Title of Invention

METHOD FOR CONTROLLING PARTICULAR INSECT PESTS BY APPLYING ANTHRANILAMIDE COMPOUNDS

Abstract A benzoxazinone compound of Formula 10 wherein R4 is H. C1 - C6 alkyl, C2-C6 alkenyl, C2-C6 aLkynyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, CN, halogen, C1-C4 alkoxy, C1-C4 haloalkoxy or NO2; R5 is H. C1-C6 alkyl, C1-C6 haloalkyl, C1-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C(0)R10, CO2R10, C(0)NR10R11, halogen, C1 C4 alkoxy, C1 C4 haloalkoxy, NR10R11N(R11)C(0)R10, N(R11)CO2R10 or S(O)„R12; R6 is H. C1-C6 alkyl, C1-C6 haloalkyl, halogen, CN, C1 C4 allcoxy or C1-C4 haloalkoxy; 10 R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6-haloalkynyl or C3-C6 halocycloalkyl; or 117 is a phenyl ring, a benzyl ring, a 5- or 6- membered heteroaromatic ring, a naphthyl ring system or an aromatic 8-, 9- or 10-membered fused heterobicyclic ring system, each ring or ring system optionally substituted with one to three substituents independently selected from R9; R8 is H. C1-C6 alkyl, C1-C6 haloalkyl, halogen, C1-C4 alkoxy or C1-C4 haloalkoxy; each R9 is independently C1-C4 alkyl, C2-C4 allcenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, NO2, C1-C4 alkoxy, C1-C4 haloalkoxy' C1-C4 alkylthio, C1-C4 alkylsulfmyl, C1-C4 alkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3.C6 cycloalkylamino, C4-C8 (alkyl) (cycloalkyl)amino, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C3-C6 trialkylsilyl; R10 is H. C1-C4 alkyl or C1-C4 haloalkyl; R11 is H or C1-C4alkyl; R12 is C1-C4 alkyl or C1-C4 haloalkyl; and n is 0, 1 or 2. provided that (a) when R4 attached at position 2 is CH3, F, CI or Br, R5 attached at position 4 is halgen of CF3, R6 is CF3, CI, Br or OCH2CHF3 and R8 is H, then R7 is other than 3-Cl-2-pyridinyl or 3-Br-2-prydinyl; (b) when R4,R5 and R8 are H and R6 is CI, then R7 is other than methyl.
Full Text THE PATENTS ACT, 1970 COMPLETE SPECIFICATION
Section 10
"Method for Controlling Particular Insect Pests by Applying Anthranilamide
Compounds."
E.I. DU PONT DE NEMOURS AND COMPANY, a corporation organized and existing under the laws of the State of Delaware, USA of 1007 Market Street, Wilmington, Delaware 19898, USA


The following specification particularly describes the nature of this invention and the manner in which it is to be performed:

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15

1
TITLE
METHOD FOR CONTROLLING PARTICULAR INSECT PESTS BY APPLYING
ANTHRANTLAMIDE COMPOUNDS
BACKGROUND OF THE INVENTION This invention relates to a method of use for controlling invertebrate pests in both agronomic and nonagronomic environments of certain anthranilamides, their //-oxides, agriculturally suitable salts and compositions.
The control of invertebrate pests is extremely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of invertebrate pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, environmentally safer or have different modes of action.
NL 9202078 discloses W-acyl anthrauilic acid derivatives of Formula i as insecticides


wherein, utter alia,
X is a direct bond;
20 YisHorC1-C6alkyl;
Z is NH2, NH(C1-C3 alkyl) or N(CrC3 alkyl)2; and
ll1 through R9 are independently H, halogen, Cj-Qj alkyl, phenyl, hydroxy, Cj-C6 alkoxy or Cj-C-7 a.cyloxy.
SUMMARY OF THE INVENTION
25 This invention pertains to a method for controlling lepidopteran, homopteran,
hemipteran, tli3'sanopteran and coleopteran insect pests comprising contacting the insects or

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10
15
20
OS

wherein
A and B are independently O or S;
R1 is H, Cj-Cfi alkyl, C2-Cg alkoxycarbonyl or C2-Cg alkylcarbonyl;
RzisHorCrC6alkyl;
R3 is H; Cj-Cg alkyl, C2-Cg alkeoyl, C2-Cg alkynyl, or C3-Cg cycloalkyl, each optionally substituted with one or. more substituents selected from the group consisting of halogen, CN, N02, hydroxy, Cj-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Cj-^ alkyJthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C2-Cg alkoxycarbonyl, C2-C$ alkylcarbonyl, CyC6 trialkylsilyl, phenyl, phenoxy, 5-membered heteroarornatic rings, and 6-mernbered heteroarornatic rings; each phenyl, phenoxy, 5-inenibered heteroarornatic ring, and 6-rnembered heteroai'omatic ring optionally substituted with one to three substituents independently selected from the group consisting of C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C1-C4haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, CrCg halocycloalkyl, halogen, CN, NO2, C1-C4 alkoxy, C2-C4 haloalkoxy, CrC4 alkylthio, CrC4 alkylsulfinyl, CrC4 alkylsulfonyl, CrC4 aJkylamino, C2-Cg dialkylaniino, C3-Cg cycloalkyiamino, C4-C$ (alkyl)(cycloalkyl)arnino5 C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylauiinocarbonyl, C^-Cg dialkykminocarbonyl and CyC$ trialkylsilyl; C1-C4 alkoxy; C1-C4 alkylamino; C2-Cg dialkylamino; C3-Cg cycloalkyiamino; C2-Cg alkoxycarbonyl or C2-Cg alkylcarbonyl;
R4 is H, CrC6 alkyl, C2-C6 alkenyl C2-C6 alkynyl, C3-C6 cycloalkyl, CrC6 haloalkyl, CN, halogen, CrC4 alkoxy, C\~C^ haloalkoxy orN02;

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R5 is H, CrC6 alkyl, CrC6 haloalkyl, Ci-C4 alkoxyalkyl, CrC4 hydroxyalkyl,
C(0)Rl°, CO2R103 C(0)NRlORllj halogen. CrC4 alkoxy, CrC4 haloalkoxy,
NRlORll, N(R11)C(O)Rl0, NfRi^COzR10 or S(0)nR12;
R6 is H, CrC6 alkyl, CrC6 haloalkyl, halogen, CN, CrC4 alkoxy or CrC4
5 haloalkoxy;
R7 is CrC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, CrC6 haloalkyl,
C2-C6 haloalkenjd, C2-C6 haloalkynyl or C3-C6'halocycloalkyl; or R7 is a phenyl ring, a benzyl ring, a 5- or 6-membered tieteroaromatic ring, a
naphthyl ring system or an aromatic 8-, 9- or 10-membered fused heterobicyclic
10 ring system, each ring or ring system optionally substituted with one to three
substituents independently selected from R9;
R8 is H, Ci-C6 allcyl, CrC6 haloalkyl, halogen, Cj-C4 alkoxy or Cj-Q haloalkoxy;
each R9 is independently C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6
cycloalkyl, C]~C4 haloalkyl, C2-C4haloalkenyL. C2-C4 haloalkynyl, C3-C6
15 halocycloalkyl, halogen, CN, N02, C;pC4 alkoxy, C]-C4 haloalkoxy, Ci~C4
alkylthio, Cj-C4 alkylsulfmyl, Cj-Q. alkylsulfonyl, C1-C4 alkylamino, C2-C8
dialkylamino, Cy-C$ cycloalkylarnino, C4-Cg (alkyl)(cycloallcyl)amino, C2-C4
alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaniinocarbonyl, Qj^Cg
dialkylaminocarbonyl or C3-C6 trialkylsilyl;
20 Rl0 is H, C]-C4 alkyl or CrC4 haloalkyl;
10
R11 is H or C]-C4 alkyl; R12 is C1-C4 allcyl or C]-C4 haloalkyl; and n is 0, 1 or 2. This invention also relates to such a method wherein an invertebrate pest or its 25 envkonment is contacted with a composition comprising a biologically effective amount of a compound of Formula I or a composition comprising a compound of Formula I and a biologically effective amount of at least one additional biologically active compound. This invention further relates to a benzoxazinone compound of Formula 10

30 wherein

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R4, R5, R6, R7 and R8 are defined as aboved in Formula I. The compound of Fonnula 10 is useful as a synthetic intermediate for preparing a compound of Formula I.
DETAILS OF THE INVENTION
In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. "Allcenyl" includes straight-chain or branched alkenes such as 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. "AUcynyl" includes straight-chain or branched alkynes such as 1 -propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "AUcynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadi3'nyl. "Alkoxy" includes, for example, methoxy, ethoxy, 72-propyloxy, isopropyloxy and the different butoxy, pentoxy audhex)doxy isomers. "Alkoxyalkyl" denotes atkoxy substitution on alkyl. Examples of "allcoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CII2CH2OCH2 and CH3CH2OCH2CH2. "AlkyltMo" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio andhexylthio isomers. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl aud cyclohexyl.
The term "heterocyclic ring" or heterocyclic ring system" denotes rings or ring systems in which at least one ring atom is not carbon and comprises 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more thau 2 sulfurs. The heterocyclic ring can be attached through any available carbon or nitrogen by replacement of hydrogen on said carbon or nitrogen. The term "aromatic ring system" denotes fully unsaturated carbocycles and heterocycles in which at least one ring of the polycyclic ring system is aromatic (where aromatic indicates that the Hiickel rule is satisfied for the ring system). The term "heteroaromatic ring" denotes fully aromatic rings in which at least one'ring atom is not carbon and comprises 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs (where aromatic hidicates that the Hiickel rule is satisfied). The heterocyclic ring can be attached through any available carbon or nitrogen by replacement of hydrogen on said carbon or nitrogen. The term "aromatic heterocyclic ring system" includes fully aromatic heterocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic (where aromatic indicates that the Hiickel rule is satisfied). The teiin "fused heterobicyclic ring system" includes a ring system comprised of two fused rings in which at least one ring atom is not carbon aud can be aromatic or non aromatic, as defined above.

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The team "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F3C, CICE^, CF3CH2 and CF3CCI2. The tenns "haloalkenyl", "haloalkynyl", "haloalkoxy", and the like, are defined analogously to the tram "haloalkyl". Examples of "haloalkenyl" include (Ci)2C=CHCH2 and CF3CH2CH=CHCH2. Examples of "haloalkynyl" include HOCCHC1, CF3OC, CCl3CsC and FCH2CsCCH2. Examples of "haloalkoxy" include CF30, CC13CB20, HCF2CH2CH20 and CF3CH20.
The total number of carbon atoms in a substituent group is indicated by the "Cj-Cj" prefix where i and j are numbers from 1 to 8. For example, C]-C4 alkylsulfonyl designates methylsulfoiiyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3CH(OCTi3), CH3OCH2CFI2 or CH3CH2OCH2; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2 and CH3CH2OCH2CH2. hi the above recitations, when a compound of Formula I comprises a heterocyclic ring, all. substituents are attached to this ring through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
The term "optionally substituted with one to tkee substituents' indicates that one to three of the available positions on the group may be substituted. When a group contains a substituent which can be hydrogen, for. example R6, then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
Compounds of Formula I can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer^) or when separated from the other stereoisomers). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the compounds of Formula I may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active fomi. Similarly, compounds of Foimula 10 can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the ait; will appreciate that one stereoisomer of a compound of Formula 10 may be more useful in preparing a specific stereoisomer of Foimula I. Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the compounds of Foimula 10 may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active foim.

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The salts of the compounds of Formula I include acid-addition salts with inorganic or
organic acids such as hydrobromic, hydro chloric, nitric, phosphoric, sulfuric, acetic, butyric,
fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-tolUenesuffonic or
valeric acids.
As noted above, R7 is (among others) a phenyl, a benzyl, a 5- or 6-membered
heteroaromatic ring, a naphthyl ring system or an aromatic 8-, 9- or 10-membered fused
heterobicyclic ring system, each ring or ring system optionally substituted with one to three
substituents independently selected from R9. The term "optionally substituted" in
connection with these R7 groups refers to groups which are unsubstituted or have at least one
non-hydrogen substituent that does not extinguish the invertebrate pest control activity
possessed by the unsubstituted analog. Note also that J-l through J-4 below denote 5- or
6-membered heteroaromatic rings. An example of a phenyl ring optionally substituted with
1 to 3 R9 is the ring illustrated as J-5 in. Exhibit 1, wherein r is an integer from 0 to 3. An
example of a benzyl riug optionally substituted with 1 to 3 R9 is the ring illustrated as J-6 in
Exhibit 1, wherein r is an integer from 0 to 3. An example of a naphthyl ring system
optionally substituted with 1 to 3 R9 is illustrated as J-59 in Exhibit 1, wherein r. is an integer
from 0 to 3. Examples of a 5- or 6-membered heteroaromatic ring optionally substituted
with 1 to 3 R9 include the rings J-7 through J-58 illustrated in Exhibit 1 wherein r is an
integer from 0 to 3. Note that J-7 through J-26 are examples of JM, J-27 through J-41 are
examples of J-2, and J-46 through J-58 are examples of J-3 and J-4. The nitrogen atoms that
require substitution to fill then valence are substituted with H or R9. Note that some J
groups can only be substituted with less than 3 R9 groups (e.g. J-l9, J-20, J-23 through J-26
and J-37 through. J-40 can only be substituted with one R9). Examples of aromatic 8-, 9- or
10-membered fused heterobicyclic ring systems optionally substituted with 1 to 3 Rp include
J-60 through J-90 illustrated in Exbibit 1 wherein r is au integer from 0 to 3. Although R9
groups are shown in the structures J~5 through J-90, it is noted that they do not need to be
present since they are optional substituents. Note that when the attachment point between
(R9),. and the J group is illustrated as floating, (R9)r can be attached to any available carbon
atom of the J group. Note that when the attachment point on the J group is illustrated as
floating, the J group can be attached to the remainder of Formula I through any available
carbon of the J group by replacement of a hydrogen atom.
ExhjbiU
A* ■ -Xt ■ & ■ & ■

J-5

J-6

J-7

J-8

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10

Prefeixed methods for reasons of cost, ease of synthesis or application, and/or biological efficacy are:
■ Prefen-ed 1. Methods comprising a compoimd of Foimula I wherein AandB are both 0;
R7 is a phenyl ring or a 5- or 6-mernbered heteroarornatic ring selected from the group consisting of




10

J-l J-2 J-3
each ring optionally substituted with one to three substituents independently selected from R9; QisO,S,NHorNR9;and

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W, X, Y and Z are independently N, CH or CR9, provided that in J-3 and J-4
at least one of W, X, Y or Z is N.
Preferred 2. Methods of Preferred 1 wherein
R*,R2andR8areallH;
5 R3 is CrC4 alkyl optionally substituted with halogen, CN, OCH3 or
S(0)pC%
R4 group is attached at position 2;
R4 is CH3, CF3, OCF3, OCIiF2) CN or halogen;
R5 is H, CH3 or halogen;
10 R6 is CH-,, CF3 or halogen;
R7 is phenyl or 2-pyridinyl, each optionally substituted; and
p is 0, 1 or 2.
Preferred 3. Methods of Preferred 2 wherein R3 is C1-C4 alkyl and R6 is CF3.
Preferred 4. A compound of Preferred 2 wherein R3 is CrC4 alkyl and R6 is CI or Br.
15 Piefened compounds of Formula 10 are:
Preferred A. Compounds of Formula 10 wherein
R7 is a phenyl ring or a 5- or 6-rnembered heteroaromatic ring selected frorn the group consisting of

Z , JL .Q , I II and II
J-l J-2 J-3 J-4
each ring optionally substituted with one to three substituents
20 independently selected from R9;
QisO,S,NIiorNR9;and
W, X, Y and Z are independently N, CH or CR9, provided that in J-3 and J-4
at least one of W, X, Y or Z is N.
Preferred B. Compounds of Preferred A wherein
25 , RSisH;
R4 group is attached at position 2;
R4 is CH3, CF3, OCF3, OCHF2, CN or halogen;
R5 is H, CH3 or halogen;
R6 is CH3, CF3 or halogen; and
30 R7 is phenyl or 2-pyridinyl, each optionally substituted.
Preferred C. Compounds of Preferred B wherein R*5 is CF3. Piefened D. Compounds of Preferred B wherein R^ is CI or Br.

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Of note are compounds of Formula 10 wherein R4 is at the 2 position and is CH3, CI or Br; R5 is at the 4 position and is F, CI, Br, I or CF3; R6 is CF3, CI or Br; R? is 3-C1-2-pyridinyl or 3-Br-2-pyridinyl; and Rb is H.
One or more of the following methods and variations as described in Schemes 1-22 can be used to prepare the compounds of Formula I. The definitions of A, B and R1 through R9 in the compounds of Formulae 2-40 below are as defined above in the Summary of the hivention unless indicated otherwise. Compounds of Formulae Ia-d, 2a-d, 3a, 4a-d, 5a-b, 17a-c, 18a and 32a-b are various subsets of the compounds of Formula I, 2, 3, 4, 5, 17, 18 and 32. In the schemes, Het is the moiety shown below:

A typical method for preparation of a compound of Fomrula la is described in Scheme 1.
Scheme 1

The metliod of Scheme 1 involves coupling of an amine of Formula 2 with an acid chloride of Formula 3 in the presence of an acid scavenger to provide the compound of Formula la. Typical acid scavengers include amine bases such as uietbylamine, /XW-dusopropylethylamine and pyridine; other scavengers include hydroxides such as sodium aud potassium hydroxide and carbonates such as sodium carbonate and potassium carbonate. In certain instances it is useful to use polymer-supported acid scavengers such as polymer-bound A^,7V-diisopropylethylamine and polymer-bound 4-(dimemylamino)pyridine. The coupling can be run in a suitable inert solvent such as tetrahydrofuran, dioxane, diethylether or dicliloromethane to afford the anilide of Fomrula la.

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A thioamide of Formula lb can be obtained in a subsequent step from the corresponding amide of Formula la by treatment with one of a variety of standard thio transfer reagents including phosphorus pentasulfide and Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2j4-diphosphetane-2,4-disulfide).
As shown in Scheme 2, an alternate procedure for the preparation of compounds of Formula la involves coupling of an amine of Formula 2 with an acid of Formula 4 in the presence of a dehydrating agent such as dicyclohexylcarbodiirmde;(DCC), l.l'-carbonyl-diimidazoie, bis(2-oxo-3-oxazoh'dmyj)phosphinic chloride or benzoiiiazoi-1-yjloxy-riis-(diinethyla]rjiiao)phosphoniumhexafluorophosphate.
10

Polymer-supported reagents are again useful here, such as polymer-bound cycloliexylcarbodiimide. The coupling can be run in a suitable- inert solvent such as dichloromethane or A^V-dimethylform amide, llie synthetic methods of Schemes 1 and 2 are
15 just representative examples of a wide variety of coupling methods useful for the prepai'ation of Foimula I compounds; the synthetic literature is extensive for, this type of coupling reaction.
One skilled in the ait will also realize that acid chlorides of Foimula 3 may be prepared from acids of Formula 4 by numerous well-known methods. For example, acid chlorides of
20 Formula 3 are readily made from carboxylic acids of Formula 4 by reacting the caiboxylic acid 4 with thionyl chloride or oxalyl chloride in au inert solvent such as toluene or dichloromethane in the presence of a catalytic amount of//,A^dimethylformamide.
As shown in Scheme 3, amines of Formula 2a are typically available from the corresponding 2-nitrobenzamides of Formula 5 via catalytic hydrogenation of the nitro
25 group.
Scheme 3


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Typical procedures involve reduction with hydrogen in the presence of a metal catalyst such as palladium on carbon or platinum oxide and in hydroxylic solvents such as ethanol and isopropanol. Amines of Formula 2a can also be prepared by reduction with zinc in acetic acid. These procedures are well documented in the chemical literature. R1 substituents such as Cj-Cg alkyl can be introduced at this stage through well known methodologies including either direct alkylation or through the generally prefened method of reductive alkylation of the amine. As is further shown in Scheme 3, a commonly employed procedure is to combine the amine 2a with an aldehyde in the presence of a reducing agent such as sodium C3'anoborohydride to produce the Formula 2b compounds where R1 is C^-Cg alkyl.
Scheme 4 shows that compounds of Formula Ic can be alkylated or acylated with a suitable alkylating or acylating agent such as an alkyl halide, alk3'l chlorpformate or acyl chloride in the presence of a base such as sodium hydride or rc-butyllithium in an inert solvent such as tetrahydrofuran or N.Tv'-dimethylformamide to afford anilides of Formula Id wherein R1 is other than hydrogen.
Scheme 4

The intermediate amides of Formula 5a are readily prepared from commercially available 2-nitrobenzoic acids. Typical methods for amide formation can be used. As shdwn in Scheme 5, these methods include direct dehydrative coupling of acids of Formula 6 with amines of Formula 7 using for example DCC, and conversion of the acids to activated forms such as the acid chlorides or anhydrides aud subsequent coupling with amines to form amides of Formula 5a,


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AUcyl chloroformates, such as ethyl chioroformate or isopropyl chloroformate, are especially useful reagents for this type of reaction involving activation of the acid. The chemical literature is extensive regarding methods for amide formation. Amides of Formula 5a are readily converted to thioamides of Formula 5b by using commercially available tbio transfer reagents such as phosphorus pefttasulfide andLawesson's reagent.
Intermediate anthranilic amides of Formula 2c or 2d may also be prepared from isatoic anhydrides of Formula 8 or 9, respectively, as shown in Scheme 6.
Scheme 6

Typical procedures involve combination of equimolar amounts of the amine 7 with the isatoic anhydride in polar aprotic solvents such as pyridine and //,7V-dimethylformamide at temperatures ranging from room temperature to 100 °C. R1 substituents such as alkyl and substituted alkyl may be introduced by the base-catalyzed alkylation of isatoic anhydride 8 with known alkylating reagents R^-Lg (wherein Lg is a nucleophilic displaceable leaving group such as halide, alkyl or aryl sulfonates or alkyl sulfates) to provide the alkyl substituted intermediate 9. Isatoic anhydrides of Formula 8 may be made by methods described in Coppola, Synthesis 1980, 505-36.
As shown in Scheme 7, an alternate procedure for the preparation of specific compounds of Formula Ic involves reaction of an amine 7 with a benzoxazinone of Formula 10.

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10

The reaction of Scheme 7 can be ran neat or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, pyridine, dichloromethane or chloroform with optimum temperatures ranging from room temperature to the reflux temperature of the solvent. The general reaction of benzoxazinones with amines to produce anthranilainides is well documented in the chemical literature. For a review of benzoxazinone chemistry see Jakobsen et al., Biorganic and Medicinal Chemistry 2000, 8, 2095-2103 and references cited therein. See also Coppola,./. Heterocyclic Chemistry 1999, 36, 563-588.
Benzoxazinones of Formula 10 can be prepared by a variety of procedures. Two procedures that are especially useful are detailed in Schemes 8-9. In Scheme 8, a benzoxazmone of Formula 10 is prepared directly via coupling of a pyrazolecarboxylic acid of Formula 4a with an anthranilic acid of Formula 11.

Scheme 8


15
20


3. tertiary amine
4. MeS(0)2Cl
This involves sequential addition of methanesulfon3'l chloride in the presence of a tertiary amine such as triethylamine or pyridine to a pyrazolecarboxylic acid of Formula 4a, followed by the addition of an authranilic acid of Formula 11, followed by a second addition of tertiary amine and methanesulfonyl chloride. This procedure generally affords good yields of the benzoxazmone and is illustrated with greater detail in Examples 6 and 8.

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Scheme 9 depicts an alternate preparation for benzoxazinones of Formula 10 involving coupling of a pj'razole acid chloride of Formula 3a with an isatoic anhydride of Formula 8 to provide the Formula 10 benzoxazinone directly.
Scheme 9


10


10

Solvents such as pyridine or pyridhie/acetonitrile are suitable for this reaction. The acid chlorides of Formula 3a are available from.the corresponding acids of Formula 4a by a variety of synthetic methods such as chlorination with thionyl chloride or oxalyl chloride.
Isatoic anlrydrides of Formula 8 can be prepared from isatins of Formula 13 as outlined in Scheme 10.






15

Isatins of Formula 13 are obtained from aniline derivatives of Formula 12 using methods biown in the literature. Oxidation of isatin 13 with hydrogen peroxide generally affords good yields of the corresponding isatoic anhydride 8 (Angew. Chem. Int. Ed. Engl. 1980,19, 222-223). Isatoic anhydrides are also available from the anthranilic acids 11 via many known procedures involving reaction of 11 with phosgene or a phosgene equivalent.
The syntheses of representative acids of Formula 4 are depicted in Schemes 11-16. Syntheses of pyrazoles of Formula 4a are shown in Scheme 11.

20


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The synthesis of compounds of Formula 4a in Scheme 11 involves as the key step introduction of the R7 substituent via alkylation or arylation of the pyrazole of Formula 14 with compounds of Formula 15 (wherein Lg is a leaving group as defined above). Oxidation of the methyl group affords the p3iazole carboxylic acid. Some of the more preferred R6 groups include haloalkyl.
Synthesis of pyrazoles of Formula 4a is also shown in Scheme 12.




10

These acids may be prepared via metallation and carboxylation of compounds of Formula 18 as the key step. The R7 group is introduced in a manner similar to that of Scheme 11, i.e. via alkylation or arylation with a compound of Formula 15. Representative R6 groups include e.g. cyano, haloalkyl and halogen.
This procedure is particularly useful for preparing l-(2-pyridmyi)pyrazolecarboxylic acids of Formula 4b as shown in Scheme 13.


15

Reaction of a pyrazole of Formula 17 with a 2,3-dilialopyridine of Formula 15a affords good yields of the 1-pyridylpyrazole of Formula 18a with good .specificity for the desired regiochemistry. Metallation of 18a with lithium diisopropylamide (LDA) followed by quenching of the lithium salt with carbon dioxide affords the l-(2-pyridinyl)pyrazole-carboxylic acid of Formula 4b. Additional details for these procedures are provided in Examples 1, 3, 6, 8 and 10.
The synthesis of pyrazoles of Formula 4c is described in. Scheme 14.

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Scheme 14 involves reaction of an optionally substituted phenyl hydrazine of Formula 19 with a ketopyruvate of Formula 20 to yield pyrazole esters of Formula 21. Hydrolysis of the esters affords the pyrazole acids of Foixuula 4c. This procedure is paiticularly useful fox the preparation of compounds in which R7 is optionally substituted pkenylandR6 is haloalkyl. An alternate synthesis of pyrazole acids of Formula 4c is described in Scheme 15.
Scheme 15

10 The method of Scheme 15 mvoives 3+2 cycloaddition of an appropriately substituted iininohalide 22 with either substituted propiolates of Formula 23 or acrylates of Foiinula 25. Cycloaddition with an acrylate requires additional oxidation of the intermediate pyrazoline to the pyrazole. Hydrolysis of the esters affords the pyrazole acids of Foiinula 4c. Preferred immohalides for this reaction include the trifluoromethyl inrinochloride of Formula 26 and
15 the imiiiodibromide of Formula 27. Compounds such as 26 are known (/. Heterocycl. Cliem.

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1985, 22(2), 565-8). Compounds such as 27 are available by known methods (Tetrahedron Letters 1999, 40. 2605). These' procedures are particularly useful for the preparation of compounds where R7 is optionally substituted phenyl and R6 is haloalkyl or broino.
The stalling p3i-azoles of Formula 17 are known compounds or can be prepared according to known methods. The pyrazole of Formula 17a (the compound of Foimula 17 wherein R6 is CF3 and R8 is H) can be prepared by literature procedures (J. Fluorine Chem. 1991, 55(1), 61-70). Thepyrazoles of Formula 17c (compounds of Formula 17 wherein is CI or Br and R8 is H) can also be prepared by literature procedures (Chem. Ber. 1966, PP(10), 3350-7). A useful alternative method for the preparation of compound 17c is depicted in Scheme 16.


Scheme 16
TFA ■
H H
!7b (R.6 isdorBt) 17c
In the method of Scheme 16, metallation of the sulfamoyl pyrazole of Foimula 28 with n-butyllitlrium followed by direct halogenation of the anion with either hexachloroethane (for R6 being CI) or 1,2-dibromotetrachloroethane (for R6 being Br) affords the halogenated derivatives of Formula 29. Removal of the sulfamoyl group with trifluoroacetic acid (TFA) at room temperature proceeds cleanly aud in good yield to afford the pyrazoles of Formula 17c. One skilled hi the art will recognize that Foimula 17c is a tautomer of Formula 17b, Further experimental details for these procedures are described in Examples 8 and 10.
Pyrazolecarboxylic acids of Foimula 4d wherein R6 is H, Cj-Cg alkyl or CrC6 haloalkyl can be prepared by the method outlined in Scheme 17.

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Scheme 17
4d
Reaction of a compound of Formula 30 wherein R13 is C1-C4 alkyl with a suitable base in a suitable organic solvent affords the cyclized product of Formula 31 after neutralization with an acid such as acetic acid. The suitable base can be, for example but not limitation, sodium hydride, potassium r-butoxide, dimsyl sodium (CH3S(0)CH2~ Na+), alkali metal (such as lithium, sodium or potassium) carbonates or hydroxides, tetraalkyl (such as methyl, ethyl or butyl)ammonium fluorides or hydroxides, or 2-fe;t-butyhmmo-2-diemylarnino-l,3-drmethyl-perhydro-l,3,2-diazaphosphoniue. The suitable organic solvent can be, for example but not limitation, acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethylsulfoxide, or AVV-dhnethylformamide. The cyclization reaction is usually conducted in a temperatui'e range from about 0 to 120 °C. The effects of solvent, base, temperatui'e and addition time are all interdependent, and choice of reaction conditions is important to minimize the formation of byproducts. A preferred base is teti'abutylammonium fluoride.
Dehydration of the compound of Formula 31 to give the compound of Formula 32, followed by converting the carboxylic ester function to carboxylic acid, affords the compound of Formula. 4d. The dehydration is effected by treatment with a catalytic amount of a suitable acid. This catalytic acid can be, for example but not limitation, sulfuric acid. The reaction is generally conducted using an organic solvent. As one skilled in the art will realize, dehydration reactions may be conducted in a wide variety of solvents in a temperature range generally between about 0 and 200 °C, more preferably between about 0 and 100 °C. For the dehydration in the method of Scheme 17, a solvent comprising acetic acid and temperatures of about 65 °C are preferred. Carboxylic ester compounds can be converted to carboxylic acid compounds by numerous methods including nucleophilic

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cleavage under anhydrous conditions or hydro lytic methods involving the use of either acids or bases (see T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed., John Wiley & Sons, Inc., New York, 1991, pp. 224-269 for A review of methods). For the method of Scheme 17, base-catalyzed hydrolytic methods are preferred. Suitable bases mclude allcali metal, (such as lithium, sodium or potassium) hydroxides. For example, the ester can be dissolved in a mixture of water and an alcohol such as ethanol. Upon treatment with sodium hydroxide or potassium hydroxide, the ester is saponified to provide the sodium or potassium salt of the carboxylic acid. Acidification with a strong acid, such as hydrochloric acid or sulfuric acid, yields the carboxylic acid of Formula 4d. The carboxylic acid can be isolated by methods known to those skilled in the art, including crystallization, extraction and distillation.
Compounds of Formula 30 can be prepared by the method outlined in Scheme 18.
Scheme 18


0
H2NV
cr "CO9R!3
36
>-30
acid
scavenger

wherein K6 is H, CrC6 alkyl or CrC6 haloalkyl and ll13 is C1-C4 alkyL
Treatment of a hydrazine compound of Formula 33 with a ketone of Fonnula 34 in a solvent such as water, methanol or acetic acid gives the hydrazone of Formula 35. One skilled in the ait will recognize that this reaction may require catalysis by an optional acid and may also require elevated temperatures depending on the molecular substitution pattern of the hydiazone of Formula 35. Reaction of the hydrazone of Fonnula 35 with the compound of Fonnula 36 in a suitable organic solvent such as, for example but not limitation, dichloromethane or telrahydrofuran hi the presence of an acid scavenger such as triethylamine provides the compound of Formula 30. The reaction is usually conducted at a temperature between about 0 and 100 °C. Further experimental details for the method of Scheme 18 are illustrated in Example 17. Hydrazine compounds of Formula 33 can be prepared by standard methods, such as by contacting the corresponding halo compound of Fonnula 15a with hydrazine.
Pyrazolecarboxylic acids of Fonnula 4d wherein R6 is halogen can be prepared by the method outlined in Scheme 19.

