MHz, CDCIj) 5 66.40 (t. J = 10.4 Hz),216.01 -220.60 (m)

595

880	(thin film) 1660	ESIMS m/z 433 ([M+H]*)	’H NMR (400 MHz, CDCI3) Ô 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 Hz, 1H), 3.55 (d, J =7.3 Hz, 2H), 2.85 (t, J = 7.2 Hz, 2H), 2.72 - 2.62 (m, 2H), 2.47 (t, J = 7.2 Hz, 2H), 2.44 - 2.29 (m, 2H), 0.98 (tt, J = 7.7,4.8 Hz, 1H), 0.56-0.46 (m, 2H), 0.25-0.16 (m, 2H)	’9F NMR (376 MHz, CDCIj) δ -66.40.
881	(thin film) 2913, 1595	ESIMS m/z 313 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 9.56 (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, 1 H). 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)
882	(thin film) 1661	ESIMS m/z 424 ([M+Hf)	’H 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, 2.7,1.5 Hz, 1H), 7.95 (s. 1H), 7.47 (dd, J =8.4, 4.8 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

883	(thin film) 1661	ESIMS m/z 416 ([M+H]*)	’H NMR (400 MHz, CDCIj) 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]*)	’H NMR (400 MHz, CDCIj) 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)	”F NMR (376 MHz, CDCIj) 6 -66.40.
885		ESIMS m/z 313 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.96 (d, J =2.5 Hz, 1H). 8.81 (s, 1H), 8.62 (s, 1H), 8.55 (dd, J =4.7,1.4 Hz, 1 H), 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

886		ESIMS m/z 327 ([M+H]*)	’HNMR(400MHz, CDCI3) 5 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), 8.568.51 (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+H]* calcd for C17H2iCIF3N4 02S. 437.1020; found, 437.1043.	’H NMR (400 MHz. Chloroform-d) δ 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 (brs, 2H), 3.58 (brs, 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) δ -66.40.

598

888		ESIMS m/z 468 ([M+H]*)	’H NMR (CDClj) δ 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, J =8.3, 4.8 Hz, 1H). 3.71 (q, J =7.0 Hz. 2H), 3.52 (t, 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)	”FNMR (CDClj) δ 66.14
889		ESIMS m/z 403 ([M+H]*)	’H NMR (CDClj) δ 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, 1 H), 7.47 (ddd, J = 8.4, 4.7, 0.8 Hz, 1H), 3.72 (q, J =7.2 Hz, 2H), 2.83 (t, J = 7.3 Hz, 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)	19F NMR (CDClj) δ 91.57

599

890		ESIMS m/z 405 ([M+H]*)	’H NMR (CDCIj) δ 8.95 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.7,1.4 Hz, 1 H), 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 (CDCIj) δ 62.15
891	(thin film) 1670	HRMS-FAB (m/z) [M+H]* calcd for CieHt9CIF5N4 OS. 469.0883; found, 469.0900.	’H NMR (400 MHz, CDCIj) δ 8.95 (d, J = 2.6 Hz, 1 H), 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, 1 H), 1.17-1.03 (m, 1H)

600

892	(thin film) 1668	HRMS-FAB (m/z) [M+Hf calcd for CirHaC^N, os, 439.0977; found, 439.0988.	’H NMR (400 MHz, CDCI3) δ 8.96 (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), 7.99 (s, 1H), 7.47 (ddd, J =8.2, 4.7, 0.7 Hz, 1H), 4.55 (dt, J = 47.1,5.7 Hz, 2H), 3.81 (t, J = 7.3 Hz, 2H), 2.84 (t, J = 7.2 Hz, 2H), 2.71 - 2.58 (m, 2H), 2.46 (t, J = 7.2 Hz, 2H), 2.44 - 2.27 (m, 2H), 2.01 (dit, J = 26.1,7.1,5.7 Hz, 2H)
893		ESIMS m/z 421 ([M+H]*)	’H NMR (CDCI3) δ 8.96 (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, 1 H), 7.46 (ddd, J = 8.4, 4.7, 0.8 Hz, 1H), 3.80 (br. s, 1H), 3.61 (br.s, 1H), 3.41-3.22 (m, 1H), 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)	’8F NMR (CDCI3) δ 66.14

60I

894		ESIMS m/z 454 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (d, 7=2.5 Hz, 1H), 8.65 (dd,7=4.7,1.4 Hz, 1H), 8.15-7.89 (m, 2H), 7.48 (ddd, 7= 8.3, 4.8, 0.6 Hz, 1H), 3.94 (bs, 2H), 3.72 (q, 7 = 7.2 Hz, 2H), 3.52 - 3.29 (m, 2H), 3.02 (s, 3H), 2.86 - 2.60 (m, 2H), 1.19 (t, 7= 7.2 Hz, 3H)
895	(thin film) 1680	ESIMS m/z 426 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.6 Hz, 1 H), 8.68 (dd, 7=4.8,1.3 Hz, 1H), 8.09-7.95 (m, 2H), 7.48 (dd, 7=7.8, 4.8 Hz, 1H), 3.94 (bs, 2H), 3.73 (q. 7 = 7.4 Hz, 2H), 3.18 (S, 3H). 1.19 (t, 7 = 7.2 Hz, 3H)
896	(thin film) 1665	ESIMS m/z 419.2 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.93 (d, 7 = 2.7 Hz, 1H). 8.63 (dd, 7 = 4.7,1.4 Hz, 1H), 8.03 (ddd, 7= 8.3, 2.7.1.4 Hz, 1H), 7.93 (s. 1H), 7.46 (dd, 7=8.3, 4.7 Hz, 1H), 5.85 (ddt, 7 = 16.7.10.1.6.4 Hz, 1 H), 5.26 - 5.06 (m, 2H), 4.27 (s, 2H), 2.86 (t, 7 = 7.2 Hz, 2H), 2.71 - 2.61 (m, 2H), 2.49 (t,7=7.2 Hz, 2H), 2.45 - 2.29 (m, 2H)	19F NMR (376 MHz, CDCI3) δ -66.40.

602

897	(thin film) 1659	HRMS-FAB (m/z) [M+H]* calcd for C18H22F3N4O S, 399.1461; found, 399.1479.	’H NMR (400 MHz, CDCI3) δ 8.96-8.89 (m, 1H), 8.57 (dd, 7= 4.8,15 Hz, 1 H), 8.02 (ddd, 7=8.3, 2.7,1.5 Hz, 1 H), 7.84 (s, 1H), 7.42 (ddd, 7 =8.4, 4.8, 0.7 Hz, 1H), 5.86 (ddt, 7= 16.7, 10.1,6.4 Hz, 1H), 5.23 — 5.09 (m, 2H), 4.23 (s, 2H), 2.84 (t,7=7.1 Hz, 2H), 2.69-2.61 (m, 2H), 2.43 (t,7=7.1 Hz, 2H), 2.402.31 (m, 2H), 2.26 (s, 3H)	’®F NMR (376 MHz, CDCIa) δ -66.42.
898	(thin film) 1659	ESIMS m/z 423 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (d,7 = 2.4 Hz, 1H), 8.63 (bd. 7= 3.7 Hz. 1H), 8.05 (ddd, 7 = 8.3, 2.7,14 Hz, 1 H), 7.96 (s, 1H), 7.47(ddd, 7= 8.1, 4.6 Hz, 1H), 4.07 (t, 7 = 6.9 Hz, 2H), 3.72 (q, 7 = 7.2 Hz, 2H), 2.87 (t, 7=7.2 Hz, 2H), 2.79 (t, 7 =7.0 Hz, 2H), 2.45 (t,7 = 7.2 Hz, 2H). 117 (t, 7= 7.2 Hz, 3H)
899	(thin film) 1675	ESIMS m/z 440 ([M+H]*)	’HNMR(400MHz, CDCI3) δ 8.96 (d, 7=2.4 Hz, 1H), 8.65 (dd, 7 =4.7,1.4 Hz, 1H), 8.07-7.98 (m, 2H), 7.48 (ddd, 7= 8.4, 4.8, 0.7 Hz, 1H), 4.11 (q,7=9.4 Hz, 2H), 3.98 (bs, 2H), 3.71 (q, 7=7.1 Hz, 2H), 3.03 (s, 3H), 119 (t, 7 = 7.2 Hz, 3H)

603

900	(thin film) 1684	HRMS-FAB (m/z) [M+Hf calcd for CieHieCIFaNj os. 418.0711; found, 418.0724.	’H NMR (400 MHz, CDCh) δ 9.03-8.97 (m, 1H), 8.67 (dd, J =4.8,1.4 Hz, 1H), 8.20 (s. 1H), 8.05 (ddd, J = 8.4, 2.7,1.4 Hz, 1H), 7.49 (ddd, J =8.3,4.7, 0.7 Hz, 1H), 4.61 (s, 2H). 2.86 (t. J = 7.1 Hz, 2H), 2.79-2.60 (m, 2H), 2.52 (t, J =7.1 Hz, 2H), 2.46 - 2.26 (m, 2H)	19F NMR (376 MHz, CDCh) δ -66.38.
901		ESIMS m/z 407 ([M+H]*)	’H NMR (CDCh) 0 8.95 (d, J = 2.8 Hz, 1H), 8.63 (dd, J = 4.6, 1.5 Hz, 1 H), 8.09- 8.00 (m, 2H), 7.46 (ddd, J = 8.3,4.8, 0.7 Hz, 1H), 3.71 (s, 2H), 3.10 (s, 2H). 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)	19F NMR (CDCh) δ - 66.08
902		ESIMS m/z 393 ([M+H]*)	’H NMR (CDCh) δ 8.95 (d, J=2.0Hz, 1H), 8.64 (dd, J = 4.8,1.5 Hz, 1H), 8.09- 7.99 (m, 2H), 7.47 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 3.72 (s, 2H), 3.14 (s, 2H), 2.90 - 2.81 (m, 2H), 2.54 - 2.37 (m, 2H), 1.18 (t, J = 7.2 Hz. 3H)	19F NMR (CDCh) δ 66.17

604

903		ESIMS m/z 415 ([M+H]*)	’HNMR (CDCI3) δ 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, 7 = 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), 1.781.61 (m, 2H), 1.56 (ddd, 7 = 14.0,11.1,6.9 Hz, 1H), 1.47 (d, 7=6.9 Hz, 3H), 1.39 (dddt, 7= 12.6,11.3, 7.7, 3.9 Hz, 1H), 1.17 (t, 7 = 7.2 Hz, 3H), 0.93 (ddtd, 7 = 12.4, 8.6, 7.4, 3.4 Hz, 1H)	19F NMR (CDCI3) δ - 128.06, - 128.47,- 143.57,- 144.01
904	(thin film) 1746,1709	HRMS-FAB (m/z) [M+H]* calcd for C19H23CIF3N4 o3s, 479.1126; found, 479.1139.	’H NMR (400 MHz, CDCI3) δ 8.93 (d, J =2.7 Hz, 1H), 8.59 (dd. 7 =4.8,1.4 Hz, 1H). 8.03 (ddd, 7 =8.4, 2.7,1.4 Hz, 1H), 7.91 (s, 1H), 7.43 (dd, 7 =8.3, 4.8 Hz, 1H), 3.36 (t, 7=7.2 Hz, 2H), 2.90 (t, 7= 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) δ -66.39.

605

905	3090, 2931, 1660	ESIMS m/z 437 ([M+H]*), 439 ([M+2+H]*)	Ή NMR (400 MHz, Chloroform-d) δ 8.95 (d, J = 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 m/z 421 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.96 (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), 2,952.83 (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 m/z 425 ([M+H]*)	’H NMR (400 MHz, CDClj) 5 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

908	(thin film) 1664	ESIMS m/z 418 ([M+H]*)	’H NMR (400 MHz, CDCIj) Ô 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, 1 H), 7.47 (ddd, J =8.4, 4.8, 0.8 Hz, 1H), 5.58 (dddd, J= 11.4,10.8, 7.7, 1.3 Hz, 1 H), 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)
909	(thin film) 1782	ESIMS m/z 380 ([M+H]*)	’H NMR (400 MHz. CDCIj) δ 8.96 (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 Hz. 1H), 3.72 (q, J =7.2 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

910	(thin film) 1721	ESIMS m/z 401 ([M+H]*)	’H NMR (400 MHz, CDClj) 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 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)
911		ESIMS m/z 431 ([M+H]*), 433 ([M+2+H]*)	’HNMR (400 MHz, Chloroform-d) δ 8.95 (dd, J = 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 (ddt, J = 8.5, 5.0,1.1 Hz, 1H), 3.25 (S, 3H), 2.88 (t, J = 7.3 Hz, 2H), 2.61 (ddt, J = 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 (dddd, J = 12.4,11.2, 7.9, 4.6 Hz, 1H), 1.05 (dtd, J = 13.2, 7.7,3.7 Hz, 1H)	’eFNMR(376 MHz, CDClj) δ -128.13 (d, J = 157.9 Hz),· 142.85 (d, J = 156.7 Hz)

608

912		ESIMS m/z 393 ([M+H]*)	’H NMR (CDCIj) δ 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), 3.523.40 (m, 1 H), 2.87 (t, J = 7.3 Hz, 2H). 2.58 (dd, J = 18.4, 7.8 Hz, 1H), 2.522.28 (m. 4H), 2.28-2.10 (m, 2H), 2.02-1.88 (m, 1H), 1.17 (t, J =7.2 Hz, 3H)	13C NMR (CDCIj) δ 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 m/z 349 ([M2MeOH]*)	’H NMR (CDCIj) δ 8.97 (d, J =2.6 Hz, 1H), 8.63 (dd, J = 4.8.1.4 Hz, 1 H), 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=7.2Hz, 3H)	13C NMR (CDCIj) δ 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

914		ESIMS m/z 469 ([M+2+H]*), 467 ([M+2- HT)	’H NMR (400 MHz, CDCI3) 5 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, 2.7,1.5 Hz, 1H). 7.96 (d, J = 3.8 Hz, 1 H), 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)	”F NMR (376 MHz, CDCI3) δ -44.55
915	(thin film) 1655	ESIMS m/z 437([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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), 3.022.74 (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]*)	Ή NMR (400 MHz, Chloroform-d) δ 8.95 (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, 1 H), 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)	’®F NMR (376 MHz, CDCI3) δ -51.30

610

917	(thin film) 1659	ESIMS m/z 440 ([M+Hf)	qH NMR (400 MHz, CDClj) 5 8.95 (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 m/z 387 ([M+Hf)	’H NMR (400 MHz, Chloroform-d) δ 9.00 - 8.91 (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)	”F NMR (376 MHz, CDClj) δ -86.38 (d, J = 39.7 Hz), 89.46 (d, J = 39.7 Hz)

611

919		ESIMS m/z 421 ([M+H]*)	’H NMR (CDCI3) δ 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, 1H), 7.47 (ddd, J = 8.4, 4.8,0.8 Hz, 1H), 3.72 (q, J = 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)	19F NMR (CDCI3) δ 73.06
920		ESIMS m/z 439 ([M+H]*)	'H NMR (CDCl3)ô8.98 (d, J = 2.7 Hz, 1 H), 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 Hz, 1H), 3.98 (dd, J =13.6, 7.0 Hz, 1H), 3.70-3.49 (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)	19F NMR (CDCI3) δ 65.88

612

921		ESIMS m/z 423 ([M+H]*)	1H NMR (CDClj) δ 9.01 8.94 (m, 1H). 8.68-8.60 (m, 1 H), 8.18-8.06 (m, 1H), 8.06-7.98 (m, 1H), 7.51-7.41 (m, 1H), 4.01 3.77 (m, 1.8H), 3.65 (br. s, 1.2H), 3.14 (br. s, 0.4H). 3.07-2.86 (m, 1H), 2.862.70 (m. 0.6H), 2.70-2.44 (m. 2H), 1.46 (br.d, J = 6.8 Hz, 3H), 1.24-1.12 (m, 3H)	’9F NMR (CDClj) δ 65.71,-65.73
922	(thin film) 3091,2965, 1658	ESIMS m/z 467 ([M+H]*)	’HNMR (400 MHz. Chloroform-d) δ 8.95 (dd, J = 2.7, 0.7 Hz, 1H), 8.64 (dd. J =4.8,1.4 Hz, 1H), 8.05 (s, 1H). 8.04 (ddd, J = 2.7,1.5, 0.7 Hz, 1H), 7.46 (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 (m, 2H), 2.502.30 (m, 2H), 2.21 (s, 3H)

613

923		ESIMS m/z 421 ([M+Hf)	’H NMR (CDC!3) G 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, 1H), 3.72 (q, J =7.1 Hz, 2H), 3.02 (ddd, J =9.0, 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)	ieF NMR (CDCI3)063.70
924	(thin film) 1662	ESIMS m/z 409 ([M+Hf)	’HNMR(400MHz, CDCI3) 0 8.96 (d, J =2.5 Hz, 1H), 8.63 (dd, J = 4.8,1.4 Hz, 1H), 8.07 (s, 1H), 8.03 (ddd, J =8.3, 2.7,1.4 Hz, 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)
925	(thin film) 3350,1736, 1668	HRMS-FAB (m/z) [M+H]* calcd for CieH21CIF3N4 03S. 465.0970; found, 465.0972	’H NMR (400 MHz, CDCI3) 0 8.96 (d, J =2.6 Hz, 1H), 8.64 (dd, J =4.8,1.5 Hz, 1H), 8.11 (s, 1H), 8.05 (ddd, J =8.3, 2.7,1.4 Hz, 1H), 7.47 (dd, J= 8.3, 4.8 Hz, 1H), 4.27(brs, 2H), 3.92(brs, 2H), 2.83 (t, J = 7.2 Hz, 2H), 2.71 - 2.57 (m, 2H), 2.46 (t, J =7.1 Hz, 2H), 2.42 - 2.26 (m,2H), 2.03 (s, 3H)	19F NMR (376 MHz, CDCI3) G -66.40.

614

926		ESIMS m/z 415 ([M+H]*)	’H NMR (CDCIj) δ 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. 1 H), 7.47 (dd, J =8.3, 4.7 Hz, 1H), 3.72 (q, J = 7.3 Hz, 2H), 3.323.17 (m, 1H), 2.84 (t, J = 7.3 Hz, 2H), 2.61 - 2.47 (m, 1H), 2.43 (t, J =7.4 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)	19FNMR (CDCIj) δ 89.43 (d, J = 228.9 Hz), 91.14(d, J = 228.5 Hz)
927		ESIMS m/z 389 ([M+H]*)	’H NMR (CDCIj) δ 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 (tt, J = 56.5, 4.4 Hz, 1H), 3.72 (q, J =7.2 Hz, 2H), 2.83 (t, J =7.2 Hz, 2H), 2.67 - 2.56 (m, 2H), 2.44 (t, J =7.3 Hz, 2H), 2.10 (ttd, J = 17.0, 7.5, 4.6 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H)	19F NMR (CDCIj) δ 117.68

615

928	(thin film) 3505, 3100, 1671	HRMS-FAB (m/z) [M+H]* calcd for C17H19CIF3N4 O2S, 435.0861; found, 435.0868	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 7.46 (dd, J =8.3, 4.8 Hz, 1H), 3.26 (s, 1 H), 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)	”F NMR (376 MHz, CDCI3) δ -66.43
929		ESIMS m/z 426 ([M+H]*)	’H NMR (CDCI3) δ 9.02 (d, J = 2.7 Hz, 1H), 8.62 (dd, J = 4.8,1.4 Hz, 1H), 8.138.04 (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) δ 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 CieH18CIF4N4 OS. 425.0820; found, 425.0830	’H NMR (400 MHz, CDCI3) δ 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) δ -66.42, 223.86.

