OA16403A - Pesticidal compositions and processes related thereto. - Google Patents

Abstract

This document discloses molecules having the following formula (I) :

Description

FIELD OF THE DISCLOSURE

This disclosure is related to the field of processes to produce molécules that are useful 10 as pesticides (e.g., acaricides, insecticides, molluscicides, 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 in agriculture. The world-wide agricultural losses amount to billions 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 importantly, 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 older pesticides, such as DDT, the carbamates, and 25 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 in the définitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molécule to which it is attached.

Alkenyl means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.

Page 1 of 619

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, (C₃)alkyl which represents n-propyl and isopropyl), (C₄)alkyl which represents n-butyl, sec-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 biphenyl.

“(C_x-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, (C₁-C₄)alkyl means methyl, ethyl, npropyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl, each individually.

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

“Cycloalkenyloxy means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

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

Halo means fluoro, chloro, bromo, and iodo.

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, 2,2Page 2 of6l9 difluoropropyl, 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, îndazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1/-/-pyrazolyl, 4,5-dihydroisoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl. Additional examples include the following

---S O thietanyl thietanyl-dioxide.

DETAILED DESCRIPTION

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

wherein (a) A is either

Page 3 of 6I9

attachment bond

(b) R1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted CpCe alkoxy, substituted or unsubstituted C₂-C_e alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted Ci-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, S(O)nN(R9)₂, or R9S(O)_nR9, wherein each said R1, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C^Cg alkyl, C₂-C₅ alkenyl, C_rC₆ haloalkyl, C₂-C₆ haloalkenyl, C^Ce haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or C_rC₂₀ 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 Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted Ci-Ce alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-Ci₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C1-C20 heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂₁ 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, NO₂₁ C_rC₆ alkyl, C₂-C₆ alkenyl, CrC₆ haloalkyl, C₂-C₆ haloalkenyl, C^Cg haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or Ci-C₂₀ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

Page 4 of619 (d) R3 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted CrC₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted CrC₂₀ 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 R3, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC_e alkyl, C₂-C₆ alkenyl, CrC₆ haloalkyl, C₂-C₆ haloalkenyl, Ci-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-Ci₀ cycloalkenyl, C₃-Cio halocycloalkyi, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or C_rC₂₀ 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 ^R4 n-n attachment bond to nitrogen attachment bond to carbon

Ail where R4 is H, NO₂, substituted or unsubstituted C_rC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted CrC₆ alkoxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Cio cycloalkenyl, substituted or unsubstituted C₆-C₂o aryl, substituted or unsubstituted CrC₂₀ heterocyclyl, C(=X1)R9, C(=X1)OR9, C(=X1 )N(R9)_Z, N(R9)₂, N(R9)C(=X1)R9, 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, Ci-C₆ alkyl, C₂-C₆ alkenyl, Ci-C₆ haloalkyl, C₂C₆ haloalkenyl, Ci-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyi, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂d aryl, or C_rC₂₀ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9), or (b) A12

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attachment bond to nitrogen

Al2 where R4 is a C_rC₆ alkyl, (2) A2 then R4 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C^Cê alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted C₆-C₂o aryl, substituted or unsubstituted Ci-C₂₀ heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂, N(R9)_Z, 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, C^Cg alkyl, C₂-C₆ alkenyl, C!-C₆ haloalkyl, C₂C₆ haloalkenyl, C^Ce haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C_w cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Ci₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂o aryl, or CrC₂₀ 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^Ce alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted C₂-C6 alkenyloxy, substituted or unsubstituted C₃-Cio cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ 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)_nR9, wherein each said R5, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC₆ alkyl, C₂-C₆ alkenyl, C_rC_e haloalkyl, C₂-C_s haloalkenyl, CrC₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, or C₆-C₂₀ aryl, (each of which that can be substituted, may optionally be substituted with R9);

(9) (1) when A is A1 then R6 is substituted or unsubstituted C_rC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted CrC₆ alkoxy, substituted or unsubstituted C₂-C₀ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂o aryl,

Page 6 of619 substîtuted or unsubstituted heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1 )N(R9)₂, N(R9)₂, N(R9)C(=X1 )R9, SR9, S(O)_rOR9, R9S(O)_nR9, C_rC₆ alkyl C₆-C₂₀ aryl (wherein the alkyl and aryl can independently be substîtuted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9, R9X2R9, C(=O)(C_rC_e alkyl)S(O)_n(Ci-C₆ alkyl), C(=O)(C_rC_e alkyl)C(=O)O(C_r C₆ alkyl), (Ο,-Ο₆ alkyl)OC(=O)(C₆-C₂₀ aryl), (C_rC₆ alkyl)OC(=O)(C_rC₆ alkyl), C_rC₆ alkyl-(C₃-C₁₀ cyclohaloalkyl), or (C_rC₆ alkenyl)C(=O)O(Ci-C₆ alkyl), or R9X2C(=X1 )X2R9, wherein each said R6, which is substîtuted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, CrC₆ alkyl, C₂-C₆ alkenyl, C_rC₆ haloalkyl, C₂-C₆ haloalkenyl, C^Cg haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or C_rC₂o heterocyclyl, R9aryl, (each of which that can be substîtuted, may optionally be substîtuted with R9), optionally R6 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 H, substîtuted or unsubstituted CpCg alkyl, substîtuted or unsubstituted C₂-C₆ alkenyl, substîtuted or unsubstituted C_rC_c alkoxy, substîtuted or unsubstituted C₂-C₆ alkenyloxy, substîtuted or unsubstituted C₃-C₁₀ cycloalkyl, substîtuted or unsubstituted C₃-C₁₀ cycloalkenyl, substîtuted or unsubstituted C₆-C₂₀ aryl, substîtuted or unsubstituted CrC₂₀ 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, R9S(O)_nR9, C_rC₆ alkyl C₆-C₂₀ aryl (wherein the alkyl and aryl can independently be substîtuted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1 )R9, R9X2R9, C(=O)(C_rC₆ alkyl)S(O)n(CrC₆ alkyl), C(=O)(C_rC₆ alkyl)C(=O)0(C_r Οθ alkyl), (Ci-Cg alkyl)OC(⁼O)(C6-C2Q aryl), (C-i-Cg alkyl)OC(⁼O)(C-i-C6 alkyl), Ci-Cg alkyl-(C3-Cio cyclohaloalkyl), or (C_rC₆ alkenyl)C(=O)O(C₁-C₆ alkyl), or R9X2C(=X1 )X2R9, wherein each said R6, which is substîtuted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂₁ Ο_Ί-Ο₆ alkyl, C₂-C₆ alkenyl, ΟτΟ₆ haloalkyl, C₂-C₆ haloalkenyl, Ci-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C3-C10 halocycloalkyl, C3-C10 halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or Ci-C₂₀ heterocyclyl, R9aryl, (each of which that can be substîtuted, may optionally be substîtuted with R9), optionally R6 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;

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

Page 7 of 619 (i) R8 is substituted or unsubstituted C-|-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted Ci-C₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C3-C1Q cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂o aryl, substituted or unsubstituted CrCa heterocyclyl OR9, OR9S(O)_nR9, C(=X1)R9, C(=X1)OR9, R9C(=X1)OR9, R9X2C(=X1)R9X2R9, C(=X1 )N(R9)₂, N(R9)_Z, N(R9)(R9S(O)_nR9), N(R9)C(=X1)R9, SR9, S(O)_nOR9, 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, CrC₆ alkyl, C₂-C₆ alkenyl, CrC₆ haloalkyl, C₂-C₆ haloalkenyl, Ci-C₆ haîoalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-Ci₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C3-C10 haiocycloalkenyl, N(R9)S(O)_nR9, oxo, OR9, S(O)_nOR9, R9S(O)_nR9, S(O)_nR9, C₆-C₂₀ aryl, or C_rC₂₀ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9);

(j) R9 is (each independently) H, CN, substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃“C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted Ci-C₂₀ heterocyclyl, S(O)_nCi-C₆ alkyl, NiCrCgalkyl)^ wherein each said R9, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC₆ alkyl, C₂-C₆ alkenyl, C_rC₆ haloalkyl, C₂-Ce haloalkenyl, C_rC_e haîoalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-Ci₀ haiocycloalkenyl, OC^Ce alkyl, OCrC₆ haloalkyl, SiO^CrCealkyl, S(O)_nOC₁-C₆ alkyl, C₆-C₂₀ aryl, or CrC₂₀ heterocyclyl;

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

(l) X is N or CR_ni where R_n1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted CvCe alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂o aryl, substituted or unsubstituted C_rC₂₀ heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂, N(R9)_2j N(R9)C(=X1)R9, SR9, S(O)_nR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said R_ni which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C,-C₆ alkyl, C₂-C₆ alkenyl, Ci-C₆ haloalkyl, C₂-C₆ haloalkenyl, CrC₆ haîoalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-Ci₀ cycloalkenyl, C3-C10 halocycloalkyl, C₃-Ci₀ haiocycloalkenyl, OR9, S(O)_nOR9, Ce-C₂o aryl, or Ci-C₂₀

Page 8 of 619 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; and (ο) Z is CN, NOa, C,-C₆ alkyl(R9), C(=X1 )N(R9)₂; and (P) 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 linked in a cyclic arrangement with only -CH₂-, that when A is A2 then R5 is not C(=O)OH, that when A is A2 and R6 is H then R8 is not a -(CrC₆ alkyl)-O (substituted aryl), and (6) that when A is A2 then R6 is not -(Cialkyl)(substituted aryl).

In another embodiment of this invention A is A1.

In another embodiment of this invention A is A2.

In another embodiment of this invention R1 is H.

In another embodiment of this invention R2 is H.

In another embodiment of this invention R3 is selected from H, or substituted or unsubstituted Ci-C₆ alkyl.

In 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.

In another embodiment of the invention when A is A1, and A1 is A11, then R4 is selected from H, or substituted or unsubstituted C^Cg alkyl, or substituted or unsubstituted C_GC₂₀ aryl.

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

In another embodiment of the invention when A is A1, and A1 is A12, then R4 is CH₃.

In another embodiment of this invention when A is A2 then R4 is selected from H, or substituted or unsubstituted C^Ce alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C,₀ cycloalkyl, substituted or unsubstituted C₆-C₂₀ aryl, wherein each said R4, which is substituted, has one or more substituents selected from F, Cl, Br, or I.

In another embodiment of this invention when A is A2 then R4 is H or C^Cg alkyl.

Page 9 of 619

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

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

In another embodiment of this invention R5 is H, F, Cl, Br, I, or substituted or unsubstituted C_rC₆ alkyl, substituted or unsubstituted C_rC₆ alkoxy .

In 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^Cg alkyl.

In another embodiment of this invention when A is A2 then R6 is selected from is substituted or unsubstituted C_rC_e alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C₁₀ cycloalkyl, C(=X1 )R9, C(=X1 )X2R9, R9X2R9, C(=O)(C_rC₆ alkyl)S(O)_n(CrC₆ alkyl), (CrCg alkyl)OC(=0)(C₆-C₂o aryl), (C_rC_e alkyl)OC(=O)(C_rC₆ alkyl), or R9X2C(=X1)X2R9.

In another embodiment of this invention when A is A2 then R6 and R8 are connected in a cyclic arrangement, where optionally such arrangement can 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 is C_rC₆ alkyl, or CrC₆ alkyl-phenyl.

In another embodiment of this invention R6 is 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)phenyl, CH₂OCH₃, CH₂OC(=O)CH₂OCH₂CH₃₁ CH₂CH₂OCH₃, CH₂OC(=O)OCH(CH₃)₂, ch₂ch₂och₂och₃, CH₂CH₂OCH₃, CH₂CH₂OC(=O)CH₃, ch₂cn.

In another embodiment of this invention R6 is methyl or ethyl.

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

In another embodiment of this invention R8 is selected from substituted or unsubstituted C_rC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C_w cycloalkyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C^C^ heterocyclyl, R9C(=X1)OR9, SR9, S(O)_nOR9, R9S(O)_nR9, or R9S(O)_n(NZ)R9.

In another embodiment of this invention R8 is CH(CH₃)CH₂SCH₃, CH(CH₃)₂, C(CH₃)₂CH₂SCH₃, CH₂CH₂SCH₃, CH₂CF₃, CH₂CH_zC(=O)OCH₃, N(H)(CH₂CH₂SCH₃), OCH₂CH₂SCH_3i CH(CH₂SCH₃)(CH₂phenyl), thiazolyl, oxazolyl, isothiazolyl, substituted-furanyl, CH₃, C(CH₃)₃, phenyl, CH₂CH₂OCH₃, pyridyl, CH₂CH(CH₃)SCH₃, OC(CH₃)₃. C(CH₃)₂CH₂SCH₃, CH(CH₃)CH(CH₃)SCH₃, CH(CH₃)CF₃₁ CH₂CH₂-thienyl, CH(CH₃)SCF₃₁CH₂CH₂CI, CH₂CH₂CH₂CF₃₁ CH₂CH₂S(=O)CH₃, CH(CH₃)CH₂S(=O)CH₃, CH₂CH₂S(=O)₂CH₃, CH(CH₃)CH₂S(=O)₂CH₃, NCH₂CH₃, N(H)(CH₂CH₂CH₃), C(CH₃)=C(H)(CH3), N(H)(CH₂CH=CH₂), CH₂CH(CF₃)SCH₃, CH(CF₃)CH₂SCH₃, thietanyl, CH₂CH(CF₃)₂, CH₂CH₂CF(OCF₃)CF₃, CH₂CH₂CF(CF₃)CF₃, CF(CH₃)₂, CH(CH₃)phenyl-CI, CH(CH₃)phenyl-F, Page 10 of 619

CH(CH₃)phenyl-OCF₃₁ CH₂N(CH₃)(S(=O)₂N(CH₃)₂, CH(CH₃)OCH₂CH₂SCH₃, CH(CH₃)OCH₂CH₂OCH₃, OCH_3t CH(CH₃)SCH₃, CH₂SCH_3i N(H)CH₃₁ CH(Br)CH₃Br, or CH(CH₃)CH₂SCD₃.

In another embodiment of this invention R8 is selected from (substituted or unsubstituted CrC₉ alkyl)-S(O)_n-(substituted or unsubstituted CrCe alkyl) wherein said substituents on said substituted alkyls are selected from F, Cl, Br, I, CN, NO₂. N(R9)S(O)_nR9, OR9, S(O)_nOR9, R9S(O)_nR9, S(O)_nR9, C₆-C₂₀ aryl, or Ci-C₂₀ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9).

In another embodiment of this invention X is CR_n1 where R_n, is H or halo.

In another embodiment of this invention X is CR_n1 where R_n, is H or F.

In another embodiment of this invention X1 is O.

In another embodiment of this invention X2 is O.

While these embodiments hâve been expressed, combinations of these embodiments are envisioned. Furthermore, other embodiments, and combinations of these expressed embodiments and other embodiments are possible.

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

The following schemes illustrate 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 aminopyrazole of Formula Va where R5 = H as in step c of 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 I

Page 11 of 619

Another approach to aminopyrazoles is illustrated in Scheme II. In step a, the nitrile of Formula VI wherein X, R1, R2 and R3 are as previously defined and R5 is hydrogen, is 5 condensed as in Dhananjay, B. Rendre et al. J. Het Chem 2008, 45, (5), 1281-86 with hydrazine of Formula VII, 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 \ Ré

Préparation of aminopyrazoles such as those of Formula Xlla is demonstrated in Scheme III. 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 appropriate aryl halide of Formula Villa where Q is bromo in the presence of a base such as césium carbonate, a copper catalyst such as copper (II) oxide and a ligand such as salîcylaldoxime in a polar aprotic solvent such as acetonitrile. Compounds of Formula IX, as shown in Scheme III, wherein R4 = Cl and R5 = H, can be prepared as in Pelcman, B. et al\N0

Page 12 of 619

2007/045868 A1. Nitration of the pyridylpyrazole of Formula X as in step b of Scheme III and as in Khan. Misbanul Ain et al. J. Heterocyclic Chem. 1981, 18, 9-14 by reaction with nitric acid and sulfuric acid gave compounds of Formula Xla. Réduction of the nitro functionality of compounds of Formula Xla in the presence of hydrogen with a catalyst such as 5% Pd/C in a polar aprotic 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 d of Scheme 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 = Cl, can be allowed to react under Suzuki coupling conditions with a boronic acid such as phenylboronic 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 III

Page 13 of 619

Villa

IX

In step a of Scheme IV, the compounds of Formula XIIb can be treated with triethylorthoformate and an acid such as trifluoroacetic acid. Subséquent addition of a reducing 5 agent such as sodium borohydride in a polar protic solvent such as éthanol gave a compound of Formula XIIla, wherein R6 = methyl.

In step b of Scheme IV, the compound of Formula XIIb 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 XIlia, wherein R6 = isopropyl.

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

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

Page 14 of 6I9 with benzotriazole and an aldéhyde in éthanol followed by réduction using, for example, sodium borohydride, to afford compounds of Formula XIIla. 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 XIIla, wherein R6 = propyl. As in step f, acylation of compounds of Formula XIlia 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

XIHa

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 Λ/,Ν-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° amide may be subsequently alkylated in step b of Scheme V with an alkyl halide such as iodoethane, in the presence of a base such as sodium hydride and a polar aprotic solvent such as N,N-dimethylformamide (DMF) to yield the desired compounds of Formula Ib. The acid chlorides used in the acylation reactions herein are either commercially available or can be synthesized by those skilled in the art.

Scheme V

Page 15 of619

In step a of Scheme VI and as in Sammelson et al. Bioorg. Med. Chem. 2004, 12, 33453355, the aminopyrazoles of Formula Vd, wherein R1, R2, R3, R4, R6 and X are as previously defined and R5 = H, can be halogenated with a halogen source such as N-chlorosuccinimide or N-bromosuccinimide in a polar aprotic solvent such as acetonitrile to provide the R5-substituted pyrazole. In step b, acylation of this compound using the conditions described in Scheme V affords the compound of Formula le, wherein R1, R2, R3, R4, R5, R6, R8 and X are as previously defined.

Scheme VI

In step a of Scheme VII, 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 in step c, respectively, to generate a urea of Formula Id or a carbamate of Formula le, respectively, wherein R9 is as previously defined.

Scheme VII

Page 16 of 619

In step a of Scheme VIII, compounds of Formula XIle, wherein X, R1, R2, R3, R4 and R5 are as previously defined, can be treated with di-tert-butyl dicarbonate (Boc₂O) 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 Boc10 group can be removed under conditions that are well-known in the art, such as under acidic conditions such as trifluoroacetic acid (TFA) in a polar aprotic solvent like dichloromethane to give compounds of Formula Xlllb as in step c.

Scheme VIII

Page 17 of 619

XHIb

In steps a, b and c of 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, wherein 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-(3dimethylamrnopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCI) and a base such as N,Ndimethylaminopyridine (DMAP) in a polar aprotic solvent such as dîchloroethane (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_l8-hexahydro-1H-pyrimido[1,2a]pyrimidine 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 amides of Formula Id, when R6 = H, with an acid chloride in the presence of a base such as diisopropyl ethylamine in a polar aprotic solvent such as dîchloroethane (DCE) yields imides of Formula le, as shown in step d. Furthermore, alkylation of amides of Formula Id, when R6 = H, with an alkyl halide in the presence of a base such as sodium hydride in a polar aprotic solvent such as Λ/,/V-dimethylformamide (DMF) yields alkylated amides of Formula le, as shown in step e. Halogénation of compounds of Formula Id, wherein R1, R2, R3, R4, R6, R8 and X are as previously defined and R5 = H, with a halogen source such as Nbromosuccinimide in a polar aprotic solvent such as DCE or a halogen source such as Nchlorosuccinimide in a polar aprotic solvent such as DCE or acetonitrile or a halogen source such as Selectfluor® in a mixture of polar aprotic solvents such as acetonitrile and DMF give

Page I8 of'619 halogenated pyrazoles of Formula le, wherein R5 = halogen, as shown in step f of Scheme IX. Amides of Formula Id can be converted to thioamides of Formula If in the presence of a thionating agent such as Lawesson's reagent in a polar aprotic solvent such as dichloroethane (DCE), as shown in step g.

Scheme IX

le

If

In step a of Scheme X, compounds of Formula Xllld, wherein X, R1, R2, R3, R4, R5 and R6 are as previously defined, can be treated with compounds of Formula XIX, wherein R8 is as previously defined, in a polar aprotic solvent such as dichloroethane (DCE) to yield compounds of Formula XX. Additionally, when R6 = H and R8 contains a halogen, compounds of Formula XX can be treated with a base, such as sodium hydride, in a polar aprotic solvent, such as THF, to yield compounds of Formula XXI, where m is an integer selected from 1, 2, 3,

4, 5, or 6, as shown in step b of Scheme X.

Scheme X

Page 19 of 619

XXI

Oxidation of the sulfide to the sulfoxide 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 polar protic solvent such as glacial acetic acid to give the sulfoxide of Formula XXIII as in step a of Scheme XI. Alternatively, the sulfide of Formula XXIIa can be oxidized with an oxidant such as hydrogen peroxide in a polar protic solvent such as hexafluoroisopropanol to give the sulfoxide of

Formula XXIII as in 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. Alternatively, the sulfone of Formula XXIV can be generated in a one-step procedure from the sulfide of Formula XXIIa by using the aforementioned conditions with >2 équivalents of sodium perborate tetrahydrate, as in step b of 15 Scheme XI.

Scheme XI

Page 20 of 619

Oxidation of the sulfide to the sulfoximine is accomplished as in Scheme XII where (~S~) can be any sulfide previously defined within the scope of R8 of this invention. The sulfide of Formula 5 XXIIb, wherein X, R1, R2, R3, R4, R5 and R6 are as previously defined, is oxidized as in step a with iodobenzene diacetate in the presence of cyanamide in a polar aprotic solvent such as methylene chloride (DCM) to give the sulfilîmîne of the Formula XXV. The sulfilimine of Formula XXV may be further oxidized to the sulfoximine of Formula XXVI with an oxidant such as metaChloroperoxybenzoic acid (“mCPBA) in the presence of a base such as potassium carbonate 10 in a protic polar solvent System such as éthanol and water as in step b of Scheme XII.

Scheme XII

Page 21 of619

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 iodine in the presence of acids such as iodic acid and sulfuric acid in a polar protic solvent such as acetic acid gives compounds of Formula XXVII. In step b of Scheme XIII and as in Wang, D. et al. Adv. Synth. Catal. 2009, 351, 1722-1726, aminopyrazoles of Formula XIIle 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 aprotic solvent such as DMSO.

Scheme XIII

Page 22 of 619

Xb

XXVII

XHIe

In 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) by Tolf, Bo-Ragnar and Dahlbom, R. In a similar manner, compounds of the Formula XXIX, wherein R4 is Br, X’ represents Br‘ and R5 is as defined previously, can be prepared by treating compounds of the Formula XXVIII with hydrogen gas in the presence of a métal catalyst such as 5% Pd on alumina and a solution of 50% aqueous HBr in a solvent such as éthanol, Alternatively, 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 triethyl silane in the presence of a métal catalyst such as 5% Pd on alumina and an acid such as HCl or HBr, respectively, in a solvent such as éthanol.

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 ditert-butyl dicarbonate (Boc₂O) in the presence of a mixture of solvents such as THF and water and a base such as sodium bicarbonate.

In step c of the Scheme XIV, compounds of the Formula XVIa, wherein X, R1, R2, R3 and R5 are as defined previously and R4 is Cl or Br can be obtained by treating compounds of the Formula XXX, wherein R4 is Cl or Br and R5 is as defined previously, with compounds of the Formula Vlllb, wherein X, R1, R2 and R3 are as defined previously and Q is bromo or îodo, in the presence of a catalytic amount of copper sait such as CuCI₂, an ethane-1,2-diamine dérivative such as N¹,N²-dimethylethane-1,2-diamine and a base such as K₃PO₄ in a polar

Page 23 of 619 aprotic solvent such as acetonitrile at a suitable température.

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 dof Scheme 5 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 boronic ester such as vinylboronic acid pinacol ester or cyclopropylboronic acid pinacol ester in the presence of a

Page 24 of 619 catalyst such as palladium tetrakis, 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 vinyl group of compounds of Formula XXXIII, wherein R1, R2, R3, R5, R6, R8 and X are as previously defined, can be reduced in the presence of hydrogen with a catalyst such as 10% Pd/C in a polar protic solvent such methanol to give compounds of Formula XXXIV, as shown in step a of Scheme XVI. Oxidation of the vinyl group of compounds of Formula XXXIII using an oxidant such as osmium tetroxide in the presence of sodium periodate in mixture of a polar protic solvent such as water and a polar aprotic solvent such as THF gave compounds of Formula XXXV, as shown in step b of Scheme XVI. Réduction of the aldéhyde of compounds of Formula XXXV, as shown in step c of Scheme XVI, with a reducing agent such as sodium borohydride in a polar protic solvent such as methanol gave the corresponding alcohol of Formula XXXVI. Treatment of compounds of Formula XXXVI with a chlorinating agent such as thionyl chloride in a polar aprotic solvent such as dichloromethane gave compounds of Formula XXXVII, as shown in step d of Scheme XVI.

Page 25 of6l9

Scheme XVI

b

r₈

XXXV

HO

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

Scheme XVII

Page 26 of 619

EXAMPLES

The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.

Starting materiaîs, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. 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 is named using conventional naming rules. Ail NMR shifts are in ppm (δ) and were recorded at 300, 400 or 600 MHz unless otherwise stated.

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

To a room-temperature suspension of sodium hydride (NaH, 60% suspension in minerai oil; 4.13 g, 86 mmol) in 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 perîod of 45 min. Stirring was continued for an additional 18 hours (h) under N₂. The reaction was quenched with cold water (H₂O, 50 mL). The dark solid was filtered and washed with ice-cold ethyl alcohol (EtOH) until the washings were colorless. The off-white solid product was dried under vacuum at 60 ’C to provide 3,3-bismethylsulfanyl-1-pyridin-3-yl-propenone as a brown solid (4.8 g, 51 %): ¹H NMR (300 MHz, CDCI₃) Π 9.13 (d, 7 = 1.8 Hz, 1H), 8.72 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.23 (ddd, 7= 7.9, 2, 2 Hz, 1 H), 7.40 (dd, J = 7.9, 4.8 Hz, 1 H). 6.73 (s, 1 H), 2.58 (d, J = 9.4 Hz, 6H); MS m/z 226.2 (M+1 ).

Page 27 of 619

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; ’H NMR (400 MHz, CDCi₃) 5 8.93 (t, 7 = 1.6 Hz, 1H),

Example 1, Step 2: Préparation of (Z)-3-methylamino-3-methylsulfanyl-1-pyridin-3-yl· propenone

A solution of 3,3-bis-methylsulfanyl-1-pyridin-3-yl-propenone (18.6 g, 82.5 mmol) in absolute alcohol (400 mL) under N₂ was treated with methylamine 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 ethyl acetate (EtOAc; 150 mL). The solution was washed with H₂O (2 x 50 mL) and brine (50 mL), dried over Na₂SO_4i, concentrated under reduced pressure and purified by silica gel chromatography eluting with 10% EtOAc in petroleum ether to yield (Z)-3-methylamino-3methylsulfanyl-1-pyridin-3-yl-propenone as a pale yellow solid (8.6 g, 50%): ¹H NMR (300 MHz, CDCI₃)D 11.8 (br s, 1H), 9.06 (s, 1 H); 8.67 (d. J =3.9 Hz, 1 H), 8.26 (d, J =8.0 Hz1H), 7.46 (dd, J= 7.6, 4.9 Hz 1H), 5.62 (s, 1H), 3.10 (d, J = 5.2 Hz, 3H), 2.52 (s, 3H); MS (m/z) 209.2 [M+1J.

(Z)-3-(ethylamino)-3(methylthîo)-1-(pyridin-3-yl)prop-2-en-1-one was prepared as described in Example 1, Step 2:¹H NMR (400 MHz, CDCI₃) 5 11.81 (bs, 1H), 9.04 (dd, J = 2.2, 0.7 Hz, 1H), 8.64 (dd, J =4.8, 1.7 Hz, 1H), 8.29- 7.98 (m, 1H), 7.35 (ddd, J= 7.9, 4.8,0.9 Hz, 1H), 3.45 (q, J = 7.2, 5.6 Hz, 2H), 2.50 (s, 3H), 1.35 (t, J = 7.2 Hz, 3H).

(Z)-3-(cyclopropylmethyl)amino-3(methylthio)-1-(pyridin-3-yl)prop-2-en-1-one was prepared as described in Example 1, Step 2: 'H 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, 1 H). 7.35 (ddd, 7= 7.9, 4.8, 0.8 Hz, 1 H), 5.62 (s, 1H), 3.27 (dd, J = 7.0, 5.5 Hz. 2H), 2.50 (s, 3H), 1.20-1.07 (m, 1H),0.730.49 (m, 2H), 0.41 - 0.17 (m, 2H).

Example 1, Step 3: Préparation of methyl-(2-methyl-5-pyridin-3-pyrazol-3-yl)-amine

Page 28 of 6I9

A solution of (Z)-3-methylamino-3-methylsulfanyl-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 N₂, 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 regioisomer as a brown solid (1.0 g, 27%): ¹H NMR (300 MHz, CDCI₃) □ 8.97 (d, J = 1.3 Hz, 1 H), 8.51 (dd, J = 3.6, 1.0 Hz, 1 H), 8.07 (ddd, J = 5.9, 1.4, 1.4 Hz, 1 H), 7.30 (dd, J = 5.9, 3.6 Hz, 1 H), 5.82 (s, 1 H), 3.69 (s, 3H), 2.93 (s, 3H); MS (m/z) 188.6 [M+1].

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

N-ethyl-1-methyl-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]).

/V-(cyciopropylmethyl)-1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine was prepared as described in Example 1, Step 3: ESIMS m/z 230 ([M+2H]).

1-lsopropyl-/\/-methyl-3-pyridin-3-yl)-1H-pyrazol-5-amine was prepared as described in Èxample 1,Step 3: ¹H NMR (300 MHz, CDCI₃) δ 8.53 (s, 1H), 8.06 - 7.90 (m, J = 7.2 Hz, 2H), 7.13 (dd, J = 7.9, 5.6 Hz, 1 H), 5.33 (s, 1H), 3.70 (bs, 1H), 3.65 (dt, J= 13.2, 6.6 Hz, 1H), 2.31 (s, 3H), 0.88 (d, J= 6.6 Hz, 6H); ESIMS m/z 217 ([M+H]).

3-(5-Fluoropyridin-3-yl)-/V, 1-dimethyl-1/7-pyrazol-5-amine was prepared as described in Example 1, Step 3:¹H NMR (300 MHz, CDCI₃) δ 8.28 (s, 1 H), 7.87 (t, J ~ 1.3 Hz, 1 H), 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])

Page 29 of 619

Example 2: Préparation of (4-chloro-2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-methyl amine

A mixture of methyl-(2“methyl-5-pyrïdin-3-yl-2H-pyrazol-3-yl)-amine (0.35 g, 1.8 mmol) and Nchlorosuccinimide (0.273 g, 2 mmol) was combined in 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; ¹H 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, 1H), 3.80 (s, 3H), 2.91 (d, J = 5.8 Hz, 3H); ESIMS (m/z) 225.6 [M+2].

The reaction also gave 4-chloro-2-methyl-5-pyridin-3-yl-2/7-pyrazol-3-ylamine 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 (br s, 1H), 8.16 (dt, J ~ 8.0, 2.0 Hz, 1H), 7.33 (dd, J= 7.8, 4.8 Hz, 1H), 3.76 (s, 3H); ESIMS (m/z) 207.0 [M-1].

Example 3: Préparation of Z./V-dimethyl-N-^-methyl-S-pyridin-S-yl-ZH-pyrazol-S-yO-Smethylsulfanyl-propionamide (Compound 1)

To a solution of methyl-(2-methyl-5-pyridin-3-yl-2/7-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-methylsulfanyl-propionylchloride (146 mg, 0.9 mmol) in DCE (1.5 mL). After stirring for 10 minutes (min), a solution of 4-A/,/\/-dimethylaminopyridine (DMAP; 107 mg, 0.9 mmol) in 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,/V-dimethyl-/V-(2-methyl-5-pyridin-3-yl-2/-/pyrazol-S-ylJ-S-methylsulfanyl-propionamide, was isolated as a yellow semi-solid (44 mg, 24%):

Page 30 of 619

¹H NMR (400 MHz, CDCI₃) □ 9.00 (s, 1H). 8.58 (s, 1 H), 8.08 (br d, J = 7.0 Hz, 1 H), 7.35 (br dd, J = 7.3, 4.8 Hz, 1H), 6.58 (br s, 0.5 H), 6.49 (br s, 0.5 H), 3.89-3.79 (m, 3H), 3.25 (s, 3H), 2.962.80 (m, 1H), 2.42-2.40 (m, 1H), 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+1J.

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

Example 4: Préparation of 1-methyl-1-(2-methyl-5-pyridin-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) in ice-cold DCE (2 mL) under N_z was added a solution of phosgene in toluene (20%, 0.43 mL, 0.88 mmol). The ice bath was removed after 30 min, and the mixture was stirred at room 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 in an ice bath. To this was added a solution of 2-methylthioethylamine (80 mg, 0.88 mmol) in DCE (2 mL). The ice bath was removed after 10 min, and the reaction mixture 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-(2methylsulfanyl-ethyl)-urea as a yellow gum (14 mg, 6%): ¹H NMR (400 MHz, CDCI₃) □ 8.99 (d, J= 1.5 Hz, 1H), 8.57 (dd, J =4.8, 1.5 Hz. 1H), 8.08 (ddd, J = 8.1,2.1, 2.1 Hz, 1H), 7.34 (dd, J = 7.9, 4.8 Hz, 1H), 6.52 (s, 1H), 4.88 (br t, J = 5.5 Hz, 1H), 3.80 (s, 3H), 3.41 (q, J = 6.3 Hz, 2H), 3.24 (s, 3H), 2.61 (t, J = 6.3, 2H), 2.06 (s, 3H); ESIMS (m/z) 292.2 [M+2].

Compound 8 was made in accordance with the procedures disclosed in Example 4 using 2-(methylthio)ethanol in place of 2-methylthioethylamine.

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

Page 31 of 619 \^{1 2} ,Ν-Ν

² ’/

To éthanol (8.53 ml) was added 3-oxo-3-(pyridin-3-yl)propanenitrile (0.82 g, 5.61 mmol) and methylhydrazine (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 -1methyl-5-(pyridin-3-yl)-1H-pyrazol-3-amine (0.060 g; 6.14%): ¹H NMR (300 MHz, CDCI3) □ 8.72 (s, 1 H), 8.53 (d, 1 H), 7.76-7.63 (m, 1 H), 7.43-7.33 (m, 1 H), 5.75 (s, 1 H), 3.76-3.57 (m, 5H) and 1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine (0.150 g, 15.35%): ¹H NMR (300 MHz, CDCI3) δ

8.88 (s, 1H), 8.48 (d, 1H), 7.99 (d, 1H), 7.38-7.07 (m. 1 H). 585 (s, 1H). 3.80-3.59 (m, 5H).

Example 6, Step 1: Préparation of 3-pyrazol-1-yl-pyridine

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 %): ¹H NMR (400 MHz, CDCI₃) □ 8.99 (d, J = 2.8 Hz, 1 H), 8.48 (dd, J = 4.8, 1.2 Hz, 1H), 8.11 -8.08 (m, 1H), 7.99 (d, J - 1.2 Hz, 1H), 7.78 (d, J~ 1.2 Hz, 1H), 7.38 -

7.35 (m, 1H), 6.53 (t, J= 1.2 Hz, 1H); MS (m/z) 146 [M+1].

3-(3-chloro-1 H-pyrazol-1-yljpyridine was prepared as in Example 6, Step 1: mp 98-106 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.93 (d, 7 = 2.6 Hz, 1H), 8.57 (dd,7 = 4.8, 1.4 Hz, 1H), 8.03 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1 H), 7.90 (d, 7 = 2.5 Hz, 1 H), 7.42 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1 H), 6.46 (d, 7 =

2.5 Hz, 1H); ¹³C (DMSO-d₆) 148, 142, 140, 136, 131, 126, 125, 108.

2-methyl-3-(3-methyl-1 H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 1:¹H NMR (400 MHz, CDCI₃) δ 8.53 (d, 7 = 4.7 Hz, 1 H), 7.67 (d, 7 = 7.9 Hz, 1 H), 7.54 (t, 7 = 8.0 Hz, 1 H),

Page 32 of 619

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 materials as described in Example 6, Step 1.: mp 59.0-61.0 °C; ’H NMR (400 MHz, CDCI3) δ 9.00 (s, 1H), 8.70-8.59 (m, 1H), 8.11 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 8.05-7.98 (m, 1H), 7.46 (dd, J =8.3, 4.8 Hz, 1H), 6.79 (d, J = 2.4 Hz, 1H); EIMS m/z 213.

3-Fluoro-5-(3-methyl-1 H-pyrazol-1-yljpyridine was prepared from the appropriate starting materials as described in Example 6, Step 1: mp 70.0-72.0 °C; ¹H 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 materials as described in 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:

¹H NMR (400 MHz, CDCI₃) δ 8.94 (bs, 1 H), 8.51 (d, J = 3.9 Hz, 1 H), 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 -yljpyrtdine was prepared as in Example 6, Step 1:¹H NMR (400 MHz, CDCI3) δ 8.77 (d, J = 2.5 Hz, 1H), 8.65 (dd, J = 4.8, 1.5 Hz, 1H), 7.84 (ddd, J = 8.2, 2.5, 1.5 Hz, 1H), 7.63 (d, J= 1.6 Hz, IH), 7.44 (ddd, J = 8.2, 4.8, 0.7 Hz, 1H), 6.225 (dd, J = 1.6, 0.7 Hz, 1H), 2.40 (s, 3H).

Example 6, Step 2: Préparation of 3-(4-nitro-pyrazol-1-yl)-pyridine nY-no₂

3-Pyrazo!-1-yl-pyridine (2 g, 0.032 mol) was dissolved in concentrated H₂SO₄ (32 mL 0.598 mmol.) and cooled to -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

Page 33 of619 stirred at room température overnight. After the reaction was complété, the mixture was poured over crushed ice and neutralized with saturated NaHCO₃, filtered, washed with water and dried to furnish the nitro pyrazole as pale yellow solid (1.8 g, 68%): ’H NMR (400 MHz, DMSO-d_e) □ 9.03 (d, J = 2.8 Hz, 1 H); 8.70 (dd. J = 4.8, 1.6 Hz, 1 H), 8.69 (s, 1 H), 8.33 (s, 1 H), 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-1 H-pyrazol-1 -yl)pyridine was prepared as in Example 6, Step 2: mp 139-142 °C, ’H NMR (400 MHz, CDCI₃) δ 9.01 (d, J = 2.0 Hz, 1H), 8.73 (d, J = 4.9 Hz, 2H), 8.08 (ddd, J = 8.3, 2.5, 1.3 Hz, 1H), 7.52 (dd, J= 8.3, 4.8 Hz, 1H), EIMS m/z 224.

3-(5-methyl-4-nitro-1 H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 2: ’H NMR (400 MHz, CDCI₃)ô8.81 —8.71 (m, 2H), 8.32 (s, 1H), 7.83 (ddd, J = 8.2, 2.5, 1.6 Hz, 1H), 7.54 (dd, J = 8.2, 4.8 Hz, 1H), 2.72(s, 3H).

2- methyl-3-(3-methyl-4-nitro-1 H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step 2:¹H NMR (400 MHz, d₆-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); .¹³C 154, 150, 146, 135, 134.9, 134.8, 134.3, 122, 21, 14; EIMS m/z 218.

3- (3-methyl-4-nitro-1 H-pyrazol-1-yljpyridine was prepared as in Example 6, Step 2: mp 122124 °C; ’H NMR (400 MHz, CDCI₃) δ 9.01 (d, J = 2.5 Hz, 1H), 8.77 - 8.56 (m, 2H), 8.07 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 7.56 - 7.37 (m, 1 H), 2.66 (s, 3H); EIMS m/z 208.

3-Fluoro-5-(3-methyl-4-nitro-1 H-pyrazol-1-yl)pyridine was prepared from the appropriate starting material as described in Example 6, Step 2: mp 90.0-92.0 °C; ’H NMR (400 MHz, CDCI3) δ 8.82 (d, J = 2.0 Hz, 1H), 8.69 (s, 1H), 8.54 (d, J = 2.5 Hz, 1H), 7.89 (dt, J = 8.9, 2.4 Hz, 1H). 2.66 (s, 3H); EIMS m/z 222.

3-(4-Nitro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)pyridine was prepared from the appropriate starting material as described in Example 6, Step 2: mp 121.0-123.0 ’C; ’H NMR (400 MHz, CDCI3) δ 9.04 (d, J = 2.5 Hz, 1H), 8.79 (s, 1H), 8.77 (d, J = 0.9 Hz, 1H), 8.13 (ddd, J = 8.3, 2.7,

1.4 Hz, 1H), 7.55 (dt, J =10.8, 5.4 Hz, 1H); EIMS m/z 258.

3-(3-Chloro-4-nitro-1 H-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; ’H NMR (400 MHz, CDCI₃) δ

8.83 (d, J = 2.1 Hz, 1H), 8.75 (s, 1H), 8.60 (d, J =2.4 Hz, 1H), 7.89 (dt, J = 8.6, 2.4 Hz, 1H); EIMS m/z 242.

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3-(3-Bromo-4-nitro-1 H-pyrazol-1-yljpyridine was prepared from the approprîate starting material as described in Example 6, Step 2: mp 139.0-141.0 ’C; ¹H NMR (400 MHz, CDCI₃) δ 9.01 (d, J = 2.5 Hz, 1H), 8.73 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.71 (s, 1H), 8.15-8.00 (m, 1H), 7.52 (dd, 7=8.3,

4.8 Hz, 1H); ESIMS m/z 271 ([M+2]⁺).

Example 6, Step 3: Préparation of 1-pyridin-3-yl-1H-pyrazol-4-ylamine

To a solution of 3-(4-nitro-pyrazol-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): ¹H NMR (400 MHz, DMSO-d₆) □ 8.89 (dd, 7 = 2.8. 0.4 Hz, 1H); 8.48 (dd, 7 = 4.8, 1.2 Hz, 1H), 7.99-7.96 (m, 1H), 7.54 (d, 7= 1.2 Hz, 1H), 7.45 (d, 7=0.4 Hz, 1H), 7.38-7.35 (m, 1H), 4.81 (bs 1 H); ESIMS (m/z) 161 [M+1],

5-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Example 6, Step 3:¹H NMR (400 MHz, CDCI3) δ 8.74 (d, 7 = 2.3 Hz, 1 H). 8.63 - 8.50 (m, 1 H), 7.81 (ddd, 7 = 8.2, 2.5, 1.5 Hz, 1 H), 7.46 - 7.33 (m, 2H), 2.64 (bs, 1 H), , 2.29 (s, 3H); ¹³C (DMSO-d6) 147, 144,137, 133, 130, 129, 124, 123, 10; EIMS m/z 174

3-methyl-1-(pyrimidin-5-yl)-1/7-pyrazol-4-amine was prepared as in Example 6, Step 3: mp 211215 ’C; ¹H NMR (400 MHz, CDCI₃) δ 9.10 - 8.87 (m, 3H), 7.51 (s, 1H), 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 146148 ’C; ¹H NMR (400 MHz, CDCI₃) δ 9.07 (s, 1H), 9.02 (s, 2H), 7.52 (s, 1 H), 3.45 (s, 2H); ESIMS m/z 196 ([M+H]).

Example 7: Préparation of methyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine

Page 35 of6l9

Method A:

To a 25 ml round bottom flask containing 1-pyridin-3-yl-1/7-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 to 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 in dry tetrahydrofuran (25.6 mL), cooled to 0°C and sodium borohydrîde (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 %): ¹H NMR (400 MHz, d₆-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, 1H), 7.45 (s, 1H), 7.30 (s, 1H), 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-ylamine (1.0 g, 6.2 mmol) was dissolved in triethyl orthoformate (5 ml, 30 mmol) and to that was added trifluoroacetic acid (3-4 drops). The reaction mixture was refluxed at 120°C for 3 hours and was then concentrated. The crude was dissolved in éthanol (5 ml), cooled to 0°C and treated with sodium borohydrîde (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, CDCI₃) δ 8.91 (bs, 1 H), 8.46 (d, J = 4.5 Hz, 1 H), 7.99 (d, 7=8.3 Hz, 1H), 7.43 (s, 1H). 7.41 (s, 1H), 7.36 (dd, 7 = 8.3, 4.7 Hz, 1H), 2.86 (d, 7= 12.4 Hz, 3H); ESIMS m/z 175 {[M+1]).

Example 8: Préparation of ethyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine

Page 36 of 619

Method A:

To 1-pyridin-3-yl-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 (5ml) 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 collected 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%); ’H NMR (400 MHz, CDCI₃) δ 8.90 (d, J = 2.7 Hz, 1 H), 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, 7 = 8.3,4.7, 0.7 Hz, 1H), 3.10 (q, 7 = 7.1 Hz, 2H), 1.27 (t, 3H).

Method B:

To a solution of tert-butyl ethyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (3.4 g, 11.79 mmol) in dichloromethane (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%); ¹H NMR (400 MHz, CDCI₃) δ 8.90 (dd, 7 = 1.8, 0.8 Hz, 1H), 8.51 - 8.39 (m, 1H), 7.97 (ddt, 7 = 8.3, 2.7, 1.3 Hz. 1 H). 7.41 (d,7 = 0.8 Hz, 2H). 7.38-7.30 (m, 1H), 3,21 -

2.93 (m, 2H), 1.34-1.19 (m, 3H).

3-chloro-A/-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as described in Example 8, Method B: ¹H NMR (400 MHz, CDCI₃) δ 8.87 (d, 7 = 2.5 Hz, 1H), 8.47 (dd, 7 = 4.7, 1.2 Hz, 1H),

7.96 (ddd, 7 = 8.4, 2.6, 1.4 Hz, 1H), 7.38-7.32 (m, 2H), 3.11 (q, 7 = 7.1 Hz, 2H). 2.97 (bs, 1H), 1.31 (t, 7= 7.1 Hz, 3H).

3-chloro-A/-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Example 8, Method B: mp 108-118 C; ¹H NMR (400 MHz, CDCI₃) δ 8.88 (d, 7 = 2.4 Hz, 1 H), 8.48 (dd, 7 = 4.7, 1.4

Page 37 of 6I9

Hz, 1 H), 7.96 (ddd, J = 8.3, 2.7, 1.4 Hz, 1 H), 7.41 - 7.29 (m, 2H), 2.87 (s, 3H); EIMS m/z 208.

A/,3-dimethyl-1-(pyridin-3-yl)-1M-pyrazol-4-amine was prepared as in Example 8, Method B: ¹H NMR (400 MHz, CDCI₃) δ 9.03 - 8.73 (m, 1 H), 8.41 (dd, J = 4.7, 1.4 Hz, 1 H), 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-A/-(cylopropylmethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Example 8, Method B: ¹H 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-W-propyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Example 8, Method B: 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), 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-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: mp 142.0-143.5 °C; ¹H 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+H]⁴).

W-ethyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: mp 85.0-86.0 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.66 (s, 1 H), 8.25 (d, J = 2.5 Hz, 1 H), 7.72 (dt, J = 10.0, 2.3 Hz, 1 H), 7.27 (s, 1 H), 3.07 (q, J =

7.1 Hz, 2H), 2.71 (s, 1 H), 2.25 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); ESIMS m/z 221 ([M+H]*).

3-Methyl-A/-propyl-1-(pyridin-3-yl)-1/-/-pyrazol-4-amine was prepared from the appropriate Bocamine 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, 1 H), 8.40 (dd, J = 4.7, 1.4 Hz, 1 H), 7.94 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 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]⁴).

N-(cyclopropylmethyl)-3-methyl-1-(pyridin-3-yl)-1/-/-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: mp 73.0-75.0 °C; ¹H 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, 1H), 7.35 - 7.28 (m, 2H), 2.87 (d, J = 6.9 Hz, 2H), 2.75 (s, 1H), 2.28 (s, 3H), 1.22 -1.05 (m, 1H), 0.63 - 0.56 (m, 2H), 0.26 (q, J = 4.7 Hz, 2H); ESIMS m/z 229 ([M+H]⁴).

Page 38 of 619 /V-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 (thin film) 3303 cm'¹; ¹H NMR (400 MHz, CDCI3) δ 8.86 (d, 7 = 2.3 Hz, 1 H), 8.41 (dd, J = 4.7, 1.4 Hz, 1 H), 7.94 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.36-7.28 (m, 2H), 3.30 (hept, J = 6.3 Hz, 1H), 2.25 (s, 3H), 1.24 (d, 7 = 6.3 Hz, 6H); EIMS m/z 216.

5-Ethoxy-1-(5-fluoropyridin-3-yl)-/\/,3-dimethyl-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: IR (thin film) 3340 cm’¹; ’H NMR (400 MHz, CDCI₃) δ 8.91 (s, 1H), 8.31 (d, 7 =2.5 Hz, 1H), 7.88 - 7.80 (m, 1H), 4.24 (q, 7 = 7.1 Hz, 2H), 2.79 (s, 3H), 2.24 (s, 3H), 1.36 (t, 7 = 7.1 Hz, 3H); EIMS m/z 250.

5-Bromo-N-methyl-1-(pyridin-3-yl)-1H-pyrazoi-4-amine was prepared from the appropriate Bocamine as described in Example 8, Method B: mp 77.0-79.0 °C; ¹H NMR (400 MHz, CDCI₃) δ

8.90 (d, 7=2.0 Hz, 1H), 8.63 (d, 7 =3.9 Hz, 1H), 7.93 (ddd, 7 = 8.2, 2.4, 1.5 Hz, 1H), 7.51 (s, 1H), 7.43 (dd, 7= 8.2, 4.8 Hz, 1H), 4.49 (s, 1H), 2.91 (s, 3H); ESIMS m/z 255 ([M+2f).

5-Fluoro-A/,3-dimethyl-1-(pyridin-3-yl)-1/7-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ¹H NMR (400 MHz, CDCI₃) δ 8.91 (t, 7 = 2.1 Hz, 1 H), 8.50 (dd, 7 = 4.8, 1.5 Hz, 1 H), 7.93 (ddt, 7 = 8.3, 2.8, 1.5 Hz, 1 H), 7.37 (ddd, 7 = 8.3,

4.8, 0.7 Hz, 1 H), 2.86 (d, 7 = 1.6 Hz, 3H), 2.43 (s, 2H), 2.24 (s, 3H); EIMS m/z 206.

5-Bromo-N,3-dimethyl-1-(pyridin-3-yl)-1/7-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ¹H NMR (400 MHz, CDCI₃) δ 8.86 (dd, 7 = 2.5, 0.5 Hz, 1 H), 8.59 (dd, 7 = 4.8,1.5 Hz, 1 H), 7.88 (ddd, 7 = 8.2, 2.6, 1.5 Hz, 1 H), 7.40 (ddd, 7 = 8.2, 4.8, 0.7 Hz, 1H), 2.85 (s, 3H), 2.69 (s, 1H), 2.35 (s, 3H); ESIMS m/z 268 ([M+Hf).

5-Chloro-A/,3-dimethyl-1-(pyridin-3-yl)-1/7-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: ¹H NMR (400 MHz, CDCI₃) δ 8.87 (d, 7 = 2.3 Hz, 1 H), 8.59 (dd, 7 = 4.8, 1.3 Hz, 1 H), 7.90 (ddd, 7 = 8.2, 2.6, 1.5 Hz, 1 H), 7.40 (ddd, 7 = 8.2,

4.8, 0.6 Hz. 1 H), 2.87 (s, 3H), 2.45 - 2.19 (m, 4H); EIMS m/z 223.

3-Chloro-1-(5-fluoropyridin-3-yl)-/\/-methyl-1/7-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: mp 117.5-119.0 °C; ¹H NMR (400 MHz, CDCI3) δ 8.68 (d, 7=1.1 Hz, 1H), 8.33 (d, 7 = 2.5 Hz, 1 H). 7.75 (dt, 7 = 9.6, 2.4 Hz, 1H), 7.31 (s, 1H), 3.14 (s, 1H), 2.87 (s, 3H); ESIMS m/z 227 ([Mf).

3-ChIoro-A/-ethyl-1-(5-fluoropyridin-3-yl)-1/7-pyrazol-4-amine amine was prepared from the

Page 39 of 619 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)-W-methyl-3-vinyl-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: 105.0-107.0 °C; ’H NMR (400 MHz, CDCI₃) δ 8.72 (s, 1 H), 8.31 (d, J = 2.5 Hz, 1 H), 7.81 (dt, J = 9.8, 2.4 Hz, 1 H), 7.33 (s, 1 H),

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; ¹H NMR (400 MHz, CDCIa) 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, 1 H), 3.09 (s, 1 H), 2.86 (s, 3H), 1.78- 1.63 (m, 1 H), 0.99 - 0.90 (m, 4H); ESIMS m/z 233 ([M+Hf).

3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate Boc-amine as described in Example 8, Method B: mp 137.9-139.9; 'H NMR (400 MHz, CDCI₃) δ 8.84 (d, J = 2.4 Hz. 1H), 8.50 (dd, J = 4.7, 1.4 Hz, 1H), 7.95 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.52 (s, 1H),

7.37 (ddd, J = 8.4, 4.7, 0.7 Hz, 1 H), 3.18 (s, 2H); ESIMS m/z 196 ([M+Hf).

2- ((3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)amino)acetonitrile was prepared from tert-butyl (3chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(cyanomethyl)carbamate as in Example 8, Method B: mp 141-143 °C; ¹H NMR (300 MHz, CDCI₃) δ 8.91 (d, J = 2.7 Hz, 1H), 8.54 (dd, J= 5.1, 1.8 Hz,

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, 1H); EIMS m/z 235 ([M+1 f).

A/-3-dimethyl-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as in Example 8, Method B: mp 139-143 °C; ¹H NMR (400 MHz, CDCI₃) δ 9.02 (s, 2H), 9.00 (s, 1H), 7.30 (s, 1H), 2.87 (d, J = 11.5 Hz, 3H), 2.27 (s, 3H); ESIMS m/z 190 ([M+H]).

3- chloro-A/-methyl-1-(pyrimidin-5-yl)1-1H-pyrazol-4-amine was prepared as in Example 8, Method B: mp 111-114 °C; ¹H NMR (400 MHz, CDCI₃) δ 9.09 - 9.04 (m, 1H), 9.02 (s, 2H), 7.30 (s, 1H), 3.14 (bs, 1H), 2.88 (s, 3H); ESIMS m/z 196 ([M+H]).

1-(5-Fluoro-3-pyridyl)-3-methyl-/V-(trideuteriomethyl)pyrazol-4-amine was prepared from compound 380 using the procedure as described in Example 8, method B: mp 146-148 °C; ¹H 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. 1 H),

7.27 (s, 1H), 2.87 (s, 1 H), 2.24 (s, 3H); ESIMS m/z 210 ([M+H]*); IR (Thin film) 1599 cm'¹.

Page 40 of 619

3-Chloro-1-(3-pyridyl)-N-(trideuteriomethyl)pyrazol-4-amine was prepared from compound 381 using the procedure as described in Example 8, method B: mp 104-106 °C; ¹H NMR (400 MHz, CDCI3) δ 8.87 (d, 7 = 1.9 Hz, 1H), 8.47 (d, 7=4.7 Hz, 1H). 8.00-7.90 (m, 1H), 7,40-7.30 (m, 2H), 3.10 (s, 1H); ESIMS m/z 212 ([M+Hf); IR (Thin film) 1579 cm'¹.

3-Chloro-N-(cyclopropylmethyl)-1-(pyridin-3-yl)-1/7-pyrazol-4-amine was prepared from compound 361 using the procedure as described in Example 8, method B: mp 82-83 °C; ¹H NMR (400 MHz. CDCI₃) δ 8.86 (d, 7 = 2.5 Hz, 1H), 8.47 (dd, 7 = 4.7, 1.3 Hz, 1H), 7.95 (ddd, 7 = 8.4, 2.7, 1.5 Hz, 1H), 7.38 - 7.32 (m, 2H), 3.22 (s, 1H), 2.90 (d, J = 6.9 Hz, 2H), 1.23 - 1.06 (m, 1 H), 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 in Example 8, method B: mp 92-94 °C; ’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), 7.95 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 7.35 (ddd, 7 = 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, 7 = 7.4 Hz, 3H); ESIMS m/z 237 ([M+Hf).

Example 9: Préparation of isopropyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine

N

1-pyridin-3-yl-1H-pyrazol-4-ylamine (0.6 g, 3.7 mmol) was dissolved in isopropyl acetate (8.5 ml). To the mixture, acetone (0.261 g, 4.5 mmol), trifluoroacetic acid (0.855 g, 7.5 mmol) 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 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; ’H NMR (300 MHz. CDCI₃) δ 8.82 (d. J = 2.2 Hz, 1 H), 8.63 (dd, 7 = 4.8, 1.5 Hz, 1H), 8.13 (d, 7=1.8 Hz, 1H), 8.03 (d, 7 = 2.7 Hz, 1H), 7.94 - 7.77 (m, 1H), 7.38 (dt, 7= 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).

Page 41 of 619

Example 10: Préparation of propyl-(1-pyridin-3-yl-1H-pyrazol-4-yl-amîne

To 1-pyridin-3-yl-1H-pyrazo!-4-ylamine (0.5 g, 3.12 mmol) in dichloromethane (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 reaction was taken up in dichloromethane and was washed with water and brine. The organic layer was dried (MgSO₄), filtered and concentrated to dryness. The crude material was purified by silica gel chromatography eluting with 0-5% 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, CDCIa) δ 8.92 (d, J = 2.6 Hz. 1 H), 8.48 (dd. J = 4.7, 1.4 Hz, 1 H), 8.00 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.47-7.40 (m, 2H), 7.37 (dd. J = 8.3, 4.7 Hz, 1H), 3.04 (t, J =7.1 Hz, 3H), 1.92-

1.46 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H).

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

A solution of isobutyryl chloride (0.138 g, 1.3 mmol) in dichloroethane (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 dichloroethane (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 dichloroethane (1.5 mL). The cooling bath was removed after 30 minutes, stirred under nitrogen at room température for 14 hours, diluted with dichloroethane (40 mL), washed with water (30 mL), brine (10 mL), dried over MgSO₄ and purified by reversed phase column chromatography to give a yellowish 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. 1 H), 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])·

Page 42of6l9

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, 197198, 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_l4,4-trifluoro-2-methyl-/V-(1-(pyridin-3-yl)-1H-pyrazol-4yl)butanamide (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 4,4,4-trifluoro-2-methylbutanoic acid (0.14 g, 0.93 mmol) and 4-N,/Vdimethylaminopyridine (0.23 g, 1.87 mmol) followed by 1-(3-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride (0.36 g, 1.87 mmol). The reaction stirred at room température overnight. 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, 7= 2.4 Hz, 1H), 8.62 - 8.47 (m, 2H), 8.01 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.68 (s, 1H), 7.53 (bs, 1H), 7.40 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 2.92-2.61 (m, 2H), 2.32- 2.05 (m, 1H), 1.38 (d, 7 = 6.6 Hz, 3H); ESIMSm/z300 ([M+2]).

Compounds 53, 58, 62-63, 72, 76, 80 - 81, 107 - 108, 136-138,147,151 - 159, 164 - 168, 176 - 179, 187 -196, 201, 203 - 207, 209 - 214, 220, 224 - 249, 251, 259 - 275, 286, 292 - 296, 303 - 313, 323 - 326, 341 - 344, 356 - 359, 371, 378 - 379, 382, 384, 419 - 426, 439 -443, 455, 458 - 461, 464, 466, 476, 486, 490 - 493, 505, 508, 517, 528 - 529, 536 537, 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-(pyridin-3-yl)-1H-pyrazol-4-ylcarbamate (Compound 57)

Page 43 of 619

Method A:

To a solution of 1-(pyridin-3-yl)-1/-/-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 overnight. The réaction mixture was partitioned between ethyl acetate and water. The organic portion was dried (MgSO₄), filtered and concentrated to dryness. The crude product was purified by siiica gel chromatography eluting with 0-100% ethyl acetate/hexanes to yield a white solid (2.0 g, 41%); mp 108 - 112 °C; ¹H NMR (400 MHz, CDCI₃) δ 9.02 (d, J = 2.2 Hz, 1 H), 8.51 (t, J - 8.7 Hz, 1 H), 8.37 (s, 1 H), 8.30 (s, 1H), 7.98 (ddd, 7= 8.3, 2.4, 1.3 Hz, 1H). 7.68 (s, 1H), 7.36 (dd, 7 = 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-yl)-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 overnight. The reaction was diluted with water and extracted with ethyl acetate. The combined organic phases were concentrate to give tert-butyl 1-(pyridin3-yl)-1H-pyrazol-4-ylcarbamate (135 mg, 0.519 mmol, 83 %), for which the analytical data was consistent with that reported in Example 13, Method A.

Compounds 150,172, 223, and 317 were prepared in accordance with the procedures disclosed in Example 13, Method B. Compound 172 and 317 was also prepared in accordance 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-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 67)

Page 44 of 619

To a solution of tert-butyl 1-(pyridin-3-yl)-1H-pyrazol-4-ylcarbamate (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 oil) in one portion and the suspension was stirred for 30 minutes. The ice bath was removed and stirred for an additional 30 minutes, lodomethane (0.46 ml, 7.38 mmol) was added in one portion and stirred overnight at room température. Water and ethyl acetate were added and the resulting biphasic mixture was separated. The aqueous layer was extracted one time with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO₄), filtered and concentrated to dryness. The crude product was purified by silica gel chromatography eluting with 0-35% ethyl acetate/hexanes to yield a light yellow semi-solid (0.85 g, 50%): IR (KBr) 1703 cm’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 amides in accordance with the procedures disclosed in Example 14.

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

Example 15: Préparation of N-ethyl-N-(1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5yljisobutyramide (Compound 23)

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To a solution of A/-(1-methyl-3-(pyridine-3-yl)-1H-pyrazol-5-yl)isobutyramide (0.08 g, 0.33 mmol) in 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, lodoethane (0.06 g, 0.39 mmol) was added in one portion and stirred overnight at room température. Water and ethyl acetate were added and the resulting biphasic mixture was separated. The aqueous layer was extracted one lime with ethyl 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 to give the title compound as a clear oil (27.5 mg, 30%): ¹H NMR (300 MHz, CDCh) δ 9.00 (bs,

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, 1H), 2.33 (m, 1H), 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 in accordance with the procedures disclosed in Example

15.

Example 16: Préparation of 5-bromo-1H-pyrazol-4-amine, HBr

Br

A mixture of 4-nitro-1/-/-pyrazole (10 g, 88 mmol) and 5% palladium on AI₂O₃ (1 g) in 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 éthanol. 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, ether was added to complété the crystallization. The solid was filtered, was washed with ether and dried under high vacuum to afford 5-bromo-1Hpyrazol-4-amine, HBr (18.1 g, 84 % yield) as a white solid: mp 248 °C dec; ¹H NMR (400 MHz, DMSO-dg) 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 hydrochlorlde

Page 46 of619

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 4-nitro-1Hpyrazole (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 OC 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 oc, 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 °C in the refrigerator. The solids were filtered and washed with acetonitrile (100 mL) to afford the titled compound 3-chloro-1Hpyrazol-4-amine 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)); ¹³C-NMR (101 MHz, DMSO) δ 128.24, 125.97, 116.71.

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

Page 47 of6l9 acetate (2 x 200 mL) and the ethyl acetate extracts were combined, washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and rotary evaporated to give an auburn thick oil (160 g,). The thick oil was suspended in hexane (1000 mL) and stirred at 55 °C for 2 h. This gave a Iight brown suspension. The mixture was cooled to 0 °C 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% purîty) as a Iight brown solid: mp 137-138 °C; ’H NMR (400 MHz, CDCI₃) δ 10.69 (s, 1H), 7.91 (s, 1 H). 1.52 (s, 9H).

Example 17, Step 3: Préparation of tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4yljcarbamate (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), (3-chloro-1Hpyrazol-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 W^Af-dimethylethane-l^-diamine 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 Erlenmeyer flask equipped with mechanical stirrer and diluted with water until the total volume was about 4 L. The mixture was stirred for 30 minutes at room 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-(pyridin-3-yl)-1/-/-pyrazol-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 ([M-t-Bu]*), 220 ([M-O-t-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 in Example 17 from tert-butyl (3-bromo-1H-pyrazol-4-yl)carbamate and also in accordance with the procedures disclosed in Example 13.

Page 48 of 619

Example 18: Préparation of 3-(3'methyl-1H-pyrazol-1-yl)pyridine and 3-(5-methyl-1 H~ pyrazol-1-yljpyridine

To a solution of 3-methyl-1 H-pyrazole (10.99 g, 134 mmol) in /V,A/-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 overnight. 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-1 H-pyrazol-1 -yljpyridine (8.4g, 52.77 mmol, 51.2 %) and 3-(5-methyl-1 H-pyrazol-1 -yljpyridine (1.0 g, 6%). Analytical data of both products is consistent with that reported under Example 6, Step 1.