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wherein R.^ is C1-C4 aLkyl.
Oxidization of the compound of Formula 37 optionally in the presence of acid to give the 5 compound of Formula 32 followed by conversion of the carboxylic ester function to the carboxylic acid provides the compound of Formula 4d. The oxidizing agent can be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate (e.g., Oxone®) or potassium permanganate. To obtain complete conversion, at least one equivalent of oxidizing agent versus the compound of Formula 37
>
10 should be used, preferably between about one to two equivalents. This oxidation is typically carried out in the presence of a solvent. The solvent can be an ether, such as tetrahydrofuran, p-dioxane and the like, an organic ester, such as ethyl acetate, dimethyl carbonate and the like, or a polar aprotic organic such as 7\yV-dimethylfonnamide, acetonilrile and the like. Acids suitable for use in the oxidation step include inorganic acids, such as sulfuric acid,
15 phosphoric acid and the like, and organic acids, such as acetic acid, benzoic acid and the like. The acid, when used, should be used in greater than 0.1 equivalents versus the compound of Formula 37. To obtain complete conversion, one to five equivalents of acid can be used. The preferred oxidant is potassium persulfate and the oxidation is preferably carried out in the presence of sulfuric acid. The reaction can be carried out by mixing the
20 compound of Formula 37 in the desired solvent and, if used, the acid. The oxidant can then be added at a convenient rate. The reaction temperature is typically varied from as low as about 0 °C up to the boiling point of the solvent in order to obtain a reasonable reaction time to complete the reaction, preferably less than 8 hours. The desired product, a compound of Formula 32 can be isolated by methods known to those skilled in the art, including
25 crystallization, extraction and distillation. Methods suitable for converting the ester of Formula 32 to the carboxylic acid of Formula 4d are already described for Scheme 17. Further experimental details for the method of Scheme 19 are illustrated in Examples 12 and 13.
Compounds of Formula 37 can be prepared from corresponding compounds of
30 Formula 38 as shown in Scheme 20.'

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10
15
20
25

wherein Ri3 is C1-C4 alkyl and R6 is halogen.
Treatment of a compound of Formula 38 with a halogenating reagent, usually in the presence of a. solvent, affords the corresponding halo compound of Formula 37. Halogenating reagents that can be used include phosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalides, thionyl chloride, dihalotrialkylphosphoranes, dihalodiphenylphosphoranes, oxalyl cliloride and phosgene. Preferred are phosphorus oxyhalides and phosphorus pentahalides. To obtain complete conversion, at least 0.33 equivalents of phosphorus oxyhalide versus the compound of Formula 38 (i.e. the mole reatio of phosphonis oxyhalide to Formula'18 is at least 0.33) should be used, preferably between about 0.33 aud 1.2 equivalents. To obtain complete conversion, at least 0.20 equivalents of phosphorus pentahalide versus the compound of Formula 38 should be used, preferably between about 0.20 and 1.0 equivalents. Compounds of Formula 38 wherein R13 is C1-C4 alkyl are preferred for this reaction. Typical solvents for this halogenation include halogenated alkanes, such as dichloromethane, chloroform, chlorobutane and the like, aromatic solvents, such as benzene, xylene, chlorobenzene and the like, ethers, such as tetrahydrofuran, j7-dioxane, diethyl ether, and the, like, and polar aprotic solvents such as acetonitrile, jV,//-dimethylformamide, and the like. Optionally, an organic base, such as triethylamine, pyridine, A^-dimethylaniline or the like, cau be added. Addition of a catalyst, such as N,N-dimethylforrnamide, is also an option. Preferred is the process in which the solvent is acetonitrile and a base is absent. Typically, neither a base nor a catalyst is required when acetonitrile solvent is used. The preferred process is conducted by mixing the compound of Formula 38 in acetonitrile. The halogenating reagent is then added over a convenient time, and the mixture is then held at the desired temperature until the reaction is complete. The reaction temperature is typically between 20 °C and the boiling point of acetoniti'ile, and the reaction time is typically less than 2 hours. The reaction mass is then neutralized with an inorganic base, such as sodium bicarbonate, sodium hydroxide and the like, or an organic base, such as sodium acetate. The desired product, a compound of Formula 37, can be

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isolated by methods known to those skilled in the art, including crystallization, extraction and distillation.
Alternatively, compounds of Formula 37 wherein R^ is halogen can be prepared by treating the corresponding compounds of Formula 37 wherein R6 is a. different halogen (e.g., 5 CI for making Formula 37 wherein R3 is Br) or a sulfonate group such as^-toluenesuTfonate, benzenesulfonate and methanesulfonate with the appropriate hydrogen halide. By this method the R6 halogen or sulfonate substituent on the Formula 37 starting compound is replaced with, for example, Br or Cl from hydrogen bromide or hydrogen chloride, respectively. The reaction is conducted in a suitable solvent such as dibromomethane, 10 dichlorom ethane or acetonitrile, The reaction can be conducted at or near atmospheric pressure or above atmospheric pressure hi a pressure vessel. When R6 in the starting compound of Formula 37 is a halogen such as Cl, the reaction is preferably conducted in such a way that the hydrogen halide generated from the reaction is removed by sparging or other suitable means. The reaction can be conducted between about 0 and 100 °C, most 15 conveniently near ambient temperature (e.g., about 10 to 40 °C), aud more preferably between about 20 and 30 °C. Addition of a. Lewis acid catalyst (such as aluminum tribromide for preparing Formula 37 wherein R6 is Br) can facilitate the reaction. The product of Formula 37 is isolated by the usual methods known to those skilled in the art, including extraction, distillation and crystallization. Further details for this process are 20 illustrated in Example 14.
Starting compounds of Formula 37 wherein R6 is Cl or Br can be prepared from corresponding compounds of Formula 38 as already described. Starting compounds of Formula 37 wherein R6 is a sulfonate group can likewise be prepared from corresponding compounds of Formula 38 by standard methods such as treatment with a sulfonyl chloride 25 (e.g.,y>toluenesulfonyl chloride) and base such as a tertiary amine (e.g., hiemylamine) in a suitable solvent such as dichloromethane; further details for this process are illustrated in Example 15.
Pyrazolecarboxylic acids of Formula 4d wherein R6 is CJ-C4 alkoxy or C1-C4 haloalkoxy can also be prepared by the method outlined in Scheme 21.
Scheme 21


\VO0J/(M55!R PCT/US02/25613
26
wherein R13 is C1-C4 alkyl, andX is a leaving group.
hi this method, instead of being halogenated as shown in Scheme 20, the compound of Formula 33 is oxidized to the compound of Formula 32a. The reaction conditions for this oxidation are as already described for the conversion of the compound of Formula 37 to the compound of Formula 32 in Scheme 19.
The compound of Formula 32a is then alkylated to form the compound of Formula 32b by contact with au alkylating agent CF3CH2X (39) in the presence of a base. In the alkylating agent 39, X is a nucleophilic reaction leaving group such as halogen (e.g., Br, I), OS(0)2CH3 (methanesulfonate), OS(0)2CF3, OS(0)2Ph^-CH3 (p-toluenesulfonate), and the like; methanesulfonate works well. The reaction is conducted in the presence of at least one equivalent of a base. Suitable bases include inorganic bases, such as alkali metal (such as lithium, sodium or potassium) carbonates and hydroxides, and organic bases, such as triethylamine, diisopropylethylamine and l,S-diazabicyclo[5.4.0]undec-7-ene. The reaction is generally conducted in a solvent, which can comprise alcohols, such as methanol and ethanol, halogenated alkaues, such as dichloromeuiaue, aromatic solvents, such as benzene, toluene and chlorobenzene, ethers, such as tetrahydi'ofuran, and polar aprotic solvents, such as acetonitrile, such as such as acetonitrile, N,AMiraethylformamide, and the like. Alcohols and polar aprotic solvents are preferred for use with inorganic bases. Potassium carbonate as base and acetonitrile as solvent are preferred. The reaction is generally conducted between about 0 and 150 °C, with most typically between ambient temperature and 100 °C. The product of Formula 32b can be isolated by conventional techniques such as extraction. The ester of Formula 32b can then be converted to the carboxylic acid of Formula 4d by the methods already described for the conversion of Formula 32 to Formula 4d in Scheme 17. Further experimental details for the method of Scheme 21 are illustrated in Example 16.
Compounds of Formula 38 can be prepared from compounds of Formula 33 as outlined in Scheme 22.
Scheme 22

wherein R13 is C1-C4 alkyl.
In mis method, a hydrazine compound of Formula 33 is contacted with a compound of Formula 40 (a fumarate ester or maleate ester or a rnixture thereof may be used) in the presence of a base and a solvent. The base is typically a metal alkoxide salt, such as sodium

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methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium fe/Y-butoxide, lithium tert-butoxide. and the like. Greater than 0.5 equivalents of base versus the compound of Formula 33 should be used, preferably between 0.9 and 1.3 equivalents. Greater than 1.0 equivalents of the compound of Formula 40 should be used/preferably 5 between 1.0 to 1.3 equivalents. Polar protic and polar aprotic organic solvents can be used, such as alcohols, acetomtrile, tetrahydrofuraii, JV^-dimemylformamide, dimethyl sulfoxide-and the like. Preferred solvents are alcohols such as methanol and ethanol. It is especially preferred that the alcohol be the same as that making up the funiarate or maleate ester and the alkoxide base. The reaction is typically conducted by mixing the compound of Formula 10 33 and the base in the solvent. The mixtiue can be heated or cooled to a desired temperature and the compound of Formula 40 added over a period of time. Typically reaction temperatures are between 0 °C and the boiling point of the solvent used. The reaction may be conducted under greater than atmospheric pressure in order to increase the boiling point of the, solvent. Temperatures between about 30 and 90 °C are generally preferred The 15 addition time can be as quick as heat transfer allows. Typical addition times are between 1 minute and 2 hours. Optimum reaction temperature and addition time vary depending upon the identities of the compounds of Formula 33 and Formula 40. After addition, the reaction mixture can be held for a time at the reaction temperature. Depending upon the reaction temperature, the required hold time may be from 0 to 2 hours. Typical hold times 20 are 10 to 60 minutes. The reaction mass then can be acidified by adding an organic acid, such as acetic acid and die like, or an inorganic acid, such as hydro chloric acid, sulfuric acid aud the like. Depending on the reaction conditions and the means of isolation, the -C02R1;* function on the compound of Formula 38 may be hydrolyzed to -CO2H; for example, the presence of water in the reaction mixture can promote such hydrolysis. If the carboxylic 25 acid (-C02H) is formed, it can be converted back to -C02R13 wherein R13 is C1-C4 allcyl using esterification methods well-known in the art. The desired product, a compound of Formula 38, can be isolated by methods known to those skilled in the art, such as crystallization, extraction or distillation.
It is recognized that some reagents and reaction conditions described above for 30 preparing compounds of Formula I may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene. T. W.: Wuts, P. G. M. Protective Groups in 35 Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described ha detail to complete the s^vnthesis of compounds of Formula I. One skilled in the

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art will also recognize, that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula I.
It is believed that one skilled in the ait using the preceding description can prepare compounds of Fonnula I of the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. lENMR spectra are reported in ppm downfield from tetraroethylsilane; s means singlet, d means doublet, t means triplet, q means quartet, m means multiplet, dd means doublet of doublets, dt means doublet of triplets, br s means broad singlet.
EXAMPLE 1
Preparation of 2~fl -Ethyl-3-trijfluorQinethylpyra2;ol-5-yl carbamoyl]-3-methyl-iV-(l-
metliylethvl'lbenzamide
Step A: Preparation of 3-Methyl-A^-(l-metliylethyl)-2-mtiobenzamide
A solution of 3-methyl-2-nitrobenzoic acid (2.00 g, 11.0 mmol) and triethylamiae (1.22 g, 12.1 mmol) in 25 niL of methylene chloride was cooled to 10 °C. Ethyl chloroforoiate was carefully added and a solid precipitate formed. After stirring for 30 minutes isopropylamine (0.94 g, 16.0 mmol) was added and a homogeneous solution resulted. The reaction was stirred for an additional hour, poured into water and extracted with ethyl acetate. The organic extracts were washed with water, dried over magnesium sulfate and evaporated under reduced pressure to afford 1.96 g of the desired intermediate as a white solid melting at 126-128 °C. . ]IINMR (CDC13) 5 1.24 (d, 6H), 2.38 (s, 3H), 4.22 (m, 1H), 5.80 (br s, IE), 7.4 (m, 3H).
StepB^ Preparation of 2-Amino-3-nieth3'Wv"-(l-methylethyl)benzamide
The 2-nitrobenzaniide of Step A (1.70 g, 7.6 mmol) was hydrogenated over 5% Pd/C in 40 mL of ethanol at 50 psi. When the uptake of hydrogen ceased the reaction was filtered through Celite® diatomaceous filter aid and the Celite® was washed with ether. The filtrate was evaporated under reduced pressure to afford 1.41 g of the title compound as a solid melting at 149-151 °C.
lH NMR (CDCI3) 5 1.24 (dd, 6H), 2.16 (s, 3H), 4.25 (ni, 1H): 5.54 (br s, 2H), 5.S5 (br s, HI), 6.59 (t, 1H), 7.13 (d, 1H), 7.17 (d, 1H).
Step C: Preparation of l-Ethyl-3-trifluorometlrylpyrazol-5-yl carboxylic acid
To a mixture of 3-frifluoroinethylpyrazole (5 g, 37 mmol) and powdered potassium carbonate (10 g, 72 mmol) stirring hi 30mL of 7Y,Ar-dimethylfonnamide, iodoethane (8 g,

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51 mrnol) was added dropwise. After a mild exotherm, the reaction was stilted overnight at
room temperature. The reaction mixture was partitioned between lOOmL of diethyl ether
and 100 mL of water. The ether layer was separated, washed with water (3X) and brine, and
dried over magnesium sulfate. Evaporation of solvent in vacuo gave 4 g of oil.
5 To 3.8 g of this oil stilting in 40 mL of teuahydrofuran under nitrogen in a dry
ice/acetone bath, 17 mL of a 2.5 M solution of /i-butyllithium in tetrabydrofufan (43 tomol) was added dropwise and the solution stirred for 20 minutes at -78 °C. An. excess of gaseous carbon dioxide was bubbled into the stirred solution at a moderate rate for 10 minutes. After addition of carbon dioxide, the reaction was allowed to slowly reach room temperature and
10 stirred overnight. The reaction mixture was partitioned between diethyl ether (100 mL) and 0.5 N aqueous sodium hydroxide (100 mL). The basic layer was separated and acidified with concentrated hydrochloric acid to a pH of 2-3. The aqueous mixture was extracted with ethyl acetate (100 mL) and the organic extract washed with water and brine and dried over magnesium sulfate. The oily residue, which remained after evaporating the solvent in vacuo,
15 was triturated to a solid from a small amount of 1-chlorobutane. After filtering and drying, a slightly impure sample of l~etbyl-3-nifluoromethyl-py.razol-5-yJ cavboxylic acid (1.4 g) was obtained as a broad-melting solid. ]H NMR (CDC13) 5 1 -51 (*» 3H)> 4-68 ( Step D: Preparation of 2-[l -Eth.yl-3-ti'ifluoromethylpyrazol-5-yl cavbarnoyl]-3-methyl-
20 Ar-(l-metliyletl)yl)benzamide
To a solution of l-ethyl-3-tiifluoromethyl-pyrazol-5-yl cavboxylic acid (i.e. the product of Step C) (0.5 g, 2.4 mnioJ) stilting in 20 mL of metliylene chloride, oxalyl chloride (1.2 mL, 14 mmol) was added. Upon addition of 2 drops of A^W-dimethylformamide, foaming and bubbling occulted. The reaction mixture was heated at reflux for 1 hr as a
25 yellow solution. After cooling, the solvent was removed in vacuo and the resulting residue dissolved in 20 mL of tetrahydrofuran. To the stilted solution, 2-arrrino-3-rnethyl-iV-(l-methylethyl)beiizamide (i.e. the product of Step B) (0.7 g, 3.6 rnnaol) was added followed by the dropwise addition of iV,iV-diisopropylethylamuie (3 mL, 17 mttiol). After stirring at room temperature overnight, the reaction mixture was partitioned between ethyl acetate
^0 (100 mL) and LV aqueous hydrochloric acid (75 mL). The separated organic layer was washed with water and brine and dried over magnesium sulfate. Evaporating in vacuo gave a while solid residue, which .on purification by flash column chromatography on silica gel (2:1 hexanes/etlryl acetate) afforded 0.5 g of the title compound, a compound of the present invention, melting at 223-226 °C.
35 iRNMR (DMSO-rf6) 6 1.06 (d, 6H), 1.36 (t, 3H), 2.45 (s, 3H), 3.97 (m, 1H), 4.58 (q, 2H), 7.43-7.25 (m, 3H), 7.45 (s, IB), 8.05 (d, IB), 10.15 (s, IB).

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EXAMPLE 2
Preparation of A/'42-Methv]-6-rf('l-methvlethvnammo]cai-bonvl]phenvl1-l-phenvl-3-(nifluorornethvl)-1 H-pvrazole-5-r.mhnyamide
Step A: Preparation of 2-Methyl-1 -phenyl-4-(frifluoromethyl)-1 ff-pyrazole
5 A solution of l,l,l-hifluoropentane-2,4-dione (20.0 g, 0.130 mole) in glacial acetic
acid (60 mL) was cooled to 7 °C using an ice/water bath. Phenylhydrazine (14.1 g, 0.130 mole) was added dropwise over a period of 60 minutes. The reaction mass temperature increased to 15 °C during the addition. The resulting orauge solution was held under ambient conditions for 60 minutes. The bulk of the acetic acid was removed by stripping on
10 a rotary evaporator at a bath temperature of 65 °C. The residue was dissolved iu methylene chloride (150 mL). The solution was washed with aqueous sodium bicarbonate (3 g hi 50 niL of water). The purple-red organic layer was separated, treated with activated charcoal (2 g) and MgS04, then filtered. Volatiles were removed on a rotary evaporator. The crude product consisted of 28.0 g of a rose-colored oil, which contained -89% the desired product
15 and 11% l-phenyl-5-(trifluoromethyl)-3-niemylpyrazole,
hi NMR (DMS'0-d6) 8 2.35 (s, 311), 6.76 (s, IB), 7.6-7.5 (m, 5H).
Step B: Preparation of l-Phenyl-3-(U-Jfluoromethyl)-lff-p3'razole-5-carboxylic acid
A sample of crude 2-merliyl-l-phenyl-4-(tdfluorometbyl)-l//'-pyrazoJe (i.e. the product of Step A) (-89%, 50.0 g, 0.221 mole) was mixed with water (400 mL) aud
20 cetyltiimethylammonium chloride (4.00 g, 0.011 mole). The mixture was heated to 95 °C. Potassium permanganate was added in 10 equal portions, spaced at ~8 minute intervals. The reaction mass was maintained at 95-100 °C during this period. After the last portion was added, the mixture was held for ~15 minutes at 95-100 °C, whereupon the purple, permanganate color had been discharged. The reaction mass was filtered while hot (~75 °C)
25 through a 1-cm bed of Celite® diatomaceous filter aid in a 150-mL coarse glass frit funnel. The filter cake was washed with warm (-50 °C) water (3xl00rnL). The combined filtrate and washings were extracted with ether (2x100 mL) to remove a small amount of yellow, water-insoluble material. The aqueous layer was purged with nitrogen to remove residual elher. The clear, colorless alkaline solution, was acidified by adding concentrated
30 hydrochloric acid dropwise until the pH reached ~1.3 (28 g, 0.28 mole). Gas evolution was vigorous during the first two-thirds of the addition. The product was collected via filtration, washed with water (3x40 mL), then dried overnight at 55 °C in vacuo. The product consisted of 11.7 g of a white, crystalline powder, which was essentially pure based upon 1H NMR.
35 III NMR (CDC13) 5 7.33 (s, 1H), 7.4-7.5 (m, 5H).

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Step C: Preparation of 1 -Pb.enyl-3-(tnfluoromethyl)-l//-pyi-azole-5-carbonyl chloride
A sample of crude l-piienyl-3-(trifluoromethyl)p)Tazole-5-cai'boxylic acid (i.e. the product of Step B) (4.13 g, 16.1 mmol) was dissolved in methylene chloride (45 mL). The solution was treated with oxaryl chloride (1.80 mL, 20.6 mmol), followed by N,N-5 dimethylformamide (0.010 mL, 0.13 mmol). Off-gassing began shortly after adding the TVjTV-dimefhylformamide catalyst. The reaction mixture was stirred for -20 minutes under ambient conditions, then was heated to reflux for a period of 35 minutes. Volatiles were removed by stripping the reaction mixture on a rotaiy evaporator at a bath temperature of 55 °C. The product consisted of 4.43 g of a light-yellow oil. The only impurity observed by 10 lll NMR was JV,7V-dmietbylformamide.
Il-INMR (CDC13) 5 7.40 (m, 1H), 7.42 (s, 1H), 7.50-7.53 (m, 4H).
Step D: Preparation of 7\^-[2-Methyl-6-[[(l -metJi3'letbyl)ammo]cai-bonyl]phenylj-l -
phenyl-3 -(trifluoromethyl)- l//-pyrazole-5-caiboxamide
A sample of 3-methylisatoic anhydride (0.30 g, 1.7 mmol) partially dissolved in 15 pyridine (4.0 mL) was treated with 1 -phenyl-3-(trifluoromethylpyrazole)-5-carboxyl chloride (i.e. the product of Step C) (0.55 g, 1.9 mmol). The mixture was heated to ~95°C for a period of 2 hours. The resulting orange solution was cooled to 29 °C, then was treated with isopropylarnme (1.00 g, 16.9 mmol). The reaction mass exothermically warmed to 39 °C. It was further heated to 55 °C for a period of 30 minutes, whereupon much precipitate formed.
20 The reaction mass was dissolved in dichloroniethaue (150 mL). The solution was washed with aqueous acid (5 mL of cone. HC1 in 45 mL of water), then with aqueous base (2 g sodium carbonate in 50 mL of water). The organic layer was dried over MgS04, filtered, then concentrated on a rotaiy evaporator. Upon reduction to ~4 mL, product crystals had formed. The slurry was dihvted with -10 mL of ether, whereupon more product precipitated.
25 The product was isolated by filtration, washed with ether (2x10 mL), then washed with water (2x50 mL). The wet cake was dried for 30 minutes at 70 °C in vacuo. The product, a compound of the present invention, consisted of 0.52 g of an off-white powder melting at 2G0-262 °C. U-INMR (DMSO-c/6) 5 1.07 (d, 6H), 2.21 (s, 3H), 4.02 (octet, 1H), 7.2-7.4 (m, 3H), 7.45-7.6
30 (m, 611), 8.10 (d, 1H), 10.31 (s, 1H).

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EXAMPLE 3
Preuai-ationof^-r2-Methvl-64rn-melhylef:livl)amino]caitonvllphRnYl]-3-rnifluoromethvl)-143-fhifluoromethvl)-2-pyi-idinyl]-l//-pvi-a2ole-5-cai-boxarnide
Step A: Prepai-ation of 3-Trifluoromethyl-2-[3-(tiifluoromethyl)-li^-pyi"azol-l-
5 yljpyi'idine ■
A mixture of 2-chloro-3-trifluorometliylp3Tidine (3.62 g., 21 minor), 3-trifluoro-methylpyrazole (2.7 g., 20 nxraol), aud potassium carbonate (6.0 g, 43 mmol) were heated at 100 °C for 18 h. The cooled reaction mixture was added to ice/water (100 mL). The mixture was extracted twice with ether (100 mL) and the combined ether extracts were 10 washed twice with water (100 mL). The organic layer was dried with magnesium sulfate and concentrated to an. oil. Chromatography on silica gel with hexanes:ethyl acetate (8:1 to 4:1) as eluent gave the title compound (3.5 g) as an oil. 'HNMR (CDC13) 5 6.75 (m, 1H), 7.5 (m, 1H), 8.2 (m, 2H), 8.7 (m, 1H).
Step B: Preparation of 3-(Tnfl.uoromethyl)-l-[3-(trifJ.uorometbyl)-2-pyi-idinyl]--Ui'-
15 pyrazole-5-ca.rboxylic acid
A mixture of the title compound of Example 3, Step A (3.4 g, 13 mmol) was dissolved in tetrahydrofuran (30 mL) and cooled to -70 °C. Lithium diisopropylamide (2N m heptane/tetrahydrofuran, (Aldrich) 9.5 mL, 19 mmol) was added and the resulting dark mixture was stirred for 10 minutes. Diy carbon dioxide was bubbled through the mixture for 20 15 minutes. The mixture was allowed to warm to 23 °C and treated with water (50 mL) and IN sodium hydroxide (10 mL). The aqueous mixture was extracted with ether (100 nxL) aud then ethyl acetate (100 mL). The aqueous layer was acidified with 6Nhydrochloric acid to pH 1-2 and extracted twice with dichlorornethane. The organic layer was dried with magnesium sulfate and concentrated to give the title compound (1.5 g). 25 IH.NMR (CDCI3) 5 7.6 (m, 1H), 7.95 (m, 1H), 8.56 (m, 1H), 8.9(m, 1H), 14.2 (br, 1H)
Step C: Preparation of//-[2-Meth3d-6-[[(l-methylethyl)amino]carbonyl]phenyl]-3-
(Uifluoromelhyl)-l-[3-(tiifluoi"omethyl)-2-pyi"idmyl]-l/f-pyi"azole-5-
cavboxamide
A mixture of the title compound of Example 3, Step B (0.54 g, 1.1 mmol), the title
30 compound from Example 1, Step B (0.44 g, 2.4 mmol) and BOP chloride (bis(2-oxo-oxazolidinyl)phosphinyl chloride, 0.54 g, 2.1 mmol) in acetonitrile (13 mL) was treated with triethylamiue (0.9 mL). The mixture was shaken in a closed scintillation vial for 18 h. The reaction was partitioned between ethyl acetate (100 mL) and IN hydrochloric acid. The ethyl acetate layer was washed successively with 1/Y hydrochloric acid (50 mL), 17V sodium
35 Jiydtoxide (50 mL) and saturated sodium chloride solution (50 mL). The organic layer was dried over magnesium sulfate and concentrated. The residue was subjected to column

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chromatography on silica gel with hexanes/ethyl acetate (5:1 to 3:1) as eluent. The title compound (0.43 g)3 a compound of the present invention, was isolated as a white solid, m.p. 227-230 °C.
*H NMR (CDC13) 5 1.2 (rn. 6H), 4.15 (m, 1H), 5.9 (br d, 1H), 7.1 (m, 1H), 7.2 (m, 2H), 7.4 5 (s, 1H), 7.6 (m, 1H), 8.15 (m, 1H), 8.74 (m, 1H), 10.4 (br, 1H).
EXAMPLE 4
Preparation of l-r3-CMoro-2-pvridmvlVN42-meu^
phenyl1-3-rtdfluoromethyl)-17J-pyrazole-5-cai-boxarnide
Step A: Preparation of 3-Chloro-2-[3-(1iifluoromethyl)-l//'-pyrazol-l"yl]pyridme
10 To a mixture of 2,3-d.ichloropyridine (99.0 g, 0.67 mol) and 3-(tiifluoromethyl)-
pyrazole (83 g, 0.61 mol) hi dry //,/V-diniethylfoii)iamide (300 niL) was added potassium
carbonate (166.0 g, 1.2 mol) and the reaction was then heated to 110-125 °C over 48 hours.
The reaction was cooled to 100 "C and filtered through Celite® diatomaceous filter aid to
remove solids. AyV-Dimethylformaniide and excess dicmoropyridine were removed by 15 distillation at atmospheric pressure. Distillation oftlie product at reduced pressure (b.p. 139-
141 °C, 7 mm) afforded the desired intermediate as a clear yellow oil (113.4 g).
ll-INMR (CDC13) 5 6.78 (s, 111), 7.36 (t, 1I-I), 7.93 (d, III), 8.15 (s, 1H), 8.45 (d, III).
Step B: Preparation of l-(3-Chloro-2-p3iidhiyl)--3-(triiluoromethyl)-lJff--pyrazole-5-
carboxylic acid
20 To a solution of 3-chloro-2-[3-(tiifluoromediyl)-liif-pyrazol-l-yl]pviidme (i.e. the
product of Step A) (105.0g, 425mmol) in dry telrahydrofurari (700 mL) at -75 °C was added via cannula a -30 °C solution of lithium diisopropylamide (425 mmol) hi dry telrahydrofuran (300 mL). The deep red solution was stirred for 15 minutes, after which time carbon dioxide was bubbled through at -63 °C until the solution became pale yellow
25 and the exothennicity ceased. The reaction was stirred for an additional 20 minutes and then quenched with water (20 rnL). The solvent was removed under reduced pressure, and the reaction mixture partitioned between ether and Q.5N aqueous sodium hydroxide solution. The aqueous extracts were washed with ether (3x), filtered through Celite® diatomaceous filter aid to remove residual solids, and then acidified to a pH of approximately 4, at which
30 point an orange oil formed. The aqueous mixture was stirred vigorously and additional acid was added to lower the pH to 2.5-3. The orange oil congealed into a granular solid, which was filtered, washed successively with water and \N hydrochloric acid, and dried under vacuum at 50 °C to afford the title product as an off-white solid (130 g). (Product from another 11m following similar procedures melted at 175-1.76 °C.)
35 1H NMR (DMSO-^) 5 7.61 (s, 1H), 7.76 (dd; 1H), 8.31 (d, 1H), 8.60 (d, 1H).