616

931	(IR thin film) 1666	HRMS-FAB (m/z) [M+Hf calcd for CjoHmCIFsNs os, 476.1493; found, 476.1498	’H NMR (400 MHz, CDCI3) δ 8.93 (dd, J = 2.8, 0.7 Hz, 1H), 8.63 (dd, 7=4.7,1.4 Hz, 1H), 8.10 (s, 1H), 8.04 (ddd, 7= 8.3,2.7,1.5 Hz, 1H), 7.46 (ddd. 7= 8.3, 4.8, 0.7 Hz, 1H), 3.77 (s, 2H), 2.84 (t, 7=7.2 Hz, 2H), 2.66 (ddd, 7= 8.4, 6.2, 3.8 Hz, 4H), 2.54 (brs, 4H), 2.46 (t, 7 = 7.2 Hz, 2H), 2.43-2.29 (m, 2H), 1.87-1.56 (multiple peaks, 4H)	’®F NMR (376 MHz, CDCI3) δ -66.42.
932		ESIMS m/z 425 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7=2.4 Hz. 1H), 8.64 (dd, 7=4.8,1.4 Hz, 1H), 8.12-7.92 (m,2H), 7.47 (ddd, 7 =8.3, 4.8,0.7 Hz, 1H), 3.44 (t, 7=6.7 Hz, 2H), 3.37-3.15 (m, 5H), 2.84 - 2.57 (m, 4H)
933	(thin film) 1659	ESIMS m/z 367 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.63 (dd,7 = 4.7,1.4 Hz, 1H), 8.05 (ddd, 7 =8.3, 2.7,1.4 Hz, 1 H), 7.97 (s. 1H), 7.47 (ddd, 7 =8.3, 4.8, 0.6 Hz, 1H), 3.72 (q, 7 = 7.2 Hz, 2H), 2.80 (t, 7 = 7.5 Hz, 2H), 2.45 (dt, 7 = 15.0,7.3 Hz, 4H). 1.581.43 (m, 2H), 1.42-1.30 (m, 2H), 1.16 (t, 7 =7.2 Hz, 3H), 0.92-0.75 (t. 7 = 7.3 Hz, 3H)

617

934	(thin film) 1436,1360	ESIMS m/z 409 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (d, J = 2.5 Hz, 1H), 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, 1 H), 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]*)	’HNMR (400 MHz. CDCIj) δ 8.96 (d, J = 2.3 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, 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=7.2Hz, 3H)
936	(thin film) 2977, 2938, 1663, 1441, 1326	ESIMS m/z 400 ([M+H]*)	’H NMR (CDCIj) δ 9.01 (d. J =2.7 Hz. 1H), 8.62 (dd. J = 4.8,1.4 Hz, 1H), 8.118.03 (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

937	(thin film) 2975, 2935, 1663,1441, 1332	ESIMS m/z 412 ([M+H]*)	’H NMR (CDCIj) δ 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 m/z 440 ([M+H]*)	’H NMR (CDCIj) δ 8.98 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.8,1.5 Hz, 1 H), 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, 1 H), 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 (CDCIj) δ 74.83
939	(thin film) 2977,1665, 1442,1323	ESIMS m/z 516 ([M+H]*)	’H NMR (CDCIj) δ 9.03 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 4.7,1.4 Hz, 1H), 8.128.04 (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)	’9F NMR (CDCIj) δ 63.13

619

940	(thin film) 2976, 2936, 1662, 1487,1441, 1335	ESIMS m/z 482 ([M+H]*)	’H NMR (CDCI3) δ 9.03 (d, J = 2.7 Hz, 1H), 8.63 (dd, J = 4.7, 1.4 Hz, 1H), 8.158.05 (m, 2H), 8.01 (dd, J = 7.9,1.6 Hz, 1 H), 7.54- 7.43 (m, 3H), 7.37 (ddd, J = 8.6,6.9, 1.8 Hz, 1H), 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)	•
941	(thin film) 2977, 2935, 2234,1663, 1441, 1344	ESIMS m/z 473 ([M+H]*)	’HNMR (CDCl3)5 9.02 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 4.7, 1.5 Hz, 1H). 8.128.02 (m, 3H), 7.98 (dt, J = 8.0,1.5 Hz, 1H), 7.87 (dt, J = 7.8,1.4 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.47 (ddd, 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

942	(thin film) 2977, 1664, 1532, 1441, 1351	ESIMS m/z 493 ([M+H]*)	’H NMR (CDCIj) δ 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, 1 H), 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+H]*)	’H NMR (CDCIj) Ô 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), 7.687.55 (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 m/z 452 ([M+H]*)	’H NMR (CDCIj) δ 9.05 (d, 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, 1 H), 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

945	(thin film) 2929, 1662, 1487, 1441	ESIMS m/z 526 ([M+H]*)	’H NMR (CDCI3) δ 9 02 (d, J =2.6 Hz, 1H), 8.63 (dd,7 = 4.7, 1.4 Hz, 1H), 8.168.04 (m, 4H), 8.01 - 7.91 (m, 2H), 7.51 - 7.42 (m, 1H), 3.79-3.64 (m, 2H), 3.37 (t, 7 = 6.8 Hz, 2H). 3.11 (s. 3H), 2.83 (s, 3H), 2.52 (t, 7 = 6.9 Hz, 2H), 1.18 (t, 7= 7.1 Hz, 3H)
946		ESIMS m/z 437 ([M+H]*)	’H NMR (CDCIa) δ 8.97 (d, 7 = 2.7 Hz, 1H), 8.65 (dd,7 = 4.7,1.4 Hz, 1 H), 8.06 (ddd, 7 = 8.3, 2.7,1.5 Hz, 1H), 8.02 (s, 1H), 7.537.43 (m, 1H), 7.13 (dq. 7 = 15.2,1.8 Hz, 1H), 6.78 (dq, 7=15.3, 6.1 Hz, 1H), 3.71 (q, 7=7.2 Hz. 2H). 3.49 (t, 7 = 6.7 Hz, 2H), 2.70 (t. 7 = 6.7 Hz. 2H), 1.17 (t, 7 = 7.2 Hz, 3H)	19F NMR (CDCIa) δ65.07
947		ESIMS m/z 421 ([M+H]*)	’HNMR (CDCIa) Ô 8.96 (d, 7=2.6 Hz, 1H), 8.64 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.04 (ddd, 7= 8.3, 2.7,1.4 Hz, 1H), 7.97 (s, 1H), 7.47 (dd, 7 = 8.4,4.7 Hz, 1H), 7.24 (dq, 7= 15.0,1.9 Hz, 1H), 6.45 (dq, 7= 15.0,6.5 Hz. 1H), 3.81-3.60 (m, 2H), 3.35-3.22 (m, 1H), 3.183.02 (m, 1H), 2.72-2.52 (m, 2H). 1.16 (t, 7= 7.2 Hz, 3H)	19F NMR (CDCIj) δ 63.65

622

948	(thin film) 1661	ESIMS m/z 490 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.95 (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, 1 H). 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 m/z 547 ([M+H]*)	“Tî NMR (4ÔÔ MHz? Chloroform-d) δ 8.95 (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), 7.96 (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

950	(thin film) 1678	HRMS-FAB (m/z) [M+H]* calcd for CieH17CIF5N4 OS. 443.0726; found, 443.0732	’H NMR (400 MHz, CDClj) δ 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 (tt, J =56.2, 4.4 Hz, 1H), 3.98(brs, 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 ([M+H]*), 453 ([M+2+H]*)	’HNMR (400 MHz, Chloroform-d) δ 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, 1 H), 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), 1.241.12 (m, 3H)
952	(thin film) 1690	HRMS-FAB (m/z) [M+H]* calcd for CieHieCIFeN4 OS, 461.0632; found, 461.0637	’H NMR (400 MHz, CDClj) δ 8.96 (dd, J = 2.7, 0.7 Hz, 1H), 8.66 (dd, J = 4.8,1.4 Hz, 1H), 8.08-8.00 (multiple peaks, 2H), 7.48 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 3.00-2.80 (multiple peaks, 3H), 2.80 - 2.56 (multiple peaks, 3H), 2.52 (t, J =7.1 Hz, 2H), 2.452.29 (m, 2H)	’9F NMR (376 MHz, CDClj) δ -66.40, -69.87.

624

953	(thin film) 1671	HRMS-FAB (m/z) [M+H]* calcd for CieHieC!2F3N <0S, 441.0525; found, 441.0537	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.7 Hz, 1H), 8.65 (dd, J = 4.8,1.4 Hz, 1H), 8.10 (s, 1 H), 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 (brs, 2H), 2.84 (t. J =7.2 Hz, 2H), 2.722.61 (m,2H), 2.49 (t, J = 7.2 Hz, 2H), 2.45-2.28 (m, 2H)	19F NMR (376 MHz, CDCI3) δ -66.39.
954	(thin film) 1672	HRMS-FAB (m/z) [M+H]* calcd for C17H18CIF8N4 OS, 475.0789; found, 475.0795	’H NMR (400 MHz, CDCI3) 5 8.96 (dd, J =2.7, 0.7 Hz, 1H), 8.65 (dd, J = 4.8,1.5 Hz, 1 H), 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) δ -64.93, -66.40

625

955	(thin film) 1689	ESIMS m/z 324 ([M+H]*)	’H 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, 7 = 8.3, 2.7,1.4 Hz, 1H), 7.41 (ddd, 7= 8.3, 4.7, 0.7 Hz, 1H), 4.15- 3.90 (m, 2H), 3.08 (dd, 7 = 13.1,3.9 Hz, 1H), 2.88 (td, 7 = 8.9, 3.9 Hz, 1 H), 2.72 (dd, 7= 13.1,8.8 Hz, 1H), 2.47 (dddd, 7=12.9, 8.8, 7.5, 3.2 Hz, 1H), 2.18 (s, 3H), 2.16-2.06 (m, 1H)
956	(thin film) 1690	ESIMS m/z 340 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.91 (dt, 7=2.2,1.0 Hz, 1H), 8.54 (dd, 7 =4.7,1.4 Hz, 1H), 8.45 (d, 7=1.0 Hz, 1H), 7.97 (ddt, J = 8.3, 2.4.1.1 Hz, 1H), 7.457.35 (m, 1H), 4.10-3.90 (m, 2H), 3.29 (td, 7= 13.1, 4.1 Hz, 1H), 3.24-3.07 (m, 1H), 2.79 (ddd, 7 = 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

957	3091,2967, 1654	ESIMS m/z x467 ([M+H]*), 469 ([M+2+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.97 (dd, J = 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, 1 H), 7.46 (ddd, J =8.4,4.8,0.8 Hz, 1H), 3.72 (m. 2H), 3.253.09 (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) [M+H]* calcd for CieHigCIFjN4 OS, 431.0915; found, 431.0925	’H NMR (400 MHz, CDCIj) δ 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, CDCIj) δ -66.40.
959	(thin film) 1660	ESIMS m/z 469 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.94 (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

960	(thin film) 1659	ESIMS m/z 469 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 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

962	(thin film) 1690	ESIMS m/z 382 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 9.01-8.90 (m, 1 H), 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 (ddd, J =8.3, 4.7, 0.8 Hz, 1 H), 4.78 (dd, J = 7.7, 6.2 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)
963	(thin film) 1661	ESIMS m/z 508 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 7.96 (s, 1H), 7.47 (ddd, J =8.5, 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

964		ESIMS m/z 437 ([M+H]*)	’H NMR (CDCI3) δ 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 (tt, 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) δ 62.92, -63.40
965		ESIMS m/z 468 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.97 (d, J = 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, 1 H), 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)	’9F NMR (376 MHz, CDCI3) δ -65.30 (d, J = 12.7 Hz)

630

966	(thln film) 1662	ESIMS m/z 558 ((M+H)*)	’H NMR (400 MHz, CDCI3) 5 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]*)	’H NMR (400 MHz, CDCI3) 5 8.96 (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) [M+H]* calcd for CnHieClN4O 2S. 341.0834; found, 341.0835	’H NMR (400 MHz, CDCI3) δ 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 (brs, 2H), 3.67 (q, J =7.2 Hz, 2H), 2.69 (brs, 2H), 2.07 (brs, 3H), 1.20 (t, J =7.1 Hz, 3H)

631

969	(thin film) 1437,1424	ESIMS m/z 439 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.98 (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, 1 H), 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+H]* calcd for C15H17CIF3N4 o2s, 409.0707; found, 409.0716	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 7.92 (s, 1 H), 7.43 (dd, J =8.4, 4.7 Hz, 1H), 4.51 -4.15 (multiple peaks, 3H), 3.78 3.57 (m, 2H), 3.28-3.07 (m, 1H), 3.00 (d, J =9.5 Hz, 1H), 2.85 (brs, 1H), 1.20 (t, J = 7.1 Hz, 3H)	”F NMR (376 MHz, CDCI3) δ -66.64
971		ESIMS m/z 407 ([M+H]*)	’H NMR (CDCI3) δ 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) δ 66.39

632

972	(thin film) 1708	HRMS-FAB (m/z) [M+H]* calcd for Ci4H15CIF3N4 o2s, 395.0551; found, 395.0546	’H NMR (400 MHz, CDCI3) δ 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), 7.95- 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) δ -41.14
973	(thin film) 1661	ESIMS m/z 455 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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+H]* calcd for Ci5H18CIF3N5 OS, 408.0867; found, 408.0881	’H NMR (400 MHz, CDCI3) δ 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) δ -66.54

633

975	(thin film) 1662	ESIMS m/z 374 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.97 (dd, J = 2.7,0.7 Hz, 1H), 8.64 (dd, J = 4.7,1.4 Hz, 1H), 8.17-7.85 (m, 2H), 7.46 (ddd, J = 8.4, 4.8,0.8 Hz, 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).
976	(thin film) 1660	ESIMS m/z 535 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 2H), 7.46 (ddd, J =8.4, 4.7, 0.8 Hz, 1H), 3.823.61 (m, 2H), 3.18 (dt, J = 13.0, 7.6 Hz, 1H), 3.072.85 (m, 3H), 2.76 - 2.49 (m, 4H), 1.18 (t, J = 7.2 Hz, 3H)
977	(thin film) 1708	HRMS-FAB (m/z) [M+H]* calcd for C15H17CIF3N4 O2S, 409.0707; found, 409.0708	’H NMR (400 MHz, CDCIj) δ 8.93 (d, J = 2.7 Hz. 1H), 8.65-8.55 (m, 1H), 8.02 (ddd, J =8.3,2.8,1.5 Hz, 1H), 7.90 (s. 1H), 7.44 (dd, J = 8.4, 4.7 Hz, 1H), 4.414.03 (m, 2H), 3.77-3.59 (m, 2H), 3.57-3.38 (m, 1H), 1.59-1.28 (m, 3H), 1.29-1.13 (m, 3H)	”F NMR (376 MHz, CDCIj) δ -39.33

634

978		ESIMS m/z 468 ([M+H]*)	’H NMR (CDCI3) δ 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. 1H), 7.46 (ddd, J =8.3, 4.7, 0.8 Hz, 1H), 3.72 (q, J = 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)	19F NMR (CDCI3) 5 65.23
979	(thin film) 1666	HRMS-FAB (m/z) [M+H]* calcd for C17H19CIF3N4 O2S, 435.0864; found, 435.0877	’H NMR (400 MHz, CDCI3) 5 8.97 (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), 8.01 (s, 1 H), 7.46 (ddd, J = 8.4, 4.8, 0.8 Hz, 1H), 3.70 (q, J = 7.2 Hz, 2H), 3.09 - 2.98 (m, 2H), 2.92 (t, J = 6.6 Hz, 2H), 2.50 (t, J =6.6 Hz, 2H), 2.44 - 2.28 (m, 2H), 1.15 (t, J = 7.2 Hz, 3H)	19F NMR (376 MHz, CDCI3) 5 -66.58.
980	(thin film) 1661	ESIMS m/z 383 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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, 2H), 7.47 (ddd, J = 8.3, 4.8, 0.8 Hz, 1 H), 3.71 (q, J = 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

981		ESIMS m/z 405 ([M+Hf)	’H NMR (CDCh) δ 8.97 (dd, 7=2.7,0.7 Hz, 1H), 8.63 (dd, 7 = 4.8,1.5 Hz, 1H), 8.09-8.00 (m, 2H), 7.46 (ddd. 7 = 8.3,4.8, 0.8 Hz, 1H), 6.02 (tt, 7=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, 7 = 7.2 Hz. 3H)	19F NMR (CDCh) δ 112.36-121.41 (m)
982	(thin film) 3084, 1672	HRMS-FAB (m/z) [M+Hf calcd for C17HieCIFeN4 02S. 491.0738; found, 491.0750	’H NMR (400 MHz, CDCh) δ 8.97 (dd, 7 = 2.7, 0.7 Hz, 1H), 8.65 (dd, 7 = 4.8,1.5 Hz, 1H), 8.07 (s, 1H), 8.04 (ddd, 7 = 8.4. 2.7,1.5 Hz, 1H), 7.47 (ddd, 7 = 8.3, 4.8, 0.8 Hz, 1H), 3.91 (brs, 2H), 3.16 (dt, 7= 14.3,7.4 Hz, 1H), 3.01-2.79 (multiple peaks, 3H), 2.71 (s, 2H), 2.67-2.54 (m. 2H), 2.49 (dt, 7= 10.5, 7.4 Hz, 2H)	’9F NMR (376 MHz, CDCh) δ -64.96, -65.82.

636

983	(thin film) 1659	ESIMS m/z 470 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.96 (d, J = 2.5 Hz, 1 H), 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, 1 H), 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) [M+H]* calcd for C14HieCIFjN5 os, 394.0711; found, 394.0718	’H NMR (400 MHz, CDCIj) δ 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, 1 H), 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)	”F NMR (376 MHz, CDCIj) δ -66.62.