3-(3-Bromo-1 H-pyrazol-1 -yljpyridine was prepared from 3-fluoropyridine and 3-bromopyrazole, which was made as in W02008130021, as described Example 18: mp 89.5-92.5 °C; ¹H 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, 1 H), 7.87 (d, J = 2.5 Hz, 1 H), 7.42 (dd, J = 8.2, 4.7 Hz, 1 H), 6.54 (d, J = 2.5 Hz, 1 H); ESIMS m/z 224 ([M]*).

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

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 MgSO₄ and concentrated in vacuo to give a brown solid. This solid was dissolved in ethyl acetate and the resulting solution was saturated with

Page49 of6l9 hexanes to precipitate 3-chloro-1-(5-fluoropyridin-3-yl)-1/-/-pyrazoi-4-amine (2.31g, 10.32 mmol, 79 % yield) as a brown solid: ¹H NMR (400 MHz, DMSO-d_e) δ 8.89 - 8.82 (m, 1 H), 8.45 (d, J =

2.5 Hz, 1H), 8.07 (d, J= 10.4 Hz, 1H), 7.94 (s. 1H), 4.51 (s, 2H); EIMS (m/z) 213 ([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; ¹H NMR (400 MHz, CDCI₃) δ 8.65 (d, J =

1.7 Hz. 1H), 8.36 (d, 7 = 2.5 Hz, 1H), 7.76 (dd, 7= 5.9, 3.6 Hz, 1H), 7.48 (s, 1H), 3.22 (s, 2H). ¹³C NMR (101 MHz, CDCI₃) 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+1]+).

Example 20: Préparation of l-ÎS-fluoropyridîn-S-ylJ-S-methyl-IH-pyrazol^-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-fluoropyridin-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; ¹H 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; ¹H NMR (400 MHz, CDCI3) δ 8.89 (d, 7 = 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, 1 H), 7.56 (d, 7 = 0.7 Hz, 1 H), 7.41 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1 H), 3.47 - 3.31 (m, 2H); EIMS m/z 228.

Example 21: Préparation of 3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine

Page50of6l9

To 3-(3-chloro-4-nîtro-1 H-pyrazol-1 -yl)pyridine (0.95 g, 4,23 mmol) in acetic acid (8.46 mL), éthanol (8.46 mL) and water(4.23 mL) was 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 Μ 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% ): ¹H 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, 7=8.3, 2.7, 1.5 Hz, 1H), 7.53 (s, 1H). 7.37 (ddd, 7 = 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, 7 = 4.8, 1.6 Hz, 1 H), 7.62 (dd, 7 = 8.0, 1.6 Hz, 1 H), 7.23 - 7.18 (m, 2H). 2.91 (bs, 2H), 2.55 (s, 3H), 2.28 (s, 3H); EIMS m/z 188.

3-Phenyl-1-(pyridin-3-yl)-1/7-pyrazol-4-amine was prepared from the appropriate nitropyrazole as described in Example 21: IR (thîn film) 3324 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 8.94 (d, 7 =

2.2 Hz, 1H), 8.47 (dd,7 = 4.7, 1.4 Hz, 1H), 8.07 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.87-7.80 (m, 2H), 7.60 (s, 1 H), 7.50 - 7.44 (m, 2H), 7.40 - 7.34 (m, 2H), 3.86 (s, 2H); EIMS m/z 236.

3-Chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate nitropyrazole as described in Example 21: mp 149.0-151.0 °C; ’H NMR (400 MHz, CDCI₃) δ 8.65 (d, 7= 1.6 Hz, 1H), 8.35 (d,7 = 2.4 Hz, 1H), 7.75 (dt, J = 9.5, 2.4 Hz, 1H), 7.51 (s, 1H), 3.21 (s, 2H); ESIMS m/z 213 ([M]⁺).

3-Bromo-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from the appropriate nitropyrazole as described in Example 21: mp 143.0-146.0 °C; ’H NMR (400 MHz, CDCI₃) δ 8.85 (d, 7 = 2.4 Hz, 1H), 8.50 (dd, 7 = 4.7, 1.4 Hz, 1H), 7.96 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.49 (s, 1H), 7.37 (ddd, 7 = 8.4, 4.7, 0.7 Hz, 1 H), 3.21 (s, 2H); ESIMS m/z 241 ([M+2]⁺).

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

Page 51 of 619

To a solution of (E)-tert-butyl 1-{dimethylamino)-3-oxobut-1-en-2-ylcarbamate (0.59 g, 2.58 mmol) in 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 (thîn film) 3268, 2978 and 1698 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 8.75 (dd, J = 2.5, 0.5 Hz, 1H), 8.62 (dd, 7 = 4.8, 1.5 Hz, 1H), 7.82 (ddd, 7=8.2, 2.6, 1.5 Hz, 1H), 7.78 (s, 1H), 7.43 (ddd, J - 8.1, 4.8, 0.6 Hz, 1H), 6.04 (s, 1H), 2.29 (s, 3H), 1.52 (s, 9H); ESIMS m/z 275 ([M+Hf), 273 ([M-H]).

Example 23: Préparation of fert-butyl 1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4ylcarbamate (Compound 111) and fert-butyl 5-ethoxy-1-(5-fluoropyridin-3-yl)-3-methyi-1Hpyrazol-4-ylcarbamate (Compound 112)

To a solution of 3-fluoro-5-(3-methyl-4-nitro-1/-/-pyrazol-1-yl)pyridine (3.133 g, 14.10 mmol) in éthanol (28.2 ml) was added ethyl acetate until ail of the sterling 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 solvent was removed under reduced pressure. The residue was dissolved in tetrahydrofuran (32.0 ml) and water (9.61 ml). Di-fert-butyl dicarbonate (2.52 g, 11.55 mmol) was added followed by saturated aqueous sodium bicarbonate (9.54 ml, 11.45 mmol). The reaction was stirred at room température overnight, diluted with water and extracted with ethyl acetate. The combined organic phases were concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give fert-butyl 1-(5fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (1.673 g, 5.72 mmol, 41.0 %) as a yellow solid and the fert-butyl 5-ethoxy-1-(5-fluoropyridin-3-yl)-3-methyl-1/7-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; ’H NMR (400 MHz, CDCI₃) δ 8.75 (s, 1H), 8.32 (d, 7 = 2.5 Hz, 1H), 8.28 (s, 1H), 7.77 (dt, J = 9.7, 2.4 Hz, 1H), 6.15 (s. 1H), 2.29 (s. 3H), 1.54 (s, 9H); ESIMS m/z 293 ([M+Hf).

Page52of6l9

Tert-butyl 5-ethoxy-1 -(5-fluoropyridin-3-yl)-3-methyl-1 H-pyrazol-4-ylcarbamate (Compound 112): IR (thin film) 1698 cm'¹; ¹H NMR (400 MHz. CDCI₃) δ 8.88 (s, 1 H), 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+Hf).

Example 24: Préparation of Bis tert-t-butyl (1-(pyridin-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%): ¹H NMR (400 MHz, CDCI₃) δ 9.12 - 8.86 (m. 1H), 8.55 (dd, J~ 4.7, 1.4 Hz, 1 H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 8.01 (d, J = 0.5 Hz, 1 H), 7.84 - 7.65 (m, 1 H), 7.41 (ddd, J= 8.3, 4.8, 0.7 Hz, 1H), 1.51 (s, 18H).

Example 25: Préparation of 3-chloro-1-(pyridin-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) in 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

Page 53 of 619 combined organic layers were concentrated to give 3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.954g, 4.90 mmol, 72.2 %) as a white solid: mp 137.9-139.9 °C; ¹H NMR (400 MHz, CDCI₃) δ

8.84 (d, J = 2.4 Hz, 1 H), 8.50 (dd, /= 4.7, 1.4 Hz, 1H), 7.95 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.52 (s. 1 H), 7.37 (ddd, J = 8.4, 4.7, 0.7 Hz, 1 H), 3.18 (s, 2H); ESIMS m/z 196 ([M+Hf).

Example 26: Préparation of /V-allyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine hydrochloride

To a solution of tert-butyl allyl(1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-yl)carbamate (908 mg, 2.73 mmol) in dioxane (5 mL) was added HCl (1M in 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 M-allyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4amine, HCl (688 mg, 94 % yield) as a white solid: mp 189-190 °C; ’H NMR (400 MHz, CDCI₃) δ 8.79-8.68 (m, 1H), 8.32-8.26 (m, 1H), 8.23 (s, 1H), 7.98-7.86 (m, 1H), 5.86-5.68 (m, 1H), 5.28-5.17 (m, 1H), 5.17-5.03 (m, 1H), 3.59 (d, J = 6.2 Hz, 2H), 2.11 (s, 3H); EIMS (m/z) 233 ([M+1]+).

N-Allyl-3-chloro-1-(pyridin-3-yl)-1/-/-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; ¹H 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, 1H),8.24(s, 1H), 7.93 (dd, J = 8.6, 5.3 Hz, 1H), 3.66 (dt,/=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 iert-butyl allyl(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl): mp 195-197 °C; ’H NMR (400 MHz, DMSO-d₆) δ 9.12 (d, / = 2.4 Hz, 1H), 8.58 (dd,/ = 5.0, 1.2 Hz, 1H), 8.48 (s, 1H), 8.43 (d, / = 9.7 Hz, 1H), 7.77 (dd, / = 8.4, 5.0 Hz, 1H), 6.04-5.92 (m, 1H), 5.44(dd,/ = 17.2, 1.4 Hz, 1 H), 5.32 (d, / = 9.4 Hz, 1 H), 3.81 (d, / = 6.2 Hz, 2H); EIMS (m/z) 249 ([M-1 ]+).

3-Bromo-1-(5-fluoropyridin-3-yl)-/V-methyl-1W-pyrazol-4-amine, HCl was prepared as described in Example 26 from iert-butyl 3-bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl(methyl)carbamate; mp 167-168 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.93 (s, 1H), 8.50 (d, /= 2.5

Page 54 of 619

Hz, 1 H), 8.23 (s, 1H), 8.14 (dt, J = 10.4, 2.3 Hz, 1 H), 2.73 (s, 3H).

3-Bromo-M-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)-1/7-pyrazol-4-yl)(methyl)carbamate (160 mg, 0.45 mmol) in dioxane (1 mL) was added 4M HCl: mp. 226-228 °C; ¹H NMR (400 MHz, DMSO-d₆) 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, 1 H), 2.82 - 2.67 (s, 3H); EIMS (m/z) 253 ([M+1J+), 255 ([M+2HJ+).

3-Bromo-/V-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was prepared as described in Example 26 from 3-bromo-M-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl: mp 216-217 °C; ’H NMR (400 MHz, DMSO-d₆) δ 10.66 - 10.05 (s, 3H), 9.28 - 9.20 (d, J = 2.5 Hz, 1H), 8.74 - 8.67 (m, 1H), 8.67 - 8.56 (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+1J+).

3-Chloro-/V-(2-methoxyethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was prepared as described in Example 26 from tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(2methoxyethyl)carbamate, HCl: mp 157-158 °C;’H NMR (400 MHz, DMSO) δ 9.22 - 9.14 (d, J =

2.5 Hz, 1 H), 8.70 - 8.65 (s, 1 H), 8.65 - 8.59 (m, 1 H), 8.38 - 8.33 (m, 1 H), 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-/V-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine hydrochloride

Cl

NH 2HCI

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-yl)(ethyl)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 °C. 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.

Page 55 of 619

The title compound was isolated as a pale yellow solid (18.2 g, 95%); ¹H NMR (400 MHz, MeOD) δ 9.52 (d, J = 2.5 Hz, 1H), 9.17 (s, 1H), 9.14 (ddd, J = 8.7, 2.5, 1.1 Hz, 1H), 8.93 (ddd, J = 5.7, 1.1, 0.6 Hz, 1H), 8.31 (ddd, J = 8.7, 5.7, 0.5 Hz, 1H), 3.58 (q, J = 7.3 Hz, 2H). 1.48 (t, J =

7.3 Hz, 3H); ESIMS m/z 223 ([M+Hf).

3-Chloro-/V-methyl-1-(pyridin-3-yl)-1H-pyrazole-4-amine, 2HCI was prepared as described in Example 27: ¹H NMR (400 MHz, MeOD) δ 9.28 (d, J = 2.5 Hz, 1 H), 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-yOpyridine

To a suspension of phenylboronic acid (0.546 g, 4.47 mmol) in toluene (6.63 ml) was added 3(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine (0.335 g, 1.492 mmol) followed by 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 purging with nitrogen (3 times). To the reaction mixture was added palladium tetrakis (0.086 g, 0.075 mmol) and the flask was heated at 110 °C under nitrogen for hours. The aqueous layer was removed and the organic layerwas concentrated. The crude product was purified via silica gel chromatography (0-100% ethyl acetate/hexanes) to give 3-(4nitro-3-phenyl-1H-pyrazol-1-yl)pyridine (499 mg, 1.874 mmol, 80 %) as a yellow solid: mp 144.0-146.0 °C; ’H 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, 1 H), 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)

Page 56 of 619

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-bromopyrrolidîne-2,5-dione (0.260 g, 1.458 mmol) and the reaction was stirred overnight 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 tert-butyl 5-bromo-1-(pyridin-3-yl)-1H-pyrazol-4yl(methyl)carbamate (256 mg, 0.725 mmol, 99 %) as a brown oil: IR (thîn film) 1697 cm’¹; ¹H NMR (400 MHz, CDCI₃) δ 8.89 (s, 1 H), 8.68 (d, J = 4.1 Hz, 1 H), 7.93 (ddd, J = 8.2, 2.5, 1.5 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, J = 8.1, 4.8 Hz, 1H), 3.22 (s, 3H), 1.44 (s, 9H); ESIMS m/z 352 ([ΜΗ]).

Example 30: Préparation of Bis tert-t-butyl (5-chlorO'1-(pyridin-3-yl)-1H-pyrazol-4yl)carbamate (Compound 109)

To Bis tert-t-butyl (1-(pyridin-3-yl)-1W-pyrazol-4-yl)carbamate (1.30 g, 3.61 mmol) in acetonitrile (21.22 mL) was added N-chlorosuccinimide (0.96 g, 7.21 mmol) and the reaction was stirred at 45 °C for 48 hours. The reaction was cooled to room température and poured into water and extracted with dichloromethane. The dichloromethane 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; ’H NMR (400 MHz, CDCI₃) δ 8.90 (d, J = 2.3 Hz, 1 H)_T 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 dichloroethane as the solvent as described in Example 30: ESIMS m/z 324 ([M+H]⁺).

Page57of6l9

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

Tert-butyl 5-bromo-3-methyl-1-(pyridin-3-yl)-1/7-pyrazol-4-yl(methyl)carbamate was prepared from the appropriate pyrazole in dichloroethane as described in Example 30:¹H NMR (400 MHz, CDCIs) δ 8.88 (d, J = 2.3 Hz, 1H), 8.69 - 8.60 (m, 1H), 7.96 - 7.86 (m, 1H), 7.48 - 7.39 (m, 1H), 3.18 (s, 3H), 2.26 (s, 3H), 1.60 - 1.36 (m, 9H); ESIMS m/z 368 ([M+H]*).

Example 31: Préparation of bis tert-butyl (5-fluoro-1-(pyridin-3-yl)-1H-pyrazol-4yl)carbamate (Compound 135)

To a solution of bis tert-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-yl)-1 H-pyrazol-4yl)carbamate (16 mg, 0.042 mmol, 20.32 %) as an off-white solid: ’H NMR (400 MHz, CDCI₃) δ

8.97 (t, 7=2.0 Hz, 1H), 8.61 (dd, J = 4.8, 1.4 Hz, 1H), 7.99 (ddt, 7 = 8.3, 2.6, 1.3 Hz, 1H), 7.57 (d, 7= 2.5 Hz, 1H), 7.44 (ddd, 7= 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-yl)(methyl)carbamate was prepared as described in Example 31: ’H NMR (400 MHz, CDCI₃) δ 8.94 (s, 1H), 8.57 (d, 7 = 4.2 Hz, 1H), 7.96 (d, 7=7.7 Hz, 1H), 7.41 (dd, 7=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 /V-cyclopropyl-S-methyl-l-Îpyridin-S-ylJ-IH-pyrazol^-amine

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

Page 58 of 619

To a mixture of 3-(3-methyl-1 H-pyrazol-1 -yl)pyridîne (6.7 g, 42.1 mmol), iodic acid (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 reaction mixture heated to 70 °C for 30 minutes. The reaction mixture was poured onto ice with sodium thiosulfate and was extracted with diethyl ether. The combined organic phases were washed with saturated aqueous sodium bicarbonate. The organic phases were then dried with 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-iodo-3-methyl-1 H-pyrazol-1-yl)pyridine (11.3 g, 35.7 mmol, 85 %) as a white solid: mp 131 °C; ’H NMR (400 MHz, CDCl₃) δ 8.958.85 (m, 1H), 8.52 (dd, 7=4.8, 1.4 Hz, 1H), 8.00-7.94 (m, 1H), 7.91 (s, 1H), 7.38 (ddd, 7 = 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-4amine

NH

To a solution of 3-(4-iodo-3-methyl-1 H-pyrazol-1-y!)pyridine (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), cyclopropanamine (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 N-cyclopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (269 mg, 1.255 mmol, 17.90 %) as a yellow solid: mp 104.0-107.0 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.89 (dd, 7 = 2.7, 0.5 Hz, 1H), 8.41 (dd, 7 = 4.7, 1.4 Hz, 1H), 7.96 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.51 (s, 1H), 7.33 (ddd, 7= 8.3, 4.7, 0.7 Hz, 1H), 3.42 (s, 1 H), 2.53-2.42 (m. 1H), 2.22 (s, 3H), 0.72 - 0.65 (m, 2H). 0.60 - 0.53 (m, 2H); ESIMS m/z 215 ([M+H]*).

3-Methyl-M-(3-(methylthio)propyi)-1-(pyridîn-3-yl)-1H-pyrazol-4-amine was prepared as

Page 59 of 619 described in Example 32: IR (thin film) 3298 cm'¹; ’H NMR (400 MHz. CDCI₃) δ 8.87 (d, J = 2.3 Hz, 1 H), 8.40 (dd, J = 4.7, 1.4 Hz, 1 H), 7.93 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 7.35 (s, 1 H), 7.34 -

7.29 (m, 1 H), 3.16 (t, J = 6.8 Hz, 2H), 2.89 (s, 1 H), 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+H]⁺).

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'¹; ’H NMR (400 MHz, CDCI₃) δ 8.86 (d, J = 2.5 Hz, 1 H), 8.40 (dd, J = 4.7, 1.2 Hz, 1 H), 7.93 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 7.35 (s, 1 H), 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.

Example 33: Préparation of tert-butyl (3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4· yl)carbamate (Compound 434) and tert-butyl (1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl)carbamate (Compound 489)

To a suspension of 2-cyclopropyl-4,4,5,5-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 mi) and 2 M aqueous potassium carbonate (3.08 mL, 6.16 mmol). The solution was degassed by applying vacuum and then purging with nitrogen (3 times). To the reaction mixture was added palladium tetrakis (0.178 g, 0.154 mmol) and the flask was heated at 100 °C under nitrogen for 36 hours. Water (5 mL) was added and the mixture was extracted with ethyl acetate. The combined organics were concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give tert-butyl (3cyciopropyl-1-(5-fluoropyridin-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-pyrazol-4-yl)carbamate (242 mg, 0.870 mmol, 28.2 % yield) as a yellow solid.

tert-Butyl (3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 156.5-158.0; ¹H NMR (400 MHz, CDCI3) δ 8.73 (s, 1 H), 8.30 (d, J = 2.5 Hz, 1 H), 8.27 (s, 1 H), 7.76 (dt, J = 9.8,

2.4 Hz, 1H), 6.43 (s, 1H), 1.55 (s. 9H), 1.01-0.91 (m, 4H); ESIMS m/z 319 ([M+H]*). (1-(5-Fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 121.0-123.0 “C; ¹H NMR (300 MHz, CDCI3) δ 8.78 (s, 1 H), 8.37 (s, 1 H), 8.28 (s, 1 H), 7.81 (d, J = 9.6 Hz, 1 H), 7.59 (s, 1 H), 6.44 (s, Page 60 of 619

H). 1.53 (s. 9H). ESIMS m/z 278

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

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

To a N2-purged solution of tert-butyl (1-(5-fluoropyridin-3-yl)-3-vinyl-1/7-pyrazol-4yl)(methyl)carbamate (0.730 g, 2.293 mmol) in methanol (15.29 ml) was added 10% palladium on carbon (0.036 g, 0.339 mmol). The reaction was purged with hydrogen and run under 80 psi of hydrogen at room température for 60 hours. The reaction gave less than 20% conversion. The reaction mixture was filtered 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 tert-butyl (3-ethyl-1-(5fluoropyridin-3-yl)-1H-pyrazo!-4-yl)(methyl)carbamate (616 mg, 1.923 mmol, 84 % yield) as yellow oil: IR (thin film) 1692 cm'¹; ’H NMR (300 MHz, CDCI₃) δ 8.71 (t, J = 1.4 Hz. 1H), 8.35 (d, 7= 2.6 Hz, 1H), 7.83 (dt, 7 = 9.5, 2.3 Hz, 2H), 3.18 (s, 3H), 2.65 (q, 7 = 7.5 Hz, 2H), 1.44 (s, 9H). 1.25 (t. 7= 7.1 Hz, 3H); EIMS m/z 320.

Example 35: Préparation of M-tl-tS-fluoropyridin-S-ylJ-S-formyl-IH-pyrazol^yl)isobutyramide (Compound 560)

To a solution of A/-(1-(5-fluoropyridin-3-yl)-3-vinyl-1H-pyrazol-4-yl)isobutyramide (0.706 g, 2.57 mmol) in tetrahydrofuran (12.87 ml) and water (12.87 ml) was added osmium tetroxide (0.164

Page 61 of619 ml, 0.026 mmol), After 10 minutes at room température, sodium periodate (1.101 g, 5.15 mmol) was added in 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-yl)-3-formyl1H-pyrazol-4-yl)isobutyramide (626 mg, 2.266 mmol, 88 % yield) as a yellow solid: mp 140.0142.0 ’C; ’H NMR (300 MHz, CDCI₃) δ 10.12 (s, 1H), 9.14 (s, 1H), 8.90 (d, J= 2.0 Hz, 1H), 8.82 (s, 1H), 8.51 (d, J = 2.5 Hz, 1H), 7.92 (dt, J = 9.2, 2.4 Hz, 1 H), 2.65 (dt, J = 13.8, 6.9 Hz, 1H), 1.31 (d, J= 6.9 Hz, 6H); ESIMS m/z 277 ([M+Hf).

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

Example 36: Préparation of /V-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4yl)isobutyramide (Compound 435) and /V-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl)isobutyramide (Compound 436)

To a solution of N-(1-(5-fluoropyridin-3-yl)-3-formyl-1H-pyrazol-4-yl)isobutyramide (0.315 g, 1.140 mmol) in methanol (5.70 ml) at 0 ’C was added sodium borohydride (0.086 g, 2.280 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% ethyl acetate/hexanes) to give A/-(1-(5-fluoropyridin-3-yl)-3(hydroxymethyl)-1/7-pyrazol-4-yl)isobutyramide (180 mg, 0.647 mmol, 56.7 %) as a white solid and A/-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-y!)isobutyramide (9 mg, 0.036 mmol, 3.18 %) as a white solid.

/\/-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1/7-pyrazol-4-yl)isobutyramide: mp 144.0-146.0 ’C; ¹H NMR (400 MHz, CDCI₃) δ 8.74 (d, J = 1.1 Hz, 1H), 8.64 (s, 1 H), 8.37 - 8.29 (m, 2H), 7.74 (dt, J = 9.5, 2.3 Hz, 1H), 4.95 (d, 7 = 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+Hf).

Page 62 of 619

N-( 1 -(5-fluoropyridin-3-yl)-1 H-pyrazol-4-yl)isobutyramide: IR (thin film) 1659 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 6.79 (d, J =1.2 Hz, 1H), 8.60 (s, 1H), 8.38 (d, J = 2.5 Hz, 1H), 7.81 (dt, J = 9.5,

2.3 Hz, 1H), 7.68 (s, 1H), 7.54 (s, 1H), 2.63-2.51 (m, 1H), 1.28 (d, J = 6.9 Hz, 6H); ESIMS m/z 249 ([M+H]*).

Example 37: Préparation of N-(3-(chloromethyl)-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4yl)isobutyramide (Compound 561)

To a solution of N-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)isobutyramide (0.100 g, 0.359 mmol) in dichloromethane ( 3.59 ml) was added thionyl chloride (0.157 ml, 2.151 mmol). The reaction was stirred at room 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 Λ/-(3(chloromethyl)-1-(5-fluoropyridin-3-yl)-1/-Lpyrazol-4-yl)isobutyramide (100 mg, 0.337 mmol, 94 % yield) as a white solid: mp 172.0-177.0 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.79 (s, 1H), 8.67 (s, 1H), 8.40 (s. 1H), 7.80 (dt, J= 9.4, 2.3 Hz, 1H), 7.42 (s, 1H), 4.77 (s, 2H), 2.63 (hept, J = 6.9 Hz, 1H), 1.30 (d. J = 6.9 Hz. 6H); ESIMS m/z 298 ([M+Hf).

Example 38: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-A/-ethyl-2methoxyacetamide (Compound 512) (see also Example 11)

To a solution of 3-chîoro-A/-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, 2HCI (0.130 g, 0.502 mmol) and in DCM (2.508 ml) was added A/-ethyl-N-isopropylpropan-2-amine (0.257 ml, 1.505 mmol) followed by 2-methoxyacetyl chloride (0.109 g, 1.003 mmol) and the reaction mixture was stirred at ambient 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

Page 63 of619 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; ’H NMR (400 MHz, CDCI₃) δ 8.96 (d, J = 2.4 Hz, 1 H), 8.63 (d, J ~ 3.8 Hz, 1 H), 8.09 - 8.03 (m, 1 H), 7.99 (s, 1 H), 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); ESIMSm/z295 ([M+Hf).

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

Example 39: Préparation of N-(3-chloro-1-(5-fluoropyridin-3-yl)-1M-pyrazol-4-yl)-N-ethyl-2methyl-3-(methylthio)butanamide (Compound 182) and (Z)-N-(3-chloro-1-(5-fluoropyridin3-yl)-1 H-pyrazol-4-yl)-N-ethyl-2-methylbut-2-enamide (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 dimethylformamide. Oxalyl dichloride (0.178 ml, 2.078 mmol) was added dropwise and the reaction was stirred at room température overnight. The solvent was removed under reduced pressure. The residue was redissolved in dichloromethane (1 mL) and the solvent was removed under reduced pressure. The residue was redissolved in dichloromethane (0.5 mL) and the solution was added to a solution of 3chloro-/V-ethyl-1-(5-fluoropyridin-3-yl)-1W-pyrazol-4-amine (0.100 g, 0.416 mmol) and 4dimethylaminopyridine (0.254 g, 2.078 mmol) in dichloromethane (1.5 mL) and stirred at room température overnight. The solvent was removed under reduced pressure and the residue was purify by chromatography (0-100% ethyl acetate/hexanes) to give A/-(3-chloro-1-(5fluoropyridin-3-yl)-1/-/-pyrazol-4-yl)-A/-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)-1/-/-pyrazol-4yl)-/V-ethyl-2-methylbut-2-enamide (38 mg, 0.118 mmol, 28.3 % yield) as a yellow oil.

A/-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-/\/-ethyl-2-methyl-3-(methylthio)butanamide: IR (thin film) 1633 cm'¹; ¹H 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, 1H), 2.59 - 2.33 (m, 1H), 2.04 (s, 2H), 2.02 (s, 1H), 1.32 (d, J = 6.7 Hz. 1H), 1.27 (d, J = 6.2 Hz, 1H), 1.23 (d, J = 6.9Hz, 2H),

Page 64 of 619

1.18 - 1.12 (m, 5H); ESIMS m/z 371 ([Μ]*).

(Z)-/V-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-A/-ethyl-2-methylbut-2-enamide: ¹H NMR (400 MHz, CDCI₃) δ 8.73 (d, J = 2.0 Hz, 1 H), 8.46 (d, J = 2.4 Hz, 1 H), 7.87 (d, J = 4.9 Hz, 1 H), 7.84 (dt, J = 9.2, 2.4 Hz, 1 H), 5.93 - 5.76 (m, 1 H), 3.73 (q, J = 7.1 Hz, 2H), 1.72 (s, 3H), 1.58 (dd, 7 = 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 in Example 39.

Example 40: Préparation of N-(3-chloro-1-(pyrïdin-3-yl)-1H-pyrazol-4-yl)-/V-methyl-2(methylthio)acetamide (Compound 337)

To an ice cold solution of 2-(methylthio)acetic acid (0.092 g, 0.863 mmol) in DCM (2 mL) was added A/-ethyl-N-isopropylpropan-2-amine (0.111 g, 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-A/-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%): ¹H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1 H), 8.62 (dd, J = 4.8, 1.4 Hz, 1H), 8.13 (s, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.50-7.43 (m, 1H), 3.26 (s, 3H), 3.12 (s, 2H), 2.24 (s. 3H); ¹³C 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-ch!oro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-/V-ethyl-2-methyl3-oxobutanamide (Compound 499)

Page 65 of 619

To a solution of 3-chloro-/V-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 heated in a microwave (CEM Discover) at 150 °C for 1.5 h, with externat IR-sensor température monitoring from the bottom of the vessel. LCMS (ELSD) indicated a 40% conversion to the desired product The mixture was diluted with ethyl acetate (50 ML) and saturated aqueous 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 /V-(3-chloro-1-(pyridin-3-yl)-1Hpyrazol-4-yl)-N-ethyl-2-methyl-3-oxobutanamide (37 mg, 11 % yield, 96% purîty) 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, 1H), 7.96 - 7.87 (s, 1H), 3.87 - 3.58 (d. J - 3.0 Hz, 2H), 3.49 - 3.38 (m, 1H), 2.16-2.08 (s, 3H). 1.39- 1.32 (d, J = 7.0 Hz, 3H), 1.22- 1.13 (m, 3H); EIMS (m/z) 321 ([M+1]⁺), 319 ([M-1]·).

Example 42: Préparation of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-/Vethylcyclopropanecarboxamide (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,/V-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 overnight. The reaction mixture was concentrated to dryness and the crude product was purified by reverse phase silica gel chromatography eluting with 0-50% acetonitrile/water to give a white solid (0.03 g, 25%); mp 111-119 °C; ’H 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

Page 66 of 619 <7 (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 with the procedures disclosed in Example 42.

Example 43: Préparation of W-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)-N-(3-(methylthio)propanoyl)propanamide (Compound 407)

To a solution of /V-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(methylthio)propanamide (0.216 g, 0.728 mmol) in 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 Initiator microwave reactor for 3 hours at 100 °C, with external IR-sensor température monitoring from the side of the vessel. The crude mixture was concentrated and purified using reverse phase ΟΙ 8 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; ¹H NMR (300 MHz, CDCI₃) δ 8.96 8.92 (d, J = 2.7 Hz, 1H), 8.64-8.59 (dd, J = 4.9, 1.4 Hz, 1H), 8.07 - 7.99 (m, 2H), 7.50-7.40 (dd, J = 8.4, 4.8 Hz, 1H), 3.39 - 3.28 (m, 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, 1H), 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+H]⁺).

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

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

Page 67 of 619

To a 7 mL vial was added 3-chloro-N-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 °C. Then the solution of DCC (0.500 mL, 0.500 mmol, 1.0M in DCM) was added. The solution was allowed to warm up to 25 °C slowly and stirred at 25 °C overnight. White precipitate formed during the reaction. The crude reaction mixture was filtered through a cotton plug and purified by silica gel chromatography (0-100% EtOAc/hexane) to giveN-[3-chloro-1 -(3-pyridyl)pyrazol-4-yl]-2,2-dideuterio-N-ethyl-3methylsulfanyl-propanamide (97 mg, 0.297 mmol, 59.4 % yield) as a colorless oil: ¹H NMR (400 MHz, CDCIs) 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. 1H), 7.52-7.40 (m, 1H), 3.72 (q, J = 7.2 Hz, 2H), 2.78 (s, 2H), 2.06 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H); ESIMS m/z 327 ([M+Hf); 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-(pyridin-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 turned from a clear solution to a suspension with white solid material. The reaction mixture was concentrated and purified using silica gel chromatography (0-20% MeOH/DCM) to yield the title compound as a white solid (0.135 g, 95%); mp 197-200 °C; ’H NMR (400 MHz, CDCI₃) δ 8.94 (d, J = 2.3 Hz, 1H), 8.48 -

8.37 (m, 1H), 8.32 (s, 1H), 7.94 (d, J = 8.3 Hz, 1H), 7.52 (br s, 1H), 7.41 - 7.25 (m, 1H), 5.79 (br s, 1 H), 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

Page 68 of 619 m/z 246 ([M+Hf), 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.

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

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, 2HCI (0.130 g, 0.502 mmol) in DCE (1.25 ml) was added A/-ethyl-N-isopropylpropane-2-amine (0.21 mL, 1.255 mmol) followed by 1-isocyanatobutane (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 using silica gel chromatography (0-20% MeOH/DCM) to yield the title compound as a beige solid (0.131 g, 77%): IR (thin film) 3326, 2959, 2931, 1648 cm'¹; ’H NMR (400 MHz. CDCI₃) δ 8.95 (s, 1H), 8.62 (d, 7=4.0 Hz, 1H), 8.08-8.01 (m, 1H), 7.97 (s, 1H), 7.46 (dd, 7 = 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+Hf).

Compounds 479 - 480, 501 - 504, 513, 518 and 519 were prepared according to Example 46.

Example 47: Préparation of 1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)imidazolidin-2-one (Compound 374)

To a solution of 1-(3-chloro-1-(pyridîn-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

Page 69 of 619

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, 1H), 8.56 (dd, J = 4.7,1.4 Hz, 1H), 8.33 (s, 1H), 7.99 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.40 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 5.00 (s, 1H), 4.14-4.07 (m, 2H), 3.68-3.58 (m, 2H); ESIMS m/z 264 ([M+Hf).

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

47.

Example 48: Préparation of S-tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4yl)(ethyl)carbamothioate (Compound 514)

To a solution of 3-chloro-A/-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, 2HCI (0.13 g, 0.502 mmol) în DCM (2.508 ml) was added /V-ethyl-A/-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; ¹H NMR (400 MHz, CDCI₃) δ 8.96 (d, J = 2.5 Hz, 1H), 8.60 (dd, J = 4.7, 1.4 Hz, 1H), 8.08 -8.03 (m, 1 H), 7.97 (s, 1H), 7.47 - 7.41 (m, 1H), 3.69 (q, J = 7.2 Hz. 2H), 1.47 (s, 9H), 1.21 -1,13 (m. 3H); ESIMS m/z 339 ([M+Hf).

Compounds 333, 338, 339, 346, 368 and 373 were prepared in accordance with the procedures disclosed in Example 48.

Example 49: Préparation of /V-(3-chloro-1-(pyridin-3-yl)-1 W-pyrazol-4-yl)-W-ethyl-2-methyl3-(methio)propanethioamîde (Compound 364)

Page 70 of619

To a microwave reaction vessel was added /V-(3-chloro-1 -(pyridin-3-yl)-1 H-pyrazol-4-yl)-/V-ethyl-

2-methyl-3-(methio)propanamide (0.07 g, 0.22 mmol) in dichloroethane (1.87 mL) and Lawesson’s reagent (0.05 g, 0.12 mmol). The vessel was capped and heated in a Biotage Initiator microwave reactor for 15 minutes at 130 °C, with external IR-sensor température monitoring from the side of the vessel. The reaction was concentrated to dryness and the crude material was purified by silica gel chromatography (0-80% acetonitrile/water) to give the desired product as a yellow oil (0.33 g, 44%): IR (thin film) 1436 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 8.97 (d, J = 2.5 Hz, 1H), 8.77 - 8.52 (m, 1 H), 8.11 - 7.89 (m, 2H), 7.60 - 7.38 (m, 1H), 4.62 (bs, 1 H). 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.

Example 50: Préparation of A/-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-W-ethyl-4,4,4trifluoro-3-(methylsulfinyl)butanamide (Compound 570)

To a 20 mL vial was added W-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-4,4,4-trifiuoro-3(methylthio)butanamide (82 mg, 0.209 mmol) and hexafluoroisopropanol (1.5 mL). Hydrogen peroxide (0.054 mL, 0.626 mmol, 35% solution in water) was added in one portion 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-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-/\/-ethyl-4,4,4-trifluoro-3(methylsulfinyl) butanamide (76 mg, 0.186 mmol, 89 % yield) as white semi-solid: ¹H NMR (400 MHz, CDCIa) δ 8.98 (d, J- 2.3 Hz, 1H), 8.63 (td, J = 4.8, 2.4 Hz, 1 H), 8.14 - 8.01 (m, 2H), 7.46 (ddd, J = 8.3, 4.8, 0.7 Hz, 1 H), 4.26 (dd, J = 17.2, 8.4 Hz, 1 H), 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

Page 71 of 619 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 materials in accordance with the procedures disclosed in Example 50.

Example 51: Préparation of /V-(3-chloro-1-(pyridin-3-y!)-1H-pyrazol-4-yl)-N-ethyi-3(methylsulfinyl)propanamide (Compound 362)

To /V-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(methylthio)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 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 material was purified by silica gel chromatography (0-10% methanol/ dichloromethane) to give the desired product as a clear oil (0.03 g, 40%); IR (thin film) 1655 cm’¹; ¹H NMR (400

MHz, CDC|₃) 6 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, 1H), 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 N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3(methylsulfonyl)propanamîde (Compound 363)

Page 72of6l9

To A/-(3-chloro-1-(pyridin-3-yl)-1/-/-pyrazol-4-yl)-N-ethyl-3-(methylthio)propanamïde (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 MgSO₄, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (0 to 10% methanol/dichloromethane) to give the desired product as a clear oil (0.04, 47%): (thin film) 1661 cm'¹; ¹H NMR (400 MHz, CDCI₃) δ 8.95 (t, J= 11.5 Hz, 1H), 8.64 (dd, J = 4.8, 1.4 Hz, 1 H),

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+Hf).

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-methyi-1-(3-fluoropyridin-5-yl)-1H-pyrazol-4-yl)N-ethyl-2methyl-(3-oxido-D⁴-sulfanylidenecyanamide)(methyl)propanamide (Compound 250)

To a solution of A/-ethyl-N-(1-(5-fluoropyridin-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 iodobenzenediacetate (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 in one portion. The reaction was stirred for 1 hour at 0 °C. The excess mCPBA was quenched with 10% sodium thiosutfite 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

Page 73 of 619 a clear oil (0.16 g, 56%): IR (thin film) 1649 cm’¹; ¹H NMR (400 MHz, CDCI₃) δ 8.80 (dd, J =

43.8, 10,1 Hz, 1H), 8.51 - 8.36 (m, 1H), 8.11 (d, 7 = 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+Hf).

Example 54: Préparation of W-ethyl-4,4,4-trifluoro-3-methoxy-W-(3-methyl-1-(pyridin-3-yl)1 H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide (Compound 276)

To a solution of A/-ethyl-4,4,4-trifluoro-3-hydroxy-/V-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3(trifluoromethyl)butanamide (184 mg, 0.448 mmol) in DMF (3 mL) stîrring 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 overnight. 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 Na₂SO₄ and concentrated. Silica Gel chromatography (0-100% EtOAc/hexane) gave A/-ethyl-4,4,4-trifluoro-3-methoxy-A/-(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; ¹H NMR (400 MHz, CDCI₃) δ 8.94 (d, 7 = 2.5 Hz, 1 H), 8.59 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.01 (ddd. 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.85 (s, 1 H), 7.44 (ddd, 7= 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, 7 = 7.1 Hz, 3H); ESIMS m/z 425 ([M+Hf); IR (Thin film) 1664 cm’¹.

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

Example 55, Step 1: Préparation of N-(2-((fert-butyldimethylsilyl)oxy)ethyl)-W-(3-chloro-1(pyrîdin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide

Page 74 of 619

A solution of W-(3-chloro-1-(pyridin-3-yl)-1/-/-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide (0.150 g, 0.483 mmol) in /V,N-dimethylformamîde (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)(terf-butyl)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-((tertbutyldimethylsilyl)oxy)ethyl)-/V-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)propanamide (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, 1 H), 8.55 (dd, J = 4.7, 1.4 Hz, 1 H), 8.05 (s, 1H), 7.98 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.41 (ddd, J = 8.4, 4.8, 0.5 Hz, 1H), 4.35-3.06 (m. 4H), 2.86-2.73 (m, 1H), 2.73-2.59 (m, 1 H), 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-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-(2hydroxyethyl)-2-methyl-3-(methylthio)propanamide (Compound 535)

To a solution of N-(2-((terî-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-

4-yl)-2-methyl-3-(methylthio)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 A/-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-A/-(2-hydroxyethyl)-2methyl-3-(methylthio)propanamide as a white oil (0.081g, 0.217 mmol, 56.5 %): IR (thin film) 3423, 1654 cm'¹; ’H NMR (400 MHz, CDCI₃) δ 9.00 (d, J = 2.5 Hz, 1 H), 8.62 (dd. J = 4.7, 1.2 Hz, 1 H), 8.25 (s, 1 H), 8.07 (ddd, J = 8.3, 2.4, 1.3 Hz, 1 H), 7.47 (dd, J = 8.3, 4.7 Hz, 1 H), 4.47 3.70 (m, 3H), 3.65 - 3.09 (m, 2H), 2.91 - 2.68 (m, 2H). 2.48 (dd, J= 12.4, 5.0 Hz, 1H), 2.01 (s, 3H), 1.18 (d, J = 6.5 Hz, 3H); ESIMS m/z 356 ([M+H]*).

Example 56: Préparation of 2-(N-(3-chloro-1-(pyridin-3-yl)-1W-pyrazol-4-yl)-2-methyl-3Page 75 of 619 (methylthio)propanamido)ethyl acetate (Compound 547)

To a solution of N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-2-methyl-3(methylthio)propanamide (0.045 g, 0.127 mmol) in dichloromethane (1.27 ml) was added N,Ndimethylpyridin-4-amine (0.023 g, 0.190 mmol) and triethylamine (0.019 g, 0.190 mmol) followed by acetyl chloride (0.015 g, 0.190 mmol). The reaction was stirred at room température overnight. Water was added and the mixture was extracted with dichloromethane. The combined organic phases were concentrated and chromatographed (0-100% ethyl acetate/hexanes) to give 2-(N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3(methylthio)propanamido)ethyl acetate as a yellow oil (0.015 g, 0.034 mmol, 26,8 %): IR (thin film) 1739, 1669 cm'¹; Ή NMR (400 MHz, CDCI₃) δ 8.97 (d, J = 2.3 Hz, 1 H). 8.64 (dd, 7 = 4.7,

1.4 Hz, 1H), 8.15 (s, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.47 (ddd, 7=8.3, 4.8, 0.7 Hz, 1H), 4.50 - 3.40 (m, 4H), 2.84 (dd, 7 = 12.7, 8.9 Hz, 1H), 2.78 - 2.63 (m, 1H), 2.46 (dd, 7 = 12.7, 5.4 Hz, 1H), 2.03 (s, 3H), 2.01 (s, 3H), 1.16 (d, 7 = 6,6 Hz, 3H); ESIMS m/z 398 ([M+H]⁺).

Example 57: Préparation of 2,2-dideuterio-3-methylsulfanyl-propanoic 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 in D₂O), the solution was heated to reflux overnight. NMR showed ca. 95% D at alpha-position. The réaction was cooled down and quenched with concentrated HCl until pH<2. White precipitate appeared in aqueous layer upon acidifying. Reaction mixture was extracted with 3 x 50 mL EtOAc, the combined organic layers were dried over Na₂SO₄₁ concentrated in 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 colorless 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..

Page 76 of 619

2-Deuterio-2-methyl-3-methylsulfanyl-propanoic acid was prepared as described in Example 57 to afford a colorless oil (3.62 g, 26.8 mmol, 60.9 %): IR (Thin film) 2975, 1701 cm'¹; ¹H NMR (400 MHz, CDCI3)ô 11.39- 10.41 (brs, 1H), 2.88-2.79 (d, J = 13.3 Hz. 1H), 2.61-2.53 (d, J = 13.3 Hz, 1H), 2.16-2.09 (s, 3H), 1.32- 1.25 (s, 3H); ¹³CNMR(101 MHz, CDCI3) 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-methylpropanoic acid (5 g, 41.6 mmol), followed by MeOH (15 mL), the solution was stirred at 25 ^qC. Potassium hydroxide (5.14 g, 92 mmol) was added slowly as the reaction is exothermic. Iodomethane-d₃ (6.63 g, 45.8 mmol) was added slowly and then the reaction mixture was heated at 65 °C overnight. The reaction was worked up by addition of 2 N 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-(trideuteriomethylsulfanyl)propanoic acid (4.534 g, 33.0 mmol, 79 %) as colorless oil: IR (Thin film) 3446, 1704 cm'¹; ¹H 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-(methylthio)propanoic acid

O

SMe

OH

Sodium methanethiolate (4.50 g, 64.2 mmol) was added at 25 °C to a solution of 3-chloro-2hydroxypropanoic 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 2-hydroxy-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’¹; ¹H 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, 1H), 2.20 (s. 3H); EIMS m/z

Page 77 of 619

136.

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

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 overnight 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(methylthio)propanoic acid (126 mg, 0.839 mmol, 45.7 % yield) as colorless oil: ¹H NMR (400 MHz, CDCI₃) δ 9.10 (s, 1H), 4.03 (dd, J = 6.9, 4.4 Hz, 1H), 3.51 (s, 3H), 2.98 - 2.93 (m, 1H), 2.86 (dd, J ~ 14.1, 6.9 Hz, 1H), 2.21 (s, 3H); EIMS m/z 150.

Example 61: Préparation of 2-(acetylthiomethyl)-3,3,3-trifluoropropanoic acid

O O

cf₃

To a 50 mL round bottom flask was added 2-(trifluoromethyl)acrylic acid (6 g, 42.8 mmol), followed by thioacetic acid (4.59 ml, 64.3 mmol). The reaction was slïghtly exothermic. The mixture was then stirred at 25 °C overnight. NMR showed some starting material (-30%). One more equiv of thioacetic acid was added and the mixture was heated at 95 °C for 1 hour, then allowed to cool to room 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)-3,3,3trifluoropropanoic 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; ¹H NMR (400 MHz, CDCI₃) 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); ¹³C 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); ¹⁹F NMR (376 MHz, CDCI₃) δ -67.82.

Page 78 of 619

Example 62: Préparation of 3,3,3-trifluoro-2-(methylthiomethyl)propanoic acid

O

To a solution of 2-(acetylthiomethyl)-3,3,3-trifluoropropanoic acid (649 mg, 3 mmol) in MeOH (5 mL) stirring at 25 °C was added pellets of potassium hydroxide (421 mg, 7.50 mmol) in four portions over 5 minutes. Reaction was exothermic. Then Mel was added in once, the reaction mixture was then heated at 65 °C for 18 hours. The reaction was then cooled down and quenched with 2N 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-(methylthiomethyl)propanoic acid (410 mg, 2.179 mmol, 72.6 % yield) as a Iight yellow oil: ¹H NMR (400 MHz, COCI3) δ 10.95 (s, 1H), 3.49-3.37 (m, 1H), 3.02 (dd, J = 13.8, 10.8 Hz, 1H), 2.90 (dd. J = 13.8, 4.0 Hz, 1H), 2.18 (s, 3H); ¹³C NMR (101 MHz, CDCI3) δ 172.04 (q, J = 2.8 Hz), 123.55 (q, J - 281.2 Hz), 50.89 (q, J = 27.5 Hz), 29.62 (q, J = 2.3 Hz), 15.85; ¹⁰F NMR (376 MHz, CDCI₃) δ -67,98.

Example 63: Préparation of 3-(methylthio)pentanoic acid

O HO'^^x^'S'^X

S,S-dimethyl carbonodithioate (1.467 g, 12.00 mmol) was added with vigorous stirring to a solution of (E)-pent-2-enoic acid (2.002 g, 20 mmol) in 30% KOH solution (prepared from potassium hydroxide (3.87 g, 69 mmol) and Water (10 mL)). The reaction mixture was slowly heated to 90°C over a period of 20-30 min. Heating was continued for 3 hours before the reaction was cooled down to 25 °C and quenched slowly wîth 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 Iight orange oil: IR (Thin film) 2975, 1701 cm’¹; ¹H NMR (400 MHz, CDCI3) δ 2.92 (qd, J = 7.3, 5.6 Hz. 1 H), 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-(methylthio)pentanoïc acid was prepared as described in Example 63 and isolated as a colorless oil: IR (Thin film) 2960, 1704 cm’¹; ¹H NMR (400 MHz, CDCI₃) δ 2.88 (ddd, J =

Page 79of619

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.

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

O

A 1M solution of lithium aluminum tri-fert-butoxyhydride in tetrahydrofuran (70.90 mL, 70.90 mmol) was added to a stirred solution of diethyl cyclopropane-1,T-dicarboxylate (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 (brs, 1H), 1.22-

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

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

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-(methylthiomethyl)cyclopropanecarboxylate

O

Page 80 of 619

Sodium methanethiolate (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,Ndimethylformamide (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, 7 = 7, 4 Hz, 2H), 1.25 (t, 7 = 7 Hz, 3H), 0.89 (dd, 7=7, 4 Hz, 2H).

Example 67: Préparation of 1-(methylthiomethyl)cyclopropanecarboxylic 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 pH=1 with concentrated hydrochloric acid and extracted with dichloromethane. The combined organic layers were dried (Na₂SO₄), filtered, and concentrated and concentrated to dryness to give the desired product as a light brown oil (2.10 g, 46%): ’H NMR (300 MHz, CDCI₃) δ 2.82 (s, 2H), 2.17 (s, 3H), 1.41 (dd, 7 = 7, 4 Hz, 2H), 0.99 (dd, 7 = 7, 4 Hz, 2H).

Example 68: Préparation of 2,2-dimethyl-3-(methylthio)propanoic acid

O

OH

2,2-Dimethyl-3-(methylthio)propanoic acid can be prepared as demonstrated in the literature (reference Musker, W. K.; et al. 7. Org. Chem. 1996, 51, 1026-1029). Sodium methanethiolate (1.0 g, 14 mmol, 2.0 equiv) was added to a stirred solution of 3-chloro-2,2-dimethylpropanoic acid (1.0 g, 7.2 mmol, 1.0 equiv) in N,A/-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 pH=1 with concentrated hydrochloric acid and

Page 81 of 619 extracted with diethyl ether (3 x 75 mL). The combined organic layers were dried (sodium sulfate), gravity filtered, and concentrated to afford a colorless oil (1.2 g, 99% crude yield). ’H NMR (300 MHz, CDCI₃) δ 2.76 (s, 2H), 2.16 (s, 3H), 1.30 (s, 6H).

Example 69: Préparation of 4,4,4-trifIuoro-3-(methylthio)butanoic acid

To a 100 mL round bottom flask was added (E)-4,4,4-trifluorobut-2-enoic acid (8 g, 57.1 mmol) and Methanoi (24 mL), the solution was stirred in a water bath, then sodium methanethiolate (10.01 g, 143 mmol) was added in three portions. Vigorous bubbling was observed, the mixture was stirred at 25 °C overnight, NMR showed no more starting material. To the reaction mixture was added 2 N HCl until acidic. The mixture was extracted with chloroform (5 x 50 mL), combined organic layer was dried over Na₂SO₄, concentrated in vacuo and further dried under hîgh 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 colorless oil: 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, 1H), 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^= 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-butyric acid

3-methyl-3-methylsulfanyl-butyric acid was made using the procedures disclosed in 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., 1985, 15(7), 623-32.

Page82of6l9

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

O

Tetrahydro-thiophene-3-carboxylic acid was made using the procedures disclosed in

Heterocycles, 2007, 74, 397-409.

Example 73: Préparation of 2-methyl-3-methylsulfanyl-butyric acid

2-Methyl-3-methylsulfanyl-butyric acid was made as described in J.Chem Soc Perkin 1, 1992,

10, 1215-21.

Example 74: Préparation of (1S,2S)-2-(methylthio)cyclopropanecarboxylic acid

O

(1 S,2S)-2-(Methylthio)cyclopropanecarboxylic acid was made using the procedures disclosed in Synthetic Comm., 2003, 33 (5); 801-807.

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

2-(2-(Methylthio)ethoxy)propanoic acid was made as described in WO 2007/064316 A1.

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

Page 83 of 619

ο °Ό

2-((Tetrahydrofuran-3-yl)oxy)propanoic acid was made as described in WO 2007/064316 A1,

Example 77: 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, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed résistance to many pesticides.

Certain molécules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, “Table 3: GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA) Ratîng Table was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in H₂O to obtain the solution at 200 ppm test compound. A handheld 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 aphids 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 aphids on solvent check plants and

Y = No. of live aphids on treated plants

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The results are indicated in the table entitled Table 4. Biological Data for GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA) (See Table Section).

Example 78: Insecticidal test for sweetpotato whitefly-crawler (Bemisia tabaci) (BEMITA) in foliar spray assay

Cotton plants grown in 3-inch pots, with 1 small (3-5 cm) true leaf, 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. Adults were blown off leaves using a hand-held Devilbiss sprayer (23 psi). Plants with egg infestation (100-300 eggs per plant) were placed in a holding room for 5-6 days at 82 °F and 50% RH for egg hatch and crawler stage to develop. Four cotton plants were used for each treatment. Compounds (2 mg) were dissolved in 1 mL of acetone solvent, forming stock solutions of 2000 ppm. The stock solutions were diluted 10X with 0.025% Tween 20 in H₂O to obtain a test solution at 200 ppm. A hand-held Devilbiss sprayer was used for spraying a solution to both sides of cotton leaf until runoff. Référencé plants (solvent check) were sprayed with the diluent only. Treated plants were held in 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 correction formula and presented in Table 4. Biological Data for GPA (MYZUPE) and sweetpotato whitefly-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, benzenesuifonic, 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

Page 85 of 619 (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine 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 particularly 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 in the same manner as the invention disclosed in this document is applied.

Molécules of Formula One may be made as various crystal polymorphs. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molécule 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 ²H (also known as deuterium) in place of ¹H.

Molécules of Formula One may be made with different radionuclides. Of particular importance are molécules having ¹⁴C.

STEREOISOMERS

Molécules of Formula One may exist as one or more stereoisomers. Thus, certain molécules 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. Individuel stereoisomers may be obtained by known sélective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molécules disclosed in this document can exist as two or more isomers. The various isomers include géométrie isomers, diastereomers, and enantiomers. Thus, the molécules disclosed in this document include géométrie isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the présent disclosure are drawn in only one géométrie form for clarity, but are intended to represent ail géométrie forms of the molécule.

COMBINATIONS

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 compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties. Additionally, the molécules of Formula One may also be used in combination (such as, in a compositional mixture, or a

Page 86 of 619 simultaneous or sequential 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 groupe that may be used with the Molécules of Formula One are - (3ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic 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-ethylhexyl, 2,4,5-T-3-butoxypropyl, 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-triethylammonium, 2,4,5-T-tro!amine,

2.4- D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 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-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 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-lïthium, 2,4-Dmeptyl, 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-trïs(2hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPAsodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydimsodium, allyl alcohol, allyxycarb, alorac, a/pha-cypermethrin, a/pha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amîcarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulamsodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphosmethyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium,

Page 87 of 619 bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarbisopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, betà-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bîspyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvînfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromoDDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirîmate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxîm, 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, carboxin, 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, chloramben-methylammonium, chloramben-sodium, chloramine phosphores, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidîne, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon,

Page 88 of 619 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 II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephionO, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, dfanshiluquebingjuzhl, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-dtglycolamine, 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-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil,

Page 89of6l9 dicyclonon, dîeldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, dîethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, dîfethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, dîflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, dinîconazole, diniconazole-M, dinitramine, dinobuton, drnocap, dinocap-4, dinocap-6, dînocton, dinofenate, dinopenton, dinoprop, dînosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinosebsodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacînone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, dîsul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothaldiammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujlxiancaoan, 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, ethohexadîol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl anaphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethyücin, 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, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph,

Page 90 of 619 fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flampropM, 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, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, 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, fiurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldéhyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetylaluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosatedimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosatepotassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acétates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalii, imazalil nitrate, imazalii sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamoxPage9l of6l9 ammonium, imazapic, imazapic-ammonîum, imazapyr, imazapyr-tsopropylammonium, imazaquin, imazaquin-ammonium, imazaquîn-methyl, imazaquin-sodîum, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, îminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, 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, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvénile hormone I, juvénile hormone II, juvénile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuîcaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatfn, linuron, lirimfos, litlure, looplure, lufenuron, Ivdingjunzhi, Ivxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, ΜΑΜΑ, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPAdiolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPAolamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPBethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecopropethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-Ppotassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxylM, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon,

Page 92 of 6I9 methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-ptoluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalamsodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, novifiumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrîne, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, paradichlorobenzene, parafiuron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury dérivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphores, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloramtriethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, pîperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos,

Page 93 of 619 pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, poiyoxins, polyoxorim, polyoxorim-zînc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quîntîofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-lll, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sïntofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime,

Page 94 of 619 sulfur, sulfuric acid, sulfuryl 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, tebuthiuron, 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, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuronmethyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultapmonosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydîm, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutîl, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyrtriethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralîn, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trîmedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropîndan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zetacypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, a-ecdysone, a-multistriatin, and anaphthaleneacetic 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.

Page 95 of 619

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 for grape 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 thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinernema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolérant or résistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect résistant property to the genetically modified organism. In one embodiment, the molécules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology-based control) products. Copping L.G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.

OTHER ACTIVE COMPOUNDS

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 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-(4’-chloro-2,4-dimethyl[1,1 ’-biphenyl]-3-yl)-4-hydroxy-8-oxa-1 -azaspiro[4,5]dec-3-en-2one;

3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5/-/)-furanone;

4. 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;

5. 3-ch lo ro-A/2-[( 1 S)-1 -methyl-2-(methylsulfonyl)ethyl]-N1 -[2-methyl-4-[1,2,2,2-tetrafluoro1 -( tri f I uorome thyl )ethy I] pheny I]-1,2-benzenedicarboxamide;

6. 2-cyano-/V-ethyl-4-fluoro-3-methoxy-benenesulfonamide;

Page 96 of 619

7. , 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;

8. 2-cyano-3-difluoromethoxy-A/-ethyl-4-fluoro-benzenesulfonamide;

9. 2-cyano-3-fluoromethoxy-A/-ethyl-benzenesulfonamide;

10. 2-cyano-6-fluoro-3-methoxy-A/,/V-dimethyl-benzenesulfonamide;

11. 2-cyano-/V-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;

12. 2-cyano-3-difluoromethoxy-A/,/\/-dimethylbenzenesulfon-amide;

13. 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1 -methyl-1 H-pyrazole-4-carboxamide;

14. N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-p-tolyl) hydrazone;

15. N-ethyt-2,2-dichloro-1 -methylcyclopropane-carboxamide-2-(2,6-dichloro-a,a,a-trifluorop-tolyl) hydrazone nicotine;

16. O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1 -(2-trifluoromethyIphenyI)-vinyl]} S-methyl thiocarbonate;

17. (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-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;

19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and

20. N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloroalpha, alpha, alpha-tri f I uoro- p-toly I )h yd razo n e.

SYNERGISTIC MIXTURES

Molécules 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 molécules of Formula One are the same, similar, or different Examples of modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acétylcholine receptor agonist; acétylcholine receptor antagonist; 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 molécules 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

Page 97 of 619 maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated émulsions, dusts, emulsifiable concentrâtes, fumrgants, gels, granules, microencapsulations, seed treatments, suspension concentrâtes, suspoemulsions, 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 CropLife 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 solïds, 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, comprisîng from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesuîfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic 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 is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin dérivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrâtes are selected from conventional anionîc and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mîxing it into a carrier comprised of water and surfactants. Ingrédients, such as inorganic salts and synthetîc or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, bail mill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% Page 98 of619 by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine.

It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aérosol composition. In such compositions the pesticide is dissolved or dispersed in 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.

Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that hâve a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest's respiratory System or being absorbed through the pest's cuticle. Fumigants are applied to contrai stored product pests under gas proof sheets, in gas sealed rooms or buildings or in spécial chambers.

Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingrédient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.

Oil solution concentrâtes are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better pénétration of crevices, and better adhesion to greasy surfaces.

Page 99 of 619

Another embodiment is an oîl-in-water émulsion, wherein the émulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar 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

Generally, when the molécules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, pénétrants, buffers, sequestering agents, drift réduction agents, compatibility 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 liquids 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 particles and helps to preserve the state of dispersion of the particles and prevents them from reaggregatîng. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrâtes and water-dispersible granules. Surfactants that are used as dispersing agents hâve the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The Page 100 of 619 most commonly used surfactants are anionic, non-ionîc, 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-ionics 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 developed 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 stabilîty to suspension concentrâtes because the hydrophobie backbones hâve many anchoring points onto the particle surfaces. Examples 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.

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 liquide would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil-soluble calcium sait of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (HLB) values from 8 to 18 will normally provide good stable émulsions. Emulsion stabilîty can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in water at concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobie part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additives such as minerai or vegetable oils as adjuvants to spray-tank mixes to împrove 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: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water-dispersible granules.

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V

Organic solvents are used mainly in the formulation of emulsifiable concentrâtes, oil-inwater émulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation of suspension 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-insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnésium aluminum silicate, and attapulgite. Watersoluble polysaccharides hâve been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are 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 anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling 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 phydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-silicones. Silicones are usually aqueous émulsions of dimethyl polysiloxane, whîle the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.

Green agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodégradable and

Page 102 of 619 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 in Agriculture and Environment - Retrospects and Prospects by A.S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

PESTS

In general, the 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.

In another embodiment, the molécules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molécules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molécules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.

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 is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, 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 is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but Is 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

Page 103 of 619 assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nénuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus margînatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus commuais, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinocéros, Oryzaephilus mercator, Oryzaephilus surinamensis, Ouléma melanopus, Ouléma oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica,, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.

In 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 Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.

In 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 is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Délia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, 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, Liriomyza 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.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular généra includes, but is not limited 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., Philaenus

Page 104 of 619 spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is 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 solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis 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 striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxéra vitifoliae, Physokermes piceae,, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis gramînum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Hymenoptera. 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/istes 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 invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molécules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular généra includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp.. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Page 105 of 619

Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.

In another embodiment, the molécules 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., Caloptilia 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, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehnîella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta îndicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesla botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, 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, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusîa nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sltotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, 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., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to,

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Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissîmilis, Goniodes gigas, Menacanthus stramineus, 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 includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa 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 to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, 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 includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips cîtri, Scirtothrips dorsa/is, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips tabaci.

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 includes, 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 includes, but is not limited to, Acarus spp., Acu/opsspp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus cîtri, Panonychus ulmi, 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. includes, but is not limited to, Scutigerella immaculata.

Page I07of6l9

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 includes, 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 list of particular sp. includes, 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

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 preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.

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 ornamental 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 in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molécule of Formula One include areas where apples, corn, 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 valuable 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 in an area. This can corne about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.

The molécules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root System, to better withstand stressful growing conditions). Such other compounds are, for

Page 108 of 619 example, 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 valuable 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 fruîting portions of plants to control pests. The molécules will either corne in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The molécules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a moiecule takîng it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.

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, or slant 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 moiecule of Formula One.

The molécules of Formula One can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the molécules of Formula One may be désirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the moiecules of Formula One to a different portion of the plant. For example, control of foliar-feeding insects can be achieved 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 modifîed 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 moiecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This résulte in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the moiecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, Page 109 of 619 amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefîts, 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 sector or 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 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 molécules 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 trcks 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 molécules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animais listed above.

The molécules 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 molécules of Formula One may also be used on such new invasive species to control them in such new environment.

The molécules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, plantîng, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molécules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, împroving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingrédients), improving the vigor of a plant (e.g. improved plant 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 abiotic and/or biotic stress of the plant.

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Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy évaluation processes by various governmental 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 thïrd 5 party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental 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.

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 molécule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to thïrd parties.

The headings in this document are for convenience only and must not be used to interpret any portion hereof.