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Step C: Preparation of 8-Methyl-2#-3,l-beuzoxazine--2,4(lff)-dione
To a solution of 2-ammo-3-naethylbenzoic acid (6 g) in dry 1,4-dioxane (50 rnL) was added dropwise a solution of trichloromethyl chloroforniate (8 mL) in dry 1,4-dioxane (25 mL), with ice-water cooling to keep the reaction temperature below 25 °C. A white 5 precipitate began to form during the addition. The reaction mixture was stirred at room temperature overnight. The precipitated solids were removed by filtration and washed with 1,4-dioxane (2x20 mL) and hexane (2x15 mL) and air-dried to yield 6.51 g of off-white solid. llI-NMR(DMSO-d6) 6 2.33 (s, 3H), 7.18 (t, 1H), 7.59 (d, 1H), 7.78 (d, 1H), 11.0 (hr s, 1H).
10 Step D: Preparation of 2-[l-(3-Chloro-2-pyridinyl)-3-(li-ifluoroniethyi)-lif-pyrazol-
5-yl]-S-methyl-4//-3,l-benzoxazm-4-one
To a suspension of the carboxylic acid product prepared as in Step B (146 g, 500 mmol) in dichloromethane (approximately 2 L) was added A^-dhnethylfonnamide (20 drops) and oxalyl chloride (67 mL, 750 mmol) in approximately 5-niL portions over
15 approximately 2 h. Vigorous gas evolution occurred during the addition. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo to provide the crude acid chloride as an opaque orange mixture. This material was taken up in dichloromethane, filtered to remove some solids and then reconcentrated and used without further purification. The crude acid chloride was dissolved in acetonitrile (250
20 mL) and added to a suspension of the product fiom Step C in acetonitiile (400 mL). Pyridine (250 mL) was added, the mixture was stirred for 15 mk at room temperature, then wanned to reflux for 3 h. The resulting mixture was cooled to room temperature aud stirred overnight to provide a solid mass. Additional acetonitrile was added and the mixture was mixed to form a thick slurry. The solids were collected aud washed with cold acetonitrile. 25 The solids were air-dried and the dried in vacuo at 90 °C for 5 h to yield 144.8 g of fluffy white solid.
*H NMR (CDC13) 5 1.84 (s, 311), 7.4 (t, 1H), 7.6 (m, 3H), 8.0 (dd, 1H), 8.1 (s, 1H), 8.6 (d, HI).
Step E: Preparation of l-(3-Chloi'o-2-pyridmyl)-i^-[2-methyl-6-[[(l-methyleuiyl)-
30 animo]caibonyl]phenyl]-3-(nifluoiomethyl)-liJ-pyrazole-5-carboxamide
To a suspension of the beozoxazinone product of Step D (124 g, 300 mmol) in dichloromethane (500 rnL) was added dropwise isopropylamine (76 mL, 900 mmol) at room temperature. The temperature of the reaction mixture rose and the suspension thinned during the addition. The reaction mixture was then warmed to reflux for 1.5 h. A new suspension 35 formed. The reaction mixture was cooled to room temperature and diethyl ether (1.3 L) was added and the mixture stirred at room temperature overnight. The solids were collected and washed with ether. The solids were air-dried and then dried in vacuo at 90 °C for 5 h to

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yield 122 g of the title compound, a compound of the present invention, as a fluffy white solid, melting at 194-196 °C.
1HNMR (CDC13) 5 1.23 (d, 6H), 2.21 (s, 3H), 4.2 (m, 1H), .5.9 (d, Hi), 7.2 (t, 1H), 7.3 (m, 2H), 7.31 (s, 1H), 7.4 (m, 1H), 7.8 (d, 1H), 8.5 (d, 1H), 10.4 (s, IB).
5 EXAMPLE 5
Alternate preparation of l-f3-chloro-2-pyridrnylVA/-[2-methvl-6-rr(l-methvlpthy1)aTniTin'|-
carbonvl]phenvl]-3-(tiiRuoromethvl)A ff-pyrazole-5~caihoxaim.de
To a solution of the carboxylic acid product prepared as in Example 4, Step B (28 g,
96 mmol) in dichloromethane (240 niL) was added N,A'-dimethylformamide (12 drops) and
10 oxalyl chloride (15.8 g, 124 mmol). The reaction mixture was stirred at room temperature
until gas evolution ceased (approximately 1.5 h). The reaction mixture was concentrated in
vacuo to provide the crude acid chloride as an oil that was used without further purification.
The crude acid chloride was dissolved in acetonitrile (95 mL) and added to a solution of the
benzoxazin-2,4-dione prepared as in Example 4, Step C iii acetonitrile (95 mL). The
15 resulting mixture was stirred at room temperature (approximately 30 min). Pyridine (95 mL)
was added and the mixture heated to about 90 °C (approximately 1 h). The reaction mixture
was cooled to about 35 °C and isopropylamiue (25 niL) was added. The reaction mixture
exothermically warmed during the addition and then was maintained at about 50 °C
(approximately 1 h). The reaction mixture was then poured into ice water and stirred. The
20 resulting precipitate was collected, by filtration, washed with water and dried in vacuo
overnight to provide 37.5 g of the title compound, a compound of the present invention, as a
tan solid.
lIl NMR (CDCI3) 8 1.23 (d, 6H), 2.21 (s, 3H), 4.2 (m, 1H), 5.9 (d, 1H), 7.2 (t, 1H), 7.3 (m, 2H), 7.31 (s, 1I-I), 7.4 (m, 1H), 7.8 (d, III), 8.5 (d, 1H), 10.4 (s, 1H).
25 , EXAMPLE 6
Prepai-ationof7Y44-chlorO"2-methvl-6-[rfl-memylemyl)aiTiinn1carhonvl1phenyll-l-f3" cMoro-2-pvridmvl^3-(faifluoromemylV17J-p\Tazole-5-caitoxamide
Step A: Preparation of 2-Ajnino-3-ruethyl-5-chlorobenzoic acid
To a solution of 2-ammo-3-meihylbenzoic acid (Aldrich, 15.0 g, 99.2 mmol) in
30 A^A^-dimethylformamide (50 mL) was added Ar-clilorosuccinimide (13.3 g, 99.2 mmol) and the reaction mixture was heated to 100 °C for 30 minutes. The heat was'removed, the reaction was cooled to room temperature and let staud overnight. The reaction mixture was then slowly poured into ice-water (250 mL) to precipitate a white solid. The solid was filtered and washed four times with water and then taken up in ethyl acetate (900 mL). The
35 ethyl acetate solution was dried over magnesium sulfate, evaporated under reduced pressure

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and the residual solid was washed with ether to afford the desired intermediate as a white
solid (13.9 g).
*H NMR (DMSO-rf6) 5 2.11 (s, 3H), 7.22 (s, 1H), 7.55 (s, 1H).
Step B: Preparation of 3-chloro-2-[3-(trifluorornethyl)-lff-pyi'azol-l--yl]p3/i'iduie
5 To a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and 3-trifluoromethyl pyrazole
(83 g, 0.61 mol) in dry yY.jV-dirnethylforraarnide (300 mL) was added potassium carbonate (166.0 g, 1.2 mol) and the reaction was then heated to 110-125 °C over 48 hours. The reaction was cooled to 100 °C and filtered through Celite© diatornaceous filter aid to remove solids. A^, N-Diniemylformarnide and excess dichloropyridine were removed by distillation at 10 atoraospheric pressure. Distillation of the product at reduced pressure (b.p. 139-141 °C, 7 nun) afforded the title compound as a clear yellow oil (113.4 g). 'II NMR (CDC13) 6 6.78 (s, 1H), 7.36 (t, 111), 7.93 (d, 1H), 8.15 (s, 1H), 8.45 (d, 1H).
Step C: Preparation of l-(3-Chloio-2-pyridJnyl)-3-(trifluoromelhyl)-l/f-pyrazole-5-
carboxylic acid
15 To a solution of the pyrazole product frorn Step B (105.0 g, 425mmol) in dry
teUaliydrofuran (700 mL) at -75 °C was added via cannula a -30 °C solution of lithium diisopropylamide (425 mmol) in dry tetrahydrofuran (300 rnL). The deep red solution was stirred for 15 minutes, after which time carbon dioxide was bubbled through at -63 °C until the solution became pale yellow and the exothermicity ceased. The reaction was stirred for
20 an additional 20 minutes and then quenched with water (20 mL). The solvent was removed under reduced pressure, and the reaction mixture was partitioned between ether and 0.5 N aqueous sodium hydroxide solution. The aqueous extracts were washed with ether (3x), filtered through Celite® diatornaceous filter aid to remove residual solids, and then acidified to a pH of approximately 4, at which point an orange oil formed. The aqueous rxiixture was
25 stirred vigorously and additional acid was added to lower the pH to 2.5-3. The orange oil congealed into a granular solid, which was filtered, washed successively with water and IN hydrochloric acid, and dried under vacuum at 50 °C to afford the title product as an off-white solid (130 g). (Product from another run following similar procedure melted at 175-176 °C.) ]HNMR (DMSO-d6) 5 7.6.1 (s, IH), 7.76 (dd, 1H), 8.31 (d, IH), 8.60 (d, 1H).
30 Step D: Preparation of 6-chloro-2-[l-(3-chlo.ro-2-pyridinyl)-3-(trifluoromethyl)-li//-
pyrazol-5-yl]-8-memy]-4//-3.1-benzoxazin-4-one
To a solution of methanesulfonyl chloride (2.2 rnL, 28.3 mmol) hi acetonitrile (75 mL) was added dropwise a mixture of the carboxylic acid product from Step C (7.5 g, 27.0 mmol) and triethylamine (3.75 mL. 27.0 mmol) in acetonitrile (75 mL) at 0-5 °C. The reaction
35 temperature was then maintained at 0 °C throughout successive addition of reagents. After stirring for 20 minutes, 2-amino-3-methyl-5-chlorobenzoic acid from Step A (5.1 g, 27.0 mmol) was added and stirring was continued for an additional 5 minutes. A solution of

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triethylamine (7.5 niL, 54.0 mrnol) in acetonitiile (15 mL) was then added dropwise, and the reaction mixture was stirred 45 lniuutes, followed by the addition of methanesulfonyl chloride (2.2 mL, 28.3 mmol). The reaction mixture was then wanned to room temperature and stirred overnight. Approximately 75 niL of water was then added to precipitate 5.8 g of 5 a yellow solid. An additional 1 g of product was isolated by extraction from the filtrate to provide a. total of 6.8 g of the title compound as a yellow solid. !HNMR (CDC13) 5 1.83 (Si 3H), 7.50 (s, IH), 7.53 (m, 2H), 7.99 (m, 2H), 8.58 (d, IH).
Step E: Preparation of iV44-Chloro-2-methyl-6-[[(l-memyle%l)amino]cavbonyl]-
phenyl]-l-(3-chloro-2-pyridinyl)-3-(tiifluoromethyl)-liif-pyrazole-
10 5-carboxaniide
To a solution of the benzoxazinone product of Step D (5.0 g, 11.3 mmol) in tetrahydrofuran (35 mL) was added dropwise isopropylamine (2.9 mL, 34.0 mmol) hi tetrahydrofuran (10 mL) at room temperature. The reaction mixture was then warmed until all solids had dissolved and stilted an additional five minutes, at which point thin layer
15 chromatography on silica gel confirmed completion of the reaction. The tetiahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by chromatography on silica gel, followed by trituration with ether/hexane to afford the title compound, a compound of the present invention, as a solid (4.6 g), melting at 195-196 °C. *H NMR (CDCI3) 8 1.21 (d, 6H), 2.17 (s, 3H), 4.16 (m, IH), 5.95 (br d, IH), 7.1-7.3 (m,
20 2H), 7.39 (s, IH), 7.4 (m, IH), 7.84 (d, IH), 8.50 (d, IH), 10.24 (br s, IH).
EXAMPLE?
Preparation of Af"[4-Chloro-2-methyl-6-[(methylammo)caibonyl]phenyl]-l-(3-chloro-2-
pyridhiyl)-3-(tiifluoromemyl)-l/f-pyi,azole-5-cai'boxamide
To a solution of the benzoxazinone product of Example 6, Step D (4.50 g, 10.18
25 mmol) in tetrahydrofuran (THF; 70 mL) was added methylamine (2.0 M solution in THF, 15 mL, 30.0 mmol) dropwise aud the reaction mixture was stirred at room temperature for 5 minutes. The tetrahydrofuran solvent was evaporated under reduced pressure and the residual solid was purified by chromatography on silica gel to afford 4.09 g of the title compound, a compound of the present invention, as a white solid melting at 185-186 °C.
30 U-INMR (DMSO-tftf) 6" 2.17 (s, 3H), 2.65 (d, 3H), 7.35 (d, IH), 7.46 (dd, IH), 7.65 (dd, IH), 7.74 (5, IH), 8.21 (d, IH), 8.35 (br q, IH), 8.74 (d, IH), 10.39 (s, IH).

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EXAMPLE 8
Preparation of 3-Cliloro-7V44-ckloro-2-m^
1 -(3 -chloro-2-pvriduivl)- lff-pvrazole-5-carboxamide
Step A: Preparation'of 3-Chloro-yV,A^-dtmethyl- l#-pyra_ole-1 -sulfonamide
5 To a solution of TV-dim ethylsulfamoylpyrazole (188.0 g, 1.07 mol) in dry
tetrahydrofuran (1500 mL) at -78 °C was added dropwise a solution of 2.5 M /i-butyllithium (472 mL, 1.18 mol) in hexane while maintaining the temperature below -65 °C. Upon completion of the addition the reaction mixture was maintained at -78 °C for an additional 45 minutes, after which time a solution of hexachloroethane (279 g, 1.18 mol)
10 hi tetrahydiofman (120 mL) was added dropwise. The reaction mixture was maintained for an hour at -78 °C, warmed to -20 °C and then quenched with water (1 L). The reaction mixture was extracted with methylene chloride (4x500 mL); the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using methylene chloride as eluent to afford the title product
15 compound as a yellow oil (160 g).
Hi NMR (CDC13) 5 3.07 (d, 6H), 6.33 (s, 1I-I), 7.61 (s, 11-I).
Step 13; Preparation of 3-Chloropyrazole __
To trifluoroacetic acid (290 mL) was added dropwise the chloropyrazole product (160 g) from Step A, and the reaction mixture was stirred at room temperature for 1.5 hours 20 and then coucentrated at reduced pressure. The residue was taken up in hexane, insoluble solids were filtered off, and the hexane was concentrated to afford the crude product as an oil. The crude product was further purified by chromatography on silica gel using ether/hexane (40:60) as eluent to afford the title product as a yellow oil (64.44 g). HiNMR (CDCI3) 5 6.39 (s, 1H), 7.66 (s, 1H), 9.6 (br s, 1H).
25 Step C; Preparation of 3-Chloro-2-(3-chloro- 1/f-pyrazol-l-yl)pyridine
To a mixture of 2,3-dichloropyridme (92.60 g, 0.629 mol) and 3-chloropyrazole (i.e. the product of Step B) (64.44 g, 0.629 mol) in ^^-dimethylformamide (400 mL) was added potassium carbonate (147.78 g, 1.06 mol), and the reaction mixture was then heated to 100 °C for 36 horns. The reaction mixture was cooled to room temperature and slowly poured
30 into ice water. The precipitated solids were filtered and washed with water. The solid filter cake was taken up hi ethyl acetate, dried over magnesium sulfate and concentrated. The crude solid was chromatographed on silica gel using 20% ethyl acetate/hexane as eluent to afford the title product as a white solid (39.75 g). lHNMR (CDC1,) 5 6.43 (s, 1H), 7.26 (m, 1H), 7.90 (d, 1H), 8.09 (s, 1H), 8.41 (d, 1H).

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Step D: Preparation of 3-Chloro- l-(3-chloro-2-pyridinyl)-lTf-pyrazole-5-carboxylic
acid
To a solution of the pyrazole product from Step C (39.75 g, 186mmol) in dry letrahydrofuran (400 mL) at -78 °C was added dropwise a solution of 2.0 M lithium 5 diisopropylamide (93 mL, 186 mmol) in tetrahydrofuran. Carbon dioxide was bubbled through the amber solution for 14 minutes, after which time the solution became pale brownish-yellow. The reaction was made basic with IN aqueous sodium hydroxide solution and extracted with ether (2x500 mL). The aqueous extracts were acidified with 6N hydrochloric acid and extracted with ethyl acetate (3x500 mL). The ethyl acetate extracts 10 were dried over magnesium sulfate and concentrated to afford the title product as an off-white solid (42.96 g). (Product from another run following similar procedure melted at 198-199 °C.) H-l NMR (DMSO-d6) 5 6.99 (s, 1H), 7.45 (m, 1H), 7.93 (d, III), 8.51 (d, 1H).
Step E: Preparation of 6^Chloro-2-[3-chloro-l-(3-chloro-2-pyiidinyl)-l^-pyi-azol-
15 5-yl]-8-methyl-4ff-3,l-ben20xazin-4-one
To a solution of inethinesulfonyl chloride (6.96 g, 61.06 mmol) in acetonitrile (150 mL) was added dropwise k mixture of the carboxylic acid product from Step D (15.0 g, 58.16 mmol) and triethylamiue (5.88 g, 58.16 mmol) in acetonitrile (150 mL) at -5 °C. The reaction mixture was then stirred for 30 minutes at 0 °C. Then, 2-amino-3-methyl-5-20 clilorobenzoic acid from Example 6, Step A (10.79 g, 58.16 mmol) was added, and stirring was continued for an additional 10 minutes. A solution of triethylamine (11.77 g, 116.5 mmol) in acetonitrile was then added dropwise while keeping the temperature below 10 °C. The reaction mixture was stirred 60 minutes at 0 °C, and then methanesulfonyl chloride (6.96 g, 61.06 rnmol) was added. The reaction mixture was then warmed to room 25 temperature and stirred for an additional 2 hours. The reaction mixture was then concentrated, and the crude product was chromatographed on silica gel using methylene , chloride as eluent to afford the title product as a yellow solid (9.1 g). ill NMR (CDCI3) 5 1.81 (s, 31-1), 7.16 (s, 1H), 7.51 (m, 2H), 7.98 (d, 2H), 8.56 (d, 1H).
Step F: Preparation of 3-chloro-yV-[4-chloro-2-memyl-6-[[(l-melh.yle%l)amiaoj-
30 carbonyljphenyl]-1 -(3-chloro-2-pyridinyl)-l/f-pyrazole-5-cai-boxamide
To a solution of the benzoxazrnone product of Step E (6.21 g, 15.21 mmol) in
tetrahydrofuran (100 mL) was added isopropylamine (4.23 g, 72.74 mmol) and the reaction
mixture was then heated to 60 °C, stirred for 1 hour and then cooled to room temperature.
The leuahydrofxuau solvent was evaporated under reduced pressure, and the residual solid 35 was purified by chromatography on silica gel to afford the title compound, a compound of
the present invention, as a white solid (5.05 g) melting at 173-175 °C.

^'0 (U/015518 PCT/US02/2561J
40
JH NMR (CDC13) 5 1.23 (d, 6H), 2.18 (s, 3H), 4.21 (in, IB), 5.97 (d, 1H), 7.01 (m, 1H), 7.20 (s, 1H), 7.24 (s, 1H), 7.41 (d, 1H), 7.83 (d, 1H), 8.43 (d, 1H), 10.15 (brs, 1H).
EXAMPLE 9
Preparation of 3-Ckloro-A^-[4-chloro-2-methyl-6-[(me1nylamino)carbonyl]phenyl]-l-(3-
5 chloro-2-pyridinyl)-lJy-pyLazole-5-carboxamide
To a solution of the benzoxazinone product of Example 8, Step E (6.32 g, 15.47 minol) in tetrahydi-ofuran (50 IUL) was added methsdaruine (2.0 M solution in THF, 38 mL, 77.3S mmol), and the reaction mixture was heated to 60 °C, stirred for 1 hour and then cooled to room temperature. The tetrahydrofuran solvent was evaporated under reduced 10 pressuie, and tlie residual solid was purified by chromatography on silica gel to afford the title compound, a compound of tine present invention, as a wliite solid (4.57 g) melting at 225-226 °C.
il-INMR (CDC13) 8 2.15 (s, 3C-I), 2.93 (s, 3H), 6.21 (d, III), 7.06 (s, 1H), 7.1S (s, 1H), 7.20 (s, Hi), 7.42 (m, 1H), 7.83 (d, J.H), 8.42 (d, 1H), 10.0S (brs, III).
15 . EXAMPLE 10
Pj^paratiojLoO^Broinc^^
l-(3-chloro-2-pvriduiyl)-lJ/-pyfazole-5-cai-boxamide
Step A: Preparation of 3-Bromo-.A/,N-dimethyl-1 ff-pyrazole-1 -sulfonamide
To a solution of A^-dimethylsulfamojdpyiazole (44.0 g, 0.251 rnol) in dry
20 tetraliydiofurau. (500 mL) at -78 °C was added dropwise a solution of /7-butyllithiuirj (2.5 M in hexaue, 105.5 mL, 0.264 mol) while mahitaining the temperature below -60 °C. A thick solid formed during the addition. Upou completion of the addition the reaction mixture was maintained for an additional 15 minutes, after which time a solution of 1,2-dibromo-tetrachloro ethane (90 g, 0.276 mol) in tetrahydrofuran (150 mL) was added dropwise while
25 maintaining the temperature below -70 °G. The reaction mixture toned a clear orange; stirring was continued for an additional 15 minutes. The -78 °C bath;was removed and the reaction was quenched with water (600 mL). The reaction mixture was ■ extracted with methylene chloride (4x), and the organic extracts were dried over magnesium sulfate and concentrated. The crude product was further purified by chromatography on silica gel using
30 methylene chloride/hexaue (50:50) as eluent to afford the title product as a clear colorless oil (57.04 g). ^-INMRtCDCy 5 3.07 (d, 6H), 6.44 (in, 1H), 7.62 (in, 1H).
j>tepB: Preparation of 3-Bromopyrazole
To trifluoroacetic acid (70 mL) was slowly added the bromopyrazole product (57.04 g)
35 from Step A. The reaction mixture was stirred at room temperature for 30 minutes and then
concentrated at reduced pressuie. The residue was taken up in hexane, insoluble solids were

WO 0J/OJ55IS PCT/US02/25613
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filtered off, and the hexane was evaporated to afford the crude product as an oil. The crude product was further purified by chromatography on silica, gel using ethyl acelate/dichloroniethane (10:90) as eluent to afford an oil. The oil was taken up in dichloromethane, neutralized with aqueous sodium bicarbonate solution, extracted with 5 methylene chloride (3x), dried over magnesium sulfate and concentrated to afford the title product as a white solid (25.9 g), ni.p. 61-64 °C. 1HNMR (CDC13) 5 6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, IE).
Step C: Preparation of 2-(3-Bromo-l/f-pyrazol-l-yl)-3-chIoropyridine
To a mixture of 2,3-dicbdoropyridine (27.4 g, 185 rnmol) and 3-bromopyrazole (i.e. the
10 product of Step B) (25.4 g, 176 miuol) in dry A/,Ar-dimethylforrnamide (88 mL) was added potassium carbonate (48.6 g, 352 mmol), and the reaction mixture was heated to 125 °C for 18 hours. The reaction mixture was cooled to room temperature and poured into ice water (800 mL). A precipitate formed. The precipitated solids were stirred for 1.5 hrs, filtered and washed with water (2x100 mL). The solid filter cake was taken up in methylene
15 chloride and washed sequentially with water, IN hydrochloric acid, saturated aqueous sodium bicarbonate solution, and brine. The organic extracts were then dried over magnesium sulfate and concentrated to afford 39:9 g of a pink solid. The crude solid was suspended in hexane and stirred vigorously for 1 hr. The solids were filtered, washed with hexane and dried to afford the title product as an off-white powder (30.4 g) determined to be
20 > 94 % pure by NMR. This material was used without further purification m Step t>. Jl-INMK^CDCl-,) 8 6.52 (s, 1H), 7.30 (dd, III), 7.92 (d, 1H), 8.05 (s, 1H), 8.43 (d, 1H).
Step D: Preparation of 3"Bromo-l-(3-chloro-2-p3aidiny])-l/f-pyrazole-5-carboxyHc
acid
To a solution of the pyrazole product from Step C (30.4 g, 118 mmol) hi dry
25 tetrahydrofuran (250 mL) at -76 °C was added dropwise a solution of lithium diisopropyl-amide (118 mmol) in tetrahydrofuran at such a rate as to maintain the temperature below -71 °C. The reaction mixture was stirred for 15 minutes at -76 °C, and carbon dioxide was then bubbled through for 10 minutes, causing warming to -57 °C. The reaction mixture was warmed to -20 °C and quenched with water. The reaction mixture was concentrated and
30 then taken up in water (1 L) and ether (500 mL), and then aqueous sodium hydroxide solution (1 N, 20 nil.) was added. The aqueous extracts were washed with ether and acidified with hydrochloric acid. The precipitated solids were filtered, washed with water and dried to afford the title product as a tan solid (27.7 g). (Product from another run following similar procedure melted at 200-201 °C.)
35 lH NMR (DMSO-rf6) 5 7.25 (s, 1H), 7.68 (dd} 1H), 8.24 (d, 1H), 8.56 (d, 1H).

WO (13/(115518
42
Step E: Preparation of 2-[3-Bromo-l-(3-chIoro-2-pyridittyI)-l/r-pyra2ol-5-ylJ-
6-chloro-8-niethyl-4#-3,1 -benzoxazin-4-one
A procedure analogous to that of Example 6, Step Step F: Preparation of 3-Bromo-7V-[4-chloro-2-methyl-6-[[( 1 -me%lemyl)atTuno]-
cavbonyljpheny]]-1 -(3-chloro-2-pyridmy.l)- lff-pyrazole-5-carboxamide
To a solution of the benzoxazinone product of Step E (0.20 g, 0.44 mmol) in tetrahydrofuran was added isopropylamine (0.122 mL, 1.42 mmol), and the reaction mixture was heated to 60 °C for 90 minutes and then cooled to room temperature. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was triturated with ether, filtered, and dried to afford the title compound, a compound of the present invention, as a solid (150 mg), m.p. 159-161 °C.
*!_ NMR (CDCI3) 5 ]-22 (d> GH), 2.19.(s, 3H), 4.21 (m, 1H), 5.99 (m, 1H), 7.05 (m, 1H), 7.22 (in, 2H), 7.39 (ra, III), 7.82 (d, 1H), 8.41 (d, 1H).
EXAMPLE 11
Prepm*ationof3-Bromo-//-[4-chlojo-2-methy]-6-f(methylamirio)caibonylJpJjenylJ-l-(3-
chloro-2-pyridinyl)- l//-pyrazole-5-carboxamide
To a solution of the benzoxazinone product of Example 10, Step E (0.20 g, 0.44 mmol) in teu-ahydrofuran was added methylamine (2.0 M solution in THF, 0.514 mL, 1.02 mmol), and the reaction mixture was heated to 60 DC for 90 minutes and then cooled to room temperature. The tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was triturated with ether, filtered, and dried to afford the title compound, a compound of the present invention, as a solid (40 mg), m.p. 162-164 °C. !HNMR (CDCI3) 52.18 (s, 3H), 2.95 (s, 3H), 6.21 (m, 1H), 7.10 (s, 1H), 7.24 (in, 2H), 7.39 (m, 1H), 7.80(d, J'H), 8.45 (d, 1H).
The following Example 12 illustrates an alternative preparation of 3-chloro-l-(3-chloro-2-pyridmyl)~l#-pyrazole-5-carboxylic acid, which can be used to prepai-e, for example, 3-chloro-yV-[4-chloro-2-metiiyl-6-[[(l-memylethyl)amino]cai-bonyl]phenyl]-l-(3-chloro-2-pyriduiyl)- l/f-pyrazole-5-carboxamide and 3-chloro-7Y-[4--chloro-2-methyi-6-[(niethylanimo)caitonyljphenyl]-l
WO J/(115518 PCT/US02/25613
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EXAMPLE 12
Preparation of 3-cliloro-l-G-chloro-2-pvridinvlVl^pviazole-5-carboxvlic acid
Step A: Preparation of Ethyl 2-(3-chloro-2-pyridiuyl)-5-oxo-3-
pjTazolidinecarboxylate (alternatively named ethyl l-(3-chloro-2-pyridinyl)-
3 -pyrazolidinone-5-carboxylate) _____
A 2-L four-necked flask equipped with a mechanical stirrer, thermometer, addition. funnel, reflux condenser, and nitrogen inlet was charged with absolute ethanol (250 mL) and an ethanolic solution of sodium ethoxide (21%, 190 mL, 0.504 mol). The mixture was heated to reflux at about 83 °C. It was then, treated with 3-chloro-2(l#)-pyridinone
10 hydrazone (68.0 g, 0.474 mol). The mixture was re-heated to reflux over a period of 5 minutes. The yellow slurry was then treated dropwise with diethyl maleate (88.0 mL, 0.544 mol) over a period of 5 minutes. The reflux rate increased markedly during the addition. By the end of the addition all of the starting material had dissolved. The resulting orange-red solution was held at reflux for 10 minutes. After being cooled to 65 °C, the reaction mixture
15 was U-eated with glacial acetic acid (50.0 mL, 0.873 mol). A precipitate formed. The mixture was diluted with water (650 mL), causing the precipitate to dissolve. The orange solution was cooled in an ice bath. Product began to precipitate at 28 °C. The slurry was held at about 2 °C for 2 hours. The product was isolated via filtration, washed with aqueous ethanol (40%, 3 x 50 mL), and then air-dried on the filter for about 1 hour. The title product
20 compound was obtained as a highly crystalline, light orange powder (70.3 g, 55% yield). No significant impurities were observed by ^-INMR.
41NMR (DMSO-rf6) 5 1.22 (t, 3H), 2.35 (d, 1H), 2.91 (dd, 1H), 4.20 (q, 2H), 4.84 (d, 1H), 7.20 (dd, 1I-I), 7.92 (d, 1H), 8.27 (d, 1H), 10.18 (s, 1H).
Step B: Preparation of Ethyl 3-chloro-l-(3-chloro-2-pyridinyl)-4,5-dihydro-
25 . l/f-pyrazole-5-carboxylate (alternatively named ethyl l-(3-chloro-
2-pyrJdinyl)-3-chloro-2-p)Ta2olme-5-carboxylate)
To a 2-L four-necked flask equipped with a mechanical stirrer, thermometer, reflux condenser, and nitrogen inlet was charged acetonittile (1000 rnL), ethyl 2-(3-chloro-2-pyridhyl)-5-oxo-3-pyrazoHdmecarboxyJate (i.e. the product of Step A) (91.0 g, 0.337 mol) 30 and phosphorus oxychloride (35.0 mL, 0.375 mol). Upon adding the phosphorus oxychloride, the mixture self-heated horn 22 to 25 °C aud a precipitate formed. The light-yellow slurry was heated to reflux at 83 °C over a period of 35 minutes, whereupon the precipitate dissolved. The resulting orauge solution was held at reflux for 45 minutes, whereupon it had become black-green. The reflux condenser was replaced with a distillation 35 head, and 650 mL of solvent was removed by distillation. A second 2-L four-necked flask equipped with a mechanical stirrer was charged with sodium bicarbonate (130 g, 1.55 mol) and water (400 rnL). The concentrated reaction mixture was added to the sodium