637

985		ESIMS m/z 497 ([M+H]*)	’H NMR (CDCI3) δ 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, 1 H). 7.85 (s, 1H), 7.46 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 7.33- 7.25 (m, 2H), 7.25-7.15 (m, 3H), 3.70 (q, J = 7.6 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, 1 H), 2.84-2.70 (m, 2H), 2.46 - 2.30 (m, 4H), 1.15 (t, J =7.2 Hz, 3H)	19F NMR (CDCI3) δ 63.14
986		ESIMS m/z 393 ([M+H]*)	’H NMR (CDCI3) δ 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, 2.7,1.5 Hz, 1H), 7.47 (ddd, J = 8.3,4.8, 0.8 Hz, 1H), 3.43 (q, J = 6.8 Hz, 1H), 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)	19F NMR (CDCh) δ 66.19

638

987		ESIMS m/z 407 ([M+H]*)	’H NMR (CDCI3) δ 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). 2.752.59 (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) δ 66.16
988	(thin film) 3315,1719	HRMS-FAB (m£) [M+Na]* calcd for C17H19CIF3N3 NaO2S, 472.0792; found, 472.0812	’H NMR (400 MHz, CDCI3) 6 9.01 -8.92 (m, 1 H). 8.89 (s, 1H), 8.62 (dd, J =4.8, 1.5 Hz, 1H). 8.09-7.98 (multiple peaks, 2H), 7.45 (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=7.3Hz, 3H)	’9F NMR (376 MHz, CDCIj) δ -66.39
989	(thin film) 1660	HRMS-FAB (m/z) [M+H]* calcd for C13H14CIF3N3 OS, 380.0554; found, 380.0557	’H NMR (400 MHz, CDCI3) 6 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)	’®F NMR (376 MHz, CDCIj) δ -40.06

639

990	(thîn film) 3305,1655	HRMS-FAB (m/z) [M+H]* calcd for C15H18CIF3N3 os, 408.0867; found, 408.0873	’H NMR (400 MHz, CDCI3) δ 8.95 (dd, 7 = 2.8, 0.8 Hz, 1H), 8.64 (dd, 7 = 4.7,1.4 Hz, 1H), 8.05 (ddd, 7 = 8.3, 2.7.1.4 Hz, 1H). 7.98 (s, 1H), 7.47 (ddd, 7 = 8.3, 4.8,0.8 Hz, 1H), 4.77 (t, 7 = 6.4 Hz, 1H), 4.44 (d, 7 = 6.4 Hz, 2H), 3.69 (q, 7 = 7.1 Hz, 2H), 2.91 -2.72 (m, 2H), 2.60-2.38 (m, 2H), 1.17 (t, 7=7.2 Hz, 3H)	’9F NMR (376 MHz, CDCI3) δ -66.26
991		ESIMS m/z 457 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.89 (d, J =2.5 Hz, 1H), 8.62 (dd, 7 =4.7,1.4 Hz, 1H), 8.39 (d, 7=5.5 Hz, 1 H), 8.04-7.95 (m,2H), 7.88 (S, 1 H), 7.47-7.42 (m, 1H), 3.73 (q, 7=7.2 Hz, 2H), 3.49 (t, 7 = 6.8 Hz, 2H), 2.69 (t, 7=6.8 Hz, 2H), 1.17 (t, 7=7.2 Hz, 3H)
992		ESIMS m/z 425 ([M+H]*)	’H NMR (CDCI3) δ 8.97 (dd, 7=2.7,0.8 Hz, 1H), 8.65 (dd, 7 = 4.8,1.5 Hz, 1H), 8.20 (s, 1H), 8.00 (ddd, 7=8.3,2.7,1.4 Hz, 1 H), 7.46 (ddd, 7=8.3, 4.8, 0.7 Hz, 1H), 4.15 (q, 7 = 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, 7=7.1 Hz, 3H)	’9F NMR (CDCI3) δ 65.85

640

993		ESIMS m/z 409 ([M+H]*)	’H NMR (CDCh) δ 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, 1H). 4.03 (q. J =6.9 Hz. 1H), 3.33 (s, 1.5H), 3.31 (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);	1flF NMR (CDCh) δ 65.73
994		ESIMS m/z 439 ([M+H]*)	’H NMR (CDCh) δ 8.97 (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, 1H), 7.45 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 4.11 (q. J = 7.1 Hz, 1H), 3.47 (dt. J = 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)	”F NMR (CDCh) δ 66.44

641

995		ESIMS m/z 423 ([M+H]*)	’H NMR (CDCIj) δ 9.03 8.93 (m, 1H), 8.70-8.61 (m, 1H), 8.19 (s, 0.5H), 8.16 (s, 0.5H), 8.07-7.95 (m, 1H), 7.51-7.40 (m, 1H), 4.08-3.90 (m, 1H), 3.32 (s, 1.5H), 3.30 (s, 1.5H), 3.06-2.90 (m, 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), 1.511.35 (m, 3H)	1®FNMR (CDCI3) δ 66.14
996	(thîn film) 3325,1651	HRMS-FAB (m/z) [M+H]* calcd for CuHieCIFaNs OS. 394.0711; found, 394.0723	’H NMR (400 MHz, CDCI3) δ 9.01 - 8.90 (m, 1 H), 8.63 (dd, J = 4.8, 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), 4.81 (t, J =6.0 Hz, 1H). 3.68 (q, J =7.1 Hz, 2H), 3.48 (q, J =6.3 Hz, 2H), 3.11-2.97 (m, 2H), 1.16 (t, J = 7.1 Hz, 3H)	19F NMR (376 MHz, CDCh) δ -40.58

642

997	(thin film) 3314,1644	HRMS-FAB (m/z) [M+H]* calcd for C15H,aCIF3N5 os, 408.0867; found, 408.0884	’H NMR (400 MHz, CDCI3) 5 8.96 (dd, 7 = 2.7, 0.7 Hz, 1H), 8.63 (dd, 7 = 4.7,1.4 Hz, 1H), 8.04 (ddd, 7 =8.3, 2.7.1.4 Hz, 1H), 7.97 (s, 1H), 7.46 (ddd, 7= 8.4, 4.8,0.7 Hz, 1 H), 4.37 (d. 7 = 7.7 Hz, 1H), 4.17 (p, 7 = 6.4 Hz, 1H), 3.77-3.57 (m, 2H), 3.16-2.99 (m, 2H), 1.20 (d,7 = 6.8 Hz, 3H), 1.15 (t, 7= 7.2 Hz, 3H)	19F NMR (376 MHz, CDCI3) 5 -40.72
998	(thin film) 1657	ESIMS m/z 407 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.95 (d, 7 = 2.4 Hz, 1H), 8.64 (dd, 7 = 4.7,1.4 Hz, 1H), 8.05 (ddd, 7 = 8.3, 2.7,1.5 Hz, 1H), 7.89 (s, 1H), 7.47 (ddd, 7 = 8.4, 4.8,0.6 Hz, 1H), 7.21 (dd. 7 = 4.9, 3.0 Hz, 1H), 7.06 (dd,7=1.9,1.0 Hz, 1H), 7.01 (dd, 7=5.0,1.2 Hz, 1H), 3.78-3.59 (m, 4H), 2.75 (t, 7 =7.4 Hz, 2H), 2.34 (t, 7 =7.4 Hz, 2H), 1.15 (t, 7 = 7.2 Hz, 3H)

643

999	(thin film) 3321, 3083, 1649	HRMS-FAB (m/z) [M+H]* calcd for CieH^CIFjNs os. 422.1024; found, 422.1027	’H NMR (400 MHz, CDClj) 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, 1 H), 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)	”F NMR (376 MHz, CDClj) 6 -66.30
1000	(thin film) 1710	HRMS-FAB (m/z) [M+H]* calcd for C15H17CIF3N4 O2S, 409.0707; found, 409.0718	’H NMR (400 MHz. CDClj) 6 9.01-8.86 (m, 1H), 8.59 (dd, J = 4.9,1.4 Hz, 1H), 8.02 (ddd, J = 8.3, 2.7,1.5 Hz, 1 H), 7.88 (s, 1H), 7.43 (dd, J = 8.3, 4.7 Hz, 1H), 4.21 (brs, 2H). 3.66 (q, J = 7.1 Hz, 2H), 2.85(brs, 2H), 1.99 (brs, 2H), 1.20 (t, J =7.1 Hz, 3H)	’®F NMR (376 MHz. CDClj) 6 -41.32

644

1001		ESIMS m/z 435 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.95 (dd, J = 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 (ddd, J =8.3, 4.8,0.8 Hz, 1H), 4.07 (p, J =5.9 Hz, 1H), 3.70 (q, J =7.1 Hz, 2H), 2.84 - 2.69 (m, 1H), 2.67 (d, J = 5.5 Hz, 1 H), 2.64 - 2.48 (m, 2H), 2.30 (S, 3H), 1.16 (t, J =7.2 Hz, 3H)	’9F NMR (376 MHz, CDClj) δδ -63.69
1002	(thin film) 1656	ESIMS m/z 374 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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 (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

1003	(thin film) 1658	ESIMS m/z 390 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 4.02- 3.85 (m, 2H), 3.80-3.58 (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)
1004	(thin film) 1662	ESIMS m/z 354 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.97 (dd, J =2.7, 0.7 Hz. 1 H), 8.63 (dd, J =4.8,1.5 Hz, 1H), 8.09-7.99 (m, 2H), 7.46 (ddd, J =8.4, 4.7, 0.8 Hz, 1H), 6.62 (dd, J =16.4, 9.8 Hz, 1H), 6.10 - 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

10C	5		ESIMS m/z 484 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.95 (d, J = 2.7 Hz, 1H), 8.64 (dd, J = 4.8,1.5 Hz, 1H), 8.598.50 (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, 1 H) 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, CDCIj) δ -63.42
10(	I6		ESIMS m/z 482 ([M+H]*)	’H NMR (CDCIj) δ 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 (t, 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 (CDCIj) δ 66.09
I 1C	J7		ESIMS m/z 400 ([M+H]*)	’H NMR (CDCIj) δ 9.01 (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)	’3C NMR (CDCIj) δ 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

1008		ESIMS m/z 490 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 2.7,1.5 Hz, 1H). 8.04 (s, 1H), 7.46 (ddd, J =8.3, 4.8, 0.8 Hz, 1H), 7.25- 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)	19F NMR (376 MHz, CDCIj) δ -63.45
1009	(thln film) 1660	ESIMS m/z 388 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 9.00 - 8.92 (m, 1H). 8.63 (dd, J =4.8, 1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7,1.4 Hz, 1 H), 7.97 (s, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 3.72 (q, J = 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

1010	(thin film) 1661	ESIMS m/z 404 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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) [M+H]* calcd for CieHîoFahhO S, 373.1304; found, 373.1312	’H NMR (400 MHz, CDCI3) 5 9.05-8.94 (m, 1 H), 8.58 (dd, J =4.8,1.7 Hz, 1H), 8.14-8.00 (m, 1 H), 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)	’®F NMR (376 MHz, CDCI3) δ -66.41
1012		ESIMS m/z 327 ([M+H]*)	’H NMR (CDCI3) δ 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)	’3C NMR (CDCI3) δ 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

1013	(thin film) 1674	HRMS-FAB (m/z) [M+H]* calcd for C19H24F3N4O S, 413.1617; found, 413.1637	’H NMR (400 MHz, CDCIj) 5 9.00 (d, 7 = 2.4 Hz, 1H), 8.58 (dd, 7 = 4.8,1.7 Hz, 1H), 8.09 (dt, 7 = 7.9,1.9 Hz, 1H), 7.35 (ddd, 7= 8.0, 4.8, 0.9 Hz, 1H), 6.52 (s, 1H), 3.83 (s, 3H), 3.57 (qd, 7=13.8, 7.3 Hz, 2H), 2.99 -2.73 (m,2H), 2.73-2.56 (m, 2H), 2.55-2.15 (multiple peaks, 4H), 1.07 - 0.89 (m, 1H), 0.62-0.40 (m, 2H), 0.35 - 0.08 (m, 2H)	1flF NMR (376 MHz, CDCIj) δ -66.41.
1014		ESIMS m/z 487 ([M+H]*)	’H NMR (CDCIj) δ 9.00 (dd, 7 = 2.8, 0.8 Hz, 1 H), 8.63 (dd, 7 = 4.7,1.4 Hz, 1H), 8.08 (ddd, 7 =8.3, 2.7.1.5 Hz, 1H), 8.01 (s, 1H), 7.55 (1,7=1.1 Hz, 1H), 7.47 (ddd, 7= 8.3, 4.7, 0.8 Hz. 1H), 7.06 (t, 7 = 1.1 Hz. 1H), 7.01 (d, 7 = 1.3 Hz, 1H), 4.22 (dd, 7 = 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, 7= 13.4,6.8 Hz, 1H), 2.69 (dt, 7 =13.1, 6.5 Hz, 1H), 2.52-2.39 (m, 1H), 2.39-2.23 (m, 3H), 1.16 (t, 7= 7.2 Hz, 3H)	’9F NMR (CDCIj) δ 63.20

650

1015	(thin film) 3096, 2976, 1660	ESIMS m/z 783 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 9.02 (d, J = 2.4 Hz, 1 H), 9.01-8.97 (m, 1H), 8.63 (m, 2H), 8.12 (s, 1H), 8.12-8.04 (m, 3H), 7.46 (m, 2H), 3.803.61 (m. 4H), 3.53-3.36 (m, 2H), 2.75-2.41 (m, 8H), 1.14 (m, 6H)	’®F NMR (376 MHz, CDCI3) δ -63.32, -63.21
1016	(thin film) 3094, 2977, 2934, 1662	ESIMS m/z 407 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 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)	’flF NMR (376 MHz, CDCh) δ -63.50

651

1017	(thin film) 1673	HRMS-FAB (m/z) [M+H]* calcd for CmHîsFjN^O S, 407.1712; found, 407.1711	’HNMR(400 MHz, CDCIj) δ 9.10-8.93 (m, 1 H), 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, 1 H), 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)	’9F NMR (376 MHz, CDCIj) δ -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 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.94 (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

1019	(thin film) 1661	ESIMS m/z 485 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.95 (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+H]* calcd for C18H23F2N4O 3s, 413.1453; found, 413.1463	’H NMR (400 MHz, CDCI3) δ 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 (multiple peaks, 3H), 3.09 (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)	19F NMR (376 MHz, CDCh) δ -130.35 (dd, J = 159.2,11.8 Hz), -141.01 (dd, J =159.1, 20.0 Hz)

653

1021	(thin film) 1661	ESIMS m/z 485 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.95 (d, J = 2.5 Hz, 1H), 8.64 (dd, J =4.7,1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7,1.5 Hz, 1 H), 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+H]*)	’H NMR (400 MHz, CDClj) δ 8.94 (d, J = 2.5 Hz, 1H), 8.64 (dd. J =4.7,1.4 Hz, 1H). 8.04 (ddd, J =8.3, 2.7,1.5 Hz, 1 H), 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]*)	’H NMR (400 MHz, CDClj) δ 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, 1.5 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

1024	(thin film) 1652	ESIMS m/z 501 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.5 Hz, 1H), 8.59 (dd, 7= 4.7,1.4 Hz, 1H), 8.01 -7.94(m,2H), 7.37 (dd, 7= 8.4, 4.8 Hz, 1H), 7.02 (bs, 1H), 6.88 (s, 2H), 3.67 (q, 7 = 7.1 Hz, 2H), 2.91 -2.83(m, 4H), 2.66 (t, 7 = 6.7 Hz, 2H), 2.49 (t, 7 = 6.7 Hz, 2H), 2.25 (s. 3H), 2.20 (s, 6H), 1.12 (t, 7= 7.2 Hz, 3H)
1025	(thin film) 1660	ESIMS m/z 429 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 8.92 (d, 7 = 2.5 Hz, 1H), 8.63 (dd, 7 = 4.7,1.4 Hz, 1H), 8.01 (ddd, 7 = 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, 7 = 7.1 Hz, 2H). 2.91 (dq,7 = 13.9, 7.0 Hz, 1H), 2.792.71 (m, 3H), 2.70-2.61 (m, 1H), 2.38 (t, 7 = 7.4 Hz, 2H), 1.32 (d, 7=6.9 Hz, 3H), 1.15 (t, 7 = 7.2 Hz, 3H)

655

1026	(thin film) 1660	ESIMS m/z 415 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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, 1 H), 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 m/z 429 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.99 (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), 7.497.39 (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]*)	’H NMR (400 MHz, CDCI3) 5 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)

656

1029	(thin film) 1660	ESIMS m/z 423 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 9.01 (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 Hz, 2H), 3.18 (dt, J =13.2, 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)
1030	(thin film) 1660	ESIMS m/z 382 ([M+H]*)	Ή NMR (400 MHz, CDCIj) δ 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, 1 H), 7.96 (s, 1H), 7.46 (ddd, J = 8.4, 4.8, 0.8 Hz, 1 H), 3.72 (q, J = 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

1031	(thin film) 1660	ESIMS m/z 380 ([M+H]*)	’HNMR (400 MHz, CDCh) 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, 1 H). 3.72 (q, J = 7.2 Hz, 2H), 2.82 (dd, J = 7.9, 7.0 Hz, 2H), 2.62- 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)
1032	(thin film) 1661	ESIMS m/z 416 ([M+H]*)	1H NMR (400 MHz, CDCI3) 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 = 7.2 Hz, 2H), 2.91 - 2.75 (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

1033	(thin film) 1662	ESIMS m/z 457 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.93 - 8.85 (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).
1034	(thin film) 1662	ESIMS m/z 457 ([M+H]*)	’HNMR (400 MHz, CDClj) δ 8.97-8.88 (m, 1H), 8.67 (d, J = 2.2 Hz, 1 H), 8.658.60 (m, 2H), 8.02 (ddd, J = 8.3,2.7,1.5 Hz, 1 H), 7.91 (s, 1H), 7.81 (td, J = 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

1035	(thin film) 1662	ESIMS m/z 457 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.92 (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- 7.40 (m, 2H), 7.25 (dd, J = 5.3,1.8 Hz, 1 H), 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)
1036	(thin film) 1659	ESIMS m/z 457 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 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=7.0Hz, 2H), 2.64 (t, J = 7.0 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H)

660

1037	(thin film) 1662	ESIMS m/z 484 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 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 m/z 484 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 9.01-8.88 (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, 1 H), 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

1039	(thin film) 1662	ESIMS m/z 484 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 7.94 (s, 1H), 7.60-7.49 (m, 2H), 7.46 (ddd, J = 8.3, 4.8, 0.8 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)
1040	(thin film)1660	ESIMS m/z 408 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 7.96 (s, 1H), 7.46 (ddd, J =8.3, 4.8, 0.8 Hz, 1H), 3.72 (q, J = 7.1 Hz, 2H), 2.81 (dd. J = 8.0, 7.0 Hz, 2H), 2.542.35 (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

1041	(thin film) 1661	ESIMS m/z 384 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 9.03-8.93 (m, 1H), 8.63 (dd, 7 = 4.8,1.4 Hz, 1H), 8.05 (ddd, 7 = 8.4,2.7,1.5 Hz, 1H), 7.98 (s, 1H), 7.47 (ddd, 7 =8.4, 4.8, 0.8 Hz, 1H), 3.72 (q, 7=7.2 Hz, 2H), 3.42 (t, 7 = 6.1 Hz, 2H), 3.30 (s, 3H), 2.81 (dd, 7=7.8,7.0 Hz, 2H), 2.55 (t, 7= 7.3 Hz, 2H), 2.44 (t, 7=7.4 Hz, 2H), 1.81 (tt, J = 7.1,6.1 Hz, 2H), 1.16 (t, 7 = 7.2 Hz, 3H)
1042	(thin film) 1656	ESIMS m/z 404 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 9.04 - 8.94 (m, 1H), 8.63 (dd, 7=4.7,1.4 Hz, 1H), 8.06 (ddd, 7=8.4, 2.7,1.5 Hz, 1H), 8.03 (s, 1H), 7.46 (ddd, 7=8.3, 4.8, 0.8 Hz, 1H), 3.90 (d, 7 =0.9 Hz, 2H), 3.72 (q, 7 = 7.2 Hz, 2H), 3.12 (t, 7= 6.6 Hz, 2H), 2.98 (s, 3H), 2.57 (t, 7 = 6.6 Hz, 2H), 1.17 (t, 7 = 7.2 Hz, 3H)

663

1043	(thln film) 1658	ESIMS m/z 465 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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), 7.597.53 (m, 2H), 7.44 (ddd, J = 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)
1044	(thin film) 1660	ESIMS m/z 480 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 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 (m, 1H), 7.61 -7.55 (m, 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