TABLE SECTION

Table 1: Compound number, appearance, and structure

Compound No.	Appearance	Structure
1	yellow gum	CH, / 3 ο N—N Y\ Z CH3 < -J CH CH3
2	yellow solid	/CH’o rN\ V’ M U

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3	yellow gum	CH, / o N-N \\ _ CHj \ CH 3 N-^ ch3
4	yellow oil	CH, jX \\ /CH, y-xY X Kx f CH 3
5	yellow oil	zCH’o V r-^Λ X X7^ iï Vx^-n \X ch3

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6	yellow gum	CH, CH 3
7	yellow gum	CH, / 0 c }/_N\ 1 Z--- C!l3 ryAA(K CH3
8	yellow gum	CH, r< ch.
9	beige gum	CH, / O -U N—N \\ ,ch3 λ ί 7Y\ Cl CHî

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10	colorless gum	ch3 / O nu ίτΎ^ι Br CH3
12	colorless glass	7C% __ /7 N\ L/CHj γυΑ>~/ύ L «.c·
18	Brown oil	H,C J \ Ω N—N ÏL/^· /CHj
19	Yellow oil	h3c \_N CHj K fi

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20	Yellow oïl	H,C 3 \ O /“K \\ CH, x CH CH3 N-^ ch3
21	Yellow oil	h3c \-N CH3 Cpr3
22	clear oil		C	/CH3\\ /CH3 rVH l/'’! ch3 /—CH, h3c
23	clear oil			/CH3<\\ /CH3 r \ W A/~-Ns CH, h3c

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24		Ο A ch? Y h3c
25		A. q H \ ,N~N H3C'
26		CH, «A ) N-, HjCr^Y \_ /P [ |] inc VA I l3C
27		AA H3C \_r!| H 3 C

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32	Gold syrup	CHj C”3
33	Brown solid		M	O N^\ /—CH3
34	Off white solid		0	C) ch3 JA» ch’
35	Off white solid			o ch3 Nî=\ r-\-CH> CHj

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44	White solid	H3C—S |f CH3 M
45	Brown thick mass		0	0. ch, ch’ ch3
46	Pale yellow thick mass		0	h3c N^A. 2--CH3 I \—N ch3 O ch3
47	Pale yellow thick mass		M	h3c N^\ /--CIÎ3 /X / HjC—s

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52	tan solid	O	O __ ch3
53	White Solid	O	CH, Hh,c ch3
54	Clear Oil	CH, °w~s/ CH3
55	White Semi Solid	ç	λ-< ,N^/~Nx CH3 h3cZ

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56	Brown Solid	HiC q V zc 3 r\ Q “ NT
57	White Solid	H3Ç CH3 °V XcH, Γζν./ 0 M
58	Clear Oil	CH, o ÇHj ^CHj ch,
59	White Solid	CHj o /CH3 CHj

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60	White Solid	rt K CH3 Q
61	Light Yellow Solid
62	Clear Oil	H Λ s-CH, H A / q
63	Light Yellow Solid	h3c ry KA

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64	White Solid	O	H3c CH,
65	White Solid			° _jvF h ch3 f
66	White Semi Solid	S—CH 3 σ
67	Yellow Semi Solid			h3c ch3 3~'CH3 CH 3

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80	White Solid	ch3 s ,CI 0 \ N / V/~CH3 H CH3
81	White Solid	F F cî:î>-a
82	White Solid	F F )Cq /CH’ Φ X_/~s σα
83	White Solid	F F CH,

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84	White Solid	c
85	Off-White Solid	ch3 O z CH3
86	Yellow Solid		A	CH n ΗΛΡΗ3 rC KXc· h3c
87	Yellow Solid		M	/ch’ <?,H V3 A XcA3 ch3

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96	Yellow Solid	A H’c
97	Yellow Oil	VHjo\ CH’ A HaC
98	Yellow Oil	ÇH3 o /CH3 H,C
99	Yellow Solid	O Wn /”3 rC

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100

Clear Oil

101 Clear Oil

102

Clear Oil

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104	Faint Yellow Oil	ch3 CH3 n ,__/ JKr° J, /)—N CH3 JJ H3C N
105	Off-White Solid	ch3 o ch3 TT
106	Faint Yellow Oil	O Wo /CHJ N\ U N
107	White Solid	C H 3 o rK- T/CHî CHj

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108	Clear Oil		ch3 s ycl CH3
109	Yellow Solid		0	H A,.. Cl </ ^CH, h3c
110	Brown Oil			HaC CH3 X~ch3 Λ-θ \ CH3 Br
111	Yellow Solid	H 1 C p II CH3 0 3 \zCH3 J W /-CH. /—t/ 'iy>s

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112	Brown Oil	H i C c m PHj ο V 3 F V ΎΥν NT \ CHj
113	Yellow Oil	Λ CHj 0 / i F5 bT
114	Brown Oil	HjC CH, Z Z CHj
115	Light Brown Solid	HjC CH, /c“3 VL F >-</ j vyA

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116	Yellow Solid	/CH- H V,J
117	Yellow Oil	Q /CH> F=\ y~(^S Q Xch’CH!
118	Brown Oil	?\ C H 3 rv CH, i η \ ch, < Br >r
119	Brown Oil	ch3 o /chî n=Z /-y~~s u > ch3

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120	Brown Oil	CH3 q /h3 γγγ uCHj Χ?Γ ζ ch3
121	Off-White Solid	ch3 o ch3 CH3 O CHI N
122	Faint Yellow Solid	CH3 Ω Y YCH3 \ CH, O c· N
123	Clear Oil	ch3 o zch3 ίΥΛ-χ'5

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124	Yellow Solid	ch3 o CH, ’Ύΐγ'Ο'Λ CH, H,C
125	White Solid	CH3 o CH, H’C
126	Yellow Oil	CH3o zCH3 CH3
127	Yellow Oil	CH3O CH3 r< K7'1 cr “ N CH;

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128	Néon Yellow Oil	.CH, o /CH3 σν» N
129	Néon Yellow Oil	CH, o CH, t CH, U : c' N
130	Pink Solid	jO X YL CH, 0 y=J n-=À y—n j \_V H oX1 N
131	Red Oil	CH, 0 CH, ΓΥΥ u CHî M Br

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132	Yellow Oil	CH3 o /CHî σν··
133	Yellow Oil	CH, H’C
134	Clear Oil	X K-'“'
135	Off-White Solid	113C X CHj n er / K h3 c ch3

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136	Yellow Oil	CH,0 vCH’
137	Yellow Oil	H3C CH ÇH, 0 \ s/ ’ CHJ M
138	Yellow Oil	F F cih 0 J F A TT N
139	Faînt Yellow Oil	CHj o CH3 A LAS A br

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140	Faint Yellow	CHjo CH, ry/V·
141	Light Yellow Solid		h3c ch3 CH,0 )ACh3 nA_ / ° r \
142	Clear Oil	ci o /CHî H,C
143	Colorless Oil	O s/	CH, / 3 CH3 0 >—s ï /—N Yh2

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144	Colorless Oil	CH, / 3 CH3 O y--S ch3 Cf N
145	White Solid	C	CHÛ j--CH, h
146	Gray Oil	0	H 3 C r il />0 5\/H3 \ ch3 Br
147	Colorless Oil	σ

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148	White Solid	çh3ov ch, JH CH3 [ΦΓ ych
149	Yellow Solid	h3c ch3 y J ^ch2 bT
150	White Solid	H3C CH3 Xx·'
151	Clear Oil	CH H3C\ CH3 ,CH3O \ / ch= Q c’ bT

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152	Clear Oil	CH H3C, CH3 ,LH3O \__/ K( —N Cf hr
153	White Solid	CHjo __/ J. —N F a N
154	Faint Orange Oil	,ch3 <λ - A CH3 Q
155	Clear Oil	/CHj0 S /CHJ ch, i J H,/ N

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156	Clear Oil	P'A-Z’ CH3 H’c
157	Clear Oil	CH HîC\ >CH3 yCH3O \__/ k( ---N rr^) < h3c FF
158	Clear Oil	ch30 __/ / --N F rr^> h3c
159	Clear Oil	ρΗ1ρ,- Φ I A—jj \ F CHI ΙΙφ H,C

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160	White Solid	N
161	Brown Oil	ci HjC\/CH’ y^··· ΧΓ/)
162	Light Brown Solid	X kX-
163	White Solid	X K’ FyyM N\ ch, hX N

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164	White Solid	ci HjC\ CH3 ZCI <λ W
165	White Solid	r1 ij CH, C H , n / J H P7 Q cHj bF
166	Yellow Oil	ru CH, C H i n / J OA> bT
167	Grey Oil	ri CH, TA 'rA < HjC

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168	Faint Purple Oil	P <λ r M /)--N F < X h3c NT
169	White Solid		CHO /--CH3 yyf L H3C
170	White Solid	O	ch3 CH, / NJ\ Xj 1 />-* h3c
171	White Solid			ch3 çh3 o --/

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172	White Solid
173	White Solid	î-C >Ύ“· N\ ch3 Il Ί CHî
174	Clear Oil	Ci 0 ZCH, A__
175	White Solid	d o /η3 ch, ÏJ N

176	Yellow Oil	CHi Cl n / * ^bT
177	White Solid	CI Ά CH3 n/ci νΛ'5' - xi zZ—N bT
178	Yellow Oil	Γ1 / / Q ^_Z,F r xi zz—N F bT
179	White Solid	P 0.- /r ΓΎΎ*θ~*εΗ>CH1F ^br

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180	Yellow Solid	Cl F / °5 /—Z-F N\ CH> Γ ILJ H,C
181	Faint Yellow Oil	c, o A /H’ FYV~ CHi
182	Faint Yellow Oil	ci HîC\ CHJ / v/-y CHj H’C
183	Yellow Oil	h3c Ρ'Υ^ζΝν/ CH3 H3C^ N

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184	Colorless Oil	Cl-Ij ÇH3 o >—s I z)—N Όι X rr
185	White Solid	CH, Γ o s CHl U S ^H, N
186	White Solid	CIIO CH, CH3 I % CH>
187	Yellow Solid	CH,0 __/p ch, y H,C

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188	Yellow Oil		o N	CH 3 0 n==\ y— j \ /	F /--\ F F
	Ύ h3c
					CHjo Ç	Ή3 Y Z—s
				NI xN'
		F.			CHj
189	Yellow Oil		if>
					H3C
					CH3 o	/CH 3
					Y
		s		I	Y	M
190	Yellow Oil	I	u ht		/ II3C
					CH3° H'	C\ CH3 Y/
				N- I
191	Yellow Oil		Π	Υλ CH,

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192	Yellow Oil	H J C p m ,ch30 \ /3 h>c
193	Yellow Solid	CH, o __/ -Q e.„ N
194	White Solid	.CHjo __/ N
195	White Soiid	/CIIF\ /S^CH> Z

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200	Yellow Oil	O	H3C CH3 J’yA' JX CHj
201	Gold Oil	r-y Xz' XX
202	White Semi Solid	0	X H CH3 h3c
203	Yellow Oil	ΓΙ H3C\ CHj zci y~s' bX

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204	Yellow Oil	H ί C p ti ci ο V / 3 ch, M
205	Yellow Oil	AND Enantiomcr CH, rp>·....... rrN>> < HjC N
206	Yellow Oil	Cl O __Z F rr^)
207	White Solid	Cl o ___/ CH, Γ M h>c

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208	White Solid	A K' CI,3 fl ch3
209	Yellow Oil	0 s/CHa ^.N^~N X CH, Q c“· N
210	Yellow Oil	C' o U /-/~s Q c, N
211	Yellow Oil	ri HjC\ CH3 J X )~s N

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212	Yellow Oil	a	Cl	0 ......... N \ ch3	CH, r
			Cl	0	F /—X F
213	Yellow Oil	a	N==\	N \ ch3	F
			Cl	o	F /--\ F
214	Yellow Oil	Π'		N \ ch3	\ F ch3
		M
215	Clear Oil		CH N^=\	CH 3 ’y<’ —N CH3
		L	J	7

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216	Cream Colored Solid	ch3 CH p y--S cH> AA r1· T J H3C br
217	Clear Oil	/H 3 CH0. t--S xA ' ' ch3
218	ClearOil	X'' „ x /)--N CH, W ) L J «JC ^bT
219	Clear Oil	ch3 AA

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220	Yellow Oil	ΥΧΊ ’-Χ
221	White Solid	c	CH, c«3 Yh h3c
222	White Solid	0	CH, Y CH£) y---' γΑ Xs
223	White Solid	n CHj /.Χ \0/NX H

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224	Colorless Oil	F F CH3O V zCHî Q CH, bT
225	Light Yellow Oil	CH3n CH, M h’c F br
226	White Solid		CHj O I CH3
227	White Solid		/TA' Pf CH,

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228	Colorless Oil	F F /Chj° °--4ρ o v
229	Colorless Oil	F ,C[,3O A v
230	Colorless Oil	CH3 n c \ CH3 il Ί CH3
231	Colorless Oil	CH, Q c”· br

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232	White Soiid	c„ fX K / 3 °\ A/ O J. ---N σ—
233	White Solid	xA YY ''ch, ch>
234	White Solid	cllîO o M —N c h 3 Q
235	Colorless Oil	CHj

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236

Colorless Oil

237

White Solid

239

Colorless Oil

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240	White Solid		h3cZ	-o-
			F F-A
			o. )
241	Colorless Oil	fiY	r<	rF F
		M	h3c
				F
			CH3Ox	/\ F
242	Colorless Oil	σ	'—ch3	y: F
				F
				aÂ~~f
243	Colorless Oil	a	A·./ x—ch3	R F

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244	White Solid	fix \ CHi [i T / h3c
245	White Solid	ch, H’c
246	Colorless Oil	i'7 < HjC
247	White Solid	xCHj h,c

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248	Colorless Oil	H*c
249	White Solid	PH3 0 F 1 --N rr > <N·^ h=c
250	Clear Oil	cnJO \yCH3 c> H,C
251	Brown Oil	A' Xï

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252	Off White Solid	Br 0 U N
253	Off White Solid	CH, / 3 Br 0 j S —N CH, X
254	Brown Solid	H i C CH, ,Br Q V 3 rC 17 “
255	White Solid	CH, Ci c, W ργΧ-Η

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256	White Solid	Cl 0 y--CH3 χ—n I \ / H Jr />—N
257	White Solid	ch3 Cl C) y----'
258	Brown Oi)	A A-- CH,
259	White Solid	ζ F PHJ0 \ ch3 A >_A-S ΥΓ ) <, A H,C bT 3

Page 174 of 619

260	Colorless Oil	CHjO CH3 HjC
261	White Solid	Îl H3C bT
262	White Solid	A? bT
263	Colorless Oil	F /CH30 p r Μ /Z-N A--F A ' - NT

Page ï 75 of 619

264	Colorless Oil	F ch3° ύΧ> 7< M >c F
265	White Solid	X' CH3 ÎL, Λ HjC V
266	Colorless Semi-Solid	χΧ CHa V x
267	Colorless Oil	·;Ζ X

Page 176 of 619

268	White Solid	F pn3O r —N V-N, YY > CHl HsC
269	White Solid	CHjq xj- „>
270	White Solid	CH3r)
271	Colorless OU	CH, YY XNJ H,C f/R

Page I77 of 619

272	White Solid	<^30 χΛλΤ·
273	Colorless Oil	'Xp/Y? ch, H’c
274	Colorless Oil	T Ι·γ^γΝ'~Υ'ί\ cll> H,c
275	White Solid	CH H3S O ° c ! -J HjC

Page 17S of 6I9

276	White Solid	CH, n P H,C φ F
277	Brown Amorphous Solid	CH, / 3 Br 0 > S n; CH3
278	White Solid		CHÛ /--CH, r< h ιΤΎ'^0·
279	White Solid		CH3 CH O / /

Page I79of6l9

280	White Solid	0	CH, // Clip y--J CHj
281	Orange Foam	CHj h_J/'cHj / O Z N
282	Colorless Oil		ch3 Cl c> ,—s ......ό U JT Xch2 N
283	Colorless Oil		0	CHj / 3 Cl <3 y---S FF CH2

Page 180 of 619

284	Colorless Oil	Cl 0, CH, r< M CH’ 1¾. JJ Xch2 N
285	Clear Oil	CH3 zCHj J, ---N σ bT
286	Yellow Oil	\ F ph30 Λ-’-' H,C
287	Yellow Oil	CH3 /H,

Page I8l of619

288	Yellow Oil	O	CH 3 NzA. / )>—N	CH, \—θ '—-c II3
			CH j o'	CH3 _/—7
289	Dark Yellow Oil	O	\ CH3
			CHj nA	CH j
290	Yellow Oil		hCHi
		M		V-s \ ch3
				h3c
			Cl	CH3C—)--C H 3
			Ντ=\ ,ν-Ζα	\\ / 7—0
291	Clear Oil		A	N )—ch3
			A	H 3	c

Page 182 of 619

292	Tan Solid	CUj Γ Jk JL ^o. kii, s [I J CH, ch3
293	Clear Oil	ch3 /N==\^ JL /X ZH1 H I ch3 ch3
294	Yellow Oil	CH, __/ O F H I CHj CH,
295	White Semi- Solid	Cll3 i °ΎΧ° H I ci-h ch3 '—1 bT

Page 183 of6I9

296	Colorless Oil
297	White Solid	Br Ov >—CH, x ΥΓ
298	White Solid	CH, Br 0. /----'
299	White Solid	CH 2 Br Ci /---

Page 184 ο!'6Ι9

Page 185 of 619

Page 186 of 619

308	Colorless Oil		Cl X ch3
Y N	H3C
			P 0		Y
				f\^F
309	Colorless Oil	ΙΙΊ	)		XOH
		Μ	h3c
					F y
			J' X
310	Light Yellow Semi-Solid	Γτ		ch3
			h3c
					F
			,C! 0		F \ - Υ/ΓF
			J. —N		\ F
311	Colorless Oil			F F X F
		Μ	H3C

Page 187 of 619

312	White Solid	iTV ) CHj Y h>c
313	Light Yellow Solid	Y Ht? ρΧΎ VJ CH, ί. h3c
314	Faint Yellow Oil	Cfl3 o CHj nY σΥ N
315	Faint Yellow Oil	CHj o /CHj Q-f>Y N

316	Faint Yellow Solid		X Kl »»> kJ i> N
317	White Solid		R CH3 C kZc,,‘ M
318	Brown Solid	CHj Cl 0 ,----'
319	Brown Solid	CH, Cl Ov >----z

Page 189 of 6I9

Page 190 of 619

324	White Solid	H,C J —N rr > bT
325	White Solid	H,C ™3α \ r xi N YY'-'O < HjC N
326	Colorless Oil	H,C /cl o V J —N rr >
327	White Solid	ch3 o h,C\ R J- /Τ'N\ ΎΎ >xvF HjC N

Page I9l of 619

328	White Foam	ch3 Cl o >—s' br
329	White Foam	CH, „ / Cl 0 /—y nA / \ 0 AA CH> CT “ br
330	White Foam	ch3 Cl o y-- ;:A N
331	White Foam	/CH 3 Cl o y--S^o ΝίΛ / \ o CH1 J HJC N

Page 192 of 619

332	Clear Yellow Oil			h3c ch. Cl 0 'V—CH3
333	Clear Oil	C	A f’' h3c
334	Light Brown Solid	Cl Ot i—ch3 Kh U
335	White Solid		y	fiR“‘ \ ch3 ch3

336	White Solid	ci o ^/CHî l \ / ° CH 3 θ' C ίγ
337	Pale Yellow Oil	Cl n X ps~c· X N
338	Clear Oil	Cl n X p/~CH3 IL h3c N
339	Clear Oil	F F Cl o λ/ vX 2^o /\f rrN>> < h3c N

Page 194 of 619

340	White Solid	H 2 Çk t i r ,, 3\/CH> a>Zchi
341	Yellow Oil	ch30 Y J -N A κ bT
342	Yellow Oil	ch C H □ /CH3O / 3 A>^ a v br
343	Yellow Oil	.CHjo __/ J. —N F AK br

Pagel95of6i9

344	Yellow Oil	/CH30 X X .. br
345	Yellow Solid		Cl O. ch3 X^X I CH3 M
346	White Solid		X χχpX-x^ \ X h3C N
347	Pale Yellow Oil	P 0 < X fl3C N

Page I96of6l9

348	Brown Solid	Cl Cl ov >----/ T W
349	Beige Solid	O	CH3 O,
350	Colorless Oil	CH, / 3 Br 0 >---S 'TT
351	White Solid		TH- J

Page 197 of 619

352	Yellow Solid	4 K/· Yr
353	Yellow Oil	’S 0 /« O N
354	Yellow Oil	H2C ) 0 CH)
355	Yellow Solid	h2c. N-Λ °V_/CH3 N\ CH3 I Ί CH3

Page î 98 of 619

356	Yellow Oil	H y H C* yy -
357	Yellow Oil	H2% /h, - ^br
358	Off-White Solid
359	Off White Solid	Br 0 φΧλ CH3

Page 199 of 619

360	White Solid	HjC CHj σ ? ch3
361	Tan Solid	h3c. CH3 OQ
362	Clear Oil	ri CH3 Cl o / 3 σΑ
363	Clear Oil	n CH3 P O \\/ 3 h>c

Page 200 of 619

364	Yellow Oil	σΥ ci
365	Yellow Oil	A οΆ CH,
366	Yellow Oil	ri CH3 °K~ Q-^V13 ch3
367	Clear Oil	ri CH, P1 o / J K-s p/A/’ ch3

Page20l of6!9

368	White Solid	ci r. /CHî O __/
369	Light Brown Oil	0 HjCvch3 ϊΎ ΧοΑ’ o cH- br
370	Colorless Gum	HjC /Hj Br 0 λ--S ΐ />— / xr -
371	Colorless Gum	CH 3 / 3 Br O a·.....S 4'P χΥ 'Cl

372	Yellow Oil	Cl s /CH3 F F~s rrN>> < F H3C N
373	White Solid	H 3 C pu zvz Ιχ xÿj HjC N
374	Beige Solid	A	Cl 0 N^=\ /NH AFF
375	White Solid	F	ÇH3 0 y--CHj

Page 203 of6!9

376	White Solid	CH, Ç», ?_/ .^>-0
377	White Solid	ch2 ÇH, 0 // X Ή I />—N IX
378	White Solid	,Χ0 f t! —N V- X XQ
379	White Solid	ci o N=_y VVY J, /%— N 'X- N /y '^7^) CH’ >bC

Page 204 of6l9

380	White Solid	H»C CH, rC W br
381	White Solid	Cl Η’5 /CHj A KXc“‘ H | Ad Y D
382	Clear Oil	\ F A rvN>> H>C
383	Pale Yellow Oil	Cl 0 rcz-T CH> U -Y sz \ ch3

Page 205 of 619

384	Coloriess Oil	P LJ C H J CT bT
385	White Solid	/—CH3 rA» TT CHj N
386	White Solid	zch3 CHj n ___/ TT
387	White Solid	ch2 ch3 n .___/J ]| Ap ch3 M

Page 206 of 619

388	White Solid	/CH3OV/-°r Il Ί CHs
389	Colorless Oil	R D T/r CH1 H3C
390	Off-White Solid	D C11JO Χλ<· CH> ’C
391	Colorless Oil	R D P <λ Ad rC AA \ CHÎ Q- br

Page 207 of6!9

392	Colorless Oil	R D /cl CH, (L J CH1
393	Colorless Oil	CH 3 /' ^z-s7 il / HjC
394	Colorless Oil	Cl h o S /Cfl3 i—jj' So rvy^) D H,C
395	Pink Solid	/' V/-Br Br Q >r

Page 208 of6!9

396	Colorless Oil	/> 0 | CHj
397	Colorless Oil	/CH3 0 Τ'4’ γΚ_ N
398	White Solid	ru CHj ,CH3 0 /
399	White Solid	,Br 0 rC H F V^N^/-N \CHj

400	Yellow Oil	CH3 zCH3 Q X ch3
401	Yellow Oil	ch3 zch3 αχ s \ ch3
402	Yellow Oil	.C» 3 /CHj σχ C1I3
403	Yellow Oil	ch3 zch3 αχ h3c

Page 2 ΙΟ of 619

404	Yellow Solid	Η2^ ΦΧ· H CH, V
405	Colorless Oil	P 0 /CHa
406	Colorless Oil	/' Vp/CHi O-y ch,
407	Pale Yellow Oil	F' o r( CX HaC-y0 sz \ ch3

Page2l I of6!9

408	Yellow Oil	HjC ) O H3C\/CH3 wA,
409	White Solid	χΑ S -CH, —X if CH3 M
410	Orange Oil	X'1 σχ sz \ CH3
411	Beige Solid	p o a-ch3 xA / h χ/χ IL J H,C N

Page2l2of6l9

412	White Solid	ch3 ÇH3 o / A yjy J H,c N
413	White Solid	ch2 çh3 O A A A br
414	Yellow Oil	H3C CH-> Br o \/ 3 J W Z^CH3 A /A ifA^ 'ch3
415	Off-White Solid	h3c ch3 a ypoa I ch3

Page 213 of 619

416	Yellow Oil	h3c
417	Yellow Oil	h3c ) °\ s/CH3 ’γγ'θΛκ,c,i!
418	Yellow Solid	h3c -Λ V—/CH3 ch, bT
419	Yellow Oil	Fl î Ç. H t C \ Mî\ ch3 ? V/^s/ c Λ --N br

Page2l4of6l9

420	Yellow Oil	h3c \ CHj TT
421	Light Yellow Oil	iI3C χΥ
422	Light Yellow Oil	II,C d-y0 cr > Y Y h3c NT
423	Light Yellow Oil	0 ch3 o

Page2I5of6l9

424	Tan Solid	CHj o Y-Zr Hjc
425	Colorless Oil	P o. \ F F ) <-/ M
426	Colorless Oil	.Cl θ ,?F_ αρτM
427	Yellow Oil	/«2 ci o H>c

Page 216 of 619

428	Yellow Oil	/CH 2 P o /—7 ΡΑΠ Ά >c
429	Yellow Oil	ycl <λ s^11· AK.
430	Light Yellow Oil	ci 0 ” x
431	White Solid	r °/VH1 yZ xZCH> /γΝ>-νεΗ3

Pagc2l7of6l9

432	Yellow Oil	Y °yys~CH> M / HjC
433	Yellow Oil	P o zCHj \ CH3 u <Pchi N
434	White Solid	Fx	p> h3c ch3 Y M
435	White Solid	R	HO i T CHî

Page 218 of 619

436	White Solid	-χΛ·· y
437	Yellow Oil	n CH, Cl Q / J C. u x CH,
438	Yellow Oil	/ xxCH1 χ^ΧCH, CT N
439	White Solid	CH3 o 1 Ί CH’

Page 219 of 619

Page 220 of 619

444	Brown Solid	/CHj 0. ch3 H br
445	Brown Solid	Cl / Q CHj H n'^V'n^'n\ (I \ CH,
446	Yellow Solid	/CHîQ CHj Qzn7'\h,CHi
447	Dark Oil	Cl / Q Clt, K Y ry^V-

Page221 of6!9

				CH N=r<	3 0 V.	CII3
448	Brown Solid		r	•N	ch3
					ch3
				Cl N=r\	K	CH,
449	Tan Solid		r	N	ch3
		< J			ch3
				y /	0 /
			Ni .iL,	y- v	Y	S-CH]
				k	ch3
450	White Oil	M		0 \	CH	3
				<y	\ ch3
				ci o		ZCH 3 -S
			N / ,N.	/
				CH	J
451	Yellow Oil	ΓΎ	-0
		M			^•'CHj

Page 222 of 619

452	Colorless Oil	/Br Q /CHs Q
453	White Solid	/Br ° ργΟ~\Η, CHj
454	White Solid	Br C> CH3 YM 3
455	Colorless Gum	F F Br O /—Y «X M -

Page 223 of6!9

456	Yellow Oil		P o Y/? I 1 chj A·/
457	White Oil	Cl 0 Q \ ch3 o
458	White Solid	AND Enantiomer zch3 Br Ο λ......S Y-K
459	Colorless Oil		I13C ch3 AA’ PY^\h3

Page224of6l9

Page 225 of 619

Page 226 of 619

468	Light Yellow Solid			Br Ox S—CH 3 VA \--CH3
469	White Solid			Br Ov S—CH, Ah
470	Light Yellow Oil		ri CH3 Cl n / J
471	Light Yellow Oil	O A	/ Va-/”’ I Z>--N VCH3 \ ό ch3

Page 227 of6!9

472	Light Yellow Oil	Cl o Z™3 N
473	Light Purple Solid	CHl IL H)/ br
474	Yellow Oil	Cl 0 σ S;·
475	Light Yellow Oil	Z o-X<CH> 1 CH, CH,

Page 228 of 619

476	White Solid		Br Ok S—CH, XX h 5 CH3 M
477	Off-white Solid		/CHî °\ n„n y_cH3 /X' I pr CH3 X
478	Clear Oil		CH, N^X X~S îYx
479	Beige Solid		Cl Sx >---CH, t h3c N

Page 229 of 619

480	White Solid		Ç	S /—CH3 H r<y h3c
481	Light Yellow Oil			Cl Cl 0 y---/ ,sR h3c
482	Beige Solid		Cl n CH3 Y H’c
483	Clear Viscous Oil		ci o V’ / A /-'CH3 y

Page 230 of 619

Page 231 of 619

488	Light Yellow Solid	HjC CH3 aT N o / h3c
489	Yellow Solid	hjÇ ch3 / °
490	Light Yellow Oil			ch3
491	Light Yellow Oil			m -T...... 1 U tV \__

Page 232 of6!9

492	White Solid	Cl o ^CH} θ—ch, CT bT
493	Light Orange Oil	F F X _ pvH1 An CM 3C N
494	Yellow Oil	<-! H3C\ CHj P Q V / Xo J. ---N fr > x h’c
495	Clear Oil	0 Hî\VH3 U yy- *0 I X—N A ) X Hjc

Page 233 of6l9

496	Light Yellow Oil	CC'X..... N Q / h3c
497	Light Yellow Oil	Cl c> ch3 Xk pJ-A A N o / H3C
498	Light Yellow Oil	Ç	Cl 0 CH, X M r ( 0 / h3c
499	Colorless Oil	0	h3c h3c

Page 234 of 619

500	Beige Solid	/--CHj Ci o ,—f σ_χ> N
501	White Solid	CH3 Cl O. y----' σχ br
502	Thtck Yellow Oil	CH 3 O /---' σΧ> N
503	Beige Solid	h3c ch3 Cl o W 5 L h’c N

Page 235 of 619

504	Beige Solid	h3c ch3 y-A A NT
505	Colorless Gum	Br O ^bA
506	Clear Colorless Oil		CH3 P o / r( A'5 A\ <J
507	Clear Colorless Oil	O A	/' yAH’

Page 236 of 619

508	Clear Colorless Oil	Cl	0 -N ?	H>C> CHj
û br	Νΐ=\
				CHJO' Ν-Λ )
509	Pale Yellow Gum		M	zt/	—N \__ ch3 CH3
				Cl	0	zch3 /—s
510	Yellow Oil	[	a N	'V	ch3 -0 A°\ ° /—CH, h3c
				Cl	O	/h3 /s
511	White Oil		ΓΎ		-N V	ch3
						\ °~A o—ch3

Page 237 of6!9

512	Pale Yellow Oil			Cl o Y H3C
513	Thick Clear Oil	^ch3 o /--- aY N
514	White Solid			P °/VH’ X h3c
515	White Oil	Cl o N o > H,C

Page 238 of 619

516	Dark Brown Oil	P ο ,--/ Q br
517	White Solid	ri / Cl 0 /
518	White Solid	s—ch3 O y--/ / h σ-0:) br
519	White Solid	S—CHj Cl O >----f Vf-rr^> Λ Hjc br

Page 239 of 619

Page 240 OÎ6I9

524	Light Brown Solid	/Cl (| I H’C HjC
525	Faint Yellow Solid	/ ZCH3 O CHi bF
526	Faint Yellow Solid	/ °x /CH3 CH, N
527	Yellow Oil	Uk if CHj

528	Light Brown Oil	ï> ch3 n Λ vXs/ C J —N Y N
529	Faint Yellow Solid	ch3 ‘rr
530	Clear Oil	Cl 0 /F /) N F \ ch3
531	Yellow Oil	F F ci 0 \ Cll3

Page 242 of6l9

532	White Solid	,.M·: ' 0 r 0 h3cz
533	Orange Oil	Cl o 0 / H3c
534	Red Oil	Cl o U ;ms-ch> XX
535	White Oil	Cl O Q ? N OH

Page 243 of 619

Page 244 of 619

540	Clear Oil	Cl Q F F rY YY YY I / Y h’c
541	Light Yellow Oil	,jy cY br o / HjC
542	Colorless Oil	P 0 ___/CH’ t J bT
543	White Solid	/' Ά Y σ>ν“·

Page 245 of 619

544	White Solid		FF F
545	White Fluffy Solid		P 0 F F /Zp/N-z'ii F
546	Brown Solid	F°Fi. /Z/F \ Br Q bZ
547	Yellow Oil	ci 0 z^NZ \ I Q ? F '0 F 0

Page 246 of 619

Page 247 of6!9

Page 248 of 619

556	Pale Yellow Gum	H,C Y CH3 xch3
557	Pale Yellow Gum	h,c ch 3 n-n /Ch3 11 N CH, i TA < A 0 ch3 N
558	Faint Yellow Oil	,CI o __ J. /)—N rr > < A h3c N
559	Faint Yellow Oil	A ,Cl 0 r~~-/ nA /—/ (VA V

Page 249 of 619

Page 250 of 619

564	Pale Yellow Gum	x-	CH3O r V X X~V \ CH3 C1I3
565	Pale Yellow Gum		ch3 CH3o .__/ y >X
566	Pale Yellow Gum	ch3 m X7 XN\ x Ji //X CH3 XX
567	Off-white Solid	ch, „ ! 3 o N-H CH3 F. XXX^ \ ch3 ch3 x·^

Page25l of6!9

568	Pale Yellow Gum	ch,o U >-Λ
IL X N	γ ch.	---S \ CH,
			p o	\zCHî
569	Colorless Oil	ΓΥ		F
		U	H,C
570	White Semi- Solid			Z' o
		y	/ H,C
571	White Semi- Solid	σ N	C' o H,C	CH, Λ -F

Page 252 of6!9

572	Colorless Oil	F Cl ο J. Xz)--N F F a
573	Colorless Oil	F u
574	Colorless Oil	.y %Y' σΎ ^bT CH3
575	Colorless Oil	σ>νν bT

Page 253 of 619

576	Colorless Oil	O br	N I	Cl -A	h3c- o —N \ ch3	C H 3 V /CH3
					h3c.	CH3
				Cl	0	\ CH3 L / 3 X—C
			N			O
577	Colorless Oil	Pï	I P'	-A	—N ^~ch3
				Br	R /	ch3
			Ni			\___ς
578	Colorless Oil	a bT	A	A	Λ ch3	Ah> h3c
				Cl /		,ch3
579	Colorless Oil	o N	Ni „N-		-N C	h3c

Page 254 of 619

580	Colorless Oil	JT. H I CH, H,c
581	Colorless Solid	P 0 X &H, στ
582	Clear Oil	CI N. / O / <ïï HjC h3c >T
583	Brown Oil	/Cl C\ /—-Λ''''« Nc=X J--/ >===(. O < H3C N

Page 255 of6!9

584	Dark Yellow Oil	/ci °\ ' (YA h3c
585	White Solid	P 0 Î| T / H3C < A H3c N
586	Yellow Solid	H3C A
587	Purple Solid	P o AP Q- ...

Page 256 of 619

Page 257 of 619

592	Brown Oil	Q X“· r-r
593	Brown Oil	Cl Y*' O ___7 l 7^—N σ br
594	Faint Yellow Solid	/Cl °\ H n A. —/ AA, Q », W br
595	White solid	N^\ AA I T A~°X/ CH3 kyj ° )Ach3 h3c

Page 258 οί'6Ι9

Table 2: Compound number and analytîcal data

Compound No.	MP (°C)	IR (cm-1)	MASS	1HNMR	NMR
1		1668.7	305	δ 9.00 (s, 1H), 8.58 (br, 1H), 8.08 (br d, J = 7.0 Hz, 1H), 7.35 (br dd, J = 7.3, 4.8 Hz, 1H), 6.58 (br s, 0.5 H), 6.49 (br s, 0.5 H), 3.89-3.79 (m, 3H), 3.25 (s, 3H), 2.96- 2.80 (m, 1H), 2.42- 2.40 (m, 1H), 2.02-1.99 (m, 3H), 2.62 (m, 1H), 1.15 (d, 7 = 6.0 Hz. 3H).
2	117— 120	1670.5	258.9	δ 9.01 (s, 1H), 8.51 (d, 7=3.8 Hz, 1H), 8.15 (br d, J = 8.0 Hz, 1H). 7.45 (dd, 7=7.9, 4.8 Hz, 1H), 6.98 (s, 1H). 3.73 (s, 3H), 3.12 (s, 3H), 2.36 (septet, 7 = 6.5 Hz, 1H), 0.98 (d, 7 = 6.3 Hz, 6H).

Page 259 of6!9

3		1654.9	319.6	6 9.02 (s, 1H), 8.51 (d, J =3.8 Hz, 1H), 8.16 (ddd, J1 = 7.8 Hz, J2 = J3 unresolved, 1H), 7.44 (dd, J = 7.8, 4.8 Hz, 1H), 6.99 (s, 1H), 3.75 (s, 3H), 3.10 (s, 3H); 2.07(s, 2H), 1.03 (s, 6H).
4		1676.9	292.2	6 9.00 (s, 1H), 8.52 (dd, J = 4.5, 1.0 Hz, 1H), 8.14 (ddd, J1 = 8.0 Hz, J2 = J3 unresolved, 1H), 7.45 (dd. J = 8.1, 5.1 Hz, 1H), 6.93 (s. 1H), 3.76 (m, 3H), 3.14 (s, 3H), 2.65 (t, J =7.1 Hz, 2H), 2.36 (br, 2H), 1.95 (s, 3H).

Page 260 of 619

5		1691.6	299.5	δ 8.99 (s, 1H), 8.53 (dd, J = 4.8, 1.2 Hz, 1H), 8.13 (ddd, J = 6,1, 1.8 Hz, J3 = unresolved, 1H), 7.46 (dd, J = 7.9, 4.8 Hz, 1H), 6.96 (s, 1H). 3.77 (s, 3H). 3.42 (q, J = 10.6 Hz, 2H ), 3.16 (s, 3H).
6		1735.6, 1678.1	303	δ 8.99 (s, 1H), 8.56 (d, J =3.2 Hz, 1H), 8.08 (ddd, J = 7.8, 1.8, 1.8 Hz, 1H), 7.34 (dd, J = 7.8, 4.8 Hz, 1H), 6.52 (s, 1H), 3.85 (s, 3H), 3.68 (s. 3H), 3.24 (s, 3H), 2.67 (br, 2H), 2.37 (br, 2H).

Page 261 of 619

7		1665.3	307.6	δ 8.99 (d, J= 1.5 Hz, 1H), 8.57 (dd, J = 4.8, 1.5 Hz, 1H), 8.08 (ddd, J = 8.1, 2.1,2.1 Hz, 1H), 7.34 (dd, J = 7.9, 4.8 Hz, 1H), 6.52 (s, 1H), 4.88 (br t, J =5.5 Hz, 1H), 3.80 (s. 3H), 3.41 (q, J = 6.3 Hz, 2H), 3.24 (s, 3H), 2.61 (t, J = 6.3 Hz, 2H), 2.06 (s, 3H).
8		1722.4	308.7	δ 8.97 (br, 1H), 8.55 (br, 1H), 8.06 (ddd, J= 8.1, 1.8, 1.8 Hz, 1H), 7.33 (brdd, J =7.9, 4.8 Hz, 1H), 6.43 (s, 1H), 4.31 (br, 2H), 3.14 (s, 3H), 3.78 (s, 3H), 3.28 (s, 3H), 2.70 (br, 2H), 2.13 (br, 3H).

Page 262 of6l9

9		1691.6	327.3	δ 9.18 (s, 1H), 8.64 (brd, J = 2.8 Hz, 1H), 8.21 (ddd, J = 7.9,1.8, 1.8 Hz, 1H), 7.38 (dd, J = 7.8,4.8 Hz, 1H), 3.83 (s, 3H), 2.90-2.83 (m, 1H), 2.79-2.73 (m, 1H), 2.53-2.45 (m, 1H). 2.33-2.25 (m, 1H), 2.06 (s, 3H).
10		1685.9	371	δ 9.19 (s, 1H), 8.64 (br, 1H), 8.21 (d, J = 7.9 Hz, 1H), 7.39 (dd, J = 7.1,4.5 Hz, 1H), 3.83 (s. 3H), 2.90- 2.83 (m, 1H), 2.79-2.72 (m, 1H), 2.53-2.45 (m, 1H), 2.33-2.25 (m, 1H), 2.06 (s, 3H).

Page 263 of 6I9

12		1686.7	340.3	δ 9.19 (s, 1H), 8.64 (br d, J = 2.8 Hz, 1H), 8.49 (d, J = 6.7 Hz, 1H), 8.21 (ddd, J =7.9, 1.8, 1.8 Hz, 1H), 3.83 (s, 3H), 3.25 (s, 3H), 2.35 (septet, J = 6.7 Hz, 1H), 1.15 (d, J = 6.7 Hz, 1H), 1.11 (d, J = 6.6 Hz, 6H).
18		1655	305.3	1H NMR (400 MHz, DMSO) δ 8.79 (s, 1H), 8.67 (dd, J = 4.8, 1.3 Hz, 1H), 8.03 (brd, J =7.8 Hz, 1H), 7.56 (dd, J = 7.8, 5.0 Hz, 1H), 6.60 (s, 1H), 3.87 (s. 3H), 3.15 (s, 3H), 2.94-2.89 (m, 1H), 2.75-2.70 (m, 1H), 2.38-2.33 (m, 1H), 1980 (s, 3H), 1.06 (d, J = 6.5 Hz, 3H).

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19		1662	291.5	8.73 (s, 1H), 8.70 (d, J = 4.0 Hz, 1H), 7.77 (d. 7 = 8.1 Hz, 1 H), 7.44 (dd, 7 = 6.6, 5.1 Hz, 1H), 6.21 (s, 1H), 3.87 (s, 3H), 3.29 (s, 3H), 2.82 (t, 7 = 7. Hz, 2H), 2.64 (t, 7= 7.6 Hz, 2H), 2.08 (s, 3H).
20		1660,7	260.3	1H NMR (400 MHz, DMSO) δ 8.79 (br, 1H), 8.66 (dd, 7 = 4.8, 1.5 Hz, 1 H), 8.04 (brd, 7=7.6 Hz, 1H), 7.55 (dd, 7=7.3, 4.8 Hz, 1H), 6.59 (br, 1H), 3.66 (s, 3H), 3.13 (br, 3H), 2.77 (br, 1H), 1.00 (d, J = 5.5 Hz, 6H).

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21		1641.4	319.3	1H NMR (400 MHz, DMSO) δ 8.79 (d, 7 = 2.1 Hz, 1H), 8.66 (dd, 7 = 4.8, 1.2 Hz, 1H), 8.03 (ddd, 7 = 1.8, 72 and 73 unresolved, 1H), 7.56 (dd, 7 = 8.1, 5.1 Hz, 1H), 6.59 (s, 1H), 3.87 (s, 3H), 3.10 (s, 3H), 2.67 (s, 2H), 2.03 (s, 3H), 1.10 (s, 6H).
22				1H NMR (300 MHz, CDCI3) δ 8.64 (bs, 1H), 8.49 (bs, 1H), 8.07 (d, 1H), 7.42- 7.2 (m, 1H), 6.0 (s, 1H), 5.37-5.09 (m, 1H), 3.7 (s, 3H), 3.10-2.89 (m. 1H), 1.32 (d. 6H), 1.11 (d, 6H).

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23			273.3 (M+1)	’H NMR (300 MHz, CDCI3) ô 9.00 (bs, 1H), 8.57 (s, 1H), 8.09 (dd, J = 7.9 Hz, 1 H), 7.34 (dd, 1H), 6.48 (s, 1H), 4.00 (m, 1H), 3.76 (s, 3H), 3.36 (m, 1H), 2.33 (m, 1H), 1.17 (t, 7 = 7.1 Hz, 3H), 1.08 (t, 7 = 6.7 Hz, 6H).
24		1675	341.3 (M+1)	δ 8.95 (d, 7= 1.6 Hz, 1H), 8.57 (dd, 7 = 4,8, 1.6 Hz, 1H), 8.01 (dt, 7 = 7.9, 1.9 Hz. 1H), 7.34 (ddd, 7=7.9, 4.9, 0.8 Hz, 1H), 6.43 (s. 1H), 5.90 (s, 1H), 3.83 (s, 3H), 3.31 (s, 3H), 2.53-2.17 (m, 2H), 1.09 (d, 7 = 131.0 Hz, 6H).

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25		1669	381.3 (M+1)	δ 8.96 (s, 0.4H), 8.78 (s, 0.6H), 8.55 (d, J =3.3 Hz, 1H), 8.04 (d, J = 7.9 Hz. 0.4H), 7.96 (d, J = 7.9 Hz, 0.6H), 7.41 - 7.29 (m, 4H), 7.13 -7.09 (m, 1H), 7.09 (s, 0.6H), 6.59 (s, 0.4H), 4.86 (s, 1H), 3.84 (s, 2H), 3.17 (s, 2H), 3.13 (s, 1H), 3.09-2.91 (m, 2H), 2.83 (m, 2H), 2.69 (dd, J= 12.9, 4.8 Hz, 0.5H), 2.54 (dd, J= 12.9, 4.1 Hz, 0.5H), 1.99 (s, 1H), 1.96 (s, 2H).
26		1673	354.4 (M+1)	6 8.97 (s, 1H), 8.58 (d, J = 3.4 Hz, 1H), 8.07 (m, 1H), 7.35 (dd, J = 7.8, 4.9 Hz, 1H), 6.50 (s, 1H), 4.54 -4.22 (m, 1H), 3.75 (m, 2H), 3.69 (s, 2H), 3.46 (s, 1H), 3.13 (s, 2H), 2.92 (s, 1H), 2.47 (s, 3H), 2.30 (s, 3H), 1.20 (d, J = 6.8 Hz, 3H).

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27		1650	300.2 (M+1)	6 8.92 (s, 1H), 8.58 - 8.47 (m, 2H), 8.10-7.96 (m, 2H). 7.30 (dd. 7=7.9,4.9 Hz, 1H), 6.30 (s, 1H), 3.80 (s, 3H), 3.43 (s, 3H).
28		1668	284.2 (M+1)	6 9.00 (d, 7=1.7 Hz, 1H), 8.59 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.09 (ddd, 7 = 6.4, 4.1, 2.2 Hz, 1H), 7.88 (s, 1H), 7.39 - 7.33 (m, 1H), 6.57 (s. 1H), 6.55 (s, 1H), 3.75 (s, 3H), 3.43 (s, 3H).
29		1637	300.2 (M+1)	6 9.02 (d, 7= 1.7 Hz, 1H), 8.60 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.37 (d, 7 = 1.8 Hz, 1H), 8.16 -8.08(m, 1H), 7.38 (dd, 7 = 4.8, 0.7 Hz, 1H), 7.36 (d, 7 = 1.8 Hz, 1 H), 6.66 (s, 1H), 3.70 (s, 3H), 3.45 (s, 3H).

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30		1657.04	343.3 (M+1)	δ 8.99 (d, J= 1.6 Hz, 1H), 8.57 (dd, J = 4.8, 1.6 Hz, 1H), 8.21-7.93 (m, 1H), 7.34 (m,, 1H), 6.50 (s, 1H), 6.20 (bs, 1H), 6.18 (d, 1H), 3.74 (s, 3H), 3.52 (s, 2H), 3.39 (s, 3H), 1.96 (s, 3H).
31		1691	426 (M+1)	δ 9.00 (d, J= 1.8 Hz, 1H), 8.74- 8.37 (m, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.80-7.56 (m, 2H), 7.61 7.09 (m, 5H), 7.19 (d, J= 15.5 Hz, 1H), 6.98 (s, 1H), 3.78 (s, 4H), 3.15 (s, 2H). 2.80 (s, 3H), 2.54 (s, 3H).
32		1641.1	305.2	8.99 (br, 1H), 8.59 (br d, J = 2.5 Hz, 1H), 8.19 (br s, 1H), 8.06 (ddd, J = 8.0, 2.5, 1.3 Hz, 1H), 7.76 (s, 1H), 7.44 (dd, J =8.4, 4.8 Hz, 1H), 3.31 (s, 3H), 2.67 (s, 2H), 2.13 (s. 3H), 1.29 (s, 6H).

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33	160- 165		203.1	1H NMR (300 MHz, CDCI3) δ 9.01 (d, J = 2.0 Hz, 1H), 8.52 (m, 2H), 8.03 (dd. J = 7.1, 1.2 Hz, 1H), 7.63 (s, J - 13.0 Hz, 1H), 7.41 (dd, J= 8.3, 4.7 Hz, 1H), 7.32 (s, 1H), 2.16 (s, 3H).
34	130- 135		231.2	’H NMR (300 MHz, CDCI3) δ 9.01 (s, 1H), 8.59 (s, 1H), 8.53-8.23 (m, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.68 (s, 1H), 7.40- 7.38 (m, 2H), 2.57 (m, 1H), 1.44- 1.10 (m,6H).
35	101- 105		245.1	1H NMR (300 MHz, CDCI3) δ 9.0 (s, 1H), 8.60 (d, J= 15.1 Hz. 1H), 8.49 (m, 1H), 8.12-7.94 (m, 1H), 7.70 (s, 1H), 7.51 -7.31 (m, 2H), 1.34 (s, 9H).

Pagc27l of6!9

36	175- 180		271	1H NMR (300 MHz, DMSO) δ 10.68 (s, 1H), 9.10 (d, 1H), 8.73 (d, / = 20.0 Hz, 1H), 8.60-8.43 (m, 1H), 8.24 (ddd, / = 8.4, 2.7, 1.4 Hz, 1H), 7.84 (d, / = 20.2 Hz, 1H), 7.73-7.39 (m, 1H), 3.53 (q,/ = 11.2 Hz, 2H).
37	1/Ο- Ι 75		265	1H NMR (300 MHz, CDCI3) δ 9.04 (d,/ = 2.5 Hz, 1H), 8.73 (s, 1H), 8.55 (dd,/ = 4.7, 1.3 Hz, 1H), 8.09-7.95 (m, 2H), 7.94-7.85 (m, 2H), 7.80 (s, 1H), 7.60-7.49 (m, 14.5, 7.1 Hz, 3H), 7.42 (dd,/ = 8.3, 4.8 Hz, 1H).

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38	85-90		247.1	’H NMR (300 MHz, CDCI3) δ 9.01 (d, 7=2.3 Hz, 1H), 8.56 (s, 1H), 8.53 (dd, 7 = 4.7, 1.2 Hz, 1H). 8.34 (s, 1H), 8.02 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.66 (s, 1H), 7.40 (dd, 7=8.2, 4.7 Hz, 1H), 3.74 (t, 7 = 5.6 Hz, 2H), 3.47 (s, 3H), 2.67 (t, J = 5.6 Hz, 2H).
39	140- 146		263.1	’H NMR (300 MHz, CDCI3) δ 9.01 (bs, 1H), 8.56 (s, 1H), 8.54 (d, 7 = 4.3 Hz, 1H), 8.03(d, 1H), 7.81 (bs, 1H), 7.65 (d, 7= 16.0 Hz. 1H), 7.40 (dd, 7= 8.2, 4.8 Hz. 1H), 2.93 (t, 7 = 19.6, 12.7 Hz, 2H), 2.71 (t, 2H), 2.18 (s, 3H).

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40	160- 163		266	’H NMR (300 MHz, CDCI3) δ 9.14 (d, 1H), 9.05 (d, J = 2.4 Hz. 1H), 8.81 (dd, J = 3.4 Hz, 1H), 8.73 (s, 1H). 8.57 (d. J = 3.7 Hz, 1H), 8.26 (d. J = 8.1 Hz, 2H). 8.07 (d. J = 8.3 Hz, 1H), 7.84 (s, 1H), 7.46 (ddd, J = 17.0, 8.0, 4.8 Hz, 2H).
41		1650.91	321.4	1H NMR (300 MHz, CDCI3) δ 8.95 (bs, 0.2H), 8.83 (bs, 0.8H), 8.63 (bs, 0.2H), 8.57 (bs, 0.8H), 8.11 -7.80 (m, 1H), 7.62-7.11 (m, 8H), 5.01 (s, 0.4H), 4.81 (s, 1.6), 2.96-2.82 (m, 0.2H), 2.802.62 (m, 0.8H), 1.18 (d, 1.2H), 1.10 (d, J = 6.7 Hz, 4.8H).

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42		1650.55	245,1	1H NMR (300 MHz, CDCI3) δ 9.01-8.93(m, 1H), 8.67 (s, 0.4H), 8.61 (d, 7 = 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,7=6.1 Hz, 2.4H), 1.09 (d, 7 = 6.6 Hz, 3.6H).
43	126- 128		285.1	1H NMR (300 MHz, CDCI3) δ 9.00, 8.99 (d, 7 = 7.6, 2.6 Hz, 1 H), 8.65 (s, 0.2H) 8.63(d, 0.8H), 8.55 (d, 7=3.4 Hz, 0.2H), 8.10 8.07 (m, 1H), 7.99 (bs, 0.8H) 7.79 (s, 0.2H), 7.71 (s, 0.8H), 7.43 m, 7 = 18.7, 8.3, 4.7 Hz, 1H), 3.54-3.35 (m. 1 .OH), 3.31 (s, 2.4H), 3.14 (q, 7 = 10.0 Hz, 1.6H).

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44	68-70		277	1H NMR (300 MHz, CDCI3) δ 9.00, 8.99 (d. J = 5.7 Hz, 1H), 8.72 -8.40(m, 1H), 8.03 (m, J= 18.9, 11.0 Hz, 2H), 7.79 (s, 0.4H), 7.71 (s, 0.6H), 7.60-7.35 (m. 1H), 3.45 (s, 1.2H), 3.29 (s, 1.8H), 3.07-2.73 (m, 2H). 2.55 (t, J = 7.3 Hz, 2H), 2.19 (s, 1.2H), 2.07 (s, 1.8H).
45		1635.19	259.1	1H NMR (300 MHz, CDCI3) δ 9.01 (d, J = 2.5 Hz, 1H), 8.59 (dd, J = 4.8, 1.4 Hz, 1H), 8.26 (s, 1H), 8.07 (ddd, J = 8.3, 2.6, 1.5 Hz, 1H), 7.76 (s, 1H), 7.45 (dd, J = 8.3, 4.7 Hz, 1H), 3.39 (s, 3H), 1.29 (s, 9H).

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46		1641.96	273.1	1H NMR (300 MHz, CDCI3) δ 9.11 (bs, 1H), 8.63 (d, J = 4.2 Hz, 1H), 8.31 (bd, J = 8.4 Hz, 1H), 7.92 (m, J= 14.8 Hz, 2H). 7.92(s, 1H), 5.02 (m, J = 13.5, 6.7 Hz, 1H), 2.52 (m, J = 13.4, 6.7 Hz, 1H), 1.14 -0.89(m, 12H).
47		1649.15	305.1	1H NMR (300 MHz, CDCI3) δ 9.01 (d, J = 2.6 Hz, 1H), 8.62 (d, J = 3.2 Hz. 1Η), 8.16-8.06 (m, 1H), 7.89 (s, 1H), 7.61 (s, 1H), 7.47 (dd, J = 8.3, 4.7 Hz, 1H), 5.17-4.91 (m, 1H). 2.8 (t, 2H), 2.4 (t, 2H), 2.05 (s, 3H), 1.07 (d, J = 6.7 Hz. 6H).

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48

1649.64

305.1

1H NMR (300 MHz, CDCI3) δ 9.12 (d, 0.3H), 9.07 (d, 7 = 2.3 Hz, 0.7H), 8.63 (d, 0.7H), ), 8.59 (d, 7 = 5.0 Hz, 0.3H), 8.30-8.19 (m, 1H), 8.00 (s, 1H), 7.76 (s, 0.3H), 7.70 (s, 0.7H), 7.66 - 7.56 (m, 1H), 3.66-3.55 (m, 2H), 2.79 (t, 7 = 7.3 Hz. 2H), 2.49 (t, 7= 7.3 Hz, 2H), 2.18 (s, 0.9H), 2.06 (s, 2.1 H), 1.84-1.68 (m. 0.6H), 1.67- 1.47 (m, 1.4H). 1.02 (t, 7 = 7.5 Hz, 0.9H), 0.9(t, 7 = 7.4 Hz, 2.1 H).

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49	124- 126		217.1	5 9.01 (d, J = 2.3 Hz, 0.5H), 8.98 (d, J = 2.5 Hz,0.5H), 8.63-8.57 (m, 1H), 8.54 (d, J = 5.6 Hz, 0.5H), 8.07-8.02 (m, J = 15.9, 5.2 Hz, 1H), 7.94 (s, 0.5H), 7.78 (s, 0.5H), 7.70 (s, 0.5H), 7.45 (dd, J =8.3, 4.7 Hz, 0.5H), 7.40 (dd, J = 8.3, 4.7 Hz, 0.5H), 3.44 (s, 1.5H), 3.27 (s, 1.5H), 2.33 (s, 1.5H), 2.04 (s, 21.5H).
50		1643.65	273.1	5 8.99 (d, J = 2.5 Hz, 1H), 8.71 8.45 (m, 1H), 8.07-8.02(m, 1H>, 7.92 (s, 1H), 7.69 (d, J= 16.1 Hz, 1H). 7.54-7.35 (m, 1H), 3.81 3.66 (m, ,2H), 3.69-3.51 (m, 1.8H), 2.96 (bs, 0.2H), 2.70-2.68 (m, 0.8H), 1.691.51(m, 2H), 1.05 (dd, J= 19.7, 6.8 Hz. 6H), 0.96 0.82 (m, 3H).

51

1648.53

291.1

5 9.01, 8.99 (t, 7 = 4.8 Hz, 1H), 8.67 (s, 0.25H), 8.61 (dd, 7 = 4.7, 1.2 Hz, 0.75H), 8.54 (d, 7 = 3.8 Hz, 0.25H), 8.12 - 7.98 (m, 1.75H), 7.80 (s, 0.25H), 7.74 (s, 0.75H), 7.46 (dd, 7= 8.3, 4.7 Hz, 0.75H), 7.39 (dd, 7=8.2, 4.8 Hz, 0.25H), 3.49 (s, 0.75H), 3.29 (s, 2.25H), 3.2-3.1 (m, 0.25H), 3.05- 2.82 (m, 2H), 2.63 (dd, 7= 13.0, 6.2 Hz, 0.25H), 2.45 (dd, 7= 12.0, 4.3 Hz, 0.75H), 2.17 (s 0.75H), 2.03 (s 2.25H), 1.32 (d, 7 = 6.8 Hz, 0.75H), 1.14 (d, 7 = 6.5 Hz, 2.25H).

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52	100- 103		280.51	δ 9.0-8.5 (m, 5H), 8.0-7.6 (m, 3H), 7.49-7.32 (m, 2H), 3.44 (bs 3H).
53		(thin film) 1640.83	ESIMS m/z 292.2 ([M+2HD, 289.23 ([M-H]')	1H NMR (400 MHz, CDCI3) δ 9.01 (s, 1H), 8.61 (s, 1H), 8.53 (s, 1H), 8.01 (ddd, J = 8.3, 2.5, 1.3 Hz, 1H), 7.96 (s, 1H). 7.72 (s, 1H), 7.39 (dd, 7 = 8.3, 4.7 Hz, 1H), 2.82 (s, 2H), 2.15 (s, 3H), 1.40 (s, 6H).

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54		(thin film) 1663	ESIMS m/z 278 ([M+2H]+), 275 ([Μ-HD	’H NMR (400 MHz, CDCI3) δ 9.01 (t, J = 4.3 Hz, 1H), 8.60 (s, 1H), 8.53 (dd, J = 4.7, 1.3 Hz, 1H), 8.01 (ddd, J = 8.3, 2.6, 1.5 Hz, 1 H), 7.79 (bs, 1H), 7.70 (s, 1H), 7.40 (dd, J = 8.3, 4.8 Hz, 1H), 2.88 (dt, J = 11.4, 5.8 Hz, 1H), 2.732.56 (m, 2H), 2.15 (s, 3H), 1.34 (d, J = 6.7 Hz, 3H).
55		(thin film) 1651	ESIMS m/z 260 ([M+2H]*)	1H NMR (400 MHz, CDCI3) δ 9.03 (bs, 1H), 8.68 (bs, 1H), 8.07 (d, J = 8.3 Hz, 1H), 7.93 (s, 1H). 7.74 (s, 1H). 7.67 (s, 1H), 7.50 (d, J = 21.1 Hz, 1H), 3.69 (q, J = 7.1 Hz, 2H), 2.67 (dt, J = 13.4, 6.7 Hz, 1H), 1.15 (t, J = 7.1 Hz, 3H), 1.07 (d, J = 6.7 Hz, 6H).

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56		(thin film) 1678	ESIMS m/z 278 ([M+2H]4), 275 ([M-H])	’H NMR (400 MHz. CDCI3) δ 9.10 (s, 1H). 9.00 (d. J = 2.5 Hz, 1H), 8.57 (s, 1H), 8.52 (dd, J = 4.8, 1.4 Hz, 1H), 8.00 (ddd, J = 8.3, 2.6, 1.5 Hz, 1H), 7.69 (s, 1H), 7.49- 7.35 (m, 1H), 3.26 (m, 1H), 2.62 (m, 2H), 2.13 (s, 3H), 1.37 (d, J = 6.8 Hz, 3H).
57	1 8- 112		ESIMS m/z 261 ([M+H]4), 259 ([M-H]')	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, 1H), 8.30 (s, 1H), 7.98 (ddd, J = 8.3, 2.4, 1.3 Hz, 1H), 7.68 (s, 1H), 7.36 (dd, J = 8.2, 4.8 Hz, 1H), 1.52 (s, 9H).

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58		(thin film) 1659	ESIMS m/z 304 ([M+2Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.4 Hz, 1H), 8.55 (s, 1H), 8.48 (dd, J = 4.7, 1.4 Hz, 1H), 7.97 (ddd, J ~ 8.3, 2.7, 1.5 Hz, 1H), 7.93 (bs, 1H), 7.36 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 2.83 (s, 2H), 2.37 (s, 3H), 2.18 (s, 3H), 1.41 (s, 6H).
59	109- 113		ESIMS m/z 292 ([M+2H]+), 289 ([M-H]’)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.4 Hz, 1H), 8.55 (s, 1H), 8.48 (dd, J = 4.7, 1.4 Hz, 1H), 7.97 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.54 (s, 1H), 7.36 (ddd, J = 8.4, 4.7, 0.6 Hz, 1H), 2.942.80 (m, 1H), 2.75 -2.62 (m, 2H), 2.36 (s, 3H), 2.17 (s, 3H), 1.35(d, 3H).

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60	168- 173		ESIMS m/z 246 ([M+2H]+), 243 ([M-HD	1H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H). 8.55 (s, 1H), 8.48 (dd, 7 = 4.7, 1.3 Hz. 1H), 7.97 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.43-7.31 (m, 1H), 6.97 (bs, 1H), 2.59 (hept, 7 = 6.9 Hz, 1H), 2.34 (s, 3H), 1.29 (d, 7 = 6.9 Hz, 6H).
61	128- 133		ESIMS m/z 278 ([M+2HD	1H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz. 1H), 8.53 (s, 1H), 8.49 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.02-7.91 (m, 1H), 7.57 (bs, 1H), 7.36 (ddd, 7 = 8.3, 4.7, 0.5 Hz, 1H), 2.91 (t. 7 = 6.7 Hz, 2H), 2.72 (dd, 7 = 8.0, 5.5 Hz, 2H), 2.35 (s, 3H), 2.20 (s, 3H).	•

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62		(thin film) 1659	ESIMS m/z 306 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.73 (d, J - 2.3 Hz, 1H), 8.61 (dd, 7 = 4.8, 1.5 Hz, 1H), 7.86-7.79 (m, 2H), 7.75 (s, 1 H). 7.44 (ddd, 7 = 8.2, 4.8, 0.6 Hz, 1H), 2.82 (s, 2H), 2.28 (s, 3H), 2.17 (s, 3H), 1.39 (s, 6H).
63	122- 142		ESIMS m/z 292 ([M+2H]+)	1H NMR (400 MHz, CDCI3) δ 9.01 (t, 7 = 3.7 Hz, 1H), 8.59 (d, 7 = 11.1 Hz, 1H), 8.53 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.21 (s, 1H), 8.01 (ddt, 7 = 8.3, 2.8, 1.4 Hz, 1H), 7.71-7.66 (m, 1H), 7.39 (ddd, 7 = 8.3, 4.8, 0.8 Hz, 1H), 3.102.87 (m, 1H), 2.65 (qd, 7 = 7.0, 5.2 Hz, 1H), 2.50 (dq, 7 = 14.0, 7.0 Hz, 1H), 2.15 (d, 7 = 17.6 Hz, 3H), 1.34 (dd, 7 = 11.7, 7.0 Hz, 6H).