WO (13/0J5518 PCT/US02/256I3
bicarbonate slurry over a period of 15 minutes. The resulting, two-phase mixture was stirred vigorously for 20 minutes, at which time gas evolution had ceased. The mixture was diluted with dichloromethane (250 mL) and then was stirred for 50 minutes. The mixture was treated with Celite® 545 diatomaceous earth filter aid (11 g) and then filtered to remove a 5 black, tarry substance that inhibited phase separation. Since the filtrate was slow to separate into distinct phases, it was diluted with dichJoroniethane (200 mL) and water (200 mL) and treated with more Celite® 545 (15 g). The mixture was filtered, and the filtrate was transferred to a separately funnel. The heavier, deep green organic layer was separated. A rag layer (50 mL) was refiltered and then added to the organic layer. The organic solution
10 (800 mL) was treated with magnesium sulfate (30 g) and silica gel (12 g), and the slurry was stirred magnetically for 30 minutes. The slurry was filtered to remove the magnesium sulfate and silica gel, which had become deep blue-green. The filter cake was washed with dichloromethane (100 mL). The filtrate was concentrated on a rotary evaporator. The product consisted of dark amber oil (92.0 g, 93% yield). The only appreciable impurities
15 observed by hiNMR were 1% starting material and 0.7% acetonitrile.
lR NMR (DMSCw/6) 5 1.15 (t, 3H), 3.26 (dd, III), 3.5S (dd, 1H), 4.11 (q, 2H), 5.25 (dd, 1H), 7.00 (dd, III), 7.84 (d, III), 8.12 (d, 1H).
Step C: Preparation of Ethyl 3-chloro- l-(3-chloro-2-pyridiuyl)~ 1/f-pyrazole-
5-carboxylate (alternatively named ethyl 1 -(3-chloro-2-pyridinyl)-
20 3-chloropyrazole-5-carbox3'late)
A 2-L four-necked flask equipped with a mechanical stirrer, thermometer, reflux condenser, and nitrogen inlet was charged with ethyl 3-chloro-l-(3-chloro-2-pyridinyl)-4J5-dihydro-l^r-pyrazole-5-carboxylate (i.e. the product of Step B) (95% pure, 99.5 g, 0.328 mol), acetonitrile (1000 mL) and sulfuric acid (98%, 35.0 mL, 0.661 mol). The
25 mixture self-heated from 22 to 35 °C upon adding the sulfuric acid. After being stin-ed for several minutes, the mixture was treated with potassium persulfate (140 g, 0.518 mol). The slurry was heated to reflux at 84 °C for 4.5 hours. The resulting orange slurry while still warm (50-65 °C) was filtered to remove a fine, white precipitate. The filter cake was washed with acetonitrile (50 mL). The filtrate was concentrated to about 500 mL on a rotary
30 evaporator. A second 2-L four-necked flask equipped with a mechanical stirrer was charged with water (1250 mL). The concentrated reaction mass was added to the water over a period of about 5 minutes. The product was isolated via filtration, washed with aqueous acetonitrile (25%, 3 x 125 mL), washed once with water (100 mL), and then dried overnight in vacuo at room temperature. The product consisted of a crystalline, orange powder (79.3 g, 82%
35 yield). The only appreciable impurities observed by !H NMR were about 1.9% water and 0.6% acetonitrile.
lli NMR (D'MSO-rf6) 8 1.09 (t, 3H), 4.16 (q, 2H), 7.31 (s, 1H), 7.71 (del, 1H), 8.38 (d, 1H), S.59 (d, 1H),

WO IU/0I55I8 PCT/US02/256J3

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Step D: Preparation of 3-Chloio-l-(3-chloro-2-pyridinyl)-l/f-pyrazole-5-carboxylic
acid (alternatively named l-(3-chloro-2-pyridinyl)-3-chloropyrazole-
5-carboxylic acid)
A 1-L four-necked flask equipped with a mechanical stirrer, thermometer, and nitrogen 5 inlet was charged with etliyl 3-chloro-l-(3-chloro-2-pyndinyl)-l_f-pyiazole-5-caj-boxylate (i.e. the product of Step C) (97.5% pure, 79.3 g, 0.270 inol), methanol (260 mL), water (140 mL) and sodium hydroxide pellets (13.0 g, 0.325 mol). Upon adding the sodium hydroxide the mixture self-heated froin 22 to 35 °C, and the stalling material began to dissolve. After being stirred for 45 minutes under ambient conditions, all of the starting 10 material had dissolved. The resulting deep orange-brown solution was concentrated to about 250 mL on a rotary evaporator. The concentrated reaction mixture was then diluted with water (400 mL). The aqueous solution was extracted with ether (200 mL). Then the aqueous layer was transferred to a 1-L Erlenmeyer flask equipped with a magnetic stirrer. The solution was treated dropwise with concentrated hydrochloric acid (36.0 g, 0.355 mol) 15 over a period of about 10 minutes. The product was isolated via filtration, reslurried with water (2 x 200 mJS), cover washed once with water (100 mL) arid then air-dried on the filter for 1.5 hours. The product consisted of a crystalline, light brown powder (58.1 g, 83% yield). About 0.7% ether was the only appreciable impurity observed by lH NMR. 1I-I NMR (DMSO-tf6) 5 7.20 (s, 1H), 7.68 (eld, 1EQ, 8.25 (d, 1H), 8.56 (d, IB), 13.95 (br s, 20 HI).
The followiug Example 13 illustrates an alternative preparation of 3-brorno-l-(3-chloi"0-2-pyridm)d)-l//-pyj-azole-5-cai-boxylic acid, which can be used to prepare, for example, 3-bromo-^-[4-cbJoro-2-methyl-6-[[(l -memyletbyl) amino] carbonyljphenyl] -1 -(3-chloro-2^pyridinyl)-l/f-pyrazole-5-carboxamide and 3-bromo-//-[4-chloro-2-methyl-6-25 [(memylanmio)cmbonyl]pheiiyl]-l-(3-chloi-o-2-p3'ridmyl)-l//-pyrazole-5-cai-boxar_ide, by fuilher steps illustrated in Examples 10 and U.
EXAMPLE 13
Preparation of 3-Bromo- l-(3-chlorn-2-pyi-irii»vl)-l_f-pvrazole-5-cai-boxvlic acid
Step Al: Preparation of Ethyl 3-bromo- 3 -(3-chloro-2-pyridmyl)~4,5-a_iydro-
30 l/f-py.razole-5-carboxylate (alternatively named ethyl l-(3-chloro-
2-pyridinyl)-3-bromo-2-pyrazoline-5-cai-boxylate) using phosphorus
oxybromide
A 1-L four-necked flask equipped with a mechanical stirrer, thermometer, reflux
condenser, and nitrogen inlet was charged with acetonitrile (400 mL), ethyl 2-(3-chloro-2-
35 pyi-idinyl)-5-oxo-3-pyr_zolidinecafboxylate (i.e. the product of Example 12, Step A) (50.0 g,
0.185 mol) and phosphorus oxybromide (34.0 g, 0.119 mol). The orange slurry was heated
to reflux at 83 °C over a period of 20 minutes. The resulting turbid, orange solution was

vithi-vin-'ois

PCT/US02/25613

46
held at reflux for 75 minutes, at which time a dense, tan, crystalline precipitate had formed. The reflux condenser was replaced with a distillation head, and a cloudy, colorless distillate (300 mL) was collected. A second 1-L four-necked flask equipped with a mechanical stirrer was charged with sodium bicarbonate (45 g, 0.54 mol) and water (200 rnL). The 5 concentrated reaction mixture was added to the sodium bicarbonate slurry over a period of 5 minutes. The resulting two-phase mixture was stilted vigorously for 5 minutes, at which time gas evolution had ceased. The mixture was diluted with dichloromethane (200 mL) and then was stirred for 75 minutes. The mixture was treated with 5 g of Celite© 545 diatomaceous filter aid and then filtered to remove a brown, tarry substance. The filtrate was
10 transferred to a sepaiatoty funnel. The brown organic layer (400 mL) was separated and then was treated with magnesium sulfate (15 g) and Darco® G60 activated charcoal (2.0 g). The resulting sluny was stirred magnetically for 15 minutes and then filtered to remove the magnesium sulfate and charcoal. The green filtrate was treated with silica gel (3 g) and stirred for several minutes. The deep blue-green silica gel was removed by filtration, and the
15 filtrate was concentrated on a rotaiy evaporator. The product consisted of a light amber- oil (58.6 g, 95% yield), which crystallized upon standing. The only appreciable impurity observed by 1H NMR was 0.3% acetonitrile.
Hi NMR (DMSO-rf6) 5 1.15 (t, 311), 3.29 (dd, 1H), 3.60 (dd, 1H), 4.11 (q, 2H), 5.20 (dd, 1H), 6.99 (dd, JH), 7.84 (d, 111), 8.12 (d, 1H).
20 Step A2: Preparation of Ethyl 3-bromo-l-(3-chloro-2-pyridmyl)-4,5~dihydro-
l/y-pyrazole-5-carboxylate using phosphorus pentabromide
A 1-L four-necked flask equipped with a mechanical stirrer, therrnometer, reflux condenser, and nitrogen inlet was charged with acetonitrile (330 rnL), ethyl 2-(3-ckloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (i.e. the product of Example 12, Step A) (52.0 g,
25 0.193 mol), and phosphorus pentabromide (41.0 g, 0.0952 mol). The orange sluny was hea'ted to reflux at 84 °C over a period of 20 minutes. The resulting brick-red mixture was held at reflux for 90 minutes, at which time-a dense tan crystalline precipitate had formed. The reflux condenser was replaced with a distillation head, and a cloudy, colorless distillate (220 mL) was collected. A second 1-L four-necked flask equipped with a mechanical stirrer
30 was charged with sodium bicarbonate (40 g, OAS mol) and water (200 mL). The concentrated reaction mixture was added to the sodium bicarbonate slurry over a period of 5 minutes. The resulting, two-phase mixture was stirred vigorously for J 0 minutes, at which lime gas evolution had ceased. The mixture was diluted with dichloromethane (200 mL) and then was stirred for 10 minutes. The mixture was treated with Celite® 545 diatomaceous
35 filter aid (5 g) and then filtered to remove a purple, tarry substance. The filter cake was washed with dichloromethane (50 mL). The filtrate was transferred to a separately funnel. The purple-red organic layer (400 mL) was separated and then was treated with magnesium sulfate (15 g) and Darco® G60 activated charcoal (2.2 g). The sluny was stirred

47
magnetically for 40 minutes. The slurry was filtered to remove the magnesium sulfate and charcoal. The filtrate was concentrated on a rotary evaporator. The product consisted of a dark amber oil (61.2 g, 95% yield), which crystallized iipon standing. The only appreciable impurity observed by !HNMR was 0.7% acetonitrile. 5 lH NMR (DMSO-rf6) S 1.15 (t, 3H), 3.29 (dd, 1H), 3.60 (dd, 1H), 4.11 (q, 2H), 5.20 (dd, 1H), 6.99 (dd, 1H), 7.84 (d, 1H), 8.12 (d, 1H).
Step B: Preparation of Ethyl 3-bromo-1 -(3-chloro-2-pyridinyl)- l#-pyrazole-
5-carboxylate (alternatively named ethyl l-(3-chloro-2-pyridinyl)-
3-bromopyrazole-5-carboxyla.te)
10 A 1-L four-necked flask equipped with a mechanical stirrer, thermometer, reflux
condenser, and nitrogen inlet was charged with ethyl 3-bromo-1 -(3-chloro-2-pyriduryi)-4,5-dUiydro-l/7-pyrazo}e-5-carboxylate (i.e. the product of Steps Al and A2) (40.2 g, 0.121 mol), acetonitrile (300 mL) and sulfuric acid (98%, 13.0 mL, 0.245 mol). The mixture self-heated from 22 to 36 °C upon adding the sulfuric acid. After being stirred for several 15 minutes, the mixture was treated with potassium persulfate (48.0 g, 0.178 mol). The slurry was heated to reflux at 84 °C for 2 hours. The resulting orange slurry while still warm (50-65 °C) was filtered to remove a white precipitate. The filter cake was washed with acetonitrile (2 x 50 mL). The filtrate was concentrated to about 200 mL on a rotary evaporator. A second 1-L four-necked flask equipped with a mechanical stirrer was charged 20 widi water (400 mL). The concentrated reaction mass was added to the water over a period of about 5 minutes. The product was isolated via filu-ation, washed sequentially with aqueous acetoniuile (20%, 100 mL) and water (75 mL), and was then air-dried on the filter for 1 hour. The product consisted of a crystalline, orange powder (36.6 g, 90% yield). The only appreciable impurities observed by ^K NMR were about 1% of an unknown and 0.5% 25 acetonitrile.
^i NMR (DMSO-rf6) 5 1.09 (t, 3H), 4.16 (q, 2H), 7.35 (s, 1H), 7.72 (dd, 1H), 8.39 (d, 1H), 8.59 (d, H-f).
Step C: Preparation of 3-Bromo-l-(3-chloro-2-pyridinyl)-l/iLpyrazole-5-cai-boxylic
acid (alternatively named l-(3-chloro-2-pyridinyl)-3-bromopyrazole-
30 5-carboxylic acid)
A 300-mL four-necked flask equipped with a mechanical stirrer, thermometer, and nitrogen inlet was charged with ethyl 3-bromo-1 -(3-chloro-2-pyridinyl)- 1/7-pyrazole-5-carboxylate (i.e. the product of Step B).(98.5% pure, 25.0 g, 0.0756 mol), methanol (75 mL), water (50 ml.), and sodium hydroxide pellets (3.30 g, 0.0825 mol). Upon adding
35 the sodium hydj-oxi.de the mixture self-heated from 29 to 34 °C and the starting material began to dissolve. After being stirred for 90 minutes under ambient conditions, all of the stalling material had dissolved. The resulting dark orange solution was concentrated to

WO 03/0.15518 PCT/US02/25 48
about 90 mL on a rotary evaporator. The concentrated reaction mixture was then diluted with water (160 mL). The aqueous solution was extracted with ether (100 mL). Then the aqueous layer was transferred to a 500-mL Erlenmeyer flask equipped with a magnetic. stirrer. The solution was treated dropwise with concentrated hydrochloric acid (8.50 g, 5 0.0S39 mol) over a period of about 10 minutes. The product was isolated via filtration, reslurried with, water (2 x 40 mL), cover washed once with water (25 mL), and then air-dried on the filter for 2 hours. The product consisted of a crystalline, tan powder (20.9 g, 91% yield). The only appreciable impurities observed by *H NMR were about 0.8% of an unknown and 0.7% ether. 10 III NMR (DMSO-^j 8 7.25 (s, IH), 13.95 (br s, IH), 8.56 (d, IH), 8.25 (d, IH), 7.6S (dd,
IH).
The following Example 14 illustrates an alternative preparation of ethyl 3-bronio-l-(3-c]iloro-2-pyridinyl)"4,5-diliydi-o-l//-pyrazole-5-carboxylate) which can be used to prepare, for example, ethyl 3-bromo-l-(3-cbloro-2-pyridinyl)-l//--pyra2o]e-5-carboxylate (i.e. product 15 of Example 13, Step B).
EXAMPLE 14
Preparation of Ethyl. 3-bromo-1 -(3-chloro-2-pyiidinyl)-4,5-dihydi-o-l#-pyrazole-5-carboxylate from ethyl 3-chl.oro- l-(3-diloro-2-pyridinyl)-4,5-dihydro-l/f-pyrazole-5-
carboxylate using hydrogen bromide
20 Hydrogen bromide was passed through a solution of ethyl 3-chloro-l-(3-chloro-2-
pyridiuyl)-4,5-dihyd.ro-l//-pyrazoI.e-5-carboxylate (i.e. product of Example 12, Step B) (8.45 g, 29.3 nnnol) in dibromomethane (85 mL). After 90 minutes the gas flow was terminated, and the reaction mixture was washed with aqueous sodium bicarbonate solution (100 mL). The organic phase was dried and evaporated under reduced pressure to give the 5 title product as an oil (9.7 g, 99% yield), which crystallized on standing.
lI-fNMll (C.DCI3) 5 1.19 (t, 3H), 3.24 (1/2 of AB in ABX pattern, J = 9.3, 17.3 Hz, IH), 3.44 (1/2 of AB in ABX pattern, J= 11.7, 17.3 Hz, IH), 4.18 (q, 2H), 5.25 (X of ABX, IH, J = 9.3, 11.9 Hz), 6.85 (dd, ./ = 4.7, 7.7 Hz, IH), 7.65 (dd, /= 1.6, 7.8 Hz, IH), 8.07 (dd, /= 1.6,4.8 Hz, IH). '
30 The following Example 15 illustrates the preparation of ethyl l-(3-chloro-2-pyridinyl)-
4,5-dihydro-3-[[(4-metliylphenyl)sulfonyl]oxy]- l/Y-pyrazole-5-carboxylate, which can be used to prepare ethyl 3-bromo- l-(3-cbloro-2-pyridinyl)-4,5-dmydi-o-l^-pyrazole-5-carboxyiate by procedures similar to that described in Example 14.

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EXAMPLE 15
Preparation of ethyl l-(3-chloro-2-p3Tidiuyl)-4,5-dihydro-
3-[[(4-methylphenyl)sulfoDyl]oxy]-liy-pyrazole-5~cai-boxylate •
Triethylamine (3.75 g, 37.1 zrunol) was added dropwise to a mixtui-e of ethyl 2-(3-5 chloio-2-pyi-idinyl)-5-oxo-3-pyrazol.idinecarboxylate (i.e. the product of Example 12, Step A) (10.0 g, 37.1 mmol) and jy-tohzenesulfonyl chloride (7.07 g, 37.T mmol) in dichlorornethane (100 mL) at 0 °C. Further portions of^-toluenesulfonyl chloride (0.35 g, 1.83 mmol) and triethylamine (0.19 g, 1.88 mmol) were added. The reaction mixture was then allowed to warm to room temperature and was stirred overnight. The mixture was then
10 diluted with dichlorometliaue (200 mL) and washed with water (3 x 70 mL). The organic phase was dried and evaporated to leave the title product as an oil (13.7 g, 87% yield), which slowly formed crystals. Product recrystalHzed from ethyl acetate/hexanes melted at 99.5-100 °C. lR(nujol).v 1740, 1638, 1576, 1446, 1343, 1296, 122S, 1191, 1178, 1084, 1027, 948, 969,
15 868, 845 cur*.
lHNMR (CDC13) 5 1.19 (t, 311), 2.45 (s, 3H), 3.12 (1/2 of AB hi ABX pattern, J= 17.3, 9 Hz, III), 3.33 (1/2 of AB hi ABX pattern, .7= 17.5,11.8 Hz, 1H), 4.16 (q, 2H), 5.72 (X of ABX, J= 9, 11.8 Hz, 1H), 6.79 (dd, J= 4.6, 7.7 Hz, 111), 7.36 (d, ./= 8.4 Hz, 111), 7.56 (dd, ./= 1.6, 7.8 Hz, 1H), 7.95 (d, ./= 8.4 Hz, 211), 8.01 (ddU= 1.4,4.6 Hz, 1H).
20 EXAMPLE 16
PrepaiationofA^-f4-CMoio-2-medivl~64(memvlaminolcarbouvl1phenvl1-l-r3-chloro-2-pvridmvl)-3-(2.2.2-hifiuoroethoxvVl/i-pvi-azole-5"Cai-boxaniide
Step A: Preparation of Ethyl l-(3-chloro-2-pyridinyl)-2,3-dihydro-3-oxo-liy-
pyrazole-5-carboxylate
25 . To a suspension of ethyl 2-(3-chloro-2-p)a-idinyl)-5-oxo-3-p_yrazohdinecarboxylate
(i.e. product of Example 12, Step A) (27 g, 100 mmol) stirred in dry acetonitrile (200 mL) was added sulfuric acid (20 g, 200 mmol) in one portion. The reaction mixture thinned io form a pale green, nearly clear solution before thickening again to form a pale yellow suspension. Potassium persulfate (33 g, 120 mmol) was added in one portion, and then the
30 reaction mixture was heated at gentle reflux for 3.5 hours. After cooling using an ice bath, a precipitate of white solid was removed by filtration and discarded. The filtrate was diluted with water (400 mL) and then extracted three times with ethyl ether (700 mL total). Concentration of the combined ether extracts to a reduced volume (75 mL) caused precipitation of an off-white solid (3.75 g), which was collected by filtration. The ether
35 motlier liquor was further conceuti'ated to yield a second crop of an off-white precipitate (4.2 g), which was also collected by filtration. An off-white solid also precipitated from the

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aqueous phase; this sohd (4.5 g) was collected by filtration to provide a combined total of 12.45 g of the title compound.
iHNMR (DMSO-rf6) 5 1.06 (t, 3H), 4.11 (q, 2H), 6.34 (s, 1H), 7.6 (t, 1H), 8.19 (d, 1H), 8.5 (d, 1H), 10.6 (s, 1H).
5 StepB: Preparation of Ethyl l-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-
l#-pyrazole-5-carboxylate
To a suspension of ethyl l-(3-chloro-2-pyiidinyl)-2,3-dihydi-o-3-oxo-l/f-pyrazole-5-carboxylate (i.e. product of Step A) (0.8 g, 3 mmol) stirred in dry acetonitrile (15 mL) at -5 °C was added potassium carbonate (0.85 g, 6.15 mmol). The suspension was stuxed for
10 15 minutes at 20 °C. The stuxed suspension was then, cooled to 5 °G, and 2,2,2-trifhioro-elhyl trifluoromethanesulfonate (0.8 g, 3.45 mmol) was added dropwise. The reaction mixture was warmed to room temperature and then heated to reflux, at which time thin layer chromatography showed the reaction to be complete. Water (25 mL) was added to the reaction mixture, which was then extracted with ethyl ether. The ether extract was dried
15 over magnesium sulfate and concentrated to yield the title product compound (1.05 g) as a pale yellow oil.
^-INMR (CDC13) 5 1.21 (t, 3H), 4.20 (q, 2H), 4.63 (q, 2H), 6.53 (s, 1H), 7.4 (t, 1H),.7.9 (d, 1H), 8.5 (d, IB).
Step C: Preparation of l-(3-Chloro-2-pyiidinyl)-3-(2,2,2-Uifluoroetlioxy)-
20 177-pyrazo1e-5-carboxylic acid
To a stirred solution of ethyl l-fS-diloro^-pyridiny^-S-tl^.l-tiifluoroethoxy)-l/i-pyrazole-5-carboxylate (i.e. product of Step B) (0.92 g, 2.8 mmol) in methanol (15 mL) was added water (5 mL), which caused the reaction mixture to become cloudy. An aqueous solution of sodium hydroxide (50%, 1.5 g, 19.2 mmol) was added dropwise, and the reaction 25 mixture was stuxed at room temperature for 30 mmutes, during which time the reaction mixture became again clear. Water (20 mL) was added and the reaction mixture was extracted with ethyl ether, which was discarded. The aqueous phase was acidified to pH 2 using concentrated hydrochloric acid and then extracted with etiiyl acetate (50 mL). The ethyl acetate extract, which was washed with water (20 mL) and brine (20 mL), dried over 30 magnesium sulfate and concentrated to give the title compound, isolated as a white sohd (0-8 g).
]H NMR (DMSO-rf6) 5 4.9 (q, 211), 6.75 (s, 1H), 7.6 (t, 1H), 8.2 (d, 1H), 8.55 (d, 1H), 13.7 (bs, 1H).
Step D; Preparation of 6-Cbloro~8-methyl-2H-3il-ben2oxazme-2,4(lH)-dione
35 To a suspension of 2-amJrio-3-meth54-5-chlorobeiLzoic acid (i.e. product of Example 6,
Step A) (97 g, 520 mmol) stirred in dry dioxane (750 mL) at room temperature, hi chlorom ethyl chloroform ate (63 g, 320 mmol) was added dropwise. The reaction mixture

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exothermically warmed slowly to 42 °C, and the solid almost completely dissolved before a thick suspension formed again. After the suspension was stirred at ambient temperature for 2.5 hours, the title compound was isolated by filtration, washed with ethyl ether, and dried to yield the title product compound, obtained as a white solid (98 g). 5 lH NMR (DMSO-tf6) 5 2.3 (s, 3H), 7.70 (s, 1H), 7.75 (s, 1H), 11.2 (s, 1H).
Step E: Preparation of 6-Chloro-2-[l-(3-chloro-2-pyiidinyl)-3-(252,2-n-ifluoroethoxy)-
lff-pyrazol-5 -yl] -8 -methyi-4ff-3,1 -benzoxazin-4-one _____
To a suspension of l-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-lJff'-pyrazole-5-carboxylic acid (i.e. product of Step C) (7.9 g, 24 mmol) stirred in dichloromethane
] 0 (100 mL) was added W,//-dimetb.ylformamide (4 drops). Oxalyl chloride (4.45 g, 35 mmol) was added dropwise over a period of 45 minutes. The resulting solution was stirred at room temperature for 4 hours and men concentrated under vacuum. The isolated acid chloride was dissolved in dry acetonitrile (10 mL) and added to a suspension of 6-chloro-8-methyl-2/f-3,l-benzoxaz.ine-2,4(l/y)-dione (i.e. product of Step D) (4.9 g, 23 mmol) stirred in dry
15 acetonitrile (14 mL). Pyridine (10 mL) was added, and the solution heated at reflux 6 hours. After cooling using an ice bath, a precipitate of white solid (9.15 g) was collected. The *H NMR spectrum of the collected precipitate showed peaks consistent with the title compound and residual 6-chloro~S-me1iiyl-2H~3,UbeDzoxazme-2,4(lH)-dion.e stalling material. A small portion of the collected precipitate was recrystallized from acetonitrile to yield the
20 pure title product melting at 178-18 0 °C.
JHNMR (DMSO-d6) 8 1.72 (s, 311), 4.96 (q, 2H), 7.04 (s, 1H), 7.7 (t, 1H), 7.75 (s, 1H), 7.9 (s, 1H), 8.3 (d, IB), 8.6 (d, lfl).
Step F: Preparation of /Y-[4-chloro-2-methyl-6-[(metliylamino)carbonyl]phenylj-
1 -(3-chIoro-2-pyridinyl)"3-(2,2,2-tiifluoroethox)')- l#-pyrazole-
25 5-carboxamide
To a suspension of the 6-chloro-2-[l-(3-chloro-2-pyi'idinyl)-3-(2,2,2-tiifluoroethoxy)-l/i-p}'i-azol-5-yl]-8-memyl-4/7-3,l-benzoxazin-4-one (i.e. precipitate product of Step E) (3.53 g, 7.5 mmol) in teu-ahydrofuran (15 mL), methylamine (2.0 M solution in THF, 11 mL, 22 mmol) was added dropwise, and the resulting solution was stirred at room temperature for
30 45 minutes. Thin layer chi'omatography then showed the reaction to be complete. Ethyl ether (100 rnL) was added, and the reaction mixture was stirred for 2 horns while a precipitate formed. The precipitate was collected by filtration and then recrystallized from acetonitrile to yield a white solid (0.82 g). A second crop of white solid (0.35 g) precipitated from tire acetonitrile mother liquor and was collected by filtration. The initial
35 ether/tefrahydrofuran mother liquor was concentrated to dryness, and the residual solid was recrystallized from acetonitrile to yield a third crop of white solid (0.95 g). The three crops

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were combined, totaling 2.12 g (after drying) of the title compound, a compound of the present invention, isolated as a white solid, melting at 195-197 °C.
1HNMR (CDC13) 5 2.18 (s, 3H), 2.92 (d, 3H), 4.66 (q, 2H), 6.15 (q, 1H), 6.6 (s, 1H), 7.2 (s, 1H), 7.25 (s, 1H), 7.35 (t, 1H), 7.8 (d, 1H), 8.45 (d, 1H), 10.0 (s, 1H).
5 The following Example 17 illustrates an alternative preparation of l-(3-chloro-2-
pyriduiyl)-3-(tiifluoromethyl)-l/^-pyrazole-5-carboxyHc acid, which can be used to prepare, for example, l-(3-cMoro-2-^pyridmyl)-^-[2-memyl-6^[(l-methylemyl)amino]cai-bonyl]-phenyl]-3-(hifluorometliyl)-l//-pyrazole-5-carboxamide, by further steps illustrated in Examples 4.
10 EXAMPLE 17
Preparation of l-G-chloro^-DVi'idmvD^-rhiiluoromethvlVUi-PVi-azole^-cai-boxvlic acid
Step A: Preparation of 3-chloro-2(l/^)-pyridinone (2,2,2-trifluoro-
1 -methylethyrideue)hydrazone ■
1,1,1-Trifluoroacetone (7.80 g, 69.6 mmol) was added to 3-cmon>2(l#)-pyridinone
15 hydiazone (alternatively named (3-chloro-pyridin-2-yl)-hydrazme) (10 g, 69.7 nirnol) at 20-25 °C. After the addition was complete, the mixture was stirred for about 10 minutes. The solvent was removed under reduced pressure and the mixture partitioned between ethyl acetate (100 mL) and saturated aqueous sodium carbonate solution (100 mL). The organic layer was dried and evaporated. Chromatography on silica gel (eluted with ethyl acetate)
20 gave the product as an off-white solid (11 g, 66% yield), m.p. 64-64.5 °C (after crystallization from ethyl acetate/hexanes).
Ill (nujol) v 1629, 1590, 1518, 1403, 1365, 1309, 1240, 1196, 1158, 1100, 1032, 992, 800 cm-1. JHNMR (CDCI3) 5 2.12 (s, 3H), 6.91-6.86 (m, 1H), 7.64-7.61 (m, 1H), 8.33-8.32 (m, 2H).
25 MS m/z 237 (M+).
Step B: Preparation of ethyl hydrogen ethanedioate (3-chloro-
2-p3Tidmyl)(2,2,2-tdfluoro-l-methylethyhdene)hydrazide (alternatively
named ethyl hydrogen ethanedioate (3-chloro-2-pyridinyl)(2,2,2-trifiuoro-
___ l-metlrylethylidene)hydrazriie)
30 Triethylamme (20.S1 g, 0.206 mol) was added to 3-chloro-2(l/T)-pyridinone (2,2,2-
lrifluoro-l-memyledrylidene)hydrazone (i.e. the product of Step A) (32.63 g, 0.137 mol) in dichloromethane (68 mL) at 0 °C. Ethyl chlorooxoacetate (IS.75 g, 0.137 mol) in dicliloromethane (69 mL) was added dropwise to the mixture at 0 °C. The mixture was allowed to wami to 25 °C over about 2 hours. The mixture was cooled to 0 °C and a further
35 portion of ethyl chlorooxoacetate (3.75 g, 27.47 mmol) in dichloromethane (14 mL) was added dropwise. After about an additional 1 hour, the mixture was diluted with dichloromethane (about 450 mL), and the mixture was washed with water (2 x 150 mL).