1045	(thin film) 1660	ESIMS m/z 498 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.97 (dd, J = 2.7, 0.8 Hz, 1 H), 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, 1 H), 7.95 - 7.87 (m, 2H), 7.46 (ddd, J = 8.3, 4.8, 0.8 Hz, 1 H), 7.28 - 7.23 (m, 2H), 3.70 (q, J = 7.2 Hz, 2H), 3.363.27 (m, 2H), 2.82 - 2.74 (m, 4H), 2.41 (t, J = 7.1 Hz, 2H), 1.15 (t, J =7.2 Hz, 3H).
1046	(thin film) 1657	ESIMS m/z 418 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 3.72 (q, J = 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

1047	(thin film) 1661	ESIMS m/z 432 ([M+H]*)	’HNMR (400 MHz, CDCI3) 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), 7.307.23 (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]*)	’H NMR (400 MHz, CDCIj) 5 9.01-8.91 (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)

66«

1049	(thin film) 1662	ESIMS m/z 476 ([M+H]*)	’HNMR(400 MHz, CDCI3) δ 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, 1 H), 7.45 (ddd, J = 8.4, 4.8, 0.8 Hz, 1 H), 6.77 (d, J = 8.7 Hz, 1H), 6.73-6.68 (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)
1050	(thin film) 1660	ESIMS m/z 420 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 7.99 (s, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.8 Hz, 1H), 6.89 (d, J = 1.3 Hz, 1H). 6.85 (d, J = 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

1051	(thin film) 1663	ESIMS m/z 471 ([M+H]*)	’H NMR (400 MHz, CDCIj) 0 8.96 (dd, J = 2.7, 0.8 Hz, 1 H), 8.62 (dd, J = 4.8,1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7,1.5 Hz, 1 H), 8.02 (s, 1 H), 7.82 (td, J =7.8, 0.8 Hz, 1 H), 7.59 (d, J = 7.9 Hz, 1H), 7.52 (dd, J =7.8, 1.0 Hz, 1 H), 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]*)	’H NMR (4ÔÔ MHz, Chloroform-d) δ 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

1053		ESIMS m/z 463 ([M+H]*)	’H NMR (CDCI3) δ 8.95 (dd, 7 = 2.7, 0.8 Hz, 1H), 8.63 (dd, 7 = 4.8,1.4 Hz, 1H), 8.04 (ddd, 7 =8.4, 2.7,1.5 Hz, 1H), 7.95 (s, 1H), 7.47 (ddd, 7 = 8.3, 4.8, 0.8 Hz, 1H), 3.72 (q, 7 = 7.1 Hz, 2H), 2.95-2.72 (m, 3H), 2.56 - 2.37 (m, 3H), 2.37-2.21 (m, 1H), 1.82 (dp. 7= 13.3, 6.7 Hz, IH). 1.55-1.36 (m, 2H), 1.16(17=7.2 Hz, 3H), 0.89 (d, 7 = 6.7 Hz, 3H), 0.86 (d, 7 =6.5 Hz, 3H)	’9F NMR (CDCh) δ 63.40
1054	(thin film) 1673	HRMS-FAB (m/z) [M+H]* calcd for C17H22F3N4O S, 387.1461; found, 387.1468	’H NMR (400 MHz, CDCI3) 6 9.06-8.93 (m, 1H), 8.58 (dd, 7 =4.8,1.7 Hz, 1H), 8.09 (dt, 7=7.9,2.0 Hz, 1H), 7.35 (ddd, 7 = 7.9, 4.8, 0.9 Hz, 1 H), 6.49 (s, 1H), 4.11 - 3.97 (m, 1 H), 3.79 (s, 3H), 3.49 - 3.30 (m, 1H), 2.83 (dt,7=10.2, 6.8 Hz, 2H), 2.72-2.58 (m, 2H), 2.53-2.16 (multiple peaks, 4H), 1.19 (t, 7=7.2 Hz, 3H)	’9F NMR (376 MHz, CDCh) δ -66.60

669

1055		ESIMS m/z 435 ([M+H]*)	’H NMR (CDCIj) δ 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 (CDCIj) δ63.70
1056	(thin film) 3455, 1673	HRMS-FAB (m/z) [M+H]* catcd for C17H22F3N4O 2s. 403.1410; found, 403.1428	’H NMR (400 MHz, CDCIj) δ 8.99 (s, 1H), 8.58 (dd, J = 4.9,1.7 Hz, 1H), 8.168.02 (m, 1 H), 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), 3.523.32 (m, 1H), 3.29-3.03 (m, 1H), 3.03-2.80 (multiple peaks, 3H), 2.80 2.38 (multiple peaks, 4H), 1.20 (t, J = 7.2 Hz, 3H)	19F NMR (376 MHz, CDCIj) δ -65.83

670

1057	(thin film) 3548,1674	HRMS-FAB (m/z) [M+Na]* calcd for c17h21f3n4n aO3S, 441.1179; found, 441.1180	’H NMR (400 MHz, CDCI3) δ 9.06-8.92 (m, 1H), 8.58 (dd, 7=4.9,1.6 Hz. 1H), 8.10 (dt, 7= 7.9,1.9 Hz, 1H), 7.36 (ddd, 7 =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 (multiple peaks, 4H), 2.83 2.61 (multiple peaks, 3H), 2.60-2.43 (m, 1H), 1.20 (t, 7 = 7.2 Hz, 3H)	19F NMR (376 MHz, CDCI3) δ -65.94
1058	(thin film) 1675	HRMS-FAB (m/z) [M+H]* calcd for Ct7H2tF2N4O S, 367.1399; found, 367.1401	’H NMR (400 MHz, CDCÏy δ 8.99 (dd, 7=2.3, 0.9 Hz, 1H), 8.57 (dd, 7 = 4.8,1.7 Hz, 1H), 8.07 (dt, 7 = 7.9, 1.9 Hz, 1H), 7.35 (ddd, 7 = 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, 7= 7.4, 2.3, 1.2 Hz, 2H), 2.41 (d, 7 = 59.4 Hz, 2H), 1.74 (ddq, 7=13.1,11.1, 7.4 Hz, 1H), 1.57-1.39 (m, 1H), 1.03 (dtd, 7=13.2,7.6, 3.7 Hz, 1H)	19F NMR (376 MHz, CDCI3) δ -128.19 (d, 7 = 156.9 Hz),- 142.74 (d, 7 = 157.7 Hz)

671

1059	(thin film) 3098, 2976, 2935, 2250, 1660	ESIMS m/z 446 ([M+Hf)	’H NMR (400 MHz, Chloroform-d) δ 9.05 - 8.93 (m, 1H), 8.63 (dd, J = 4.8, 1.5 Hz, 1H), 8.15-8.01 (m. 2H), 7.47 (ddd, J =8.4, 4.8, 0.8 Hz, 1H), 3.75 (ddq, J = 21.1,13.6,7.0 Hz, 2H), 3.44 (p, J =6.8 Hz. 1H), 2.96 - 2.80 (m, 2H), 2.72 (td, J =7.4, 6.4 Hz, 2H), 2.59-2.55 (m, 2H),2.552.43 (m, 2H), 1.30-1.09 (m, 3H)	’®F NMR (376 MHz, CDCIa) δ -63.59
1060	(thin film) 3422,1671	HRMS-FAB (m/z) [M+H]* calcd for Ci8H23F2N4O S, 381.1555; found, 381.1550	’H NMR (400 MHz, CDCIa) δ 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 = 8.0, 4.8, 0.9 Hz, 1H), 6.48 (s, 1H), 4.11-3.95 (m. 1H), 3.79 (s, 3H), 3.473.33 (m, 1H), 2.97-2.76 (m, 2H), 2.59 (dt, J =7.8, 1.6 Hz, 2H), 2.54-2.36 (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)	’®FNMR(376 MHz, CDCIa) δ -128.16 (d, J = 156.9 Hz),- 142.76 (d, J = 157.0 Hz)

672

1061	(thin film) 3445,1672	HRMS-FAB (m/z) [M+H]* calcd for C18H23F2N4O 2s, 397.1504; found, 397.1510	’H NMR (400 MHz, CDCI3) 6 8.99 (s, 1 H), 8.57 (dd, J = 4.8,1.6 Hz, 1H), 8.09 (d, J =8.0 Hz, 1 H), 7.35 (ddd, J = 7.9, 4.9,0.9 Hz, 1H), 6.52 (d, </ = 11.4 Hz. 1H), 4.13-3.95 (m, 1H). 3.82 (d, J= 7.7 Hz, 3H), 3.47- 3.33 (m, 1H), 3.29-2.32 (multiple peaks, 6H), 2.17 - 1.85 (m, 1H), 1.79-1.62 (m, 1 H), 1.39-1.24 (m, 1 H), 1.20 (t, J =7.2 Hz, 3H)	’9F NMR (376 MHz, CDCh) δ -124.54-133.44 (m),136.13-147.71 (m)
1062	(thin film) 1662	ESIMS m/z 469 ([M+H]*)	’H NMR (400 MHz, CDCI3) 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, 1H), 7.66 - 7.54 (m, 2H), 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

1063	(thin film) 2959,1660	ESIMS m/z 397 ([M+H]*)	’HNMR (400 MHz, CDClj) 6 8.89 (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), 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)
1064	(thin film) 2975,1650	ESIMS m/z 341 ([M+H]*)	’HNMR (400 MHz, CDClj) 6 8.90 (d, J = 2.5 Hz, 1 H). 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, 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)
Y2000		ESIMS m/z 313 ([M+H]*)	’H NMR (400 MHz, CDClj) 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 (ddd, J =8.3, 4.8, 0.5 Hz, 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

Y2001			’H NMR (400 MHz, CDCI3) 5 8.95 (d, 7 = 2.6 Hz, 1H), 8.64 (dd, 7 = 4.7,1.2 Hz, 1H), 8.03 (ddd, 7=8.3, 2.7,1.4 Hz, 1H), 7.97 (s, 1H), 7.47 (dd, 7=8.3,4.7 Hz, 1H). 4.22 (d, 7 = 6.1 Hz, 1H), 3.75 (m, 4H), 1.35 (d, 7 = 6.6 Hz, 3H), 1.18 (t, 7 = 7.2 Hz, 3H)	’9F NMR (376 MHz, CDCI3) 5 -74.00 (s)
Y2002	(thin film) 1485	ESIMS m/z 337 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.96 (d, 7 = 2.4 Hz, 1H), 8.69-8.58 (m, 1H), 8.11 8.01 (m, 1H), 7.97 (s, 1H), 7.48 (dd, 7 =8.3,4.7 Hz, 1H), 3.72 (bs, 2H), 3.11 2.93 (m, 2H), 2.92-2.81 (m, 2H), 2.80-2.68 (m, 1 H), 2.31 -2.09(m, 2H), 1.21 -1.10 (m, 3H)
Y2003		ESIMS m/z 295.6 ([M+H]*)	’H NMR (400 MHz, DMSO-de) 5 9.08 (d, 7 = 2.5 Hz, 1 H). 8.98 (s, 1H), 8.58 (dd, 7 = 4.7,1.1 Hz, 1H), 8.23 (ddd, 7 = 8.4, 2.6,1.3 Hz, 1H), 7.59 (dd, 7 = 8.3, 4.7 Hz, 1H), 4.97 (d, 7=7.6 Hz, 1H), 4.08 (m, 1H), 3.57 (d, 7 =50.6 Hz, 2H), 1.10 (d, 7 = 6.5 Hz, 3H), 1.07 (t, 7 = 7.1 Hz, 3H)

675

Y2004	(thin film) 1695	ESIMS m/z 365 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 1 H), 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]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (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+H]*), 363 ([M-H])	1H NMR (400 MHz, CDCIj) δ 8.93 (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, 1 H), 7.47 (dd, J =8.3, 4.8 Hz, 1H), 3.37 (s, 3H)	’®F NMR (376 MHz, CDCIj) δ -55.44 (s)
Y2007		ESIMS m/z 299 ([M+H]*)	’HNMR (400 MHz, CDCIj) δ 9.21 (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

Y2008	(thin film) 2980, 2936, 1676	ESIMS m/z 373.6 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 9.00 (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)
Y2009		ESIMS m/z 309 ([M+H]*)	’H NMR (300 MHz, CDCI) 5 8.92 (d, J = 2.6 Hz, 1H), 8,61 (dd, J =4.8,1.4 Hz, 1H), 8.05-8.00 (m, 1H), 7.99 (s, 1 H), 7.44 (dd, J = 8.4, 4.8 Hz, 1H), 3.86 (dq, J = 11.9,6.1 Hz. 1H), 3.31 (s, 3H), 3.24 (s, 3H), 2.52 (dd, J =15.2,7.3 Hz, 1H), 2.23-2.08 (m, 1H), 1.14 (d, J = 6.2 Hz. 3H)	l3CNMR(101 MHz, CDCI3) 5 171.74, 148.59, 140.21, 140.01, 135.70, 126.33, 126.23, 125.94, 124.10,74.22, 56.52, 40.64, 36.80, 19.18
Y2010		ESIMS m/z 251 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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 Hz, 1H), 7.56 (s, 1H), 7.38 (dd, J = 8.3, 4.7 Hz, 1H), 5.16 (s, 1H), 2.94 (s, 3H), 1.91 (s, 3H)

677

Y2011	(thln film) 3440, 2923, 1663	ESIMS m/z 251 ([M+H]*)	’H NMR (400 MHz, CDCIj) 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]*)	’H NMR (400 MHz, CDCI3) 6 8.91 (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, 1 H), 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)	’3C 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]*)	’HNMR (400 MHz, CDCIj) 6 8.96 (d, J = 2.5 Hz, 1H), 8.64 (dd, J = 4.8,1.4 Hz, 1H), 8.14 (s, 1 H), 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)	’3CNMR(101 MHz, CDCIj) 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

Y2014	(thin film) 1677	ESIMS m/z 277 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 8.96 (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+H]*)	’H NMR (400 MHz, CDCIj) 5 8.97 (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+H]*)	’H NMR (400 MHz, CDCIj) 5 8.98 (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, 1 H), 3.30 (s, 3H), 1.53 (d, J «7.1 Hz, 3H)
Y2017	(thin film) 2962, 1674	ESIMS m/z 305 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 8.92 (d, J). = 1.8 Hz, 1H), 8.58 (d, J = 4.0 Hz, 1H), 8.10 (s, 1 H). 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, 3H), 1.13 (t. J =7.2 Hz, 3H)

679

Y2018	(thin film) 1673	ESIMS m/z 331 ([M+H]*)	’H NMR (400 MHz, CDCI3) 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-H]')	’H NMR (400 MHz, CDCI3) 6 8.95 (d. J =2.6 Hz, 1H), 8.63 (s, 1 H), 8.06 (s, 1H), 8.04-7.96 (m, 1H), 7.527.42 (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+H]* )	’H NMR (400 MHz, CDCI3) 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

Y2022	(thin film) 2975,1664	ESIMS m/z 346 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.91 (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, 1 H), 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 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.90 (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

Y2024	(thin film) 2975,1658	ESIMS m/z 360 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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 = 2.1 Hz, IH), 7.09(8,1 H), 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)
Y2025	(thin film) 2973,1658	ESIMS m/z 376 ([M+H]*)	'H NMR (400 MHz, CDCI3) δ 8.80 (s, 1H). 8.60 (dd, J = 4.7,1.3 Hz. 1 H), 7.96 (d, J = 8.3 Hz, 1 H), 7.44 (dd, J = 8.3,4.7 Hz, 1H), 7.18 (d, J =4.8 Hz, 1H), 7.04-6.95 (m,1H), 6.78 (d, J =3.3 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, 1 H), 1.20 (d, J =6.6 Hz, 3H), 1.08 (t. J = 7.2 Hz, 3H)

682

Y2026	(thin film) 1663	ESIMS m/z 332 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.89 (d, J = 2.5 Hz, 1H), 8.62 (dd, J = 4.8,1.4 Hz, 1H), 8.00 (ddd, J =8.3, 2.7,1.5 Hz, 1H), 7.62 (s, 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)
Y2027	(thin film) 2975,1663	ESIMS m/z 346 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.86 (d, J = 2.6 Hz, 1H), 8.61 (dd, J =4.8,1.3 Hz, 1 H), 7.99 (ddd, J =8.3, 2.6, 1.4 Hz, 1H), 7.54 (d, J = 1.6 Hz, 1H), 7.45 (dd, J = 8.3, 4.8 Hz, 1H), 7.41 (d, J = 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)
Y2028	(thin film) 2971, 1658	ESIMS m/z 362 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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 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

Y2029		ESIMS m/z 359 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 8.99 (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)
Y2030		ESIMS m/z 325 ([M+H]*)	’HNMR (400 MHz, CDCIj) 5 8.95(bs, 1H), 8.61 (d, J = 4.4 Hz, 1H), 8.05 (ddd, J = 8.3,2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.44 (dd, J = 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)
Y2031		ESIMS m/z 339 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 8.96 (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 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

Y2032		ESIMS m/z 322 ([M+H]*)	’H NMR (400 MHz, DMSO-de) δ 11.38 (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, 1 H), 4.55 - 4.37 (m, 2H), 4.35-4.17 (m, 2H), 2.24 (s, 3H)
Y2033		ESIMS m/z 307 ([M+H]*)	’H 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, 1 H), 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+H]*)	’H NMR (400 MHz, DMSO-de) δ 11.39 (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-de) 6 9.06 (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

Y2036	(thin film) 1669	ESIMS m/z 320 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 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+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (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, 1 H), 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+H]*)	’H NMR (400 MHz, CDCI3) 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

¥2039	(thîn film) 1671	ESIMS m/z 406 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 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, 7=8.3,4.7 Hz, 1H), 3.65 (t, 7=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 m/z 340 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.92 (d, 7 =2.5 Hz, 1H), 8.57 (dd, 7 =4.7,1.3 Hz, 1H), 8.02 (d, 7=8.3 Hz, 1H), 7.89 (s, 1H), 7.42 (dd, 7 = 8.3,4.7 Hz, 1H), 4.53 (t, 7 = 5.8 Hz, 1H), 4.41 (t, 7=5.6 Hz, 1H), 3.61 (t,7 = 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+H]*)	’H NMR (300 MHz, CDCIj) 6 8.84 (d,7 = 2.7 Hz, 1H), 8.47 (dd, 7 = 4.7,1.4 Hz, 1H). 7.93 (ddd, 7 = 8.3, 2.6,1.4 Hz, 1H), 7.64 (s, 1 H), 7.35 (dd, 7=8.3, 4.8 Hz, 1H), 4.60 (s, 2H), 1.51 (m, 1H), 1.04 (m, 2H), 0.89 (m, 2H)

687

Y2042		ESIMS m/z 277 ([M+H]*)	’HNMR (400 MHz, CDCI3) 6 8.95 (d, 7=2.5 Hz, 1H), 8.62 (d, 7 = 3.9 Hz, 1H), 8.08 - 8.00 (m, 2H), 7.45 (dd, 7= 8.3, 4.7 Hz, 1H), 3.26 (s, 3H), 1.54-1.49 (m, 1 H), 1.10 - 0.97 (m, 2H), 0.73 (dd, 7=7.5, 3.1 Hz, 2H)
Y2043	(thin film) 1650	ESIMS m/z 317 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 8.96 (d, 7 = 2.5 Hz, 1H), 8.66-8.40 (m, 1H), 8.107.92 (m, 2H), 7.45 (dd, 7 = 8.2,4.7 Hz, 1 H), 3.55 (s, 2H), 1.48 (td, 7= 8.0, 4.0 Hz, 1H), 1.09-0.92 (m, 3H), 0.72 (d, 7=4.9 Hz, 2H), 0.53 - 0.43 (m, 2H), 0.22-0.14 (m, 2H)
Y2044	(thin film) 1649	ESIMS m/z 291 ([M+H]*)	’H NMR (400 MHz, CDCI3f 6 8.96 (d, 7 =2.5 Hz, 1H), 8.62 (d, 7=4.7 Hz, 1H), 8.14-7.94 (m, 2H), 7.45 (dd, 7 = 8.2, 4.8 Hz, 1H), 3.24 (s, 3H), 1.41 (d,7 = 6.2 Hz, 1H), 1.30-1.15 (m, 2H), 102 (d, 7 = 6.0 Hz, 3H), 0.56 (bs, 1H)