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64	121- 124		ESIMS m/z 275 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (s, 1H), 8.47 (dd, J = 4.7, 1.2 Hz, 1H), 8.26 (s, 1H), 7.96 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.35 (dd, J = 8.3, 4.7 Hz, 1H), 6.16 (s, 1H), 2.30 (s, 3H), 1.54 (s, 9H).
65	144- 145		ESIMS m/z 300([M+2Hf)	1H NMR (400 MHz, CDCI3) δ 9.00 (d, J = 2.4 Hz, 1H), 8.62- 8.47 (m, 2H), 8.01 (ddd,/ = 8.3, 2.7, 1.5 Hz, 1H), 7.68 (s, 1H), 7.53 (bs, 1H), 7.40 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 2.92-2.61 (m, 2H), 2.32- 2.05 (m, 1H), 1.38 (d, / = 6.6 Hz, 3H).

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66		(thin film) 1650	ESIMS m/z 278 ([M+2H]+)	1H NMR (400 MHz, CDCI3) δ 8.74 (d, 7 = 2.3 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.3 Hz. 1H), 7.89-7.75 (m, 2H), 7.52 (d, 7 = 14.4 Hz, 1H), 7.50 - 7.39 (m, 1H), 2.90 (t, 7 = 6.9 Hz, 2H), 2.69 (t, 7 = 6.9 Hz, 2H), 2.30 (s, 3H), 2.18 (s, 3H).
67		(thin film) 1703	ESIMS m/z 275 ([M+Hf)	1H NMR (400 MHz. CDCI3) δ 8.98 (bs, 1H), 8.52 (d, 7 = 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, 7 = 8.0, 4.8 Hz, 1H), 3.30 (s, 3H), 1.56 (s, 9H).

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68		(IRthin film) 1682	ESIMS m/z 351 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.92 (d, J = 2.6 Hz, 1H), 8.57 (d, J = 3.5 Hz, 1H), 8.02 (d, J = 7.4 Hz, 1H). 7.85 (bs, 1H), 7.47-7.32 (m, 1H), 3.40 (d, J = 7.4 Hz, 2H), 1.84- 1.72 (m, 1H), 1.57 (s, 9H), 0.94 (d, J = 6.7 Hz, 6H).
69		(IR thin film) 1662	ESIMS m/z 348 ([M+HJ+)	1H NMR (400 MHz, CDCI3) δ 8.87 (s, 1H), 8.61 (d, J =4.1 Hz. 1H), 8.00 (ddd, J = 8.4, 2.6, 1.4 Hz, 1H), 7.50-7.40 (m,2H), 7.12 (dd, J = 5.1, 1.1 Hz, 1H), 6.92 (dd, J = 5.1,3.4 Hz, 1H), 6.79 (d, J = 2.8 Hz, 1H), 3.23 (s, 3H), 3.19 (t, J = 7.2 Hz, 2H), 2.52 (t, J = 7.2 Hz, 2H).

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70		(IR thin film) 1665.	ESIMS m/z 365 ([M+H]*), 363 ([M-HD	’H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.5 Hz, 1H), 8.678.63 (m, 1H), 8.03 (s, 1H), 8.02- 7.99 (m, 1H), 7.50 -7.45 (m, 1H), 4.07 - 3.92 (m, 1H), 3.28 (s, 3H), 1.63-1.59 (m, 3H).	’3C NMR (101 MHz, CDCIs) δ 171.35, 148.99, 140.22, 135.62, 132.10, 129.01, 126.56, 126.18, 124.54, 124.18, 39.70, 37.71, 19.66.
71	85-86		ESIMS m/z 313 ([M+HJ+)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.6 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 = 8.4, 4.8, 0.6 Hz, 1H), 3.80 (t, 7 = 6.7 Hz, 2H), 3.74 (q, 7 = 7.1 Hz, 2H), 2.64 (t, 7 = 6.7 Hz, 2H), 1.18(1,7 = 7.2 Hz, 3H).

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72		(thin film) 1630		’H NMR (400 MHz, CDCI3) δ 9.01 (d, J = 2.5 Hz, 1H), 8.60 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.13-8.01 (m, 2H), 7.79 7.69 (s, 1H), 7.52 -7.41 (m, 1H), 3.66 (q, 7 = 7.1 Hz, 2H), 2.59 (s, 2H), 2.12 (s, 3H), 1.23 (s, 6H), 1.18 (t, 7 = 6.7 Hz, 3H).
73		(thin film) 1600	ESIMS m/z 258 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7= 2.4 Hz. 1H), 8.56 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.94 (s, 1H), 7.43 (dd, 7=8.2, 4.7 Hz, 1H), 3.21 (s, 3H), 2.65 (hept, 7 = 6.7 Hz, 1H), 2.27 (s, 3H), 1.07 (d, 7 = 6.8 Hz, 6H).

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74		(thin film) 1654	ESIMS m/z 291 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.94 (bs, 1H), 8.57 (d, 7 = 3.9 Hz, 1H), 8.15- 7.97 (m, 1H), 7.91 (s, 1H), 7.43 (dd, 7=8.3, 4.7 Hz, 1H), 3.24 (s, 3H), 2.79 (t, 7 = 7.3 Hz, 2H), 2.45 (t, 7 = 7.3 Hz, 2H), 2.28 (s, 3H), 2.06 (s, 3H).
75		(thin film) 1649	ESIMS m/z 305 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d. 7 = 2.5 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.03 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 8.03 (s, 1H), 7.43 (ddd, 7=8.3, 4.8, 0.6 Hz, 1H), 3.25 (s, 3H), 2.95 -2.72(m, 2H), 2.53 - 2.38 (m, 1H), 2.37 (s, 3H), 2.01 (s, 3H), 1.13 (d,7 = 6.6 Hz, 3H).

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76		(thin film) 1630	ESIMS m/z 319 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.5 Hz, 1H), 8.56 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.05-8.01 (m, 1H), 7.99 (s, 1H), 7.46-7.37 (m, 1H), 3.19 (s, 3H), 2.71 (s, 2H). 2.31 (s, 3H), 2.14 (s, 3H), 1.19 (s, 6H).
77	173- 176		ESIMS m/z 264 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7=2.6 Hz, 1H), 8.66 (s, 1H), 8.55 (dd, 7 = 4.7, 1.3 Hz, 1H), 7.98 (ddd, 7= 8.3, 2.7, 1.4 Hz, 1H), 7.51-7.31 (m, 1H). 7.21 (s, 1H), 2.63 (hept, 7 = 6.9 Hz, 1H), 1.30 (d, 7 = 6.9 Hz, 6H).

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78	140- 143		ESIMS m/z297([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.64 (s, 1H), 8.55 (dd, 7 = 4.7, 1.3 Hz, 1H), 7.99 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.77 (s, 1H), 7.40 (ddd, 7=8.3, 4.8, 0.6 Hz, 1H), 2.91 (dd,7= 10.3, 3.5 Hz, 2H), 2.75 (dd, 7= 10.3, 3.6 Hz, 2H), 2.19 (s, 3H).
79	119- 124		ESIMS m/z 311 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.98 (d, 7 = 2.4 Hz, 1H), 8.67 (s, 1H), 8.55 (dd,7 = 4.7, 1.4 Hz, 1H), 8.11 (s, 1H), 7.98 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.40 (ddd, 7= 8.3, 4.8, 0.6 Hz, 1H), 2.89 (dd, 7= 12.8, 8.6 Hz, 1 H), 2.822.71 (m, 1H), 2.68 (dd, 7 = 12.8, 5.0 Hz, 1H), 2.15 (s, 3H), 1.35 (d, 7 = 6.8 Hz, 3H).

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80	83-90		ESIMS m/z 325 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.5 Hz, 1H), 8.68 (s, 0.3H), 8.65 (s, 0.7H), 8.54 (dd, J = 4.7, 1.3 Hz, 1H), 8.41 (bs, 0.7H), 8.03 - 7.94 (m, 1H), 7.85 (bs, 0.3H), 7.40 (dd, J = 8.3, 4.8 Hz, 1H), 3.07-2.90 (m, 1H), 2.74 (qd. J = 7.0, 5.1 Hz, 0.7H), 2.63 (dq, J =13.9, 6.9 Hz, 0.3H), 2.19 (s, 2H), 2.14 (s, 1H), 1.41 - 1.25 (m, 6H).
81	112- 122		ESIMS m/z 333 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, J =2.5 Hz, 1H), 8.63 (s, 1H), 8.56 (dd, J = 4.7, 1.4 Hz, 1H), 7.99 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.40 (ddd, J = 8.4, 4.8,0.6 Hz, 1H), 7.19 (s, 1H), 2.56 (t, J= 7.2 Hz, 2H), 2.34-2.14 (m, 2H), 2.12-1.91 (m, 2H).

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82	109.5 111.5		ESIMS m/z 331 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.01 (dd, J= 7.4, 2.3 Hz, 1H), 8.84 (d, 7=0.4 Hz, 1H), 8.62 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.12 (s, 1H), 8.07 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.44 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H), 2.90 (t, 7 = 6.5 Hz, 2H), 2.75 (t, 7 = 6.7 Hz, 2H), 2.18 (s, 3H).
83	107.5 110.5		ESIMS m/z 345 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.02 (d, 7 = 2.4 Hz, 1H), 8.85 (s, 1H), 8.62 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.89 (s, 1H), 7.44 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H). 2.932.81 (m, 1 H). 2.75 -2.63 (m, 2H), 2.16(5, 3H), 1.34 (t, 7=6.2 Hz, 3H).

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84	157.5 160.0		ESIMS m/z 299 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.02 (d, 7 = 2.4 Hz, 1H), 8.908.80 (m, 1H), 8.62 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.06 (ddd, 7 = 8.3,2.7, 1.5 Hz, 1H), 7,44 (ddd, 7= 8.3, 4.8, 0.7 Hz, 1H), 7.37 (s, 1H), 2.61 (hept, 7 = 6.9 Hz. 1H), 1.29 (d, J = 6.9 Hz, 6H).
85	135.0 136.0		ESIMS m/z 295 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.79 - 8.74 (m, 1H), 8.55(s, 1H), 8.34 (d, 7 = 2.5 Hz. 1H). 7.79 (dt, 7 = 9.7, 2.4 Hz, 1H), 7.62 (s, 1H), 2.91 (t, 7=6.7 Hz, 2H), 2.72 (t, 7 = 6.7 Hz, 2H), 2.35 (s, 3H), 2.20 (s, 3H).

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86	74.0- 77.0		ESIMS m/z 303 ([M+Hf)	’H NMR {400 MHz, CDCI3) δ 8.92 (d, J = 2.4 Hz, 1H), 8.51 (dd, J = 4.7, 1.3 Hz, 1H), 8.02 (s, 1H), 7.76 (d, J= 37.6 Hz, 1H), 7.38 (dd, J =8.3, 4.7 Hz, 1H), 3.58 (q, J = 13.0, 6.2 Hz, 2H), 2.25 (s, 3H), 1.44 (s, 9H), 1.16 (t, J = 7.1 Hz, 3H).
87	72.5- 74.5		ESIMS m/z 317 ([M+HD	1H NMR (400 MHz, CDCI3) δ 8.92 (d, J = 2.2 Hz, 1H), 8.50 (dd, J = 4.7, 1.3 Hz, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.79 (s, 1H). 7.38 (dd, J = 8.2, 4.7 Hz, 1H), 3.48 (t. J = 8.0 Hz, 2H), 2.25 (s, 3H), 1.63 1.52 (m, 2H), 1.43 (s, 9H), 0.91 (t, J = 7.4 Hz, 3H).

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88	118.0 119.5		ESIMS m/z 313 ([M+H]4)	1H NMR (400 MHz, CDCI3) δ 8.99 (d, J = 2.3 Hz, 1H), 8.69 (d, J = 4.1 Hz, 1 H), 8.12 (d, J = 8.3 Hz, 1H), 8.04 (d. J = 0.7 Hz, 1H), 7.50 (dd, J= 8.2, 4.8 Hz, 1H), 3.23 (s, 3H), 2.59 (hept, J = 6.3 Hz, 1H), 1.08 (d, J = 6.7 Hz, 6H).
89	92-95		ESIMS m/z 317 ([M+HD	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.1 Hz, 1H), 8.51 (dd, J =4.7, 1.2 Hz, 1H), 8.03 (ddd, J = 8.3, 2.4, 1.4 Hz, 1H), 7.74 (s, 1H), 7.39 (dd, J = 8.3, 4.7 Hz, 1Η), 4.64 (s, 1H), 2.21 (s, 3H), 1.41 (s, 9H). 1.10 (d, J = 6.7 Hz, 6H).

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90		(thin film) 1689	ESIMS m/z 329 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.93 (s, 1H), 8.50 (dd, J = 4.7, 1.1 Hz, 1H), 8.01 (d, J = 8.1 Hz, 1H), 7.87 (s, 1H), 7.38 (dd, J= 8.3, 4.7 Hz, 1H), 3.41 (d, J = 6.9 Hz, 2H), 2.28 (s, 3H), 1.44 (s, 9H), 1.11 - 0.96 (m, 1H), 0.49 (q, J = 5.1 Hz, 2H), 0.24-0.14 (m, 2H).
91		(thin film) 1569	ESIMS m/z 345 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 9.00 (d, J = 2.5 Hz, 1H), 8.70 (dd, J = 4.7, 1.3 Hz, 1H), 8.13 (ddd, J = 8.4, 2.6, 1.4 Hz, 1H), 8.10 (s, 1H), 7.51 (dd, J = 8.3, 4.7 Hz, 1H), 3.26 (s, 3H), 2.79 (t, J = 7.3 Hz, 2H), 2.45 (t, J = 7.3 Hz, 2H), 2.06 (s, 3H).

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92		(thin film) 1658	ESIMS m/z 359 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.00 (d, 7 = 2.5 Hz, 1H), 8.69 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.18 (s, 1H), 8.12 (ddd. 7= 8.3, 2.6, 1.4 Hz, 1H), 7.50 (dt, 7= 13.2, 6.6 Hz, 1H), 3.27 (s, 3H), 2.902.68 (m, 2H), 2.51 (dd, 7= 12.5, 5.0 Hz, 1H), 2.03 (s, 3H), 1.13 (d, 7 = 6.6 Hz, 3H).
93	127.0 130.0		ESIMS m/z 271 ([M-HÏ)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.56 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.86 (s, 1H), 7.42 (ddd, 7 = 8.3, 4.8, 0.5 Hz, 1H), 3.67 (app s, 2H), 2.55 (hept, 7 = 6.7 Hz, 1H), 2.26 (s, 3H), 1.13 (t, 7 = 7.1 Hz, 3H), 1.06 (d, 7 = 6.7 Hz, 6H).

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94

thin film) 1650

ESIMS m/z 319 ((M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.4 Hz, 1H), 8.57 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.89 (s. 1H), 7.43 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.59 (s, 2H), 2.78 (t, J = 7.3 Hz, 2H), 2.41 (t, J = 7.3 Hz, 2H), 2.27 (s, 3H), 2.05 (s, 3H), 1.64 -1.49 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H).

———

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95		(thin film) 1651	ESIMS m/z 332 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7=2.4 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.05 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.94 (s. 1H), 7,43 (ddd, 7= 8.3, 4.8, 0.6 Hz, 1H), 3.53 (app s, 2H), 2.79 (t, 7 = 7.3 Hz. 2H), 2.43 (t, 7 = 7.2 Hz, 2H), 2.30 (s, 3H), 2.06 (s, 3H), 1.05-0.92 (m, 1H), 0.54- 0.42 (m, 2H), 0.27 -0.14(111, 2H).
96	70.0- 72.5		ESIMS m/z 305 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7= 2.4 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.04 (ddd, 7 = 8.3,2.7, 1.5 Hz, 1H), 7.90 (s, 1 H), 7.43 (ddd, 7 =8.3, 4.8, 0.6 Hz, 1H), 3.70 (app s, 2H), 2.78 (t, 7 = 7.3 Hz, 2H), 2.41 (t, 7 = 7.3 Hz, 2H), 2.28 (s. 3H), 2.05 (s, 3H), 1.15 (t, 7 = 7.2 Hz, 3H).

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97

(thin film) 1647

ESIMS m/z 319 ([M+H]*)

1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.3 Hz, 1H), 8.57 (dd, J = 4.7, 1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.96 (s, 1H), 7.43 (ddd, J =8.3, 4.8,0.7 Hz, 1H), 3.71 (s, 2H), 2.88 (dd, J= 12.6, 9.4 Hz, 1H), 2.73 (d, J = 4.1 Hz, 1H), 2.42 (dd, J =12.8, 5.1 Hz, 1H), 2.31 (s, 3H), 2.01 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H).

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98

(thin film) 1647

ESIMS m/z 319 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.99 (dd, 7 = 7.9, 2.6 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.83 (s, 1H), 7.44 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 5.154.97 (m, 1H), 2.77 (t. 7 = 7.3 Hz, 2H), 2.45-2.27 (m, 2H), 2.26 (s, 3H), 2.04 (s, 3H), 1.15 (d, 7 = 6.6 Hz, 3H), 1.01 (d, J = 6.8 Hz, 3H).

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99	124.0 126.0		ESIMS m/z 339 ([M+H]*)	'H NMR (400 MHz, CDCI3) δ 9.06 (d, J =2.2 Hz, 1H), 8.77 (s, 1H), 8.52 (dd. J = 4.7, 1.4 Hz, 1H), 8.09 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.81 (s, 1 H), 7.69 (dt, J =8.1, 1.7 Hz, 2H), 7.58 7.49 (m, 2H), 7.49 -7.43(m, 1H), 7.39 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 2.89 (t, J = 6.8 Hz, 2H), 2.69 (t, J = 6.8 Hz, 2H), 2.15 (s. 3H).
100		(thin film) 1710	ESIMS m/z 442 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.05 (d, J =2.5 Hz, 1H), 8.60 (dd, J= 4.7, 1.3 Hz, 1H), 8.16 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 8.09 (s, 1H), 7.67 (dt, J = 8.5, 2.2 Hz, 2H), 7.51 7.36 (m, 4H), 2.96 (t, J = 6.9 Hz, 4H), 2.74 (t, J = 7.0 Hz, 4H), 2.03 (s, 6H).

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101		(thin film) 1652	ESIMS m/z 321 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.3 Hz. 1H), 8.57 (d, J = 4.7 Hz, IH), 8.03 (ddd, J = 8.3, 2.4, 1.3 Hz, 1H), 7.94 (s, 1H), 7.42 (dd, J = 8.3, 4.8 Hz, 1H), 3.70 (s, 2H), 3.14 (dt, J = 13.2, 7.7 Hz, 1H), 2.94-2.81 (m, 1H), 2.74-2.53 (m, 5H), 2.28 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H).
102		(thin film) 1647	ESIMS m/z 335 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.11 -8.94 (m, 1H), 8.59-8.48 (m, 1H), 8.21 - 7.95 (m, 2H), 7.46 -7.34(m, 1H), 4.35 - 3.81 (m, 0.5H), 3.34 - 3.05 (m, 2.5H), 2.74- 2.52 (m, 4H), 2.35 -2.27(m, 3H), 1.24 -1.11 (m, 6H).

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103		(thin film) 1656	ESIMS m/z 337 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.4 Hz, 1H), 8.648.54 (m, 1H), 8.04 (ddd, /=8.3, 2.5, 1.4 Hz, 1H), 7.96 (s, 1 H). 7.43 (dd, /=8.3, 4.7 Hz, 1H), 3.70 (s, 2H), 3.41 (t, / = 6.9 Hz, 2H), 2.96 (s, 3H), 2.66 (t, J = 6.5 Hz, 2H), 2.28 (s, 3H), 1.16 (t, / = 7.1 Hz, 3H).
104		(thin film) 1656	ESIMS m/z 351 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.01 (s, 1H), 8.56 (dd, / = 4.7, 1.3 Hz, 1H), 8.09 (s, 1H), 8.01 (d./ = 8.1 Hz, 1H), 7.41 (dd, / = 8.3, 4.7 Hz, 1H), 4.16 (s. 0.5H), 3.84 (dd, / = 13.7, 10.7 Hz, 1H), 3.45-3.09 (m, 1.5H), 3.072.91 (m, 4H), 2.86 (dd, /= 13.7, 2.7 Hz, 1H), 2.32 (s, 3H), 1.19-1.11 (m, 6H).

Page 308 of 619

105	53.0- 55.5		ESIMS m/z 309 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J= 1.7 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.94 (s, 1H), 7.85 (dt, J = 9.4, 2.4 Hz, 1H), 3.23 (s, 3H), 2.79 (t, J = 7.3 Hz, 2H), 2.44 (t, 7=7.3 Hz, 2H), 2.28 (s, 3H), 2.06 (s, 3H).
106		(thin film) 1659	ESIMS m/z 353 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.05 (d, 7 = 2.3 Hz, 1H), 8.61 (dd, J = 4.7, 1.4 Hz, 1H), 8.16 (ddd, J = 8.3, 2.7, 1.5 Hz, 1 H), 8.07 (s, 1H), 7.84-7.77 (m, 2H), 7.52-7.38 (m, 4H), 3.31 (s, 3H), 2.69 (t, <7 = 7.2 Hz, 2H), 2.46 (t, 7= 7.1 Hz, 2H). 1.92 (s, 3H).

Page 309 of6!9

107	144- 147		ESIMS m/z 258 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.52 (dd, J = 4.8, 1.6 Hz. 1H), 8.21 (s, 1H), 7.62 (dt, J = 46.6, 23.3 Hz, 1H), 7.25-7.19 (m, 1H), 6.89 (s, 1H), 2.60 (m, 1H), 2.56 (s, 3H), 2.33 (s, 3H), 1.29 (d, J = 6.9 Hz, 6H).
108		(thin film) 1668	ESIMS m/z 325 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.5 Hz, 1H), 8.66 (s, 1H). 8.54 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.06 (s, 1H), 8.01 -7.94 (m, 1H), 7.39 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 2.83 (s, 2H), 2.17 (s, 3H), 1.41 (s, 6H).

Page 310 of 619

109	109- 115		ESIMS m/z 395 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.90 (d, 7 = 2.3 Hz, 1H), 8.68 (dd, 7 = 4.8, 1.5 Hz, 1H), 7.94 (ddd, 7 = 8.2, 2.5. 1.5 Hz, 1H), 7.70 (s, 1H), 7.47 (dtd. 7 = 11.0, 5.6, 5.5, 4.8 Hz, 1H), 1.49 (s, 18H).
110		(thin film) 1697	ESIMS m/z 352 ([M-H])	’H NMR (400 MHz, CDCI3) δ 8.89 (s, 1H), 8.68 (d,7=4.1 Hz, 1H), 7.93 (ddd, 7 = 8.2, 2.5, 1.5 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, 7 = 8.1, 4.8 Hz, 1H), 3.22 (s, 3H), 1.44 (s, 9H).
111	131.5 133.0		ESIMS m/z 293 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (s, 1H), 8.32 (d, 7 = 2.5 Hz, 1H), 8.28 (s. 1H), 7.77 (dt, 7=9.7, 2.4 Hz, 1H), 6.15 (s, 1H), 2.29 (s. 3H), 1.54 (s, 9H).

Page 311 of6!9

112		(thin film) 1698	ESIMS m/z 337 ([M+Hf)	1H 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).
113		(thin film) 1661	ESIMS m/z 357 ([M+2]*)	1H NMR (400 MHz, CDCI3) δ 8.93 (d, J = 2.4 Hz. 1H), 8.73 (dd, J = 4.8, 1.3 Hz, 1H), 7.97 (ddd, J = 8.2, 2.4, 1.5 Hz, 1H), 7.77 (s, 1H), 7.51 (dd, J = 8.2, 4.8 Hz, 1H), 3.25 (s, 3H), 2.80 (t, J = 7.4 Hz, 2H), 2.47 (t, J = 7.4 Hz, 2H), 2.08 (s, 3H).

Page3l2of6l9

114		(thin film) 1703	ESIMS m/z 351 ([M+Hf)	1H NMR (400 MHz. CDCI3) δ 8.95-8.86 (m, 1H), 8.35 (s, 1H), 7.92 - 7.79 (m, 1H), 4.28 (qd, 7 = 7.1, 1.6 Hz, 2H), 3.15 (s, 3H). 2.15 (s, 3H), 1.55- 1.41 (m, 9H), 1.39 (t, 7 = 7.1 Hz, 3H).
115	93.5- 95.5		ESIMS m/z 307 ([M+HD	1H NMR (400 MHz, CDCI3) δ 8.71 (d, 7= 0.9 Hz, 1H), 8.36 (d, 7 = 2.5 Hz, 1H), 8.02 (s, 1H), 7.91 -7.74 (m, 2H), 3.20 (s, 3H), 2.27 (s, 3H), 1.45 (s, 9H).
116	112.0 114.0		ESIMS m/z 321 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.72 (s, 1H), 8.36 (d, 7 = 2.5 Hz, 1H), 7.82 (m, 2H), 3.58 (dd, 7= 13.3, 6.4 Hz, 2H), 2.24 (s, 3H), 1.44 (s, 9H), 1.16 (t, 7 = 7.1 Hz, 3H).

Page 313 of 6I9

117		(thin film) 1662	ESIMS m/z 371 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.93 (d, 7 = 2.2 Hz, 1H), 8.73 (dd, 7=4.8, 1.5 Hz, 1H), 7.96 (ddd, 7 = 8.2, 2.6, 1.5 Hz, 1H), 7.80 (s, 1H), 7.50 (ddd, 7 = 8.2, 4.8, 0.7 Hz, 1H), 3.27 (s, 3H), 2.87 (dd, 7=12.9, 8.5 Hz, 1H), 2.81 2.66 (m, 1H), 2.46 (dd, 7= 12.9, 5.7 Hz, 1H), 2.02 (s, 3H), 1.17 (d, 7 = 6.7 Hz, 3H).
118		(thin film) 1658	ESIMS m/z 325 ([M+2]+)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.3 Hz, 1H), 8.73 (dd, 7 = 4.8, 1.2 Hz, 1H), 8.00 (ddd, 7 = 8.2, 2.5, 1.5 Hz, 1H), 7.76 (d, 7 = 2.6 Hz, 1H), 7.52 (dd, 7 = 8.2, 4.8 Hz, 1H), 3.23 (s, 3H), 2.59 (hept, 7 = 6.7 Hz, 1H), 1.10 (d, 7=6.7 Hz, 6H).

Page 314 of 619

119

(thin film) 1663

ESIMS m/z 353 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 4.1 Hz. 1H). 8.40 (d.7 = 2.5 Hz, 1H), 7.91 - 7.84 (m, 1H), 4.42-4.27 (m, 1H). 4.26- 4.16 (m, 1H), 3.23 (s, 3H), 2.89 - 2.72 (m, 2H), 2.60 - 2.39 (m, 2H), 2.19(5, 3H), 2.08 (s, 3H), 1.42 (t, 7 = 7.0 Hz, 3H).

Page3I5 of6!9

120

(thin film) 1661

ESIMS m/z 367 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.92 (d, J = 7.6 Hz, 1H), 8.40 (t, J = 2.3 Hz, 1H), 7.88 (dt. 7 = 9.8, 2.3 Hz, 1H), 4.66 (dq,7=9.0, 7.0 Hz, 0.5H), 4.35 (dq, 7= 9.2, 7.1 Hz, 0.5H), 4.194.08 (m, 1H), 3.24 (s, 1.5H), 3.24 (s, 1.5H), 2.95 (dd, 7 = 12.8, 8.7 Hz, 0.5H), 2.91 -2.75 (m, 1.5H), 2.482.38 (m, 1H), 2.27 (s, 1.5H), 2.21 (s. 1.5H), 2.06 (s, 1.5H), 1.96 (s, 1.5H), 1.41 (app qd, 7 = 6.8, 2.7 Hz, 3H), 1.20 (d, 7 = 6.5 Hz, 1.5H). 1.09 (d, 7 = 6.8 Hz, 1.5H).

Page 316 of 6 i 9

121	102.5 105.0		ESIMS m/z 323 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J = 1.6 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.97 (s, 1H), 7.85 (dt, J = 9.4, 2.4 Hz. 1H), 3.24 (s, 3H), 2.88 (dd, J = 12.6, 9.4 Hz, 1H), 2.84-2.71 (m, 1H), 2.44 (dd, J = 12.6, 4.8 Hz, 1H), 2.31 (s, 3H), 2.01 (s, 3H), 1.13 (d. J = 6.7 Hz, 3H).
122	116.5 119.5		ESIMS m/z 277 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J= 1.2 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.92 (s, 1H), 7.85 (dt, J = 9.4, 2.3 Hz, 1H), 3.21 (s, 3H), 2.61 (hept, J = 6.7 Hz, 1H), 2.27 (s, 3H), 1.07 (d, J = 6.7 Hz, 6H).

Page 317 of 619

123		(thin film) 1650	ESIMS m/z 323 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.79 (d, J= 1.5 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.98 (s, 1H), 7.88 (dt, J =9.4, 2.3 Hz, 1H), 3.69 (s, 2H), 2.78 (t, J = 7.3 Hz, 2H), 2.41 (t, J =7.3 Hz, 2H), 2.28 (s, 3H), 2.05 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H).
124	87.0- 88.5		ESIMS m/z 337 ([M+Hf)	4H NMR (400 MHz, CDCI3) δ 8.76 (d, J= 1.6 Hz, 1 H), 8.43 (d, J = 2.5 Hz, 1H), 7.93 (s, 1H), 7.85 (dt, J = 9.4, 2.4 Hz, 1H), 3.70 (s, 2H), 2.88 (dd, J = 12.7, 9.5 Hz, 1H), 2.69 (s, 1H), 2.43 (dd, J= 12.8, 5.0 Hz, 1H), 2.30 (s, 3H), 2.01 (s, 3H). 1.15 (t, J= 7.1 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H).

Page 318 of 619

125	139.0 141.0		ESIMS m/z 291 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.76 (d, 7 = 1.0 Hz, 1H), 8.42 (d, J = 2.4 Hz. 1H), 7.88 (s, 1H), 7.88 -7.83(m, 1H), 3.67 (s, 2H), 2.52 (hept, J = 6.7 Hz, 1H), 2.26 (s, 3H), 1.13 (t, 7 = 7.1 Hz, 3H), 1.06 (d, 7 = 6.7 Hz, 6H).
126		(thin film) 1647	ESIMS m/z 305([M+H]+)	’H NMR (400 MHz, CDCI3) δ 8.52 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.21 (s, 1H), 7.74 (s, 1H), 7.65 (dd,7 = 8.0, 1.6 Hz, 1H), 7.27-7.16 (m, 1H), 2.93-2.82 (m, 1H), 2.74- 2.61 (m, 2H), 2.56 (s, 3H), 2.34 (s, 3H), 2.16 (s, 3H), 1.34 (d, 7 = 6.6 Hz, 3H).

Page 319 of 619 «r A*

127		(thin film) 1654	ESIMS m/z 291 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.51 (dd, J = 4.8, 1.6 Hz, 1H), 8.32 (s, 1H), 8.19 (s. 1H), 7.65 (dd, J = 15.0, 7.5 Hz, 1H), 7.29-7.20 (m, 1H), 2.88 (t, J = 6.8 Hz, 2H), 2.70 (t, J = 6.9 Hz, 2H), 2.55 (s, 3H), 2.32 (s. 3H), 2.15 (s, 3H).
128		(thin film) 1666	ESIMS m/z 309 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (t, J = 2.0 Hz, 1H), 8.62 (dd, J = 4.8, 1,4 Hz, 1H), 7.99 (ddt, J = 8.3, 2.7, 1.4 Hz, 1H), 7.45 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 3.22 (s, 3H), 2.91 - 2.73 (m, 2H), 2.55-2.38 (m, 2H), 2.25 (s, 3H), 2.08 (s, 3H).

Page 320 of 6I9

129		(thin film )1667	ESIMS m/z 323 ([M+H]4)	’H NMR (400 MHz, CDCI3) δ 8.97 (dt, J = 3.9, 2.1 Hz. 1H), 8.62 (dd, J = 4.7, 1.2 Hz, 1H). 8.04- 7.95 (m, 1H), 7.50 -7.42 (m, 1H), 3.24 (s, 3H), 2.95 -2.69(m, 2H), 2.51-2.38 (m, 1H), 2.36-2.23 (m, 3H), 2.07- 1.96 (m, 3H), 1.20 - 1.13 (m, 3H).
130			ESIMS m/z 275 ([M+H]4)	1H NMR (400 MHz, CDCI3) δ 8.97(d, J= 1.4 Hz, 1H), 8.46 (d, J = 4.1 Hz, 1H), 8.27 (s, 1H), 8.04-7.88 (m, 1H), 7.33 (dd, J = 8.3, 4.8 Hz, 1H), 7.12 (s, 1 H), 2.28 (s, 3H), 1.49 (s, 9H).

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131		(thin film) 1663	ESIMS m/z 385 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.90 (app dd, J = 9.1, 2.4 Hz, 1H), 8.70 (app d, J = 4.8 Hz, 1H), 8.007.89 (m, 1H), 7.48 (app dd, J = 8.2, 4.8 Hz, 1H), 3.23 (s, 2H), 3.22 (s, 1H), 2.92-2.81 (m, 1H), 2.702.58 (m, 1H), 2.53 -2.42 (m, 1H), 2.38 (s, 2H), 2.30 (s, 1H), 2.03 (s, 2H), 1.97 (s, 1H), 1.19 (app t, 7 = 6.5 Hz, 3H).
132		(thin film) 1667	ESIMS m/z 371 ([M+2]*)	1H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 2.2 Hz, 1H), 8.69 (dd, 7 = 4.8, 1.5 Hz, 1H), 7.95 (ddd, 7 = 8.2, 2.6, 1.5 Hz, 1H), 7.48 (ddd, 7 = 8.2, 4.8, 0.7 Hz, 1H), 3.22 (s, 3H), 2.88-2.73 (m, 2H), 2.50-2.32 (m,2H), 2.30 (s, 3H), 2.08 (s, 3H).

Page 322 of6!9

133		(thin film) 1651	ESIMS m/z 339 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz. 1H), 8.63 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.08-8.01 (m, 1H), 8.01 (s, 1H), 7.46 (dd, 7 = 8.3, 4.8 Hz, 1H), 3.74 (bd, 7 = 82.2 Hz, 2H), 2.86 (dd, 7= 12.8, 8.9 Hz, 1H), 2.70 (s. 1H), 2.47 (dd, 7= 12.8, 5.4 Hz, 1 H). 2.02 (s, 3H), 1.26- 1.08 (m, 6H).
134		(thin film) 1655	ESIMS m/z 325 {[M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.95 (s, 1 H), 8.63 (d, 7 = 4.3 Hz, 1 H), 8.05 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.67 - 7.36 (m, 1H), 3.72 (q, 7 = 7.2 Hz, 2H), 2.80 (t, 7= 7.4 Hz, 2H), 2.45 (t, 7 = 7.4 Hz, 2H), 2.07 (s, 3H), 1.17 (t, 7 = 7.2 Hz, 3H).

Page 323 of6l9

135

ESIMS m/z 379 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.97 (t, J =2.0 Hz, 1H), 8.61 (dd, J = 4.8, 1.4 Hz, 1 H), 7.99 (ddt, J =8.3, 2.6, 1.3 Hz, 1H), 7.57 (d, J = 2.5 Hz, 1H), 7.44 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 1.50 (s, 18H).

Page 324 of 619

136

thin film) 1647

ESIMS m/z 337 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.76 (d, J= 1.7 Hz, 0.66H), 8.75 (d, J= 1.7 Hz, 0.33H), 8.43 (d, J = 2.6 Hz, 0.33H), 8.42 (d, J = 2.5 Hz, 0.66H), 8.00 (s, 0.66H), 7.90 (s, 0.33H), 7.85 (app ddt, J = 9.4, 3.4, 2.4 Hz, 1H), 3.24 (s, 2H), 3.23 (s, 1H), 2.992.81 (m, 1H). 2.63 -2.48 (m, 1H), 2.31 (s, 2H), 2.28 (s, 1H), 2.02 (s, 2H), 2.01 (s, 1H), 1.30 (d, 7=6.7 Hz, 1H), 1.25 (d, 7 = 6.1 Hz, 1H), 1.23 (d, 7 = 6.9 Hz, 2H), 1.11 (d, J = 6.8 Hz, 2H).

Page 325 of6!9

137

(thin film) 1645

ESIMS m/z 352 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.78 - 8.76 (m, 0.66H), 8.76 (d, J = 1.7 Hz, 0.33H), 8.43 (d, J = 2.6 Hz, 0.33H), 8.42 (d, J = 2.5 Hz, 0.66H), 7.97 (s, 0.66H), 7.89 - 7.82 (m, 1.33H), 3.70 (app d, J = 61.9 Hz, 2H), 2.99 -2.80 (m, 1H), 2.49 (dq, J =9.3, 6.8 Hz, 1H), 2.30 (s, 2H), 2.27 (s, 1H), 2.02 (s, 2H), 2.01 (s, 1H). 1.30 (d, J = 6.7 Hz, 1H), 1.25 (d, J = 5.2 Hz, 1H), 1.22 (d, J =6.9 Hz, 2H), 1.19-1.12 (m, 3H), 1.10 (d, J = 6.8 Hz, 2H).

Page 326 of 619

138		(thin film) 1658	ESIMS m/z 264 ([M+2]*)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J= 1.7 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1 H), 7.93 (s, 1H), 7.85 (dt, J =9.3, 2.4 Hz, 1H), 3.24 (s, 3H), 3.13 (t. J = 6.7 Hz, 2H), 2.56 (t, J = 6.6 Hz, 2H), 2.27 (s, 3H).
139		(thin film) 1670	ESIMS m/z 325 ([M])	1H NMR (400 MHz, CDCI3) δ 8.92 (dd, J =2.6, 0.5 Hz, 1H), 8.69 (dd, J =4.8, 1.5 Hz, 1H), 7.96 (ddd, J = 8.2, 2.6, 1.5 Hz, 1H), 7.48 (ddd, J = 8.2, 4.8, 0.7 Hz, 1H), 3.22 (s, 3H), 2.87 2.73 (m, 2H), 2.51 - 2.32 (m, 2H), 2.28 (s. 3H), 2.08 (s, 3H).

Page 327 of 619

140

(thin film) 1666

ESIMS m/z 339 ((MJ)

’H NMR (400 MHz, CDCI3) δ 8.93 (d, 7 = 2.3 Hz, 0.6H), 8.90 (d, 7 = 2.3 Hz, 0.4H), 8.69 (app dt, 7 = 4.8, 1.4 Hz, 1H), 7.99 - 7.90 (m, 1H), 7.48 (app ddd, 7 = 8.2, 4.8, 0.4 Hz, 1H), 3.23 (s, 1.8H), 3.23 (s. 1.2H), 2.89 (dd, 7 = 13.0, 8.8 Hz, 0.6H), 2.83 (dd, 7 = 13.1,6.4 Hz, 0.4H), 2.72 - 2.59 (m, 1H), 2.53- 2.40 (m, 1H), 2.36 (s. 1.8H), 2.29 (s, 1.2H), 2.03 (s, 1.8H), 1.97 (s, 1.2H), 1.18 (app d, 7 = 6.8 Hz, 3H).

Page 328 of 619

141	63-64		ESIMS m/z 315 ([M+Hf).	1H NMR (DMSOd6) δ 9.03 (d, J = 2.5 Hz, 1H), 8.55 (s, 1H), 8.47 (dd, J = 4.7, 1.3 Hz, 1H), 8.15 (ddd, J = 8.4, 2.7. 1.4 Hz, 1H), 7.56-7.44 (m, 1H). 5.84 (s, 1H), 5.14 (dd, J = 13.3, 7.4 Hz, 2H), 4.09 (d, J =5.8 Hz, 2H), 2.14(5, 3H), 1.39 (s, 9H);
142		(thin film) 1653	ESIMS m/z 357 ([M])	1H NMR (400 MHz, CDCI3) δ 8.77 (d, J= 1.9 Hz, 1H), 8.49 (d, J = 2.5 Hz, 1H), 8.03 (s, 1H), 7.86 (dt, J = 9.1, 2.4 Hz, 1H), 3.99- 3.48 (m, 2H), 2.86 (dd, J= 12.8, 9.0 Hz, 1H), 2.75- 2.60 (m, 1H), 2.47 (dd, J =12.8, 5.3 Hz, 1H), 2.03 (s, 3H), 1.57 (S, 3H), 1.20-1.13 (m, 6H).

Page 329 of 619

143

ESIMS m/z 317 ([M+H]

H NMR (400 MHz. CDCI3) δ 8.93 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 4.7, 1.3 Hz, 1H), 8.057.97 (m, 1H), 7.85 (s, 1H), 7.42 (dd, / = 8.3, 4.8 Hz, 1H), 5.86 (ddt. / = 16.6, 10.1,6.4 Hz, 1H), 5.16 (ddd,/ = 18.5, 13.6, 1.3 Hz, 2H), 4.23 (s, 2H), 2.79 (t, / = 7.3 Hz, 2H), 2.44 (t, /=7.3 Hz, 2H), 2.26 (s, 3H), 2.05 (s. 3H);

13C NMR (101 MHz, CDCI3) δ 171.57, 148.61, 147.12, 139.96, 132.81, 125.97, 125.50, 125.11, 124.02. 118.63, 52.02, 33.86, 29.83, 15.98, 11.25.

Page 330 of6!9

144

ESIMS m/z 331 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.94 (d, J= 2.5 Hz, 1H), 8.56 (dd. J = 4.7, 1.4 Hz, 1H), 8.02 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.88 (s, 1H), 7.42 (ddd, 7 = 8.3, 4.7, 0.5 Hz, 1H), 5.87 (ddt, J = 16.6, 10.2, 6.3 Hz, 1H), 5.22-5.09 (m, 2H), 4.29 (s, 2H), 2.89 (dd, J = 12.5, 9.5 Hz, 1H), 2.77 (s, 1H), 2.44 (dd, 7= 12.7, 5.0 Hz, 1H), 2.30 (s, 3H), 2.01 (s, 3H), 1.14 (d, J = 6.7 Hz, 3H)

’3CNMR(101 MHz, CDCIs) δ 175.71, 148.54, 147.75, 140.09, 136.14, 132.82,126.04 , 125.96, 125.43, 123.93, 118.41, 51.90, 18.41, 16.58, 15.19, 15.07, 11.24

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145	197- 200		ESIMS m/z 246 ([M+H]*), 244 ([M-H])	’H NMR (400 MHz. CDCI3) δ 8.94 (d, J = 2.3 Hz, 1H), 8.48- 8.37 (m, 1H), 8.32 (s, 1H), 7.94 (d, J = 8.3 Hz, 1H), 7.52 (br s, 1H), 7.41 - 7.25 (m, 1H), 5.79 (brs, 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).
146			ESIMS m/z 368 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.88 (app d, J = 2.3 Hz, 1H), 8.69- 8.60 (m, 1H), 7.96 - 7.86 (m, 1H), 7.48 - 7.39 (m, 1H), 3.18 (app s, 3H), 2.26 (app s, 3H), 1.60-1.36 (m, 9H).

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147

ESIMS m/z 337 ([M+H]*)

’H NMR (400 MHz, CDCI3) δ 8.94 (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), 7.84 (s, 1H), 7.43 (ddd, J ~ 8.3, 4.8, 0.6 Hz, 1 H), 5.85 (ddt, J = 16.7, 10.1, 6.5 Hz, 1H), 5.23-5.09 (m, 2H), 4.22 (s, 2H), 2.59 - 2.43 (m, 2H), 2.41 - 2.32 (m, 2H), 2.26 (s, 3H).

13C NMR (101 MHz, CDCI3) δ 170.38, 148.29, 147.92, 140.10, 136.04, 132.44, 126.09, 125.01, 124.93, 123.98, 118.90, 77.34, 77.02, 76.70, 52.22, 29.68, 29.39, 26.75, 11.14.

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148	82-89		ESIMS m/z 285 ([M+Hf)	'H NMR (400 MHz. CDCI3) δ 8.94 (d, J =2.5 Hz. 1H), 8.56 (dd, J = 4.7,1.3 Hz, 1 H), 8.02 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.83 (s, 1H), 7.41 (dd, J = 8.4, 4.7 Hz, 1H), 5.86 (ddt, J = 16.6, 10.1,6.4 Hz. 1H). 5.13 (ddd, J = 18.5, 13.6, 1.3 Hz, 2H). 4.20 (s, 1H), 2.59 (dt, J= 13.4, 6.7 Hz, 1H), 2.25 (s, 3H), 1.07 (d, J = 6.7 Hz, 6H).	13C NMR (101 MHz, CDCI3) δ 177.78, 148.63, 147.71, 140.03, 136.13, 136.10, 133.07, 125.92, 124.69, 123.95, 118.26, 77.33, 77.01, 76.69, 51.89, 31.16, 19.67, 11.16.
149	91-92		ESIMS m/z 333 ([M+H]*)	’H NMR (400 MHz, DMSO-c/6) δ 9.01 -8.87 (m, 1H), 8.60 (s, 1H), 8.49 (d. J = 2.4 Hz, 1H), 8.14 (dt, J = 10.4, 2.4 Hz, 1H), 5.84 (s, 1H), 5.24 - 5.08 (m. 2H), 4.08 (d, J = 5.8 Hz, 2H), 2.14 (s, 3H), 1.39 (s, 8H).

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150	195- 196		ESIMS m/z 255 ([M-f-Buf	1H NMR (400 MHz, DMSO-o/6) δ 1H NMR (400 MHz, CDCI3) Ô 8.76 (s, 1H), 8.39 (d, J = 2.5 Hz, 1H), 8.37 (s, 1H), 7.79 (dt, J =9.4, 2.3 Hz, 1H), 6.40 (s,1H), 1.54 (s, 9H).	13C NMR (101 MHz, CDCI3) δ 160.78, 158.18, 152.13, 136.90 (d, J = 15.5 Hz), 135.65 (d, J = 24.2 Hz), 134.88 (d. J = 4.0 Hz), 121.39, 117.90, 112.99, 112.76, 81.79, 28.24.
151		(thin film) 1653	ESIMS m/z 320 ([M+2]+)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J =2.0 Hz, 1H), 8.56 (d, J = 4.1 Hz, 1H), 8.02 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.97 (s, 1H), 7.42 (dd, J =8.3, 4.7 Hz, 1H), 3.24 (s, 3H), 2.94 (dq, J = 9.3,6.9 Hz, 1H), 2.61 (dq, J = 9.3, 6.8 Hz. 1H), 2.32 (s, 3H), 2.01 (s, 3H), 1.29-1.20 (m, 6H), 1.11 (d, J = 6.8 Hz, 3H).

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152		(thin film) 1652	ESIMS m/z 306 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J =2.5 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.93 (s, 1H), 7.43 (ddd, 7=8.3, 4.8, 0.6 Hz, 1H), 3.30-3.19 (m, 4H), 2.49 (dd, 7 = 15.5, 6.8 Hz, 1H), 2.32 - 2.23 (m, 4H), 2.05 (s, 3H), 1.28 (d,7 = 6.8 Hz, 3H).
153	93.0- 95.0		ESIMS m/z 313 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.4 Hz, 1H), 8.57 (d, 7 = 4.2 Hz, 1H), 8.04 (d, 7 = 8.3 Hz, 1H), 7.44 (dd, 7 = 8.3, 4.7 Hz, 1H), 3.25 (s, 3H), 2.59 - 2.42 (m, 2H), 2.42 - 2.34 (m, 2H), 2.28 (s, 3H).

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154		(thin film) 1663	ESIMS m/z 328 ([M+2f)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.5 Hz, 1H), 8.58 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.02 (ddd, 7 = 8.3, 2.5, 1.4 Hz, 1H), 7.90 (s, 1H), 7.43 (ddd, 7=8.3, 4.8, 0.4 Hz, 1H), 3.24 (s, 3H), 3.01 - 2.88 (m, 1H), 2.88-2.71 (m, 1H), 2.29 (s, 3H), 2.14-1.93 (m, 1H), 1.15 (d, 7 = 6.8 Hz, 3H).
155		(thin film) 1632	ESIMS m/z 334 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.56 (dd, 7= 4.7, 1.4 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.98 (s, 1H), 7.43 (ddd. 7 = 8.3, 4.7, 0.4 Hz, 1H), 3.65 (brs, 2H), 2.69 (s. 2H), 2.30 (s, 3H), 2.14 (s, 3H), 1.19-1.11 (m, 9H).

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156		(thin film) 1646	ESIMS m/z 334 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 9.05 - 8.94 (m, 1H). 8.56 (d, J = 4.1 Hz, 1H), 8.078.02 (m, 1H), 8.02 -7.87(m, 1H), 7.49 - 7.37 (m, 1H), 4.49-3.17 (m, 1H), 3.01 2.77 (m, 1H), 2.61 -2.39 (m, 1H), 2.35- 2.24 (m, 3H), 2.00 (s, 3H), 1.35- 1.07 (m, 9H).
157		(thin film) 1650	ESIMS m/z 320 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.98 (s, 1H), 8.57 (d, 7 = 4.2 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.93 (s, 1H), 7.44 (dd, 7= 8.3, 4.7 Hz, 1H), 3.71 (s, 2H), 3.25 (h, 7 = 6.8 Hz, 1H), 2.45 (dd, 7= 15.5, 6.6 Hz, 1H), 2.27 (s, 3H), 2.23 (dd, 7= 15.5, 7.5 Hz, 1H). 2.05 (s, 3H), 1.27 (d, 7 = 6.8 Hz, 3H). 1.16 (t, 7 = 7.1 Hz, 3H).

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158		thin film) 1658	ESIMS m/z 328 ([M+2D	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7=2.4 Hz, 1H), 8.58 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.92 (s, 1H), 7.44 (dd, 7=8.3, 4.7 Hz, 1H), 3.70 (s, 2H), 2.57- 2.41 (m, 2H), 2.40 - 2.30 (m, 2H), 2.27 (s, 3H), 1.16 (t, 7 = 7.2 Hz, 3H).
159		(thin film) 1653	ESIMS m/z 340 ([M])	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7=2.4 Hz, 1H), 8.58 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.02 (d, 7 = 7.5 Hz, 1H), 7.88 (d, 7= 16.9 Hz, 1H), 7.50-7.38 (m, 1H), 4.463.08 (m, 2H), 2.95 -2.69(m, 2H), 2.28 (s, 3H), 2.13 -1.91 (m, 1H), 1.18 -1.10 (m, 6H).

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160	90.0- 93.0		ESIMS m/z 343 ([M])	’H NMR (400 MHz, CDCI3) δ 8.78 (d, 7= 1.9 Hz, 1H), 8.50 (d, J = 2.4 Hz, 1H), 8.04 (s, 1H), 7.88 (dt. 7 = 9.1, 2.3 Hz, 1H), 3.72 (q, 7 = 7.1 Hz, 2H), 2.79 (t, 7 = 7.4 Hz, 2H), 2.44 (t, 7 = 7.4 Hz, 2H), 2.07 (s, 3H), 1.16 (t, 7 = 7.2 Hz, 3H).
161		(thin film) 1691	ESIMS m/z 341 ([M])	’H NMR (400 MHz, CDCI3) δ 8.76 (d, 7= 1.2 Hz, 1H), 8.43 (d, 7 = 2.5 Hz, 1H), 7.97 (d, 7 = 2.5 Hz, 1H), 7.85 (d, 7 = 9.3 Hz, 1H), 3.61 (q, 7=7.1 Hz, 2H), 1.45 (s, 9H), 1.17 (t, 7 = 7.1 Hz, 3H).

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162	109.0 112.0		ESIMS m/z 327 ([M])	’H NMR (400 MHz, CDCI3) δ 8.72 (d, J= 1.8 Hz, 1H), 8.43 (d, J = 2.4 Hz, 1H), 7.93 (s, 1H), 7.82 (dt, J = 9.2, 2.1 Hz, 1H), 3.23 (s, 3H), 1.46 (s, 9H).
163	158.0 160.0		ESIMS m/z 311 ([M])	’H NMR (400 MHz, CDCI3) δ 8.77 (d, J= 1.5 Hz, 1H), 8.49 (d, J = 2.4 Hz, 1H), 7.96 (s, 1H), 7.87 (dt, J= 9.1, 2.3 Hz, 1H), 3.70 (s, 2H), 2.51 (hept, J = 6.7 Hz, 1H), 1.15(1, J = 7.2 Hz, 3H), 1.08 (d, J = 6.7 Hz, 6H).

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164	109.5 112.5		ESIMS m/z 357 ([M])	1H NMR (400 MHz. CDCI3) δ 8.77 (d. J= 1.9 Hz. 1H), 8.49 (d. J = 2.5 Hz, 1H), 7.99 (s, 1H), 7.87 (dt, 7 = 9.1,2.3 Hz, 1H), 3.85- 3.57 (m, 2H), 3.34 -3.15(m, 1H), 2.46 (dd, 7= 15.6, 6.4 Hz, 1H), 2.25 (dd, 7= 15.6, 7.7 Hz, 1H), 2.07 (s, 3H), 1.28 (d, 7 = 6.8 Hz, 3H), 1.17 (t, 7= 7.2 Hz, 3H).
165	125.0 127.0		ESIMS m/z 303 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.56 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 8.01 (S, 1H), 7.43 (ddd, 7 = 8.3, 4.8, 0.5 Hz, 1H), 3.24 (s, 3H), 2.54 - 2.45 (m, 1H), 2.32 (s. 3H), 2.10 (s, 3H), 1.81 1.69 (m, 1H), 1.58 -1.47 (m, 1 H), 1.04-0.93 (m, 1H).

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166		(thin film) 1642	ESIMS m/z 318 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.99 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 4.7, 1.3 Hz, 1H), 8.07 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 8.00 (s, 1H), 7.44 (ddd, J = 8.3, 4.8, 0.4 Hz, 1H), 3.85- 3.53 (m, 2H), 2.52 - 2.42 (m, 1H), 2.31 (s, 3H), 2.10 (s, 3H), 1.73- 1.63 (m, 1H), 1.56-1.45 (m, 1H), 1.14 (t, J = 7.1 Hz, 3H), 1.02-0.90 (m, 1H).
167		(thin film) 1646	ESIMS m/z 355 ([M])

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168		(thin film) 1663		’H NMR (400 MHz, CDCI3) δ 8.79 (d, J = 2.0 Hz, 1 H), 8.50 (d, J = 2.5 Hz, 1H), 8.02 (s, 1H), 7.89 (dt, J = 9.1, 2.4 Hz, 1 H), 3.72 (q, J = 7.1 Hz, 2H), 2.59 - 2.43 (m, 2H), 2.42 - 2.34 (m, 2H), 1.17 (t, J = 7.2 Hz, 3H).
169	140- 143		ESIMS m/z 274 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.56 (s, 1H), 8.03 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.90 (s, 1H), 7.42 (dd, J = 8.2, 4.7 Hz, 1H), 4.37 (s, 1H), 3.66 (q. J = 7.1 Hz, 2H), 3.24 (qd, J = 7.2, 5.7 Hz, 2H), 2.26 (s, 3H), 1.13 (t, J=7.1 Hz, 3H), 1.07 (t, J= 7.2 Hz, 3H).

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170	138- 140		ESIMS m/z 288 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J =2.4 Hz, 1H), 8.56 (dd, J = 4.7, 1.4 Hz, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.89 (s, 1H), 7.42 (ddd, J = 8.3, 4.7, 0.6 Hz, 1H), 4.41 (t, J = 5.4 Hz, 1H), 3.66 (q, J = 7.1 Hz, 2H), 3.203.10 (m, 2H), 2.26 (s, 3H), 1.47 (tq, J = 14.6, 7.2 Hz, 2H), 1.13 (t. J = 7.1 Hz, 3H), 0.85 (t, J =7.4 Hz, 3H).
171	193- 195		ESIMS m/z 260 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.5 Hz, 1H), 8.50 (dd, J = 4.7, 1.3 Hz, 1H). 8.12 (s, 1H), 7.96 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7,37 (ddd, J =8.4, 4.8, 0.6 Hz, 1 H), 6.08 (s, 1H), 4.86 (t, J =5.4 Hz, 1H), 3.23 (dd, J = 7.0, 1.1 Hz, 2H), 2.28 (s, 3H), 1.601.47 (m, 2H), 0.93 (t, J =7.4 Hz, 3H).

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172	140- 143		ESIMS m/z 295 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (bs, 1H), 8.53 (d, J- 4.2 Hz, 1H), 8.36 (bs, 1H), 8.04-7.90 (m, 1H), 7.38 (dd, 7 = 8.3,4.7 Hz. 1 H), 6.45 (s, 1H), 1.54 (s, 9H).
173	129.0 130.5		ESIMS m/z 297 ([M])	’H NMR (400 MHz, CDCI3) δ 8.77 (s, 1H), 8.49 (d, 7=2.1 Hz, 1H), 8.01 (s, 1H), 7.87 (dt, 7=9.1, 2.2 Hz, 1H), 3.22 (s, 3H), 2.60 (hept, J = 6.6 Hz, 1H), 1.09 (d,7 = 6.7 Hz, 6H).
174		(thin film) 1658	ESIMS m/z 329 ([M])	’H NMR (400 MHz, CDCI3) δ 8.77 (d,7=2.0 Hz, 1H), 8.49 (d, 7 = 2.4 Hz, 1H), 8.08 (s, 1H), 7.88 (dt, 7= 9.1, 2.4 Hz, 1H), 3.25 (s, 3H), 2.80 (t, 7 = 7.3 Hz, 2H), 2.48 (t, 7 = 7.3 Hz, 2H), 2.07 (s, 3H).

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175	89.5- 92.0		ESIMS m/z 343 ([MJ)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, J =1.8 Hz, 1H), 8.49 (d, J = 2.4 Hz, 1H). 8.07 (s, 1H), 7.85 (dt, J = 9.1,2.3 Hz, 1H), 3.26 (s, 3H), 2.87 (dd, J = 12.6, 9.1 Hz, 1H), 2.81 - 2.68 (m, 1H), 2.48 (dd, J = 12.6, 5.2 Hz. 1H), 2.03 (s, 3H), 1.16 (d, J = 6.7 Hz, 3H).
176		(thin film) 1646	ESIMS m/z 341 ([M])	1H NMR (400 MHz, CDCI3) δ 8.79 (d, J= 1.5 Hz, 1H), 8.49 (d, J = 2.4 Hz, 1H), 8.10 (s. 1H), 7.89 (dt, J = 9.1,2.3 Hz, 1H), 3.25 (s, 3H), 2.56 - 2.44 (m, 1H), 2.13 (s, 3H), 1.73-1.59 (m, 1H), 1.61 - 1.49 (m, 1H), 1.07 -0.95(m, 1H).

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177	85.5- 87.5		ESIMS m/z 343 ([M])	1H NMR (400 MHz, CDCI3) δ 8.77 (d, J = 2.0 Hz, 1 H), 8.49 (d, J = 2.5 Hz, 1H), 8.07 (S, 1H), 7.87 (dt, J = 9.1, 2.3 Hz, 1H), 3.31 - 3.18 (m,4H), 2.51 (dd, J= 15.6, 6.5 Hz, 1H), 2.29 (dd, J = 15.6, 7.6 Hz, 1H), 2.07 (s, 3H), 1.29 (d, J = 6.8 Hz, 3H).
178		(thin film )1666	ESIMS m/z 351 ([M])	1H NMR (400 MHz, CDCI3) δ 8.78 (d, J = 2.0 Hz, 1H), 8.50 (d, J = 2.5 Hz, 1H), 8.06 (s, 1H), 7.88 (dt, J = 9.1,2.4 Hz, 1H), 3.26 (s, 3H), 2.58-2.37 (m, 4H).

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179	107.0 108.5		ESIMS m/z 367 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J-2.0 Hz, 1H), 8.50 (d, J = 2.4 Hz, 1H), 7.96 (s, 1H), 7.84 (dt, J = 9.0, 2.3 Hz, 1H), 3.25 (s, 3H), 2,93 - 2.67 (m, 2H), 2.12- 1.94 (m, 1H), 1.19 (d, 7 = 6.8 Hz, 3H).
180	132.0 135.0		ESIMS m/z 379 ([M])	’H NMR (400 MHz, CDCI3) δ 8.76 (d, 7 = 2.0 Hz. 1H), 8.50 (d, 7 = 2.5 Hz, 1H), 7.93 (s, 1H). 7.89 - 7.80 (m, 1H), 4.08 - 3.30 (m, 2H), 2.86 - 2.65 (m, 2H), 2.12 - 1.93 (m, 1H), 1.19 (d, 7 = 6.4 Hz, 3H), 1.16 (t, 7 = 7.2 Hz, 3H).

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181

(thin film) 1654

ESIMS m/z 357 ([M])

1H NMR (400 MHz, CDCI3) δ 8.77 (d, J= 1.9 Hz, 0.66H), 8.76 (d, J= 1.9 Hz, 0.33H), 8.50 (d, J = 2.7 Hz, 0.33H), 8.49 (d,/ = 2.5 Hz, 0.66H), 8.11 (s, 0.66H), 8.00 (S, 0.33H), 7.92 7.81 (m, 1H), 3.26 (s, 2H), 3.25 (s, 1H), 3.03-2.79 (m, 1H), 2.66- 2.40 (m, 1H), 2.04 (s, 2H), 2.02 (s. 1H), 1.31 (d, J = 6.7 Hz, 1H), 1.28 (d, / = 6.8 Hz, 1H), 1.24 (d, J = 6.9 Hz, 2H), 1.15 (d, / = 6.8 Hz, 2H).

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182

(thin film) 1633

ESIMS m/z 371 ([M])

1H NMR (400 MHz, CDCI3) δ 8.79 (d, 7=2.0 Hz, 0.66H), 8.77 (d, 7 = 2.0 Hz, 0.33H), 8.50 (d, J = 2.6 Hz, 0.33H), 8.49 (d, 7 = 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), 2.59-2.33 (m, 1H), 2.04 (s, 2H), 2.02 (s, 1H), 1.32 (d, 7 = 6.7 Hz, 1H), 1.27 (d, 7 = 6.2 Hz, 1H), 1.23 (d, 7 = 6.9 Hz, 2H), 1.18- 1.12 (m, 5H).

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183			ESIMS m/z 323 ([M])	’H NMR (400 MHz, CDCI3) δ 8.73 (d, J = 2.0 Hz, 1H), 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, 1H), 5.93-5.76 (m, 1H), 3.73 (q, J = 7.1 Hz, 2H), 1.72 (s, 3H), 1.58 (dd, J = 6.9, 0.9 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H).
184			ESIMS m/z 335 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.77 - 8.70 (m, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.86 (s, 1H), 7.84 (dt, J = 8,2.4 Hz, 1H), 5.86 (ddt, J = 16.6, 10.2, 6.4 Hz, 1H), 5.18 (dd, J = 10.1, 1.2 Hz, 1H), 5.13(dd, J = 17.1, 1.4 Hz, 1H), 4.22 (s, 2H), 2.79 (t, J = 7.3 Hz, 2H), 2.42 (t, J =7.3 Hz, 2H), 2.26 (s, 3H), 2.06 (s, 3H).	’3C NMR (101 MHz, CDCI3) δ 171.63, 149.08, 146.12, 136.99, 136.01, 135.78, 135.15, 135.11, 132.63,125.92 , 125.30, 118.74, 113.49, 113.26, 51.95, 33.84, 29.78, 15.99, 11.24

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185	65-66		ESIMS m/z 349 ([M+Hf)	’H NMR (400 MHz. CDCI3) δ 8.74 (d, J = 1.7 Hz, 1H), 8.42 (d, J = 2.5 Hz, IH), 7.89 (s, 1H), 7.84 (dt, 7 = 9.4, 2.3 Hz, 1H), 5.86 (ddt, 7= 16.6, 10.2, 6.3 Hz, 1H), 5.23- 5.09 (m, 2H), 2.87 (dt, 7 = 13.0, 9.0 Hz, 1H), 2.77- 2.64 (m, 1H), 2.44 (dd, 7 = 12.8, 4.9 Hz, 1H), 2.30 (s, 3H), 2.01 (s, 3H), 1.13(d, 7 = 6.7 Hz, 3H).
186	120- 121		ESIMS m/z 303 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.74 (s, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 7.84 (s, 1H), 7.83 (dt, 7 = 8, 2.3 Hz,1H), 5.85 (ddt, 7= 16.6, 10.1,6.4 Hz, 1H), 5.17 (d, J = 10.1 Hz, 1H), 5.10 (dd, J = 17.1, 1.4 Hz, 1H), 4.20(s, 1H), 2.56 (dt, 7= 13.5, 6.7 Hz, 1H), 2.25 (s, 3H), 1.07 (d, 7 = 6.7 Hz, 6H).