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The organic layer was dried and evaporated. Chromatography on silica gel (eluted with 1:1 ethyl acetate-hexanes) gave the product as a solid (42.06 g, 90% yield)3-m.p. 73.0-73.5 °C (after crystallization from ethyl acetate/hexanes).
IR(nujol)v 1751, 1720,1664,1572, 1417,1361, 1330,1202,1214,1184,1137,1110, 1004, 5 1043,1013,942,807,836 cm-1.
1HNMR (DMSO-rf6, 115 °Q 1.19 (t, 3H), 1.72 (br s, 3H), 4.25 (q, 2H), 7.65 (dd, / = 8.3, 4.7 Hz, 1H), 8.20 (dd, J= 7.6, 1.5 Hz, 1H), 8.55 (d, J= 3.6 Hz, 1H). MS m/z 3 37 (M+).
Step C: Preparation of ethyl 1 -(3-chloro-2-pyiidinyl)-4,5-dihydro-5-hydi-oxy-
10 3-(tiifluorometh)'])- l//-pyrazoJe-5-carboxylate
Ethyl hydrogen ethanedioate (3-chloro-2-pyi-idinyl)(2,2,2-tiifluoro-l-memyl-ethylidene)hydrazide (i.e. the product of Step B) (5 g, 14.8 mmol) in dimethyl sulfoxide (25mL) was added to tetiabutylammonium fluoride hydrate (10 g) in dimethyl sulfoxide (25 .mL) over 8 hours. When the addition was complete, the mixture was poured into acetic 15 acid (3.25 g) in water (25 mL). After stining at 25 °C overnight, the mixture was then extracted with toluene (4 x 25 mL), and the combined toluene extracts were washed with water (50 mL), dried and evaporated to give a solid. Chromatography on silica gel (eluted with 1 ;2 ethyl acetate-hexanes) gave the product as a solid (2.91 g, 50% yield, containing about 5% of 3-chloro-2(1//)-pyiidinone (2,2,2-trifluoro-l-methylethylidene)hydrazone), 20 m.p. 78-78.5 °C (after reciystallization from ediyl acetate/hexanes).
lR(nujol)v3403, 1726, 1618, 1582, 1407,1320, 1293, 1260,1217, 1187,1150,1122, 1100, • 1067,1013,873,829 cm"1.
1HNMR. (CDC13) 5 1-19 (s, 3H), 3.20 (1/2 of ABZ pattern, 7= 18 Hz, 1H), 3.42 (1/2 of ABZ pattern, J= 18 Hz, III), 4.24 (q, 2H), 6.94 (dd, J= 7.9,4.9 Hz, 1H), 7.74 (dd, /= 7.7, 25 1.5 Hz, 1H), 8.03 (dd, 7= 4.7, 1.5 Hz, 1H). MS m/z 319 (M+).
Step D: Preparation of athyl l-(3-chloro-2-pyridinyl)-3-(tiifluoromethyl)-
l/j":pyrazole-5-cai"box3date
Sulfuric acid (concentrated, 2 drops) was added to eth3'l l-(3-chloro-2-pyridinyl)--
30 4j5-dihydi-o-5-hydioxy-3-(trifluoromethyl)-l//-p3'i'a2ole-5-cai-boxylate (i.e. the product of Step C) (1 g, 2.96 mmol) in acetic acid (10 mL) and the mixture was wanned to 65 °C for about 1 horn'. The mixture was allowed to cool to 25 °C and most of the acetic acid was removed under reduced pressure. The mixture was partitioned between saturated aqueous sodium carbonate solution (100 mL) and ethyl acetate (100 mL). The aqueous layer was
35 further extracted with ethyl acetate (100 mL). The combined organic extracts were dried and evaporated to give the product as an oil (0.66 g, 77% yield).

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IR(neat) v 3147, 2986, 1734, 1577, 1547, 1466, 1420, 1367, 1277, 1236, 1135, 1082, 1031, 973, 842, 802 cm"1.
iHNMR (CDC13) 6 1.23 (t, 3H), 4.25 (q, 2H), 7.21 (s, 1H), 7.48 (dd, J= 8.1, 4.7 Hz, 1H), 7.94 (dd, J= 6.6,2 Hz, 1H), 8.53 (dd, J= 4.7,1.5 Hz, 1H). 5 MSm/z319(M+).
Step E: Preparation of l-(3-chloro-2-pyridmyl)-3-(trifluoroniethyl)-l/f'-pyrazole-
5-carboxylic acid
Potassium hydroxide (0.5 g, 85%, 2.28 rnrnol) in water (1 mL) was added to ethyl l-(3-chloro-2-pyridmyl)-3-(trifluorometlryl)-l/f-pyrazole-5-carboxylate (i.e. the product of
10 Step D) (0.66 g, 2.07 minol) in ethanol (3 mL). After about 30 minutes, the solvent was removed under reduced pressure, and the mixture was dissolved in water (40 mL). The solution was washed with ethyl acetate (20 mL). The aqueous layer was acidified with concentrated hydrochloric acid and was extracted with ethyl acetate (3 x 20 mL). The combined extracts were dried and evaporated to give the product as a solid (0.53 g, 93%
15 yield), m.p. 178-179 °C (after crystallization from hexanes-ethyl acetate).
Ill (nujol)v 1711,1586,1565, 1550, 1440, 1425,1292,1247,1219,1170, 1135,1087, 1059,
1031,972,843,816 cm"1.
iHNMR (DMSO-6) 5 7.61 (s, 1H), 7.77 (in, 1H), 8.30 (d, 1H), 8.60 (s, 1H).
Examples 18 and 19 illustrate alternatives to reaction conditions described in Example 20 10, Step E and Example 8, Step E, respectively.
EXAMPLE 18
Preparation of 2-[3-bromo-1 -(3-chloro-2-pyridinyl)-l/^pyrazol-5-yl]-6 4/7-3, l-benzoxazin-4-one
Methanesulfonyl chloride (1.0 niL, 1.5 g, 13 nnnol) was dissolved in acetonitrile
25 (10mL), and the mixture was cooled to -5 °C. A solution of 3-brorno-L(3-chloro-2-pyridinyl)-U:f-pyrazole-5-carboxylic acid (i.e. the pyrazolecarboxylic acid product of Example 10, Step D) (3.02 g, 10 inmol) and pyridine (1.4 mL, 1.4 g, 17 mniol) in acetonitrile (10 mL) was added dropwise over 5 minutes at -5 to' 0 °C. A slurry formed during the addition. The mixture was stirred 5 minutes at this temperature, and then a mixture of
30 2-amino-3-methyl-5-chlorobenzoic acid (i.e. the product of Example 6 Step A) (1.86 g, 10 mmol) audpjaidme (2.8 mL, 2.7 g, 35 mmol) in acetonitrile (10 mL) was added, rinsing with more acetonitrile (5 mL). The mixture was stirred 15 minutes at -5 to 0 °C, and then methanesulfonyl chloride (1.0 mL, 1.5 uiL, 13 mmol) in acetonitrile (5 rnL) was added dropwise over 5 minutes at a temperature of -5 to 0 °C. The reaction mixture was stirred
35 15 minutes more at this temperature, then allowed to warm slowly to room temperatm-e, and stirred 4 h. Water (20 mL) was added dropwise, and the mixture was stirred 15 minutes. Then the mixture was filtered, and the solids were washed with 2:1 acetonitrile-water (3 x 3

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mL), then with acetonitrile (2> a light yellow powder, 4.07 g (90.2% crude yield)., melting at 203-205 °C. HPLC of the
product using a Zorbax® RX-C8 chromatography column (4.6 mm x 25 cm, eluent 25-95%
acetonitrile/ pH 3 water) showed a major peak corresponding to the title compound and
5 having 95.7% of total chrornatogram peak area.
*H NMR (DMSO-c%) 8 1.72 (s, 3H) 7.52 (s, IH), 7.72-7.78 (m, 2H), 7.88 (m, IH), 8.37 (dd, lH),8.62(dd,lH).
EXAMPLE 19
Preparation of 6-chloro-2-[3-chloro-l-(3-chloro-2-pyridiayl)-lJif-pyrazol-5-yl]-8-mefliyl-
10 4/7-3,1 -benzoxazin-4-one _____
Methanesulfonyl chloride (1.0 mL, 1.5 g, 13 mmol) was dissolved in acetonitiile (10 mL), and the mixture was cooled to -5 °C. A solution of 3-cliloio-l-(3-chloro-2-pyridmyl)-l.r7-pyrazQle-5-carboxylic acid (i.e. the carboxylic acid product of Example 8, StepD) (2.58 g, 10 mmol) and pyridine (1.4 mL, 1.4 g, 17 mmol) in acetonitiile (10 mL) 15 was added dropwise over 5 minutes at -5 to 0 °C. A sluny fonued during the addition. The mixture was stirred 5 minutes jat this temperature, and then 2-arrrino-3-methyl-5-chlorobenzoic acid (i.e. the product from Example 6, Step A) (1.86 g, 10 mmol) was added all at once. Then a solution of pyridine (2.8 raL, 2.7 g, 35 mmol) in acetonitiile (10 mL) was added dropwise in 5 mm at -5 to 0 °C. The mixture was stirred 15 minutes at -5 to 0 °C,
20 and then methanesulfonyl chloride (1.0 mL, 1.5 mL, 13 mmol) in acetonitrile (5 mL) was added dropwise in 5 iniu at -5 to 0 °C. The reaction mixture was stirred 15 minutes at this temperature, then allowed to warm, slowly to room temperature, and stirred 4 h. Water (15 mL) was added dropwise, aud the mixture was stirred 15 minutes. Then the mixture was filtered, and the solids were washed with 2:1 acetonitrile-water (3 x 3 inL), then with
25 acetonitrile (2x3 mL), and dried under nitrogen to afford the title product as a pale yellow powder, 3.83 g (94.0% crude yield), melting at 199-201 °C. HPLC of the product using a Zorbax® RX-C8 chromatography column (4.6 mm * 25 cm, eluent 25-95% acetonitrile/ pH 3 water) showed a major peak corresponding to the title compound and having 97.8% of total chrornatogram peak area.
30 IH NMR (DMSO-rf6) 5 1.72 (s, 3H), 7.48 (s, IH), 7.74-7.80 (m, 2H), 7.87 (m, IH), 8.37 (dd, lH),8.62(dd, IH).
By the procedures described herein together with methods known in the ait, the following compounds of Table 1 can be prepared. The following abbreviations are used in the Tables which follow: t means tertiary, s means secondary, n means normal, i means iso, 35 Me means methyl, Et means ethyl, Pr means propyl, /-Pr means isopropyl, and Bu means butyl.







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w X Y Z R.3
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH h?r
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CLi e-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH ai /-Bu
CH CH CH CH i-Pr
CM CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH' CH CH CH /-Bu
CH CH CH CH. i-?i
CH CH CH CH /-Bu
CH CH ' CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu
CH CH CH CH i-Pr
CH CH CH CH /-Bu


R4 R6 R?
. Me CF3 F
CI CF3 F
CI CF3 F
Bi CF3 F
Br CF3 F
Me CI F
Me CI F
CI CI F
Cl a ■ F
Br Cl F
Br CJ F
Me Br F
Me Br F
CI Br F
CI Br F
Br Br F
Br Br F
Me CN F
Me CN F
CI CN F
CI CN F
Br CN F
Br CN F
Me CF3 Cl
Me CF3 Cl
a CF3 a
CI CF3 Cl
Br CF3 Cl
Br CF3 Cl
Me Cl Cl
Me Cl Cl
CI Cl Cl
CI Cl Cl
Br Cl Cl
Br Cl Cl
Me Br Cl
Me Br Cl

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w X CH Y Z R3 R4 R6 R9
CH
CH CH i-Pr CI Br CI
CH CH CH CH t-Bu CI Br CI
CH CH CH CH i-Pr Br Br a
CH CH CH CH /-Bu Br Br Cl
CH CH CH CH i-Pr Me CN Cl
CH CH CH CH /-Bu Me CN CI
CH CH CH CH i-Pr a CN Cl
CH CH CH CH /-Bu CI. CN Cl
CH CH CH CH i-Pr Br CN Cl
CI I CH CH CH /-Bu Br CN Cl
CH Cll CH CH i-Pr Me CF3 Br
CH CH CH CH /-Bu Me CF3 Br
CH CH CH CH i-Pr CI CF3 Br
CH CH CH CH /-Bu CI CF3 Br
CH CH CH CH i-Pr Br CF3 Br
CH CI I CH CH /-Bu Br CF3 Br
CH CH CH CH i-Pr Me CI Br
CH CH CH CH /-Bu Me CI Br
CH CH CH CH i-Pr a CI Br
CH CH CH CH /-Bu CI CI Br
CH CH m CH i-Yr Br CI Br
CH CH CH CH /-Bu Br CI Br
CH CH CK Cll i-Pr Me Br Br
CH CH CH CH /-Bu Me Br Br
CH- CH CH CH i-Pr CI Br Br
CH CH CH CH /-Bu ci Br Br
CH CH CH CH i-Pr Br Br Br
CH CH " CH CH /-Bu Br Br Br
CH CH CH CH i-?r Me CN Br
CH CH CH CH /-Bu Me CN Br
CH CH CH CH i-Pr CI CN Br
CH CH CH CH /-Bu CI CN Br
CH CH CH CH i-Pr Br CN Br
CH CH CH CH /-Bu Br CN Br
CH CH CH CH i-Pr Me CF3 CN
CH CH CH CH /-Bu Me CF3 CN
CH CH CH CH i-Pr CI CF3 CN

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R9
R4
W
R-1
X
Y
R6

CH CH CH CH CH(CH3)CH2OCH3 Me CF3 CI
CH CH CH CH CH(CH3)CH2SCH3 Me CF3 CI
CH CH CH CH propargyl Me CF3 CI
CH CH CH CR Me Me Br F
CH CH CH CH Et Me Br F
CH CH CH CH CH(CH3)CH2OCH3 Me Br F
CH CH CH CH " CH(CH3)CH2SCH3 Me Br F
CH CH CH CH propargyl Me Br F
CH CH CH CH Me Me Br CI
CH CH CH CH Et Me Br CI
CH CH CH CH CH(CH3)CH2OCH3 Me Br CI
CH CH CH CH CH(CH3)CH2SCH3 Me Br CI
CH CH CH CH propargyl Me Br CI
CH CH CH CH Me CI CF3 F
CH CH CH CH Et CI CF3 F
CH CH CH CH CH(CH3)CH2OCH3 CI CF3 F
CH CH CH CH CH(CH3)CH2SCH3 CI CF3 F
CH CH CH CH propargyl CI CF3 F
CH CH CH CH Me CI CF3 CI
CH CH CH CH Et CI CF3 CI
CH CH CH CH CH(CH3)CH2OCH3 CI CF3 CI
CH CH CH CH CH(CH3)CH2SCH3 CI CF3 CI
CH CH cii CH propargyl CI CF3 CI
CH CH CH CH Me CI Br F
CH- CH CH CH Et CI Br F
CH CH CH CII CH(CH3)CH2OCH3 CI Br F
CH CH CH CH CH(CH3)CH2SCH3 CI Br F
CH CH ' CH CH propargyl CI Br F
CH CH CH CH Me C! Br CI
CH CH CH CH Et CI Br CI
CH CH CH CH CH(CH3)CH2OCH3 CI Br CI
CH CH CH CH CH(CH3)CH2SCH3 CI Br CI
CH CH CH CH propargyl CI Br CI
CH CH CH N Me Me CF3 F
CH CH CH N Et Me CF3 F
CH CH CH N CH(CH3)CH2OCH3 Me CF3 F
CH CH CH N CH(CH3)CH2SCH3 Me CF3 F

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El El El R1 Ef Rl El El Rl B2
CI Cl CF3 El Br Br I Br Et a
CI CI • CF3 i-Pr Br Br ' I Br i-Pr Cl
a Cl CF3 /-Bu Br Br I Br /-Bu Cl
a Cl Cl Me Cl Br I Br Me Br
Cl Cl Cl Et Cl Br I Br Et Br
Cl Cl Cl i-Pr Cl Br I Br i-Pr Br
Cl Cl Cl /-Bu Cl Br I Br /-Bu Br
Cl Cl Cl Me Br Br CF3 CF3 Me Cl
Cl Cl Cl Et Br Br CF3 CF3 Et , Cl
CI CI a j-Pr Br Br CF3 CF3 i-Pr Cl
Cl Cl a /-Bu BT Br CF3 CF3 /-Bu Cl
Cl ■ Cl Br Me ' Cl Br CF3 CF3 Me Br
a a Br Et a Br CF3 CF3 Et Br
Cl Cl Br i-Pr Cl Br CF3 CF3 i-Pr Br
Cl Cl Br /-Bu Cl Br dT3 CF3 /-Bu Br
Cl Cl Br Me Br Br CF3 Cl Me Cl
Cl Cl Br Et Br Br CF3 Cl Et Cl
Cl Cl Br i-Pr Br Br CF3 Cl i-Pr Cl
Cl Cl Br /-Bu Br Br CF3 CI /-Bu Cl
Cl Br CF3 Me Cl Br CF3 Cl Me Br
CI Br CF3 Et Cl Br CF3 CI Et Br
Cl Br CF3 i-Pr Cl Br CF3 Cl i-Pr Br
Cl Br CF3 /-Bu Cl Br CF3 Cl /-Bu Br
Cl Br CF3 Me Br Br CF3 Br Me Cl
■a Br CF3 Et . Br Br CF3 Br Et Cl
Cl Br CF3 i-Pr Br Br CF3 Br i-Pr Cl
Cl Br CF3 /-Bu Br Br CF3 Br /-Bu Cl
Cl Br Cl Me Cl Br CF3 Br Me Br
Cl Br a El. Cl Br CF3 Br Et Br
Cl Br Cl i-Pr Cl Br CF3 Br i-Pr Br
Cl Br Cl /-Bu Cl Br CF3 Br /-Bu Br



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w X CH Y Z R4 R6 R?
CH
CH CH CI ■ CF3 CN
CH CH CH CH Br CF3 CN
CH CH CH CH Me CI CN
CH CH CH CH CI CI CN
CH CH CH CH Br CI CN
CH CH CH CH Me Br CN
CH CH CH CH CI Br CN
CH CH CH CH Br Br CN
CH CH CH CH Me CN CN
CH CH CH CH CJ CN CN
CH CH CH CH ' Br CN CN
CH CH CH N Me CF3 Me
CH CM CH N CI CF3 Me
CH CH CH N Br CF3 . Me
CH CH CH N Me CI Me
CH CH CI-I N CI CI Me
CH CH CH N Br CI Me
CH CH CH N Me Br Me
CH CH CH N CA Br Me
CH CH CH N Br Br Me
CH CH CH N Me CN Me
CH CH CH N CI CN Me
CH CH CH N Br CN Me
CH CH CH N Me CF3 F
CH CH CH N CI CF3 F
CH CH CH N Br CF3 F
CH CH CH N Me CI F
CH ' CH CH N CI CI F
CH CH CH N Br CI F
CH CH CH N Me- Br F
CH CH CH N a Br F
CH CH CH N Br Br F
CH CH CH N Me CN F
CH CH CH N CI CN F
CH CH CH N Br CN F
CH CH CH N Me CF3 CI
CH CH CH N CI CF3 CI

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W X X 5_
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH ' CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
C-Cl CH CH CH
C-F CH CH CH
CH CH CH CH


R4 R6 R?
Br CF3 CI
Me CI CI
CI CI CI
Br CI CI
Me ; Br ■ Cl
CI Br CI
Br Br Cl
Me CN Cl
CI CN Cl
Br CN Cl
Me CFi Br
CI CF3 Br
Br CF3 Br
Me CI Br
CI CI Br
Br CI Br
Me Br Br
CI Br Br
Br Br Br
Me CN Br
CI CN Br
Br CN Br
Me CF3 CN
CI CF3 CN
Br CF3 CN
Me CI CN
CI CI CN
Br CI CN
Me Br CN
CI Br CN
Br Br CN
Me CN CN
CI CN CN
Br CN CN
Me CF3 Cl
Me CF3 F
Me CF3 elJjyuyl .

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w X Y Z
CH CH CH CH
CH CH CH CH
C-CJ CH CH CH
C-F CH CH CH
CH CH CH CH
CH CH CH CH
CH CH CH CH
C-Cl CH CH CH
C-F CH CH CH
CH CH CH CH
CH CH CH CH
CH CM CH CH
C-CI CH CH CH
C-F CH CH CH
CH CH CH CH
CH CH CH CH
CH CH CH CH
C-Cl CH CH N
C-F CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
C~C1 CH CH N
C-F CH Cll N
CH CH CH N
CH • CH CH N
CH CH CH N
C-Cl " CH CH N
C-F CH CH N
CH CH CH N
CH CH CH N
CH CH CH N
C-Cl CH CH N
C-F CH CH N
CH CH CH N
CH CH CH N
CH CH CH N


R Me CF3 I
Me CF3 S02Me
CI CF3 Cl
CI CF3 F
a CF3 ethynyl
Cl CF3 I
Cl CF3 S02Me
Me Br Cl
Me Br F
Me Br elliynyl
Me Br I
Me Br S02Me
Cl Br Cl
Cl Br F
Cl Br elliynyl
Cl Br I
Cl Br S02Me
Me CF3 Cl
Me ^3 F
Me CF3 ethynyl
Me CF3 I
Me CF3 S02Me
Cl CF3 Cl
Cl CF3 F
Cl CF3 elliynyl
Cl CF3 I
Cl CF3 S02Me
Me Br Cl
Me Br F
Me Br ellrynyl
Me Br I
Me Br S02Me
Cl Br . Cl
Cl Br F
Cl Br ethynyl
Cl Br I
Cl Br S02Me

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w X
N Y Z
CH
CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH N CH N
CH CH N N
CH en N N
CH CI-I N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH ' CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N
CH CH N N


R4 R6 R9
Me CF3 H
Me CF3 Me
Me CF3 Cl
CI CF3 H
CI CF3 Me
CI CF3 Cl
Me CN H
Me CN Me
Me CN Cl
CI CN H
a CN Me
a CN Cl
Me Br H
Me Br Me
Me Br Cl
CI Br H
CI Br Me
CI Br Cl
Me CF3 H
Me CF3 Me
Me CF3 Cl
CI CF3 H
a CF3 Me
Cl CF3 Cl
Me CN H
Me CN Me
Me CN Cl
Cl CN II
Cl CN Me
Cl CN CI
Me Br H
Me Br Me
Me Br Cl
Cl Br H
Cl Br Me
Cl Br Cl
Me CF3 H

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Formulation/Utility
Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water-soluble. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can contiol or delay release of the active ingredient. Spray able formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges that add up to 100 percent by weight.
Weight Percent
Active
Ingredient Diluent Surfactant
Water-Dispercible and Water-soluble 5-90 0-94 1-15
Granules, Tablets and Powders.
Suspensions, Emulsions, Solutions 5-50 40-95 0-15
(including Emulsifiable
Concentrates)
Dusts 1-25 70-99 0-5
Granules and Pellets 0.01-99 5-99.99 , 0-15
High Strength Compositions 90-99 0-10 0-2
'typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon 's Detergents andEmuhifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity.
Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialk)'! sulfosuccinates, alkyl

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sulfates, alkylbenzene sulfonates, organosilicones, i^A^dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyeth}'lene/polyoxyprop3'lene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, 5 diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, A^A^dimethylformamide, dimethyl sulfoxide, TV-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, rung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as 10 cyclohexanone, 2-heptanbne, isophoroue and 4-hydi'oxy-4-methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decauol and tetrabydiofurfuiyl alcohol.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for 15 example, U.S, 3,06O,0S4. Granules and pellets can be prepared by spraying the active
material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967', pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and PCT Publication WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. 20 Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see T. S. Woods, "The 25 Formulator's Toolbox - Product Forms for Modem Agriculture" in Pesticide Chemistry and Bio,science, The Food-Environment Challenge, T. Brooks and T; R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 30 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klinginan, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; andHance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific. Publications, Oxford, 1989. hi the following Examples, all percentages are by weight and all formulations are 35 prepared in conventional ways. Compound numbers refer to compounds in Index Table A.

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10
15
20
25


Example A
Wettable Powder
Compound 214 65.0%
dodecylphenol polyethylene glycol ether 2.0%
sodium ligninsulfonate 4.0%
sodium silicoaluminate 6.0%
montmorillonite (calcined) 23.0%.
Example B
Granule
Compound 214 10.0%
altapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%.
Example C
Extruded Pellet
Compound 214 25.0%
anhydrous sodium sulfate 10.0%
crude calcium ligninsulfonate 5.0%
sodium alkylnaphmalenesulfouate 1.0%
calcium/magnesium benLonite 59.0%.
Example D
Emulsiliable Concentrate
Compound 214 20.0%
blend of oil soluble sulfonates
and polyoxyelltylene ethers 10.0%
, isophorone 70.0%.
Example E
Granule
Compound 214 0.5%
cellulose 2.5%
lactose 4.0%.
commeal 93.0%.

Compounds of this invention are characterized by favorable metabolic and/or soil residual patterns and exhibit activity controlling a spectrum of agronomic and non-agronomic invertebrate pests. (In the context of this disclosure "invertebrate pest control" 35 means inhibition of invertebrate pest development (including mortality) that causes significant reduction in feeding or other injury or damage caused by the pest; related

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expressions are defined analogously.) As referred to in this disclosure, the term "invertebrate pest" includes arthropods, gastropods and nematodes of economic importance as pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. The term "gastropod" includes snails, slugs and other 5 Stylommatopjhora. The term "nematode" includes all of the helminths, such as:
roundworms, heaitworms. and phytophagous nematodes (Nematoda). flukes (Tematoda), Acanthocephala, and tapeworms (Cestoda). Those skilled in the art will recognize that not all compounds are equally effective against all pests. Compounds of this invention display activity against economically important agronomic, forest, greenhouse, nursery, 10 ornamentals, food and fiber, public and animal health, domestic and commercial structure, household, and stored product pests. These include larvae of the order Lepidoptera, such as armyworms, cutworms, loopers, and heliothines in the family Noctuidae (e.g., fall armyworm (Spodopterafugiperda J. E. Smith), beet armywonn. (Spodoptem exigiia Hiibner), black cutworm (Agrotis ipsilon Hufnagel), cabbage looper {Trichoplusia ni 15 Hiibner), tobacco budworm (Heliothis virescens Fabricius)); borers, casebearers, webworms, coneworms, cabbageworms and slceletonizei's from the family Pyralidae (e.g., European com borer (Ostrinia nubilalis Hiibner), navel orangeworm (Amyelois transitella Walker), corn root webworm (Crambus caliginosellus Clemens), sod webworm (Heipetogramma licarsisalis Walker)); leafrollers, budworms, seed worms, and fruit worms in the family 20 Toitricidae (e.g., codling moth (Cydiapomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), oriental fruit moth (Grapholita molesta Busck)); and many other economically important lepidoptera (e.g., diamondback moth (Plutella xylostella Linnaeus), pink bollworm (Pectinophora gossypiella Saunders), gypsy moth (Lymantria dispar Limiaeus)); nymphs and adults of the order Blattodea including cockroaches from the 25 families Blattellidae and Blattidae (e.g., oriental cockroach (Blatta ohentalis Linnaeus), Asian cockroach (Blatella a^waz'Mzukubo), German cockroach (Blattella germanica Linnaeus), brownbanded cockroach (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunnea Burmeister), Madeira cockroach (Leucophaea maderae Fabricius)); foliar feeding larvae and adults of the 30 order Coleoptera including weevils from the families Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrus oryzophilus Kuschel), granary weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oiyzae Linnaeus)); flea beetles, cucumber beetles, rootworms, leaf beetles, potato beetles, and leafminers in the family Chrysomelidae (e.g., Colorado potato 35 beetle (Leptinotarsa decemlineaia Say), western cornrootworm (Diabrotica virgifera
virgiferaheCoRte)); chafers and other beetles from the family Scaribaeidae (e.g., Japanese beetle (Popilliajaponica Newman) and European chafer (RJiizotivgits majalis Razoumowsky)); caipet beetles from the family Dermestidae: wireworms from the family

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Elateridae; bark beetles from the family Scolytidae and flour beetles from the family Tenebrionidae. In addition it includes: adults and larvae of the order Demiaptera including earwigs from the family Forficulidae (e.g., European earwig (Foificula auricularia Linnaeus), black earwig (Chelisoches mono Fabricius)): adults and nymphs of the orders 5 Hemiptera and Homoptera such as, plant bugs from the family Miridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoasca spp.) from the family Cicadellidae, . planthoppers from the families Fulgoroidae and Delphacidae, treehoppers from the family Membracidae, psyllids from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxera from the family Phylloxeridae, mealybugs 10 from the family Pseudococcidae, scales from the famili.es Coccidae, Diaspididae and
Margarodidae, lace bugs from the family Tingidae, stink bugs from the family Pentatomidae, cinch bugs (e.g., Blissus spp.) and other seed bugs from the family Lygaeidae, spittlebugs from the family Cercopidae squash bugs from the family Coreidae, and red bugs and cotton stainers from the family Pyrrhocoridae. Also included are adults and larvae of the order 15 Acari (mites) such as spider mites and red mites in the family Tetranychidae (e.g.., European red mite (Panonychus utmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (Tetranychus mcdanieli McGregor)), flat mites in the family Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi McGregor)), rust and bud mites in the family Eriophyidae and other foliar feeding mites and mites important in human and animal health, 20 i.e. dust mites in the family Epidermoptidae, follicle mites in the family Demodicidae, grain mites in the family Glycyphagidae, ticks in the order Ixodidae (e.g., deer tick (Ixodes scapularis Say), Australian paralysis tick (Ixodes holocyclas Neumann), American dog tick (Dennacentor variabilis Say), lone star tick (Amblyonvna americanum Linnaeus) and scab and itch mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; adults and 25 irnmatures of the order Ozihoptera including grasshoppers, locusts and crickets (e.g.,
migratory grasshoppers (e.g., Melanophis sangiiinipes Fabricius, M. diffei'eJitialis Thomas), American grasshoppers (e.g., Schistocerca americana Drury), desert locust (Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), house cricket (Acheta domesticus Linnaeus), mole crickets (Gryllotalpa spp.)); adults and irnmatures of the order 30 Diptera including leafminers, midges, fruit flies (Tephritidae). frit flies (e.g., Oscinella frit Linnaeus), soil maggots, house flies (e.g.. Musca domestica Linnaeus), lesser house flies (e.g., Faimia caniadaris Linnaeus. F.femoralis Stein), stable flies (e.g.. Stomoxys calcinwis Linnaeus), face flies, horn flies, blow flies (e.g., Chiysomya spp.. Phonnia spp.), and other muscoid fly pests, horse flies (e.g., Tabanus spp.), botflies (e.g., Gasnvphilus spp.. Oesfriis ^ sPP-): cattle grubs (e.g.. Hypoderma spp.), deer flies (e.g.. Chiysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera. mosquitoes (e.g., Aedes spp., Anopheles spp.. Culex spp-). black flies (e.g.. Prosmiidium spp., Simulium spp.), biting midges, sand flies, sciarids. and other Nematocera; adults and immahrres of the order

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Thysanoptera including onion thrips (Thrips tabaci Lindeman) and other foliar feeding thrips; insect pests of the order Hymenoptera including ants (e.g.. red carpenter ant (Camponotus femigineus Fahricius), black carpenter ant {Camponoiuspennsylvanicus De Geer), Pharaoh ant (Monomoriumpharaonis Linnaeus),, little fire ant (Wasmannia auropwxctata Roger), fire ant (Solenopsis geminata Fabricius), red imported fire ant (Solenopsis invicta Buren), Argentine ant (Iridomynnex humilis Mayr), crazy ant (Paratrechina longicornis Latreille), pavement ant (Tetramorium caespitum Linnaeus), cornfield ant (Lasius alienus Forster), odorous house ant (Tapinoma sessile Say)), bees (including carpenter bees), hornets, yellow jackets and wasps; insect pests of the order Isoptera including the eastern subterranean termite (Reticulitennes flavipes Kollai"), western subterranean termite (Reticulitermes hespems Banks), Formosan subterranean termite (Coptotermes formosanus Shiraki), West Indian drywood termite (Incisitermes immigi-ans Snyder) and other termites of economic importance,- insect pests of the order Thysanura such as silverfish (Lepisma saccharina Linnaeus) and firebrat (Thennobia domestica Packard); insect pests of the order Mallophaga and including the head louse (Pediculus humanus capitis De Geer), body louse (Pedicuhis humanus humanus Linnaeus), chicken body louse (Menacanthus stramineus Nitszch), dog biting louse (Trichodectes cams De Geer), fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus ewysternus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and chewing parasitic lice that attack man and animals; insect pests of the order Siphonoptera including the oriental rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felislouche), dog flea (Ctenocephalides canis Curtis), hen flea (Ceratophyllus gallinae Schrank), sticktight flea (Echidnophaga gallinacea Westwood), human flea (Pulex irritans Linnaeus) and other fleas afflicting mammals and birds. Additional arthropod pests covered include: spiders in the order Araneae such as the brown recluse spider (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus). Activity also includes members of the Classes Nematoda, Cestoda, Trematoda, and Acanthocephala including economically important members of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida such as but not limited to economically important agricultural pests (i.e. root knot nematodes in the genus Meloidogjme, lesion nematodes in the genus Pratylenchus\ stubby root nematodes in the genus Trichodoms. etc.) and animal and human health pests (i.e. all economically important flukes, tapeworms, and roundworms, such as Sfrongylus vulgaris m horses, Toxocara canis in dogs. Haemonchus conforms in sheep. Dirofilaria immitis Leidy in dogs. Anoplocephalapenbliata m horses. Fasciola hepatica Linnaeus in ruminanrs. etc.).