688

Y2045	(thin film) 1646	ESIMS m/z 332 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.61 (m, 1H), 8.07 (ddd, 7 = 8.4, 2.6,1.4 Hz, 1H), 8.03 (s, 1H), 7.46 (dd,7 = 8.3,4.7 Hz, 1H), 3.54 (s. 1 H), 1.41 (m, 1H), 1.291.19 (m, 2H), 1.20-1.11 (m, 2H), 1.02 (d, 7 = 6.0 Hz, 3H), 0.55 (bs, 1H), 0.48 (d. 7 =7.2 Hz, 2H), 0.19 (d, 7 = 4.8 Hz, 2H)
Y2046 i 1	(thin film) 1670	ESIMS m/z 314 ([M+H]*)	’HNMR(400MHz, CDCÎ3) δ 8.95 (d, 7 = 2.5 Hz, 1H), 8.64 (dd, 7 = 4.7,1.3 Hz, 1H), 8.03 (dd, 7 = 2.7,1.5 Hz, 1H), 8.02 (s, 1H), 7.46 (dd, 7=8.3, 4.8 Hz, 1H), 3.31 (s, 3H), 2.32 (ddd, 7 = 13.2,10.6, 7.9 Hz, 1H), 2.26-2.13 (m, 1H), 1.63 (ddt, 7= 13.4, 6.8, 3.8 Hz, 1H)

689

Y2047	(thin film) 1665	ESIMS m/z 353 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.97 (d, J = 2.6 Hz, 1 H), 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), 3.77 (dd, J =13.7,7.0 Hz, 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), 1.060.92 (m, 1H), 0.56-0.45 (m, 2H), 0.21 (td, J =4.9, 3.0 Hz, 2H)
Y2048		ESIMS m/z 297 ([M+H]*)	1H NMR (300 MHz, CDCIj) δ 8.94 (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)
Y2049	(thin film) 3050, 2931, 1583	ESIMS m/z 325 ([M+H]*)	’H NMR (300 MHz, CDCIj) δ 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, 2H), 1.44-1.28 (m, 6H)

690

Y2050		ESIMS m/z 280 ([M+H]*)	Ή NMR (400 MHz, Acetone-de) δ 9.10 (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+H]*)	’H NMR (400 MHz, CDCb) δ 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), 2.232.06 (m, 2H), 1.65-1.60 (m, 4H), 1.44 (s, 9H)
Y2052		ESIMS m/z 325 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 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, 1 H), 8.02 (s, 1H), 7.47 (ddd, J =8.3, 4.8, 0.8 Hz, 1 H), 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, 1 H), 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 ’H NMR)

691

Y2053		ESIMS m/z 394 ([M-H]')	’H NMR (400 MHz, CDCI3) δ 9.06 (d, J = 2.7 Hz, 1H), 8.61 (dd, 7 = 4.7,1.4 Hz, 1H), 8.44 (s, 1H), 8.13 (ddd, 7=8.3,2.7,1.5 Hz, 1H), 7.50 (dd, 7 = 8.4, 4.8 Hz, 1H), 6.38 (d, 7 = 9.7 Hz. 1 H), 5.96 (dt, 7=5.7, 2.1 Hz, 1H), 5.84 (ddd, 7 = 5.5, 2.5,1.2 Hz, 1H), 4.534.42 (m, 1 H), 3.69-3.58 (m, 1H), 3.26 (s, 3H), 3.00 (s, 3H), 2.34 (dt, 7= 13.6, 8.1 Hz, 1H), 2.09-1.99 (m,1H)	’3CNMR(101 MHz, CDCI3) δ 175.06, 148.34, 139.87, 139.77, 135.60, 134.26, 132.41, 126.88, 126.29, 125.25, 124.18, 58.77, 47.25,41.66, 37.52, 35.86
Y2054		ESIMS m/z 394 ([M-H]*)	’H NMR (400 MHz, CDCI3) δ 8.99 (d, 7=2.6 Hz, 1H), 8.63 (dt, 7= 4.8, 2.4 Hz, 1H), 8.22 - 8.16 (m, 1 H), 8.07 (ddd, 7 = 8.3, 2.7,1.5 Hz, 1H), 7.47 (ddd, 7 =7.4, 4.8,2.2 Hz, 1H), 6.04- 5.91 (m, 2H), 5.80 (dd, 7 = 5.6, 2.5 Hz, 1H), 4.54- 4.44 (m, 1 H), 3.58 (dt, 7 = 6.4,2.1 Hz, 1H), 3.25 (d, 7 = 2.7 Hz, 3H), 2.99 (d, 7 = 2.6 Hz, 3H), 2.26 (dt, 7 = 13.7, 8.0 Hz, 1H), 2.092.00 (m, 1 H)	’3C NMR (101 MHz, CDCI3) δ 175.08, 148.73, 140.11, 140.01, 135.58, 134.53, 132.36, 126.36, 126.17, 125.53, 124.17, 58.73, 47.33,41.89, 37.67, 35.84

692

Y2055	(thin film) 1702	ESIMS m/z 392 ([M+H]*)	’HNMR (400 MHz, CDClj) 6 8.93 (d, J = 2.6 Hz, 1H), 8.59 (d, J =3.7 Hz, 1H), 8.02 (d, J =8.2 Hz, 1H), 7.89 (s, 1 H), 7.43 (dd, J = 8.1,4.8 Hz, 1 H), 3.82(brs, 2H), 2.47 (brs, 2H), 1.48 (s. 9H)
Y2056		ESIMS m/z 263 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.96 (bd, 1H), 8.61 (s, 1H), 8.54 (dd, J= 4.7, 1.4 Hz, 1H), 7.97 (ddd, J =8.3, 2.7, 1.4 Hz, 1H). 7.39 (ddd, J = 8.4, 4.7, 0.7 Hz. 1H), 7.33 (s, 1 H). 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)
Y2057	(thin film) 1666	ESIMS m/z 307 ([M+H]*)	’HNMR (400 MHz, CDClj) δ 8.97 (d, J =2.4 Hz, 1H), 8.61 (d, J =3.6 Hz, 1H), 8.09-8.00 (m, 2H), 7.45 (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)
Y2058	(thin film) 1678	ESIMS m/z 397 ([M+H]*)	’H NMR (400 MHz, CDClj) δ 8.91 (d, J =2.6 Hz, 1H), 8.61 (bd, 1H), 8.10-7.99 (m, 4H), 7.63-7.55 (m, 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

Y2059	(thin film) 1679	ESIMS m/z 379 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J =2.4 Hz, 1H), 8.63 (d, J = 4.7 Hz, 1H), 8.10 (s, 1 H), 8.04 (m, 1 H), 7.46 (dd, J = 8.3,4.8 Hz, 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)
Y2060		ESIMS m/z 305 ([M+H]*)	'H NMR (400 MHz, CDCI3) 6 8.95 (s, 1H), 8.62 (d, J = 4.3 Hz, 1H), 8.09-7.98 (m, 2H), 7.45 (dd, J = 8.2, 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)
Y2061			’H NMR (400 MHz, CDCI3) 6 8.95 (bs, 1H), 8.61 (d,J = 4.2 Hz, 1H), 8.08-7.95 (m, 2H), 7.45 (dd, J =8.3, 4.7 Hz, 1 H), 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)
Y2062	(thin film) 2978,1709	ESIMS m/z 328 ([M+H]*)	’HNMR (400 MHz, CDCI3) 6 8.94 (s, 1H), 8.63 (d, J = 4.3 Hz, 1 H), 7.99 (d,J = 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

Y2063	(thin film) 2977, 1706	ESIMS m/z 325 ([M+H]*)	’H NMR (400 MHz, CDCI3) 5 8.80 (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+H]*)	’H NMR (400 MHz,CDCI3) 5 8.87 (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]*)	’H NMR (400 MHz, CDCI3) 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

Y2066	(thin film) 1657	ESIMS m/z 335 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 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 = 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)
Y2067	(thin film) 2978, 1705	ESIMS m/z 383 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.88 (t, J =1.9 Hz, 1 H), 8.54 (dd, J = 4.7,1.3 Hz, 1H), 7.94 - 7.86 (m, 1 H), 7.42-7.35 (m, 1H), 7.357.20 (m, 5H), 4.69 (s, 2H), 2.04-1.90 (m, 3H), 1.631.37 (m,9H)
Y2068	(thin film) 1656	ESIMS m/z 385 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.98 (d, J = 2.5 Hz, 1H), 8.63 (dd, J =4.8,1.4 Hz, 1H), 8.06-7.79 (m, 2H), 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)

69«

Y2069		ESIMS m/z 345 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 8.86 (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 m/z 345 ([M+H]*)	’HNMR (400 MHz, CDCh) 5 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 m/z 345 ([M+H]*)	’HNMR(400MHz. CDCh) δ 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

Y2072	(thin film) 3098, 2977, 1675	ESIMS m/z 381 ([M+H]*), 379 ([M-H]*)	’H NMR (400 MHz, CDCIj) 6 8.96 (d, J = 2.7 Hz, 1H), 8.65 (dd, J =4.8,1.5 Hz, 1 H), 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]*)	’H NMR (400 MHz, CDCIj) 6 9.05 (d, J =2.6 Hz, 1H), 8.63 (dd, J =4.8,1.4 Hz, 1H), 8.27 (s, 1 H), 8.09 (ddd, J =8.4,2.7,1.4 Hz, 1 H), 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), 2.962.86 (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+H]*)	’H NMR (300 MHz, CDCIj) 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

Y2075	(thin film) 1652	ESIMS m/z 297 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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, 1 H), 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 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 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 m/z 327 ([M+H]*)	’H NMR (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), 3.99 (m, 1H), 3.86 (brs, 1H), 3.60 (brs, 1H), 2.13(dt, J = 14.6, 7.3 Hz, 1 H), 1.91 (dt, J =14.5, 7.3 Hz, 1 H), 1.19 (t, J = 7.2 Hz, 3H), 0.97 (t, J = 7.3 Hz, 3H)

699

Y2078		ESIMS m/z 235 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 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]*)	’H NMR (400 MHz, CDCI3) δ 8.99 (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), 7.587.50 (m, 2H), 7.44 (ddd, J = 8.3,4.8, 0.4 Hz, 1 H), 3.43 (s, 3H), 3.16 (q, J = 7.2 Hz, 2H), 1.05 (t, J = 7.2 Hz, 3H)
Y2080	(thin film) 2928,1654	ESIMS m/z 325 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.59 (d, J =1.6 Hz, 1H), 8.39 (d, J = 2.5 Hz, 1 H), 7.75 (dt, J = 9.4,2.4 Hz, 1H), 7.48 (s, 1H), 7.357.28 (m, 3H), 7.25-7.19 (m, 2H), 4.79 (s, 2H), 2.03 (s, 3H), 1.96 (S, 3H)

700

Y2081	(thin film) 2979,1678	ESIMS m/z 353 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.90 (d, 7=2.6 Hz, 1H), 8.59 (dd, 7=4.7,1.4 Hz, 1H), 8.01 (s, 1H), 7.99 (ddd, 7 =8.3, 2.7, 1.4 Hz, 1H), 7.46-7.40 (m. 1H). 4.12 (q, 7= 7.1 Hz, 2H). 3.57 (q, 7= 7.1 Hz, 2H), 3.33 (S, 3H), 1.25 (t, J = 7.1 Hz, 3H), 1.21 (t,7=7.1 Hz, 3H)
Y2082	(thin film) 2969, 1681	ESIMS m/z 365 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 8.93 (d, 7 =2.5 Hz, 1H), 8.61 (dd, 7=4.7,1.3 Hz, 1H), 8.06 (s, 1H), 8.00 (ddd, 7 =8.3, 2.6,1.4 Hz, 1H), 7.44 (dd, 7 = 8.3, 4.7 Hz. 1H), 3.58 (q, 7 = 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]*)	’H NMR (400 MHz, CDCI3) 6 8.57 (d, 7= 1.8 Hz, 1H). 8.40 (d, 7 =2.5 Hz, 1H). 7.74 (dt, 7=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 m/z 359 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.96 (d, 7=2.6 Hz. 1H). 8.61 (dd, 7=4.7,1.4 Hz, 1H). 8.19 (s, 1H), 7.97 (ddd, 7 =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, 7 = 7.2 Hz, 3H)

701

Y2085	(thin film) 2189, 1659	ESIMS m/z 382 ([M+H]*)	’H NMR (400 MHz, CDClj) 5 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	ESIMS m/z 385 ([M+H]*)	’H NMR (300 MHz, CDClj) 0 8.94 (d, J =2.7 Hz, 1H), 8.58 (dd, J =4.7,1.4 Hz, 1H), 8.18 (S, 1 H), 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]*)	’H NMR (300 MHz, CDClj) δ 8.97 (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, 1 H), 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

Y2090	(thin film) 3965,1656	ESIMS m/z 350 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 8.95 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 4.8,1.4 Hz, 1H), 8.05 (ddd, 7=8.3, 2.8,1.5 Hz, 1H), 7.97 (s. 1H), 7.47 (dd. 7 = 8.3, 4.8 Hz, 1H), 3.71 (t, 7 = 4.7 Hz. 6H), 3.00 (s. 2H), 2.48 (t, 7 = 4.6 Hz, 4H), 1.17 (t, 7 = 7.2 Hz, 3H)
Y2091	(thin film) 3098,1664	ESIMS m/z 331 ([M+H]*), 329 ([Μ-H])	’H NMR (400 MHz, Chloroform-d) δ 8.95 (d, 7 = 2.6 Hz. 1H), 8.66 (dd, 7 = 4.8,1.5 Hz, 1 H), 8.02 (ddd, 7=8.3,2.7,1.5 Hz, 1H), 7.81 (s, 1H), 7.48 (dd, 7 = 8.3, 4.7 Hz, 1H). 7.34 (d, 7 = 1.0 Hz. 1H), 7.06 (t, 7 = 1.0 Hz, 1 H), 6.88 (t,7=1.3 Hz, 1H), 4.58 (s, 2H), 3.74 (q, 7=7.2 Hz, 2H). 1.19 (t. 7 =7.2 Hz, 3H)
Y2092	(thin film) 3232,3106. 2968, 2942, 2870, 2251, 1651,1585		’H NMR (400 MHz, CDCIj) δ 8.97 (d, 7= 2.7 Hz, 1H), 8.63 (dd, 7 = 4.8,1.5 Hz, 1H), 8.08-8.03 (m, 2H), 7.47 (dd, 7=8.4. 4.7 Hz, 1H). 6.14 (d, 7 = 8.4 Hz, 1H), 3.98-3.89 (m, 1H), 3.25 (s. 3H), 2.97 (m, 4H), 2.00- 1.72 (m, 6H)	1JCNMR(1O1 MHz. CDCIj) δ 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

Y2093	(thin film) 3086, 2980, 2936, 2548, 1657	ESIMS m/z 309 ([Μ-H]')	’H NMR (400 MHz, Chloroform-d) δ 8.96 (dd, J = 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, 1 H), 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)
Y2094	(thin film) 3082, 2983, 1649,1486, 1291	ESIMS m/z 265 ([M+H]*)	’H NMR (CDCI3) δ 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, 1 H), 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 ([M+H]*)	’H NMR (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) δ 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

Y2098		ESIMS m/z 263 ([M+H]*)	’H NMR (CDCI3) δ 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, 1 H), 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 ([M+HH2O]*)	’H NMR (400 MHz, Methanol-ch) δ 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, 1 H), 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+H]*)	’HNMR (CDCh) δ 8.96 (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, 1 H), 7.46 (dd, J =8.5, 4.8 Hz, 1H), 5.25 (t, J = 6.4 Hz, 1H), 3.433.30 (m, 2H), 3.25 (s, 3H), 2.96 (s, 3H), 2.50 (t, J = 5.5 Hz, 2H)	’3C NMR (CDCh) δ 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

Y2104	(thin film) 2139, 1655	ESIMS m/z 366 ([M+H]*)	’H NMR (400 MHz, Chloroform-d) δ 9.16 (d, J = 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+H]*)	’H NMR (400 MHz, CDCI3) δ 9.11 (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+H]*)	’H NMR (CDCIj) δ 8.91 (d, J = 2.7 Hz, 1H), 8.58 (dd, J = 4.7, 1.4 Hz, 1H), 8.097.95 (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 (CDCIj) δ 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

Y2107	(thin film) 2926.1663	ESIMS m/z 348 ([M+H]*)	’H NMR (400 MHz, CDCIa) δ 8.85 (d, J = 2.6 Hz, 1H), 8.62 (dd, 7=4.7,1.3 Hz, 1H), 7.99 (ddd, 7 = 8.3, 2.7.1.4 Hz, 1H), 7.62 (s, 1H), 7.45 (dd, 7 =8.3, 4.8 Hz, 1H), 7.18 (dd, 7= 5.2, 1.1 Hz, 1H), 6.91 (dd, 7 = 5.1.3.5 Hz, 1H), 6.77 (dd, 7 = 3.4, 0.9 Hz, 1H), 3.73 (m, 4H), 1.16 (t, 7= 7.2 Hz, 3H)
Y2108	(thin film) 2973, 1658	ESIMS m/z 348 ([M+H]*)	’HNMR (400 MHz, CDCI3) δ 8.82 (d, 7 =2.5 Hz, 1H), 8.61 (dd, 7 = 4.7,1.4 Hz, 1H), 7.96 (ddd, 7 = 8.3, 2.7,1.4 Hz, 1H), 7.48 (S. 1 H), 7.44 (dd, 7 = 8.5, 4.6 Hz, 1H), 7.24 (dd, 7 = 4.9, 3.0 Hz, 1H), 6.91 (dd,7 = 2.8,1.0 Hz, 1H), 6.87 (dd, 7 = 4.9,1.1 Hz, 1H), 3.70 (m, 2H), 3.56 (s, 2H), 1.15 (t, 7= 7.2 Hz, 3H)
Y2109	(thin film) 2972,1659	ESIMS m/z 377 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.93 (d, 7= 2.6 Hz, 1 H), 8.62 (dd, 7 =4.8,1.4 Hz. 1H), 8.03 (ddd, 7 =8.3, 2.7,1.4 Hz, 1H), 7.96 (s, 1H), 7.45 (dd, 7 =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, 7= 7.2 Hz, 3H)