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187	105- 109	(IR thin film) 1655	ESIMS m/z 359 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J= 1.8 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.85 (bs, 2H), 3.21 (s, 2H), 2.80 (s, 2H), 2.25 (d, J = 20.5 Hz, 3H), 2.00 (dd, J = 13.7, 8.6 Hz, 1H), 1.22- 1.00 (m, 6H).
188		(thin film) 1651	ESIMS m/z 345 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.74 (t, J= 11.5 Hz, 1H), 8.42 (t, J = 12.9 Hz. 1H), 8.03-7.75 (m, 2H), 3.69 (s, 2H), 2.62-2.39 (m, 2H), 2.31 (dd. J = 16.0, 8.7 Hz, 2H), 2.26 (s, 3H), 1.15 (t. 7 = 7.2 Hz, 3H).

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189		(thin film) 1618	ESIMS m/z 351 ([M+H]+)	’H NMR (400 MHz, CDCI3) δ 8.75 (d, 7=1.7 Hz, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 7.97 (s, 1H), 7.90 -7.76(m, 1H), 2.89 (d, 7=5.4 Hz. 2H), 2.68 (s, 2H), 2.26 (d, 7 = 22.4 Hz. 3H), 2.14 (d,7 = 4.9 Hz, 3H), 1.24-1.01 (m, 9H).
190		(thin film) 1640	ESIMS m/z 335 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.77 (d, 7= 1.6 Hz. 1H), 8.43 (d, 7 = 2.5 Hz, 1H), 7.91 (d, 7= 19.7 Hz, 1H), 7.87 (dt, 7 = 9.4, 2.4 Hz, 1H), 3.70 (s, 2H), 2.55-2.37 (m, 1H), 2.30 (s, 3H), 2.10 (s, 3H), 1.64 (ddd, 7 = 8.6, 5.2, 3.6 Hz, 1H), 1.54 - 1.48 (m, 1H). 1.14 (t, 7=7.2 Hz, 3H), 1.01 -0.89(m, 1H).

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191		(thin film) 1649	ESIMS m/z 323 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.73 (t, J = 9.3 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.91 (s, 1H), 7.85 (dt, J = 9.4, 2.4 Hz, 1H), 3.28-3.11 (m, 4H), 2.47 (dd, J = 15.5, 6.9 Hz, 1H), 2.31 -2.19(m, 4H), 2.06 (s, 3H), 1.28 (d, J = 6.8 Hz, 3H).
192		(thin film) 1642	ESIMS m/z 337 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, J= 1.7 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.88 (d, J = 3.3 Hz, 1H), 7.877.82 (m, 1H), 3.69 (bs, 2H), 3.25 (h, J = 6.8 Hz, 1H), 2.42 (dd, J - 15.5, 6.8 Hz, 1H), 2.26 (s, 3H), 2.242.17 (m, 1H), 2.06 (s, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H).

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193	88- 100		ESIMS m/z 345 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8,74 (d, 7=1.8 Hz, 1H), 8.44 (d, 7 = 2.5 Hz, 1H), 7.88 (s, 1H), 7.83 (dt, J = 9.3, 2.3 Hz, 1H), 3.23 (s, 3H), 2.96 - 2.69 (m, 2H), 2.25 (d, 7 = 21.3 Hz. 3H), 2.10-1.92 (m. 1H), 1.17 (dd, 7 = 13.7, 7.0 Hz, 3H),
194	91-95		ESIMS m/z 331 ((M+H]+)	ηΗ NMR (400 MHz, CDCI3) δ 8.75 (d,7= 1.7 Hz, 1H), 8.44 (d, 7 = 2.5 Hz, 1H), 7.91 (s, 1H), 7.85 (dt, 7 = 9.3. 2.4 Hz, 1 H), 3.24 (s, 3H). 2.56-2.40 (m, 2H), 2.39- 2.32 (m, 2H), 2.27 (s, 3H).

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195	113- 120		ESIMS m/z 321 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, J= 1.7 Hz, 1H), 8.43 (d, 7 = 2.5 Hz, 1H), 7.96 (s, 1H), 7.86 (dt, 7=9.4, 2.3 Hz, 1H), 3.23 (s, 3H), 2.48 (ddd, 7 = 8.1, 5.5, 3.6 Hz, 1H), 2.31 (s, 3H), 2.10 (s, 3H), 1.70 (ddd, 7 = 8.6, 5.2, 3.6 Hz, 1H), 1.55 -1.49(m, 1H), 0.97 (ddd, 7 = 8.5, 5.5. 4.3 Hz, 1H).
196	147- 149		ESIMS m/z 264 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.90 (d, 7 = 2.3 Hz, 1H), 8.65 (dt, 7 = 28.7, 14.3 Hz, 1H), 8.34 (s, 1H), 7.93 (ddd, 7=8.2, 2.6, 1.5 Hz. 1H), 7.60-7.33 (m, 1H), 6.96 (d, 7 = 28.5 Hz, 1H), 2.60 (hept, 7 = 6.9 Hz, 1H), 1.30 (d, 7 = 6.9 Hz, 6H).

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197	101- 105		ESIMS m/z 311 ([M+H]4)	’H NMR (400 MHz, CDCI3) δ 8.90 (d, J =2.3 Hz, 1H), 8.65 (dt. J = 28.9, 14.4 Hz, 1H), 8.34 (s, 1H), 7.94 (ddd, J = 8.2, 2.5, 1.5 Hz. 1H), 7.64-7.34 (m, 2H), 3.00 - 2.76 (m, 1H), 2.732.58 (m, 2H), 2.18 (s, 3H), 1.32 (t, J = 22.1 Hz, 3H).
198	105- 116		ESIMS m/z 297 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.90 (d, J =2.3 Hz, 1H), 8.64 (dt, J = 39.7, 19.8 Hz, 1H), 8.42-8.16 (m. 1H), 7.93 (ddd, J =8.2, 2.5, 1.5 Hz, 1H), 7.62 (s, 1H), 7.47 (ddd, J = 13.7, 11.3, 5.2 Hz, 1H), 2.91 (t, J = 6.8 Hz, 2H), 2.73 (t, J = 6.9 Hz, 2H), 2.27 - 2.07 (m, 3H).

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199	79-84		ESIMS m/z 323 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.92 (d, 7 = 2.5 Hz, 1H), 8.68- 8.50 (m, 1H), 8.02 (d, 7 = 7.6 Hz, 1H), 7.88 (bs, 1H), 7.42 (dd, 7 = 8.2, 4.6 Hz, 1H), 3.61 (q. 7=7.1 Hz, 2H), 1,44 (s, 9H), 1.17 (t, 7 = 7.1 Hz, 3H).
200		(thin film) 1693	ESIMS m/z 309 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 2.5 Hz, 1H), 8.64- 8.48 (m, 1H), 8.01 (d, 7= 7.5 Hz, 1H), 7.90 (s, 1H), 7.41 (dd, 7 = 8.3, 4.8 Hz, 1H), 3.23 (s, 3H), 1.58- 1.25 (m, 9H).

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201		(thin film) 1663	ESIMS m/z 325 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.90 (d, J =2.1 Hz, 1H). 8.64 (dd, J= 17.1, 16.2 Hz, 1H), 8.34 (d, J = 3.6 Hz, 1H), 8.01 - 7.88 (m, 1H), 7.85 (s, 1H), 7.46 (ddd, J = 8.2, 4.8, 0.5 Hz, 1H), 2.91 - 2.75 (m, 2H), 2.16 (d, J= 15.0 Hz, 3H), 1.52-1.31 (m, 6H).
202		(thin film) 1651,	ESIMS m/z 293 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.4 Hz, 1H), 8.62 (d, J = 4.7 Hz, 1H), 8.05 (ddd, J =8.4, 2.6, 1.4 Hz, 1H), 7.94 (s, 1H), 7.55 -7.35 (m, 1H), 3.70 (bs, 2H), 2.53 (dt, J= 13.4, 6.7 Hz, 1H), 1.15 (t, J = 7.2 Hz, 3H), 1.08 (d, J = 6.7 Hz, 6H).

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203		(thin film) 1649	ESIMS m/z 339 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.3 Hz, 1H), 8.63 (d, J = 3.8 Hz, 1H), 8.05 (ddd, J =8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.57 - 7.37 (m, 1H), 3.72 (dt, J =13.9, 6.6 Hz, 2H), 3.40- 3.14 (m, 1H), 2.48 (dd, J = 15.6,6.3 Hz, 1H), 2.26 (dd, J = 15.6, 7.7 Hz, 1H), 2.06 (s, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H).
204		(IR thin film) 1651	ESIMS m/z 353 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.03 - 8.80 (m, 1H), 8.56 (d. J = 60.5 Hz, 1H), 8.12 - 7.73 (m, 2H), 7.44 (dt, J = 30.2, 15.2 Hz, 1H), 3.96 -3.43(m, 2H), 2.90 (dt, J = 54.3, 23.6 Hz, 1H), 2.46 (dd, J= 38.2, 29.0 Hz, 1H), 2.02 (d, J = 4.1 Hz, 2H), 1.72 (s, 1H), 1.35 - 1.10 (m, 9H).

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205		(thin film) 1646	ESIMS m/z 337[M+H]+)	’H NMR (400 MHz, CDCI3) δ 9.00 (bs, 1H), 8.66 (bs, 1H), 8.05 (t, J= 13.3 Hz, 1H), 8.00 (s, 1H), 7.46 (t, J = 28.3 Hz, 1H), 3.84 - 3.49 (m, 2H), 2.66-2.38 (m, 1H), 2.12 (s, 3H), 1.71 -1.43 (m, 2H). 1.15 (t, J = 7.2 Hz, 3H), 1.05- 0.92 (m, 1H).
206		(thin film) 1663	ESIMS m/z 347 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.64 (d, J = 4.2 Hz, 1H). 8.06 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.55- 7.38 (m, 1H), 3.72 (q, J = 7.2 Hz, 2H), 2.60 2.43 (m, 2H), 2.43 -2.30 (m, 2H), 1.17 (t, J = 7.2 Hz, 3H).

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207	98- 108		ESIMS m/z 361 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7=2.6 Hz, 1H), 8.64 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.01 (dd, 7 = 8.7 Hz, 1H), 7.89 (s, 1H), 7.527.38 (m, 1H), 3.60 (bs, 2H), 2.902.58 (m, 2H), 2.00 m, 1H), 1.26 - 1.05 (m,6H).
208	112- 120		ESIMS m/z 279 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.4 Hz, 1H), 8.62 (d, 7 = 4.0 Hz, 1H), 8.04 (d, 7= 7.2 Hz, 1H), 7.96 (s, 1H), 7.46 (dd, 7 = 8.3, 4.8 Hz, 1H). 3.23 (s, 3H), 2.62 (dt, 7= 13.4,6.7 Hz, 1H), 1.09 (d, 7 = 6.7 Hz, 6H).

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209		(thin film) 1655	ESIMS m/z 325 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.6 Hz, 1H), 8.61 (dt, 7=34.2, 17.1 Hz, 1H), 8.28-7.77 (m, 2H), 7.64- 7.35 (m, 1H), 3.27 (s, 3H), 2.87 (dd, 7= 12.5, 9.0 Hz, 1H), 2.81 -2.67 (m, 1H), 2.46 (dt, 7=42.8, 21.4 Hz, 1H), 2.04 (s, 7 = 8.9 Hz, 3H), 1.17 (d, 7 = 6.7 Hz, 3H).
210		(thin film) 1660	ESIMS m/z 311 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.5 Hz, 1H), 8.63 (dd, 7=4.8, 1.3 Hz, 1H), 8.12-8.00 (m, 1H), 7.99 (s, 1 H), 7.46 (dd, J = 7.9, 4.8 Hz, 1H), 3.25 (s, 3H), 2.80 (t, 7 = 7.4 Hz, 2H), 2.48 (t, J = 7.4 Hz, 2H), 2.07 (s, 3H).

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211		(thin film) 1657	ESIMS m/z 325 ([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 = 8.3, 2.7, 1.4 Hz, 1 H), 7.99 (s, 1H), 7.66 - 7.38 (m, 1H), 3.31-3.30 (m, 4H), 2.52 (dd, J = 15.6, 6.4 Hz, 1H), 2.30 (dd, J= 15.6, 7.7 Hz, 1H), 2.06 (s, 3H), 1.27 (d, J = 16.2, 7.0 Hz, 3H).
212		(thin film) 1649	ESIMS m/z 339 ([M+H]*	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.3 Hz, 1H), 8.63 (d, J = 3.8 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H). 7.57 -7.37 (m, 1H), 3.72 (dt, J= 13.9, 6.6 Hz, 2H), 3.40 - 3.14 (m, 1H), 2.48 (dd, J= 15.6, 6.3 Hz, 1 H), 2.26 (dd, J= 15.6, 7.7 Hz, 1H), 2.06 (s, 3H), 1.29 (d, J = 6.8 Hz, 3H), 1.17 (t. J = 7.2 Hz, 3H).

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213		(thin film) 1651	ESIMS m/z 323 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7=2.6 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.06 (ddd, 7 = 8.4, 2.7, 1.4 Hz. 1H), 8.03 (s, 1H), 7.47 (dd, 7 = 8.1, 4.6 Hz, 1H), 3.25 (s, 3H), 2.582.40 (m, 1H), 2.13 (s, 3H), 1.69 (ddd, 7= 8.6, 5.2, 3.6 Hz, 1H), 1.60- 1.48 (m,1H), 1.00 (ddd, 7 = 27.8, 17.7, 13.9 Hz, 1H).
214		(thin film) 1661	ESIMS m/z 348 ([M+2Hf,	1H NMR (400 MHz, CDCI3) δ 8.92 (t, 7 = 13.0 Hz, 1H), 8.80- 8.58 (m, 1H), 8.02 (ddd. 7 = 8.3, 2.6, 1.3 Hz, 1H), 7.94 (s, 1H), 7.51 - 7.39 (m. 1H), 3.27 (d, 7= 12.6 Hz, 3H), 2.98-2.59 (m, 2H), 2.22 - 1.92 (m, 1H), 1.19 (d, 7 = 6.8 Hz, 3H).

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215

(IR thin film) 1641

ESIMS m/z 363 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.57 (bs, 1H), 8.19 (t, J= 13.5 Hz, 1H), 7.80 (s, 1H), 7.65 (ddd, J = 17.4, 9.8, 2.7 Hz, 1H), 3.69-2.99 (m, 2H), 2.82-2.38 (m, 2H), 2.21 (dt, 7=15.9, 7.9 Hz, 1H), 2.20-2.03 (m, 3H), 1.80 (t, J = 17.1 Hz, 3H), 0.98-0.83 (m, 3H), 0.85-0.68 (m, 1H), 0.39-0.17 (m, 2H), 0.09-0.10 (m, 2H).

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216

95- 103

ESIMS m/z 351 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.78 (bs, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.91-7.79 (m, 2H), 5.06 (tt, J = 13.4,6.7 Hz, 1H), 2.97 (dd, J = 12.5, 8.1 Hz, 0.5H), 2.79 (dd, J = 12.6, 9.8 Hz, 0.5H), 2.68-2.55 (m, 0.5H), 2.522.35 (m, 1.5H), 2.34 (s, 1.2H), 2.26 (s, 1.8H), 2.06 (s, 1.3H), 1.93 (s, 1.7H), 1.22-1.09 (m, 6H), 1.10-0.95 (m, 3H).

Page 369 of 619

217		(IRthinfilm) 1648	ESIMS m/z 351 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.76 (d, J= 1.7 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.93 (s, 1H), 7.85 (dt, 7=9.4, 2.3 Hz, 1H). 3.97-3.14 (m, 2H), 2.88 (dd, 7= 12.3, 9.8 Hz, 1H), 2.71 (s, 1H), 2.43 (dd, 7= 12.8 4.9 Hz, 1H), 2.30 (s, 3H), 2.01 (s, 3H), 1.64-1.48 (m, 2H), 1.16-1.08 (m, 3H), 0.98-0.86 (m, 3H).
218		(thin film) 1648	ESIMS m/z 353 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.88-8.77 (m, 1H), 8.44-8.38 (m, 1H), 8.208.05 (m, 1H), 7.90 -7.80 (m, 1H), 4.53-3.31 (m, 2H), 3.30-3.05 (m, 2H), 2.76 2.53 (m, 4H), 2.36 -2.26 (m, 3H), 1.24-1.12 (m, 6H).

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219		(thin film) 1654	ESIMS m/z 369 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.82 (s, 1H), 8.42 (d, J = 2.4 Hz, 1H), 8.14 (s, 1H), 7.88-7.81 (m, 1H), 4.13 (s, 0.5H), 3.84 (dd, J = 13.7, 10.7 Hz, 1H), 3.29 (s, 1.5H), 3.01-2.92 (m, 4H), 2.88 (dd, 7= 13.7, 2.7 Hz, 1H), 2.32 (s, 3H), 1.21 - 1.10 (m, 6H).
220		(thin film) 1652	ESIMS m/z 359 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.77 (d, 7= 1.7 Hz, 1H), 8.43 (d,7 = 2.4 Hz, 1H), 7.90 (s, 1H), 7.86 (dt, 7= 9.4, 2.4 Hz, 1H), 3.68 (d, 7 = 5.9 Hz, 2H), 2.26 (s, 3H), 2.23 - 2.05 (m, 4H), 1.92- 1.82 (m, 2H), 1.15 (t, 7 = 7.2 Hz, 3H).

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221

108- 111

ESIMS m/z 286 ([M+H]*)

’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 4.7, 1.4 Hz, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.91 (s, 1H), 7.42 (ddd, J = 8.4. 4.8, 0.6 Hz, 1H), 5.82 (ddt, J = 17.1, 10.2, 5.6 Hz, 1H), 5.14-4.97 (m, 2H), 4.49 (t. J = 5.5 Hz, 1H), 3.83 (tt, J= 5.7, 1.5 Hz. 2H), 3.67 (q, J =7.1 Hz, 2H), 2.27 (s, 3H), 1.14 (t, J = 7.1 Hz, 3H).

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222	188- 192		ESIMS m/z 258 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.92 (d, 7 = 2.5 Hz, 1H), 8.48 (dd, 7 = 4.7, 1.4 Hz, 1H). 8.14 (s, 1H), 7.94 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.35 (ddd, 7 = 8.3, 47,0.5 Hz, 1H), 6.53 (s, 1H), 5.93 - 5.79 (m, 1H), 5.26 - 5.02 (m, 3H), 3.89 (tt, 7 = 5.8, 1.5 Hz, 2H), 2.26 (s, 3H).
223	184- 185		ESIMS m/z 301 ([M+f-Bu+Hf	1H NMR (400 MHz, CDCI3) δ 8.77 (d, 7= 1.9 Hz, 1H), 8.44 (t, 7 = 4.4 Hz, 1H), 8.03 (s, 1H), 7.87 (dt, 7= 9.3, 2.4 Hz, 1H), 4.44 (s,2H), 2.56-2.42 (m, 3H), 2.36 (dd, 7 = 127, 5.5 Hz, 2H), 2.30 (s, 3H), 2.27 (s,1H).

Page 373 of 619 <Z^

224			ESIMS m/z 360 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.95 (d. J =2.2 Hz, 1H), 8.58 (d, J = 3.9 Hz, 1H), 8.03 (ddd, J =8.3, 2.6, 1.4 Hz, 1H), 7.90 (s, 1H), 7.43 (dd, J = 8.1, 4.6 Hz, 1H), 3.77 (dqd, J= 17.2, 8.6, 3.7 Hz, 1H), 3.28 (s, 3H), 2.56 (dd, J= 16.3, 3.7 Hz, 1H), 2.44 (dd, J= 16.3, 10.0 Hz, 1H), 2.29 (s. 3H), 2.28 (s, 3H).
225		(thin film) 1669	ESIMS m/z 360 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.4 Hz, 1H), 8.59 (dd, J =4.7, 1.2 Hz, 1H), 8.09-7.84 (m, 2H), 7.44 (ddd, J =8.3, 4.8, 0.6 Hz, 1H), 3.683.52 (m, 1H), 3.31 (s, 3H), 3.18 (t, J = 12.4 Hz, 1H), 2.87 - 2.67 (m, 1H), 2.34 (s, 3H), 2.08 (s, 3H).

Page 374 of 619

226	99- 101		ESIMS m/z 289 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.93 (d, J= 2.2 Hz, 1H), 8.58 (d, J = 3.9 Hz, 1H), 8.02 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.86 (s, 1H), 7.44 (dd, 7 = 8.4, 4.7 Hz, 1H), 4.16 (p, J = 9.1 Hz, 1H), 3.71 (t, 7 = 9.2 Hz, 2H), 3.20 (s, 3H), 2.76 (dd, 7= 13.3, 5.0 Hz, 2H), 2.25 (s, 3H).	13CNMR(101 MHz, CDCI3) δ 172.48, 148.05, 147.99, 140.07, 136.00, 126.24, 126.12, 124.45, 124.03, 42.15, 37.41, 27.83, 11.04.
227	105- 107		ESIMS m/z 381 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J =2.5 Hz, 1H), 8.59 (dd, J =4.7, 1.2 Hz, 1H), 8.04 (ddd, J =8.3, 2.6, 1.4 Hz, 1H), 7.92 (s, 1H), 7.44 (ddd, J =8.3, 4.8, 0.6 Hz, 1H), 4.163.94 (m, 1H), 3.27 (s, 3H), 2.55 (d. J =5.7 Hz, 2H), 2.27 (s, 3H).

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228		(thin film) 1664	ESIMS m/z 429 ([M+HD	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J =2.5 Hz. 1H), 8.58 (dd, J =4.7, 1.4 Hz, 1H), 8.03 (ddd, J =8.3, 2.7, 1.5 Hz, 1H), 7.89 (s, 1H), 7.43 (ddd, J =8.3, 4.8, 0.6 Hz, 1H), 3.24 (s, 3H), 2.64 - 2.48 (m, 2H), 2.39 (dd, J =9.2, 6.4 Hz, 2H), 2.27 (s, 3H).
229			ESIMS m/z 413 ([M+Hf),	’H NMR (400 MHz, CDCI3) δ 8.94 (d, J =2.5 Hz, 1H), 8.58 (dd, J =4.7, 1.3 Hz, 1H), 8.03 (ddd, 7=8.3, 2.7, 1.5 Hz, 1H), 7.89 (s, 1H), 7.43 (ddd, 7=8.3, 4.8, 0.6 Hz, 1H), 3.24 (s, 3H), 2.60- 2.45 (m, 2H), 2.40 (dd, 7=9.8, 5.7 Hz, 2H), 2.26 (s, 3H).

230			ESIMS m/z 277 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.92 (d, J =2.5 Hz, 1H), 8.53 (dd, J =4.7, 1.2 Hz, 1H), 8.01 (ddd, J =8.3, 2.6, 1.5 Hz, 1H), 7.86 (s, 1H), 7.39 (dd, J =8.3, 4.6 Hz, 1H), 3.24 (s, 3H), 2.27 (s, 3H), 1.56 (d, 7=21.3 Hz, 6H).
231			ESIMS m/z 355 ([M+H]*).	’H NMR (400 MHz, CDCI3) δ 8.85 (s, 1H), 8.57 (dd, 7=4.7,1.1 Hz, 1H), 7.91 (d, 7 =7.2 Hz, 1H), 7.52 -7.31 (m, 2H), 7.25-7.14 (m, 2H), 7.03-6.90 (m, 2H), 3.67 (d, J =5.7 Hz, 1H), 3.19 (s, 3H), 1.98 (s, 3H), 1.39 (d, 7 =7.0 Hz, 3H).	13CNMR(101 MHz, CDCI3) δ 174.28, 148.35, 147.80, 140.47, 139.98, 136.03, 132.72, 128.79, 128.69, 126.86, 125.85, 124.88, 123.98, 42.93, 37.51, 20.46, 10.69.

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232	57-59		ESIMS m/z 391 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.87 (d, J =2.5 Hz, 1H), 8.57 (dd, J =4.7, 1.3 Hz, 1H), 7.97 (ddd, J =8.3, 2.7, 1.5 Hz. 1H), 7.68 (s, 1H), 7.42 (ddd, J =8.3. 4.8, 0.6 Hz, 1H), 7.28 (t, J =7.9 Hz, 1H), 7.09 (dd, J =8.3, 1.1 Hz, 1H), 7.03 (d, J =7.7 Hz, 1H), 6.96 (s, 1H), 3.57 (s, 2H), 3.23 (s. 3H), 2.14 (s, 3H).
233	179- 181		ESIMS m/z 365 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.89 (d, J =2.5 Hz, 1H), 8.55 (dd, J =4.7, 1.4 Hz, 1 H), 7.95 (d, J =8.0 Hz, 1H), 7.83 (s, 1H). 7.40 (ddd, J =8.3, 4.8,0.7 Hz, 1H), 7.04 (s, 1H), 3.81 (s, 3H), 3.37 (s, 3H), 2.19 (s, 3H).

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234	100- 102		ESIMS m/z 343 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J =2.5 Hz, 1H), 8.55 (dd, J =4.7, 1.4 Hz, 1H), 8.02 (ddd, J =8.3, 2.7, 1.5 Hz, 1H), 7.91 (s, 1H), 7.41 (ddd, J =8.3, 4.7, 0.6 Hz, 1 H), 6.37 (s, 1H), 6.13 (d, J =3.2 Hz, 1H), 3.53 (s, 2H), 3.38 (s, 3H), 2.22 (s, 3H).	13C NMR (101 MHz, CDCi3) δ 159.59, 154.79, 148.41, 147.61, 146.31, 140.04, 136.20, 127.79, 125.90, 124.35, 123.93, 117.73, 108.90, 38.56, 30.20, 15.42, 11.02.
235		(thin film) 1654	ESIMS m/z 307([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, 7=2.5 Hz, 1H), 8.58 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.03 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.85 (s, 1H), 7.44 (ddd, 7 = 8.3, 4.8,0.6 Hz, 1H), 3.24 (s, 3H), 3.02 - 2.77 (m, 3H), 2.59-2.38 (m, 2H), 2.25 (s, 3H).

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236			ESIMS m/z 397 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.4 Hz, 1H), 8.60 (dd, J = 4.7, 1.2 Hz, 1H), 8.18 (s, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.91 (s, 1H), 7.45 (ddd, J = 8.3, 4.8, 0.5 Hz, 1H), 3.29 (s, 3H), 2.70 (s, 2H), 2.28 (s, 3H).
237	112- 114	(thin film) 1629	ESIMS m/z 411 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1H), 8.61 (dd, J = 4.7, 1.3 Hz, 1H), 8.22 (s, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.88 (s, 1H). 7.45 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 4.09- 3.83 (m, 1H), 3.58 - 3.30 (m, 1H), 2.79-2.51 (m, 2H), 2.28 (s, 3H), 1.19 (t, J = 7.2 Hz, 3H).

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238

ESIMS m/z 373 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1 H), 8.58 (dd, J = 4.7, 1.3 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.88 (s, 1H), 7.43 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.77 (tdd, J = 17.3, 8.6, 3.8 Hz, 2H), 3.67 (brs, 1H), 2.54 (dd, J = 16.3, 3.6 Hz, 1H), 2.37 (dd, J = 24.4, 8.2 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H).

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239

(thin film) 1666

ESIMS m/z 373 ([M+HD

1H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.59 (d, 7 = 4.2 Hz, 1H), 8.11 -7.78 (m, 2H), 7.44 (dd, 7 = 8.3, 4.7 Hz, 1H), 4.21 (s, 1H), 3.52 (dd. 7 = 19.2, 11.9 Hz, 1H), 3.37 -3.10(m, 2H), 2.76 (dd,7 = 34.4, 11.6 Hz, 1H), 2.28 (s, 3H), 2.08 (s, 3H), 1.19 (t, 7 = 7.1 Hz, 3H). (Compound spectrum shows two rotamers; only the major one is reported)

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240	103- 105		ESIMS m/z 303 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.5 Hz, 1 H), 8.58 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.84 (s, 1H), 7.44 (ddd, 7 = 8.3, 4.8,0.4 Hz. 1H>, 4.10 (p, J = 9.1 Hz, 1H), 3.70 (t. 7 = 9.1 Hz, 2H), 3.68 - 3.46 (m, 2H), 2.75 (dd, 7 = 13.3, 5.0 Hz, 2H), 2.24 (s, 3H), 1.13 (t, 7 = 7.2 Hz, 3H).	13C NMR (101 MHz, CDCI3) δ 171.90, 148.46, 147.96, 140.05, 135.98, 126.08, 125.15, 124.31, 124.03, 44.01, 42.41,27.81, 12.95, 11.16.
241			ESIMS m/z 395 ([m+hD	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.59 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.05 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.88 (s, 1H), 7.44 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 4.05 (dtd, 7 = 14.1, 8.4, 2.6 Hz, 1H), 3.97-3.43 (m. 2H), 2.51 (d, 7 = 5.5 Hz, 2H), 2.26 (s, 3H), 1.17 (t, 7 = 7.2 Hz, 3H).

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242		(thin film) 1661	ESIMS m/z 443 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.58 (dd, J = 4.7, 1.3 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.87 (s, 1H), 7.44 (ddd, J = 8.3, 4.7, 0.5 Hz, 1H), 3.80-3.52 (m, 2H), 2.65-2.47 (m, 2H), 2.40 - 2.31 (m, 2H), 2.26 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H).
243		(thin film) 1660	ESIMS m/z 427 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.58 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.87 (s, 1H), 7.44 (ddd, J = 8.4, 4.8, 0.6 Hz, 1H), 3.69 (d, J = 6.8 Hz, 2H), 2.62 - 2.45 (m, 2H), 2.42 -2.31 (m,2H), 2.26 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H).

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244	64-68		ESIMS m/z 291 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.93 (s, 1H), 8.53 (d, J = 4.0 Hz, 1H), 8.02 (ddd. J = 8.3, 2.6, 1.4 Hz, 1 H). 7.82 (s, 1H), 7.40 (dd, J = 8.3, 4.7 Hz, 1H), 3.98 (s, 1H), 3.30 (s, 1H), 2.26 (s, 3H), 1.58 (s, 3H), 1.53 (s, 3H), 1.17 (t, J = 7.0 Hz, 3H).
245	114- 116	(thin film) 1656	ESIMS m/z 370 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.82 (brs, 1H), 8.57 (d, 7 = 3.8 Hz, 1H), 7.87 (brs, 1H), 7.41 (dd, 7 = 8.2, 4.8 Hz, 1H), 7.20 (d,7 = 8.4 Hz, 2H), 6.97 (d, 7 = 8.3 Hz, 3H), 3.88 (brs, 1H), 3.54 (brs, 2H), 2.21 (brs, 3H), 1.38 (d, 7 = 6.9 Hz, 3H), 1.10 (t, 7 = 7.1 Hz, 3H).

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246			ESIMS m/z 405 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.86 (d, J = 2.5 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.3 Hz, 1H), 7.96 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.58 (s, 1H), 7.42 (ddd, J = 8.4, 4.8, 0.6 Hz, 1H), 7.27 (t, 7 = 7.9 Hz, 1H), 7.14-7.05 (m, 1H), 7.056.92 (m, 2H), 3.68 (brs, 2H), 3.52 (s, 2H), 2.16 (s, 3H), 1.14 (t, J = 7.2 Hz, 3H).
247	170- 172		ESIMS m/z 379 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 2.1 Hz, 1H), 8.56 (d, 7 = 4.0 Hz. 1H), 7.96 (d, 7 = 8.1 Hz, 1H), 7.84 (s, 1H>, 7.40 (dd, 7 = 8.3, 4.7 Hz, 1H). 7.05 (s, 1H), 4.05 -3.56 (m, 5H), 2.16 (s, 3H), 1.23 (t, 7 = 6.9 Hz, 3H).

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248		(thrn film) 1653	ESIMS m/z 357 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1H). 8.55 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.91 (s, 1H), 7.42 (ddd, J = 8.4, 4.8, 0.6 Hz, 1H), 6.31 (s, 1H), 6.12 (d, J = 3.3 Hz, 1 H), 3.95-3.72 (m, 2H), 3.53 (s, 2H), 2.20 (s, 3H), 1.96 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H).
249	80-82		ESIMS m/z 321 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.59 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.83 (s, 1H), 7.44 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.89-3.51 (m, 2H), 2.97-2.81 (m, 3H), 2.51 (s, 2H), 2.24 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H).

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250		(thin film) 1649	ESIMS m/z 393 ([M+HD	1H NMR (400 MHz, CDCI3) 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), 7.967.77 (m, 1H), 4.32 - 3.92 (m, 2H), 3.49-3.11 (m, 6H), 2.32 (s, 3H), 1.27- 1.05 (m, 6H).
251			ESIMS m/z 357 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J= 1.7 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.86 (s, 2H), 5.96 -5.71(m, 1H), 5.20 (dd, J= 10.2, 1.2 Hz, 1H), 5.13 (dd, J = 17.1, 1.3 Hz, 1H), 4.22 (s, 2H), 2.50 (dt, J = 13.9, 6.1 Hz, 4H), 2.42 - 2.33 (m, 2H).	13C NMR (101 MHz, CDCI3) δ 170.27, 148.88, 136.14, 135.91, 135.20, 132.35, 125.45, 125.15, 119.03, 113.57, 113.34, 52.17, 38.61, 28.27, 26.76, 11.14.

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252	168- 169		ESIMS m/z 359([M]+), 361([M+2H]+)	1H NMR (400 MHz, CDCI3) δ 8.79 (d, 7=1.8 Hz, 1H), 8.63 (s, 1 H), 8.42 (d, 7 = 2.5 Hz, 1H). 7.82 (dt, 7= 9.4, 2.4 Hz, 1H), 7.68 (s, 1H). 2.91 (t, 7 = 6.9 Hz, 2H), 2.75 (dd, 7 = 10.2, 3.5 Hz, 2H), 2.20 (s, 3H).
253	106- 107		ESIMS m/z 373 ([M+Hf), 375 ([M+2Hf)	1H NMR (400 MHz, CDCI3) δ 8.78 (d, 7= 1.8 Hz, 1H), 8.65 (s, 1H), 8.41 (d,7 = 2.5 Hz, 1H), 7.81 (dt, 7= 9.3, 2.4 Hz, 1H), 7.66 (s, 1H), 2.87 (dd, 7= 14.5, 10.2 Hz, 1H), 2.74 -2.66(m, 2H), 2.18 (s, 3H), 1.36(d, 7 = 6.6 Hz, 4H).

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254	95-96		ESIMS m/z 372 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.72 (d, J= 1.9 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.85 (s, 1 H), 7.83 (s,1H), 3.22 (s, 3H), 1.45 (s, 9H).
255	221- 223		ESIMS m/z 278 ([M+H]*), 276 ([Μ-H])	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J =2.6 Hz, 1H), 8.49 (dd, J = 4.7, 1.4 Hz, 1H), 8.46 (s, 1H), 8.02 (s, 1H), 7.96 (ddd, J = 8.4, 2.7, 1.5 Hz, 1H), 7.38 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 6.46 (t, J = 5.6 Hz, 1H), 5.91 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.24 (dq, J = 17.1, 1.7 Hz, 1H), 5.13 (dq, J = 10.3, 1.5 Hz, 1H), 3.88 (tt, J = 5.6, 1.6 Hz, 2H).

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256	222- 225		ESIMS m/z 266 ([M+H]*), 264 ([M-H])	’H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.7 Hz, 1H), 8.49 (dd, J = 4.7, 1.3 Hz, 1H), 8.46 (s, 1H). 7.96 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.88 (s, 1H), 7.38 (dd, 7=8.3, 4.7 Hz, 1H), 6.26 (t, 7 = 5.2 Hz, 1H), 3.35-3.20 (m, 2H), 1.17 (t, 7 = 7.2 Hz, 3H).
257	213- 216		ESIMS m/z 280 ([M+H]*), 278 ([M-H]')	’H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.7 Hz, 1H), 8.51 8.39 (m, 2H), 8.02 -7.80 (m, 2H), 7.39-7.31 (m, 1H), 6.33 (s, 1H), 3.28-3.11 (m, 2H), 1.55 (ddd. 7 = 14.4, 7.3, 4.1 Hz, 2H), 0.95 (td, 7=7.3, 4.2 Hz, 3H).

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258			ESIMS m/z 335 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.91 (d, J = 2.4 Hz, 1H), 8.56 (dd, J = 4.7, 1.4 Hz, 1H), 8.01 (ddd, J = 8.3,2.5, 1.4 Hz, 1H). 7.87 (s, 1H), 7.41 (dd, J =8.2, 4.8 Hz, 1H), 5.96 -5.78 (m, 1H), 5.21 -5.15 (m, 2H),4.20 - 4.13 (m, 2H), 1.46 (s, 9H).	13C NMR (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.
259	104- 107	(thin film) 1648	ESIMS m/z 391 ([M+Hf)	’H NMR (400 MHz, CDGI3) δ 8.76 (d, J = 1.7 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.89 (s, 1H), 7.86 (dt, J = 9.4, 2.4 Hz, 1H), 3.77 (tdd, J = 17.2, 8.6, 3.8 Hz, 2H), 3.71 3.51 (m, 1H), 2.53 (dd, J = 16.2, 3.6 Hz, 1H), 2.36 (dd, J = 15.1,9.4 Hz, 1H), 2.29 (s, 3H), 2.27 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H).

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260		(thin film) 1665	ESIMS m/z 391 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.76 (d, J = 1.8 Hz, 1H), 8.45 (d, J = 2.5 Hz, 1H), 8.12-7.77 (m, 2H), 4.21 (s, 1H), 3.61 - 3.38 (m, 1H), 3.36-3.09 (m, 2H), 2.76 (dd, J = 35.3, 11.8 Hz, 1H), 2.28 (s, 3H), 2.09 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H). Mixture of two rotational isomers, only the major peaks reported
261	118- 120	(thin film) 1639	ESIMS m/z 321 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.74 (d, J = 1.8 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.85 (dt, J = 9.3, 2.4 Hz, 1H), 7.82 (s, 1H), 4.08 (p, J = 9.1 Hz, 1H), 3.70 (t, J = 9.2 Hz, 2H), 3.68-3.43 (m. 2H), 2.74 (t, J = 9.1 Hz, 2H), 2.24 (s, 3H), 1.13 (t, J = 7.2 Hz, 3H).

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262	109- 111	(thin film) 1657	ESIMS m/z 413 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.74 (d, J = 1.8 Hz, 1H), 8.44 (d. 7 = 2.5 Hz, 1H), 7.85 (dt, J = 9.3, 2.4 Hz, 1H). 7.82 (s, 1H), 4.08 (p, J = 9.1 Hz, 1H), 3.70 (t, 7 = 9.2 Hz, 2H), 3.68 - 3.43 (m, 1H), 2.74 (t, 7 = 9.1 Hz, 2H), 2.24 (s, 3H), 1.13 (t, 7 = 7.2 Hz, 3H).
263		(thin film) 1659	ESIMS m/z 445 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, 7 = 1.8 Hz, 1H), 8.44 (d, 7 = 2.5 Hz, 1H), 7.89 (s, 1H), 7.88 -7.84 (m, 1H), 3.69 (d, 7 = 6.8 Hz, 2H), 2.59 - 2.44 (m, 2H), 2.39 -2.31 (m, 2H), 2.25 (s, 3H), 1.15 (t, 7 = 7.2 Hz, 3H).

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264		(thin film) 1659	ESIMS m/z 461 ([M+H]+)	1H NMR (400 MHz, CDCI3) 6 8.74 (d, 7 = 1.8 Hz, 1H), 8.44 (d, 7 = 2.5 Hz, 1H), 7.85 (dt, 7 = 9.3, 2.4 Hz, 1H), 7.82 (s, 1H), 4.08 (p, 7 = 9.1 Hz, 1H), 3.70 (t, 7 = 9.2 Hz, 2H), 3.68 - 3.43 (m, 1H), 2.74 (t. 7 = 9.1 Hz, 2H), 2.24 (s, 3H). 1.13 (t, 7 = 7.2 Hz, 3H).
265	105- 107	(thin film) 1634	ESIMS m/z 309 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.73 (d, 7 = 1.5 Hz, 1H), 8.39 (d, 7 = 2.5 Hz, 1H), 7.87-7.80 (m, 2H), 3.90 (brs, 1H), 3.31 (brs, 1H), 2.25 (s, 3H), 1.58 (s, 3H), 1.53 (s, 3H), 1.17 (t, 7 = 7.0 Hz, 3H).

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266		(thin film) 1599	ESIMS m/z 387 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.58 (brs, 1H), 8.43 (d, J = 2.5 Hz. 1H), 7.73 (brs, 1H), 7.21 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 8.4 Hz, 2H), 4.03 - 3.22 (m, 3H), 2.46 - 1.98 (m, 3H), 1.38 (d, J = 6.9 Hz, 3H), 1.09 (t, J = 7.1 Hz, 3H).
267		(thin film) 1654	ESIMS m/z 423 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.64 (d, J= 1.7 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.79 (dt, J = 9.3, 2.4 Hz, 1H), 7.58 (s, 1H), 7.27 (t, J = 7.9 Hz, 1H), 7.15-7.06 (m, 1H), 7.00 (d, J = 7.7 Hz, 1H), 6.95 (s, 1 H),3.67 (brs, 2H), 3.52 (s, 2H), 2.15 (s, 3H), 1.14 (t, J =7.2 Hz, 3H).

Page 396 of 619

268	174- 176	(thin film) 1652	ESIMS m/z 397 ([M-HHD	’H NMR (400 MHz, CDCI3) δ 8.71 (d. 7 = 1.4 Hz, 1H), 8.41 (d, 7 = 2.5 Hz, 1H), 7.85 (s, 1H), 7.78 (d, 7 = 9.3 Hz, 1H), 7.07 (s, 1H), 3.82 (s, 5H), 2.16 (s, 3H), 1.22 (t, 7 = 6.9 Hz, 3H).
269	98- 100	(thin film) 1630	ESIMS m/z 375 ([M+Hf)	’H NMR (400 MHz. CDCI3) δ 8.75 (d,7 = 1.7 Hz, 1H), 8.41 (d, 7 = 2.5 Hz, 1H), 7.90 (s, 1H), 7.85 (dt, 7 = 9.4, 2.4 Hz, 1H), 6.38 (s, 1H), 6.13 (d, 7 = 3.3 Hz, 1H), 3.81 (d, 7 = 6.5 Hz, 2H), 3.52 (s, 2H), 2.19 (s, 3H), 1.95 (s, 3H), 1.24 (t, 7 = 7.1 Hz, 3H).

Page 397 of 619

270	77-79	(thin film) 1650	ESIMS m/z 339 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J = 1.8 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.89 - 7.84 (m, 1H), 7.84 (s, 1H), 3.68 (brs, 2H), 2.98 - 2.73 (m, 3H), 2.48 (ddd, J = 13.9, 8.2, 3.5 Hz, 2H), 2.23 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H).
271		(thin film) 1635	ESIMS m/z 429 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.76 (d, J = 1.9 Hz, 1H), 8.47 (d, J = 2.5 Hz, 1H), 8.16 (s, 1H), 7.90 (s, 1H), 7.88- 7.83 (m, 1H), 3.99 (brs, 1 H), 3.42 (brs, 1H), 2.63 (brs, 2H), 2.27 (s, 3H), 1.19 (t, J = 7.2 Hz, 3H).

Page 398 Of6l9

272	116- 118	(thin film)1648	ESIMS m/z 397 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.66 (S, 1H), 8.40 (d, J = 2.5 Hz, 1H), 7.85-7.70 (m, 2H), 7.27 (s, 1H). 3.89 (s, 3H), 3.82 (q, 7 = 7,0 Hz, 2H), 2.16 (s, 3H), 1.24 (t, 7 = 7.1 Hz, 3H).
273		(thin film) 1651	ESIMS m/z 371 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.59 (brs, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 7.76 (brs, 1H), 7.03-6.85 (m, 4H), 3.55 (brs, 3H), 2.25 (brs, 3H), 1.38 (d, 7 = 6.9 Hz, 3H), 1.09 (t, 7 = 7.1 Hz, 3H).

Page 399 of 619

274		(thin film) 1653	ESIMS m/z 437 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.69 (d, J = 1.7 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.78 (dt, J = 9.4, 2.4 Hz, 1H), 7.49 (s, 1H), 7.15 (d, J = 8.7 Hz, 2H), 7.10 (d, J = 8.1 Hz, 2H), 3.65 (s, 2H), 2.95 (t, J = 7.3 Hz, 2H), 2.37 (t, J = 7.4 Hz, 2H), 2.12 (s, 3H), 1.10 (t, J = 7.1 Hz, 3H).
275	114- 116	(thin film) 1670	ESIMS m/z 399 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, J = 1.7 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.92 (s, 1H), 7.85 (dt, J = 9.3, 2.4 Hz, 1H), 3.77 (s, 2H), 3.68 (s, 2H), 2.94 (s, 3H), 2.83 (s, 6H), 2.28 (s, 3H), 1.16 (t, J = 7.2 Hz. 3H).

Page 400 of6!9

276	83-86	(thin film) 1664	ESIMS m/z 425 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.5 Hz, 1H), 8.59 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.01 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.85 (s,1H), 7.44 (ddd, 7 = 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, 7 = 7.1 Hz, 3H).
277			ESIMS m/z 388 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.76 (s, 1H). 8.49 (d, 7 = 2.4 Hz, 1H), 8.03 (s, 1H), 7.87 (dt, 7=9.1, 2.3Hz, 1H), 3.26 (s, 3H), 2.942.83 (m, 1H), 2.73 (dd, 7= 14.4,6.9 Hz, 1H), 2.48 (dd, 7= 12.7, 5.3 Hz,1H), 2.03 (s, 3H), 1.17 (d, 7 = 6.7 Hz, 3H).

Page 401 of 619

278	154- 156		ESIMS m/z 260 ([M+Hf), 258 ([Μ-H])	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.3 Hz, 1H), 8.55 (dd, J = 4.7, 1.4 Hz, 1H), 8.02 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.93 (s, 1H), 7.42 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H>, 4.51 (s, 1H), 3.29 - 3.22 (m, 2H), 3.21 (s, 3H), 2.27 (s, 3H), 1.08 (t, J = 7.2 Hz, 3H).
279	159- 161		ESIMS m/z 274 ([M+Hf), 272 ([Μ-H]’)	1H NMR (400 MHz, CDCI3) δ 8.94 (dd, 7=2.6, 0.4 Hz, 1H), 8.55 (dd, J = 4.7, 1.4 Hz, 1H), 8.01 (ddd. J = 8.3, 2.7, 1.5 Hz, 1H), 7.92 (s, 1H), 7.42 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 4.53 (t, 7 = 5.4 Hz, 1H), 3.21 (s, 3H), 3.19 -3.10 (m, 2H), 2.28 (s, 3H), 1.53 -1.38(m, 2H), 0.86 (t. J = 7.4 Hz, 3H).

Page 402 of6!9

280	150- 152		ESIMS m/z 272 ([M+H]*), 270 ([M-HD	1H NMR (400 MHz, CDCI3) δ 8.96-8.90 (m, 1H), 8.55 (dd, J = 4.7, 1.4 Hz, 1H), 8.01 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.93 (s, 1H), 7.41 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H), 5.82 (ddt, 7= 17.1, 10.2, 5.6 Hz, 1H), 5.19-4.98 (m, 2H), 4.61 (t, 7 = 5.5 Hz, 1H), 3.84 (tt, 7 = 5.8, 1.5 Hz, 2H), 3.23 (s, 3H), 2.28 (s, 3H).
281		(thin film) 3268, 2978, 1698.	ESIMS m/z 275 ([M+H]*), 273 ([M-HD	1H NMR (400 MHz, CDCI3) δ 8.75 (dd, 7 = 2.5, 0.5 Hz, 1H), 8.62 (dd, 7 = 4.8, 1.5 Hz, 1H), 7.82 (ddd, 7 = 8.2, 2.6, 1.5 Hz, 1H), 7.78 (s, 1H), 7.43 (ddd, 7 = 8.1, 4.8, 0.6 Hz, 1H), 6.04 (s, 1H), 2.29 (s, 3H), 1.52 (s, 9H).

Page 403 of 619

282

ESIMS m/z 338 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.93 (d, 7 = 2.5 Hz, 1 H), 8.62 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.03 (ddd, 7 = 8.4,2.7, 1.4 Hz, 1H), 7.93 (d, 7 = 3.2 Hz, 1H), 7.46 (dd, 7=8.2, 4.7 Hz, 1H), 5.86 (ddt, 7= 16.6, 10.2, 6.4 Hz,1H), 5.25- 5.10 (m, 2H), 4.26 (s, 2H), 2.81 (t, 7 = 7.3 Hz, 2H), 2.49 (t, 7 = 7.3 Hz, 2H), 2.07 (s, 3H).

13CNMR(101 MHz, CDCI3) δ 175.72, 148.64, 140.81, 140.04, 135.64, 132.61, 130.03, 126.26, 124.10,123.76 , 118.63, 51.53, 37.19, 18.27, 16.55.

Page 404 of 619

283			ESIMS m/z 352 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.5 Hz, 1H), 8.62 (dd, J = 4.7, 1.3 Hz, 1H), 8.03 (ddd, J = 8.3,2.7, 1.4 Hz, 1H). 7.97 (s, 1H), 7.45 (dd, J =8.3, 4.8 Hz, 1H), 5.86 (ddt, J= 16.7, 10,5, 6.3 Hz, 1H), 5.18(dd, J = 9.8, 8.6 Hz, 2H), 4.41 -4.28 (m, 2H), 2.87 (dd, J= 12.7, 9.1 Hz. 1H), 2.75 (bs, 1H), 2.48 (dd, J= 12.7, 5.2 Hz, 1H), 2.02 (s, 3H), 1.18 (d, J = 6.7 Hz, 3H).	13C NMR (101 MHz, CDCI3) δ 171.59, 148.68, 140.73, 140.01, 135.62, 132.56, 126.44, 126.31, 124.11,123.77 , 118.84, 51.65,33.90, 29.65, 15.93.
284	93-94		ESIMS m/z 305 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.94 (d, J =2.5 Hz, 1H), 8.698.56 (m, 1H), 8.04 (ddd. J = 8.4, 2.6, 1.4Hz, 1H), 7.90 (s, 1H), 7.45 (dd, J = 8.3, 4.8 Hz, 1H), 5.97-5.74 (m, 1H), 5.31 4.99 (m, 2H), 4.29 (S,2H), 1.10 (d, J = 6.7 Hz, 6H).

Page 405 of 619

285		(thin film) 1654	ESIMS m/z 306 ([M+2f)	'H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.3 Hz, 1H), 8.57 (dd, J = 4.7, 1.4 Hz, 1H), 8.03 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H). 7.90 (s, 1H). 7.43 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 3.78-3.63 (m, 2H), 2.57 - 2.47 (m, 2H), 2.28 (s, 3H), 2.09 (s, 3H), 1.93 (S, 3H), 1.90 -1.80(m, 2H).
286		(thin film) 1656	ESIMS m/z 377 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J = 1.8 Hz, 1H), 8.44 (d, J = 2.5 Hz, 1H), 7.88 (s, 1H), 7.88 -7.82 (m, 1H), 3.70 (d, J = 6.0 Hz, 2H), 3.12 (t, J = 6.7 Hz, 2H), 2.51 (t, J = 6.6 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H).

Page 406 of 619

287		(thin film) 1649	ESIMS m/z 333 ([M+HD	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.4 Hz, 1 H), 8.57 (dd, 7 = 4,7, 1.4 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.91 (s, 1H), 7.43 (ddd, 7 = 8.3, 4.7, 0.5 Hz, 1H), 3.74 (s, 2H), 2.63 -2.54 (m, 1H), 2.54 - 2.47 (m, 2H), 2.26 (s, 3H), 2.10 (S, 3H), 1.90 -1.80 (m, 2H), 1.06 (d, 7 = 6.7 Hz, 6H).
288		(thin film) 1694	ESIMS m/z 335 ([M+Hf),	’H NMR (400 MHz, CDCI3) δ 8.93 (d, 7 = 2.4 Hz, 1H), 8.52 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.01 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.85 (s, 1H), 7.39 (dd, 7 = 8.3, 4.7 Hz, 1H), 4.17 (s, 2H), 3.75 3.60 (m, 2H), 2.52 (t, 7= 7.3 Hz, 2H), 2.25 (s, 3H), 2.09 (s, 3H), 1.951.81 (m, 2H), 1.43 -1.06 (m, 3H).

Page 407 of 619

289

(thin film) 1652

ESIMS m/z 366 {[M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.3 Hz, 1H), 8.57 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.91 (s, 1H), 7.43 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.72 (s, 2H), 2.78 (t, J = 7.2 Hz, 2H), 2.57-2.50 (m, 2H), 2.42 (t, J = 7.2 Hz, 2H), 2.28 (s, 3H), 2.10 (s, 3H), 2.05 (s, 3H), 1.91 - 1.81 (m, 2H).

Page 408 of6!9

290		(thin film) 1650	ESIMS m/z 380 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.4 Hz, 1 H), 8.57 (dd. 7 = 4.7, 1.4 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.95 (s, 1H), 7.43 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 4.44-3,08 (m, 2H), 2.95-2.82 (m, 1H), 2.81 2.65 (m, 1H), 2.62 - 2.47 (m, 2H), 2.47 - 2.38 (m. 1H),2.31 (s, 3H), 2.10 (s, 3H). 2.01 (s, 3H). 1.87 (p, 7 = 7.4 Hz, 2H), 1.12 (d. 7 = 6.7 Hz, 3H).
291		(IR thin film) 1684	ESIMS m/z 337 (IM+H]*)	1H NMR (400 MHz, CDCI3) δ 8.54 (d, 7 = 2.5 Hz, 1H), 8.58 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.19-7.94 (m, 1H), 7.80 (bs, 1H), 7.47-7.34 (m, 1H), 4.76- 4.38 (m, 1 H).1.57 (s, 9H), 1.13 (d, 7 = 6.7 Hz, 6H),

Page 409 of 619

292

96- 100

(thin film) 1666, 1450

ESIMS m/z 335.2 ([M+H]4)

’H NMR (400 MHz, CDCI3) δ 8.96 (d, J =2.5 Hz, 1H), 8.57 (dd, J = 4.7, 1.3 Hz, 1H), 8.03 (ddd, J = 8.3, 2.6, 1.5 Hz, 1H), 7.99 (s, 1H), 7.43 (dd, J = 8.2, 4.6 Hz, 1H). 4.10 (q, J = 6.5 Hz. 1H), 3.56 (dt. 9.1, 6.6 Hz, 1H), 3.45 (dt, J = 9.2, 6.9 Hz. 1H), 3.25 (s, 3H), 2.66 (t. J = 6.8 Hz, 2H), 2.29 (s, 3H), 2.11 (s, 3H), 1.30 (d, J = 6.5 Hz, 3H).

Page 410 of 6I9 & —

293		(thin film) 1665	ESIMS m/z 319.5 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, 7=2.5 Hz, 1H), 8.56 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.08 (s, 1H), 8.05 (ddd, 7 = 8.3, 2.5, 1.5 Hz, 1H), 7.42 (dd, 7 = 8.3, 4.8 Hz, 1H), 4.11 (q, 7 = 6.5 Hz, 1 H), 3.59-3.44 (m, 4H), 3.37 (s, 3H), 3.24 (s, 3H), 2.29 (s, 3H), 1.29 (d,7 = 6.5 Hz, 3H).
294		(thin film) 1668	ESIMS m/z 343.5 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.6 Hz. 1H). 8.58 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.01 (ddd, 7 = 8.3, 2.6, 1.5 Hz, 1H), 7.91 (s. 1H), 7.43 (dd, 7=8.3, 4.8 Hz, 1H), 4.32 (q, 7 = 6.4 Hz, 1H), 3.87 (dq,7 = 12.3, 8.9 Hz, 1H), 3.81 -3.64 (m, 1H), 3.24 (d, 7 = 12.2 Hz, 3H), 2.28 (s. 3H), 1.33 (d, 7 = 6.5 Hz, 3H).

Page 411 of 6I9

295		(thin film) 1665	ESIMS m/z 331.2 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (dd, J= 5.5, 2.5 Hz, 1H). 8.58 (dd, J = 4.7, 1.2 Hz, 1 H), 8.03 (tdd, J =7.0, 2.7, 1.5 Hz, 1H), 7.92 (d, J = 5.3 Hz, 1H), 7.43 (dd, J = 8.3, 4.8 Hz, 1H), 4.12 (dd, J= 12.0, 6.1 Hz, 2H), 3.85 (dd, J = 7.3, 4.0 Hz, 1H), 3.73 (dd, J = 17.8, 10.9 Hz, 3H), 3.25 (s, 3H), 2.29 (d, J = 4.0 Hz, 3H), 2.05 1.81 (m, 2H), 1.29 (d, J = 6.5 Hz, 3H).
296			ESIMS m/z 358 ([Mf)	’H NMR (400 MHz, CDCI3) δ 8.94 (d, J =2.6 Hz, 1H), 8.63 (dd, J = 4.7, 1.3 Hz, 1H), 8.04 (ddd, J = 8.4,2.7, 1.4 Hz, 1H), 7.92 (s, 1H), 5.85 (ddt, J = 16.7, 10.1, 6.4 Hz, 1H), 5.18 (ddd, J = 18.4, 13.6, 1.2 Hz,2H), 2.65- 2.29 (m, 4H).	13CNMR(101 MHz, CDCI3) δ 177.38, 153.53, 150.57, 148.69, 140.09, 126.70, 126.36, 124.09, 123.64,123.24 , 123.15, 72.71,37.64, 31.31, 19.49.

Page 4I2 of 619

297		(thin film) 3337, 3273, 3079, 3018, 1631.	ESIMS m/z 330 ([M+H]*2).	’H NMR (400 MHz, DMSO-ctô) δ 8.93 (s, 1H), 8.65 (s, 1H), 8.48 (d, J = 2.5 Hz, 1H), 8.28 (S, 2H), 8.18 (dt, 7 = 10.3, 2.3 Hz, 1H), 3.14 (q, 7 = 7.2 Hz, 2H), 1.08 (t, 7 = 7.2 Hz, 3H).
298		(thin film) 3322, 2963, 1636.	ESIMS m/z 344 ([M+H]*2).	’H NMR (400 MHz, DMSO-76) δ 8.94 (s, 1H), 8.66 (s, 1H), 8.52 (d, 7 = 2.5 Hz, 1H), 8.22 (dt, 7= 10.3, 2.3 Hz, 1H), 8.02 (s, 1H), 6.62 (t, 7 = 5.6 Hz, 1H), 3.07 (dd, 7= 12.6, 6.8 Hz, 2H), 1.45 (dd, 7= 14.3, 7.2 Hz, 2H), 0.89 (t, 7 = 7.4 Hz, 3H).

Page4l3 of6!9

299		(thin film) 3329, 3289, 3074, 1634.	ESIMS m/z 342 ([M+Hf2).	’H NMR (400 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.67 (s, 1H), 8.52 (d, 7 = 2.5 Hz, 1H), 8.22 (dt, 7 = 10.3, 2.3 Hz, 1H), 8.13 (s, 1 H), 6.73 (t, 7 = 5.7 Hz, 1H), 5.88 (ddt, 7 = 17.2, 10.2, 5.1 Hz, 1H), 5.18 (dq, 7 = 17.2, 1.7 Hz, 1H), 5.12-5.06 (m, 1H), 3.76 (dd, 7 = 7.3, 3.5 Hz, 2H).
300		(thin film) 3251, 3090, 2973, 1644.	ESIMS m/z 280 ([M+Hf)	1H NMR (400 MHz, DMSO-76) δ 9.06 (d, 7 = 2.5 Hz, 1H), 8.84 (s, 1H), 8.56 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.20 (ddd, 7 = 8.4, 2.7, 1.4 Hz, 1H), 7.58 (dd, 7 = 8.4, 4.7 Hz, 1 H), 6.36 (t. 7 = 5.6 Hz, 1H), 3.07 (s, 3H), 3.02 (dd, 7=7.0, 5.8 Hz, 2H), 0.97 (t, 7 = 7.1 Hz, 3H).

Page 414 of 619

301		(thin film) 3232, 3075, 1639.	ESIMS m/z 294 ([M+Hf).	1H NMR (400 MHz, DMSO-c/6) δ 9.06 (d, J = 2.6 Hz, 1H), 8.84 (s, 1H), 8.56 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.25-8.13 (m, 1H), 7.58 (dd, J- 8.4, 4.7 Hz, 1H), 6.34 (t, 7=5.6 Hz, 1H). 3.06 (d, 7 = 3.2 Hz, 3H), 2.94 (dd, 7= 13.4, 6.4 Hz. 2H), 1.45- 1.30 (m, 2H), 0.80 (t, 7= 7.4 Hz, 3H).
302		(thin film) 3227, 3078, 1635.	ESIMS m/z 292 ([M+H]*), 290 ([Μ-ΗΓ).	1H NMR (400 MHz, DMSO-76) δ 9.06 (d, 7 = 2.6 Hz, 1H), 8.86 (s, 1H), 8.59-8.52 (m, 1H), 8.25- 8.14 (m, 1H), 7.58 (dd, 7=8.4, 4.7 Hz, 1H), 6.56 (t, 7 = 5.6 Hz, 1H), 5.77 (ddt, J = 16.9, 10.1,4.9 Hz, 1H), 5.08 (dd, 7 = 17.2, 1.7 Hz, 1H), 4.99 (dd, 7= 10.3, 1.5 Hz, 1H), 3.62 (t, 7 = 5.2 Hz, 2H), 3.08 (s, 3H).

Page4l5 of6!9

303		(thin film) 1659	ESIMS m/z 393 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.7, 1.1 Hz, 1H), 8.06 (ddd, J = 8.4, 2.5,1.4 Hz, 1H), 7.98 (s, 1H), 7.47 (dd, J = 8.3, 4.8 Hz. 1H), 3.943.55 (m, 3H), 2.63 (dd, J = 16.3, 3.7 Hz, 1H), 2.41 (dd, J = 16.3, 9.9 Hz, 1 H). 2.29 (s, 3H). 1.19 (t, J = 7.2 Hz, 3H).
304		(thin film) 1669	ESIMS m/z 393 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz. 1H). 8.64 (dd. J = 4.7, 1.2 Hz, 1H), 8.21 -7.90 (m, 2H), 7.47 (ddd, J = 8.4, 4.8, 0.6 Hz, 1H), 4.12 (dd, J = 14.3, 7.1 Hz, 1H), 3.46 (brs, 2H). 3.25 - 3.06 (m, 1H), 2.80 (brs, 1H), 2.10 (s, 3H), 1.20 (t. J = 7.2 Hz, 3H).

Page 416 of 619

305	93-95	(thin film) 1654	ESIMS m/z 323 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.01 -8.88 (m, 1H), 8.64 (dd, J = 4.7, 1.3 Hz, 1H), 8.05 (ddd, J = 8.4, 2.7, 1.4 Hz, 1H), 7.93 (s, 1H), 7.48 (ddd, J = 8.4, 4.8, 0.5 Hz, 1 H), 4.13 (P, J = 9.1 Hz, 1 H), 3.73 (t, J = 9.0 Hz, 2H), 3.70 3.51 (m, 2H), 2.79 (t, J = 9.2 Hz, 2H), 1.15 (t, J = 7.2 Hz. 3H).
306	88-89	(thin film) 1666	ESIMS m/z 415 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.5 Hz, 1H), 8.65 (dd, J = 4.7, 1.3 Hz, 1H), 8.07 (ddd, J = 8.3. 2.7, 1.5 Hz, 1H). 7.99 (s, 1H). 7.48 (ddd, J = 8.4, 4.8, 0.5 Hz, 1H), 4.17-3.94 (m, 1H), 3.86-3.59 (m, 2H), 2.57 (d, J = 5.7 Hz, 2H), 1.19 (t, J = 7.2 Hz. 3H).

Page 417 of 619

307		(thin film) 1657	ESIMS m/z 341 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.64 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.94 (s, 1H). 7.48 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 3.71 (s, 2H), 2.99 -2.76(m, 3H), 2.60 - 2.39 (m, 2H), 1.17 (t, 7 = 7.2 Hz, 3H).
308		(thin film) 1663	ESIMS m/z 389 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.77 (brs, 1H), 8.67 - 8.55 (m, 1H), 7.85 (brs, 1H), 7.44 (dd, 7 = 8.3, 4.7 Hz, 1H), 7.19 (d, 7 = 8.4 Hz, 2H), 6.96 (d, J = 8.2 Hz, 2H), 3.91 - 3.32 (m, 3H), 1.40 (d, J = 6.9 Hz, 3H), 1.11 (t, 7 = 7.2 Hz, 3H). (One aromatic proton merged into baseline)

Page 418 of 619

309		(thin film) 1638	ESIMS m/z 431 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz. 1H), 8.66 (dd, J = 4.8, 1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.97 (d, J = « 5.4 Hz, 2H), 7.49 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 4.053.47 (m, 2H), 2.69 (s, 2H), 1.21 (t, J = 7.2 Hz, 3H).
310		(thin film) 1657	ESIMS m/z 373 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.78 (brs, 1H), 8.62 (dd, J = 4.7, 1.0 Hz, 1H), 7.88 (brs, 1H), 7.44 (dd, J = 8.3, 4.7 Hz, 1H), 7.04 (brs, 1H), 7.04-6.96 (m, 2H), 6.96 6.84 (m, 2H), 3.84 -3.32 (m, 3H), 1.40 (d, J = 6.9 Hz, 3H), 1.11 (t, J = 7.2 Hz, 3H).