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Compounds of the invention show particularly high activity against pests in the order Lepidoptera (e.g., Alabama argillacea Hiibner (cotton leaf worm), Archips argyrospila Walker (fruit tree leaf roller). A. rosana Linnaeus (European leaf roller) and other Archips species. Chilo suppressalis Walker (rice stem borer). Cnaphalocrosis medinalis Guenee (rice 5 leaf roller), Crambus caliginosellus Clemens (corn root webworm), Crambus tet&rellus Zincken (bluegrass webwoim), Cydiapomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vUtella Fabricius (spotted bollworrh), Belicoverpa armigera Hubner (American bollworm);, Helicoveipa zea Boddie (corn earwonn), Heliathis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (sod 10 webworm), Lobesia botrana Denis & Schiffermiiller (grape berry moth), Pectinophora ■ gossypiella Saunders (pink bollworm), Phyllocnistis citrella Starnton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly)., Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (diarn.ondback moth), Spodoptera exigiia Hiibner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), 15 Spodoptera fmgiperda J. E. Smith (fall armyworm), Trichoplusia ni Hubner (cabbage looper) and Tuta absoluta Meyrick (tomato leafminer)). Compounds of the invention also have commercially significant activity on members from the order Homoptera including: Acyrthisiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphispomi 20 De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kalteubach (foxglove aphid), Chaetosiphonfragaefolii Cockerell (strawberry aphid), Diuraphis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dys aphis plantagima Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus prion Geoffroy (mealy plum aphid), Lipaphis eiysimi Kaltenbach (turnip 25 aphid), Metopolophium durhodum Walker (cereal aphid), Macrosipum euphorbiae Thomas (pqtato aphid), Myzuspersicae Sulzer (peach-potato aphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphumpadi Linnaeus (bird cherry-oat aphid), Schizaphis gramimim Rondani (greenbug), Sitobion avenae Fabricius (English 30 grain aphid), Therioaphis maculaia Buckton (spotted alfalfa aphid), Toxoptera aurantii
Boyer de Fonscolornbe (black citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxera devastat?'Lx Pergande (pecan phylloxera); Bemisia tabaci Gerxoadius (tobacco whitefly. sweetpotato whitefly), Bemisia argentifolii Bellows & Perring (silverieaf whitefly), Dialeurodes cifri Ashmead (citrus whitefly) and 3:> Trialeurodes vaporarionon Westwood (greenhouse whitefly); Empoasca fabae Harris
(potato leafhopper), Laodelphax srriatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatiis Forbes (aster leafhopper). Nephotettix cinticeps Uhler (green leafhopper). Nephotetiix nigropictus StU (rice leafhopper).. Nilapawata lugens Stil (brown planthopper).

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Peregrinus inaidis Ashmead (com planthopper). Sogaiellafurcifera Horvatk (white-backed planthopper), Sogatodes orizicola Muir (rice delpliacid): Typhlocybapomaria McAtee white apple leafhopper, Eiyihroneoura spp. (grape leafhoppers); Magicidada septendecini Linnaeus (periodical cicada); Iceiyapurchasi Maskell (cottony cushion scale), 5 Ouadraspidiotiis pemiciosus Comstock (San Jose scale); Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsyllapyricola Foerster (pear ps3'lla)3 Trioza diospyri Ashmead (persimmon psylla). These compounds also have activity on members from the order Hemiptera including: Acrosiernum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus leucopterus leucoptenis Say (chinch 10 bug), Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturelhis Heirich-Schaffer (cotton stainer), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug). Graptosthetus spp. (complex of seed bugs), Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus lineolaris Palisot de Beauvois (tarnished plant bug), Nezara viridula Linnaeus (southern 15 green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insect orders controlled by compounds of the invention include Thysanoptera (e.g., Frankliniella occidentalis Pergande (western flower thrip), Scirthothrips citri Moulton (citrus thrip), : Sericothrips variabilis Beach (soybean thrip), and Thrips tabaci Lindeman (onion thrip); and 20 the order Coleoptera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle),
Epilachna varivestis Mulsant (Mexican bean beetle) and wireworms of the genera Agriotes, Athous or Limonius).
Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including insecticides, fungicides, nematocides. bactericides, 25 acaricides, growth regulators such as rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural utility. Thus compositions of the present invention can further comprise a biologically effective amount of at least one additional biologically k active compound or agent. .Examples of such biologically active compounds or agents with which compounds of this invention can be formulated are; insecticides such as abamectin, acephate, acetamiprid, amidoflumet (S-1955), avermectin, azadn-achtin, azinphos-methyl, bifenthrin. binfenazate, buprofezin, carbofuran. chlorfenapyr. chlorfluazuron. chlorpyrifos. chlorp5Tifos -methyl, chromafenozide, clotnianidin. cyfluthrin, beta-cyfiuthrin, cyhalothrin. 2 lambda-cyhalothrin, cypermethrm, cyromazine. deltamethrin, diafenthiuron, diazinon. diflubenzuron, dimethoate, diofenolan. emamectin, endosulfan. esfenvalerate. erhiprole. fenothicarb, fencxycarb, fenpropathrin. fenproximate, fenvalerate. fipronil flonicamid, fiucythrinate. tau-fluvalinate. fiufenerim (UR.-50701). flufenoxuron, fonophos. halofenoside,

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hexaflumuron, imidacloprid, indoxacarb. isofenphos, lufemiron, malathion, metaldehyde, methamidophos, methidathion. methomyl. methoprene. methoxychlor, monocrotophos, methoxyfenozide. nithiazin, novaluron, noviflumuron (XDE-007), oxanryl. parathion. parathion-niefhyl. pennethrin,. phorate, phosalone, phosmet phosphamidon, pirimicarb, 5 profenofos, pymetrozine, pyridalyl, pyriproxyfen, rotenone, spinosad, spiromesifk (BSN 2060), sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos. tefrachloraaphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-s odium, tralomethrin, trichdorfon and triflumuron; fungicides such as acibenzolar, azoxystrobin, benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), broniuconazole, carpropamid. captafol, captan, 10 carbendazim, chloroneb, chlorothalonil, copper oxy chloride, coppei-salts, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, (»S)-3,5-dichloro-iV:-(3-cnloro-l-ethyl-l-methyl-2-oxopropyl)-4-methylbenzamide (RH 7281), diclocymet (S-2900), diclomezine, dicloran, difenoconazole, (6)-335-o^hydro-5-methYl-2-(methylthio)-5-phenyI-3-(phenylainino)-4i^-imidazol-4-one (RP 407213), dimethomorph, drmoxystrobin, diniconazole, dirriconazole-M, 15 dodine, edifenphos, epoxiconazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fencaramid (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ffuazinam, fludioxoniL ftametover (RPA 403397), fmmorf/flumorlin (SYP-Ll 90), fluoxastrobin (HEC 5725), fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl, furametapyr (S-82658), hexaconazole, ipconazole, iprobenfos, 20 iprodione, isoprotlriolane, kasugamycin, iresoxim-methyl, mancozeb, maneb, mefenoxam, mepronil, metalaxyl, metconazole, metommosh"obh^fenoniinostrobin (SSF-126), metrafenone (AC 375839), myclobutanil, neo-asozin (fenic methanearsonate), nicobifen ■ (BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propamocarb, propiconazole, proquinazid (DPX-KQ926), prothioconazole (JAU 6476), 25 pjaifenox, pyraclostrobin, pyrimethanil, pyroquilon, quinoxyfen, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazole, thifluzainide, thiophanate-methyl, thiram, tiadinil, tiiadimefon, triadimenol, tricyclazole, trifloxystrobin, triticonazole, vaiidamycin and vinclozolin; nematocides such as aldicarb, oxamyl and fenamiphos; bactericides such as streptomycin; acai'icides such as amitraz, chiaomethionat, chlorobenzilate, cyhexatin, 30 dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thwingiensis including ssp. aizawai and kursiaki, Bacillus thuringiensis delta endotoxin. baculovims, and entomopathogenic bacteria, virus and fungi.
A general reference for these agricultural protectants, is The Pesticide Manual, J 2th 35 Edition, C. D. S. Tom-fin, Ed., British Crop Protection Council, Farnharn,' Surrey, U.K., 2000.
Preferred insecticides and acaricides for mixing with compounds of this invention include pyrethroids such as cypermethim cyhalothrin. cyfluthrin and beta-cyfluthrin.

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esfenvalerate, fenvalerate and todomethrin: carbamates such as fenothicarb; methomyL oxamyl and thiodicarb: neonicotinoids such as clothianidin. imidacloprid and thiacloprid,' neuronal sodium channel blockers such as indoxacarb. jnsecticidal macrocyclic lactones such as spinosad, abamectin, avermectin and emamectin: y-aminobutyric acid (GAB A) 5 antagonists such as endosulfan, ethiprole and fipronil; jnsecticidal ureas such as flufenoxuron and triflumuron, juvenile hormone mimics such as diofenolan and pyriproxyfen; pymetrozine; and amitraz. Preferred biological agents for mixing with compounds of this invention include Bacillus thuringiensis and Bacillus thuringiensis delta endotoxin as well as naturally occurring and genetically modified viral insecticides including 10 members of the family Baculoviridae as well as entomophagous fungi.
Most preferred mixtures include a mixture of a compound of this invention with cyhalothrin; a mixture of a compound of this invention with beta-cyfluthrin; a mixture of a compound of this invention with esfenvalerate; a mixture of a compound of this invention with methomyl; a mixture of a compound of this invention with imidacloprid; a mixture of a 15 compound of this invention with thiacloprid; a mixture of a compound of this invention with indoxacarb; a. mixture of a compound of this invention with abamectin; a mixture of a compound of this invention with endosulfan; a mixture of a compound of this invention with ethiprole; a mixture of a compound of this invention with fipronil; a mixture of a compound of this invention with flufenoxuron; a mixture of a compound of this invention with 20 pyriproxyfen; a mixture of a compound of this invention with pymetrozine; a mixtm-e of a compound of this invention with amitraz; a mixture of a compound of this invention with Bacillus thuringiensis and a mixture of a compound of this invention with Bacillus thuringiensis delta endotoxin.
In certain instances, combinations with other invertebrate pest control compounds or 25 agents having a similar spectrum of control but a different mode of action will be
particularly advantageous for resistance management. Thus, compositions of the present invention can further comprise an biologically effective amount of at least one additional invertebrate pest control compounds or agents having a similar spectrum of control but a different mode of action. Contacting a plant genetically modified to express a plant 30 protection compound (e.g., protein) orthe locus of the plant with a biologically effective amount of a compound of invention can also provide a broader spectrum of plant protection and be advantageous for resistance management.
Invertebrate pests are controlled and protection of agronomic, horticultural and specialty crops, animal and human health is achieved by applying one or more of the 35 compounds of this invention, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. Thus: the present invention further comprises a method for the control of foliar- and soil-inhabiting invertebrates and protection

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of agronomic and/or nonagronomic crops, comprising contacting the invertebrates or their environment with a biologically effective amount of one or more of the compounds of the invention, or with a composition comprising at least one such compound or a composition comprising at least one such compound and an effective amount of at least one additional 5 biologically active compound or agent. A preferred method of contact is by spraying. Alternatively, a granular composition comprising a compound of the invention can be applied to the plant foliage or the soil. Compounds of this invention are effective in delivery through plant uptake by contacting the plant with a composition comprising a compound of this invention applied as a soil drench of a liquid formulation, a granular formulation to the 10 soil, a nurs ery box treatment or a dip of transplants. Other methods of contact include
application of a compound or a composition of the invention by direct and residual sprays, aerial sprays, seed coats, microencapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others.
The compounds of this invention can be incorporated into baits that are consumed by
15 the invertebrates or within devices such as traps and the like. Granules or baits comprising
between 0.01-5% active ingredient, 0.05-10% moisture retaining agent(s) and 40-99%
vegetable flour are effective in controlling soil insects at very low application rates,
particularly at doses of active ingredient that are lethal by ingestion rather than by direct
contact.
20 The compounds of. this invention can be applied in their pure state, but most often
application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil 25 concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butpxide often enhance compound efficacy.
The rate of application required for effective control (i.e. "biologically effective amount") will depend on such factors as the species of invertebrate to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding 30 behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of aboutO.01 to 2kg of active ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.0001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 ma/square meter but as little as 5^ 0.1 mg/square meter may be sufficient or as much as 150 nag/square meter may be required. One skilled in the art can easily determine the biologically effective amount necessary for the desired level of invertebrate pest control.

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The following Tests in the Biological Examples of the Invention demonstrate the efficacy of methods of the invention for protecting plants from specific arthropod pests. "Control efficacy" represents inhibition of arthropod development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds 5 is not limited, however, to these species. See Index Table A for compound descriptions. The following abbreviations are used in the Index Table which follows: t is tertiary, n is normal, /'is is o, s is secondary, c is cyclo, Me is methyl, Et is ethyl, Pr is propyl and Bu is butyl; accordingly i-?r is usupiopyl, s-B\iis secondary butyl, etc. Tbeabbteviatioxi "Ex." stands for "Example" and is followed by a number indicating in which example the 10 compound is prepared.
INDEX TABLE A

R1, R5, and R8 are H, except where indicated; B is 0, except where indicated. "CN" is bonded through
carbon, not nitrogen; for example "CN-Ph" specifies cyanophenyl, not isocyanopheiryl

Compound R3 R2 R4,R5 R6 *7 m.p. (°C)
1 i-Pr H 2-Me CF3 CH3 200-204
2 (Ex.1) i-Pr H 2-Me CF3 Et 123-126
j i-Pr ff 2-C1 CF3 CH3 233-235
4 t-Bu H 2-Me • CF3. Et 215-218
5 i-Pr H 2-Me CH3' Ph 238-239
6 i-Pr H 2-Me CH3 CH3 206-208
7 i-Pr H 2-Me CH3 CH2CF3 246-248
8 i-Pr ' H 2-C1 Et CF3 235-237
9 i-Pr H 2-Me CH3 CB3,RsisCl 205-207
IQ i-Pr H 2-Me GR3 4-CF3-Pk 256-25?,
U i-Pr H 2-Me CH3 2-CF3-Ph 204-206
12 f~Bu H 2-Me CH3 Ph 236-238
13 i-Pr H 2-F CH3 Ph 227-229
14 ;-?r H 5-F CH3 Ph 209-211
IS i-Pr H 2-Cl CH3 Ph . 233-234

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Compound 16 17 18 19 (Ex. 2) 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 ■ 40 41 42 43 44 45 46 47 4$ 49 52
^4

101

1
RJ R2 R4, R5 ' R6
i-Pr H H CH3
i-Pr H 2-NO2 CH3
i-Pr H 2-Cl CF3
i-Pr H 2-Me CF3
i-Er H 2-1 CH3
i-Pr H 2-1 CH3
H H 2-Me CH3
Et Et 2-Me CH3
/-Bu H 2-Cl CF3
i-Pr H 2-1 CF3
/-Bu H 2-1 CF3
i-Pr H 2-Me CH3
i-Pr H 2-Br CF3
i-Pr H 2-Br CH3
i-Pr H 2-Me CF3
i-Pr H 2,5-di-Cl CF3
i-Pr, B is S H 2-Me CF3
i-Pr H 2-Me CF3
i-Pr H 2-Cl CF3
i-Pr H 2-Me CF3
i-Pr H 2-Cl CF3
i-Pr H 2-Cl CF3
i-Pr H 2-Me CF3
i-Pr H 2-Me CF3
i-Pr' H 2-Me CF2CF3
i-Pr H 2-Cl CF2CF3
/-Bu H 2-Cl CF7CF3
" i-Pr H 2-Br CF2CF3
i-Pr H 2-Me CF3
i-Pr H 2-Cl CF3
i-Pr H 2-Me CF3
i-Pr H 2-Cl CF3
i-Pr H 2-Me CF3
i-Pr H 2-Cl CF3
i-Pr H 2-CF3 CF3
i-Pr H 2-Cl CF3
V.Pr H 2-Me CF3

R7 Ph Ph Ph Ph Ph 2-CF3-Ph Ph Ph Ph Ph Ph /-Bu Ph Ph 2-pyridinyl Ph Ph 2-Cl-Ph 2-Cl-Ph 4-Cl-Ph 4-Q-Pt 2-pyridinyl 2-pyrimidinyl 2-(3-CH3-pyridmy1) Ph Ph Ph Ph 3-a-Ph 3-Cl-Ph 2-F-Ph 2-F-Pb 4-F-Ph 4-F-Pb Ph i-Pr 3-F-Ph

m.p. (°Q
215-217
236-237
240-242
260-262
250-251
251-253
253-255
•182-184
232-234
271-273
249-250
210-211
257-259
246-247
237-238
>250 169-172 208-209 234-235 289-290 276-278 239-240 205-208 183-187 231-232 206-207 212-213 219-222 278-280 272-273 217-218 220-221 269-270 279-280 247-249 255-258 277-27S

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Compound R3 R2 R4, R5 R6 R/ ntp. (°C)
55 i-Pr H 2-a CF3 3-F-Ph 256-257
. 56 i-?x H 2-Me CF3 2-CF3-PI1 215-216
57 i-Er H 2-a CF3 2-CF3-PI1 230-231
58 i-Pr H 2-Me CF3 2-Br-Ph 207-208
59 i-Pr H. 2-a CF3 2-Br-Ph 239-240
60 i-Pr H 2-OCH3 CF3 ' Ph 215-216
61 i-Pr H 5-a CF3 2-(3-CH3-pyridinyl) 224-225
62 i-Pr H 5-Me CF3 2-(3-Cl-pyridinyl) 179-181
63 • j-Bu H 2-a ■ CF3 Ph >240
64 c-Pr H 2-a CF3 Ph >240
65 Et H 2-a CF3 Ph >240
66 r-Bu H 2-CF3 CF3 Ph 230-233
61 Et H 2-CF3 CF3 ?b 246-249
68 CH(CH3)CH2SCH3 H 2-CF3 CF3 Ph- 215-217
69 CH(CH3)CH2OCH3 H 2-CF3 CF3 Ph 220-223
70 i-Pr H s-a CF3 2-(3-Cl-pyridinyl) 230-233
71 i-Pr H 5-Me CF3 2-thiazolyl 201-203
72 i-Pr ■H 5-Me CF3 2-pyrazinyl 252-253
73 i-Pr H 5-Me CF3 4-pyridinyl 224-228
74 i-Pr H 2-Me CF3 /-Pr 236-243
75 i-Pr H 2-Me CF3 2-CH3-Ph 211-212
76 i-Pr H 2-a CF3 2-CH3-Ph 232-234
77 /-Pr H 2-Br CF3 2-Cl-Ph 247-248
78 r-Bu H 2-Me CF3 2-Cl-Ph 216-217
'9 (Ex. 3) i-Pr H 2-Me CF3 2-(3-CF3-pyridinyI) 227-230
80 CH2CH2C1 H 2-Cl CF3 Ph 237-242
81 CH2CH2CH2a H 2-a CF3 Ph . 233-239
82 CH(CH3)C02CH3 H 2-a CF3 Ph 221-222
S3 CH(2-Pr)C02CH3 (5 configuration) H 2-a CF3 Ph 212-213
84 i-Pr H 2-Me CF3 2,6-di-Cl-Ph 267-268
35 :-Pr H 2-Cl CF3 2,6-di-Cl-Ph 286-287
86 i-Pr H 2-Me Br Ph 253-255
87 i-Pr H 2-Cl Br Ph 247-248
88 i-?r H 2-Me CF3 i'-Bu 205-210
89 i-Pr H 2-Me CF3 ca2Ph 235-237
' 90 i-Pr. H 2-Me CF3 2-(3-CH30-pyriQiiiyi) 221-222

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1
Compound R-1 R2 R4,R5 R6 R7 m.p. C°C)
91 i-Pr H 2-Me CF3 3-pyridmyi 260-261
92 i-Pr H 2-Me CF3 4-quinolio.yl >260
93 i-Pr H 2-Me CN 2-(3-CI-pyridinyI) 203-2Q4
94 i-Pr H 2-Me CF3 2,4-di-F-Ph 245-246
95 i-Er H 2-C1 CF3 2,4-di-F-Ph 252-253
96 i-Pr H 2-Me CF3 2-Et-Ph 207-209
97 i-Pr' H 2-CI CF3 2-Et-Ph 221-222
98 i-Pr H H CF3 2-Cl-Ph 206-207
99 A-Bu H H CF3 2-CI-PJi 197-198
100 CH(CH3)CH2OCH3 H H CF3 2-Cl-Ph 145-148
101 CH(CH3)CH2SCH3 H H CF3 2-Cl-Ph 158-160
102 CH(CH3)CH2SCH3 H 2-CI CF3 Ph 184-186
103 CH(CH3)CH2OCH3 H 2-CI CF3 Ph 217-218
104 /i-Pr H 2-CI CF3 Pb 247-248
105 i-Bu H 2-CI CF3 Ph 244-245
106 CH3 H 2-CI CF3 Ph >250
107 i-Fr Me 2-CI CF3 Ph 193-194
108 CH2OCH H 2-CI CF3 Ph ■ >250
109 CH2CH=CH2 H 2-CI CF3 Fh 248-249
110 CH2(2-furanyl) H 2-CI CF3 Ph 246-247
113 i-Pr H 2-Me CF3 4-(3,5-di-a-pyridinyI) 239-242
114 i-Pr H 2-CI CT3 4-(3,5-di-Cl-P3'ridinyl) 229-231
115 CH(CH3)CH2SCH3 H 2-Me CF3 2-Cl-Ph 194-195.
116 CH(CH3)GH2OCH3 H 2-Me CF3 2-Cl-Ph 181-183
' 117 s-B\x H 2-Me CF3 2-Cl-Ph 199-200
118 c-Pr H 2-Me CF3 2-CL-Ph 234-235
119 n-Fr H 2-Me CF3 2-Cl^Fh 222-223
120 ' i-Bu H 2-Me &3 2-CI-Ph 235-237
121 Me H 2-Me CF3 2-Cl-Ph 242-243
122 i-Pr Me 2-Me CF3 2-Cl-Ph 90-93
123 CH2C=CH H 2-Me CF3 2-Cl-Ph 215-216
124 Et H 2-Me CF3 2-Cl-Ph 228-229
125 CH2CH=CH2 H 2-Me CF3 2-Cl-Ph 227-228
126 CH2(2-furanyl) H 2-Me CF3 2-Q-Ph 218-219
127 CH(CH3)CH2SCH3 H 2-Me CF3 Ph 179-180
128 CH(CH3)CH2OCH3 H 2-Me CF3 Ph 219-220
129 s-Bu H 2-Me CF, Fh 244-24-5

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WO 03/015518
105
Compound R3 R2 R4,R5
168 i-Pr H 2-Me-4-Br
169 /-Bu H 2-Cl

PCT/US02/25613
R° R7 m.p. (°C)
CF3 2-F-Ph 232-233
CF3 2-(3-Cl-pyridinyl) 250-251
CF3 2-(3-Cl-pyridinyl) >250



171 Et Et 2-C1
172 Me Me 2-C1
133 Et Et 2-Me
174 Me Me 2-Me
176 i'-Pr H 2-CJ
111 /-Bu H 2-Me-4-Br

178 CH(CH3)CH2OCH3 H 2-Me
179 CH(CH3)CH2SCH3 H 2-Me
180 CH(CH3)CH2OCH3 H 2-C1
181 CH(CH3)CH2SCH3 H 2-C1
182 i'-Pr H 2-Me
183 i-Pr H 2-Cl'
1S4 i-Pr H 2-Me
185 i-?r H 2-Cl
186 i-Pr H 2-Me
187 i-Pr H 2-Cl
1S8 Et Et. 2-Me
189 i-Pr H 2-Me
190 i-Pr H 2-Cl
191 i-Pr H 2-Me
' 192 i-Pr H 2-Me
193 i-Pr H 2-Me
194 i-Pr H 2-Cl
195 ' i-Pr H 2-Me
196 i-Pr H 2-Cl
197 i-Pr H 2-Me
198 Me H 2-Cl
199 CH2OCH H 2-Cl
20& Mr H 2-Me
?01 Et H 2-Me
202 CH2CsCH H 2-Me
203 i-Pr H 2-Me
204 i-Fr H 2-Me


CF3 2-Q-Ph 252-253
CF3 2-Cl-Ph 234-235
cli 2-Q-Ph 237-238
CF3 2-Cl-Ph 225^226
CF3 2-pyraziny! 242-243
CF3 2-Q-Ph >260
CF3 2-(3-Cl-pyridinyl) 176-177
CF3 2-(3-Ci-pyridiayl) 196-197
CF3 2-(3-Cl-pyridiayl) 197-198
CF3 2-(3-Cl-pyrjdinyl) 202-203
CF3 2-I-Pli 221-222
CF3 2-I-Ph 238-240
CF3 2-(HCsC)-Ph . 215-217
CF3 2-(HOC)-Ph 244-246
CF3 2-a-4-F-Ph 203-205
CF3 2-Cl-4-F-Ph 218-219
CF3 2-Cl-Ph 243-247
CF3 2,6-di-Me-Ph 259-260
CF3 2,6-di-Me-Ph 268-269
CF3 2,6-di-Cl-4-CN-Pli *

CF3 2-CN-Ph 225-235
CF3 2-(CF30)-Ph 214-215
CF3 2-(CF30)-Ph 223-224
CF3 2-Br-4-F-Ph 202-203
CF3 2-Br-4-F-P£ 222-223
CF3 2 -(3 -Me-pyrazinyl) 205-207
CF3 2-(3-Cl-pyridiayl) 215-220
Cp3 2-(3-Cl-p}'ridiuyl) 197-198
CF3 2-(.?-a-pyncfiay/J 193-196
CF3 2-(3-Cl-pyridiiiyl) 204-206
2-(3-Cl-pyridinyl) 177-178
CF3 4-(8-Cl-quinolinyl) >250
CF3 4-(2-Me-quiaolinyl) >250

WO 03/015518

PCT/US02/25613

106

Compound R3 R2 R R6 R? m.p..(°C)
205 i-Pr H 2-Cl CF3 4-(2-Me-quinolinyl) >250
206 i-Pr H 2-Me CF3 4-(7-Cl-quinolinyl) >250
207 ;:-Pr H 2,4-Bri CF3 2-Cl-Pii 233-234
208 i-Pr H 2-Br Br 2-Cl-Ph 255-258
209 Me H 2-Me Br 2-Cl-Ph 236-237
210 /-Bu H 2-Cl Br 2-Cl-Ph 260-261
211 Et H 2-Me Br 2-Cl-Ph 254-255
212 /-Bu H 2-Me Br 2-Cl-Ph 259-260
213 c-Bu H 2-Cl CN 2-(3-CI-pyridinyi) 177-1SO
214 (Ex. 4, 5) i-Pr H 2-Me CF3 2-(3-Cl-pyridinyl) 237-239
215 i-Pr H 2-Me CF3 4-(6-Cl-quinolirryl) >250
216 Me Me 2-Me CF3 4-(6-Cl-quinoliiryJ) >250
218 /:-Pr H 2-Q CN 2-(3-Cl-pyridirryl) 195-200
219 /-Bu H 2-Cl CN 2-(3-Cl-pyridinyl) >250
220 Et H 2-Cl CN 2-(3-Cl-pyridinyl) 200-205
221 i-Pr H 2-Cl CF3 2-(3-Me-pyrazinyI) 225-230
222 /-Bu H 2-Cl CF3 . 2-(3-Me-p3'T3z«iy2) 235-240
223 Et H 2-Cl CF3 2-(3-Me-pyrazuryl) 210-220
224 i-Pr . H 2-Me CF3 3-(2-CI-pyridinyi) *
225 i-Pr H 2-Cl CF3 23-di-Cl-Ph 217-219
226 /-Bu H 2-Cl CF3 2,3-di-Cl-Pii 254-256
227 i-Pr H 2-Me CF3 2,3-di-Q-Ph 208-209
228 /-Bu H 2-Me CF3 2,3-di-Cl-Pli 232-233
229 /-Bu H 2-Me-4-Br Br 2-Cl-Ph 239-241
' 230 Me H 2-Me-4-Br Br 2-CI-Ph 150-152
231 Et H 2-Me-4-Br Br 2-Cl-Ph: 223-225
232 i-Pr H 2-Me-4-Br Br 2-Cl-Ph 197-198
233 " Me H 2-Me CF3 2-F-Ph 245-247
234 ■■• CH2C=CH H 2-Me CF3 2-F-Ph 222-227
235 ' Me Me 2-Cl CF3 2-Cl-Ph 234-236
■ 236 CH2C=CH H 2-Me-4-Br Br 2-Cl-Ph 187-188
237 ' i-Pr H 2-Cl CF3 2-(3 -Me-pyiidiayl) 224-225
238 i-Pr H • 2-Cl CF3 2-(3-a-pyridinyl) 230-233
239 i-Pr H 2-Me CF3 2-pyrazinyl 252-253
240 i-Pr H 2-Me CF3 2-thiazolyI 201-203
241 i-Pr H 2-Me CF3 4-pyridinyl 224—228
242 i-Pr H 2-Me CF3 2-(3-Cl-p>'ridiiiyIJ 249-250