707

Y2110	(thin film) 2975,1667	ESIMS m/z 347 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.95 (d, J = 2.6 Hz, 1H), 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]*)	’HNMR(400MHz, CDCIj) 6 8.85 (d, J =2.5 Hz, 1H), 8.61 (dd, J =4.7, 1.4 Hz, 1H), 8.49 (m, 1 H), 7.99 (ddd, J =8.3. 2.7,1.4 Hz, 1H), 7.83 (s, 1H), 7.60 (td, J = 7.7,1.8 Hz, 1H), 7.44 (ddd, J =8.3, 4.7, 0.5 Hz, 1 H), 7.24 (d, J = 7.8 Hz, 1H), 7.15 (ddd, J = 7.4, 4.9, 0.8 Hz, 1 H), 3.75 (m, 4H), 1.17 (t, J =7.2 Hz, 3H)
Y2112	(thin film) 2975, 1659	ESIMS m/z 442 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.90 (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. 2H), 1.18 (t, J =7.2 Hz, 3H)

708

Y2113	(thin film) 2190, 658	ESIMS m/z 382 ([M+H]*)	’H NMR (400 MHz,CDCI3) δ 9.08 (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, IH), 1.25 (d, J = 7.1 Hz, 3H)
Y2114	(thin film) 2190, 1660	ESIMS m/z 382 ([M+H]*)	’H NMR (400 MHz, CDCI3) 0 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]*)	’H NMR (CDCI3) δ 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

Y2116	(thin film) 3068, 2977, 2932. 2143, 1653,1440	ESIMS m/z 365 ([M+H]*)	’H NMR (CDCIj) Q 9.11 (s, 0.5H), 9.07 (s, 0.5H), 8.63 (td, J = 5.2. 1.4 Hz, 1H), 8.58(brs, 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), 7.497.41 (m, 1H), 4.22 (d, J = 8.1 Hz, 1H). 4.01 (brs, 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]*)	’H NMR (CDCIj) δ 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)	13C NMR (CDCIj) δ 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]*)	Ή NMR (400 MHz, CDCIj) 5 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), 7.527.39 (m, 1H), 5.15 (s, 2H), 3.75 (q, J= 7.2 Hz, 2H), 1.19 (t, J = 7.2 Hz, 3H)

710

Y2119	(thin film) 1655	ESIMS m/z 346 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 8.95 (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	ESIMS m/z 333 ([M+H]*)	’H NMR (400 MHz, CDCIj) δ 9.02 (d, J =2.5 Hz, 1H), 8.65 (dd, J =4.8,1.4 Hz, 1H), 8.26 (s, 1 H), 8.08 (ddd, J =8.3, 2.7, 1.4 Hz, 1 H), 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+H]*)	’H NMR (4ÔÔ MHz? Chloroform-d) δ 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, 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

Y2122	(thin film) 1676	ESIMS m/z 333 ([M+H]*)	’H NMR (400 MHz, CDCI3) C 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+H]*)	’H NMR (400 MHz, CDCI3) 5 8.96 (d, J =2.6 Hz, 1H), 8.79 (s, 1H), 8.64 (dd, J = 4.8,1.4 Hz, 1 H), 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, 1 H), 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-de): δ 9.75 (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-de): δ 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), 2.552.63 (m, 2H)

712

Y2126		ESIMS m/z 396 ([Μ-H]’)	’H NMR (400 MHz, MeOD): δ 8.99 (d, J =2.24 Hz, 1H), 8.77 (d, J = 9.16 Hz, 1H), 8.61 (d, J =1.92 Hz, 1 H), 8.44 (t, J =2.08 Hz, 1H), 2.76-2.79 (m, 2H), 2.56-2.68 (m, 2H) (note: NH proton ls not seen)
Y2127			’H NMR (400 MHz, DMSO-cfe): δ 9.73 (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, 1 H), 1.11 (d. J = 6.80 Hz, 6H)
Y2128		ESIMS m/z 349 ([M+H]*)	’H NMR (400 MHz, MeOD): δ 8.82 (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 ([ΜΗ])	’H NMR (400 MHz, DMSO-de): δ 9.71 (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-H])	’H NMR (400 MHz. DMSO-d6): δ 10.02 (s, 1H), 8.84 (m, 2H). 8.37 (s, 1 H), 8.07 (s, 1H), 2.37 (s, 3H), 2.72 (t, J =6.76 Hz, 2H), 2.55-2.69 (m, 2H)

713

¥2131		ESIMS m/z 313 ([M+H]*)	’HNMR (400 MHz, DMSO-d6): δ 9.04 (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+H]*)	’H NMR (400 MHz, MeOD): δ 9.00 (d, J =2.12 Hz, 1H), 8.71 (s, 1 H), 8.59 (d, J =1.96 Hz, 1 H), 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]*)	’H NMR (400 MHz, CDClj): δ 8.87 (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+H]*)	’H NMR (400 MHz, CDClj): δ 8.87 (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]*)	’H NMR(400 MHz, DMSOde ):5 9.03 (s, 1H), 8.66 (d, J = 2.08 Hz, 1H), 8.31 (d, J = 2.52 Hz, 1 H), 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

Y2136		ESIMS m/z 363 «M+H]*)	’H NMR (400 MHz, MeOD): δ 8.70 (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+H]*)	’H NMR (400 MHz, MeOD): δ 8.84 (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+H]*)	’H NMR (400 MHz, MeOD): δ 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 ([Μ-H]')	’H NMR (400 MHz, Chloroform-d) δ 8.98 (dd, J = 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 m/z 356 ([M]*)	’H NMR (400 MHz, CDCI3): δ 8.87 (s, 1H), 8.68 (s, 1 H), 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

Y2141		ESIMS m/z 411 ([M+2+H]*)	’H NMR (400 MHz, CDCI3):Ô8.87 (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, 7 =7.28 Hz, 2H)
Y2142		ESIMS m/z 277 ([M+H]*)	’H NMR (CDCI3) δ 8.96 (d, 7=2.6 Hz, 1H), 8.62 (dd, 7 = 4.8,1.4 Hz, 1H), 8.05 (ddd, 7 =8.3, 2.7,1.5 Hz, 1H), 7.96 (s, 1H), 7.46 (dd, 7 = 8.4, 4.7 Hz, 1H), 6.44 (dd, 7=16.8, 2.0 Hz, 1H). 6.18 (dd, 7= 16.7,10.3 Hz, 1H), 5.63 (dd, 7=10.3,1.9 Hz, 1H), 3.78 (q, 7=7.2 Hz, 2H), 1.20 (t, 7=7.2 Hz, 3H)	13C NMR (CDCI3) δ 165.8,148.6, 141.2,140.0, 135.6,129.0, 127.6,126.3, 126.3.124.1, 123.8.44.1, 13.0
Y2143	(thin film) 1649	ESIMS m/z 413 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.63 (dt, 7 = 4.7,1.6 Hz, 1H), 8.06 (ddd. 7 = 8.3, 3.9,2.5 Hz, 1H). 7.95 (s, 1H), 7.52-7.38 (m, 1H). 6.50 (d, 7 =9.2 Hz, 0.7H), 5.50 (d, 7=8.5 Hz, 0.3H), 3.90- 3.53 (m, 2H). 2.37 (dd, 7 = 8.5, 5.3 Hz, 0.4H), 1.90- 1.81 (m, 0.6H), 1.62 (d, 7 = 8.4 Hz, 0.6H), 1.39- 1.34 (m, 0.4H), 1.29 (s, 1.5H), 1.28 (s, 1.5H), 1.171.13 (m. 3H), 1.09 (s. 1.5H), 1.02 (s, 1.5H)

716

Y2144	(thin film) 1704	ESIMS m/z 355.3 ([M+H]*)	’H NMR (400 MHz, CDCIj) 6 8.92 (d, J =2.7 Hz, 1H), 8.65-8.51 (m, 1H), 8.02 (d, 7=8.3 Hz, 1H), 7.90 (s, 1H), 7.42 (dd, J =8.4, 4.8 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)
Y2145		ESIMS m/z 372 ([M+H]*)	’H NMR (CDCI3) 6 8.97 (dd, J =2.7,0.7 Hz, 1H). 8.63 (dd, 7= 4.8,1.5 Hz, 1H), 8.08-7.99 (m, 2H), 7.46 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 5.26 (t, J = 6.5 Hz, 1H). 3.71 (q, J = 7.2 Hz, 2H), 3.41 - 3.30 (m, 2H), 2.96 (s, 3H), 2.47 (dd, J = 6.2, 4.8 Hz, 2H), 1.17 (t, J = 7.2 Hz, 3H)	13C NMR (CDCIj) 6 171.6,148.8, 140.7,140.2, 135.6,126.6, 126.4,124.1, 123.3,44.0, 40.2, 39.2, 34.6,13.1
Y2146		ESIMS m/z 404 ([M+H]*)	’H NMR (CDCIj) 6 8.95 (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, 1 H), 7.95 (s, 1H), 7.47 (dd, 7=8.3,4.7 Hz, 1H), 3.71 (q, 7=7.1 Hz, 2H). 2.72 (t, 7=7.1 Hz, 2H), 2.64-2.53 (m, 2H), 2.38-2.21 (m, 4H), 2.17 (s, 3H), 1.16 (t, 7 = 7.2 Hz, 3H)	,eF NMR (CDCIj) 6 - 65.19

717

Y2147	(thin film) 3575,1703	HRMS-FAB (m/z) [M+H]* calcd for CieH2oCIN40 3, 351.1218; found, 351.1237	’H NMR (400 MHz, CDCI3) 5 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(brs, 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+H]* calcd for Ci2H12CIN4O 31 295.0592; found, 295.0600	’HNMR (400 MHz, CDCI3) 5 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, 1 H), 3.78 (dd, J =12.7, 4.0 Hz, 1H), 3.49 (s, 1H)	’3C NMR (101 MHz, CDCh) δ 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) [M+H]* calcd for CnHaCI^O 41 381.1324; found, 381.1331	’H NMR (400 MHz, CDCI3) 5 8.93 (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, J=5.4Hz, 2H), 2.03 (s, 3H), 1.42 (s, 9H)

718

Y2150	(thin film) 1660	ESIMS m/z 463 ([M+H]*)	’H NMR (400 MHz, CDCI3) 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) [M+H]* calcd for C1sH2oCIN40 3( 339.1218; found, 339.1227	’H NMR (400 MHz, CDCI3) 5 8.92 (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 CisHîtNsOî, 392.1848; found, 392.1850	’H NMR (400 MHz, CDCI3) 5 8.91 (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, 1 H), 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

Y2153	(thin film) 1704	HRMS-FAB (m/z) [M+H]* calcd for Ci5HiflCIFN4 Oj. 341.1175; found, 341.1178	’H NMR (400 MHz, CDCIj) 5 8.93 (d, 7=2.7 Hz, 1H), 8.57 (dd, 7= 4.8,1.4 Hz, 1H), 8.01 (dt, 7= 8.6,1.7 Hz, 1H), 7.93 (s, 1H), 7.42 (dd, 7 =8.4,4.7 Hz, 1H), 4.70 (br s, 1H), 4.58 (brs, 1H), 3.84 (dt, 7= 26.3, 4.8 Hz, 2H), 1.44 (s, 9H)
Y2154	(thin film) 1740, 1667	HRMS-FAB (m/z) [M+H]* calcd for C17HiflCIF3N4 o3. 419.1092; found, 419.1098	’H NMR (400 MHz, CDCIj) 5 8.96 (d, 7 = 2.7 Hz, 1H), 8.63 (dd, 7 = 4.8, 1.5 Hz, 1H), 8.05 (ddd, 7= 8.3, 2.7, 1.4 Hz, 1H), 8.02 (s, 1H), 7,46 (dd, 7 = 8.3, 4.8 Hz, 1H), 4.30 (t, 7=6.4 Hz, 2H), 3.71 (q, 7= 7.1 Hz, 2H), 2.66 (t,7=6.5 Hz, 2H), 2.57 - 2.39 (multiple peaks, 4H), 1.16 (t, 7=7.2 Hz, 3H)	’®F NMR (376 MHz, CDCIj) 5 -66.02
Y2155	(thin film) 1707	HRMS-FAB (m/z) [M+H]* calcd for ChH15CIF3N4 o2, 363.0830; found, 383.0842	’H NMR (400 MHz, CDCIj) 5 8.92 (d, 7 = 2.7 Hz, 1H). 8.59 (dd, 7= 4.8,1.5 Hz, 1H), 8.02 (ddd, 7 = 8.4, 2.7,1.5 Hz, 1H), 7.86 (S, 1H), 7.43 (dd, 7 =8.4, 4.7 Hz, 1H), 4.37 (d, 7 =43.7 Hz, 2H), 3.67 (q, 7 = 7.1 Hz, 2H), 2.49 (d, 7 = 45.5 Hz, 2H), 1.20 (t, 7=7.2 Hz, 3H)	19F NMR (376 MHz, CDCIj) 5 -64.89

720

Y2156	(thin film) 1709	HRMS-FAB (m/z) [M+H]* calcd for c,5h17cif3n4 o2, 377.0987; found, 377.0997	Ή NMR (400 MHz, CDClj) δ 8.93 (d, J = 2.6 Hz, 1 H), 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(brs, 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, CDClj) δ -64.89
Y2157	(thin film) 1647	HRMS-FAB (m/z) [M+H]* calcd for Ci5H18CIF3N5 O, 376.1146; found, 376.1155	’H NMR (400 MHz, CDClj) δ 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), 3.503.42 (m, 2H), 2.67 (s, 3H), 2.45-2.25 (m, 2H), 1.18 (t, J =7.0 Hz, 3H)	19F NMR (376 MHz, CDClj) δ -65.22
Y2158	(thin film) 3332,1650	HRMS-FAB (m/z) [M+H]* calcd for C14HieCIF3N5 O, 362.0990; found, 362.0996	’H NMR (400 MHz, CDClj) δ 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)	,9F NMR (376 MHz, CDClj) δ -64.96.

72I

Y2159	(thin film) 1664	HRMS-FAB (m/z) [M+H]* calcd for CuH15FCI3N< □S, 379.0602; found, 379.0612	Ή NMR (400 MHz, CDCI3) 5 8.95 (d, J = 2.7 Hz, 1Η), 8.63 (dd, 7=4.8,1.4 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.8,1.5 Hz, 1H), 8.01 (s, 1H). 7.46 (dd, 7 = 8.4, 4.7 Hz, 1H), 3.75 (q, 7 = 7.2 Hz, 2H), 3.00 (dd, 7=9.3, 6.3 Hz, 2H), 2.53 - 2.35 (m, 2H), 1.20 (t, 7 =7.2 Hz, 3H)	’9F NMR (376 MHz, CDCIj) 5 -66.45.
Y2160	(thin film) 3335, 1650	HRMS-FAB (m/z) [M+HJ* calcd for Ci5HteCIF3N5 0, 376.1146; found, 376.1155	’H NMR (400 MHz, CDCI3) 5 8.95 (dd, 7=2.7,0.7 Hz, 1H), 8.63 (dd, 7=4.8, 1.4 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1 H), 7.97 (s, 1H), 7.46 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H), 4.49 (t, 7 = 6.0 Hz. 1H), 3.68 (q, 7 = 7.2 Hz, 2H), 3.28 (q,7 = 6.7 Hz, 2H), 2.25 - 2.02 (m, 2H), 1.83-1.67 (m, 2H), 1.16 (t, 7 = 7.1 Hz, 3H)	’9F NMR (376 MHz, CDCIj) 5 -66.15
Y2161	(thin film) 1708	HRMS-FAB (m/z) [M+H]* calcd for Ci5Hi8CIF2N4 o2. 359.1081; found, 359.1085	’H NMR (400 MHz, CDCIj) 5 8.93 (d, 7=2.7 Hz, 1H), 8.58 (dd, 7 = 4.8,1.4 Hz, 1H), 8.01 (dt, 7=8.2, 2.1 Hz, 1H), 7.92 (s, 1H), 7.43 (dd, 7=8.3, 4.7 Hz, 1H), 6.07 (t, 7 =56.1 Hz, 1H), 3.84 (dt, 7= 13.5, 7.3 Hz, 2H), 1.61-1.32 (m,9H)	’9F NMR (376 MHz, CDCIj) 5 -122.47

722

Y2162	(thin film) 1716	HRMS-FAB (m/z) [M+H]* calcd for c15h17cif3n4 o2. 377.0987; found, 377.0991	’HNMR(400MHz, CDCt3) 5 8.93 (d, J = 2.7 Hz, 1H), 8.59 (dd, 7=4.6,1.4 Hz, 1H). 8.01 (d, 7 = 8.5 Hz, 1H). 7.95 (s, 1H), 7.49- 7.37 (m, 1H), 4.17 (q, 7 = 8.6 Hz, 2H), 1.54 (s, 3H), 1.43 (s, 6H)	’9F NMR (376 MHz, CDCI3) 5 -70.99
Y2163	(thin film) 1701	HRMS-FAB (m/z) [M+H]* calcd for C15Hi9CI2N4 o2, 357.0880; found, 357.0885	’H NMR (400 MHz. CDCÿ~ 5 8.93 (d, 7=2.6 Hz, 1H), 8.58 (dd, 7 = 4,8,1.5 Hz, 1H), 8.07-7.99 (m, 1H), 7.97 (s, 1H), 7.43 (dd,7 = 8.4, 4.8 Hz, 1H), 3.88 (t, 7 = 6.2 Hz, 2H), 3.70 (s, 2H), 1.62-1.32 (m, 9H)
Y2164	(thin film) 3334, 1650	HRMS-FAB (m/z) [M+HJ* calcd for C14HieCIF3N5 O, 362.0990; found, 362.0993	’H NMR (400 MHz, CDCI3) 5 8.91 (d,7 = 2.6 Hz, 1H), 8.60 (dd, 7=4.8, 1.4 Hz, 1H), 7.97 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.77 (s, 1H), 7.44 (ddd, 7 = 8.3, 4.8, 0.8 Hz, 1 H), 3.99 (q, 7 = 9.2 Hz, 2H), 3.57 (q,7 = 7.1 Hz, 2H), 2.72 (br s, 3H), 1.20 (t, 7 = 7.1 Hz, 3H)	19F NMR (376 MHz, CDCI3) 5 -70.24

723

Y2165	(thin film) 3302, 1661	HRMS-FAB (m/z) [M+H]* calcd for C13HuCIF3N5 0, 348.0833; found, 348.0838	’H NMR (400 MHz, CDCI3) 5 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)	’9F NMR (376 MHz, CDCIj) 5 -73.10
Y2166	(thin film) 1686	ESIMS m/z 300 ([M+H]*)	’HNMR(400MHz, CDCI3) 5 8.97 (dd, J =2.6, 0.8 Hz. 1H), 8.63 (s, 1H), 8.55 (dd, J = 4.8,1.5 Hz, 1 H), 7.99 (ddd, J =8.3, 2.7, 1.4 Hz, 1H), 7.40 (ddd, J = 8.3, 4.7,0.8 Hz, 1 H), 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]*)	’H NMR (400 MHz, CDCI3) 5 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

Y2168	(thin film) 1691	ESIMS m/z 276 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (dd, J =2.8, 0.7 Hz, 1H), 8.67 (s, 1 H), 8.58 (dd, J =4.7,1.4 Hz, 1H), 8.01 (ddd, J =8.3, 2.7,1.5 Hz, 1 H), 7.42 (ddd, J =8.4, 4.8,0.8 Hz, 1H), 6.15 (td, J = 2.8, 0.6 Hz, 1 H), 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+H]* calcd for C17H2oCIN40 21 347.1269; found, 347.1282	’H NMR (400 MHz, CDCI3) δ 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 C13H13OF3N4 OS, 365.0445; found, 365.0450	’H NMR (400 MHz, CDCI3) δ 8.97 (dd, J =2.7, 0.7 Hz, 1H). 8.64 (dd, J = 4.8,1.4 Hz, 1H), 8.10-8.01 (multiple peaks, 2H), 7.47 (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)	”FNMR(376 MHz, CDCI3) δ -66.63