Page 419 of 619

311		(thin film) 1666	ESIMS m/z 447 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.6 Hz, 1H), 8.64 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.97 (s, 1H), 7.47 (ddd, 7 = 8.3, 4.8, 0.4 Hz, 1H), 3.72 (q, 7 = 7.2 Hz, 2H), 2.60 - 2.46 (m, 2H), 2.46 - 2.33 (m, 2H), 1.17 (t, 7 = 7.2 Hz, 3H).
312	181- 183	(thin film) 1653	ESIMS m/z 399 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.88 (d, 7 = 1.9 Hz, 1H), 8.60 (d, 7 = 4.1 Hz, 1H), 7.92 (ddd, 7 = 8.3, 2.5, 1.3 Hz, 1H), 7,86 (s, 1H), 7.42 (dd, 7 = 8.3, 4.7 Hz, 1H), 7.36 (s, 1H), 3.84 (s, 3H), 3.84-3.75 (m, 2H), 1.24 (t, 7 = 7.1 Hz, 3H).

Page 420 of 619

313

58-61

(thin film) 1636

ESIMS m/z 377 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.6 Hz, 1H). 8.61 (dd, 7 = 4.7, 1.4 Hz, 1 H), 8.05 (ddd. J = 8.3, 2.7, 1.5 Hz, 1H), 7.96 (s, 1H), 7.45 (ddd, 7 = 8.3. 4,8. 0.6 Hz, 1H), 6.64 (d. J = 3.2 Hz, 1H). 6.16 (d. J = 3.4 Hz, 1H), 3.84 (q, 7 = 7.1 Hz, 2H), 3.49 (s, 2H). 1.91 (s, 3H). 1.26 (t, 7 = 7.1 Hz, 3H).

Page 421 of 619

314

(thin film) 1657

ESIMS m/z 318 ((M+2]+)

1H NMR (400 MHz, CDCI3) δ 8.94 (s. 0.75H), 8.91 (s. 0.25H), 8.60 - 8.53 (m, 0.75H), 8.51 (s. 0.25H), 8.07 - 7.95 (m. 1H), 7.83 (s, 0.25H), 7.80 (s, 0.75H), 7.46 7.33 (m. 1H), 3.34 - 3.23 (m, 0.5H), 3.14-3.00 (m, 1H), 2.91 (s, 0.5H), 2.78 (t, J = 7.2 Hz, 1.5H), 2.47 - 2.30 (m. 1.5H), 2.25 (s, 3H), 2.20 (s, 0.75H), 2.05 (s, 2.25H), 0.99 (s, 0.5H), 0.80 (d, J = 6.7 Hz, 1.5H), 0.72 (s, 0.5H), 0.47 (s, 1.5H).

Page 422 of619

315

(thin film) 1654

ESIMS m/z 331 ([M+H]*)

’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.4 Hz, 0.8H), 8.91 (s, 0.2H), 8.56 (dd, J = 4.7, 1.0 Hz, 0.8H), 8.50 (d, J = 4.2 Hz, 0.2H), 8.06 - 7.96 (m, 1H), 7.84 (s, 1H), 7.42 (dd, J =8.3, 4.7 Hz, 0.8H), 7.37 (dd, J =7.9, 4.7 Hz, 0.2H), 3.79 - 3.65 (m, 0.2H), 3.35 - 3.25 (m, 0.8H), 3.22 - 3.12 (m, 0.2H), 3.03 - 2.81 (m, 1H), 2.77-2.57 (m, 1H), 2.42 (dd, J= 12.8, 5.0 Hz, 0.8H), 2.29 (s, 2.4H), 2.26 (s, 0.6H), 2.18 (s, 0.6H), 2.00 (s, 2.4H), 1.31 (d, J = 6.7 Hz, 0.6H), 1.11 (d, J = 6.7 Hz, 2.4H), 1.00 (d, J = 6.6 Hz, 0.4H), 0.89-0.67 (m, 2H), 0.56 - 0.39 (m, 1.6H).

Page 423 of 619

316	118.0 120.5		ESIMS m/z 385 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.98 - 8.86 (m, 1H), 8.61 -8.44 (m, 1H), 8.09- 7.94 (m, 1H), 7.87 - 7.73 (m, 1H), 7.48 - 7.30 (m, 1H), 3.52 (s, 0.2H), 3.27 (s, 0.8H), 3.11 (s, 0.2H), 2.62 - 2.41 (m, 0.8H), 2.23 (s, 3H), 1.32-1.17 (m, 1.2H), 1.06 (d, J = 6.2 Hz, 4.8H), 0.97 (s, 0.4H), 0.79 (d, J =5.7 Hz, 1.6H), 0.72 (s, 0.4H), 0.44 (s, 1.6H).
317	119.0 121.0		ESIMS m/z 341 <[M+2]+)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J =2.1 Hz, 1H), 8.54 (dd, J = 4.7, 1.4 Hz. 1H), 8.33 (s, 1 H), 7.99 (ddd, J =8.3, 2.7, 1.5 Hz, 1H), 7.38 (dd, J = 8.1, 4.7 Hz, 1H), 6.35 (s, 1H). 1.54 (s, 9H).

Page 424 of619

318		(thin film) 3319, 2964, 1638.	ESIMS m/z 298 ([M+H]+), 296 ([Μ-H])	1H NMR (400 MHz. DMSO-c/6) δ 8.94 (s, 1H), 8.71 (s, 1H), 8.52 (d, J = 2.5 Hz, 1H), 8.22 (dt, J = 10.3, 2.3 Hz, 1H), 8.16 (s, 1H), 6.53 (t, J = 5.7 Hz, 1H), 3.08 (dd, J = 12.7, 6.8 Hz, 2H), 1.52 1.38 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H).
319		(thin film) 3311, 3093, 1635.	ESIMS m/z 296 ([M+Hf), 294 ([Μ-H]')	1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J= 1.2 Hz, IH), 8.72 (s, 1H), 8.52 (d, J = 2.5 Hz, 1H), 8.27 (s, 1H), 8.22 (d, J = 10.3 Hz, 1H), 6.64 (t, J = 5.7 Hz, 1H), 5.88 (ddt, J = 17.2, 10.2, 5.1 Hz, 1H), 5.18 (dq, J = 17.2, 1.7 Hz, 1H), 5.09 (dq, J = 10.3, 1.6 Hz, 1H), 3.83- 3.67 (m, 2H).

Page 425 of 619

320		(thin film) 3264, 3071,2980, 1640,	ESIMS m/z 294 ([M+Hf).	1H NMR (400 MHz, DMSO-c/6) δ 9,08 (d, 7=2.6 Hz, 1H), 8.85 (s, 1H), 8.56 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.22 (ddd, 7 = 8.4, 2.6, 1.4 Hz, 1H), 7.58 (dd, 7 = 8.4, 4.7 Hz, 1H), 6.23 (t, J = 5.6 Hz, 1H), 3.50 (q, 7 = 7.1 Hz, 2H), 3.07 2.94 (m, 2H), 1.04 (t, J = 7.1 Hz, 3H), 1.00-0.92 (t, 7 = 7.0 Hz, 3H).
321		(thin film) 3256, 3081,2960, 1633.	ESIMS m/z 308 ([M+Hf).	1H NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 2.5 Hz, 1H), 8.85 (s, 1H), 8.56 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.22 (ddd, 7 = 8.4, 2.7, 1.4 Hz, 1H), 7,58 (ddd, 7 = 8.4, 4.8, 0.5 Hz, 1H), 6.22 (t, J = 5.7 Hz, 1H), 3.50 (q, 7 = 7.0 Hz, 2H), 2.93 (dd, 7 = 13.5, 6.3 Hz, 2H), 1.441.30 (m, 2H), 1.04 (t, 7 = 7.1 Hz, 3H), 0.79 (t, J = 7.4 Hz, 3H).

Page 426 of619

322

(thin film) 3260, 3067, 1638.

ESIMS m/z 306 ([M+HD.

1H NMR (400 MHz, DMSO-76) δ 9.08 (d, J= 2.5 Hz, 1H). 8.87 (s, 1H), 8.56 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.22 (ddd, 7 = 8.4, 2.7, 1.4 Hz, 1H), 7,62-7.52 (m, 1H), 6.43 (t, 7 = 5.7 Hz, 1H), 5.76 (ddt, 7 = 17.2, 10.1, 5.0 Hz, 1H), 5.07 (dq,7 = 17.2, 1.7 Hz, 1H), 4.98 (dq, 7 = 10.3, 1.6 Hz, 1H), 3.60 (t, 7 = 5.3 Hz, 2H), 3.51 (q, 7 = 7.0 Hz, 2H), 1.05 (t, 7 = 7.1 Hz, 3H).

Page 427 of 619

323		(thin film) 1650	ESIMS m/z 274 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 4.7, 1.3 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, IH), 7.87 (s, 1H), 7.42 (ddd, J = 8.4, 4.8, 0.6 Hz, 1H), 3.22 (s, 3H), 2.26 (s, 3H), 2.24 - 2.11 (m, 1H), 2.03 (d, J = 7.0 Hz, 2H), 0.89 (d, J = 6.6 Hz, 6H).
324	60-63	(thin film) 1647	ESIMS m/z 287 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.5 Hz, 1H), 8.56 (dd, J = 4.7, 1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.84 (s. 1H), 7.43 (ddd, J = 8.3, 4.8, 0.6 Hz, 1H), 3.67 (s, 2H), 2.25 (s, 3H), 2.23 - 2.11 (m, 1H), 1.99 (d, J = 7.0 Hz, 2H), 1.14 (t, J = 7.1 Hz, 3H), 0.88 (d, 7 = 6.6 Hz, 6H).

Page 428 of 619

325	74-76	(thin film) 1642	ESIMS m/z 305 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.77 (d, J = 1.6 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.92 - 7.80 (m, 2H), 3.67 (s, 2H), 2.25 (s, 3H), 2.23 -2.11 (m, 1H), 1.97 (d, J = 7.0 Hz, 2H), 1.14 (t, J = 7.1 Hz, 3H), 0.88 (d, J = 6.7 Hz, 6H).
326		(thin film) 1653	ESIMS m/z 307 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.5 Hz, 1H), 8.62 (dd, J = 4.7, 1.3 Hz, 1H), 8.08 (tdd, J = 8.4, 2.7, 1.4 Hz, 1H), 7.93 (s, 1H), 7.46 (ddd, J = 8.3, 4.8, 0.4 Hz, 1H), 3.70 (q, J = 7.0 Hz, 2H), 2.25 2.09 (m, 1H), 2.02 (d, J = 7.0 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H), 0.90 (d, J = 6.6 Hz, 6H).

Page 429 of 619

327	90-92	(thin film) 1656	ESIMS m/z 443 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d. J = 1.8 Hz, 1H), 8.45 (d, 7 = 2.5 Hz, 1H), 7.88 (s, 1H), 7.84 (dt, J = 9.3, 2.4 Hz, 1H), 4.00 (brs, 1H), 3.73 (s, 3H), 3.39 (brs, 1H), 2.85 (s, 2H), 2.26 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H).
328		(thin film) 1651	ESIMS m/z 341 ([M])	1H NMR (400 MHz, CDCI3) δ 9.03 (d, J ~2.5 Hz, 0.6H), 8.99 (d, J = 2.4 Hz, 0.4H), 8.63 - 8.55 (m, 1H), 8.29 (s. 0.6H), 8.21 (s, 0.4H), 8.06 - 7.98 (m, 1H), 7.46- 7.38 (m, 1H), 3.38 -3.23(m, 4H), 3.22-3.12 (m, 1H), 2.76-2.56 (m, 4H), 1.26 (d, 7 = 6.9 Hz, 1.2H), 1.21 (d, 7=6.9 Hz, 1.8H).

Page 430 of619

329

(thin film) 1660

ESIMS m/z 357 ([M])

’H NMR (400 MHz, CDCI3) δ 9.00 (d, 7=2.4 Hz, 1H), 8.62 (dd, J = 4.8, 1.4 Hz, 1H), 8,22 (s, 1H), 8.00 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.43 (ddd, 7=8.3, 4.8, 0.7 Hz, 1H). 3.83 (dd, 7= 13.6, 10.8 Hz, 1H), 3.42 -3.30(m, 1H), 3.28 (s, 3H), 2.95 (s, 3H), 2.89 (dd, 7= 13.7, 2.7 Hz, 1H), 1.21 (d, 7 = 7.0 Hz, 3H).

Page 431 of619

330

(thin film) 1650

ESIMS m/z 355 ([M])

1H NMR (400 MHz, CDCI3) δ 9.04 (d, 7 = 2.5 Hz, 0.6H), 8.99 (d, 7 = 2.5 Hz, 0.4H), 8.60 (m, 1H), 8.23 (s, 0.6H), 8.17 (s, 0.4H), 8.06 - 7.97 (m, 1H), 7.47- 7.38 (m, 1H), 4.26 -3.73 (m, 1H), 3.56 - 3.29 (m, 1H), 3.31 -3.05 (m, 2H), 2.78- 2.54 (m, 4H), 1.26 (d, 7 = 6.7 Hz, 1.2H), 1.22 (d, 7 = 6.7 Hz, 1.8H), 1.21 -1.13 (m, 3H).

Page 432 of 619

331		(thin film) 1657	ESIMS m/z 371 ([M])	’H NMR (400 MHz, CDCI3) δ 9.02 (d, 7 = 2.5 Hz, 1H), 8.62 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.19 (s, 1H), 8.01 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.44 (ddd, 7=8.3, 4.8, 0.6 Hz, 1H), 4.10 (s, 1H), 3.82 (dd, 7= 13.6, 11.0 Hz, 1H), 3.43- 3.21 (m, 2H), 2.94 (s, 3H), 2.88 (dd, 7= 13.6, 2.5 Hz, 1H), 1.21 (d, 7 = 7.0 Hz, 3H), 1.17 (t, 7= 7.2 Hz, 3H).
332		(IR thin film) 1699	ESIMS m/z 385 ([M+Hf)	’H NMR (400 MHz. CDCI3) δ 8.92 (d,7 = 2.5 Hz, 1H), 8.58 (dd. 7 = 4.7, 1.3 Hz, 1H), 8.05-7.97 (m, 1H), 7.91 (bs, 1H), 7.50-7.31 (m, 1H). 4.21 - 3.83 (m. 1H), 3.54 -3.08 (m, 1H), 1.90 (d, 7 = 6.9 Hz, OH), 1.581.33 (m, 10H), 1.24-0.92 (m, 1H),

Page 433 of619

333		(IR thin film)1701		1H NMR (400 MHz, CDCI3) Ô 8.93 (bs, 1H), 8.59 (d, J = 4.2 Hz, 1H), 8.03 (ddd, J =8.3, 2.6, 1.4 Hz, 1H), 7.89 (s, 1H), 7.443 (dd, J = 8.3, 4.7 Hz, 1H), 3.84-3.54 (m, 5H), 1.19 (t, J = 7.2 Hz, 3H).
334		(thin film) 3272, 3080, 1642.	ESIMS m/z 284 ([M+Hf), 282 ([Μ-H])	’H NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.71 (s, 1H). 8.52 (d, J = 2.5 Hz, 1H), 8.22 (dt, J = 10.3, 2.4 Hz, 1H), 8.15 (s, 1H), 6.47 (t, J = 5.5 Hz, 1H), 3.21 - 3.07 (m, 2H), 1.07 (t, J = 7.2 Hz, 3H).

Page 434 of 619

335	128- 133		ESIMS m/z 311 ([M+H]+).	1H NMR (400 MHz, CDCI3) δ 8.94 (d, 7=2.4 Hz, 1H), 8.62 (d, 7 = 3.8 Hz, 1H). 8.15 (s, 1H), 8.03 (d, 7 = 8.3 Hz, 1H), 7.46 (dd, 7 = 8.3, 4.8 Hz, 1H), 3.34 (q, 7 = 6.8 Hz, 1H), 3.26 (s, 3H), 2.10 (s, 3H), 1.45 (d, 7 = 6.9 Hz, 3H).
336	128- 133		ESIMS m/z 309 ([M+H]+).	1H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 2.4 Hz. 1H), 8.60- 8.55 (m, 1H), 8.01 (d, 7 = 7.5 Hz, 1H), 7.91 (s, 1H), 7.42 (dd, 7 = 8.2, 4.8 Hz, 1H), 3.993.84 (m, 2H), 3.28 (s, 3H), 2.06 - 1.79 (m, 1H), 1.06 - 0.73 (m, 6H).

Page 435 of 619

337			ESIMS m/z 297 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.5 Hz, 1H), 8.62 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.13 (s, 1H), 8.04 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.50 - 7.43 (m, 1H), 3.26 (s, 3H), 3.12 (s, 2H), 2.24 (s, 3H).	13CNMR(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.
338			ESIMS m/z 295 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.93 (d, 7=2.6 Hz, 1H), 8.58 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.03 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.90 (s, 1H), 7.42 (dd, 7 = 8.3, 4.8 Hz, 1H), 4.18 (bs, 2H), 3.66 (q, 7 = 7.1 Hz, 2H), 1.33-1.10 (m, 6H).

Page 436 of 619

339		(IR thin film) 1720	ESIMS m/z 349 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.93 (d, J =2.3 Hz, 1H), 8.60 (d, J = 4.2 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.90 (s, 1H), 7.44 (dd, J = 8.1,4.6 Hz, 1H), 4.67-4.42 (m, 2H), 3.70 (q, J = 7.2 Hz, 2H), 1.22 (t, J =6.8 Hz, 3H).
340	134.0 136.0		ESIMS m/z 305 ((M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.80 (s, 1H), 8.41 -8.30(m, 2H), 7.84 (dt, J =9.6, 2.4 Hz, 1H), 6.67 (dd, J= 17.8, 11.4 Hz, 1H), 6.45 (s, 1H), 5.93 (d, J = 17.8 Hz, 1H), 5.51 (dd, J= 11.4, 1.1 Hz, 1H), 1.54 (s, 9H).

Page 437 of 619 t

341

(thin film) 1660

ESIMS m/z 331 ([M+H]*)

1H NMR (400 MHz, CDCI3) δ 9.00-8.87 (m, 1H), 8.61 -8.46 (m, 1H), 8.08- 7.95 (m, 1H), 7.86 - 7.75 (m, 1H), 7.47 - 7.33 (m, 1H), 3.40-3.04 (m, 2H), 2.85 (dd, J= 15.9, 7.4 Hz, 0.33H), 2.43 (dd, J =15.5, 6.5 Hz, 0.67H), 2.32 2.11 (m, 5H), 2.05 (s, 2H), 1.41 (d, J = 6.9 Hz, 1H), 1.27 (d, J = 6.7 Hz, 2H), 1.06- 0.93 (m, 0.67H), 0.88-0.76 (m, 1.33H), 0.77- 0.63 (m, 0.67H), 0.56-0.38 (m, 1.33H).

Page438of6l9

342

(thin film) 1646

ESIMS m/z 329 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 9.00-8.86 (m, 1H), 8.61 -8.45 (m, 1H), 8.09- 7.92 (m, 1H), 7.85 (s, 1H), 7.51 - 7.32 (m, 1H), 3.32 -3.16(m, 1H), 2.66-2.44 (m, 1H), 2.31-2.21 (m, 4H), 2.08 (s, 2H), 1.69-1.49 (m, 2H), 1.23- 0.88 (m, 1.67H), 0.88-0.71 (m, 2H), 0.58 - 0.39 (m, 1.33H).

Page 439 of 619

ESIMS m/z 339

¹H NMR (400 MHz, CDCI3) δ

8.98 - 8.87 (m, 1H), 8.62-8.46 (m, 1H), 8.07-

7.93 (m, 1H), 7.85 -7.78 (m, 1 H), 7.48 - 7.33 (m, 1H), 3.33-3.21 (m, 0.67H), 3.133.04 (m, 0.33H), 3.04 - 2.95 (m, 0.67H), 2.70 -

2.28 (m, 3.33H),

2.24 (s, 3H), 1.08 -0.96 (m, 0.67H),

0.87 -0.76 (m, 1.33H), 0.760.65 (m, 0.67H),

0.55 - 0.39 (m, 1.33H).

Page 440 of 619 r~ --—

344

(thin film) 1657

ESIMS m/z 353 ((M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.98-8.88 (m, 1H), 8.57 (dd, 7 = 4.7, 1.1 Hz, 0.67H), 8.52 - 8.48 (m, 0.33H), 8.08 - 7.93 (m, 1H), 7.78 (m, 1H), 7.46 - 7.33 (m, 1H), 3.90-3.77 (m, 0.33H), 3.303,19 (m, 0.67H), 3.15-3.06 (m, 0.33H), 2.98 - 2.61 (m, 1.67H), 2.30-2.13 (m, 3H), 2.04-1.92 (m, 1H), 1.40 - 1.32(m, 1H), 1.13 (d, 7 = 6.6 Hz, 2H), 1.08-0.94 (m, 0.67H), 0.93- 0.65 (m, 2H), 0.56 -0.34 (m, 1.33H).

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345			ESIMS m/z 266 <[M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.92 (d, 7=2.6 Hz, 1H), 8.60 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.04-8.00 (m, 1H), 8.00 (s, 1H), 7.45 (dd, 7 = 8.3, 4.8 Hz, 1H), 4.51 (d, 7 = 3.8 Hz, 1H), 3.24 (s, 3H), 2.80 (d, 7 = 4.7 Hz, 3H).	nCNMR(101 MHz, CDCh) δ 157.55, 148.53, 140.74, 139.94, 135.66, 126.17, 125.05, 124.09, 37.11, 27.78
346	76-82			1H NMR (400 MHz. CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.61 (m, 1H), 8.05 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.99 (s, 1H), 7.45 (ddd, 7 = 8.3, 4.8,0.6 Hz, 1H), 3.74 (q, 7 = 7.2 Hz, 2H), 2.87 (q, 7 = 7.4 Hz, 2H), 1.26 (t, 7 = 7.4 Hz, 3H), 1.19 (t, 7 = 7.2 Hz, 3H)

Page 442 of 619

347			ESIMS m/z 427 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.98 (d, J = 2.6 Hz, 1H), 8.64 (dd, J = 4.7, 1.4 Hz, 1H), 8.09 (s, 1H), 8.06 - 8.01 (m, 1H), 7.46 (dd, J = 8.3, 4.8 Hz, 1H), 3.94 - 3.57 (m, 3H), 3.13-3.01 (m, 1H), 2.95 (dd, J = 13.3, 6.1 Hz, 2H), 2.76 - 2.61 (m, 3H), 2.06 (d, J = 2.2 Hz, 5H), 1.19 (t, J = 7.2 Hz, 3H).	13C NMR (101 MHz, CDCI3) δ 148.76, 140.35, 140.24, 135.58, 128.34, 126.41, 124.10, 60.39, 53.43, 44.29, 33.06, 27.67, 21.06, 15.80, 14.23, 12.89.
348	250- 253		ESIMS m/z 300 ([M+H]*), 298 ([M-H]')	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.6 Hz, 1H), 8.53- 8.47 (m, 1H), 8.44 (d, J = 2.3 Hz, 1H), 8.08 (s, 1H), 8.00 - 7.93 (m, 1H), 7.41 - 7.33 (m, 1H), 6.75 (s, 1H), 3.72-3.56 (m, 4H).

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349		(thin film) 3377, 1662.	ESIMS m/z 243 ([M+H]*).	’H NMR (400 MHz, CDCI3) δ 8.93 (d, 7 = 2.5 Hz, 1H), 8.51 (dd, 7=4.7, 1.3 Hz, 1H). 8.19 (s, 1H), 7.99 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.38 (ddd, 7 = 8.3, 4.8, 0.5 Hz, 1H), 3.87- 3.83 (m, 2H), 2.57 (t, 7 = 8.1 Hz, 2H), 2.38 (s, 3H), 2.27 2.16 (m, 2H).
350			ESIMS m/z 374 ([M+2H]*)	’H NMR (400 MHz, CDCI3) δ 8.76 (d, 7= 1.6 Hz, 1H), 8.50 (d,7 = 2.4 Hz, 1H), 8.00 (s, 1H), 7.88 (dt, 7=9.1,2.3 Hz, 1H), 3.25 (S, 3H), 2.80 (t, 7 = 7.4 Hz, 2H), 2.46 (t, 7 = 7.4 Hz, 2H), 2.07 (s, 3H).	’3CNMR(101 MHz, CDCI3) δ 171.94, 137.14, 136.91, 135.08, 129.74, 128.83, 126.10, 114.00, 113.77, 77.34, 77.02, 76.70, 37.13, 33.76, 29.68, 15.96.

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351	142- 143		ESIMS m/z 342 ([M+2H]*), 340 «MD	1H NMR (400 MHz, CDCI3) δ 8.76 (s. 1H). 8.49 (d, J = 2.4 Hz, 1H), 7.96 (s, 1H), 7.88 (dt, 7 = 9.1, 2.3Hz, 1H), 3.22 (s, 3H), 2.57 (dd, 7=13.4, 6.7 Hz, 1H), 1.09 (d, 7 = 6.7 Hz, 6H).
352	58.5- 61.5		ESIMS m/z 319 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (S, 1H), 8.40 (s, 1H), 7.98- 7.78 (m, 2H), 6.65 (dd, 7= 17.9, 11.4 Hz, 1H), 5.94 (dd, 7= 17.9, 1.4 Hz, 1H), 5.46 (dd, 7 = 11.4, 1.4 Hz, 1H), 3.20 (s, 3H), 1.41 (s, 9H).

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353		(thin film) 1653	ESIMS m/z 321 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.78 (d, J= 1.8 Hz, 1H), 8.46 (d, J = 2.4 Hz, 1H), 7.98 (s, 1H), 7.91 (dt, J = 9.3, 2.4 Hz, 1H), 6.67 (dd, J= 18.0, 11.5 Hz, 1H), 5.92 (dd, J = 18.0, 1.0 Hz, 1H), 5.52 (dd, J= 11.5, 1.0 Hz, 1H), 3.25 (s, 3H), 2.77 (t, J = 7.3 Hz, 2H), 2.46 (t, J = 7.3 Hz, 2H), 2.04 (s, 3H).
354		(thin film) 1650	ESIMS m/z 335 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.79 (d, J =1.7 Hz, 1H), 8.45 (d, J = 2.5 Hz. 1H), 8.04 (s, 1H), 7.91 (dt, J = 9.3, 2.4 Hz, 1H), 6.69 (dd, J = 18.0, 11.5 Hz, 1H), 5.99 (d, J = 18.0 Hz, 1H), 5.53 (dd, J= 11,5, 1.1 Hz, 1H), 3.26 (s, 3H), 2.90 - 2.74 (m, 2H), 2.44 (dd, J = 12.0, 4.4 Hz, 1H), 1.99 (s, 3H), 1.12 (d, J = 6.5 Hz. 3H).

Page 446 of 619

355

112.0 114.5

ESIMS m/z 289 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.78 (d, J= 1.0 Hz, 1H), 8.45 (d, J = 2.4 Hz, 1H), 7.94 (s, 1H), 7.90 (dt, J =9.3, 2.3 Hz, 1H), 6.66 (dd, J = 18.0, 11.5 Hz, 1H), 5.91 (dd, J = 18.0, 1.1 Hz, 1H), 5.52 (dd, J= 11.6, 0.8 Hz, 1H), 3.21 (d, J = 6.5 Hz, 3H), 2.73-2.56 (m, 1Η), 1.05 (d, J = 6.7 Hz, 6H).

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356

(thin film) 1651

ESIMS m/z 335 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.79 (d, J= 1.8 Hz, 1H), 8.46 (d, J = 2.5 Hz, 1H), 7.98 (s, 1H). 7.91 (dt, 7 = 9.3, 2.4 Hz, 1H), 6.66 (dd, 7= 18.0, 11.5 Hz, 1H), 5.92 (dd, 7 = 18.0, 1.0 Hz, 1H), 5.52 (dd, 7=11.5, 1.0 Hz, 1H), 3.303.16 (m,4H), 2.51 (dd, 7= 15.7, 6.6 Hz, 1H), 2.27 (dd, 7= 15.7, 7.5 Hz, 1H), 2.03 (s, 3H), 1.26 (d, 7 = 6.8 Hz, 3H).

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357		(thin film) 1644	ESIMS m/z 333 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.80 (d, J =1.7 Hz, 1H), 8.46 (d, J = 2.5 Hz, 1H), 8.03 (s, 1H), 7.93 (dt, J = 9.3, 2.4 Hz, 1H), 6.69 (dd, J= 18.0, 11.5 Hz, 1H), 5.94 (dd, J = 18.0, 1.1 Hz, 1H), 5.53 (dd, J= 11.5, 1.1 Hz, 1H), 3.25 (s, 3H), 2.47 (ddd, J= 8.2, 5.5, 3.6 Hz, 1H), 2.08 (s, 3H), 1.73 (ddd, J = 8.6, 5.2, 3.6 Hz, 1H), 1.51 (ddd, J = 8.2, 5.1,4.4 Hz, 1H). 0.97 (ddd, J = 8.5, 5.5, 4.3 Hz. 1H).
358	107- 108		ESIMS m/z 394 ([M+Hf), 396 ([M+2Hf)	’H NMR (400 MHz, CDCI3) δ 8.75 (t, J =9.6 Hz, 1H), 8.51 (d, J = 2.5 Hz, 1H), 7.98 (s, 1H), 7.89 (dt, J= 9.0, 2.4 Hz, 1H), 3.25 (s, 3H), 2.67-2.44 (m, 2H). 2.44-2.33 (m, 2H).

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359	177- 178		ESIMS m/z 400 ([M+2H]*), 398	’H NMR (400 MHz, CDCI3) δ 8.77 (d, 7 = 2.0 Hz, 1H), 8.53 (d, 7 = 2.5 Hz, 1H), 8.03 (s, 1 H), 7.90 (d, 7=9.0 Hz, 1H), 3.68 (t, 7= 10.4 Hz, 1H), 3.473.31 (m, 1H), 3.27 (s, 4H), 2.98 (dd, 7= 16.7, 11.8 Hz,1H), 2.60 (s, 1H).
360			ESIMS m/z 337 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.92 (d, 7 = 2.4 Hz, 1H), 8.57 (d, 7 = 3.6 Hz, 1H), 8.00 (t, 7= 14.2 Hz, 1H), 7.79 (d, 7 = 62.4 Hz, 1H), 7.52 - 7.32 (m, 1H), 3.51 (dt, 7 = 17.0, 7.9 Hz, 2H), 1.68- 1.46 (m, 11 H), 0.93 (t, 7 = 7.4 Hz, 3H).

Page 450 of 619

361	62-72		ESIMS m/z 349 ([M+Hf)	’H NMR (400 MHz, CDC!3) δ 8.92 (d, 7 = 2.4 Hz, 1H), 8.57 (d, J = 3.7 Hz, 1H), 8.03 (d, 7 = 7.3 Hz, 1 H), 7.92 (s, 1H), 7.42 (dd, 7 = 8.3, 4.7 Hz, 1H), 3.43 (d, 7 = 6.9 Hz, 2H), 1.37 (bs, 9H), 1.13-0.87 (m, 1H), 0.59- 0.39 (m, 2H), 0.29 -0.09 (m, 2H).
362		(thin film) 1655	ESIMS m/z 341 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (t. 7 = 9.2 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.20 - 7.86 (m. 2H), 7.59 - 7.33 (m, 1H), 3.73 (ddt, 7 = 20.5, 13.4, 6.8 Hz, 2H), 3.23 - 3.06 (m, 1H), 2.94 -2.81 (m, 1H), 2.74-2.62 (m, 2H), 2.59 (s, 3H), 1.25- 1.07 (m, 3H).

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363		(thin film) 1661	ESIMS m/z 357 ([M+Hf)	1H 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, 1H), 3.73 (d, J = 7.0 Hz, 2H), 3.44 (dd, J = 22.5, 15.7 Hz, 2H), 2.96 (s, 3H), 2.71 (t, J = 6.9 Hz, 2H), 1.18 (dd, J = 8.8, 5.5 Hz, 3H).
364		(thin film) 1436	ESIMS m/z 355 ((M+Hf)	1H NMR (400 MHz, CDCI3) 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, 1 H), 3.21 -2.46 (m, 3H), 2.01 (s, 3H), 1.35-1.15 (m, 6H).

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365

(thin film) 1660

ESIMS m/z 339 ([M+H]+)

Ή NMR (400 MHz, CDCI3) δ 8.94 (t, J = 8.8 Hz, 1H), 8.62 (dt, J = 17.9, 9.0 Hz, 1H), 8.06 (tdd, J =8.4, 2.7, 1.5 Hz, 1H), 7.97 (d, J =3.8 Hz, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.5 Hz, 1H), 3.733.50 (m, 2H), 2.87 -2.73(m, 2H), 2.53 - 2.37 (m, 2H), 2.07 (s, 3H), 1.64- 1.47 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H).

Page 453 of 619

366

(thin film) 1654

ESIMS m/z 353 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7=2.6 Hz, 1H), 8.62 (d, 7 = 4.7 Hz, 1H), 8.04 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 8.00 (s, 1H), 7.46 (dd,7 = 8.3, 4.8 Hz, 1H), 3.71 (dd, 7= 113.8, 59.4 Hz, 2H), 2.86 (dd, 7= 12.7, 9.0 Hz, 1H), 2.71 (d, 7 = 6.6 Hz, 1H), 2.45 (dt. 7=30.4, 15.2 Hz, 1H), 1.57 (dt, 7= 14.9, 7.5 Hz, 2H), 1.16 (d, 7 = 6.7 Hz, 3H), 0.94 (t, 7 = 7.4 Hz, 3H).

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367		(thin film) 1658	ESIMS m/z 353 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.95 (t, J =8.0 Hz, 1H), 8.61 (dd, J~ 12.3, 11.3 Hz, 1H), 8.06 (tdd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.96 (d, J = 3.8 Hz. 1H), 7.47 (dd, 7=8.3, 4.7 Hz, 1H), 3.50 (s, 2H), 2.82 (dd, 7 = 21.9, 14.6 Hz, 2H), 2.47 (t, 7 = 7.3 Hz, 2H), 2.07 (s, 3H), 1.90- 1.62 (m, 1H), 0.95 (d, 7 = 6.7 Hz. 6H).
368	84-92		ESIMS m/z 325 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.61 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.05 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.99 (s, 1H), 7.45 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H). 3.74 (q,7 = 7.2 Hz, 2H), 2.85 (t, 7 = 7.3 Hz, 2H), 1.66- 1.58 (m, 2H), 1.19 (t, 7 = 7.2 Hz, 3H), 0.96 (t, 7=7.4 Hz, 3H).

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369			ESIMS m/z 321 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 10.07 (d, J = 0.5 Hz, 1H), 8.85 (s, 1H), 8.52 (s, 1H), 8.28 - 7.88 (m, 2H), 3.26 (s, 3H), 1.49 (s, 9H).
370			ESIMS m/z 388 ([M+2H]+), 386 ([MD	1H NMR (400 MHz, CDCI3) δ 8.76 (d, 7 = 2.0 Hz, 1H), 8.50 (d, 7 = 2.5 Hz, 1H), 7.99 (s, 1H), 7.88 (d, 7= 9.1 Hz, 1H), 3.30-3.22 (m, 1H), 3.25 (s, 3H), 2.54-2.44 (m, 1H), 2.28 (dd, 7 = 15.6, 7.6 Hz, 1H), 2.07(s, 3H), 1.29 (d, 7 = 6.8 Hz, 3H).

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371			ESIMS m/z 386 ([M+2H]*), 384 ([M])	’H NMR (400 MHz, CDCI3) δ 8.78 (d, J= 1.8 Hz, 1H), 8.50 (d, J = 2.4 Hz, 1H), 8.02 (s, 1H), 7.90 (dt, J= 9.1,2.3 Hz, 1H), 3.25 (s, 3H), 2.55-2.44 (m, 1H), 2.12(s,3H), 1.72-1.48 (m, 3H), 1.08-0.93 (m. 1H).	’3C NMR (101 MHz, CDCI3) δ 172.01, 160.77, 158.18, 136.88, 135.14, 129.87, 128.91, 126.19, 114.04,37.25, 24.97, 23.16, 18.09, 16,47.
372		(thin film) 1421	ESIMS m/z 341 ([M+Hf>	’H NMR (400 MHz, CDCI3) δ 8.95 (dd, J =12.3, 2.6 Hz, 1H), 8.65 (dd, J = 4.7, 1.4 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.99 (d, J =7.2 Hz, 1H), 7.53-7.43 (m. 1H), 4.29 (s, 2H), 2.97 (t, J = 7.5 Hz, 2H), 2.852.62 (m, 2H), 2.04 (s, 3H), 1.29 (td, J = 7.1, 3.4 Hz, 3H).

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373	103- 113		ESIMS m/z 339 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1H), 8.61 (dd, J = 4.7, 1.4 Hz, 1H), 8.06 (ddd, J = 8.3, 2.7,1.4 Hz, 1H), 7.99 (s, 1H), 7.44 (ddd, J =8.3, 4.8, 0.6 Hz, 1H), 3.73 (q, J= 7.2 Hz, 2H), 3.44 (h, J = 6.9 Hz, 2H), 1.64- 1.52 (m, 1H), 1.29 (d, J = 6.9 Hz, 2H), 1.19 (t, J= 7.2 Hz, 3H), 0.95 (t, J =7.4 Hz, 3H).
374	167- 170		ESIMS m/z 264 ([M+H]*).	’H NMR (400 MHz, CDCI3) δ 8.93 (d, J = 2.5 Hz, 1H), 8.51 (dd, J = 4.7, 1.3 Hz, 1H), 8.19 (s. 1H), 7.99 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.38 (ddd, J = 8.3, 4.8, 0.5 Hz, 1H), 3.87-3.83 (m, 2H), 2.57 (t, J = 8.1 Hz, 2H), 2.38 (s, 3H), 2.27 - 2.16 (m, 2H).

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375		(thin film) 3313, 3113, 2967, 1636.	ESIMS m/z 262 ([M-H]').	’H NMR (400 MHz, DMSO-t/6) δ 8.90 (s, 1H), 8.50 (s, 1H), 8.42 (d, J = 2.4 Hz, 1 H), 8.10 (dt, J = 10.6, 2.3 Hz, 1H), 7.97 (s, 1H), 6.19 (t, J = 5.6 Hz, 1H), 3.19-3.04 (m, 2H), 2.20 (s, 3H), 1.06 (t, J = 7.2 Hz, 3H).
376		(thin film) 3321. 3288, 1632.	ESIMS m/z 276 ([M-H]·).	’H NMR (400 MHz, DMSO-d6) δ 8.90 (s, 1H), 8.50 (s,1H), 8.42 (d, J = 2.5 Hz, 1H), 8.10 (dt, J = 10.6, 2.3 Hz, 1H), 7.98 (s, 1H), 6.24 (t, J = 5.7 Hz, 1H), 3.06 (dd, J = 12.9, 6.7 Hz, 2H), 2.21 (s, 3H), 1.531.36 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H).

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377		(thin film) 3310, 3103,1631.	ESIMS m/z 276 ([M+H]*), 274 ([Μ-HD,	1H NMR (400 MHz, DMSO-ctô) δ 8.90 (s, 1H), 8.51 (s, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 8.12 (t, 7 = 2.3 Hz, 1H), 8.09 (d, 7 = 2.1 Hz, 1H), 6.38 (t, 7 = 5.8 Hz, 1H), 5.87 (ddt, 7 = 17.2, 10.3, 5.1 Hz, 1H). 5.17 (dq. 7 = 17.2, 1.7 Hz, 1H), 5.10-5.03 (m, 1H), 3.80-3.70 (m, 2H), 2.22 (s, 3H).
378	143- 145	(thin film) 1619	ESIMS m/z 329 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, 7 = 1.4 Hz, 1H), 8.43 (d, 7 = 2.5 Hz, 1H), 7.94 (s, 1 H), 7.87 (dt, J = 9.4, 2.4 Hz, 1H), 7.44 (s, 1H), 6.98 (s, 1H), 3.80 (s, 5H), 2.17 (s, 3H), 1.22 (t,7 = 7.1 Hz, 3H).

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379	135- 138	(thin film) 1614	ESIMS m/z331 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.94 (s. 1H), 8.63 (s, 1H), 8.05 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 7.96 (s, 1H), 7.51 (s, 1H), 7.46 (dd, 7 = 8.3, 4.7 Hz, 1H), 7.07 (s, 1H), 3.82 (s, 5H), 1.24 (t, 7 = 7.2 Hz, 3H).
380	97-99	(thin film) 1684	ESIMS m/z 310 ([M+HD	’H NMR (400 MHz, CDCI3) δ 8.71 (s, 1H), 8.36 (d, 7 = 2.4 Hz, 1 H), 7.98-7.74 (m, 2H), 2.27 (s, 3H), 1.45 (s, 9H).
381	96-99	(thin film) 1693	ESIMS m/z 312 ([M+HD	’H NMR (400 MHz, CDCI3) δ 8.91 (d,7 = 2.5 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.01 (d, 7 = 7.8 Hz, 1H), 7.91 (brs, 1H), 7.41 (dd, 7 = 8.3,4.7 Hz, 1H), 1.46 (s, 9H).

Page461 of6l9

382		(thin film) 1660	ESIMS m/z 380 ([Μ+ΗΠ	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7=2.0 Hz, 1H), 8.64 (d, J = 4.0 Hz, 1H). 8.05 (ddd, 7 = 8.4, 2.7, 1.4 Hz, 1H), 7.97 (s, 1H). 7.47 (dd, 7 = 8.3, 4.7 Hz, 1H), 3.73 (q, 7 = 7.2 Hz, 2H), 3.14 (t, 7 = 6.7 Hz, 2H), 2.58 (t, J = 6.7 Hz, 2H), 1.18 (t, 7= 7.2 Hz, 3H).
383		(thin film) 2975, 2916, 1711.	ESIMS m/z 427 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.5 Hz. 1H), 8.62 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.06 (d, 7 = 0.8 Hz, 1H), 8.068.02 (m, 1H), 7.45 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 3.44- 3.30 (m, 2H), 2.94 (dt, 7 = 13.2, 8.5 Hz, 2H), 2.54 (ddd, 7 = 13.2, 6.0, 2.3 Hz, 2H), 2.09 (d, 7 = 5.3 Hz, 6H), 1.32 (t, J = 6.7 Hz, 6H).

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384			EIMS m/z 286	’H NMR (400 MHz, Acetone) δ 9.09 (d, J = 2.5 Hz, 1H), 8.51 (dd, J =5.3, 2.0 Hz, 2H), 8.19 (ddd, J = 8.3, 2.7, 1.5 Hz. 1H), 7.51 (ddd, J = 8.3, 4.7, 0.7 Hz, 1H), 3.14 (s, 3H), 2.71 -2,63 (m, 2H), 2.36-2.30 (m, 2H), 2.28 (s, 3H), 2.09 (s, 3H).	’3C NMR (101 MHz, CDCI3) δ 207.75 (s), 172.62 (s), 149.98 (s), 141.33 (s), 137.98 (s), 134.83 (s), 130.19(5), 128.68 (s), 126.05 (s), 125.47 (s), 38.29 (s), 37.07 (s), 30.00 (s), 27.64 (s), 11.09 (s).
385		(thin film) 3342, 2972, 1644.	ESIMS m/z 278 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.74 (d, J =0.9 Hz, 1H), 8.41 (d, J = 2.4 Hz, 1H), 7.94 (s, 1H), 7.84 (dt, J = 9.4, 2.3 Hz, 1H), 3.30- 3.22 (m, 2H), 3.21 (s, 3H), 2.27 (s, 3H), 1.08 (t, J = 7.2 Hz, 3H).

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386		(thin film) 3330, 1647.	ESIMS m/z 292 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 8.74 (d. J= 1.6 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.93 (s, 1H), 7.84 (dt, J = 9.4, 2.3 Hz, 1H). 4.47 (s, 1 H), 3.21 (s, 3H), 3.19-3.10 (m, 2H). 2.27 (s, 3H), 1.53- 1.38 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H).
387		(thin film) 3334, 3088, 1641.	ESIMS m/z 290 ([M+H]*), 288 ([M-HD.	1H NMR (400 MHz, CDCI3) δ 8.74 (d, J = 1.4 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.96 (s, 1H), 7.84 (dt, J = 9.4, 2.3 Hz, 1H), 5.82 (ddt, J = 17.1, 10.2,5,6 Hz, 1H), 5.09 (ddq, J = 10.3, 8.7, 1.5 Hz, 2H), 4.57 (t, J = 5.5 Hz, 1H), 3.84 (tt, J = 5.7, 1.5 Hz, 2H), 3.22 (s, 3H), 2.28 (s, 3H).

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388		(thin film) 1670.	ESIMS m/z 422 ([M+H]*2).	1H NMR (400 MHz, CDCI3) δ 8.77 (s, 1H), 8.46 (s, 1H), 8.05 (d, J = 13.3 Hz, 1H), 7.85 (dt, J = 9.2, 2.2 Hz, 1H), 4.48 (s, 1H). 4.13 (dd. 7 = 11.7, 9.2 Hz, 1H), 3.57 (dd, 7 = 9.2, 3.7 Hz, 1H), 3.31 (d, 7 = 2.9 Hz, 3H), 2.35 (d, J = 4.5 Hz, 3H).
389		(thin film) 1646	ESIMS m/z 322 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.57 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.92 (s, 1H), 7.43 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 4.20 - 3.27 (m, 2H), 2.87 (dd,7 = 12.6, 9.4 Hz, 1H), 2.72 (s, 1H), 2.42 (dd, 7 = 12.8, 5.1 Hz. 1H). 2.31 (s, 3H), 1.16 (t, 7 = 7.1 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H).

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390	81-84	(thin film) 1646	ESIMS m/z 340([M+H]+)	’H NMR (400 MHz, CDCI3) δ 8.82 - 8.70 (m, 1H), 8.48-8.39 (d, J = 2.5 Hz, 1H), 8.00-7.91 (s, 1H), 7.91 7.82 (m, 1H), 4.13 -3.25 (s, 3H), 2.96 - 2.80 (m, 1 H), 2.76-2.57 (s, 1H), 2.482,36 (m, 1H), 2.36 - 2.26 (s, 3H), 1.19 -1.13 (m, 3H), 1.13-1.08 (d, J = 6.7 Hz, 3H).
391		(thin film) 1655	ESIMS m/z 328 ([M+H]*)	’H NMR (400 MHz. CDCI3) δ 9.01 -8.89 (d, J = 2.6 Hz, 1H), 8.678.57 (m, 1H), 8.06 -8.01 (m, 2H), 7.50-7.43 (m, 1H), 3.30-3.23 (s, 3H), 2.91 - 2.83 (m, 1H), 2.82 -2.71 (m, 1H), 2.52-2.41 (m, 1H), 1.20-1.12 (d, 7 = 6.6 Hz, 3H).

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392		(thin film) 1652	ESIMS m/z xxx ([M+H]+) 342	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.07-8.03 (m, 1H), 8.01 (s, 1H), 7.46 (ddd, 7 = 8.3, 4.8, 0.4 Hz, 1H), 3.94-3.51 (m, 2H), 2.86 (dd, 7 = 12.8, 8.9 Hz, 1H), 2.76-2.63 (m, 1H), 2.47 (dd, 7 = 12.8, 5.4 Hz, 1H), 1.18 (t, 7 = 7.2 Hz. 3H), 1.16 (d, 7 = 6.7 Hz, 3H).
393		(thin film) 1652	ESIMS m/z 327 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.4 Hz, 1H), 8.63 (dd, 7 = 4.6, 0.9 Hz, 1H), 8.06 (ddd, 7 = 8.4, 2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.52 - 7.40 (m, 1H), 3.72 (q,7 = 7.2 Hz, 2H), 2.78 (s, 2H), 2.06 (s, 3H), 1.17 (t, 7 = 7.2 Hz, 3H).

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394		(thin film) 1642	ESIMS m/z 325 ([M+Hf) 1	1H NMR (400 MHz, CDCI3) δ 8.76 (d, J = 1.6 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.91 (s. 1H), 7.86 (dt, J = 9.4, 2.4 Hz, 1H), 3.69 (d. J = 5.0 Hz, 2H), 2.77 (s, 2H), 2.27 (s, 3H), 2.05 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H).
395		(thin film) 1675.	ESIMS m/z 424 ([M+Hf2).	1H NMR (400 MHz, CDCI3) δ 8.99 - 8.90 (d, J = 2.6 Hz, 1H), 8.68 8.59 (m, 1H), 8.19 -8.13 (s, 1H), 8.06-8.00 (m, 1 H), 7.51 -7.41 (m, 1H), 4.51 - 4.40 (s, 1H), 4.17 -4.04(m, 1H), 3.63-3.56 (m, 1H), 3.38-3.28 (s, 3H).

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396		(thin film) 1654	ESIMS m/z 313 ([Μ+ΗΠ	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.63 (dd, J = 4.7, 1.4 Hz, 1H), 8.05 (ddd, J = 8.4, 2.7, 1.4 Hz, 1H), 8.01 (s, 1H), 7.47 (ddd, J = 8.4, 4.8, 0.5 Hz, 1H), 3.25 (s, 3H), 2.79 (s. 2H), 2.07 (s, 3H).
397		(thin film) 1649	ESIMS m/z 312 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d, J = 1.6 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.94 (s, 1H), 7.85 (dt, J = 9.4, 2.4 Hz, 1H), 2.79 (t, J = 7.3 Hz, 2H), 2.44 (t, J = 7.3 Hz, 2H), 2.28 (s, 3H), 2.06 (s, 3H).

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398	103- 105	(thin film) 1645	ESIMS m/z 326 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.75 (d. J = 1.7 Hz, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.97 (s, 1H), 7.85 (dt, 7 = 9.4, 2.4 Hz, 1H), 2.88 (dd, 7 = 12.6, 9.4 Hz, 1H), 2.85-2.70 (m, 1H), 2.44 (dd, 7 = 12.6, 4.8 Hz, 1H), 2.31 (s, 3H), 2.01 (s, 3H), 1.13 (d, 7 = 6.7 Hz, 3H).
399	165.5 166.5		ESIMS m/z 329 ([M+2]+)	1H NMR (400 MHz, CDCI3) δ 8.78 (d, 7= 1.8 Hz, 1H), 8.64 (s, 1H), 8.41 (d, 7 = 2.3 Hz, 1H), 7.81 (dt, 7 = 9.4, 2.4 Hz, 1H), 7.13 (s, 1H), 2.64 (hept, J = 6.9 Hz, 1H), 1.30 (d, 7 = 6.9 Hz, 6H).

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400

(thin film) 1650

ESIMS m/z 380 «M+Hf)

1H NMR (300 MHz, CDCI3) δ 8.93 (d, 7=2.5 Hz, 1H), 8.54 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.00 (ddd, 7 = 8.3, 2.6, 1.5 Hz, 1H), 7.89 (s, 1H), 7.40 (dd, 7 = 8.3, 4.8 Hz, 1H), 4,32 - 3.03 (m, 2H), 2.76 (t, 7 =7.2 Hz, 2H), 2.57 (dd, 7 = 12.7, 5.5 Hz, 1H), 2.46-2.31 (m. 3H), 2.25 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H), 1.97- 1.84 (m, 1H), 1.03 (d, 7 = 6.7 Hz, 3H).

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401

(thin film) 1650

ESIMS m/z 394 ((M+Hf)

’H NMR (300 MHz, CDCI3) δ 8.92 (d, J = 2.4 Hz, 1H), 8.53 (d, J = 3.9 Hz, 1H), 8.00 (ddd, 7 = 8.0, 2.3, 1.2 Hz, 1H), 7.92 (s, 1H), 7,39 (dd, 7 = 8.3, 4.8 Hz, 1H), 4.263.04 (m, 2H), 3.03 -2.60(111, 2H), 2.59-2.34 (m, 3H), 2.28 (s, 3H), 2.12-2.01 (m, 3H), 2.00-1.85 (m. 4H), 1.09 (d. 7 = 6.5 Hz, 3H), 1.01 (d, 7 = 6.7 Hz, 3H).

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402

(thin film) 1649

ESIMS m/z 347 ([M+H]*)

’H NMR (300 MHz, CDCI3) δ 8.93 (d, J =2.6 Hz, 1H), 8.53 (dd, J = 4.7, 1.2 Hz, 1H), 8.00 (ddd, J = 8.3,2.5, 1.5 Hz, 1H), 7.87 (s, 1H), 7.39 (dd, J = 8.4, 4.8 Hz, 1H), 4.382.87 (m, 2H), 2.64 -2.45(m, 2H), 2.42 - 2.29 (m, 1H), 2.23 (s, 3H), 2.03 (s, 3H), 1.98 -1.83 (m, 1H), 1.08-0.98 (m, 9H).

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403

(thin film) 1694

ESIMS m/z 349 ([M+HD

’H NMR (300 MHz, CDCI3) δ 8.90 (d, 7 = 2.6 Hz, 1H), 8.49 (dd, 7=4.8, 1.3 Hz, 1H), 7.98 (ddd, 7 = 8.3, 2.5, 1.5 Hz, 1H), 7.82 (d, 7 = 2.0 Hz, 1H), 7.36 (dd, 7=8.4, 4.8 Hz, 1H), 4.234.09 (m, 2H), 3.64 (dd,7= 13.8, 6.7 Hz, 1H), 3.47 (dd, 7= 13.8, 7.7 Hz, 1H), 2.53 (dd, 7 = 12.8, 5.8 Hz, 1H), 2.36 (dd, 7= 12.8, 7.5 Hz. 1H), 2.23 (s, 3H), 2.03 (s, 3H), 2.00-1.87 (m, 1H), 1.271.12 (m, 3H), 1.03 (d, 7 = 6.7 Hz, 3H).

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404			ESIMS m/z 375 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.80 (d, J= 1.2 Hz, 1H), 8.67 (s, 1H), 8.38 (d. J = 2.5 Hz, 1H), 7.85 (dt, J = 9.6, 2.3 Hz, 1H), 7.24 (s, 1H), 6.73 (dd, 7 = 17.9, 11.4 Hz, 1H), 5.90 (dd, J 17.9,1.0 Hz, 1H), 5.56 (dd, J= 11.4, 1.0 Hz, 1H), 2.662.55 (m, 1H), 1.29 (d, J = 6.9 Hz, 6H).
405		(thin film) 1656	ESIMS m/z 314 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.6 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.05 (ddd, J = 8.7, 2.6, 1.4 Hz, 1H). 8.02 (s, 1H), 7.47 (dd, 7 = 8.3, 4.8 Hz, 1H), 2.80 (t, 7 = 7.4 Hz. 2H), 2.49 (t, J = 7.4 Hz, 2H). 2.07 (s, 3H).

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406

(thin film) 1651

ESIMS m/z 328 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.95 (d, J =2.5 Hz, 1H), 8.63 (dd, J = 4.7, 1.2 Hz, 1H), 8.12-8.01 (m, 2H). 7.47 (dd, J = 8.3, 4.7 Hz, 1H), 2.87 (dd, J = 12.5, 9.0 Hz, 1H), 2.83-2.73 (m, 1H), 2.48 (dd, J = 12.5, 5.1 Hz, 1H), 2.02 (s, 3H), 1.17 (d, J =6.6 Hz, 3H).

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407		(thin film) 2916, 1713.	ESIMS m/z 413 ([M+H]*).	1H NMR (300 MHz, CDCI3) δ 8.96-8.92 (d, J = 2.7 Hz, 1H), 8.648.59 (dd, J = 4.9, 1.4 Hz, 1H), 8.077.99 (m, 2H), 7.50 - 7.40 (dd, J = 8.4, 4.8 Hz, 1H), 3.393.28 (m, 1H), 3.10 - 2.99 (td, J - 7.2, 3.9 Hz, 2H), 2.96 2.86 (dd, J= 13.2, 8.7 Hz, 1H), 2.862.79 (t, J = 7.3 Hz, 2H), 2.58-2.48 (dd, 7= 13.1, 5.8 Hz, 1H). 2.14 2.12 (s, 3H), 2.09 -2.06 (s, 3H), 1.30- 1.26 (d, 7 = 6.9 Hz, 3H).
408		(thin film) 1692	EIMS m/z 320 ([M])	’H NMR (300 MHz, CDCI3) δ 8.71 (t, 7= 1.4 Hz, 1H), 8.35 (d, 7 = 2.6 Hz, 1H), 7.83 (dt, 7=9.5, 2.3 Hz, 2H), 3.18 (s, 3H). 2.65 (q, 7 = 7.5 Hz, 2H), 1.44 (s, 9H), 1.25 (t,7 = 7.1 Hz, 3H).

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409	165- 168		ESIMS m/z 400 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.64 (s, 1H), 8.41 (d, J = 2.5 Hz, 1H), 7.80 (s, 1H), 7.72 (d, J =9.2 Hz, 1H), 3.40 (s, 3H), 2.63 (s, 3H), 2.26 (s, 3H).
410		(thin film) 2916, 1713.	ESIMS m/z 399 ([M+H]*), 397 ([M-H]·)	1H NMR (300 MHz, CDCI3) δ 8.96-8.91 (d, J = 2.6 Hz, 1H), 8.65- 8.56 (d, J = 4.6 Hz, 1H), 8.068.01 (m, 1H), 8.01 -8.01 (s, 1H), 7.49 - 7.40 (dd, J = 8.4, 4.8 Hz, 1H), 3.03-2.97 (m, 4H), 2.84 - 2.78 (t, J = 7.2 Hz, 4H), 2.13-2.10 (s, 6H).

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411

(thin film) 3336, 2973, 1644, 1599.

ESIMS m/z 292 ([M+Hf).

1H NMR (400 MHz, CDCI3) δ 8.78 - 8.73 (dd, J = 2.0, 1.1 Hz, 1H), 8.44-8.38 (d, J = 2.5 Hz, 1H), 7.947.90 (s, 1H), 7.89 - 7.81 (dt, J = 9.4, 2.3 Hz. 1H), 4.384.31 (m, 1H), 3.69 -3.60 (q, J = 7.1 Hz, 2H), 3.29 - 3.16 (qd, J = 7.2, 5.6 Hz, 2H), 2.30 - 2.17 (S, 3H), 1.16 -1.10 (t. J = 7.1 Hz, 3H), 1.101.04 (t, J = 7.2 Hz, 3H).

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412

(thin film) 3340, 2965, 2931, 1644, 1599.

ESIMS m/z 306 ([M+Hf).

1H NMR (400 MHz, CDCI3) δ 8.77 - 8.73 (dd, J = 2.4, 1.0 Hz, 1H), 8.43-8.39 (d, J = 2.5 Hz, 1H), 7.947.91 (s, 1H), 7.88 -7.82 (dt, 7=9.4, 2.3 Hz, 1H), 4.444.36 (m, 1H), 3.70 -3.59 (q,7=7.1 Hz, 2H), 3.19 3.09 (ddd, 7 = 8.1, 7.1, 5.9 Hz, 2H), 2.28 - 2.24 (s, 3H), 1.52-1.37 (h, 7=7.4 Hz, 2H), 1.16-1.08 (t, 7= 7.1 Hz, 3H), 0.89 - 0.80 (t, 7 = 7.4 Hz, 3H).

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413		(thin film) 3292, 3084, 1638, 1602.	ESIMS m/z 304 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 8.81-8.67 (dd, J = 2.4, 1.0 Hz, 1H), 8.46-8.34 (d, J = 2.5 Hz, 1H), 7.977.89 (s, 1H), 7.88 -7.75 (dt, 7= 9.4, 2.3 Hz, 1H), 5.88- 5.72 (ddt, J = 17.1, 10.2, 5.6 Hz, 1H), 5.15-4.99 (m, 2H), 4.52 - 4.40 (t, J = 5.7 Hz, 1H), 3.87-3.75 (tt, 7 = 5.7, 1.6 Hz, 2H), 3.71 - 3.58 (q, 7=7.1 Hz, 2H), 2.32 - 2.20 (s, 3H), 1.191.04 (t, 7= 7.1 Hz, 3H).
414			ESIMS m/z 354 ([M+2H]*)	1H NMR (400 MHz, CDCI3) δ 8.95-8.89 (d,7 = 2.7 Hz, 1H), 8.61 -8.54 (dd, 7 = 4.8, 1.5 Hz, 1H), 8.07- 7.98 (m, 1H), 7.93-7.79 (s, 1H), 7.467.36 (m, 1H), 3.25 -3.17 (s, 3H), 1.52- 1.39 (s, 8H).

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415	85.5- 87.5		ESIMS m/z 412 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.93 (d, J = 2.5 Hz, 1H), 8.63 - 8.54 (m, 1H), 8.06 -7.98 (m, 1H), 7.95 (s, 1H), 7.45 -7.37 (m, 1H), 4.08-3.93 (m, 1H), 3.02-2.91 (m, 1H), 2.57 (dd, 7= 13.1, 6.5 Hz, 1H). 2.17 (s, 3H), 1.48 (s, 9H), 1.37 (d, 7 = 6.8 Hz, 3H).
416		thin film) 1653	ESIMS m/z 323 ([M+Hf)	’H NMR (400 MHz. CDCI3) δ 8.76 (s, 1H), 8.43 (s, 1 H), 7.93 (s, 1H), 7.87 (dt, 7 = 9.4, 2.2 Hz, 1H), 3.23 (S, 3H), 2.78 (t, 7= 7.3 Hz, 2H), 2.63 (q,7 = 7.6 Hz, 2H), 2.44 (t, 7 = 7.3 Hz, 2H), 2.05 (s, 3H), 1.32 (t, 7 = 7.6 Hz, 3H).

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417		(thin film) 1649	ESIMS m/z 337 ([M+H]*) «	1H NMR (400 MHz, CDCI3) δ 8.76 (s, 1H), 8.42 (s, 1H), 7.98 (s, 1H), 7.87 (dt, J = 9.4, 2.2 Hz, 1H), 3.24 (s. 3H). 2.87 (m, 1H), 2.79 (m, 1H), 2.67 (q, J = 7.5 Hz, 2H), 2.45 (dd, J= 12.6, 5.0 Hz, 1H), 2.03 (s, 3H), 1.34 (t, J = 7.6 Hz. 3H), 1.13 (d, J = 6.7 Hz, 3H).
418	105.0 108.0		ESIMS m/z 292 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.76 (s, 1H), 8.41 (s, 1H), 7.92 (s, 1H), 7.87 (d, J = 9.4 Hz, 1H), 3.21 (s, 3H), 2.62 (q, J = 7.6 Hz, 3H), 1.32 (t, J = 7.6 Hz, 3H), 1.07 (d, J = 6.7 Hz, 6H).

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419		(thin film) 1650	ESIMS m/z 337 ([M+H]*)	'H NMR (400 MHz, CDCI3) δ 8.75 (s, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 7.91 (s, 1H), 7.87 (dt. 7 = 9.4, 2.4 Hz, 1H), 3.333.13 (m. 1H), 2.63 (q, J = 7.6 Hz, 2H), 2.47 (dd, J = 15.5, 6.7 Hz, 1H), 2.25 (dd. 7 = 15.5, 7.3 Hz, 1H), 2.05 (s, 3H), 1.32 (t. 7 = 7.6 Hz, 3H), 1.27 (d. 7 = 6.8 Hz, 3H).
420		(thin film) 1643	ESIMS m/z 335 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.76 (s, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 7.97 (s, 1H), 7.88 (dt, J = 9.4, 2.3 Hz, 1H), 3.23 (s, 3H), 2.68 (q, 7 = 7.6 Hz, 2H), 2.48 (ddd, 7 = 8.1, 5.5, 3.6 Hz, 1H), 2.10 (s, 3H), 1.74 -1.67 (m, 1H), 1.54- 1.47 (m, 1H), 1.33 (t, 7 = 7.6 Hz, 3H), 0.99- 0.92 (m, 1H).

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421		(thin film) 1655	ESIMS m/z 385 ([M+HD	1H NMR (400 MHz, CDCI3) δ 8.62 (s, 1H), 8.42 (d, 7 = 2.5 Hz, 1H), 7.76 (dt, 7 = 9.4, 2.4 Hz, 1H), 7.46 (s, 1H), 7.13 (d, 7 = 8.3 Hz, 2H), 6.96 (d,7 = 8.2 Hz, 2H), 3.63 (s, 2H), 3.45 (s, 2H), 2.45 (s, 3H), 2.15 (s, 3H), 1.12 (t, 7 = 7.1 Hz, 3H).
422		(thin film) 1661	ESIMS m/z 388 ([M+Hf)	1H NMR (400 MHz. CDCI3) δ 8.80 (d,7 = 2.6 Hz. 1H), 8.62 (dd, 7 = 4.7, 1.3 Hz, 1H), 7.90 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1 H), 7.44 (dd, 7 = 8.7, 4.8 Hz, 1H), 7.42 (s, 1H), 7.12 (d, 7=8.3 Hz, 2H), 6.97 (d, 7 = 8.3 Hz, 2H), 3.68 (d, 7 = 8.3 Hz, 2H), 3.51 (s, 2H), 2.43 (s, 3H), 1.14 (t, 7= 7.2 Hz, 3H).