WO 03/015518

PCT/US02/25613

107

Compound 243 i-Pr R2 H R4:R5 2-Me. CF3 R7 PkR?isCH3 *-p.(°C) 246-248
244 245 Me i-Pr Me H 2-Me 2-Me, CF3 CF3 2-Cl-Ph CH=CHCH3 234-235 225-228
246 i-Pr H 2-Me CF3 2-Cl-6-M6-Hi
247 i-Pr H 2-C1 CF3 2-Cl-6-Me-Pli
248 i-Pr- H 2-C1 CF3 4-CN-Pb. *
249 i-Pr H 2-C1 ■ CF3 2,6-di-Cl-4-CN-Ph *
250 i-Pr H 2-Cl CF3 2-Cl-4-CN-Ph *
251 252 i-Pr i-Pr H H 2-C1 2-Me CN CF3 Ph 4-CN-Ph * 271-272
253 i-Pr H 2-Me CF3 3-CN-Ph 263-264
254 i-Pr H 2-Me ■ CF3 2-Cl-4-CN-Prj *
255 i-Pr H 2-Me CN . Fh #
256 i-Pr H 2-Cl CF3 3-CN-Ph Hf
257 i-Pr H 2-Me CF3 2-Me-4-F-Ph 204-206
258 i-Pr H 2-Cl CF3 2~Me-4-F-?h 212-213
259 i-Pr H 2-Me CF3 2,4-di-Me-Pii 189-190
260 f-Bu H 2-Me CF3 2,4-di-Me-Ph 197-198
261 t-Bu H 2-Cl CF3 2,4-di-Me-Pii 234-235
262 i-Pr H 2-Me CF3 /7-Bu, R8 is CI 95-98
263 Me H 2-Cl CF3 4250
264 Et H 2-Cl CF3 4-(7-Cl-quiiioliriyl) >250
265 CH2CH=CH2 H 2-Cl CF3 4-(7-Cl-quinolinyl) >250 ,
266 i-Pr H 2-Cl CF3 4-(8-Cl-quinolinyl) >250
• 267 i-Pr H 2-Me CF3 2-(3-CN-pyridinyl) 237-239
26S i-Pr H 2-Me CF3 1 -(6-Cl-isoquinolinyI) >250
269 t-Bu H 2-Me CF3 i-(6-Cl-isoquinoIinyl) 227-229
270 ' Me Me 2-Me CF3 l-(6-Cl-isoquinoIinyI) >250
271 i-Pr H 2-Me CF3 2-Cl-4-CN-6-Me-Pli *
272 i-Pr H 2-Me-4-Br Br 2-Q-Ph 1S7-18S
273 CH2CH(OCH3)2 H 2-Me CF3 2-CI-Ph 205-207
274 CH2CH(OCH3)2 Me 2-Me CF3 2-Q-Eh 185-190
275 CH2CH2CH(OCH3)2 H 2-Me &3 2-CI-Ph 85-90
276 Me H 2-Me CF3 2,6-di-Cl-Ph 280-282
277 Et H 2-Me CF3 2,6-di-Q-Ph 274-275
278 r-Bu K 2-Me if J t-Bu H 2-Cl CF3 2,6-di>Cl-Ph 290-291

WO 03/015518

PCT/US02/25613

108

Compound R R2 R4,R5 R6 R7 in.p. (°Q
280 i-Fr H 2-Me H 2-CI-Pli *
281 z-Pr H 2-Me H 2-Me-Ph *
282 i-Pr H 2-Me H 2-F-Fb *
283 i-Fr H 2-Me Br 2-(3-Cl-pyridinyl) 206-209
284 CH2CH2CN H 2-Me CF3 2-a-Pb 189-195
285 z-Pr H 2-Me CN 2-Cl-Pb *
286 z-Pr H 2-Me CF3 2-(3-CH30-pyra2diiyl] 1 195-200
287 z-Pr H 2-Me Br 2,6-di-Cl-Ph 265-267
288 /-Bu H 2-Me Br 2,6-di-Cl-Ph 282-284
289 z'-Fr H 2-Cl Br 2,6-di-Cl-Ph 277-279
290 /-Bu H 2-Cl Br 2,6-di-Cl-Ph 296-298
291 z-Pr H 2-Me Br 2-Cl-4-F-Ph 236-238
292 /-Bu H 2-Me Br 2-CM-F-Hi 249-250
293 i-Fr H 2-Cl Br 2-C1-4-F 176-177
294 /-Bu H 2-Cl Br 2-Cl-4-F-Ph 257-258
295 z-Pr H 2-1 Br 2-C1-4-F 227-229
296 c-Bu H 2-Cl CF^, 2-(3-Cl-pyridinyl) 230-231
297 z-Pr H 2-Cl Br 2-(3-Cl-pyridinyl) 231-234
298 /-Bu H 2-Cl Br 2~(3-Cl-pyridinyl) 245-248
299 Et H 2-Cl Br 2-(3-Cl-pytidiuyl) 219-222
300 Et H 2-Me Br 2-(3-Cl-pyridiiyl) 217-220
301 /-Bu H 2-Me Br 2-(3-Cl-pyridinyl) 237-240
302 CH2CN H 2-Me Br 2-(3-Cl-pyridinyl) 227-229
303 /-Bu H 2-Me CN 2-(3-Cl-pyridiD.yl) 215-225
■ 304 c-Bu H 2-Me CN 2-(3-Cl-pyridinyl) 105-115
305 c-Bu H 2-Me CF3 2-(3-Cl-pyridinyl) 187-190
306 c-pentyl H 2-Me CF3 2-(3-Cl-pyridinyI) 190-195
307 ' J-BU H 2-Me CF3 2-(3-Cl-pyridinyl) 170-180
308 c-pentyl H 2^CI CF3 2-(3 -Cl-pyridiuyl) 215-222
309 j-Bu H 2-Cl CF3 2-(3-Cl-pyridinyl) 210-220
313 z-Pr H 2-Me CI 2-(3-Cl-pyridinyl) 204-206
314. /-Bu H 2-Me CI 2-(3-Cl-pyridinyl) 210-213
315 /-Bu H 2-Cl a 2-(3-Cl-pyridinyl) 237-239
316 i-Pr H 2-Cl Cl 2-(3-Cl-pyridinyl) 159-162
317 CH(CH3)2CH2CH3 H 2-Me . CN 2-(3-Cl-pyridinyl) 165-175
318 c-kexyl H 2-Cl CF3 2-(3-Cl-pyridinyl) 250-260
319 CH(CH3)2CH2CH3 P 2-Cl CF3 2-(3-CI-pyridinyl) 200-210

WO 03/015518 PCT/US02/25613
109

Compound R3 R? R4,R5 R6 R7 m.p. (°C)
320 /-Pr H •2,4-di-Me CF3- 2-Cl-Fb 239-240
321 /-Pr H 2-Me CF3 . 2-C1-5-CN-PI1 *
322 /-Pr H 2-Me H 2-(3-Cl-pyridin}'I) 111-115
323 /-Pr H 2-Me CF3 . 2-C02Me-Pli
324 /-Pr H 2-Me-4-Br CF3 2,6-di-Cl-Fli 230-233
325 r-Bu H 2-Me-4-Br CF3 2,6-di-Cl-Ph >250
326 Me H 2-Me-4-Br CF3. 2,6-di-Cl-Ph ' 228-230
327 CH2CN H 2-Me-4-Br CF3 2,6-di-Cl-Ph 228-230
328 /-Pr H 2,4-di-CI CF3 2-Cl-Fh 223-224
329 /-Pr H 2-Me CF3 2-CI-4-CF3-6-CI-PI1 206-207
330 /-Pr H 2-Me CF3 S-(I,3-di-Me-4-Cl- 231-232
/ pyrazolyl)

331 /-Pr H 2-Me CF3 2-(4,6-di-Me-pyrimidinyl) 220-222
332 /-Pr H 2-C1 CF3 2-(4,6-di-Me-pyriuiidinyl) 152-154
333 t-Bu H 2-Me CF3 2-(4I6-di-Me-pyriDiidinyl) 124-127
334 r-Bu H 2-C1 CF3 2-(4,6-di-Me-pyriinidinyl) 179-182
335 ■ /-Pr H 4-1 CF3 2-CI-Pli 218-219
336 /-Pr H 2-Me-4-OCH3 CF3 2-(3-Cl-pyridinyl) 187-188
337 /-Pr H 2-Me CF3 2-F-4-a-5-(i-PrOJ-Hi 214-216
338 CH2CN H 2-Me CI 2-(3-Cl-pyridinyl) 190-195
339 Et H 2-ci CF3 2-(3-Cl-pyridinyl) 217-219
340 /-Pr H 2-Me-4-Br CF3 2,3-di-Cl-Ph >250
341 /-Pr H 2-Me CF3 2,5-di-a-Pli >250
342 /-Pr H 2-CM-Br CF3 2,3-di-Cl-Ph 251-253
343 CH2CN H 2-C1 CF3 2,3-di-Cl-Ph 185-190
344 CH2CH2SCH2CH3 H 2-Me •CF3 2-(3-Cl-pyridinyl) 197-200
345 CH2CH2CH9SCH3 H 2-Me CF3 2-(3-Cl-pyridinyl) 185-190
346 CH2(2-furanyl) H 2-Me CF3 2-(3-Cl-pyridinyl) 210-215
347 CH2C(=CH2)CH3 H 2-Me CF3 2-(3-CI-pyridinyI) 225-229
348 CH2CH2OCH3 H 2-Me CF3 2-(3-Cl-pyridinyl) 215-218
349 CH2CH2CH2OH H 2-Me CF3 2-(3-CI-pyridinyI) 210-212
350 CH7CH7CI H 2-Me CF3 2-(3-Cl-pyridinyl) 206-216
331 CH2CH2OH H 2-Me CF3 2-(3-Cl-pyridinyJ) 217-220
352 CH(CH3)CH2OH H 2-Me CF3 2-(3-Cl-pyridinyl) 110-115
353 CH2CH(Br)CH2Br H 2-Me CF3 2-(3 -Cl-p3Tidiiiyl) 217-220
354 CH9CO2CH3 H 2-Me CF3 2-(3-Ci-pyridinyl) >250
355 CH2CH(OH)CH2OH H 2-Me CF3 2-(3-Cl-pyridinyI) >250

WO 03/015518

PCT/US02/25613

110

Compoun d R3 R2 R4: R5 R6 B? m.p. (°C)
356 CH2CH2CH2a H 2-Me CF3 2-(3-Cl-pyridinyl) 207-212
357 CH(CH2OH)CH2CH: j H 2-Me CF3 2-(3-Cl-pyridinyl) 173-176
358 i-Pr H 2-Me CF3 2-(5-CF3-pyridinyl) 270-275
359 ' Et H 2-Me CF3 2-(3,6-di-Me-pyra2iiiyi; 210-215
360 i-Pr H 2-Me CF3 2-(3,6-di-Me-pyraziDyiJ 215-220
361 t-Bv. H 2-Me CF3 2-(3,6-di-Me-pyraziiiyl) 265-270
362 Et H 2-C1 CF3 2-(3,6-di-Me-pyrazin.yl) 214-217
363 i-Pr H 2-C1 CF3 2-(3,6-di-Me-pyra2myl) 215-218
364 i-Pr H 2-Me OCH3 2-Cl-Ph 137-140
365 i-Pr H 2-C1 OCH3 2-Cl-Ph 155-158
^66 i-Pr H 2-Me Me 2-Cl-Pli 151-154
367 i-Fr H 2-C1 Me 2,6-di-Cl-Pli 242-244
368 C3H2CH(OH)CH3 H 2-Me CF3 2-(3-Cl-pyridinyl) 123-125
369 CH2CH(OH)CH2CH3 H 2-Me CF3 2-(3-Cl-pyridinyl) 175-180
' 370 CH2CN H 2,4-di-Br CF3 2-(3-CI-pyridinyl) 142-143
371 c-Pr H 2,4-di-Br CF3 2-(3-CI-pyridinyl) 21-3-214
372 CH2CN H 2,4-di-Cl CF3 2-(3-Cl-pyridinyI) 201-202
373 i-Pr H 2,6-di-Me CF3 2~(3-Cl-pyridinyl) 204-205
374 i-Bu H 2,6-di-Me CF3 2-(3-ClijyridinyI) 242-243
375 /-Bu H 2-Me CF3 2-(5-CF3-pyridinyl) 220-230
376 C(CH3)2CH2OH H 2-Me CF3 - 2-(3-CJ-pyridinyI) 205-210
377 CH2CH2F H 2-Me CF3 2-(3-Cl-pyridinyl) 127-130
378 i-Pr H 2-Me CF3 2-(4-Me-pyriinidinyl) 196-197
379 i-Pr H . 2-C1 CF3 2-(4-Me-pyriinidirryl) 208-210
380 f-Bu H 2-Me CF3 2-(4-Me-pyriirridinyl) 180-182
381 f-Bu H 2-C1 CF3 2-(4-Me-p>iimidiiiyl) 182-184
382 j-Bu H 2-Me CF3 2-(3-Et-pyraziiiyl) 16Q-165
383 " Et H 2-Me CF3 2-(3-Et-pyrazinyl) 185-190
384 i-Pr H 2-Me CF3 2-(3-Et-pyrazinj'l) 180-183
385 CH2CF2CF3 H 2-C1 CF3 2-Cl-Ph 258-260
3S6 r-Bu H 2-Me CF3 2-(3-Et-pyrazinyI) 180-185
387 CH2CF3 H 2-C] CF3 2-Cl-Ph 262-264
388 CH2CN H 2-Me-4-Br CF3 2-(3-Cl-p)Tidinyl) 192-193
3S9 CH(CH3)CH2OH H 2-Me CF3 2-Cl-Ph 203-205
390 i-Pr H 2-Me CI 2-d-Eh 207-209
391 i-Pr H 2-C1 a 2-Ct-Ph 236-237
392 i-Pr H 2-Me 1 2-a-Pb. .liO-i-iO

WO (13/0.15518

PCT/US02/25613

111


Compound R-1 R2 R4,R5
393 j'-Pr H 2-Cl
394 CH(CH3)CH2C1 H 2-Me
395 H H 2-Me
396 i-Pr H 2-Cl
397 t-Bu H 2-Cl
398 j-Pr H 2-Cl

R6 R7' m.p: (°C)
I 2-Cl-Ph . 251-253
CF3 2-Cl-Ph 212-214
CF3 2-(3-Cl-pyridkyI) 217-220
CF-, 4~(5.6-di~Me-pyriinidinyl) 218-220
CF3 4-(5,6-di-Me-pyriimdinyl) 212-214
CF 4-(2,5,6-tri-Me- 162-164

pyrimiditiyl)


399 i-Pr H 2-Me
400 CH2CH(OH)CH3 H 2-Me
401 H H 2-Me
402 CH2CH(C1)CH3 H 2-Me
403 CH2CH2CN H 2-Cl
404 CH2CH2F H 2-Cl
405 CH2CH2CN H 2-Cl
406 i-Pr H 2-Me-4-Br
407 CH2CN H 2-Me-4-CF3
408 /-ft- H 2-Me
409 i-ft: H 2,4-di-Br
410 /-Bu H 2,4-di-Br
411 Me H 2,4-di-Br
412 Et H 2,4-di-Br
413 Me H 2-Me-4-Br
414 . t-Bu H 2-Me-4-Br
415 i-Pr H 2-Me-4-Br
■ 416 Et H 2-Me-4-Br
417 i-Pr H 2-Me
418 Me H 2-Me
419 ' i-Er H 2-Me-4-Cl
420 /-Bu H 2-Me-4-Cl
421 Me H 2-Me-4-Cl
422 Me H 2-Me
423 H H 2-Cl
424 H H 2-Me-4-Br
425 /-Bu ' H 2-Me


CF3 4-(5,6-di-Me-pyriirddinyl) 162-164
CF3 2-Cl-Ph 207-209
CF3 2-Cl-PJi 230-232
CF3 2-Cl-Ph 230-232
CF3 2-(3-Cl-pyridinyl) 215-217
CF3 2-(3-Cl-pyridinyi) 212-214
CF3 2-CUPh *
CN 2-(3-Cl-pyridinyl) *
CF3 2-(3-Cl-pyridrayI) 211-213
CF3 2,5-di-F-Pu 179-181
CN 2-(3-Cl-p)Tidinyl) ije
CN 2-(3-Ci-pyridinyl) » 145-147
CN 2-(3-Cl-pyridiayl) 165-168
CN 2-(3-Ci-pyridinyi) 179-181
Me 2-(3-Cl-pyridinyl) 141-143
Me 2-(3-Cl-pyridroyl) 161-163
Me 2-(3-Cl-pyridinyl) 141-143
Me 2~(3-Cl-pyridinyl) 161-163
Me 2-(3-Cl-pyridinyl) 193-195
Me 2-(3-CI-pyridinyl) 194-196
CN 2-(3-Cl-pyridinyl) 188-190
CN 2-(3-Cl-pyridinyl) 148-151
CN 2-(3-Cl-pyridinyl) 182-184
Br 2-(3-Cl-pyridinyl) 210-212
CF3 2-Cl-Ph 203-205
CF3 2-(3-Cl-pyridinyI) 243-245
CF3 5-(l,3-
pyrazolyl)

426 i-Pr H 2-Cl

CF3 5-(l,3-di-Me-4-CL- 264-266
pyrazolyl)

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R3 R2 R4, R5 R6 R^ ULP. (°C)
/-Bu H 2-CJ CF3 5-(l:3-di-Me-4-CI-
pyrazolyl) 231-232
CH2CN H 2-BM-Mfe CF3 2-(3-Cl-pyridinyl) 149-150
i-Pr H 2-Me-4-Cl a 2-Cl-Ph 130-181
i:-Pr H 2-Me-4-Br Br 2,6-di-Cl-PJi 238-239
*-Er H 2-Cl-4-Me a?3 2-(3-Cl-pyridinyI) 170-171
/-Bu H 2-Cl-4-Me CF.3 2-(3-Cl-pyridinyl) 167-169
Me H 2-Cl-4-Me CF3 2-(3-CI-pyridinyl) 162-164
H ■ H 2-Me-4-Br Br 2-(3-CJ-pyridrayI) 235-237
Me H 5-Cl CF3 '2-(3-Cl-pyridinyl) 207-203
CH2CN H 5-Cl ®3 2-(3-Cl-pyridinyl) 178-179
Me H 5-Me CF3 2-(3-Cl-pyridinyl) 166-167
CH2CN H ■ 5-Me CF3 2-(3-CJ-pyridinyI) 191-192
H H 2-Me-4-Br CF3 2-(3-Cl-pyridkyl) 243-244
i-Pr H 2-Me CF3 4-pyriinidinyl
i-Pr H 2-C1 GF3 4-pyrunidinyl
/-Bu H 2-Me CF3 4-pyrhnidin.yl -
/-Bu H 2-C1 GF3 4-pyriiuidiiiyl
/-Pr H 2,3-di-Me CF3 2-(3-Cl-pyridinyl) 173-175
/-Bu H 2,3-di-Me CF3 2-(3-Cl-pyridiny]) 149-150
Me H 2,3-di-Me CF3 2-(3-Cl-pyridinyi) 164-166
H H 2,3-di-Me CF3 2-(3-CI-pyridinyI) 201-203
H H 2-Cl-4-Br CF3 2-(3-Cl-pyridiayI) 240-242
H H 2-Cl-4-Me CF3 2-(3-Cl-pyridinyl) 223-225
/-Pr H 2-Me CF3 4-(5-Cl-pyrimidmy])
/-Bu H 2-Me CF3 4-(5-Cl-pyriinidinyl)
/-Bu H 2-C1 CFj 4-(5-Cl-pyrimidinyl)
' c-Fr H 2-C1 CT3 2-(3-C]-pyridinyl) 224-228
CH2CN H 2-Me-4-Br Br 2-(3-CJ-pyridinyI) ■ 232-234
CHiCN H ■ 2-Me-4-I CF3 2-(3-Cl-pyridiayl) 221-222
Me H 2,4-di-Cl CF3 2-Cl-Ph 232-233
Et H 2,4-di-Cl CF3 2-Cl-Ph 247-248
/-Bu H 2,4-di-Cl CF3 2-Cl-Ph 223-224
CH2CN H 2;4-di-Cl CF3 2-Cl-Ph 229-231
i-Pr H 2-Me CF3 5-(l-Me-pyrazolyl) 240-241
/-Bu H 2-Me CF3 5-(l-Me-p}iazolyl) 233-234
i-Pr H 2-Q CF3 5-(l -Me-pyrazolyl) 247-248

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11:

Compound R2 R4,R5 R« R7 m:p. (°C)
463 r-Bu H 2-C1 CF3 5-(l-Me-pyrazolyl) 262-263
464 i-Pr H 2-Me CF3 4-(2..6-di-Me-5-a-pyriujidinyl)
465 i-Pr H 2-C1 CF3 4-(2,6^i-Me-5-Cl-pyriraidiiryl)
466 . f-Bu H 2-Me CF3 4-(2;6-di-Me-5-Q-pyriinidinyl)
467 f-Bu H 2-C1 CF3 4-(2,6-di-Me-5-CI-pyriuridinyl)
468 Et H 2-Me CI 2-(3-Cl-pyridinyl) 220-221
469 Me H 2-Me CI 2-(3-Cl-pyridiny]) 217-218
470 CH2OCH H 2,4-di-Br CI 2-(3-Cl-pyridinyl) 199-201
471 CH2OCH H 2-Me-4-Cl CI 2-(3-Cl-pyridinyl) 219-221•
472 H H 2-Me-4-Cl CI 2-(3-Cl-pyridinyI) 231-233
473 H H 2,4-di-Cl CI 2 474 CH2OCH H 2,4-di-Cl CI 2-(3-Cl-pyridinyl) 166-168
475 H H 2-Me CI 2-(3-Cl-pyridinyI) 243-244
476 H H 2-Me-4-I CF3 2 477 CH2CN H 2-M&-4-CI Br 2-(3-Cl-pyridinyI) 225-226
478 CH2CsCH H 2-Me-4-Br CI 2-(3-Cl-pyridiayI) 218-220
479 H H 2-Me-4-Br CI 2-(3-CI-pyridinyI) 224-225
480 H H 2,4-di-Br CI '2-(3-Cl-pyridinyl) . 250-252
481 i-Pr H 2-Me-4-Cl CF3 2-(3-Me-pyridinyl) 228-229
482 Me H 2-Me-4-Cl CF3. 2-(3-Me-pyridinyl) 226-227
' 483 t-Bu H 2-Me CF3 5-( 1 -Me-4-Cl-pyrazolyI) 216-217
484 i-Pr H 2-Me CF3 5-(l-Me-4-Cl-pyrazolyl) 220-221
485 /-Pr H 2-Me-4-(HOCH2), CF3 2-(3-CI-pyridinyl) 199-201
486 CH2CsCH H 2-Me-4-Cl CF3 2-(3-Ci-pyridinyl) 200-202
487 i-Pr, B is S H 2-Me-4-Br CF3 . 2-(3-Cl-pyridinyl) 214-217
483 /-Pr H 2-Me-4-C02Me CF3 2-(3-Cl-pyridinyl) 204-206
4S9 2-R- H 2-Ivfe-4-CONHMe CF3 2-(3-Cl-pyridinyI) 168-170
490 CH(CH3)Pt H H CF3 Me 212-214
491 CH(CH3)Fh H H CF3 Et 202-203
40? GH2CH2N(;-Pr) TT 2-Me CF3 2-Cl-Ph. 188-190

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Compound R3 R- R4. R5 R6 R7 m.p. (°C)
494 i-Pr H 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 197-198
495 i-Pr H 2-Me CF3 2-CH2NHC(=0)CF3-Pli *
496 i-Pr H 2-Me CF3 2-CH2NH2-PliHCI *
497 (Ex, 6) i-Pr H 2-Me-4-Cl CF3 2-(3-Cl-pyridinyl) 196-197
498 i-Pr H 2-Me CF3 234-di-Cl-5-OCH2OCH- 246-249 Ph
499 r-Bu H 2-Me4-Cl CF3 ■A U
2-(3-Cl-pyridinyl) 223-225
500 (Ex. 7) Me H 2-Me-4-Cl CF3 2-(3-Cl-pyridinyl) 148-150
501 i-Pr H 2,4-di-Br CF3 2-(3-Cl-pyridinyl) 192-193
502 t-B\i H 2,4-di-Br CF3 2-(3-Cl-pyridinyl) 246-247
505 CH2CH2OCH2CH2 H
Me 0 H 2-Me CF3 2-(3-Cl-p)TidinyI) 132-135
506
H 2,4-di-Br CF3 2-(3-Cl-pyridiiryl) 162-163
507 OCH(CH3)2 H 2-C1 CF3 2-Cl-Ph 218-219
508 OCH(CH3)2 H 2-CI CF3 2-(3-Cl-pyridinyl) 205-206
509 OCH(CH3)2 H 2-Me CF3 2-(3-Cl-pyridinyl) 210-211
510 OCH(CH3)2 H 2-Me 511 i-Pr H 2-Me CF3 2-CONHMe-Ph *
512 Et ■ H 2,4-di-Br CF3 2-(3-Cl-pyridinyl) 188-189
513 i-Pr H 2,4-di-Cl CF3 2-(3-Cl-pyridinyl) 200-201
514 /-Bu H 2,4-di-C] CF3 2-(3-Cl-pyridinyI) 170472
515 Me H 2,4-di-Cl CF3 2-(3-Cl-p3TidinyI) 155A57
516 Et H 2,4-di-C] CF3 2-(3-Cl-pyridinyI) 201-202
517 f-Bu H 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 247-248
■ 518 Et H 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 192-193
519 i-Pr H 2-Me-4-F Cf3 2-(3-Cl-pyridinyl) 179-180
520 i-Pr H 2-Me-4-Br Br 2-(3-Cl-pyridinyl) 185-187
521 " i-Pr H 2-Me-4-CF3 CF3 2-(3-Cl-pyridinyl) 235-236
522 Et H 2-Me-4-CF3 CF3 2-(3-Cl-pyridiayl) 216-217
523 i-Pr H 2-Me-4-I CF3 2-(3-Cl-pyridinyl) 188-189
524 i-Bu H 2-Me-4-CF3 CF3 2-(3-Cl-pyridinyl) 148-149
525 Me H 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 208-210
526 .i-^r H 2-Br-4-Me CF3 2-(3-Cl-pyridjnyl) 127-128
527 f-Bu H 2-Br-4-Me CF3 2-(3-Cl-pyridinyl) 159-160
528 Et H 2-Br-4-Me CF3 2-(3-Cl-pyridinyI) 224-225
529 Me H 2-Br-4-Me CF3 2-(3-Cl-pyridinyl) 208-209
530 (Ex. 10) i-Pr H 2-Me-4-CJ T5T-
J—'1 2-(3-CI-pyridiayi) 159-151

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Compound ■7
R3 R2 R4,R5 R* R7 rn.p. (°C)
5.11 (Ex. 11} Ms H 2-Me-4-Cl Br 2-(3-CJ-pyridinyI) 162-164
532 /-Bu H 2-Me-4-Cl Br 2-(3-Cl-p}iidinyl) 159-161
533 f-Pr H 2,4-di-Br Br 2-(3-Cl-pyridirryl) 162-163
534 Me H 2,4-di-Br Br 2-(3-Cl-pyridinyl) 166-168
535 /-Bu H 2,4-di-Br Br. 2-(3-Cl-pyridinyl) 210-212
536 /-ft H 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 188-190
537 Me H 2.4-di-a Br 2-(3-Cl-pyridinyl) 179-UO
53 S Me H 2-Me-4-Br Br 2-(3-Cl-pyridinyl) 147-149
539 z-Pr H 2-Cl-4-Br CF3 2-(3-Clrpyridinyl) 200-202
540 f-Bu H 2-Cl-4-Br CF3 2-(3-Cl-pyridinyl) 143-145
541 Me H 2-Cl-4-Br CF3 2-(3-Cl-pyridinyI) 171-173
542 Me H 2-Me-4-Br CF3 2-(3-Ci-pyridinyI) 222-223
543 (Ex. 8) i-Pr H 2-Me-4-Cl CI 2-(3-Cl-pyridinyl) 142-144
544 (Ex. 9) Me H 2-Me-4-Cl CI 2-(3-Cl-pyridinyI) 175-177
545 /-Bu H 2-Me-4-Cl CI 2-(3-Cl-pyridinyl) 163-165
546 i-Pr H 2-Me-4-Br CI 2-(3-Cl-pyridinyl) 152-153
547 Me H 2-Me-4-Br Cl 2-(3-CI-pyridinyi) 140-141
548 /-Bu H 2-Me-4-Br Br 2-(3-C]-pyridinyl) 215-221
549 Me H 2-Me-4-I CF3 2-(3-CI-pyridinyI) 199-200
550 i-Pr H 2,4-di-Br a 2-(3-Cl-pyridinyl) 197-199
551 Me H 2,4-di-Br a 2-(3-CI-pyridinyi) 188-190
552 /-Bu H 2,4-di-Br a 2-(3-Cl-pyridinyl) 194-196
553 Et H 2,4-di-Br Cl 2-(3-Cl-pyridinyl) 192-194
554 i-Pr H 2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 197-199
■ 555 Me H 2,4-di-Cl Cl 2-(3-Cl-pyridinyl) 205-206
556 /-Bu H 2,4-di-Cl a 2-(3-a-pyridinyl) 172-173
557 Et H 2,4-di-Cl Cl 2'(3-Cl-pyridiQ5d) 206-208
558 ' Et H 2-Me-4-Cl a 2-(3-Cl-pyridinyI) 199-200
559 Et H 2-Me-4-Cl CF3 2-(3-Cl-pyridinyI) 163-164
560 • Et H 2-Me-4-I CF3 2-(3-Cl-pyridinyl) 199-200
561 f-Bu H 2-Me-4-I CF3 2-(3-Cl-pyridirryl) 242-243
562 Ex H 2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 194-195
563 Me H 2-Me-4-F CF3 2-(3-a-p3Tidin.vi) 213-214
564 Et H 2-Me-4-F CF3 2-(3-Cl-pyridinyl) 212-213
565 /-Bu H 2-Me-4-F CF3 2-(3-Cl-pyridinyI) 142-143
566 Me H 2-Me-4-F Br 2-(3-Cl-pyridinyl) 214-215
567 Et H 2~VIe-4-F Br 2-(3-Cl-pyridiayl) 204-205