725

Y2171	(thin film) 1659	ESIMS m/z 332 ([M+H]*)	’H NMR (400 MHz. CDCI3) δ 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, 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)
Y2172	(thin film) 1683	ESIMS m/z 319 ([M+H]*)	’HNMR(400MHz. CDCI3) δ 8.99 (dd, J =2.7, 0.8 Hz, 1H), 8.66 (dd, J = 4.8,1.4 Hz, 1H), 8.15 (s, 1H), 8.05 (ddd, J =8.3, 2.7,1.4 Hz, 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)
Y2173	(thin film) 1660	ESIMS m/z 333 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.92 (dd, J =2.8, 0.7 Hz, 1H), 8.63 (dd, J = 4.8,1.4 Hz, 1H), 8.19 (s, 1 H), 8.01 (ddd, J =8.3, 2.7,1.5 Hz, 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

Y2174	(thin film) 1660	ESIMS m/z 333 ([M+H]*)	’H NMR (400 MHz, CDCIj) 5 8.95 (d, J = 2.7 Hz, 1H), 8.80 (S, 1 H), 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), 4.944.56 (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) [M+H]* calcd for CiaHieCIN50, 356.1273; found, 356.1276	’H NMR (400 MHz. CDCIj) 5 8.91 (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, 1 H), 7.43 (ddd, J =8.4, 4.8,0.8 Hz, 1H), 7.35- 7.21 (multiple peaks, 5H), 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 ([M+H]*)	’H NMR (CDCIj) 5 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

Y2177		ESIMS m/z 359 ([M+H]*), 358 ([M-H])	’H NMR (400 MHz, Chloroform-c/) δ 9.00 - 8.91 (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, 1 H). 6.06 (d, J =15.3 Hz, 1H), 3.78 (q, J =7.1 Hz, 2H), 2.992.77 (m, 2H), 1.20 (t, J = 7.2 Hz, 3H)
Y2178		ESIMS m/z 374 ([M+H]*), 345 ([M-H])	’H NMR (MeOH-d4) δ 9.04 (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), 2.722.53 (m, 2H), 1.15 (t, J = 7.2 Hz, 3H)	13C NMR (MeOH-cL) δ 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+H]*), 391 ([M-H]')	’H NMR (400 MHz, Chloroform-d) δ 8.96 (dd, J = 2.7, 0.7 Hz, 1H), 8.64 (dd, J = 4.8,1.5 Hz, 1 H), 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(m,4H), 2.37-2.24 (m, 1H), 1.18 (t, J = 7.2 Hz, 3H)

728

Y2180		ESIMS m/z 448 ([M+H]*)	’H NMR (CDCIj) Ô 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), 7.417.34 (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 (CDCIj) δ 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		ESIMS m/z 534 ([M+H]*)	’HNMR(CDCIj) δ8.70- 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

Y2182		ESIMS m/z 355 ([M+H]*)	’H NMR (CDCI3) δ 8.95 (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, 1 H), 7.51 - 7.41 (m, 1H), 3.30 (br. s, 3H), 1.46 (brs, 2H), 1.16 (brs, 2H)	’3C NMR (CDClj) δ 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 CieH17CIN5O 2, 370.1065; found, 370.1066	’H NMR (400 MHz, CDClj) δ 8.98-8.90 (m, 1H), 8.62 (dd, J = 4.7,1.4 Hz, 1 H), 8,08 (s, 1H), 8.02 (ddd, J = 8.4, 2.7,1.4 Hz, 1H), 7.697.59 (multiple peaks, 3H), 7.56-7.48 (m, 1 H), 7.497.35 (multiple peaks, 3H), 3.77 (q, J = 7.2 Hz, 2H), 1.25 (t, J =7.2 Hz, 3H)
Y2185		ESIMS m/z 309 ([M+Na]*)	’H NMR (400 MHz, CDClj) δ 9.82 (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

Y2186	(thin film) 3424, 3274, 3152, 3080, 1658,1602. 1588	HRMS-FAB (m/z) [M+H]* calcd for CuHjjCINsO, 266.0803; found, 266.0804	’HNMR (400 MHz, CDClj) 6 8.89 (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) [M+H]* calcd for Ci4HieCIN4O 3, 323.0905; found, 323.0906	’HNMR (400 MHz,CDCI3) 6 9.00 (S,1H), 8.59 (d, J = 4.8 Hz, 1H), 8.15 (ddd, J = 8.4, 2.6,1.4 Hz, 1 H), 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+H]* calcd for C17H19CIF3N4 o2, 403.1143; found, 403.1149	’HNMR (400 MHz, CDClj) δ 8.97 (d, J =2.7 Hz, 1H). 8.63 (dd, J =4.7,1.4 Hz. 1H), 8.10-8.01 (multiple peaks, 2H), 7.46 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 3.68 (q, J =7.2 Hz, 2H), 2.842.70 (multiple peaks, 4H), 2.51 - 2.34 (multiple peaks, 4H), 1.15 (t, J =7.2 Hz, 3H)	’9F NMR (376 MHz, CDCI3) δ -66.60

731

Y2189	(thin film) 3246, 3095, 1728.1667	HRMS-FAB (m/z) [M+H]* calcd for CigHi9CIN5O 3. 400.1171; found, 400.1173	’HNMR (400 MHz, CDCI3) 6 8.95 (dd, 7=2.7, 0.7 Hz, 1 H), 8.62 (dd, 7=4.7,1.5 Hz, 1H), 8.09 (s, 1 H), 8.02 (ddd, 7= 8.3,2.7,1.4 Hz, 1H), 7.67 - 7.55 (multiple peaks, 3H), 7.45 (ddd, 7 = 8.3, 4.8, 0.8 Hz, 1H), 6.926.82 (m, 2H), 3.83 (s, 3H), 3.76 (q, 7 =7.2 Hz, 2H), 1.24 (t, 7=7.2 Hz, 3H)
Y2190	(thin film) 3097,1730, 1672	HRMS-FAB (m/z) [M+H]* calcd for C19HieCIF3N5 O3, 454.0888; found, 454.0892	’HNMR(400 MHz, CDCI3) 6 8.98-8.92 (m, 1H), 8.63 (dd, 7=4.8,1.4 Hz, 1H), 8.09 (s, 1H), 8.03 (ddd, 7 = 8.3,2.7,1.4 Hz, 1H), 7.75- 7.67 (m, 2H), 7.67 - 7.60 (m, 1H), 7.46 (ddd, 7= 8.4, 4.8, 0.8 Hz, 1 H), 7.31- 7.19 (m, 2H), 3.75 (q. 7 = 7.2 Hz, 2H), 1.24 (t,7=7.2 Hz, 3H)	19F NMR (376 MHz, CDCI3)6 -57.66.
Y2191	(thin film) 3245, 3104, 1716,1681	HRMS-FAB (m/z) [M+H]* calcd for C1BH12CIF6N5 o2, 460.0594; found, 460.0597	’H NMR (400 MHz, CDCI3) 6 8.98-8.91 (m, 1H), 8.67 (dd, 7= 4.8,1.5 Hz, 1H), 8.10 - 8.02 (multiple peaks, 2H), 7.97 (s, 1H), 7.49 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H), 3.71-3.59 (m, 2H), 1.19 (t, 7= 7.2 Hz, 3H)

732

Y2192	(thln film) 3096,1737, 1677	HRMS-FAB (m/z) [M+H]* calcd for c18h15ci3n5 Oî. 438.0286; found, 438.0291	’H NMR (400 MHz, CDCIj) δ 8.95 (dd, J = 2.7, 0.7 Hz, 1H). 8.66 (dd, J =4.8,1.5 Hz. 1H), 8.09-8.00 (multiple peaks, 2H), 7.93 (s, 1H), 7.51-7.43 (multiple peaks, 2H), 7.34 (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) [M+H]* calcd for C1flHlflCIN5O 2, 384.1222; found, 384.1227	’H NMR (400 MHz, CDCIj) 5 8.95 (s, 1H), 8.62 (d, J = 4.8 Hz, 1 H), 8.10 (s, 1H), 8.02 (ddd, J =8.4, 2.7,1.4 Hz, 1H), 7.68 (s, 1 H), 7.57 -7.49(m, 2H), 7.45 (dd, J = 8.4, 4.8 Hz, 1 H), 7.247.16 (m, 2H), 3.76 (q, J = 7.2 Hz, 2H), 2.37 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H)
Y2194	(thln film) 3247, 3095, 1741, 1677	HRMS-FAB (m/z) [M+H]* calcd for C18HieCIFNs o2, 388.0971; found, 388.0974	’H NMR (400 MHz, CDCIj) δ 8.98 (d, J =2.7 Hz, 1 H), 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, 1 H), 7.547.42 (multiple peaks, 2H), 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)	”F NMR (376 MHz. CDCIj) δ -114.79

733

Y2195		ESIMS m/z 340 ([M+1]*), 398 ([M-H]')	’H NMR (CDCI3) δ 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, 7 = 7.2 Hz, 2H), 3.65 (dd, 7=5.5, 3.3 Hz, 2H), 3.55 (dd, 7=5.5, 3.4 Hz, 2H), 3.35 (s, 3H), 1.17 (t, 7 = 7.2 Hz, 3H)
Y2196		ESIMS m/z 336 ([M+H]*)	’H NMR (CDCI3) δ 8.95 (d, 7 = 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, 7 = 8.3,4.7 Hz, 1H), 3.96 (s, 2H), 3.71 (q, 7 = 7.1 Hz, 2H), 3.33 (d, 7=7.0 Hz, 2H), 1.17 (t, 7=7,2 Hz, 3H), 1.10-0.94 (m, 1H), 0.60-0.36 (m, 2H), 0.250.11 (m, 2H)
Y2197	(thin film) 2934,1676, 1459	ESIMS m/z 365 ([M+2H]*)	’H NMR (CDCI3) δ 8.95 (s, 1H), 8.64 (s, 1H), 8.04 (d, 7 = 8.2 Hz, 1H), 7.98 (s, 1H), 7.47 (dd. 7=7.7,4.6 Hz, 1 H), 4.10 (s, 2H), 3.99 (q, 7 = 8.7 Hz, 2H), 3.72 (q, 7 = 7.1 Hz, 2H), 1.18 (t, 7 = 7.2 Hz, 3H)

734

Y2198	(thin film) 2923,1679, 1459	ESIMS m/z 378 ([M+H]*)	’H NMR (CDCI3) δ 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+H]*). 353.4 ([M-H])	’H NMR (400 MHz, CDCI3) 6 8.98 (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]*)	’H NMR (400 MHz, CDCI3) 6 8.94 (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, 1 H), 7.07 (s, 1H), 6.89 (s. 1H). 4.61 (s, 2H), 3.28 (S, 3H)

735

Y2201

(thin film) 1675

ESIMS m/z 358 ([M+H]*)

’H NMR (400 MHz, CDCI3) δ 8.95 (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, 1 H), 7.35 (s, 1H), 7.06 (s, 1H). 6.89 (s, 1H), 4.60 (s. 2H), 3.56 (d, */= 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: GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA) Ratlng Table

% Control (or Mortality)	Ratlng
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 GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA)

Com-	MYZUPE	BEMITA %
pound	% Ctrl @	Ctrl @ 200
No.	200 ppm	PPm
596	A	A
597	A	B
598	A	B
599	A	B
600	A	B
601	A	A
602	A	A

736

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

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

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

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

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

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

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

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

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

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

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

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

1023	B	A
1024	B	A
1025	A	A
1026	A	A
1027	A	A
1026	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

1058	B	A
1059	A	A
1060	A	A
1061	A	A
1062	A	A
1063	A	A
1064	A	C
Y2000	A	A
Y2001	B	B
Y2002	A	A
Y2003	A	A
Y2004	B	A
Y2005	D	B
Y2006	B	B
Y2007	B	A
Y2008	A	B
Y2009	A	A
Y2010	D	B
Y2011	C	C
Y2012	A	A
Y2013	A	A
Y2014	A	B
Y2015	A	A
Y2016	A	A
Y2017	A	B
Y2018	A	D
Y2019	B	A
Y2021	A	B
Y2022	B	A
Y2023	B	A
Y2024	A	B
Y2025	B	B
Y2026	B	A
Y2027	B	B
Y2028	B	A

750

Y2029	B	A
Y2030	B	B
Y2031	A	A
Y2032	B	B
Y2033	B	A
Y2034	A	A
Y2035	B	B
Y2036	A	A
Y2037	A	A
Y2038	A	A
Y2039	D	A
Y2040	B	A
Y2041	C	C
Y2042	A	A
Y2043	A	A
Y2044	A	A
Y2045	A	A
Y2046	A	A
Y2047	A	A
Y2048	B	A
Y2049	B	A
Y2050	A	A
Y2051	B	A
Y2052	A	B
Y2053	B	A
Y2054	D	A
Y2055	C	C
Y2056	A	B
Y2057	A	A
Y2058	A	A
Y2059	A	A
Y2060	A	A
Y2061	A	A
Y2062	D	D
Y2063	D	D

751

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

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

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

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

Claims (5)

1. WE CLAIM

   1. A composition comprising a molécule according to “Formula One wherein (a)

   A ls either attachment bond attachment bond (b) R1 ls H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted C₂-Ce alkenyl, substituted or unsubstituted CpCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Ce-C2o aryl, substituted or unsubstituted CrQro heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂, N(R9)₂,

   N(R9)C(=X1)R9, S(O)„R9, S(O)_nOR9, S(O)_nN(R9)_z, or R9S(O)„R9, wherein each said R1, which ls substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, CrCe haloalkyl, CrCe haloalkenyl, CpCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, Ce-C^ aryl, or Ci-Qro heterocyclyl, (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 C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or 756 unsubstituted Cj-Cw cycloalkenyl, substituted or unsubstituted Ce-G» aryl, substituted or unsubstituted G-C^ heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)2, N(R9)₂₁

   N(R9)C(=X1)R9, SR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said R2, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, Gj-C_w cycloalkyl, Gj-C_w cycloalkenyl, C3-C10 halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, Ce-C» aryl, or C1-C20 heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

   (d) R3 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted G-Cg alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-G_o cycloalkenyl, substituted or unsubstituted Ce-Go aryl, substituted or unsubstituted C_rGo heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9,0(=Χ1)Ν(Β9)2, N(R9)2, N(R9)C(=X1)R9, SR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said R3, which is substituted, has one or more substituents selected from F, Cl, Br, l, CN, NO_Z, G-Ce alkyl, CrCe alkenyl, Ci-Ce haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, C3-C10 cycloalkenyl, Cj-Cw halocycloalkyl, C₃-Go halocycloalkenyl, OR9, S(O)_nOR9, Ce-Go aryl, or G-Go heterocyclyl, (each of which that can be substituted, may optionaliy be substituted with R9);

   (e) when A is (1) A1 then A1 is either (a) A11 attachment bond to carbon attachment bond to nitrogen

   Ail where R4 Is H, NG. substituted or unsubstituted CrG alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted G-G alkoxy, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted G-Go aryl, substituted or unsubstituted C_rGo heterocyclyl, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂, N(R9)î, N(R9)C(=X1)R9, S(O)„OR9, or R9S(O)_nR9, wherein each said R4, which Is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rG alkyl, CrCe alkenyl, C_rG haloalkyl, Cr Ce haloalkenyl, Ci-Ce haloalkyloxy, CrCe haloalkenyloxy, Gj-Cw cycloalkyl, C₃-Go cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(O)_nOR9, G-Go aryl, or CpGo

   757 heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9), or (b) A12 attachment bond to nitrogen

   A12 where R4 ls a C_rCe alkyl, (2) A2 then R4 is H, F, Cl, Br, I, CN, NO₂₁ substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted Ci-Ce alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C_w cycloalkyl, substituted or unsubstituted C₃-C_t0 cycloalkenyl, substituted or unsubstituted Ce-C^ aryl, substituted or unsubstituted Ci-Cm heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂₁ N(R9)₂, N(R9)C(=X1)R9, SR9, S(O)_nOR9, orR9S(O)_nR9, wherein each said R4, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ C_rCe alkyl, CrCe alkenyl, C,-Ce haloalkyl, CrCe haloalkenyl, Ci-Ce haioalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, C3-C10 cycloalkenyl, C3-C10 halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, Ce-C^ aryl, or Cj-Cm heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

   (f) R5 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted Ci-Ce alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-Cto cycloalkyl, substituted or unsubstituted C3-C10 cycloalkenyl, substituted or unsubstituted Ce-C^ aryl, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)₂₁ N(R9)₂, N(R9)C(=X1)R9, SR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said R5, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, C,-Ce haloalkyl, CrCe haloalkenyl, CrCe haioalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-Cw cycloalkenyl, Ca-Cio halocycloalkyl, CrCto halocycloalkenyl, OR9, S(O)_nOR9, or Ce-C^ aryl, (each of which that can be substituted, may optionally be substituted with R9);

   (g) (1) when A ls A1 then R6 ls R11, substituted or unsubstituted CpCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C_1Q cycloalkyl, substituted or unsubstituted C₃-C_to cycloalkenyl, substituted or unsubstituted Ce-C^ aryl, substituted or

   758 unsubstituted C,-Ca heterocyclyl, OR9, C(=X1)R9, C(=X1)0R9, C(=X1)N(R9)_Z, N(R9)₂, N(R9)C(=X1)R9, SR9, S(O)_nOR9, R9S(O)_nR9, C_rCe alkyl Ce-Ca 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 alkyl)S(O)_n(CrCe alkyl), C(=O)(C_rCe alkyl)C(=O)O(CrCe alkyl). (Ο,-Οβ alkyl)OC(=O)(Ce-Ca aryl), (C,-Ce alkyl)OC(=OXC,-Ce alkyl), Ο,-Οβ alkyl-(C₃-Ci₀ cyclohaloalkyl), or (C,-Ce alkenyl)C(=O)O(Ci-Ce alkyl), or R9X2C(=X1)X2R9, wherein each sald R6 (except R11 ), which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, N0₂, C,-Ce alkyl, CrCe alkenyl, C,-Ce haloalkyl, Cr Ce haloalkenyl, C,-Ce haloalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, C3-C10 cycloalkenyl, C3-C10 halocycioalkyl, C3-C10 halocycloalkenyl, 0R9, S(O)_nOR9, Ce-Ca aryl, or C_rCa 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 arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, 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 C,-Ce alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted CpCe alkoxy, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted CrC₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted Ce-Ca aryl, substituted or unsubstituted C,-Ca heterocyclyl. 0R9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂, N(R9)_Z, N(R9)C(=X1)R9, SR9, S(O)_nOR9, R9S(O)_nR9, C,-Ce alkyl Ce-Ca aryl (wherein the alkyl and aryl can independently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9, R9X2R9, C(=OXC,-Ce alkyl)S(O)_n(C,-Ce alkyl), Ct=O)(C,-Ce alkyl)C(=O)O(Ci-Ce alkyl), (C,-Ce alkyl)OC(=OXCe-C₂o aryl), (C,-Ce alkyl)OC(=OXCi-Ce alkyl), C,-Ce alkyl-(C3-C,o cyclohaloalkyl), or (C_rCe alkenyl)C(=O)O(C_rCe 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, N0₂, C_rCe alkyl, CrCe alkenyl, C_rCe haloalkyl, Cr Ce haloalkenyl, C,-Ce haloalkyloxy, CrCe haloalkenyloxy, C₃-C_w cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycioalkyl, Cj-Ciq halocycloalkenyl, 0R9, S(O)_nOR9, Ce-Ca aryl, or CrCa heterocyclyl, R9aryl, (each of which that can be substituted, may optionally be substituted with R9).