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423			EIMSm/z332	1H NMR (400 MHz, CDCI3) δ 8.77 (s, 1H), 8.42 (d. J =2.5 Hz, 1H), 7.90 (s, 1H), 7.86 (dt, J =9.4, 2.3 Hz, 1H), 3.66 (s, 2H), 2.48 (t, J = 6.9 Hz, 2H), 2.24 (s, 3H), 2.10 (s, 5H), 1.85 (p, J = 7.0 Hz, 2H), 1.13 (t, J= 7.2 Hz, 3H).	19F NMR (376 MHz, CDCIa) δ -120.98 (S).
424	85-86		EIMS m/z 330	1H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.46 (s, 1H), 8.10 (s, 1H), 8.02 (d, J = 9.2 Hz, 1H), 3.69 (s, 2H), 3.03 (p, J = 8.2 Hz, 1H), 2.56 (dd, J = 18.1, 9.0 Hz, 1 H), 2.41 (m, 1H), 2.27 (s, 3H), 2.11 (m, 5H), 1.15 (t, J =7.2 Hz, 3H).	19F NMR (376 MHz, CDCI3) δ -121.32 (s).

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425		(thin film) 1641	ESIMS m/z 425 ((M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.62 (s, 1H), 8.39 (d, 7 = 2.5 Hz, 1H), 7.71 (s, 2H), 7.52 (s, 2H), 7.42 (s, 2H), 3.87 (s, 2H), 2.11 (s, 3H), 1.25 (t. 7=7.0 Hz, 3H).
426		(thin film) 1649	ESIMS m/z 428 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.62 (s, 1H), 8.39 (d, 7 = 2.5 Hz, 1H), 7.71 (s,2H), 7.52 (s. 2H). 7.42 (s. 2H), 3.87 (s, 2H), 2.11 (s, 3H), 1.25 (t, 7=7.0 Hz. 3H).

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427

(thin film) 3084, 2974, 1653,

ESIMS m/z 365 ([M+H]*).

1H NMR (400 MHz, CDCI3) δ 8.98 - 8,94 (d, J = 2.5 Hz, 1H), 8.658.60 (dd. J = 4,7, 1.3 Hz, 1H), 8.088.03 (m, 1H), 8.03 -7.99 (s. 1H), 7.50 - 7.43 (m, 1H), 5.80-5.62 (m, 1H), 5.09- 4.99 (m, 2H), 3.92 -3.73 (s, 1H), 3.69 - 3.53 (s, 1H), 3.13-2.94 (m, 2H), 2.87- 2.74 (dd, J= 12.7, 9.1 Hz, 1H), 2.722.58 (m, 1 H), 2.49 -2.36 (dd, J = 12.7.5.3 Hz, 1H), 1.20-1.13 (m, 6H).

Page 488 of6!9

428

(thin film) 3086, 2975, 1658.

ESIMS m/z 351 ([M+H]4).

1H NMR (400 MHz, CDCI3) δ 8.99-8.92 (d, J = 2.5 Hz, 1H), 8.668.59 (m, 1H), 8.09 -8.01 (m, 1H), 7.99 - 7.93 (s, 1H), 7.51 -7.43 (m, 1H), 5.855.63 (m, 1H), 5.14 -4.98(m, 2H), 3.77-3.63 (m, 2H), 3.14-3.03 (m,2H), 2.822.70 (m, 2H), 2.46 - 2.35 (m, 2H), 1.19- 1.09 (m, 3H).

Page 489 of 619

429

(thin film) 3087, 2974, 2930, 1656.

ESIMS m/z 351 ([M+H]*).

1H NMR (400 MHz, CDCI3) δ 8.98-8.94 (d, J = 2.5 Hz, 1H), 8.678.58 (m. 1H), 8.13 -8.01 (m, 2H), 7.51 -7.42 (m, 1H), 5.70-5.52 (m, 1H), 5.064.95 (m, 1H), 4.95 -4.85 (d, J= 10.0 Hz, 1H), 3.833.70 (dd, J= 14.3, 7.2 Hz, 1H), 3.683.57 (s, 1H). 3.33 -3.23 (m, 1H), 3.19-3.07 (m, 2H), 1.48-1.42 (d, J = 6.8 Hz. 3H). 1.19-1.15 (m, 3H).

Page 490 of 619

430		(thin film) 1719, 1687	ESIMS m/z 446 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.93 -8.85 (m, 1H), 8.65-8.56 (m, 1H), 8.098.03 (m, 3H), 8.03 - 7.99 (m, 1H), 7.64-7.51 (m, 1H), 7.50-7.37 (m, 3H), 6.15- 5.67 (m, 2H), 2.95 - 2.72 (m, 2H), 2.58-2.43 (m, 1H), 2.06-1.96 (m,3H),1.31 - 1.19 (m, 3H).
431	100- 102		ESIMS m/z 311 ((M+2-t-Buf)	1H NMR (400 MHz, CDCI3) δ 9.00-8.89 (d, J = 2.9 Hz, 1H), 8.64 -8.49 (d, J = 4.8 Hz, 1H), 8.11 7.99 (m, 1H), 7.94 -7.75 (s, 1H), 7.58-7.39 (m, 1H), 3.68-3.49 (m, 2H), 1.53- 1.30 (s, 9H), 1.23 -1.10 (m, 2H).

Page 491 of 619

432		(thin film) 3485, 3092, 2976, 1657.	ESIMS m/z 311 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 9.00-8.92 (d, J = 2.5 Hz, 1H), 8.678.59 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.11 8.07(s, 1H), 8.06 -8.01 (m, 1H), 7.50-7.42 (m, 1H), 3.79-3.65 (m, 2H), 3.103.05 (s, 2H), 2.26 -2.18 (s, 3H), 1.22-1.12 (m, 3H).
433		(thin film) 1719	ESIMS m/z 354 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97 (s. 1H), 8.61 (s, 1H), 8.09- 7.94 (m, 2H), 7.51 -7.36(m, 1H), 3.39 - 3.27 (m, 1H), 2.98-2.85 (m, 1H), 2.58- 2.49 (m, 1H), 2.46 (s, 3H), 2.08 (s, 3H), 1.29 (d, 7 = 6.9 Hz, 3H).

Page 492 of6l9

434	156.5 158.0		ESIMS m/z 319 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.73 (s, 1H). 8.30 (d, 7 = 2.5 Hz, 1H), 8.27 (s, 1H), 7.76 (dt, 7= 9.8, 2.4 Hz, 1 H), 6.43 (s, 1 H), 1.55 (s, 9H), 1.01-0.91 (m, 4H).
435	144.0 146.0		ESIMS m/z 279 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.74 (d, 7 = 1.1 Hz, 1H), 8.64 (s, 1H), 8.37-8.29 (m, 2H), 7.74 (dt, 7 = 9.5, 2.3 Hz, 1H), 4.95 (d, 7 = 3.0 Hz, 2H), 3.21 - 3.06 (m, 1H), 2.63 -2.48 (m, 1H), 1.26 (d, 7 = 6.9 Hz, 6H).
436		(thin film) 1659	ESIMS m/z 249 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.79 (d, 7= 1.2 Hz, 1H), 8.60 (s, 1H), 8.38 (d. 7 = 2.5 Hz, 1H), 7.81 (dt, 7 = 9.5, 2.3 Hz, 1H), 7.68 (s. 1H), 7.54 (s, 1H), 2.63-2.51 (m, 1H). 1.28 (d, 7 = 6.9 Hz, 6H).

Page 493 of 619

437		(thin film) 1711	ESIMS m/z 382 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.7 Hz, 1H), 8.62 (dd, J = 4.8, 1.5 Hz, 1H), 8.08-8.01 (m, 2H), 7.49 7,41 (m, 1H), 3.43 -3.30 (m, 1H), 3.23 (hept, J = 6.8 Hz, 1H), 3.002.87 (m, 1H), 2.59 -2.49 (m, 1H), 2.09 (s, 3H), 1.31 (d, J = 6.8 Hz, 3H), 1.25-1.18 (m, 6H).
438		(IR thin film) 1435	ESIMS m/z 341 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.4 Hz, 1H), 8.64 (dd, J =4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.4, 2.7, 1.4 Hz, 2H), 7.56 - 7.36 (m, 1H), 3.69 (d, J = 26.2 Hz, 3H), 3.10 (s, 2H), 2.62 (d, J= 12.7 Hz, 1H), 2.02 (s, 3H), 1.27 (d, J =6.4 Hz, 3H).

Page 494 of 619

439	101- 109		ESIMS m/z 275 ([M+H]*)	’H NMR (400 MHz, CDCI3) 6 8.95 - 8.60 (bs, 1H), 8.55-8.26 (d, J =2.5 Hz, 1H),7.95 (s, 1H), 7.89 - 7.75 (m, 1H), 3.39-2.94 (s, 3H), 2.422.23 (s, 3H), 1.34 -1.07 (m, 1H), 1.08-0.96 (m, 2H), 0.77 - 0.53 (dd, 7=7.8, 3.0 Hz, 2H).
440	132- 139		ESIMS m/z 289 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.84-8.61 (bs, 1H), 8.58-8.29 (d, 7 = 2.4 Hz, 1H), 8.10-7.71 (m, 2H), 3.32 - 3.04 (s, 3H), 2.48 -2.14 (s, 3H), 1.47- 1,29 (m, 1H), 1.27-1.09 (m, 2H), 1.05- 0.91 (d, 7 = 6.0 Hz, 3H), 0.61 - 0.41 (m, 1H).

Page 495 of 619

441	90- 100		ESIMS m/z 310 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.91 -8.60 (d, 7 = 1.8 Hz, 1H), 8.56- 8.25 (d, 7= 2.5 Hz, 1H), 8.06- 7.88 (s, 1H), 7.91 -7.72(m, 1H), 3.29 (s, 3H), 2.46 -2.06(m, 5H), 1.66- 1.59 (m, 1H).
442	70-77		ESIMS m/z 288 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.73 (bs, 1H), 8.60-8.31 (d, 7 = 2.5 Hz, 1H), 7.967.66 (m, 2H), 3.22 (s, 3H). 2.25 (s, 3H), 2.17-1.92 (d,7=6.8 Hz, 2H), 1.19-0.89 (m, 1H), 0.660.34 (m, 2H), 0.05 - 0.00 (m, 2H).

Page 496 of 619

443	82-88		ESIMS m/z 303 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.74 (s, 1H), 8.42 (d, J = 2.5 Hz, 1H), 8.13-7.64 (m, 2H), 3.21(s, 3H), 2.34-2.06 (m, 5H), 1.521.46 (m, 2H), 0.50.7 (m, 1H), 0.38 (m, 4H).
444	87-93		ESIMS m/z 292 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.27 (s, 1H), 9.10 (s, 2H),7.93 (s, 1H), 3.24 (s, 3H), 2.79 (t, J = 7.3 Hz, 2H), 2.48 (t, J = 7.2 Hz, 2H), 2.29 (s, 3H), 2.06 (s, 3H).
445	97- 104		ESIMS m/z 312 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.23 (s, 1H), 9.2 (s, 2H), 8.04 (s, 1H), 3.25 (S. 3H), 2.80 (t, J = 7.3 Hz, 2H), 2.47 (t, J = 7.3 Hz, 2H), 2.08 (s, 3H).

Page 497of6!9

446	110- 114		ESIMS m/z 306 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.16(s, 1H), 9.10(s, 2H), 7.97 (s. 1H), 3.24 (s, 3H), 2.95 - 2.82 (m, 1H), 2.822.69 (m, 1H). 2.45 (dd, J= 12.6,4.8 Hz, 1H), 2.33 (s, 3H), 2.02 (s, 3H), 1,13 (d, 7 = 6.7 Hz, 3H).
447			ESIMS m/z 326 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.22 (s, 1H), 9.11 (s, 2H), 8.08 (s, 1H), 3.27 (s, 3H), 2.94-2.79 (m, 1H), 2.79-2.64 (m, 1H), 2.49 (dd, 7= 12.6, 5.1 Hz, 1H), 2.04 (s, 3H), 1.17(d, 7 = 6.7 Hz, 3H).
448	118- 122		ESIMS m/z 260 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.16 (s, 1H), 9.10 (s, 2H), 7.91 (s, 1H), 3.21 (s, 3H), 2.60 (dt, 7= 13.4, 6.7 Hz, 1H), 2.28 (s, 3H), 1.07 (d, 7 = 6.7 Hz, 6H).

Page 498 of 6I9

449	130- 139		ESIMS m/z 279 ([M+Hp	’H NMR (400 MHz, CDCI3) δ 9.22 (s, 1H), 9.12 (s, 2H), 8.01 (s, 1 H), 3.23 (s, 3H), 2.59 (dt, J= 13.3, 6.6 Hz, 1H), 1.09 (d, J = 6.7 Hz, 6H).
450		(thin film) 1737, 1689	ESIMS m/z 412 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.93 (s, 1H), 8.62 (s, 1H), 8.06- 8.00 (m, 2H), 7.49 -7.43 (m, 1H), 5.80-5.39 (m, 2H), 2.91 - 2.80 (m, 1H), 2.80- 2.69 (m, 1H), 2.64 -2.53 (m, 1H), 2.53 - 2.43 (m, 1H), 2.01 (s, 3H), 1.58 (s, 3H), 1.21 -1.17 (m, 6H).

Page 499 of 619

451		(thin film) 1747	ESIMS m/z 284 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.94 (d, J = 2.7 Hz, 1H), 8.58 (dd, J = 4.8, 1.5 Hz. 1H), 8.08-7.99 (m, 1H), 7.96 (s, 1H), 7.45-7.39 (m, 1H), 4.34- 4.22 (m, 2H), 4.11 -3.98(m, 1H), 3.02-2.92 (m, 1H), 2.65-2.53 (m, 1H), 2.17 (s, 3H), 1.37 (d, J = 6.8 Hz. 3H), 1.28 (t, J= 7.1 Hz, 3H).
452		3499, 3189, 2914, 1657		’H NMR (400 MHz, CDCI3) δ 8.99-8.89 (d, J = 2.7 Hz, 1H), 8.66 -8.60 (m, 1H), 8.10-8.02 (m, 1 H), 7.98-7.92 (s, 1H), 7.48- 7.43 (m, 1H), 3.28 - 3.20 (s, 3H), 2.83-2.76 (m, 2H), 2.52-2.43 (m, 2H).

Page 500 of6!9

453	90-91		ESIMS m/z 370 ([M+2Hf)	1H NMR (400 MHz, CDCI3) δ 8.98-8.91 (d. J = 2.7 Hz, 1H), 8.66 -8.58(m, 1H), 8.10-8.04 (m, 1H), 8.03-7.96 (s, 1H), 7.50- 7.41 (dd, 7 = 8.3, 4.8 Hz, 1H), 3.29 -3.22 (s, 3H), 2.93-2.82 (m, 1H), 2.53-2.43 (m, 1H), 1.19 1.15 (d, 7 = 6.6 Hz, 3H).
454	130- 132		ESIMS m/z 322 ([M]*), 324 ([M+2H)+]	1H NMR (400 MHz, CDCI3) δ 9.11-8.83 (d, 7 = 2.7 Hz, 1H), 8.74 - 8.52 (d, 7 = 4.6 Hz, 1H), 8.158.03 (m, 1H), 7.99 -7.90 (s, 1H), 7.58-7.36 (m, 1H), 3.34-3.11 (s, 3H), 2.67- 2.48 (m, 1H), 1.17 - 1.00 (d, 7 = 6.7 Hz, 6H).

Page 501 of 619

455		3102,2993, 1651	ESIMS m/z 376 ([M]+), 378 ([M+2Hf)	’H NMR (400 MHz, CDCI3) δ 9.01 -8.90 (d, J = 2.7 Hz. 1 H), 8.67 -8.60(m, 1H), 8.01-7.93 (s, 1H), 7.54-7.43 (m, 1H), 3.32- 3.19 (s, 3H), 2.61 -2.45(m, 1H), 2.47-2.33 (m, 1H).
456		(thin film) 3434, 1675.	ESIMS m/z 279 ([M+H]+).	’H NMR (400 MHz, CDCI3) 6 8.99-8.91 (m, 1H), 8.66-8.60 (m, 1H), 8.11 8.07 (s, 1H), 8.07 -7.99 (m, 1 H), 7.50 - 7.42 (m, 1H), 3.40-3.37 (m, 1H), 3.323.26 (m, 3H), 3.09 -3.03 (dd, 7 = 6.5, 2.4 Hz, 1H), 2.892.81 (dd, 7 = 6.5, 4.1 Hz, 1H).

Page 502 of 619

457		(thin film) 1741, 1684	ESIMS m/z 384 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.4 Hz, 1H), 8.64 (d, J = 3.7 Hz, 1H), 8.08-8.02 (m, 2H), 7.47 (dd, J = 8.2, 4.8 Hz, 1H), 5.94 - 5.40 (m, 2H), 2.93-2.81 (m, 1H), 2.81 - 2.69 (m, 1H), 2.55 -2.43(m, 1H), 2.10 (s, 3H), 2.02 (s, 3H), 1.20 (d, J = 6.5 Hz. 3H).
458	97-98		ESIMS m/z 368 ([M+2H]*)	1H NMR (400 MHz, CDCI3) δ 9.02-8.91 (s. 1H), 8.66-8.59 (s, 1H). 8.088.04 (m. 1H). 7.52 -7.42 (m, 2H), 3.29-3.19 (s. 3H), 2.54-2.46 (m, 1H), 2.172.09 (s, 3H), 1.71 - 1.62 (m, 1H), 1.56- 1.50 (m, 1H), 1.08-0.93 (d, J =5.5 Hz, 1H).

Page 503 of6!9

459		3089, 2966, 2916, 1655	ESIMS m/z 370 ([M+2HD	’H NMR (400 MHz, CDCI3) δ 9.01-8.91 (m, 1H), 8.75-8.55 (m, 1H), 8.10- 8.01 (m, 1H), 8.00 -7.93 (s, 1H), 7.52-7.41 (m, 1H), 3.31-3.19 (s, 3H), 2.55- 2.43 (m, 1H), 2.34 -2.21 (m, 1H), 2.09 - 2.02 (s, 3H), 1.34-1.23 (d, J = 6.8 Hz, 3H).
460	95-96		ESIMS m/z 342 ([M+2Hf)	8.96-8.92 (d, J = 2.8 Hz, 1H), 8.67 -8.54 (dd, J = 4.8, 1.5 Hz, 1H), 8.12- 8.06 (s, 1H), 8.05-7.93 (m, 1H), 7.49- 7.42 (m, 1H). 3.29 -3.21 (s, 3H), 3.13- 3.07 (s, 2H), 2.27-2.19 (s, 3H)

Page 504 of 619

461		3091,2980, 2941, 1661	ESIMS m/z 392 ([M+2H]+)	’HNMR (400 MHz, CDCI3) δ 8.97-8.92 (d, J = 2.6 Hz, 1H), 8.68 -8.62 (dd, J = 4.8, 1.5 Hz, 1H), 8.10-7.99 (d, J = 8.5 Hz, 1H), 7.92 -7.86 (s, 1H), 7.50-7.44 (m, 1H), 3.28-3.21 (s, 3H), 2.92 - 2.84 (s, 1H), 2.83 -2.67 (m, 1H), 2.10-1.95 (m, 1H), 1.24-1.17 (d, J = 6.9 Hz, 3H).
462	91-92		ESIMS m/z 368 ([Mf), 370 ([Μ+2ΗΠ	’H NMR (400 MHz, CDCI3) δ 9.00-8.90 (d, J = 2.7 Hz, 1H), 8.70 -8.59 (m, 1H), 8.11 -8.02 (m, 1H), 7.95-7.89 (s, 1H), 7.51 7.39 (m, 1H). 3.79 -3.63(m, 2H), 2.85-2.72 (m, 1H), 2.51-2.37 (m, 2H), 2.102.00 (s, 3H), 1.25 -1.06(m, 2H).

Page 505 of 619

463	102- 104		ESIMS m/z 384 ([Μ+2ΗΠ	1H NMR (400 MHz, CDCI3) δ 9.01-8.91 (d, J = 2.6 Hz, 1H), 8.71 -8.57 (d, 7 = 4.8 Hz, 1H), 8.178.02 (m, 1H), 8.02 -7.92 (s, 1H), 7.51 -7.40 (m, 1H), 2.93-2.79 (m, 1H), 2.74- 2.59 (s, 1H), 2.53 -2.35 (m, 1H), 2.03-1.98 (s, 3H), 1.22-1.10 (m, 6H).
464		3092, 2975, 2935, 1663	ESIMS m/z 390 ([MD, 392 ([M+2HJ*	1H NMR (400 MHz, CDCI3) δ 9.02-8.90 (d, 7 = 2.8 Hz, 1H), 8.67 - 8.60 (d, J = 4.7 Hz, 1H), 8.128.03 (m, 1H). 7.55 -7.41 (m, 1H), 3.80-3.61 (s, 2H), 2.58 - 2.43 (m, 1H), 2.43- 2.32 (m, 2H), 1.22 -1.11 (m, 3H)

Page 506 of 619

465	142- 143		ESIMS m/z 338 ([M+2H]*	1H NMR (400 MHz, CDCI3) δ 9.00-8.90 (d, J = 2.7 Hz, 1H), 8.65 -8.57 (d, J = 4.7 Hz, 1H), 8.11 8.01 (m, 1H), 7.93 -7.87 (s, 1H), 7.51 -7.42 (m, 1H), 2.59-2.43 (m, 1H), 1.19- 1.12 (m, 3H), 1.12 - 1.03 (d, J = 6.8 Hz, 6H).
466	119- 120		ESIMS m/z 382 ([M+2H]*)	1H NMR (400 MHz, CDCI3) δ 9.01 -8.94 (d, J = 2.7 Hz, 1H), 8.69 -8.59 (d, J = 4.5 Hz, 1H), 8.148.05 (m, 1H), 8.02 -7,93 (s, 1H), 7.52-7.39 (dd, J = 8.3. 4.7 Hz, 1H). 3.85-3.52 (d, J = 44.3 Hz, 2H),2.59 -2.43 (s, 1 H), 2.17 - 2.10 (s, 3H), 1.65-1.60 (m, 1H), 1.55- 1.50 (m, 1H), 1.20 - 1.12 (m, 3H),1.04-0.93 (d, J = 4.9 Hz, 1H).

Page 507 of 619

467		3087, 2970, 2917, 1653	ESIMS m/z 384 f[M+2H]+)	1H NMR (400 MHz, CDCI3) δ 8.98-8.95 (d, J = 2.7 Hz, 1H), 8.65 -8.61 (d, J =4.7 Hz, 1H), 8.09- 8.05 (m, 1H). 7.94 -7.92 (s, 1H), 7.50 - 7.43 (m, 1H), 3.82-3.61 (s, 2H), 3.31 - 3.18 (m, 1H), 2.54 -2.41 (dd, J = 15.6, 6.3 Hz, 1H), 2.30-2.21 (m, 1H), 2.08-2.04 (s, 3H), 1.31 - 1.27 (d, J = 6.8 Hz, 3H), 1.21 - 1.13 (m, 3H).
468	73-74		ESIMS m/z 354 ([M]+), 356 ([M+2H]*)	1H NMR (400 MHz, CDCI3) δ 9.03-8.88 (d, J = 2.7 Hz. 1H), 8.69 - 8.56 (dd, J = 4.8, 1.5 Hz, 1H), 8.07- 8.05 (m, 1H), 8.04-8.03 (s, 1H), 7.497.43 (m, 1H), 3.83 - 3.62 (s, 2H), 3.09-3.07 (s, 2H), 2.25-2.20 (s, 3H), 1.21 - 1.15 (m, 3H).

Page 508 of 619

469

74-75

ESIMS m/z 368([M]+), 370 ([M+2Hf)

’H NMR (400 MHz, CDCI3) S 8.97-8.94 (d, J = 2.7 Hz, 0.7H), 8.88-8.86 (d, J = 2.6 Hz, 0.3H), 8.65-8.61 (m, 0.7H), 8.49 - 8.46 (m. 0.3H), 8.08- 8.03 (m, 1.7H), 8.01 -7.95 (m, 0.3H), 7.48-7.43 (m, 0.7H), 7.39- 7.34 (m, 0.3H), 3.99-3.84 (s,0.31 H), 3.293.19 (s, 0.7H), 3.17-3.07 (m, 2H), 1.53-1.47 (s, 0.9H), 1.47- 1.42 (d, J =6.9 Hz, 2.1H), 1.35- 1.28 (m, 0.9H), 1.20- 1.14(m, 2.1H).

Page 509 of 619 / ---16403

470		(thin film) 1699	ESIMS m/z 416 ([M+Hf)	'H NMR (400 MHz, CDCI3) δ 8.89 (d, 7 = 1.6 Hz, 1H), 8.59 (d, 7 = 4.1 Hz, 1H), 8.06 (s. 1H), 7.98 (ddd, 7= 8.3, 2.6, 1.4 Hz, 1H), 7.78 (dd, 7 = 5.2, 3.3 Hz, 2H), 7.53 7.48 (m, 1H), 7.44 -7.37(m, 3H), 3.44-3.28 (m, 1H), 2.97 (dd, 7 = 13.2, 8.8 Hz, 1H), 2.59 (dd, 7= 13.2, 5.8 Hz, 1H), 2.09 (s, 3H), 1.38 (d, 7 = 6.8 Hz, 3H).
471		(thin film) 1652	ESIMS m/z 326 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.2 Hz, 1 H), 8.63 (d, 7 = 4.1 Hz, 1H), 8.05 (s, 1H), 8.05 -8.00 (m, 1H), 7.46 (dd, 7 = 8.3, 4.7 Hz, 1H), 3.27 (s, 3H), 2.86 (d, 7 = 12.9 Hz, 1H), 2.47 (d, 7 = 12.9 Hz, 1H), 2.02 (s, 3H), 1.16 (s, 3H).

Page 510 of 619

472		(thin film) 1648	ESIMS m/z 340 ([Μ+ΗΠ	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1H), 8.63 (dd, J = 4.7, 1.2 Hz, 1H), 8.11 -7.94 (m, 2H), 7.53 7.40 (m, 1H), 3.97 - 3.46 (m, 2H). 2.85 (d, J = 13.0 Hz, 1H), 2.46 (d, J = 13.0 Hz, 1H), 2.02 (s, 3H), 1.21 -1.13(m, 6H).
473	85-87	(thin film) 1642	• ESIMS m/z 338 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.76 (d, J = 1.1 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 7.94 (s, 1H), 7.86 (dt, J = 9.4, 2.3 Hz, 1H), 4.05- 3.30 (m, 2H), 2.87 (d, J = 12.9 Hz, 1H), 2.42 (d, J = 12.9 Hz, 1H), 2.30 (s, 3H), 2.01 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H), 1.11 (s, 3H).

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474		(thin film) 1677	ESIMS m/z 356 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz. 1H), 8.62 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.07-8.01 (m, 2H), 7.45 (dd, 7 = 8.3, 4.7 Hz, 1H), 5.88-4.24 (m, 3H), 3.48 (s, 3H), 2.92-2.75 (m, 2H), 2.49 (dd, 7= 12.4, 4.8 Hz, 1H), 2.01 (s, 3H), 1.21 (d, 7 = 6,5 Hz, 3H).
475		(thin film) 1731, 1683	ESIMS m/z 426 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.02-8.90 (m, 1H), 8.66-8.57 (m, 1H), 8.21 8.00 (m. 2H), 7.47 (dt, 7 = 8.4, 4.3 Hz, 1H), 5.955.35 (m, 2H), 3.04 -2.70(m, 2H), 2.56-2.42 (m, 1H), 2.06-1.95 (m, 3H), 1.29- 1.13 (m. 12H).

Page 512 of 619

476	121- 123		ESIMS m/z 354 ([M]+), 356 ([M+2Hf)	1H NMR (400 MHz, CDCI3) δ 9.08-9.04 (d, J~ 2.7 Hz, 1H), 8.96 -8.92 (s, 1H), 8.63-8.58 (m. 1H), 8.24-8.17 (m, 1H), 7.64- 7.57 (m, 1H), 3.56 -3.45 (s, 1H), 3.17-3.11 (s, 3H), 2.00-1.94 (s, 3H),1.35- 1.27 (d, 7 = 6.8 Hz, 3H).
477	108.1 -110		ESIMS m/z 231 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.99 (s, 1H), 8.57 (d, 7 = 3.8 Hz, 1H), 8.08 (dt, 7 = 7.9, 1.9 Hz, 1H), 7.34 (dd, 7= 7.7, 4.7 Hz, 1H), 6.49 (s, 1H), 3.79 (s, 3H),3.23 (s, 3H), 1.94 (s, 3H).

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478		(thin film) 3487, 3103, 1648.	ESIMS m/z 291 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 9.02-8.93 (d,J = 2.5 Hz, 1H), 8.648.58 (m, 1H), 8.11 -8.04 (ddd, J = 8.3, 2.6, 1.5 Hz, 1H), 7.98-7.94 (s, 1H), 7.707.65 (s, 1H), 7.49 -7.42 (m, 1H), 3.78 - 3.66 (m, 2H), 2.82 - 2.74 (m, 2H), 2.55 2.43 (m, 2H), 2.10 -2.03 (s, 3H), 1.20-1.13(m, 3H).
479	143- 146		ESIMS m/z 310 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 8.98-8.93 (d, J = 2.5 Hz. 1H), 8.658.61 (m, 1H), 8.07 -8.01 (m, 1H), 8.01 - 7.99 (s, 1H), 7.49-7.44 (m, 1H), 5.675.53 (s, 1H), 4.28 -4.13(m, 2H), 3.74-3.58 (m, 2H), 1.27-1.21 (m, 3H), 1.20- 1.14 (m, 3H).

Page 514 of 619

480	160- 163		ESIMS m/z 276 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 9.03-8.97 (d, J = 2.5 Hz, 1H), 8.65- 8.58 (dd, J = 4.7, 1.4 Hz, 1H), 8.12 8.03 (m, 1H), 8.02 -7.96 (m, 1H), 7.73 - 7.68 (s, 1H), 7.50-7.43 (m, 1H), 5.69- 5.59 (s, 1H). 4.28 -4.16(m, 2H), 3.70 - 3.54 (m, 2H), 1.28-1.20 (m, 3H), 1.17 - 1.08 (m, 3H).
481		(thin film) 3092, 2972, 1657.	ESIMS m/z 328 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.98 -8.94 (d, J = 2.4 Hz, 1H), 8.658.59 (m, 1H), 8.09 -8.02 (m, 1H), 7.99 - 7.95 (s, 1H), 7.50-7.43 (m, 1H), 3.77- 3.66 (m, 2H), 3.64 - 3.55 (m, 2H), 2.38 - 2.28 (m. 2H), 2.14-2.06 (m, 2H), 1.19- 1.13 (m, 3H).

rgc 5l 5~of-6416403

482	104- 108		ESIMS m/z 325 ([M+H]*).	’H NMR (400 MHz, CDCI3) δ 8.99-8.93 (d, J = 2.5 Hz, 1H), 8.658.58 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.148.09 (s, 1H), 8.06 -8.01 (m, 1H), 7.50-7.41 (m, 1H), 3.90-3.75 (s, 1H), 3.663.51 (s, 1H), 3.31 -3.21 (d, 7 = 6.7 Hz. 1H), 2.11 2.06 (s, 3H), 1.46 -1.40 (d, 7 = 6.9 Hz, 3H), 1.23- 1.12 (m, 3H).
483		(thin film) 2953, 1654.	ESIMS m/z 321 ([M+H]*).	’H NMR (400 MHz, CDCI3) δ 8.97-8.94 (d, 7 = 2.5 Hz, 1H), 8.638.59 (m, 1H), 8.09 -8.03(m, 1H), 7.92 - 7.87 (s, 1H), 7.49-7.42 (dd,7 = 8.3, 4.8 Hz, 1H), 3.74- 3.61 (m, 2H), 2.09 - 2.06 (s, 2H), 1.17- 1.13(t,7 = 7.1 Hz, 3H), 1.03- 1.00 (s, 9H).

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484		(thin film) 2953, 1646.	ESIMS m/z 287 ([M+Hf).	’H NMR (300 MHz, CDCI3) δ 9.03 - 8.93 (d, J = 2.4 Hz, 1H), 8.62- 8.55 (d, J =4.7 Hz, 1H), 8.11 8.03 (d, J = 8.4 Hz, 1H), 7.90- 7.84 (s, 1H), 7.66 -7.59 (s, 1H), 7.49 - 7.39 (dd, J = 8.4, 4.8 Hz, 1H), 3.75 -3.62 (q, J = 7.1 Hz, 2H), 2.162.09 (s, 2H), 1.21 -1.10(m, 3H), 1.04-0.93 (s, 9H).
485		(thin film) 1758, 1689	ESIMS m/z 428 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.06-8.91 (m, 1H), 8.64 (d, J = 3.9 Hz, 1H), 8.15 -8.09 (m, 1H), 8.09-8.00 (m, 1H), 7.47 (dd, J = 8.1,4.7 Hz, 1H), 5.99-5.41 (m, 2H), 4.12 (s, 2H), 3.59 (q, J = 7.0 Hz, 2H), 3.00- 2.69 (m, 2H), 2.56 -2.42 (m, 1H), 2.04- 1.95 (m, 3H), 1.29-1.13 (m, 6H).

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486	101- 110		ESIMS m/z 351 ([M+H]*)	1H NMR (400 MHz, CDCI3) 58.95 (d, J = 2.6 Hz, 1H), 8.62 (dd, 7=4.7, 1.3 Hz, 1H), 8.26-7.91 (m, 2H), 7.46 (dd, 7 = 8.3, 4.8 Hz, 1H), 3.82-3.44 (m, 2H), 2.42 (s, 2H), 2.13 (s, 3H), 1.33-1.01 (m, 5H), 0,71 - 0.45 (m, 2H).
487		(IR thin film) 1643	ESIMS m/z 273 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.03 (s, 1H), 8.59 (d, 7 = 3.9 Hz, 1H), 8.18 (dt, 7 = 8.0, 1.8 Hz, 1H), 7.43 (dd, 7= 7.8, 5.0 Hz, 1H), 6.53 (s, 1H), 3.76 (s, 3H), 3.18 (s, 3H), 1.12 (s, 9H).

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488	81-82		ESIMS m/z 352 ([M]+), 354 ([M+2H]*)	1H NMR (400 MHz, CDCI3) δ 8.98-8.86 (d, J = 2.7 Hz, 1H), 8.62 -8.49 (m, 1H), 8.05-8.00 (m, 1 H),7.98 - 7.83 (s, 1H), 7.457.36 (m, 1H), 3.78 -3.63 (m, 2H), 3.61 -3.50(m, 2H), 1.49-1.33 (s, 9H).
489	121.0 123.0		ESIMS m/z 278 ([M])	1H 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).

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490		(thin film) 1664	ESIMS m/z 347([M+H]+)	’H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.64 (dd, J = 4.7, 1.2 Hz, 1H), 8.05 (ddd, J = 8.4, 2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.4 Hz, 1H), 3.26 (s, 3H), 3.02 -2.87 (m, 1H), 2.52 (dd, J = 16.3, 4.0 Hz, 1H). 2.13 (dd, J = 16.3, 9.1 Hz, 1H), 1.14 (d, J = 6.9 Hz, 3H).
491		(thin film) 1659	ESIMS m/z 361 ((M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.5 Hz, 1H), 8.64 (dd, J = 4.7, 1.3 Hz, 1H), 8.06 (ddd, J = 8.3,2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.5 Hz, 1H), 3.87- 3.57 (m, 2H). 3.03 - 2.85 (m. 1H), 2.49 (dd, J = 16.3, 4.2 Hz, 1H), 2.10 (dd, J = 16.3, 9.0 Hz, 1H), 1.17 (t. J = 7.2 Hz, 3H), 1.14 (d,J = 6.9 Hz, 3H).

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492	103- 106	(thin film) 1670	ESIMS m/z 341 ([Μ+ΗΠ	’H NMR (400 MHz, CDCI3) δ 8.95 (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, 2.6, 1.4 Hz, 1H), 7.47 (dd, J = 8.3, 4.7 Hz, 1H), 4.01 (t, J = 6.6 Hz, 1H), 3.32 (s, 3H), 3.31 (s, 3H), 2.80 (qd, J = 13.7, 6.6 Hz, 2H), 2.07 (s, 3H).
493		(thin film) 1655	ESIMS m/z 359 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 9.00 (d, J = 2.3 Hz, 1H), 8.62 (d, J = 4.9 Hz, 1H), 8.08 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.97 (d, J = 0.5 Hz, 1H), 7.68 (s, 1H), 7.46 (dd, J = 8.2, 4.7 Hz, 1H), 3.87-3.60 (m, 3H), 2.61 (dd, J = 16.1,4.0 Hz, 1H), 2.50 (dd, J = 16.1, 9.9 Hz, 1H), 2.29 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H).

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494		(thin film) 1660	ESIMS m/z 355 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.99 (bs, 1H), 8.64 (bs, 1H), 8.16-7.95 (m, 2H), 7.56 - 7.35 (m, 1H), 3.93- 3.51 (m,2H), 3.42 -3.03 (m, 1H), 2.87(m, 0.5H), 2.81 - 2.69 (m, 0.5H), 2.54(s, 1.5H), 2.47 (s, 1.5H), 2.38-2.15 (m, 1H), 1.32- 1.21 (m, 3H), 1.22 - 1.10 (m, 3H).
495		(thin film) 1661	ESIMS m/z 370 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.97(d, J = 2.4 Hz, 1 H),8.63 (bs, 1H), 8.20 - 7.86 (m, 2H), 7.46 (dd, 7 = 8.3, 4.8 Hz, 1H), 3.88-3.66 (m, 2H), 3.66 - 3.48 (m, 1H), 2.962.89 (m, 1H), 2.88 (s, 3H), 2.27(dd, 7 = 16.6, 7.3 Hz. 1H), 1.43 (d, 7 = 6.9 Hz, 3H), 1.22 - 1.05 (t, 3H).

Page 522 of 619

496

ESIMS m/z 355 ([M+Hfj

’H NMR (400 MHz, CDCI3) δ 8.96-8.90 (m, 1H), 8.64-8.59 (m, 1H), 8.088.05 (m, 1H), 8.04 -7.99 (s, 1H). 7.50-7.40 (m, 1H), 3.95-3.73 (s, 2H), 3.67- 3.53 (s, 2H), 3.38 - 3.30 (s, 3H), 2.83-2.77 (m, 2H), 2.54 - 2.43 (m, 2H), 2.10- 2.02 (s, 3H).

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497			ESIMS m/z 369 ([M+H]*), 367 ([M-H])	1H NMR (400 MHz, CDCI3) δ 9.01 -8.87 (d, 7 = 2.6 Hz, 1H), 8.68 -8.56 (m, 1H), 8.11-8.05 (d, 7 = 1.3 Hz, 1H), 8.03 -7.95(m, OH), 7.51- 7.40 (m, 1H), 4.49-3.86 (m, 1H), 3.73- 3.52 (s, 3H), 3.39 -3.28 (s, 3H), 2.90-2.77 (d, 7 = 10.2 Hz, 1H), 2.77 -2.66 (s, 1H). 2.52- 2.37 (m, 1H), 2.07-1.95 (s, 3H), 1.21 1.10 (d, 7 = 6.5 Hz, 3H).
498			ESIMS m/z 323 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.98-8.90 (d, J = 2.8 Hz, 1H), 8.69 -8.56 (m, 1H). 8.11 -8.04(m, 1H), 8.04-7.97 (s, 1H), 3.65- 3.53 (s, 2H), 3.37 -3.31 (s, 3H), 2.63-2.45 (m. 3H), 1.24-1.17 (d, 7= 7.0 Hz, 6H).

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499			ESIMS m/z 321 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.02 - 8.92 (dd, J = 2.6, 0.8 Hz, 1H), 8.68-8.60 (dd, J = 4.8, 1.5 Hz, 1H), 8.09-7.98 (m, 1H), 7.96-7.87 (s, 1H). 3.873.58 (d, J = 30.0 Hz, 2H), 3.493.38 (m, 1H), 2.16 -2.08 (s, 3H), 1.39- 1.32 (d, J = 7.0 Hz, 3H), 1.22 - 1.13 (m, 3H).
500		(thin film) 3326, 2959, 2931, 1648.	ESIMS m/z 322 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.95 (s, 1H), 8.62 (d, J = 4.0 Hz, 1H), 8.08-8.01 (m, 1H), 7.97 (s, 1H), 7.46 (dd, J = 8.3, 4.7 Hz, 1H), 4.42 - 4.32 (m, 1H), 3.74-3.61 (m, 2H), 3.27 3.15 (m, 2H), 1.49 -1.37(m, 2H), 1.37 - 1.22 (m, 2H), 1.19-1.12 (m, 3H). 0.940.84 (m, 3H).

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501

(thin film) 3326, 2929, 1645.

ESIMS m/z 336 ([M+Hf).

1H NMR (400 MHz, CDCI3) δ 8.95 (s, 1H), 8.62 (d, J = 4.0 Hz, 1H), 8.08 - 8.00 (m, 1H), 7.97 (s, 1H), 7.50- 7.40 (m, 1H), 4.44 - 4.34 (m, 1H), 3.73- 3.62 (m, 2H), 3.24-3.14 (m, 2H), 1.50- 1.41 (m,2H), 1.36- 1.22 (m, 4H), 1.18 - 1.12 (m, 3H), 0.87-0.81 (m, 3H).

502		(thin film) 3354, 2929, 1644.	ESIMS m/z 302 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.99 (s, 1H), 8.60 (d, J = 4.0 Hz, 1H), 8.09-8.03 (m, 1H), 8.00 (d, J = 0.6 Hz, 1H), 7.72-7.67 (m, 1H), 7.48-7.40 (m, 1H), 4.50 (s, 1H), 3.72-3.63 (m, 2H), 3.23- 3.14 (m, 2H), 1.52 -1.38 (m, 2H), 1.36-1.21 (m, 4H), 1.20-1.14 (m, 3H), 0.900.82 (m, 3H).
503		(thin film) 3269, 2964, 1647.	ESIMS m/z 322 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.97 (s, 1H), 8.62 (s, 1H), 8.09- 8.02 (m, 1H), 7.98 (s, 1H), 7.51 - 7.42 (m, 1H), 4.11 (d, J = 8.2 Hz, 1H), 3.86-3.74 (m, 1H), 3.71 - 3.63 (m, 2H), 1.45 -1.34(m, 2H), 1.18-1.11 (m, 3H), 1.08 (d, J = 6.6 Hz, 3H), 0.91 - 0.84 (m, 3H).

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504	93-96		ESIMS m/z 288 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 9.00 (s, 1H), 8.60 (s, 1H), 8.09- 8.03 (m, 1H), 8.00 (d, 7 = 0.6 Hz, 1 H), 7.69 (d, 7 = 0.6 Hz, 1H), 7.45 (dd, 7 = 8.1, 4.6 Hz, 1H), 4.26 (d, 7 = 8.2 Hz, 1H), 3.83- 3.75 (m, 1H), 3.71 -3.62 (m, 2H), 1.43- 1.38 (m, 2H), 1.19 -1.15(m, 3H), 1.08 (d. 7 = 6.6 Hz, 3H), 0.89- 0.85 (m, 3H).
505			ESIMS m/z 423 ([M+H]+)	’H NMR (400 MHz, CDCI3) δ 9.01-8.89 (d, 7 = 2.6 Hz, 1H), 8.68 -8.59 (m, 1H), 8.02-7.92 (s, 1H), 7.51 -7.42 (m, 1H), 3.853.67 (m, 1H), 3.36 -3.22 (s, 3H), 2.69-2.56 (m, 1H), 2.51-2.37 (m, 1H), 2.37- 2.25 (m, 3H).

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506		(thin film) 1657	ESIMS m/z 351 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.63 (dd, J = 4.8, 1.4 Hz, 1H), 8.10-8.02 (m, 1H), 8.00 (s, 1 H), 7.51 -7.41 (m, 1H), 3.55 (bs, 2H), 2.90 - 2.64 (m, 2H), 2.59 2.26 (m, 2H), 2.07 (s, 3H), 1.02- 0.87 (m, 1H), 0.62 - 0.35 (m, 2H), 0.27 - 0.07 (m, 2H).
507		(thin film) 1653	ESIMS m/z 365 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1H), 8.63 (dd, J = 4.7, 1.3 Hz, 1H), 8.26-7.78 (m, 2H), 7.46 (dd, J = 8.3, 4.8 Hz, 1H), 3.5 (bs, 2H), 2.86 (m, 2H), 2.48 (dd, J= 12.8, 5.4 Hz, 1H), 2.03 (s, 3H), 1.17 (d, J = 6.7 Hz, 3H), 1.090,85 (m, 1H), 0.63 - 0.37 (m, 2H), 0.31 - 0.08 (m, 2H).

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508		thin film) 1655	ESIMS m/z 365 ([M+Hf)	1H NMR (400 MHz. CDCI3) δ 8.95 (d, 7=2.5 Hz, 1H), 8.63 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.11 -8.02 (m, 1H), 7.99 (s, 1H), 7.55-7.35 (m, 1H), 3.51 (bs, 2H), 3,37 - 3.08 (m, 1H), 2.60- 2.38 (m, 1H), 2.38 -2.20(m, 1H), 2.07 (s, 3H), 1.29 (d, 7 = 6.8 Hz, 3H), 1.11 -0.85 (m, 1H), 0.65- 0.40 (m, 2H), 0.36 -0.11 (m, 2H)
509		(IR thin film) 1673	ESIMS m/z 273 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.99 (s, 1H), 8.57 (d, 7 = 3,6 Hz, 1H), 8.08 (dt. 7 = 7.9, 1.9 Hz, 1H), 7.35 (dd,7= 7.8, 4.8 Hz, 1H), 6.47 (s, 1H), 3.77 (s, 3H), 322 (s, 3H), 2.10 (bs, 2H), 1.62 (m, 2H), 1.27 (m, 2H), 0.85 (m, 3H).

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510

(thin film) 1740, 1688

ESIMS m/z 428 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.99-8.95 (m, 1H), 8.63 (d, J = 4.6 Hz, 1H), 8.25 -8.15(m, 1H), 8.06 (d, J = 8.3 Hz, 1H), 7.48 (dd, J =8.1, 4.8 Hz, 1H), 6.16-5.34 (m, 2H), 4.94- 4.78 (m, 1H), 2.93 -2.70 (m, 2H), 2.55-2.42 (m, 1H), 2.01 (s, 3H), 1.37-1.24 (m, 6H), 1.20 (d, J = 6.2 Hz, 3H).

Page 531 of 619

511		(thin film) 1663	ESIMS m/z 400 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.99 (s, 1H), 8.64 (d, J = 3.9 Hz, 1H), 8.16 (s, 1H), 8.10 (dd, J = 8.3, 1.1 Hz, 1H), 7.51 (dd, J= 8.3, 4.8 Hz, 1H), 4.63 (s, 2H), 3.82-3.67 (m, 4H), 3.35 (s, 3H), 2.86 (dd, J = 12.4, 8.9 Hz, 1H), 2.80-2.65 (m, 1H), 2.47 (dd, J = 12.8, 5.5 Hz, 1H), 2.01 (s, 3H), 1.18 (d, J = 6.6 Hz, 3H).
512		(thin film) 3514, 3091, 2978, 1676.	ESIMS m/z 295 ([M+H]*).	’H 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).

513		(thin film) 3348, 2959, 2931, 1644.	ESIMS m/z 288 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.99 (s, 1H), 8.60 (d, 7 = 4.1 Hz, 1H), 8.06 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 8.00 (d, 7 = 0.6 Hz, 1 H). 7.72- 7.67 (m, 1H). 7.50 -7.40 (m, 1H), 4.49 (s, 1H), 3.73 -3.59 (m, 2H), 3.26-3.12 (m, 2H), 1.50-1.37 (m, 2H), 1.35- 1.22 (m, 2H), 1.21 -1.14(m, 3H), 0.93-0.84 (m, 3H).
514	91-93		ESIMS m/z 338 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz. 1H), 8.60 (dd, 7 = 4.7,1.4 Hz. 1H), 8.08-8.03 (m, 1H), 7.97 (s, 1H), 7.47-7.41 (m, 1H), 3.69 (q. 7 = 7.2 Hz, 2H), 1.47 (s, 9H), 1.21 -1.13(m, 3H).

Page 533 of6!9

515

(thin film) 1664

ESIMS m/z 384 ([M+Hf)

1H NMR (400 MHz. CDCI3) δ 8.94 (d, 7=2.5 Hz, 1H), 8.62 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.12 (s, 1H), 8.04 (ddd, 7=8.3, 2.6, 1.4 Hz, 1H), 7.46 (ddd, 7=8.3, 4.8, 0.5 Hz, 1H), 4.37 - 3.53 (m, 4H), 3.50 (q, 7 = 6.9 Hz, 2H), 2.97 -2.79(m, 1H), 2.79-2.64 (m, 1H), 2.47 (dd, 7 = 12.7, 5.6 Hz, 1H), 2.01 (s, 3H), 1.23 -1.12(m, 6H).

Page 534 of6!9

516		(IR thin film) 1658	ESIMS m/z 362 ([M+H]-*-)	’H NMR (400 MHz, CDCI3) δ 8.89 (d, J= 1.0 Hz, 1H), 8.62 (d, J = 4.0 Hz, 1H), 8.01 (ddd, J = 8.4, 2.5, 1.4 Hz, 1H), 7.82 (s, 1H), 7.46 (dd, J =8.3, 4.7 Hz, 1H), 7.04 (dd, J = 5.1, 0.9 Hz. 1H), 6.85 (dd. J = 5.1, 3.4 Hz, 1H), 6.76-6.69 (m, 1H), 3.23 (S, 3H), 2.84 (t, J = 7.3 Hz, 2H), 2.24 (t, J = 7.3 Hz, 2H), 2.00 (p, J = 7.3 Hz, 2H).
517	163.5 166.5		ESIMS m/z 320 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.3 Hz, 1H), 8.61 (s, 1H), 8.56 (dd, J = 4.7, 1.4 Hz, 1H), 7.99 (ddd, J =8.3, 2.7, 1.5 Hz, 1H), 7.41 (ddd, J = 8.4, 4.8, 0.7 Hz, 1H), 7.18 (s, 1H), 2.78 -2.68(m, 2H), 2.68 - 2.54 (m, 2H).

Page 535 of 619

518	53-56		ESIMS m/z 306 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.99 (d, J = 2.5 Hz, 1H), 8.59 (dd, J= 4.7, 1.3 Hz. 1H), 8.09-8.04 (m, 1H), 8.048.01 (m, 1H), 7.72 (s, 1H), 7.47- 7.41 (m, 1H), 4.97 (d, J= 5.2 Hz, 1H), 3.74-3.61 (m, 2H), 3.46 - 3.34 (m, 2H), 2.67 -2.57(m,2H), 2.08 (s, 3H), 1.25 -1.12(m,3H).
519	110- 112		ESIMS m/z 340 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.6 Hz, 1H), 8.61 (dd. J = 4.7, 1.3 Hz, 1H), 8.07-8.01 (m, 1H), 8.00 (s, 1H), 7.48-7.42 (m, 1H), 4.94- 4.83 (m, 1H), 3.74 -3.59(m, 2H), 3.46 - 3.34 (m, 2H), 2.67 - 2.56 (m, 2H), 2.07 (s, 3H), 1.21 -1.08 (m, 3H).

520		(IR thin film) 1672	ESIMS m/z 273 ([M+Hf)	1H NMR (400 MHz, CDCÎ3) δ 9.00 (s, 1H), 8.57 (bs, 1H), 8.10 (dt, J = 8.0, 1.9 Hz, 1H), 7.34 (dd, J = 7.7, 4.7 Hz, 1H),6.47 (s, 1H), 4.02 (q, J = 7.3 Hz, 2H), 3.22 (s, 3H), 2.45 (dt, J = 13.4, 6.7 Hz, 1H), 1.51 (t, J =7.3 Hz, 3H), 1.09 (dd, J = 6.5, 4.1 Hz, 6H).
521	115- 118		ESIMS m/z 351 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.6 Hz, 1H), 8.62 (dd, J = 4.7, 1.3 Hz, 1H). 8.15 (s, 1H), 8.09-8.01 (m, 1H), 7.50-7.41 (m, 1H), 3.72 (s, 1H), 3.46-3.19 (m, 2H), 2.09 (s, 3H), 1.45 (d, J = 6.9 Hz, 3H), 1.050.90 (m, 1H), 0.58 - 0.42 (m, 2H), 0.29-0.13 (m, 2H).

Page 537 of6!9

522	92-95		ESIMS m/z 309 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.97 (s, 1H), 8.65 (s, 1H), 8.098.01 (m, 1H), 7.98 (s, 1H), 7.52- 7.45 (m. 1H), 3.93 - 3.83 (m, 1H), 3.79 (s, 1H), 3.67 (s, 1H). 3.28 (s. 3H), 1.34-1.25 (m, 3H), 1.18 (t, J = 7.2 Hz, 3H).
523	119.0 121.0		ESIMS m/z 334 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.67 (d, 7 = 0.9 Hz, 1H), 8.33 (d, 7 = 2.5 Hz, 1H), 7.94 - 7.73 (m, 2H), 3.25 (s, 3H), 1.86- 1.72 (m, 1H), 1.45 (s, 9H), 1.04-0.92 (m, 4H).

Page 538 of 619

524	109.5 111.0		ESIMS m/z 334 ([M+HJ+)	1H NMR (400 MHz, CDCI3) Ô 8.79 (s. 1H), 8.58 (dd, J = 4.7, 1.2 Hz, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.69 (s, 1H), 7.41 (dd, 7 = 8.3, 4.8 Hz, 1H), 7.18 (s, 1H), 6.86 (s, 1H), 3.41 (s, 3H), 2.32 (s, 3H).
525	92.0- 94-0		ESIMS m/z 336 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.72 (d, 7= 1.6 Hz, 1H), 8.40 (d, 7 = 2.5 Hz, 1H), 7.93 (s, 1H), 7.82 (dt, 7 = 9.5, 2.4 Hz, 1H), 3.29 (s, 3H), 2.80 (t, 7 = 7.3 Hz, 2H), 2.52 (t, J = 7.3 Hz, 2H), 2.06 (s, 3H), 1.80 -1.70 (m, 1H), 1.07 -0.99 (m, 4H).

Page 539 of 619

526	105.0 107.0		ESIMS m/z 350 ([M+2f)	1H NMR (400 MHz, CDCI3) δ 8.72 (dd, 7= 1.2, 0.8 Hz, 1H), 8.39 (d, 7 = 2.5 Hz, 1H). 7.96 (s, 1H), 7.82 (dt, 7=9.5, 2.4 Hz, 1H), 3.30 (s, 3H), 2.96 2.78 (m, 2H), 2.53 -2.39 (m, 1H), 2.01 (s, 3H), 1.87 -1.75(m, 1H), 1.16 (d, 7 = 6.6 Hz, 3H), 1.140.94 (m, 4H).
527		(thin film) 1651	ESIMS m/z 304 ([M+2]*)	1H NMR (300 MHz, CDCI3) δ 8.70 (s, 1H), 8.36 (d, 7 = 2.4 Hz, 1H), 7.89 (s, 1H), 7.80 (dt, 7=9.5, 2.3 Hz, 1H), 3.24 (s, 3H), 2.77 2.62 (m, 1H), 1.76 -1.64 (m. 1H), 1.07 (d, 7=6.7 Hz, 6H), 1.03 0.93 (m, 4H).

Page 540 of6!9

528		(thin film) 1651	ESIMS m/z 350 ((M+2f),	’H NMR (300 MHz, CDCI3) δ 8.69 (d, J= 1.7 Hz, 1H), 8.37 (d, J = 2.6 Hz, 1H), 7.88 (s, 1H), 7.79 (dt, J = 9.5, 2.3 Hz, 1H), 3.33- 3.13 (m, 4H), 2.54 (dd. J =15.6, 6.5 Hz, 1H), 2.30 (dd, J= 15.6, 7.6 Hz. 1H), 2.03 (s, 3H), 1.80- 1.65 (m, 1H). 1.27 (d, J = 6.7 Hz, 3H), 1.07- 0.90 (m, 4H).
529	112.5 114.5		ESIMS m/z 348 ([M+2]+)	’H NMR (400 MHz, CDCI3) δ 8.73 (d, J= 1.5 Hz, 1H), 8.40 (d, J = 2.5 Hz, 1H), 7.96 (s, 1H). 7.83 (dt, J = 9.4, 2.3 Hz, 1H), 3.29 (s, 3H), 2.50 (ddd, J = 8.1,5.5, 3.6 Hz, 1H), 2.11 (s, 3H), 1.85- 1.74 (m, 2H), 1.57-1.48 (m, 1H), 1.12- 0.94 (m, 5H).

Page54l of6!9

530		(thin film) 1720	ESIMS m/z 436 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.97-8.92 (m, 1H), 8.63 (dd, J = 4.7, 1.4 Hz, 1H), 8.07-8.01 (m, 2H), 7.46 (ddd, J = 8.4, 4.8, 0.7 Hz, 1H), 3.32-3.18 (m, 1H), 3.18- 3.01 (m, 2H), 2.94 -2.85 (m, 1H), 2.62-2.48 (m, 3H), 2.07 (s, 3H), 1.27 (d, J = 6.8 Hz, 3H).
531		(thin film) 1720	ESIMS m/z 450 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.10-8.83 (m, 1H), 8.76-8.52 (m, 1H), 8.078.01 (m, 2H), 7.51 -7.41 (m, 1H), 3.35-3.20 (m, 1H), 2.95-2.83 (m, 3H), 2.59- 2.47 (m, 1H). 2.28 -2.13 (m, 2H), 2.07 (S, 3H), 2.03 -1.91 (m, 2H), 1.27 (d, J = 6.8 Hz, 3H).

Page 542 of6!9

532	80-83		ESIMS m/z 355 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.4 Hz, 1H), 8.62 (d,7 = 3.8 Hz, 1H), 8.14 (s, 1H), 8.07 -7.98(m, 1H), 7.49-7.40 (m, 1H), 4.19 (s, 1H), 3.69-3.44 (m, 3H), 3.35 (s, 3H), 3.33 (brs, 1H), 2.08 (s, 3H), 1.45 (d, 7 = 6.9 Hz, 3H).
533		(thin film) 3095, 2920, 1663.	ESIMS m/z 341 ([M+H]*).	1H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.4 Hz, 1H), 8.64- 8.59 (m, 1H), 8.11 (s, 1H), 8.06 - 7.99 (m, 1H), 7,48 -7.42 (m, 1H), 3.91 (brs, 2H), 3.60 (s. 2H), 3.35 (s, 3H), 3.13 (s, 2H), 2.21 (s, 3H).

Page 543 of6l9

534		{thin film) 3082, 3004, 2919, 1657.	ESIMS m/z 337 ([M+Hf).	’H NMR (400 MHz, CDCI3) δ 8.98 (s, 1H), 8.65 (s, 1H), 8.11 (s, 1H), 8.05 (d, J = 8.3 Hz, 1H), 7.47 (s, 1H), 3.55 (brs, 2H), 3.11 (s, 2H), 2.23 (s, 3H), 1.05 - 0.92 (m, 1H), 0.54 - 0.44 (m, 2H), 0.26-0.13 (m, 2H).
535		(thin film) 3423, 1654	ESIMS m/z 356 ([M+Hf)	’H 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, 1H), 8.07 (ddd, J =8.3, 2.4, 1.3 Hz, 1H), 7.47 (dd, J = 8.3, 4.7 Hz, 1H), 4.47 -3.70(m, 3H), 3.65-3.09 (m, 2H), 2.91 -2.68 (m, 2H), 2.48 (dd, J = 12.4, 5.0 Hz, 1H), 2.01 (s, 3H), 1.18 (d, J = 6.5 Hz. 3H).

536	64-71		ESIMS m/z 291 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.92 (d, 7=2.6 Hz, 1H), 8.74- 8.49 (m, 1H), 8.09 -7.95 (m, 1H), 7.86 (s, 1H), 7.52 -7.36 (m, 1H), 5.12 (s. 2H), 3.92 -3.60(m, 2H), 1.89 (bs, 3H). 1.29- 1.03 (m, 3H).
537			ESIMS m/z 360 ([M+H]*)	1H NMR (400 MHz. CDCI3) δ 8.95(d, 7=2.6 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.13-7.99 (m, 1H), 7.94 (s, 1H), 7,55-7.34 (m, 1H), 3.87-3.46 (m, 2H), 2.28 - 2.19 (m,2H), 2.19 -2.05(m, 2H), 1.95- 1.83 (m, 2H), 1.20-1.10 (m, 3H).

Page 545 of6!9

538	111- 119		ESIMS m/z 291 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (d, 7 = 2.5 Hz, 1H), 8.67- 8.54 (m, 1H), 8.06 (ddd, 7 = 8.3, 2.6, 1.4 Hz, 1H), 8.01 (s, 1H), 7.46 (dd, 7 = 8.3, 4.7 Hz, 1H), 3.73 (q, 7 = 7.2 Hz, 2H), 1.46 (ddd, 7= 12.6, 8.1.4.7 Hz, 1H), 1.16 (t, 7 = 7.2 Hz, 3H), 1.004 (t, 7 = 3.7 Hz, 2H). 0.71 (dd, 7 = 7.7, 3.0 Hz, 2H).
539			ESIMS m/z 305 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.8.62 (d, 7 = 4.6 Hz, 1H), 8.07 (d, 7= 7.2 Hz, 1H), 8.02- 7.98 (s, 1H), 7.45 (dd, 7=8.3, 4.8 Hz, 1H), 3.71 (tt, 7 = 13.2, 6.6 Hz, 2H), 1.45-1.35 (m, 1H), 1.28- 1.21 (m, 1H), 1.21 -1.07(m, 4H), 1.04-0.96 (d, 7 = 6.0 Hz, 3H), 0.54 (t, 7=8.7 Hz, 1H).

Page 546 of6!9

540

ESIMS m/z 327 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.97 (d, 7 = 2.5 Hz, 1H), 8.64 (dd, J = 4,8, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 8.00 (s, 1H), 7.479 (ddd, 7 = 8.3, 4.8, 0.7 Hz, 1H), 3.94 (dq, 7 = 14.3, 7.2 Hz, 1H), 3.59 (dq, 7= 14.2, 7.2 Hz, 1H), 2.35 - 2.09 (m, 2H), 1.67- 1.53 (m, 1H), 1.18 (t,J = 7.2 Hz, 3H).

Page 547 of6!9

541			ESIMS m/z 367 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.02-8.93 (d, 7 = 2.7 Hz, 1H), 8.70 -8.58 (m, 1H), 8.11 -8.05 (s, 1 H),8.06 - 8.04 (m, 1H), 7.52- 7.44 (m, 1H), 3.70 (m, 2H), 3.60- 3.51 (m, 2H), 3.38 - 3.26 (s, 3H), 2.60 -2.42 (m, 1H), 2.18-2.05 (s, 3H), 1.721.61 (m, 1H), 1.55 - 1.48 (m, 1H), 1.11 -0.87 (m, 1H).
542			ESIMS m/z 321 ([M+H]+)	1H NMR (400 MHz, CDCI3 ) δ 9.03 (dd, 7 = 4.9, 2.6 Hz, 2H), 8.61 (m, 2H), 8.16 (d, 7 = 3.2 Hz, 1H), 8.11 (dddd, 7 = 8.4, 4.1,2.6, 1.3 Hz, 2H), 7.50 (dt, 7 = 8.5, 4.4 Hz, 2H), 3.66 (q, 7 = 7.0 Hz, 3H), 2.76 (t, 7 = 6.2 Hz, 4H), 2.37 (t, 7 = 6.1 Hz, 3H), 2.17 (s, 35H), 1.12 (td, 7 = 7.1, 1.3 Hz, 3H).	13CNMR(101 MHz, CDCI3) δ 207.86 (s), 172.25 (s), 148.49 (s), 141.08 (s), 140.03 (s), 135.83 (s), 126.81 (s), 126.45 (s), 124.20 (d, 7 = 8.3 Hz), 44.00 (s), 38.42 (s), 30.09 (s), 27.89 (s), 13.15 (s).

Page 548 of 61J2.

543	117- 120		ESIMS m/z 323 ([M+H]+), 321 ([M-H]-)	’H NMR (400 MHz, CDCI3) δ 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, 0.6 Hz, 1H), 3.80 (t, J = 6.7 Hz, 2H), 3.74 (q, J = 7.1 Hz, 2H), 2.64 (t, 7 = 6.7 Hz, 2H), 1.18 (t, 7 = 7.2 Hz, 3H).
544	129- 132		ESIMS m/z 297 ([M+Hf), 295 ([M-HD	’H NMR (400 MHz, CDCI3) δ 8.98 (d. 7 = 2.4 Hz, 1H), 8.63 (s, 1H), 8.58-8.53 (m, 1H), 8.037.96 (m, 1H), 7.43 -7.37 (m, 1H), 3.59 - 3.48 (m, 1H), 2.18 (s, 3H), 1.59 (d, 7 = 7.3 Hz, 3H).

545		(thin film) 3178, 2923, 1676.	ESIMS m/z 283 ([M+Hf).	1H NMR (400 MHz, CDCI3) δ 9.06-8.90 (m, 1H), 8.74 (s, 1H), 8.64 (s, 1H), 8.57 - 8.45 (m, 1H), 8.05 - 7.90 (m, 1H), 7.46-7.33 (m, 1H), 3.41 (s, 2H), 2.24 (s, 3H).
546	135.0 136.5		ESIMS m/z 413 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.82 (s, 1H), 8.60 (d, 7 = 4.1 Hz, 1H), 7.95 (d, 7 = 7.4 Hz, 1H), 7.71 (s, 1H), 7.43 (dd, 7 = 8.3,4.8 Hz, 1H), 6.69 (s, 1H), 3.38 (s, 3H), 2.47 (s, 3H).

547

(thin film) 1739, 1669

ESIMS m/z 398 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.97 (d, J = 2.3 Hz, 1H), 8.64 (dd, J = 4.7, 1,4 Hz, 1H), 8.15 (s, 1H), 8.04 (ddd, J =8.3, 2.7, 1.4 Hz, 1H), 7.47 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 4.50-3.40 (m, 4H). 2.84 (dd, J = 12.7, 8.9 Hz, 1H), 2.78-2.63 (m, 1H), 2.46 (dd, J = 12.7, 5.4 Hz, 1H), 2.03 (s, 3H), 2.01 (s, 3H), 1.16 (d, J = 6.6 Hz, 3H).

Page 551 of 619

548

(thin film) 1583

ESIMS m/z 328 ([M+H]*)

’H NMR (400 MHz, CDCI3) δ 9.56 (s, 1H), 9.27 (s, 1H), 8.99 (d, J = 2.3 Hz, 1H), 8.58 (dd, J = 4.7, 1.4 Hz, 1H), 8.00 (ddd, J =8.3, 2.7, 1.4 Hz, 1H), 7.42 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H), 3.19 -3.05 (m, 1H), 3.00 (dd, J =13.2, 8.1 Hz, 1H), 2.78 (dd, J= 13.2, 5.2 Hz, 1H), 2.15 (s, 3H), 1.44 (d, J = 6.7 Hz, 3H).

Page 552 of 619

549

(thin film) 1657

ESIMS m/z 340 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7=2.5 Hz, 1 H), 8.63 (dd, 7 = 4.7, 1.4 Hz, 1H), 8.04 (ddd, 7 = 8.4, 2.7, 1.5 Hz, 1H), 8.02 (s, 1H), 7.46 (ddd, 7= 8.3, 4.8, 0.6 Hz, 1H), 3.26 (s. 3H), 3.06 (td, 7= 13.0, 7.4 Hz, 1H), 2.43 (ddd, 7 = 22.2, 15.7, 7.0 Hz, 2H), 2.03 (s, 3H), 1.69 -1.45 (m, 2H), 0.97 (t, 7 = 7.3 Hz, 3H).

Page 553 of 619

550

(thin film) 1654

ESIMS m/z 353 ([M+Hf)

’H NMR (400 MHz, CDCI3) δ 8.96 (d, J = 2.5 Hz, 1H), 8.63 (dd, J= 4.7, 1.4 Hz, 1H), 8.06 (ddd, J = 8.4, 2.7, 1.4 Hz, 1H), 7.99 (s, 1H), 7.47 (ddd, J =8.4, 4.8, 0.6 Hz. 1H), 3.73 (ddt, J = 20.4, 13.3, 6.7 Hz, 2H), 3.18-2.99 (m, 1H). 2.44 (dd, J = 15.7, 7.3 Hz, 1H), 2.36 (dd, J = 15.7, 6.6 Hz, 1H), 2.03 (s, 3H), 1.69 -1.41 (m, 2H), 1.17 (t, J =7.2 Hz, 3H), 0.97 (t, J = 7.3 Hz, 3H).

Page 554 of 619

551

(thin film) 1667

ESIMS m/z 379 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7=2.4 Hz, 1H), 8.64 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.05 (ddd, 7 = 8.4,2.7, 1.5 Hz, 1H), 8.01 (s, 1H), 7.47 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 3.83- 3.69 (m, 1H), 3.30 (s, 3H), 2.64 (dd, 7= 16.4, 3.6 Hz, 1H), 2.46 (dd,7= 16.4, 10.1 Hz, 1H). 2.29 (s, 3H).

Page 555 of6l9

552		(thin film) 1665	ESIMS m/z 419 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.62 (dd, J = 4.8, 1.4 Hz, 1H), 8.11 -8.04 (m, 1H), 8.02 (d, J = 13.3 Hz, 1H), 7,46 (ddd, J = 8.4, 4.8, 0.6 Hz, 1H), 3.85- 3.69 (m, 1H), 3.60 (s, 2H), 2.64 (dd, J= 16.4, 3.7 Hz, 1H), 2.42 (dd, J= 16.4, 9.9 Hz. 1H), 2.28 (s, 3H), 1.09-0.89 (m, 1H), 0.51 (d, J = 8.2 Hz, 2H), 0.20 (t, J = 5.1 Hz, 2H).
553		(thin film) 1663	ESIMS m/z 329 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, J = 2.5 Hz, 1H), 8.63 (dd, J = 4.7, 1.3 Hz, 1H), 8.05 (ddd, J = 8.4, 2.7, 1.5 Hz, 1H), 8.01 (s, 1H), 7.52 - 7.43 (m, 1H), 3.25 (s, 3H), 2.43 -2.35 (m, 2H), 2.35-2.13 (m, 2H), 1.59 (t, J = 18.4 Hz, 3H).

Page 556 of 619

554		(thin film) 1661	ESIMS m/z 369 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 8,94 (d, J =2.6 Hz, 1H), 8.61 (dd, J = 4.7,1.3 Hz, 1H), 8.05 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.99 (s, 1H), 7.45 (ddd, J = 8.4, 4.8, 0.5 Hz, 1H), 3.52 (s, 2H), 2.45 - 2.33 (m, 2H), 2.23 (ddd, J = 23.9, 16.3, 7.3 Hz, 2H), 1.58 (t, J = 18.4 Hz, 3H), 0.96 (tt, J = 7.8, 4.8 Hz, 1H), 0.56-0.42 (m, 2H), 0.18 (q, J = 4.7 Hz, 2H).
555			ESIMS m/z 351 ([M+Hp	1H NMR (400 MHz, CDCI3) δ 8.96 (d, J =2.5 Hz. 1H), 8.65 (dd, J = 4.8, 1.4 Hz, 1H), 8.06 (s, 1H), 8.05 - 8.03 (m, 1H), 7.54-7.41 (m, 1H),3.70 (s, 2H), 3.29 (s. 3H).	13CNMR(101 MHz, CDCI3) δ 167.08, 148.99, 140.08, 135.51, 131.88, 128.75, 126.53, 125.99, 124.65, 124.19, 37.84, 33.12.

Page 557 of 6I9

556		(IR thin film) 1375	ESIMS m/z 305 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.00 (s, 1H), 8.57 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.10 (dt, 7 = 8.0, 2.0 Hz, 1H), 7.34 (dd, 7 = 7.2, 4.8 Hz, 1H), 6.48 (s, 1H), 4.05 (q, 7 = 7.3 Hz, 2H). 3.25 (s, 3H), 2.78 (dt, 7 = 6.8, 3.2 Hz, 2H), 2.50 (bs, 1H), 2.31 (s, 1H), 2.05 (s, 3H), 1.52 (t, J = 7.3 Hz, 3H)
557		(IR thin film) 1675	ESIMS m/z 288 ([M+2Hf)	’H NMR (400 MHz, CDCI3) δ 9.01 (s, 1H), 8.56 (d,7 = 4.0 Hz. 1H), 8.12 (dt, 7 = 7.9, 1.9 Hz, 1H), 7.34 (dd, J = 7.8, 4.8 Hz, 1H), 6.44 (s, 1H), 4.34 (dt, J = 13.2, 6.6 Hz. 1H), 3.21 (s. 3H), 2.44 (dt, 7= 13.4, 6.7 Hz, 1H), 1.52 (dd, 7 = 8.6, 6.7 Hz, 6H), 1.09 (dd, 7 = 6.7, 3.7 Hz, 6H)

Page 558 of6!9

558

(thin film) 1657

ESIMS m/z 362 ([M+H]*)

1H NMR (400 MHz, CDCI3) δ 8.88 (d, 7 = 2.6 Hz, 1H), 8.61 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.01 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.47-7.40 (m, 2H), 7.12 (dd, 7= 5.1, 1.1 Hz, 1H), 6.92 (dd, 7 = 5.1,3.4 Hz, 1H), 6.78 (dd, 7=3.3, 0.8 Hz, 1H), 3.70 (dd, 7= 14.5, 7.7 Hz, 2H), 3.18 (t, 7 = 7.2 Hz, 2H), 2.48 (t, 7 = 7.2 Hz, 2H), 1.14 (t, 7 = 7.2 Hz, 3H).

Page 559 of 619

559	•	(thin film) 1658	* ESIMS m/z 376 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 2.4 Hz, 1H), 8.62 (dd, 7=4.7, 1.4 Hz, 1H), 8.02 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.81 (s, 1H), 7.46 (ddd, 7 = 8.3, 4.8, 0.5 Hz, 1H), 7.04 (dd, 7 = 5.1, 1.1 Hz, 1H), 6.85 (dd, 7 = 5.1, 3.4 Hz, 1H), 6.77- 6.70 (m, 1H), 3.70 (q, 7= 7.1 Hz, 2H), 2.84 (t, 7 = 7.2 Hz, 2H). 2.26 2.15 (m, 2H), 2.00 (p, 7 = 7.5 Hz, 2H), 1.15 (t, 7 = 7.2 Hz, 3H).
560	140.0 142.0		ESIMS m/z 277 ((M+Hf)	'H NMR (300 MHz, CDCI3) δ 10.12 (s, 1H), 9.14 (s, 1H), 8.90 (d, 7 = 2.0 Hz, 1H), 8.82 (s, 1H), 8.51 (d, 7 = 2.5 Hz, 1H), 7.92 (dt. 7 = 9.2, 2.4 Hz, 1H), 2.65 (dt, 7 = 13.8, 6.9 Hz. 1H), 1.31 (d, 7 = 6.9 Hz, 6H).

Page 560of6!9

561	172.0 177.0		ESIMS m/z 298 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.79 (s, 1H), 8.67 (s, 1 H), 8.40 (s, 1H), 7.80 (dt, J = 9.4, 2.3 Hz, 1H), 7.42 (s, 1 H), 4.77 (s, 2H), 2.63 (hept, J = 6.9 Hz, 1H), 1.30 (d, J = 6.9 Hz, 6H).
562		(IR thin film) 1677	ESIMS m/z 319 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 9.01 (S, 1H), 8.56 (bs, 1H), 8.14 (d, J = 7,9 Hz, 1H), 7.36 (dd, J = 7.9, 4.8 Hz, 1H), 6.45 (s, 1H), 4.37 (dt, J = 13.2,6.6 Hz, 1H), 3.24 (s, 3H), 2.85-2.67 (m, 2H). 2.64-2.41 (m, 1H), 2.35-2.21 (m, 1H), 2.05 (s, 3H), 1.57-1.48 (d, J = 20.2 Hz, 6H).

Page 561 of 619

563		(IR thin film) 1675	ESIMS m/z 322 ([M+2Hf)	1H NMR (400 MHz, CDCI3) δ 9.09 (d, J= 1.7 Hz, 1H), 8.61(d, J = 3.3 Hz, 1H), 8.20 (dt, J = 7.9, 1.9 Hz, 11 H), 7.52 -7.46 (m, 4H), 7.45-7.33 (m, 2H), 6.69 (s, 1H), 3.22 (s, 3H), 2.43 (dt, J= 13.3, 6.7 Hz, 1H), 1.06 (bs, 3H), 0.73 (bs,3H).
564		(IR thin film) 1675	ESIMS m/z 305 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.00 (d, 7 = 1.5 Hz, 1H), 8.58 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.09 (dt, 7 = 8.0, 1.8 Hz, 1H), 7.35 (dd, 7=7.9, 4.8 Hz, 1H), 6.49 (s, 1H), 4.133.93 (m, 1H), 3.80 (s, 3H), 3.50 3.30 (m, 1H), 2.87 -2.68(m, 2H), 2.53-2.15 (m, 2H), 2.05 (s, 3H), 1.19 (t, 7 = 7.2 Hz, 3H).

Page 562 of 619

565

(IR thin film) 1673

ESIMS m/z 331 ([M+Hf)

1H NMR (400 MHz, CDCI3) δ 9.00 (d, J= 1.5 Hz, 1H), 8.57 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.10 (dt, 7 = 7.9, 1.8 Hz, 1H), 7.35 (dd, 7 = 7.6, 4.5 Hz, 1H), 6.52 (s, 1H), 3.83 (s, 3H), 3.57 (qd,7 = 13.9, 7.4 Hz, 2H), 2.90-2.65 (m, 2H), 2.53-2.34 (m, 1H), 2.34- 2.19 (m, 1H), 2.05 (s, 3H), 1.00 (ddd, 7= 12.7, 7.7, 4.9 Hz, 1 H), 0.62- 0.39 (m, 2H), 0.33 -0.06(m, 2H).

Page 563 of 619

566			ESIMS m/z 345 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.00 (d, J= 1.6 Hz, 1H), 8.57 (dd, 7 = 4.8, 1.6 Hz, 1H), 8.23-7.93 (m, 1H), 7.35 (dd, 7 = 7.9, 4.8 Hz, 1H), 6.51 (s, 0.40, H), 6.50 (s, 0.6) 3.92 (s, 1.60 H), 3.82 (s, 1.40H), 3.723.35 (m, 2H), 3.06 -2.70 (m, 1H), 2.63-2.28 (m, 2H), 2.05 (s, 1.60H), 1.95 (s, 1.40H), 1.15 (m, 3H), 1.01 (td, 7 = 7.6,4.8 Hz, 1H), 0.51 (d, 7= 8.3 Hz, 2H), 0.30 0.08 (m, 2H).
567	109.5 111.1		ESIMS m/z 277 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.80 (s, 1H), 8.43 (s, 1H), 7.82 (ddd, 7 = 9.5, 2.7, 1.7 Hz, 1H), 6.50 (s, 1H), 3.77 (s, 3H), 3.22 (s, 3H), 2.43 (dt, 7= 13.5, 6.8 Hz, 1H), 1.09 (d,7 = 6.7 Hz, 6H).

Page564of6l9

568		(IR thin film) 1676	ESIMS m/z 309 ([M+H]*)	’H NMR (400 MHz, CDCI3) δ 8.79 (s, 1H), 8.43 (d, J = 2.6 Hz, 1H), 7.82 (ddd, J = 9.5, 2.7, 1.7 Hz, 1H), 6.51 (s, 1H), 3.81 (s, 3H), 3.25 (s, 3H), 2.85- 2.70 (m, 2H), 2.53 -2.23 (m, 2H) 2.05 (s, 3H).
569			ESIMS m/z 343 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 9.01 (s, 1H), 8.61 (s, 1H), 8.53 (s, 1H), 8.01 (ddd, J = 8.3,2.5, 1.3 Hz, 1H), 7.96 (s, 1H), 7.72 (s, 1H), 7.39 (dd, J = 8.3, 4.7 Hz, 1H), 2.82 (s, 2H), 2.15 (s, 3H), 1.40 (s, 6H).	’3CNMR(101 MHz, CDCI3) δ 171.71 (s), 148.66 (s), 140.88 (s), 140.06 (s), 135.68 (s), 126.37 (s), 123.93 (m), 44.06 (s), 33.29 (t, J = 25.2 Hz), 26.85 (t, J = 4.1 Hz), 23.79 (t, J = 27.6 Hz). 13.07 (s).

Page 565 of 619

570

(IR thin film) 1652

ESIMS m/z 409 ((M+Hf)

1H NMR (400 MHz, CDCI3) δ 8.98 (d. 7 = 2.3 Hz, 1H), 8.63 (td, 7 = 4.8, 2.4 Hz, 1H), 8.14-8.01 (m, 2H), 7.46 (ddd, 7= 8.3, 4.8, 0.7 Hz, 1H), 4.26 (dd, 7= 17.2, 8.4 Hz, 1 H), 3.89 - 3.61 (m,2H), 3.01 (dd, 7= 17.6, 8.2 Hz, 1H), 2.77 (s, 2H), 2.48 (dd, 7 = 17.7, 3.3 Hz, 1H), 1.19 (t, 7 = 7.2 Hz, 3H).

Page 566 of 619

571		(IR thin film) 1671	ESIMS m/z 409 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.04 (d, J= 13.4 Hz, 1H), 8.61 (dt, J = 6.0, 3.1 Hz, 1H), 8.41 (s, 1H), 8.05 (dddd, J = 7.8, 6.2, 2.6, 1.4 Hz, 1H), 7.44 (dt, J = 13.4,6.7 Hz, 1H), 4.41 - 3.90 (m, 2H), 3.56 - 3.18 (m, 2H), 3.14 -2.84 (m, 1H), 2.70 (d, J= 7.1 Hz, 3H), 1.23 - 1.13 (m, 3H). (Signais of both diastereomers)
572		(IR thin film) 1667	ESIMS m/z 383 ([M+Hf),	’H NMR (400 MHz, CDCI3) δ 8.97 (s, 1H). 8.65 (s, 1H), 8.06 (dd, J = 8.3, 1.2 Hz, 1H), 8.00 (s, 1H), 7.48 (dd, J =7.8, 4.5 Hz, 1H), 3.26 (s, 3H), 2.53- 2.32 (m, 4H).

573		(IR thin film) 1666	ESIMS m/z 397 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.64 (d, J = 4.3 Hz, 1H), 8.07 (ddd, J = 8.3, 2.7,1.4 Hz, 1H), 7.98 (s, 1H), 7.48 (dd, J =8.3, 4.7 Hz, 1H), 3.72 (q, J =7.2 Hz, 2H), 2.55 - 2.35 (m, 4H), 1.17 (t, J = 7.2 Hz, 3H).
574		(IR thin film) 1667	ESIMS m/z 411 ([M+Hf),	’H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.65 (s, 1H), 8.06 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.96 (s, 1H), 7.48 (dd, J = 8.2,4.7 Hz, 1H), 3.70 - 3.52 (m, 2H), 2.57 - 2.34 (m, 4H), 1.61 (s, 3H), 1.60-1.52 (m, 2H). 0.93 (t. J = 7.4 Hz, 3H).

Page 568 of 619

575		(IR thin film) 1669	ESIMS m/z 423 ([M+Hf)	’H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.64 (s, 1H), 8.07 (ddd, 7 = 8.3, 2.6, 1.3 Hz, 1H), 8.00 (s, 1H), 7.47 (dd, 7 = 8.2, 4.7 Hz, 1H), 3.55 (s, 2H), 2.58 - 2.36 (m, 4H), 1.63 (s, 2H), 0.97 (tt. 7 = 7.8, 4.9 Hz, 1H), 0.59-0.44 (m, 2H), 0.20 (q, 7 = 4.8 Hz, 2H).
576		(IR thin film) 1657	ESIMS m/z 353 ([M+H]*)	1H NMR (400 MHz, CDCI3) δ 8.95 (d, 7 = 2.6 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.06-8.02 (m, 2H), 7.51 - 7.41 (m, 1H), 3.27 (s, 3H), 3.06 (td, 7 = 7.0, 4.2 Hz, 1H), 2.43 (d, 7 = 7.1 Hz, 2H), 2.11 (s, 3H), 1.91 (dtd, 7 = 13.5,6.7,4.3 Hz, 1H), 0.96 (d, 7 = 6.8 Hz, 3H), 0.88 (d, 7 = 6.8 Hz, 3H).

Page 569 of 619

577

(IR thin film) 1655

ESIMS m/z 367 ([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), 8.05 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 8.02 (s, 1H), 7.46 (ddd, J = 8.4, 4.8,0.6 Hz, 1H), 3.88 - 3.59 (m, 2H), 3.06 (ddd, J = 7.8, 6.2, 4.2 Hz, 1H), 2.39 (dd, J = 7.0, 2.0 Hz, 2H), 2.11 (s, 3H), 1.90 (dtd, J= 13,5, 6.8, 4.2 Hz, 1H), 1.17 (t, J = 7.2 Hz, 3H), 0.95 (d, J = 6.7 Hz, 3H), 0.88 (d, J = 6.8 Hz, 3H).

Page 570 of6!9

578			EIMS (m/z) 396 ([M+]+), 398 ((M+2]+)	’H NMR (400 MHz. CDCI3) δ 8.95 (d, 7 = 2.7 Hz. 1H), 8.63 (d, 7 = 4.8 Hz. 1H), 8.05 (d, 7= 11.1 Hz, 1H), 8.01 (s, 1H), 7.50-7.42 (m.1H), 3.26 (s, 3H), 2.93 - 2.76 (m, 2H), 2.71 (m, 1H). 2.55-2.47 (m, 1H), 1.22 (d. J = 2.9 Hz, 3H), 1,21 (d, 7 = 2.9 Hz, 3H), 1.18 (d, 7 = 6.7 Hz, 3H).
579			EIMS (m/z) 353 ([M+J+)	’H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.7 Hz, 1H), 8.62 (dd, 7 = 4.8, 1.5 Hz, 1H), 8.04 (s, 1H), 8.03 - 8.06 (m, 1H), 7.49-7.44 (m, 1H), 3.26 (s, 3H), 2.95 - 2.77 (m, 2H), 2.76 2.69 (m, 1H), 2.55 -2.48 (m, 1H), 1.23- 1.20 (m, 6H), 1.17 (d, 7 = 6.7 Hz, 3H).

Page57l of6l9

580

EIMS (m/s) 367 <[M+1]+).

1H NMR (400 MHz, CDCI3) δ 8.97-8.94 (m, 0.7H), 8.87 (dd, J = 2.8, 0.7 Hz, 0.3H), 8.62 (dd, J = 4.8, 1.4 Hz, 0.7H), 8.47 (dd, J = 4.8, 1.5 Hz, 0.3H), 8.07 - 8.03 (m, 0.7H), 8.02 (s. 1H), 7.98-7.94 (m, 0.3H), 7.49 - 7.44 (m, 0.7H), 7.36 (d, J = 0.7 Hz, 0.3H), 3.85 (bs, 1H), 3.60 (bs, 1H). 2.92-2.75 (m, 2H), 2.65 (m, 1H), 2.58-2.42 (m, 1H), 1.23- 1.18 (m, 6H), 1.18 -1.15 (m, 6H).

Page 572 of 619

581	51-53		ESIMS m/z 420.9([M+H]+), 419.0([M-H]·)	’H NMR (400 MHz, CDCI3) δ 8.97 (s, 1H), 8.64 (dd, 7 = 4.7, 1.3 Hz, 1H), 8.06 (s, 1H), 7.98 (s, 1H), 7.47 (dd, 7 = 8.2, 4.8 Hz, 1H), 3.55 (m, 5H), 3.22 (m, 1H), 2.95 (d, 7 = 8.5 Hz, 1H), 2.18 (m, 1H), 1.94 (s, 1H), 1.43 (s, 9H), 1.16 (t, 7=7.1 Hz, 3H).
582		(IR thin film) 1659	ESIMS m/z 360 ([M+H]+)	’H NMR (400 MHz, CDCI3) δ 8.91 (d, 7 = 2.5 Hz, 1H), 8.62 (dd, 7 = 4.7, 1.1 Hz, 1H), 8.02 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.63 (s, 1H), 7.45 (dd, 7= 8.3, 4.8 Hz. 1H), 7.35 (d, 7= 1.6 Hz, 1H), 5.98 (d, J = 0.8 Hz, 1H), 4.34 (t, 7 = 6.6 Hz, 2H), 3.67 (dd, 7= 12.7, 5.8 Hz, 2H), 2.73 (t, 7 = 5.7 Hz, 2H), 2.31 (s, 3H), 1.10 (t, 7 = 7.2 Hz, 3H).

Page 573 of 619

583

(IR thin film) 3302, 1652

ESIMS m/z 395 ([M+H]+)

1H NMR (400 MHz, CDCI3) δ 8.61 -8.51 (m, 2H), 8.00 (s, 1H), 7.69 (ddd, 7=8.3, 2.6, 1.4 Hz, 1H), 7.43 (d, 7=7.9 Hz, 1H), 7.40- 7.33 (m,2H), 7.14 - 7.08 (m, 1H), 7.00 (d, 7 = 2.3 Hz, 1H), 6.98- 6.92 (m, 1 H), 6.78 (s, 1H), 3.63 (s, 2H), 3.12 (t, 7 = 7.0 Hz, 2H), 2.52 (t, 7=7.1 Hz, 2H), 1.06 (1,7 = 7.2 Hz, 3H).

Page 574 of 619

584		(IR thin film) 1656	ESIMS m/z 371 (IM+H]+)	’H NMR (400 MHz, CDCI3) δ 8.94 (d, 7 = 2.6 Hz, 1H), 8.63 (dd, 7 = 4.7, 1.2 Hz, 1H), 8.43 (d, 7 = 4.1 Hz, 1H), 8.04 (ddd, 7=8.4, 2.7, 1.4 Hz, 1H), 7.91 (s, 1H), 7.57 (td, 7 = 7.7, 1.7 Hz, 1H), 7.46 (dd, 7=8.3, 4.6 Hz, 1H), 7.15 (d, 7 = 7.8 Hz, 1H), 7.05 (dd, 7 = 7.1, 5.2 Hz, 1H), 3.69 (q, 7= 7.1 Hz, 2H), 2.79 (t, 7 = 7.5 Hz, 2H), 2.22 (t, 7 = 7.3 Hz, 2H), 2.13-1.99 (m, 2H), 1.14 (t, 7 = 7.2 Hz, 3H).
585	148.0 149.0		ESIMS m/z 348 ([M+HJ+)	’H NMR (400 MHz, CDCI3) δ 8.82 (s, 1H), 8.58 (d,7 = 4.0 Hz, 1H), 7.94 (d, 7 = 8.7 Hz, 1 H), 7.74 (s, 1H), 7.41 (dd, 7 = 8.3, 4.8 Hz, 1H), 7.15 (s, 1H), 6.85 (s, 1H), 3.94 -3.76(m, 2H), 2.33 (s, 3H), 1.25 (t, 7 = 7.1 Hz, 3H).

Page 575 of6!9

586	156.5 158.0		ESIMS m/z 427 ([M+HJ+)	1H NMR (400 MHz, CDCI3) δ 8.85 (s, 1H), 8.60 (d, J = 4.7 Hz, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.76 (s, 1H), 7.43 (dd, J = 8.3, 4.8 Hz, 1H), 6.68 (s, 1H), 3.95-3.70 (m, 2H), 2.48 (s, 3H), 1.23 (t, 7=7.1 Hz, 3H).
587	132.0 134.0		ESIMS m/z 346 ([M+HJ+)	1H NMR (400 MHz, CDCI3) δ 8.90 (d, 7= 2.6 Hz, 1H), 8.61 (dd, 7 = 4.8, 1.4 Hz, 1H), 8.01 (ddd, 7 = 8.3, 2.7, 1.5 Hz, 1H), 7.67 (s, 1H), 7.45 (dd, 7=8.3, 4.7 Hz, 1H), 7.36 (d, 7= 1.6 Hz, 1H), 5.99 (s, 1H), 4.34 (t, 7 = 6.6 Hz, 2H), 3.21 (s, 3H), 2.78 (t, 7=6.6 Hz, 2H), 2.31 (s, 3H).

Page 576 of 619

588

(IR thin film) 1657

ESIMS m/z 357 ((M+H]+)

’H NMR (400 MHz, CDCI3) δ 8.92 (d, J = 2.3 Hz, 1H), 8.63 (d, J = 4.1 Hz, 1H), 8.42 (d, J =4.4 Hz, 1H), 8.02 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.92 (s, 1H), 7.55 (td, J = 7.7, 1.8 Hz, 1H), 7.46 (dd, J =8,4, 4.7 Hz, 1H), 7.13 (d, J =7.8 Hz, 1H), 7.03 (dd, J = 7.0, 5.2 Hz, 1H), 3.22 (S, 3H), 2.78 (t, J =7.4 Hz, 2H), 2.25 (t, J = 7.4 Hz, 2H), 2.07 (p, J = 7.3 Hz, 2H).

Page 577 of6!9

I

589	72-75		ESIMS m/z 328 ((M+Hf)	1H NMR (400 MHz, CDCI3) δ 8.98 (d, 7 = 2.5 Hz, 1H), 8.64 (dd, 7=4.7, 1.3 Hz, 1H), 8.07 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 8.01 (s, 1H), 7.47 (ddd, 7 = 8.3, 4.8, 0.6 Hz, 1H), 4.57 (m, 1H), 3.73 (qd, 7= 13.4, 6.7 Hz, 2H), 2.70 (dd, 7= 15.8, 8.0 Hz, 1H), 2.48 (dd, 7 = 15.8, 5.5 Hz, 1H), 1.53 (d, 7 = 6.6 Hz, 3H), 1.17 (t, 7 = 7.2 Hz, 3H).
590			ESIMS m/z 277 ([M-f-Bu]*).	1H NMR (400 MHz, CDCI3) δ 8.96 (s, 1H), 8.62 (d, 7 = 3.3 Hz, 1H), 8.10 (s, 1H), 8.07 - 7.92 (m, 1H), 7.44 (dd. 7 = 8.2, 4.7 Hz, 1H), 4.51 (s,2H), 1.46 (s, 9H).	13C NMR (101 MHz, CDCI3) δ 198.64, 155.98, 153.41, 148.56, 140.17, 126.30, 124.04, 122.20, 115.78, 81.30, 77.34, 76.70, 28.02.

Page 578 of 619

591	135- 136		ESIMS m/z 304 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 9.06-8.94 (d, J = 2.5 Hz, 1H), 8.698.59 (dd, 7 = 4.8, 1.5 Hz, 1H), 8.258.11 (s, 1H), 8.11 -7.96 (m, 1H), 7.53 - 7.42 (m, 1H), 4.70 (bs, 2H), 2.70 - 2.50 (m, 1H), 1.151.07 (d, 7 = 6.8 Hz, 7H).
592		(IR thin film) 1679	ESIMS m/z 351 ([M+Hf)	1H NMR (400 MHz, CDCI3) δ 9.00 (d, 7 = 2.6 Hz, 1 H), 8,66 (dd, J = 4.9, 1.4 Hz, 1H), 8.29 (s, 1H), 8.05 (ddd, 7 = 8.3, 2.7, 1.4 Hz, 1H), 7.48 (ddd, 7 = 8.3, 4.8, 0.4 Hz, 1H), 5.48-3.75 (m, 2H), 2.87-2.72 (m, 2H), 2.51 (dd, 7= 12.1,4.3 Hz, 1H). 2.04 (s, 3H), 1.19 (d, 7 = 6.6 Hz, 3H).

Page 579 of 619

593		(IR thin film) 1666	ESIMS m/z 332 ([M+HJ+)	1H NMR (400 MHz, CDCI3) δ 8.90 (d, J =2.6 Hz, 1H), 8.62 (dd, J = 4.7, 1.3 Hz, 1H), 8.02 (ddd, J = 8.3, 2.7, 1.4 Hz, 1H), 7.72 (s, 1H), 7.45 (dd, J = 8.2, 4.5 Hz, 1H), 7.26- 7.24 (m, 1H), 6.28 (dd, J = 3.1, 1.9 Hz, 1H), 6.01 (d, J = 3.1 Hz, 1H), 3.24 (s, 3H), 2.99 (t, J = 7.4 Hz, 2H), 2.51 (t, J =7.5 Hz, 2H).
594	69		ESIMS m/z 381 ([M+H]+)	1H NMR (400 MHz, CDCI3) δ 8.60-8.53 (m, 2H), 8.01 (s, 1H), 7.69 (ddd, J = 8.3, 2.6, 1.4 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.40- 7.34 (m, 2H), 7.13 (t, J =7.2 Hz, 1H), 7.02-6.94 (m, 2H), 6.84 (s, 1H), 3.17 (s, 3H), 3.13 (t, J =7.0 Hz, 2H), 2.56 (t, J =7.1 Hz, 2H).

Page 580 of6!9

595

1H NMR (400 MHz, CDCI3) δ 9.12-8.86 (m, 1H), 8.55 (dd, J = 4.7, 1.4 Hz, 1H), 8.04 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 8.01 (d, J =0.5 Hz, 1H), 7.84- 7.65 (m, 1H), 7.41 (ddd, J = 8.3, 4.8, 0.7 Hz, 1H). 1.51 (s, 18H).

Page 581 of 619

Table 3: GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA) Rating Table

% Control (or Mortality)	Rating
80-100	A
More than 0 - Less than 80	B
Not Tested	C
No activity noticed in this bioassay	D

Table 4. Biological Data for GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA)

Compound No.	MYZUPE % Ctrl @ 200 ppm	BEMITA % Ctrl @ 200 ppm
1	B	A
2	A	A
3	B	A
4	A	A
5	A	A
6	B	A
7	B	A
8	B	A
9	B	B
10	B	B
12	D	C
18	D	B
19	B	A

20	B	A
21	D	D
22	A	A
23	A	A
24	D	D
25	D	D
26	B	B
27	B	A
28	A	B
29	B	A
30	B	A
31	D	A
32	A	A
33	C	C
34	C	C

Page 582 of 619

35	C	C
36	C	C
37	C	C
38	C	C
39	B	B
40	C	C
41	B	D
42	A	C
43	A	C
44	A	B
45	A	C
46	B	C
47	B	c
48	B	c
49	B	B
50	B	B
51	A	B
52	A	B
53	A	B

54	A	B
55	A	A
56	B	B
57	A	A
58	A	A
59	A	A
60	A	A
61	A	B
62	D	D
63	A	B
64	A	A
65	A	B
66	B	D
67	A	A
68	C	A
69	C	C
70	A	A
71	C	C
72	A	B

Page 583 of 619

73	A	A
74	A	A
75	A	A
76	A	A
77	A	B
78	A	B
79	A	A
80	A	A
81	B	B
82	B	D
83	A	B
84	B	D
85	A	B
86	A	A
87	C	A
88	C	B
89	B	B
90	A	A
91	B	B

92	C	B
93	C	A
94	C	A
95	A	A
96	C	A
97	A	A
98	A	A
99	D	B
100	B	B
101	A	A
102	A	A
103	A	A
104	A	B
105	A	A
106	C	C
107	B	D
108	C	C
109	D	B
110	D	B

Page 584 of 619

111	A	A
112	C	C
113	D	B
114	C	C
115	A	A
116	A	B
117	B	D
118	D	D
119	B	B
120	D	B
121	A	A
122	A	A
123	A	A
124	A	A
125	A	A
126	D	B
127	B	D
128	B	A
129	B	B

130	B	D
131	D	B
132	B	A
133	A	A
134	A	A
135	B	A
136	A	A
137	A	A
138	B	A
139	B	D
140	D	B
141	A	A
142	A	A
143	A	A
144	A	A
145	A	B
146	C	C
147	B	A
148	A	B

Page 585 of6!9

149	A	B
150	A	A
151	A	B
152	A	B
153	A	A
154	A	A
155	A	A
156	A	B
157	A	A
158	A	A
159	A	A
160	A	A
161	A	A
162	A	A
163	A	A
164	A	A
165	A	A
166	A	A
167	A	B

168	A	A
169	A	B
170	A	B
171	A	B
172	A	A
173	A	A
174	A	A
175	A	A
176	A	A
177	A	A
178	B	A
179	A	A
180	A	B
181	A	A
182	A	A
183	A	A
184	B	A
185	A	A
186	A	A

Page 586 of 619

187	A	A
188	A	A
189	A	A
190	A	A
191	A	A
192	A	A
193	A	A
194	A	A
195	A	A
196	A	A
197	B	B
198	B	B
199	A	A
200	A	A
201	B	A
202	A	A
203	A	A
204	A	A
205	A	A

206	A	A
207	A	A
208	A	A
209	A	A
210	A	A
211	A	A
212	A	A
213	A	A
214	A	A
215	A	A
216	A	B
217	A	A
218	A	A
219	A	A
220	B	A
221	A	A
222	A	A
223	A	A
224	A	A

Page 587 of 619

225	A	A
226	B	A
227	A	A
228	B	A
229	A	A
230	A	B
231	B	A
232	A	A
233	A	A
234	A	A
235	A	A
236	A	A
237	A	A
238	A	A
239	A	A
240	B	A
241	A	A
242	A	A
243	A	A

244	A	A
245	B	A
246	A	A
247	A	A
248	A	A
249	A	A
250	A	B
251	B	A
252	B	A
253	A	A
254	B	A
255	A	B
256	A	B
257	A	D
258	A	A
259	A	A
260	A	A
261	A	A
262	A	A

Page 588 of 619

263	A	A
264	B	A
265	B	B
266	B	A
267	A	A
268	B	B
269	A	A
270	A	A
271	B	A
272	A	A
273	B	A
274	B	A
275	A	A
276	B	A
277	A	A
278	A	A
279	B	A
280	B	A
281	B	D

282	A	A
283	A	A
284	A	A
285	B	A
286	A	A
287	A	A
288	B	A
289	B	A
290	B	A
291	B	A
292	A	A
293	B	A
294	B	A
295	B	A
296	B	A
297	A	B
298	A	D
299	A	B
300	A	A

Page 589 of6!9

301	A	A
302	A	A
303	A	A
304	A	A
305	A	A
306	A	A
307	A	A
308	A	B
309	B	B
310	A	A
311	A	A
312	A	B
313	A	A
314	A	A
315	A	A
316	B	A
317	A	A
318	A	B
319	A	B

320	A	A
321	A	A
322	A	A
323	A	A
324	A	A
325	A	A
326	A	A
327	B	B
328	C	A
329	A	A
330	A	A
331	A	A
332	A	A
333	A	A
334	A	A
335	A	A
336	A	A
337	A	A
338	A	A

Page 590 of 619

339	A	A
340	B	A
341	A	A
342	A	A
343	B	A
344	A	A
345	A	A
346	A	A
347	B	A
348	A	B
349	B	B
350	A	A
351	A	A
352	B	B
353	A	A
354	B	B
355	B	B
356	B	B
357	B	B

358	B	A
359	B	A
360	B	A
361	A	A
362	A	A
363	A	A
364	A	A
365	A	A
366	A	A
367	B	A
368	B	A
369	D	A
370	B	A
371	A	A
372	A	A
373	B	A
374	B	A
375	A	B
376	A	B

Page 591 of 619

377	A	B
378	A	A
379	A	A
380	B	A
381	B	A
382	A	A
383	A	A
384	B	A
385	A	A
386	A	A
387	B	A
388	B	A
389	A	A
390	C	A
391	C	A
392	A	A
393	A	A
394	A	A
395	B	A

396	C	A
397	A	A
398	C	A
399	A	B
400	B	A
401	B	B
402	B	B
403	B	A
404	B	B
405	C	A
406	A	A
407	A	A
408	B	A
409	B	A
410	C	A
411	B	A
412	A	A
413	A	A
414	B	A

Page 592 of 619

415	C	A
416	B	A
417	A	B
418	D	A
419	B	B
420	B	B
421	A	A
422	A	A
423	B	A
424	B	B
425	A	A
426	A	A
427	A	A
428	A	A
429	A	A
430	A	A
431	B	A
432	A	A
433	A	A

434	B	A
435	D	A
436	B	A
437	A	A
438	C	A
439	A	A
440	C	A
441	A	B
442	B	A
443	B	A
444	A	A
445	A	A
446	A	A
447	A	A
448	B	A
449	A	A
450	A	A
451	A	A
452	A	A

Page 593 of6!9

453	A	A
454	A	A
455	A	A
456	A	B
457	A	A
458	A	A
459	A	A
460	A	A
461	A	A
462	C	A
463	A	A
464	A	A
465	A	A
466	A	A
467	A	A
468	C	A
469	A	A
470	C	A
471	A	A

472	A	A
473	C	A
474	C	A
475	C	A
476	C	A
477	C	A
478	A	A
479	A	A
480	A	A
481	B	A
482	A	A
483	B	A
484	B	B
485	C	A
486	A	A
487	C	A
488	C	A
489	C	A
490	A	A

Page 594 of 619

491	A	A
492	A	A
493	A	A
494	A	A
495	A	A
496	A	A
497	A	A
498	A	A
499	C	A
500	C	A
501	C	A
502	C	A
503	c	A
504	c	A
505	A	A
506	A	A
507	A	A
508	A	A
509	C	A

510	A	A
511	A	A
512	C	A
513	A	B
514	C	A
515	C	A
516	C	C
517	A	B
518	B	D
519	A	A
520	C	A
521	A	B
522	A	A
523	D	B
524	C	C
525	A	B
526	A	B
527	B	D
528	B	B

Paj of6!9

529	B	D
530	A	A
531	A	A
532	A	B
533	A	A
534	A	A
535	A	B
536	A	A
537	A	A
538	A	A
539	C	A
540	A	A
541	A	A
542	B	A
543	B	A
544	A	A
545	A	B
546	C	C
547	A	B

548	A	B
549	A	A
550	A	A
551	A	A
552	A	A
553	A	A
554	A	A
555	A	A
556	C	A
557	C	B
558	B	A
559	B	A
560	D	A
561	D	B
562	C	A
563	C	D
564	C	A
565	C	A
566	C	B

Page 596 of 6I9

567	C	A
568	C	A
569	C	A
570	c	C
571	c	C
572	c	C
573	c	C
574	c	C
575	c	C
576	c	C
577	c	C
578	c	C
579	c	C
580	c	C
581	c	c

582	C	c
583	C	c
584	C	c
585	C	c
586	C	c
587	C	c
588	C	c
589	C	c
590	A	A
591	A	A
592	A	A
593	C	C
594	C	C
595	c	c

Page 597 of 6I9

.¾¾ 5*st £

Claims (18)

1. Claims

   1. A composition comprising a molécule according to

   Formula One” wherein (a) A is either attachment bond (b) R1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C_rC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted Ci-C₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted Ci-C₂o 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, S(O)nN(R9)₂, or R9S(O)_nR9, wherein each said R1, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO_Z, C^Cq alkyl, C₂-C₆ alkenyl, CrC₆ haloalkyl, C₂-C_B haloalkenyl, C_rC₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-Ci₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-Ci₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or CrC^

   Page598 of6l9 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 alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted Ci-C₆ alkoxy, substituted or unsubstituted C₂'C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C2o aryl, substituted or unsubstituted CrC₂₀ 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, or R9S(O)_nR9, wherein each said R2, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, Cj-Cs alkyl, C₂-C₆ alkenyl, C_rC₆ haloalkyl, C₂-C₆ haloalkenyl, CrC₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-Ci₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or Ci-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 CrC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted CrC₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted CrC₂o heterocyclyl, OR9, C(=X1)R9, C(=X1)OR9, C(=X1)N(R9)₂₁ N(R9)_2l 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, I, CN, NO₂, C_rC₆ alkyl, C₂-C₆ alkenyl, haloalkyl, C₂-C₆ haloalkenyl, CrCe haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-Cw cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C_w halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or CrC₂o 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 attachaient bond to carbon attachment bond to nitrogen

   Ail where R4 is H, NO₂, substituted or unsubstituted Ci-C₆

   Page 599 of 619 alkyl, substituted or unsubstituted C₂-C_e alkenyl, substituted or unsubstituted CrCe alkoxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted Ci-C₂₀ heterocyclyl, C(=X1)R9, C(=X1)OR9, C(=X1 )N(R9)₂, N(R9)₂₁ N(R9)C(=X1)R9, 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, CrC₆ alkyl, C₂-C₆ alkenyl, C_rC_e haloalkyl, C₂C₆ haloalkenyl, CrC₆ haloalkyloxy, C₂-C_e haloalkenyloxy, C₃-Ci₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C3-C10 halocycloalkyi, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or C_rC₂₀ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9), or (b) attachment bond to nitrogen

   A12 where R4 is a C_rC₆ alkyl, (2) A2 then R4 is H, F, Cl, Br, I, CN, NO₂₁ substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted Ci-C₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted CrC₂₀ 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, 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-|-C₆ alkyl, C₂-C₆ alkenyl, CrCe haloalkyl, C₂C₆ haloalkenyl, CrCe haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyi, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or C_rC₂₀ 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 C₂-C₆ alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted C₂-C_B alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂₀ 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

   Page 600 of619

   R9S(O)_nR9, wherein each said R5, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC_e alkyl, C₂-C₆ alkenyl, ΟρΟβ haloalkyl, C₂-C₆ haloalkenyl, Ο,-Ο₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, Ο₃-Ο,₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyl, C₃-C₁₍) halocycloalkenyl, OR9, S(O)_nOR9, or C₆-C₂₀ aryl, (each of which that can be substituted, may optionally be substituted with R9);

   (g) (1) when A is A1 then R6 is substituted or unsubstituted CrC₆ alkyl, substituted or unsubstituted C₂-C_e alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C6-C₂o aryl, substituted or unsubstituted Οι-Ο₂₀ 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,-C_e alkyl C₆-C₂₀ aryl (wherein the alkyl and aryl can îndependently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1)R9, R9X2R9, C(=O)(C_rC₆ alkyl)S(O)_n(C_rC_e alkyl), C(=O)(C,-C₆ alkyl)C(=O)O(C_r C_B alkyl), (Ci-C₀ alkyl)OC(⁼0)(Ce-C2o aryl), (Ci-C0 alkyl)OC(⁼O)(Ci-Ce alkyl), Ο,-Οβ alkyl-(C3-Cio cyclohaloalkyl), or (Ο,-Ο₆ alkenyl)C(=O)O(C_rC₆ alkyl), or R9X2C(=X1 )X2R9, wherein each said R6, which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC₆ alkyl, C₂-C₆ alkenyl, C,-C₆ haloalkyl, C₂-C₆ haloalkenyl, Ci-C_e haloalkyloxy, C_z-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, Ο₆-Ο₂₀ aryl, or C_rC₂o heterocyclyl, R9aryl, (each of which that can be substituted, may optionally be substituted with R9).

   optionally R6 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 H, substituted or unsubstituted Ο,-Ο₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted Ci-C@ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-Ci₀ cycloalkenyl, substituted or unsubstituted Οθ-Ο₂₀ aryl, substituted or unsubstituted Οι-Ο₂₀ 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, R9S(O)_nR9, Cj-Cg alkyl C₆-C₂₀ aryl (wherein the alkyl and aryl can îndependently be substituted or unsubstituted), C(=X2)R9, C(=X1)X2R9, R9X2C(=X1 )R9, R9X2R9, C(=O)(C_rC₆ alkyl)S(O)_n(C,-C_e alkyl), C(=O)(C,-C₆ alkyl)C(=O)O(C,C₆ alkyl), (0,-0_Β alkyl)OC(=O)(C₆-C₂₀ aryl), (Ο,-Ο_β alkyl)OC(=O)(C,-C₆ alkyl), C,-C₆ alkyl-(C₃-C₁₀

   Page 601 of 619 cyclohaloalkyl), or (C_rC₆ alkenyl)C(=O)O(C_rC₆ alkyl), or R9X2C(=X1)X2R9, wherein each said R6, which is substîtuted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C,-C₆ alkyl, C₂-C₆ alkenyl, C_rC₆ haloalkyl, C₂-C₆ haloalkenyl, Ci-Cg haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-Cio halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or CrC₂₀ heterocyclyl, R9aryl, (each of which that can be substîtuted, may optionally be substîtuted with R9), optionally R6 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;

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

   (i) R8 is substîtuted or unsubstituted C_rC₆ alkyl, substîtuted or unsubstituted C₂-C₆ alkenyl, substîtuted or unsubstituted Ci-C₆ alkoxy, substîtuted or unsubstituted C₂-C₆ alkenyloxy, substîtuted or unsubstituted C₃-C₁₍} cycloalkyl, substîtuted or unsubstituted C₃-C₁₀ cycloalkenyl, substîtuted or unsubstituted C₆-C₂₀ aryl, substîtuted or unsubstituted Ci-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)_nOR9, RgSfOPRg, or R9S(O)_n(NZ)R9, wherein each said R8, which is substîtuted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC₆ alkyl, C₂-C₆ alkenyl, Ci-C₀ haloalkyl, C₂-C₆ haloalkenyl, C_rC₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-Ci₀ cycloalkenyl, C3-C10 halocycloalkyl, C₃-C₁₀ halocycloalkenyl, N(R9)S(O)_nR9, oxo, OR9, S(O)_nOR9, R9S(O)_nR9, S(O)_nR9, C₆-C₂₀ aryl, or CrC_2Q heterocyclyl, (each of which that can be substîtuted, may optionally be substîtuted with R9);

   (j) R9 is (each independently) H, CN, substîtuted or unsubstituted CrC₆ alkyl, substîtuted or unsubstituted C₂-C₆ alkenyl, substîtuted or unsubstituted C_rC_s alkoxy, substîtuted or unsubstituted C₂-C₆ alkenyloxy, substîtuted or unsubstituted C₃-C₁₀ cycloalkyl, substîtuted or unsubstituted C₃-C₁₀ cycloalkenyl, substîtuted or unsubstituted C₆-C₂₀ aryl, substîtuted or unsubstituted CrC₂₀ heterocyclyl, S(O)_nC_rC₆ alkyl, N(C_rC₆alkyl)₂, wherein each said R9, which is substîtuted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, C_rC₆ alkyl, C₂-C₆ alkenyl, CrC₆ haloalkyl, C₂-C₆ haloalkenyl, C^Cg haloalkyloxy, C₂-C₅ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C_w halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OCrCg alkyl, OC_rC₆ haloalkyl, S(O)_nCi-C₆alkyl, S(O)_nOCi-C₆ alkyl, C₆-C₂₀ aryl, or C_rC₂₀ heterocyclyl;

   Page 602 of 619 (k) n is 0, 1, or 2;

   (l) X is N or CR_ni where R_n1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted CrCs alkyl, substituted or unsubstituted C₂-C_e alkenyl, substituted or unsubstituted C_rC₆ alkoxy, substituted or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted CrC^ cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstituted C₆-C₂o aryl, substituted or unsubstituted C_rC₂₀ heterocyclyl, OR9, C(=X1 )R9, C(=X1 )OR9, C(=X1)N(R9)₂, N(R9)_2i N(R9)C(=X1)R9, SR9, S(O)_nR9, S(O)_nOR9, or R9S(O)_nR9, wherein each said R_n1 which is substituted, has one or more substituents selected from F, Cl, Br, I, CN, NO₂, Ci-C_e alkyl, C₂-C₆ alkenyl, CrCe haloalkyl, C₂-C₆ haloalkenyl, CrC₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl, OR9, S(O)_nOR9, C₆-C₂₀ aryl, or C_rC₂o 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; and (ο) Z is CN, NO₂, C_rC₆ alkyl(R9), C(=X1 )N(R9)₂; and (р) 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) that R6 and R8 are not linked in a cyclic arrangement with only -CH₂-, (4) that when A is A2 then R5 is not C(=O)OH, (5) that when A is A2 and R6 is H then R8 is not a -(Ci-C₆ alkyl)-O(substituted aryl), and (6) that when A is A2 then R6 is not -(Cialkyl)(substituted aryl).
2. 2. A composition according to claim 1, wherein said molécule (a) A is A2;

   (b) R1 is H;

   (с) R2 is H;

   (d) R3 is H or CH₃;

   (e) R4 is Cl;

   Page 603 of 619 (f) R5 is H, OCH₂CH₃, F, Cl, Br, or CH₃;

   (g) R6 is methyl or ethyl;

   (h) R7 is O or S; and (i) R8 is selected from (substituted or unsubstituted CrCe alkyl)-S(O)_n-(substituted or unsubstituted C_rC₆ alkyl) wherein said substituents on said substituted alkyls are selected from F, Cl, Br, I, CN, NO₂, N(R9)S(O)_nR9, OR9, S(O)_nOR9, R9S(O)_nR9, S(O)_nR9, C_s-C₂₀ aryl, or Ct-Cîo heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9).
3. 3. A composition according to claim 1, wherein said molécule is selected from Table 1 compounds numbers 1-12 and 18 - 595 and preferably has one of the following structures
4. 4. A composition according to claim 1,2, or 3, further comprising:

   (a) one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, 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).
5. 5. A composition according to claim 1,2, or 3, wherein the composition further comprises one or more compounds selected from: (3-ethoxypropyl)mercury bromide, 1,2-dichloropropane,

   Page 604 of 619

   1.3- dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-triiodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBApotassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5T-isoctyl, 2,4,5-T-îsopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-Ttriethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2.4-D-3butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DBisoctyi, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium,

   2.4- D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-Disopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-Dtriethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidïn, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, a/pria-cypermethrin, a/pha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlormethyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralidtris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amlsulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspîrin, asulam, asulam-potassium, asulamsodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphosmethyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquînox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodîum, benthiavalicarb, benthiavalicarbisopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobîcyclon,

   Page 605 of6!9 benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzlhiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, befa-cyfluthrin, befa-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromoDDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazîm, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carie ntrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chîoramben-diolamine, chloramben-methyl, chloramben-methylammonium, 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-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfiuazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, 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 II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin,

   Page 606 of 619 clethodim, clîmbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydîm, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazîne, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, 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-diolamîne, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamîne, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorpropethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron,

   Page 607 of 6 i 9 dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, 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, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinosebsodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dînoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodîum, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodîne, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothaldiammonium, endothal-dipotassium, endothal-disodîum, endothïon, endrin, enestraburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, 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, fenpiclonîl, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentîn acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flampropM, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen,

   Page608of6l9 flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, 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, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldéhyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetylaluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gîbberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosatedimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosatepotassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acétates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadîene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, Icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamoxammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, imînoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron,

   Page 609 of 619 iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, îoxynrl, ioxynrl octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, îprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamtdofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, îsopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvénile hormone I, juvénile hormone II, juvénile hormone lll, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, iactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, Ivdingjunzhi, Ivxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, ΜΑΜΑ, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPAdiolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPAolamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPBethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecopropethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-Ppotassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldiriocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxylM, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron,

   Page 610 of 619 metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethyimercury)-ptoluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalamsodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, paradichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury dérivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyi, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloramtriethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyi, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zînc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp'-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz,

   Page 61 lof 619 prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, progiinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propîsochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrîfenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyrimlnobac-methyl, pyrimisulfan, pyrlmitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithîobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamîd, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemîde, resmethrin, rhodethanil, rhodojaponin-llI, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthyiazine, secbumeton, sedaxane, selamectîn, semîamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, teu-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCAsodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor,

   Page 612 of 619 terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuronmethyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thïophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultapmonosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, 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, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyrtriethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trîfluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trïmethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodïum, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zetacypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomîhuanglong, α-chlorohydrin, a-ecdysone, a-multistriatin, and anaphthaleneacetic acid.
6. 6. A composition according to claim 1 wherein in said molécule said A is A1, preferably A11, or said A is A2, said R1 is H, said R2 is H, said R3 is selected from H, or substituted or unsubstituted C_rC₆ alkyl, preferably from H or CH₃.

   Page 613 of619 said R5 is selected from H, F, Cl, Br, I, substituted or unsubstituted Ci-C₆ alkyl, substituted or unsubstituted Ci-C₆ alkoxy, preferably from H, OCH2CH3, F, Cl, Br, or CH₃, said R6 is C_rC_e alkyl, C^Cg alkyl-phenyl, H, CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂₁ CH₂phenyl, CH₂CH(CH₃)₂, CH₂cyclopropyl, C(=O)CH₂CH₂SCH₃₁ C(=O)OC(CH₃)₃, CH₂CH=CH₂₁ C(=O)OCH_ZCH₃, C(=O)CH(CH₃)CH₂SCH₃, cyclopropyl, CD₃₁ CH₂OC(=O)phenyl, C(=O)CH₃, C(=O)CH(CH₃)₂₁ CH₂OC(=O)CH(CH₃)₂, CH₂OC(=O)CH₃, C(=O)phenyl, CH₂OCH₃, CH₂OC(=O)CH₂OCH₂CH₃, CH₂CH₂OCH₃, CH₂OC(=O)0CH(CH₃)₂₁ CH₂CH₂OCH₂OCH₃₁ CH₂CH₂OCH₃, CH₂CH₂OC(=O)CH₃, or CH₂CN, preferably methyl or ethyl, said R7 is O or S, said R8 is selected from (substituted or unsubstituted C_rC₆ alkyl)-S(O)_n-(substituted or unsubstituted C_rC_B alkyl) wherein said substituents on said substituted alkyls are selected from F, Cl, Br, I, CN, NO₂, N(R9)S(O)_nR9, OR9, S(O)_nOR9, R9S(O)_nR9, S(O)_nR9, C₆-C₂₀ aryl, or Ci-C₂₀ heterocyclyl, (each of which that can be substituted, may optionally be substituted with R9), substituted or unsubstituted CrC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted Cj-C^ heterocyclyl, R9C(=X1)OR9, SR9, S(O)_nOR9, R9S(O)_nR9, or R9S(O)_n(NZ)R9, or is

   CH(CH₃)CH₂SCH₃₁ CH(CH₃)₂, C(CH₃)₂CH₂SCH₃₁ ch₂ch₂sch₃, ch₂cf₃, CH_zCH₂C(=O)OCH₃₁ N(H)(CH₂CH₂SCH₃), OCH₂CH_zSCH₃, CH(CH₂SCH₃)(CH₂phenyl), thiazolyl, oxazolyl, isothiazolyl, substituted-furanyl, CH₃, C(CH₃)₃, phenyl, CH₂CH₂OCH₃, pyridyl, CH₂CH(CH₃)SCH₃, OC(CH₃)₃, C(CH₃)₂CH₂SCH₃₁ CH(CH₃)CH(CH₃)SCH₃₁ CH(CH₃)CF₃₎ CH₂CH₂-thienyl, CH(CH₃)SCF₃,CH₂CH₂CI, CH₂CH₂CH₂CF₃, CH₂CH₂S(=O)CH₃, CH(CH₃)CH₂S(=O)CH₃, CH₂CH_zS(=O)₂CH₃, CH(CH₃)CH₂S(=O)₂CH₃, nch₂ch₃₁ N(H)(CH₂CH_zCH₃), C(CH₃)=C(H)(CH₃), N(H)(CH_zCH=CH₂), CH_zCH(CF_?)SCH₃, CH(CF₃)CH_zSCH₃₁ thietanyl, CH_ZCH(CF₃)₂, CH₂CH₂CF(OCF₃)CF₃, CH_zCH_zCF(CF₃)CF₃, CF(CH₃)_2i CH(CH₃)phenyl-CI, CH(CH₃)phenyl-F, CH(CH₃)phenyl-OCF₃, CH₂N(CH₃)(S(=O)₂N(CH₃)₂, CH(CH₃)OCH₂CH_zSCH₃₁ CH(CH₃)OCH₂CH_zOCH₃, och₃, CH(CH₃)SCH₃₁ CH₂SCH₃, N(H)CH₃, CH(Br)CH₂Br, or CH(CH₃)CH_zSCD₃, said X is CRm where R_n, is H or halo, preferably where R_n1 is H or F, or said X1 or X2 or both are O.
7. 7. A composition according to claim 1 wherein in said moiecule

   Page 614 of 619 when said A is A1, and A1 is A11, then R4 is selected from H, or substituted or unsubstituted C_rC₆ alkyl, or substituted or unsubstituted C_e-C₂₀ aryl, preferably from CH_3l CH(CH₃)₂, or phenyl,

   5 when said A is A1, and A1 is A12, then R4 is CH₃, when said A is A2 then R4 is selected from H, substituted or unsubstituted C_rC₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C6-C₂₀ aryl, wherein each said R4, which Is substituted, has one or

   10 more substituents selected from F, Cl, Br, or I, preferably wherein R4 is H, C_rC₆ alkyl, CH₃, CH₂CH₃, CH=CH₂, cyclopropyl, CH₂CI, CF₃, phenyl or Cl, when said A is A1 then R6 is substituted or unsubstituted C_rC₆ alkyl,

   15 when said A is A2 then R6 is selected from substituted or unsubstituted CrC₀ alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-Ci₀ cycloalkyl, C(=X1)R9, C(=X1)X2R9, R9X2R9, C(=O)(C_rC₆ alkyl)S(O)_n(C_rC₆ alkyl), (C_rC₆ alkyl)OC(=O)(C₆-C₂₀ aryl), (C_rC_a alkyl)OC(=O)(CrC₆ alkyl), or R9X2C(=X1)X2R9, or.

   20 when said A is 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.
8. 8. A composition according to claim 1 further comprising

   25 an agriculturally acceptable carrier, a biopesticide, one or more of the following compounds:

   (a) 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;

   (b) 3-(4’-chloro-2,4-dimethyl[1,1 ’-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-

   3-en-2-one;

   (c) 4-[[(6-chloro-3-pyridÎnyl)rnethyl]methylamino]-2(5H)-furanone;

   (d) 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5/7)-furanone;

   Page 615 of 619 (e) 3-chloro-N2-[(1 S)-1-methyl-2-(methylsulfonyl)ethyl]-A/1-[2-methyl-4-[1,2,2,2tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;

   (f) 2-cyano-M-ethyl-4-fluoro-3-methoxy-benenesulfonamide;

   (g) 2-cyano-/V-ethyl-3-methoxy-benzenesulfonamide;

   (h) 2-cyano-3-difluoromethoxy-M-ethyl-4-fluoro-benzenesulfonamide;

   (i) 2-cyano-3-fluoromethoxy-A/-ethyl-benzenesu!fonamide;

   0) 2-cyano-6-fluoro-3-methoxy-A/,A/-dimethyl-benzenesulfonamide;

   (k) 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;

   (l) 2-cyano-3-difluoromethoxy-W, /V-dimethylbenzenesulfon-amide;

   (m) 3-(difiuoromethyl)-A/-[2-(3,3-dimethylbutyl)phenyl]-1 -methyl-1 H-pyrazole-4carboxamide;

   (n) M-ethyl·2₁2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl) hydrazone;

   (o) /V-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-a,a,atrifluoro-p-tolyl) hydrazone nicotine;

   (p) O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1 -(2-trifluoromethylphenyl)-vinyl]} S-methyl thiocarbonate;

   (q) (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;

   (r) 1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydroimidazo[1,2-a]pyridin-5-ol ;

   (s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and (t) N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloroalpha, alpha, a/pha-trif I uoro-p-tolyl )hydrazone,

   Page 616 of 619 a compound having one or more of the following modes of action: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acétylcholine

   5 receptor agonist; acétylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acétylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs), a seed, preferably a seed that has been genetically modified to express one or more

   10 specialized traits.
9. 9. A composition according to claim 1 wherein said molécule is in the form of a pesticidally acceptable acid addition sait, is in the form of a sait dérivative, is in the form a hydrate, is a resolved stereoisomer, is in the form a crystal polymorph, has a ^ZH in place of ¹H, or has a ¹⁴C

   15 in place of a ^1ZC.
10. 10. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule, wherein said capsule preferably has a diameter of about 100-900 nanometers or about 10-900 pm [microns],
11. 11. A process comprising applying a composition according to claim 1, to an area to control a pest, in an amount sufficient to control such pest.
12. 12. A process according to claim 11 wherein said pest is selected from beetles, earwigs,

    25 cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans, preferably from the Phyla Nematoda or Arthropoda, more preferably from the Subphyla Chelicerata, Myriapoda, or Hexapoda, even more preferably from the Class of Arachnida, Symphyla, or Insecta, particularly preferably from the Order Anoplura,

    30 Order Coleoptera, Order Dermaptera, Order Blattaria, Order Diptera, Order Hemiptera, Order Hymenoptera, Order Isoptera, Order Lepidoptera, Order Mallophaga, Order Orthoptera, Order Srphonaptera, Order Thysanoptera, Order Thysanura, Order Acarina, or Order Symphyla, and most preferably wherein said pest is Myzus persicae (MYZUPE) or Bemisia tabaci (BEMITA).

    35
13. 13. A process according to claim 11 wherein said amount is from about 0.01 grams per hectare to about 5000 grams per hectare, preferably from about 0.1 grams per hectare to about 500 grams per hectare, more preferably from about 1 gram per hectare to about 50 grams per hectare.

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14. 14. A process according to claim 11 wherein said area is an area where apples, corn, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans,

    5 are growing, or the seeds thereof are going to be planted.
15. 15. A process according to claim 11 further comprising applying said composition to a genetically modified plant that has been genetically modified to express one or more specialized traits.
16. 16. A process according to claim 11 where said composition further comprises ammonium sulfate.
17. 17. A composition according to claim 1, for controlling endoparasites, ectoparasites, or both 15 in a non-human animal by oral administration, topical application or parentéral administration.
18. 18. A process comprising applying a composition according to claim 1 to a plant to enhance the plant's health, yield, vigor, quality, or tolérance, at a time when pest activity is low.

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