   optionally R6 (except R11 ) and R8 can be connected ln a cyclic arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, S, or N, ln the cyclic structure connecting R6 and R8;

   (h) R7 is O, S, NR9, or NOR9;

   (i) R8 Is substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted C_rCe alkenyl, substituted or unsubstituted CrCe alkoxy, substituted or unsubstituted C_rCe

   759 alkenyioxy, substituted or unsubstituted C3-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted Ce-C» aryl, substituted or unsubstituted C1-C20 heterocyclyl, OR9, OR9S(O)_nR9, C(=X1)R9, C(=X1)OR9, R9C(=X1)OR9, R9X2C(=X1 )R9X2R9,

   C(=X1)N(R9)₂, N(R9}2. N(R9)(R9S(O)_nR9), N(R9)C(=X1)R9, SR9, S(O)„OR9, R9S(O)_nR9, or

   R9S(O)_n(NZ)R9, wherein each said R8, which Is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, CrCe haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C₁₀ cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, N(R9)S(O)_nR9, oxo, OR9, S(O)_nOR9, R9S(O)_nR9, S(O)_nR9, Co-Cm aryl, or Ci-Cm 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_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted CrC_e alkenyioxy, substituted or unsubstituted C₃-Ci₀ cycloalkyl, substituted or unsubstituted CrCio cycloalkenyl, substituted or unsubstituted Ce-C^ aryl, substituted or unsubstituted CpC^ heterocyclyl, substituted or unsubstituted SÎOJnCrCe alkyl, substituted or unsubstituted N(C_rCealky1)₂, wherein each said R9, which Is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ CpCe alkyl, CrCe alkenyl, C_rCe haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C₃-C₁₀ cycloalkyl, CrCw cycloalkenyl, C3-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OC_rCe alkyl, OCrCe haloalkyl, S(O)_nCrCealkyl_t S(O)„OCrCe alkyl, Ce-C^ aryl, or CpC^ heterocyclyl;

   (k) nls0,1,or2;

   (l) X is N or CRm where Rni is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C_rCe alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted C_rCe alkoxy, substituted or unsubstituted C_rCe alkenyioxy, substituted or unsubstituted C₃-Ci₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted Ce-C» aryl, substituted or unsubstituted CpC» heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂₁ N(R9)₂, N(R9)C(=X1)R9, SR9, S(O)nR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said which Is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C-rCe alkyl, CrCe alkenyl, C^-Ce haloalkyl, CrCe haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C₃-Ci₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, Cs-Cio halocycloalkyl, C3-C₁₀ halocycloalkenyl, OR9, S(O)_flOR9, Co-Cm aryl, or CpC^ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

   (m) X1 Is (each independently) O or S;

   (η) X2 Is (each independently) O, S, =NR9, or =NOR9;

   (o) Z is CN, NO₂, CrCe alkyl(R9), C(=X1 )N(R9)₂;

   760 (p) R11 is Q_t(C=C)R12, wherein Q_f ls a bond, substituted or unsubstituted Ci - Ce alkyl, substituted or unsubstituted CrCe alkenyl, substituted or unsubstituted Cj-Ce alkynyl, substituted or unsubstituted C₃-Cto cycloalkyl, substituted or unsubstituted C2-C10 cycloalkoxy, substituted or unsubstituted Ci-CealkylOR9, substituted or unsubstituted Ci-CealkylS(O)_nR9, substituted or unsubstituted C,-CealkylS(O)_n(=NR9), substituted or unsubstituted Ct-Ce aikylN(R9) (where (ChC) ls attached directly to the N by a bond), substituted or unsubstituted Ci-CealkylN(R9)2, substituted or unsubstituted CrCe alkenyloxy, substituted or unsubstituted C₃-C_t0 cycloalkenyl, substituted or unsubstituted Co-Ce alky!C(=R7)Co-Ce alkylR9, substituted or unsubstituted Co-Ce alkylC(=R7)OR9, substituted or unsubstituted C_f-Ce alkylOCo-Ce alkylC(=R7)R9, substituted or unsubstituted Ci-CealkylN(R9)(C(=R7)R9), substituted or unsubstituted Ci-CealkylN(R9)(C(=R7)OR9), substituted or unsubstituted Co-C_e alkyl C(=R7)CoCe alkylN(R9) (where (ChC) is attached directly to the N by a bond), substituted or unsubstituted Co-C6alkylC(=R7)Co-Ce alkyiN(R9)₂, OR9, S(O)_nR9, N(R9)R9, substituted or unsubstituted CeCîo aryl, substituted or unsubstituted CcCm heterocyclyi, wherein each said Q_b which is substituted, has one or more substituents selected from F, Ci, Br, I, CN, NO₂, C_rCe alkyl, CrCe alkenyl, CrCe alkynyl, C_t-Ce haloalkyl, Cr Ce haloalkenyl, C_rCe haloalkyloxy, CrCe haloalkenyloxy, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, C3-C10 halocycioalkyi, C3-C10 halocycloalkenyl, OR9, SR9, S(O)nR9, S(O)_nOR9, Cg-C^o aryl, or C,-C2o heterocyclyi, R9ary1, Ci-CealkylOR9, Ci-CealkylS(O)_nR9, (each of which that can be substituted, may optionally be substituted with R9) optionally Qi and R8 can be connected in a cyciic arrangement, where optionally such arrangement can hâve one or more heteroatoms selected from O, S, or N, ln the cyciic structure connecting Q1 and R8;

   (q) R12 ls Q, (except where Q, ls a bond), F, Cl, Br, I, Si(R9>₃ (where each R9 ls Independently selected), or R9;

   wherein said molécule ls selected from

   Y2000 ,^CI °» Cl ch₃ IL_n<I H₃c

   761

   Î9Z.

   ^εΗ3 _Μ αχ* ^£ηο^°Χ >^{Ν {}Η33«Η° ^Η3 G003A 8-.-Û Ν-/ Ν ^εΗ3-/°·^_ε Γ^{Ν £}ηΫ\^£η° ¹¹³ frOOSA □^£η ^Ί] 'Υφ ^Η0 0 J eoosA <’Χΰ 0 13 S002A 3^εΗ r^^'ji Μχί· 0 J a a LOOSA

   Y2006 /^Cl P Br A Y2007 7^C1 ° ΓΎ > li-N*¹ H,C Y2008 Cl o ^HÆ° rr^N^ “ IL_nJ h₃c Y2009 ci o^Hî v_o ^CH’ θ' ^CHî N Y2010 ch₃ ci N nX ^ch₃ CA”

   763

   Y2011 H Cl N' n5-Ç^CH3 [TV ^CH3 N Y2012 CIO /—CHj n<hT ³ N Y2013 z^cl Q ci Y2014 Cl ο J* λ-/ Cr ^fcH’ N Y2015 Cl 0 >^N Rj-⁷ Çr v

   764

   Y2016 Cl o /⁴ ^bT Y2017 Cl 0 X CH, (y h₃c> Y2018 ci o y CH₃ Q <? Y2019 ci o Cr N Y2021 Cl S’^cs y M>_f Π ^fcH3 N

   765

   Y2022 CI Q^A Y2023 P '1 o ’ Y2024 Γγ^Ν ' ^CH’ V H₃C Y2025 ci o ^cHa V h₃c Y2026 ,Λζύ CJ—· br

   766

   Y2027 N P °y/A CH, ΓΤ ^CHj br Y2028 Cl O fA”U^CH’ br Y2029 ci o ^3 n< _ N /N ΓΎ > h₃c Y2030 H₃C AA * N Λ~^Ν çA Y2031 Q «.e>

   767

   Y2032 ^ργγ^Ν>_Η N Y2033 Cl o __/^CH3 Cr ^ch> N Y2034 ,^CHS j! _ N ^~N V-J Cr N Y2035 ,^CH’o Çh₃s' ji O-K? Cr ^br Y2036 Cl 0 vf N< λ-Ζ-F Cr ^CHj bT

   768

   69L

   fj] NH |₀ ^Ζ 1V02A d <C«jû ηΛ<Η° ^d OVOZA d /Vd \ H N-f N ^£hd-/°·^ ' ⁿ c * ο n ^EH3 D^£H ^J 6E02A X.-Û N-/ N 8Ε02Λ C-.-0 H J OI3 ZEOZA

   Y2042 Cl ο N // N Cr ^fcH’ br Y2043 Cl 0 Cr '-o N Y2044 Cl 0 CH, nX_ >-<f _ N ^~^N Cr ^fcH’ N Y2045 Cl 0 CHj _Λ N ^~^N Cr N Y2046 ,^CI 0 Lf n==( Cr ^CHj N

   770 \LL

   Lo N-Y N ‘H Yh° ¹³ LSOZA 3^CH Λ ( N-Y N >^N HJ q ₁₃ OSOZA >L ^ch° AJ ^cho^/^s~^ ;*^{Ν ε}Η3-ν^Ν '3 6kOZA ‘»³ -_NXJ N-< N S=( ‘H3-T* ¹³ 8V0ZA _xbL K K-f¥ ,-W >n a ⁰ 13 ZfrOZA

   Y2052 ,^C1 Ο Çr Û Y2053 Cl nX ch₃ N Y2054 Cl N=X CH₃ Çr χρσ^Ν< Y2055 X _ N À-N ? f^Xf Y2056 Cl o Cr ^h

   772

   Y2057 Cl Ο X IL J h₃c-o N Y2058 Cl O σ·*Γ Y2059 Cl o %o 0 < ch₃ Y2060 C! n Çr N Y2061 Q

   773

   Y2062 Cl o^H)Cv^CH’ N< Cr v ^ch> N Y2063 ^ftçt - Y2064 Cl o nX ^CH3 Y2065 CI 0 z-x Y2066 Cr ^cHj N

   774

   SLL

   /··· Λ Ο 13 UOSÂ .N ^EH3 N< n<Js y* i _f 0 13 3^EH OZOSA ο 13 690SA .N ^cd3 ^ÎHD. /'m'M ϊχ-^J rç_E o 13 3^EH 990SA ΟίΑώ ^EH3-V°^ Γ^{Ν ε}ηοΥη°^£η:> Z90SA

   9LL

   P^EHjL _Eh-.^sS ^H3 0 □' 9Z0ZA □^£h A ( ^μ·Μ n~<n ^v E ,S-^ >N ^£H3 Λ n^r SZOSA .N ^[H9^[H3 ^XJ ⁱ³~(Oi N-Z~W o ° ¹³ VZOSA □ ‘H A y ,n-A î-/~^ r ^£H3 ° ¹³ CZOSA x« Λ ^J _x__ ( 13 O 13 ZZ03A

   Y2077 /^Cl Q Cl h₃c Y2078 ch₃₀ ΝΛ Kch₃ χΥ Y2079 n 0 Cl 0 °*Χ' /=^ nZ yj fV^N^^NbH₃ ^<CH’ Y2080 CH₃q nX ^ch₃ ^M o Y2081 N < Pj'^N'^’’fcH₃''^CH3 ^br

   777

   Y2082 Cl o CH₃ nX ^-n^A-CHj zAy-N k ^CH3 pr chjAhj ^k?r Y2083 CH_{3 s} N=\ λ-CHj ^u o Y2084 r> 0 Cl o °*i> A A'^CH1 fY^N^~A A Y2085 Cl ο V“³ pA / H₃C Y2088 n ⁰ Cl 0 %'___ _N;7 AA (Y A, ^<ch’

   778

   Y2089 Cl o /^S>^^CI yN'^SAj fv^ν^Λη₃ ^<ch’ Y2090 q- Y2091 Pr^N^” M h_jC Y2092 Cl nX ch₃ Çr^W¹ Y2093 Cl 0 n<_n>-^^SH AA ny ^h’^c

   779

   08Z.

   ^εΗ0 ^CHO N^. Ν γ=Α A π \ ,^νΑ ί 0 0 ο >S_N' 10 ΖΟΙ-ΖΑ □^εΗ Λ ^εΗΝ *1 Γ-i ‘H0Ô °^ΰ 660ΖΑ ^εΗ0 ”Υη*Ό 10 860ΖΑ ^εΗ3 XX 13 Ζ60ΖΑ 3^CH Λ < X - Ν-Χ Ν ^εΗ0—VN 0 13 V60ZA

   Y2104 ρ Vz-A³ Çr Y2105 ,« vX^Hi (J CHj ’ Y2106 κι z^CI ,—χ N^Z n Π<1 A V/ hX ^ch’ Y2107 »^°>F ÇQ Y2108 Cl o P nA N Λ~^Ν çF>

   781

   Y2109 CH, α° 0 CH, çX Y2110 a» Ô-“· X Y2111 çX> Y2112 ÇrX ’Λ Y2113 cio X^c»3 'N^-=N

   782

   Y2114 ci o V^H3 nX Ν-ΞΝ Q ^CHï y Y2115 N ^Cl QmVH, CH₃CH₂ Y2116 M ^C1 Ny 0 N ^N y k Y2117 N=f^CIO ON—EN O-^nVch, Y2118 P °t_,H n=\ y—' . ή zb-N Γτ > Ιψ h₃c

   783

   Y2119 Pr A V H₃C Y2120 _XI,N Cl o V ^H3^C Y2121 ci o n. _NsJ _ N 4^“N '“N Pr Ά V H,C Y2122 nA ,^cl qU N=\ A' . N A^N Pr Ά IL_nJ h₃c Y2123 ^cl 0 N_VT n< JWN n N ^“N ^N Pr > V HjC

   784

   Y2124 Cl λ'4-N CHj IJ ^{0 CH}1 N Y2125 Cl nÀ JJ 11 o V_CFJ Y2126 n<^^CFJ IJ Y2127 ^HîC'⁰J ' H CHj Ο-Ν^Λγ^ΝΊί^ΛεΗ3 N=/ m=< 0 ^w Cl Y2128 Cl H Xn

   785

   Y2129 H₃C v Cl ^H ch₃ Y2130 Ή· tfî .R F Y2131 ch₃ ci “y^ch, O-n^aV^N’^ch3 ^N=r Y2132 ^Cl Cl CH₃ F Y2133 CI O CH, nX. Λ >-N CH₃ CH ₃

   786

   Y2134 Mu, ch₃ Y2135 Μ Λ¹ N=\ .^NY 0 h₃c-o ch₃ch₃ Y2136 M >^CI N=\ JW 0 pArLy. H₃c-O CH₃ F Y2137 ». Λ· /^ΝΛ-/ί it OⁿvAnAi,^ch’ h3c CHjCHj Y2138 H₃C M ,CI Y—X 1W* n O ^N CH₃ F ^F

   787

   Y2139 Cl 0 Ù-_n^^sh N Y2140 Cl M o y=^N, /=n h₃c_A_nA,ⁿ-O ch₃ch₃ fl_r Y2141 Cl xr Ο z=N ^FF CHj Br Y2142 çyttXcH, h₃c< Y2143 Cl o /=p^{CI Cl}

   788

   Y2144 χτ Cl JW 0 CH, \=/ N 0 ^x _Ch₃ X Y2145 M Λ¹ r.—X »^NW 0 0 0 e V^Nx Jx A 's' \=/ H₃cr Y2146 (A χ Y2147 xr Cl <-x JW o ch, M-N J A Α^η, ^n^o^ch³ \° Y2148 XT Cl ryÆi <_NX θλθ OH ...

   789

   Y2149 N-/^Cl o CH, θγθ ch₃ Y2150 F F NA ^-⁷ N -- N iPr > V HjC Y2151 ζ-λ Ν=γ^α O CH, /VN \ X LCU, \=/ ^iÇo^chJ OH Y2152 N_s/^Cl o CH, ô Y2153 N^^CI _o CH, F

   790

   Y2154 _N ci ''CH, ° ^F Y2155 çAA-VA ^CH, Y2156 Q-Twp L'cHj ^f Y2157 Q-£CVA k ch₃ ch₃ ^j Y2158 Q-ΡΛ-Α ^ch₃

   791

   Y2159 ’^s,ch₃ Y2160 Q-<X_na_n^^{f k}CH₃ ^F Y2161 _{_t} N^/^C1 _o CH, Q-\X_nAo^ V¹ F Y2162 > ^^C1 o ch₃ (yq^g!; Y F Y2163 N^'o ÇHj Q-^N^_nA_oÀch₃ r> Cl

   792

   Y2164 k ch₃f ch₃ ³ Y2165 ^ch₃ Y2166 Cl 0 .___f^a N X^N Cr ^H N Y2167 Y2168 N

   793

   Y2169 Y2170 ^CHj ^F Y2171 (YZ -CH, N Y2172 Cl o JpN nX >_Λν _ N -Λ~^ν ûr ^fcH’ N Y2173 XJ^vS çr> =..

   794

   Y2174 Cl 0 ^ν··μ Çr ™· Y2175 Γ>Λ°χ__ Y2176 _N ci _{o n}=7 n^1Îs^^x^_n h₃ct Y2177 F F y °Â' rrb N^X Y2178 <-x A» CrAw W v r > A ^hn-n

   795

   Y2179 Pr^N^”> LJ h₃c N Y2180 M >^Cl /—X Η*/ 0 OO ό Y2181 θ Y2182 _ X'o 0-^νΧ_νΧβγ ^N cp Y2184 M >^Cl Nef 0 O HjCr

   796

   Y2185 h₃c^ Y2186 Π-Λ A h₃c^ Y2187 _N ci ^ch₃ ⁰ Y2188 ^{N k}CH, ° Y2189 XT Cl JW 0 0 Yam H₃c^ XîAq-^CH3

   797

   Y2190 m >^Cl x JW ο ο Λ- H₃C7 Y2191 χτ Cl W Ο Ο F ο ^νΛ^λλυ h₃c^ Αρ F Y2192 H₃cr cr^ Y2193 χτ ci r-a. JW ο 0 0¾ h₃ct Y2194 XT ^Cl r-x ?W 0 0F

   798

   Y2195 M H,C Y2196 V H₃C^Z Y2197 ÏÏ _o JA n/- Ν-*ν-°·ν- _F M H₃Z Y2198 U «k ^CH> Y2199 p O n~. v<_nH^s-ch, <V^N-F^N _> CHj ³ ψ «JC

   799

   Y2200 <^N ,^CI θ U Cr ^ch’ ΧΓ Y2201 z^CI V N-/ nX y-' N f? 7
2. 2. A composition according to claim 1 further comprising:

   (a) one or more compounds having acaricldal, algicldal, avicidal, bactericldal, fungicidal, herbicidal, Insecticidal, molluscicidal, nematicîdal, rodenticidal, or virucidal properties; 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).
3. 3. A composition according to clalms 1 or 2 further comprising an agriculturally acceptable carrier.
4. 4. A process comprising applying a composition according to daims 1,2, or 3, to an area to control a pest, in an amount sufficient to control such pest.
5. 5. A process according to claim 4 wherein said pest Is selected from beetles, earwigs, cockroaches, Aies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristietails, mites, ticks, nematodes, and symphylans.