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Compound R~ R2 R4,R5 R6 R7 m.p. (°C)
56S i-Pr H 2-MM-F Br 2-(3-Cl-pvridiayl) 206-208
569 Et H 2-Me-4-Br CI 2-(3-Cl-pyridinyl) 192-194
570 z'-Pr H 2-Me-4-F CI 2~(3-Cl-pyridinyl) 184-186
571 Me H 2-Me-4-F CI 2-(3-Cl-pyridinyl) 180-182
572 Et H 2-Me-4-F CI 2-(3-a-pyridinyl) 163-165
573 /-Bu H ' 2-Me-4-Br CI 2-(3-Cl~pyridinyl) 224-225
574 t-Bu H 2-MB-4-F Br 2-(3-Cl-pyridinyl) 124-125
575 Et H 2,4-di-Br Br 2-(3-Cl-pyridiiiyl) 196-197
576 Me E Z,4-di-C\ Br 2-(3-Cl-pyridinyl) 245-246
' 577 • Et H 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 214-215
57S Et . H 2-Me-4-Br Br 2-(3-Cl-pyridinyl) 194-196
579 Me H 2-Me-4-I Br 2-(3-Cl-pyridinyl) 229-230
580 i-Pr H 2-Me-4-I Br 2-('3-Cl-pyridinyl) 191-192
581 Me H 2-Me-4-CF3 CF3 2-(3-Cl-pyridinyl) 249-250
582 Me H 2-Me-4-I CI 2-(3-Cl-pyridinyl) 233-235
583 Et ■ H 2-Me-4-I CI 2-(3-Cl-pyridinyl) 196-197
584 z-Pr H 2-Me-4-I CI 2-(3-Cl-pyridinyl) 189-190
585 t-Bu H 2-Me-4-I CI 2-(3-Ci~pyridinyl) 228-229
586 Me H 2-Me~4-Cl I 2-(3-Cl-pyridinyl) 208-209
5S7 i-Pr- H 2-Me-4-Cl I 2-(3-Cl-pyridinyl) 183-184
588 H H 2-Me-4-Cl I 2-(3-Cl-pyridinyl) 228-230
589 Me H 2-Me-4-Cl Br 2-CM-F-Ph 250-251
590 H H 2-Me-4-Cl Br 2-CM-F-Ph 229-229
591 i-Pr H 2-Me-4-Cl Br 2-CI-4-F-Ph 189-190
: 592 t-Bu H 2-Me-4-Cl Br 2-CM-F-Fh 247-249
593 i-Pr H 2-Me-4-NCh CF3 2-CI-Ph *
594 ?h H 2-Me-4-Cl CF3 2-(3-Cl-pyridinyl) 243-244
595 2-Me-Ph H 2-Me-4-Cl CF3 2-(3-Cl-pyridinyl) 249-251
596 i-Pr H 2-Me-4-N02 CF3 2-(3 -Cl-pyridinyl) 170-172
597 z-Pr H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl) *
598 Me, B is S H 2-Me CF3 2-Cl-Ph 164-167
599 i-Pr H 2-N02 CF3 2-Cl-Ph jje
600 i-?r H 2-Me-4-Cl OCHF2 2-Cl-Ph 177-179
601 Me Me 2;4-di-Br CI 2-(3 -Cl-pyridinyl) 151-152
602 CH(CH3)CH2OCH3 H 2:4-di-Br CI 2-C3-Cl-pyridinyl) 162-163
603 CH(CH3)CH2SCH3 H 2,4-di-Br CI 2-(3-Cl-pyridinyI) 174-175
604 CH(CH0CK2OK H 2.4-di-Br Ci 2-(3-Cl-pyridinyl) 148-149

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Compound R3 R2 R4,R5
605 i-Fr: Rl is Me H 2-Me
606 z'-Pr. Rl is Me H 2-Me
607 i-Pr, Rl is Me H 2-Me
603 i-Er, B is S H 2-Me-4-Cl
609 N(CH3)2 H 2,4-di-Br
611 N(Me)2 H 2-Me-4-Cl
612 i-?i H a-a
613 /-Bu H 2-C1
614 CH(CH3)CH2C02Et H 2,4-di-Br
615 2-pyridinyl H 2-Me-4-Br
616 2-(3 -Me-pyridiziyJ) H 2-Me-4-Br
619 Me, B is S H 2-Me-4-Cl
620 Me Me 2-Me-4-Br
621 Et Et 2-Me-4-Br
622 2-pyridinyl H 2-Me-4-Cl
623 2-(3-Me-pyridinyI) H 2-Me-4-Cl
624 Et Et 2,4-di-Cl
625 Me Me 2,4-di-Cl
626 CH(CH3.)CH?SCH3 H 2,4-di-Cl
627 Et Et 2,4-di-Br
628 i-Pr Me 2-Me-4-Br
629 Me Me 2,4-di-Br

630 Et Et 2,4-di-Br
631 CH(CH3)CH2SCH3 H 2,4-di-Br
632 Et H 2-Me-4-Cl
633 i-Pr H 2-Me-4-Cl
634 Me H 2-Me-4-Br
635 ' Et H 2-Me-4-Cl
636 i-Pr H 2-Me-4-Cl
637 Me H 2-Me-4-Br
638 Et Me 2,4-di-Br
639 Et Me 2,4-di-Cl
640 Et Me 2-Me^f-Br
641 Me Me 2,4-di-Cl
642 Et St 2,4-di-Cl
643 CH(CH3)CH2SCH3 H 2,4-di-Cl
644 . Et Me 2:4-di-CI


R6 R7 m.p. (=C)
Br 2-(3-Cl-p}-7idiuyI) 223-225
CI 2-(3-a-pyridinyi) 223-225
CF3 2-(3-Cl-pyridinyl) 218-219
Br 2-(3-CI-pyridinyI) 231-235
CI 2-(3-Cl-pyridinyl) 149-151
Br 2-Q-Cl-pyridinyl) 185-138
C?3 S^l^fe-4-C^/waaty^ 111-211
CF3 5-(l-Me-4-Cl-pyrazolyl) 217-218
Ci 2-(3-Cl-pyridinyI) 113-115
CF3 2-(3-Cl-pyridinyl) 244-245
CF3 2-(3-Me-pyridinyI) 182-183
Br 2-(3-Cl-pyridhyl) 110-113
C¥3 2-(3-a-p}Tidinyl) 207-208
CF3 2-(3-CI-pyridinyl) 189-190
CF3 2-(3-Cl-pyridinyl) 233-234
CF3 2-(3-Cl-pyridinyI) 202-203
CI 2-(3-Cl-pyridinyl) 197-198
CI 2-(3-Cl-pyridiuyl) 142-143

CI 2-(3-Cl-pyridinyl) 185-186
CI 2-(3-Cl-pyridinyl) 209-210
CF3 2-('3-Ci-pyridiuyf) 133-135
Br 2-(3-Cl-pyridinyl) 185-187
Br . 2-(3-Cl-pyridinyl) 204-205
Br 2-(3-Cl-pyridinyl) 178-179
OCHF2 2-(3-Cl-pyridjnyl) 209-211
OCHF2 2-(3-Cl-pyridinyl) 179-181
OCHF2 2-(3-Cl-pyridinyl) 190-192
OEt 2-a-Ph 163-165
OEt 2-CI-Pli 173-175
OEt 2-Cl-Ph 155-158
Br 2-(3-CI-pyndinyI) 181-183
CI 2-(3-Cl-pyriduryl) 162-163
CF3 2-(3-Cl-pyridinyl) 174-175
Br 2-(3-Cl-p}Tidinyl) 216-218
Br 2-(3-Cl-pyridinyl) 190-191
Br 2-(3-Cl-pyridiayl) 182-183
Br 2-C3-Cl-pyridinyI) 165-167

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Compound RJ R2 R4, PJ R6 R7 in.p. (°C
645 Et H 2-Ms-4-Wi CF3 2-(3-CI-p\TidinyI) #
646 Me Me 2-Me-4-N02 CF3 2-(3-Cl-pyridin.yl) %
647 CH2CH=CH2 H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl) #
64S ;z-Pr H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl) *
649 CH(CH3)CH2SCH3 H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl) m
650 Me H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl)
1 * '
651 ' t-Bu H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl) *
652 CH2CH2N(Me)2 H 2-Me-4-N02 CT3 2-(3-Cl-pyridinyl) 193-195
653 CH2CH2N(Me)3+ r H 2-Me-4-N02 CF3 2-(3-Cl-pyridinyl) >250
655 N(CH3)2 H 2,4-di-Cl a 2-(3-Cl-pyridinyl) 146-148
656 N(CH3)2 H 2,4-di-Br Br 2-(3-CI-pyridinyI) 162-164
657 N(CH3)2 H 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 208-209
658 Et H 2-Me-4-Cl OCH2CF3 2-Cl-Ph 184-186
659 i-Pr H 2-Me-4-Q OCH2CF3 2-Cl-Ph 196-198
660 Me H 2-Me-4-Br OCH2CF3 2-Cl-Ph 220-223
661 N(CH3)2 H' 2-Me-4-N02, CF3 2-(3-Cl-pyridinyl) *
662 H H 2-Me-4-Cl Br 2-(3-Cl-pyridinyl) 240-242
663 w-Pr ;/-Pr 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 201-202
664 /7-Pr H 2-Me-4-Br CF3 2-(3-CI-pyridinyI) 188-190
665 Et ' Et 2-C1 CF3 2-(3-Cl-pyridkyl) 242-243
666 n-Pr n-Pr 2,4-di-Cl CI 2-(3-Cl-pyridinyl) 242-243
667 «-Pr H 2,4-di-Cl CI 2-(3-Cl-pyridinyl) 218-219
668 CH2CO2CH-CH3 Me 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 227-228
669 CH2C02CH2CH3 Me 2,4-di-Cl Br 2-(3-Cl-pyridinyl) 176-177
670 CH2CO2CJJ2CH3 Me 2,4-di-Br CI 2-(3-Cl-pyriduryI) 198-199
671 CH2C02CH3 H 2-Me-4-Br CF3 2-(3-Cl-pyridinyl) 141-142
672 N(CH3)2 H 2,4-di-Cl CF3 2-C3-CI-pyriciinyI) 136-137
673 ' Me Me 2,4-di-Cl CF3 2-(3-Cl-pyridrayl) 225-227
674 Et Et 2,4-di-Cl CF3 2-(3-Cl-pyridinyl) 228-229
675 CH2C02CH2CH3 Me 2,4-di-Cl CF3 2-(3-Cl-pyiidinyl) 219-220
676 Me H 2-Me-4-Cl CF3 5-(l-Me-4-CI-pyrazolyl) 239-241
677 i-Pr H 2-Me-4-Cl CF3 5 -(1 -Me-4-Cl-pyrazolyl) 252-254
678 e-Pr H 2-Me-t-5r OEt 2-(3-Ci--pyridmyt) 208-2 LI
679 Me H 2-Me-4-Br OEt 2-(3 -Cl-pyridinyl) 212-215
680 :-Pr H 2-Me-4-Cl OEt 2-(3-Ci-pyridkyl) 191-193
681 Ei H 2-Me-4-Cl OEt 2-(3-Cl-pyridinyl) 207-209
682 . i-Pr H 2-Me-4-Br OCK9CF3 2-(3 -Cl-pyridinyl) 213-215

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Compound R3 R2 R4, R5 R6 R? m.p. (°C)
683 Me H 2-Me-4-Br OCB2CF3 2-(3 -Cl-pyridinyl) 206-20S
684 i-?r H 2-Me-4-Cl OCH2CF3 2-(3-Cl-pyridinyl) 211-213
685 Et H 2-Me-4-Cl OCH2CF3 2-(3-Cl-p3iidinyI) 205-207
686 (Ex. 12) ' Me H 2-Me-4-Cl OCH2CF3 2-(3-CI-pyridinyI) 195-197
637 Et H 2-Me-4-Br OCH2CF3 2-(3-Cl-pyridinyI) 208-211
688 f-Bu H 2-Me-4-Br OCH2CF3 2-(3-CI-pyridiayl) 213-216
689 i-P* H 2-Me-4-Br CF3 5-(l-Me-4-Cl-pyrazoIyl) 256-258
690 t-Bu H 2-Me-4-Br CF3 5-(l~Me-4-Cl-pyrazolyl) 254-256
691 Me Me 2,4-di-Br CF3 2-(3-Cl-pyridinyl) 228-229
692 i-Pr H 2-Me-4-CJ OCF2CHF2 2-(3-Cl-pyridiny]) 189-192
693 Et H 2-Me-4-CJ OCF2CHF2 2-(3-Cl-pyridinyl) 189-192
694 Me H 2-Me-4-Cl OCF2CHF2 2-(3-Cl-pyridinyl) 162-165
695 /-ft- H 2-Me-4-Br OCF2CHF2 2-(3-Cl-pyridinyi) 185-188
696 ' Et H 2-Me-4-Br OCF2CHF2 2-(3-Cl-pyridinyl) 195-198
697 Me H 2-Me-4-Br OCF2CHF2 2~(3-Cl-pyridinyl) 164-167
698 Me Me 2-Cl-4-Br CF3 2-(3-a-pyridJnyl) 238-239
699 Et Me 2-Cl-4-Br CF3 2-(3-Cl-pyridinyI) 216-217
700 H • H H CT3 2-{3-a-pyridinyl)
701 Et H 2-Me-4-Br CF3 5-(l-Me-4-Cl-pyrazolyl) 249-251
702 z-Pr H 2,4-di-Cl OCH2CF3 2-(3-Cl-pyridinyl) 232-235
703 Me H 2,4-di-Cl OCH2CF3 2-(3-Cl-pyridinyl) 192-195
704 Me Me 2,4-di-Cl OCH2CF3 2-(3-Cl-pyridinyl) 132-135
705 i~Pr H 2,4-di-Br OCH2CF3 2-(3-Cl-pyridinyl) 225-227
706 Me H 2,4-di-Br OCH2CF3 2-(3-Cl-pyridinyl) 206-208
• 707 Me Me 2,4-di-Br OCH2CF3 2-(3-Cl-pyridinyl) 175-177
708 Me H 2-Cl-4-Br Br 2-(3-Cl-pyridinyl) 226-227
709 Me Me 2-CI-4-Br Br 2-(3-CI-pyridinyI) 237-238
710 ' Me H 2-Cl-4-.Br
CI 2-(3-a-pyridinyl) 228-229
711 Me Me 2-Cl^Br a 2-(3-Cl-pyridinyI) 236-237
712 CH2C(Me)2CH2N- H 2-Me CF3 2-(3 -Cl-pyridinyl) 197-200
(Me)2
713 Me H 2-MM-Br CF3 5 -(l-Me-4-Cl-pyrazolyl) 242-244
714 Et H 2-Me-4-CJ CF3 5- -(1 -Me-4-Cl-pyrazolyl) 252-254
715 f-3u H 2-Me-4-Cl CF3 5- -(1 -Me-4-Cl-p}Tazolyl) 259-260
716 2-Pr H 2,4-di-Cl OCBr?2 2-(3-Cl-pyridinyi) 220-222
717 Me H 2,4-di-Cl OCBrF2 2-(3-Cl-pyridinyI) 188-191
71S Me Me 2,4-di-Cl OCBrF? 2-(3-Cl-pyridinyl) 203-205

PCT/US02/25613
120
R2 R4,R5 R6 R7 m.p. (°C)
H 2-Me-4-CI OCHF2 2-(3-Cl-pyiidinyl) 210-212
H 2-Me-4-Cl OCBrF2 2-(3-Cl-pyridinyl) 194-196
H 2-iVIe-4-Cl OCBrF2 2-(3-CI-pyridinyl) 181-183
H 3,4-di-F CI 2-(3-Cl-pyridin.yl) 202-203
Me 3,4-di-F CI 2-(3-Cl-pyridinyl) 251-252
Me 2-Me-4-F . CI 2-(3-Cl-pyridinyl) 242-243
Me 2-C1-4-F Br 2-(3-Cl-pyridiayl) 245-246
H 2-C1-4-F Br 2-(3-Cl-pyridinyl) 217-218
H 2-C1-4-F Br 2-(3-Cl-pyridinyl) 168-169
Me 2-C1-4-F CI 2-(3-Cl-pyrjdinyl) 239-240
H ' 2-CM-F CI 2-(3-Cl-pyridinyI) 248-249
H 2-CI-4-F CI 2-(3-CI-pyridinyI) 169-170
Me 2-C1-4-F CF3 2-(3-Cl-pyridinyI) 215-216
H 2-C1-4-F CF3 2-(3-Cl-pyridiiiyl) 219-220
Me 2-Br-4-F Br 2-(3-Cl-pyridinyl) 235-236
H 2-Br-4-F Br 2-(3-Cl-pyridinyl) 238-239
H 2-Br-4-F Br 2-(3-Cl-pyridinyl). 236-237
Me 2-Br-4-F CI 2-(3-Cl-pyridinyr) 246-247
H 2-Br-4-F CJ 2-(3-Cl-pyridinyl) 233-234
H 2-Br-4-F CI 2-(3-Cl-pyridinyI) 153-154
H 2-Me-4~Cl OCHMe2 2-(3-CI-pyriduiyl) 208-210
H 2-Me-4-Cl OCHMe2 2-(3-Cl-pyriditiyl) 207-210
H 2,4-di-Cl OCHMe2 2-(3-CI-pyridiiiyl) 187-191
H 2,4-di-Cl OCHMe2 2-(3-Cl-pyridiayl) *
Me 2-Br-4-F CF3 2-(3-Cl-pyridinyl) 191-192
H 2-Br-4-F CF3 2-(3-a-pyridinyl) 228-229
H 2-Br-4-F CF3 2-(3-CI-pyridinyl) 224-226
Me 2-Br-4-Cl Br 2-(3-CI-p)TJdinyl) 18S-189
H 2-Br-4-Cl Br 2-(3-Cl-pyridinyl) 248-249
H 2-Br-4-Cl Br 2-(3-CI-pyridinyl) 252-253
Me 2-Br-4-CI CI 2-(3-Cl-pyridinyI) 147-148
H 2-Br-4-CI CI 2-(3-Cl-pyridinyl) 249-250
H 2-Br-4-Cl CI 2-(3-Cl-pyridinyl) 239-240
Me 2-Br-4-Cl CF3 2-(3-Cl-pyridinyI) 200-201
H 2-Br-4-Cl CF3 2-(3-Cl-pyridinyl) 158-159
H 2-Br^-Cl CF3 2-(3-Cl-pyridmyl) 250-250
Me 2-2vIe-4-Cl CI 2-(3-CI-pyridiiryi) 232-233

WO IJ3/U15518

PCT/US02/25613

121

Compound 1
R-1 R2 R4, R5 R6 R' ra.p. (°C)
756 Me H 2-CF3 CF3 2-(3-CI-pyridinyI) 218-220
757 J-Fr H 2-CF3 CF3 2-(3-C]-pyridinyl) 242-246
75S Me Me 2-CF3 CF3 2-(3-Cl-pyridinyl) 239-244
759 Me Me 2-Me-4-Cl Br 2-(3-a-pyridinyl) 210-211
760 Me Me 2,4-di-Me Ci 2-(3-Cl-pyridinyIj 223-224
761 Me Me 2,4-di-Me Br 2-(3-Cl-pyridinyl) 240-241
762 Me H 2-F Bt 2-(3-CI-pyridbyl) 215-216
763 i-Pr H 2-F Br 2-(3-Cl-pyridinyl) 213-215
764 i-Pr H 2-CF3-4-Cl CF3 2-(3-CJ-pyridinyl) 254-256
• 765 Me Me 2-CF3-4-CI CF3 2-(3-Cl-pyridirryI) 229-231
766 Me H 2-CF3-4-CI CF3 2-(3-CI-pyridinyI) 235-237
767 Me H 2,4-di-Cl CF3 2-(3-Cl-pyridinyI), R8 is CI 225-226
768 i-Tr H 2,4-di-Cl CF3 2-(3-Cl-pyridinyl), R8 is CI 230-232
769 Me Me 2,4-di-Cl CF3 2-(3-Cl-pyridin}'l), Rs is CI 194-196
770 i-Tr H 2-Me-4-CI CF3 3-isoxazolyl 255-257
771 Me H 2,4-di-F Br 2-(3~Cl-pyridinyI) 197-198
772 Me Me 2,4-di-F Br 2-(3-Cl-pyridinyl) 218-222
77.1 Me H 2-F CI 2-(3-CI-pyridinyJ) 185-187
774 Me H 2-F-4-C1 Br 2-(3-Cl-pyridinyl) 203-204
775 Me Me 2-F-4-C1 Br 2-(3-CI-pyridinyl) 226-227
776 i-Pr H 2-F-4-C1 Br 2-(3-Cl-pyridinyl) 207-208
1 777 Me H 2-F-4-CI CI 2-(3-Cl-pyridiayl) 211-212
778 Me Me 2-F, 4-C1 CI 2-(3-Cl-pyridinyl) 237-238
779 i-Pr H 2-Me-4-CN CF3 2-(3-Cl-pyridinyl) fc
780 ' H H 2-F-4-C1 CI 2-(3-Cl-pyridinyI) 116-117
781 Me H 2,4-di-F CI 2-(3-CI-pyridinyI) 159-160
7S2 Me Me 2,4-di-F CI 2-(3-Cl-pyridinyl) 225-226
783 i-Pr fi 2:4-di-F CI 2-(3-Cl-pyridinyl) 201-202
784 H H 2,4-di-F CI 2-(3-Cl'P}iidiayl) 128-129
785 Et H 2-Me-4-Cl CF3 5-(l-CH9CF3-pyrazolyI) 172-174
786 Me K 2-Me-4-Cl CF3 5-(l-CH2C2J3ijyrazolyl) 192-194
787 Me H 2.4-di-CI F 2-(3 -Cl-pyritJinyl) *
788 Me H 2-F OCH2CF3 2-(3-Cl-pyridinyl) 202-203
750 Me Me 2-F OCH2CF3 2-(3-CI-p}TicIiQyl) 178-179

WO 03/(115518 PCT/US02/25613
122

R7 in.p. (°C)
2-(3-CI-pyridinyl) 161-162
2-(3-Cl-p}-Tidinyl) 209-210
2-(3-CI-pyridinyl) 225-226
2-(3-Cl-pyridirjyl) 208-209
2-(3-CI-pyridrayI) 209-210
2-(3-Cl-pyridinyl) 244:245
2-(3-a-pyricfihyfJ 207-208
2-(3-Cl-pyridinyl) 210-211
2-(3~Cl-pyridinyl) 204-206
3 -(4-Cl-5-Me-isoxazolyl) 204-205
3-C4-Cl-5-Me-iso.\azolyl) 131-132
3-(4-Cl-5-Me-iso.xazolyl) 188-189
3-(4-Cl-5-Me-isoxazolyl) 210-211
3-(4-Cl-isoxazolyl) . 212-213
3-(4-Cl-isoxazolyl) 232
3-(4-Cl-isoxazolyl) 190-191
3-(4-CI-isoxazolyl) 209-210
3-(4-Cl-isoxazolyl) 241-242
5-(l-CH2CF3-pyrazolyl) 212-214
2-(3-Cl-pyridinyl) *
2-(3-Cl-pyridinyl) *
2-(3-Q-pyridiuyl) *
2-(3-Cl-pyridiuyl) *
2-(3-Cl-pyridinyl) *
2-(3-Cl-pyridiiiyl) *
2-(3-Cl-pyridinyl) *
5-(l-Me-4-CI-pyrazolyl) 242-244
5-(l-Me-4-Cl-pyrazolyl) 266-268
5-(l-Me-4-Cl-pyrazolyl) 241-243
5-(l-Me-4-Cl-pyrazolyl) 202-204
5-(l -Me-4-Cl-pyrazolyl) 128-131
2-(3-CI-pyridinyl) *
2-(3-C]-pyridinyl) 151-152
2-(3-Cl-pyridiiiyl) 133-134
2-(3-Cl-pyridinyl) 166-167
2-(3-Cl-pyridinyl) 148-149
-Cl-pyridinyl) 134-136
1.
'K-

Compound RJ R^ R4,R5 R6
790 z-Pr H 2-F OCH2CF3
791 Me H 2-F-4-Br Br
792 Me Me 2-F-4-Br Br
793 /-Pr H 2-F-4-Br Br
794 Me H 2-F^-Br CI
795 Me Me 2-F-4-Br CI
796 Me Me 2-F-4-Br a
797 Me H 2-F-4-Br OCH2CF3
798 Me Me 2-F-4-Br OCH2CF3
799 /-Pr H 2,4-di-Cl CF3
800 Me H 2,4-di-Cl CF3
SOI i-Pr H 2-Me-4-Cl CF3
802 Me H 2-Me-4-CI CF3
803 /-Pr H 2,4-di-Cl CF3
804 /-Pr H 2-Me-4-Cl CF3
805 Me H 2-Me-4-Cl CF3
806 Me H 2,4-di-Cl CF3
807 i-Pr H 4-C1 CF3
808 /-FT H 2,4-di-Cl CFi
809 H H 2,4-di-Cl F
810 /-FT H 2,4-di-Cl F
811 Me Me 2,4-di-Cl F
812 H H 2-Me-4-Cl F
813 /-Pr H 2-Me-4-CI F
1 814 Me H 2-Me-4-Cl F
815 Me Me 2-Me-4-Cl F
816 Me H 2,4-di-Cl CF3
817 ' Et H 2,4-di-Cl CF3
818 /-Pr H 2,4-di-CI CFB
819 Me Me 2,4-di-Cl CF3 :
820 ^-Bu H 2,4-di-Cl CF3 :
821 Me H 2.4-di-Cl CF3
822 H H 2-F-4-Br Br
S23 H H 2-C1-4-F CI
324 Me H 2,4-di-F F
825 H H 2-F-4-Br a
826 H H 2-Br-4-Cl Br

PCT/US02/25613
123

R2 R4,R5 R6 R7 m.p. (°C;
Me 2:4-di-F F 2-(3-Cl-p>Tidinyl) 211-212
H 2:4-di-F F 2-(3-Cl-pyridinyl) 115-117
H 2,4-di-F F 2-(3-Cl-p)Tidinyl) 157-158
H 2-C1-4-I CI 2-(3-Cl-pyridinyl) 192-195
H 2,4-di-Cl OCH3 2-(3-a-pyridinyl) 191-194
H 2,4-di-Cl OCH3 2-{3-Cl-pyridinyl) 143-145
H 2-Me-4-Cl Br 2-(3-Cl-5-Br-pyridinyI) 216-219
H 2-F F 2-(3-Cl-pyridiiiyl) 217-218
H 2-C1-4-F F 2-(3-Cl-pyridinyl) 207-208
Me 2-C1-4-F F 2-(3-Cl-pyridinyI} 221-222
H 2-C-4-F F 2-(3-Cl-pyridinyl) 166-167
H 2-C1-4-F F 2-(3-Cl-pyridinyl) 133-134
H 2-F-4-I Br 2-(3-Cl-pyridinyl) 216-217
Me 2-F-4-I Br 2-(3-Cl-pyridinyl) 218-219
H 2-F-4-I Br 2-(3-Cl-pyridinyI) 217-218
H 2,4-di-F Br 2-(3-Cl-pyridinyl) 178-179
H 2-I-4-F F 2-(3-Cl-pyridinyl) 217-218
Me 2-I-4-F F 2-(3-Cl-pyridinyl) 238-239
H 2-Me-4-Ci CF3 2-(3-F-pyridinyl) *
H 2-Me-4-Cl CF3 2-(3-F-pyridinyl) *
Me 2-Me-4-CI CF3 2-(3-F-pyridinyI) *
H 2-Me-4-CI CF3 2-(3-F-pyridinyl) *
H 2,4-di-Cl CF3 2-(3-F-pyridiayl) *
Me 2,4-di-Cl CF3 2-(3-F-pyridinyl) *
H 2,4-di-Cl CF3 2-(3-F-p)ddiDyl) *
H 2,4-di-Cl Br 2-(3-F-pyridiiyl) *
H 2,4-di-Cl Br 2-(3-F-pyridinyl) *
Me 2,4-di-CI Br 2-(3-F-pyridinyl) *
H 2,4-di-Cl Br 2-(3-F-pyridinyi) ji;
H 2-Me-4-Cl Br 2-(3-F-pyridinyl) *
H 2-Me-t-Cl Br 2-(3-F-pyridinyI) *
Me 2-Me-4-C2 Br 2-(3-F-pyridinyl) *
H 2-Me-4-Cl Br 2-(3-F-pyridinyl) *
H 2,4-di-Cl CF3 5-(l-CH2CF3-4-CJ-pyrazolyl) 181-183

WO 03/015518 PCVVSQ2/25613
124 ♦See Index Table B for :H NMR data
INDEX TABLE B
Compound %NMRData (CDQ^ solution unless indicated otherwise)*1
191 (DMSO-rfg) 5 1.03 (d, 6H), 2.18 (s, 3H), 3.92 fin, IH), 7.22-7.30 (in, 2H),
7.35 (in, IH), 7.62 (dd.. IH), 7.81 (s, IH), 8.02 (d, IH), 8.15 (dd, IH), 8.55
(dd, IH), 10.34 (s, IH).
, 224 (DMSO- (in, IH), 7.89 (s, IH), 7.96 (in, IH), 8.37 (s, 2H), 10.42 (s, IH).
248 (DMSO-dg) 5 1.04 (d, 6H): 4.0 (m, IH), 7.4 (m, 2H), 7.5 (m, IH), 7.6 (m IH), 7.78 (d, 2H), 8.0 (d, 2H), 8.2 (d, IH), 10.7 (bs, IH).
249 (DMSO-tf6) 5 1.16 (d, 6H), 4.1 (ro, 1H): 5.9 (d, IH), 7.1 (m, IH), 7.2 (in, 3H), 7.69 (s, IH), 7.73 (s, IH), 10.45 (s, IB).
250 (DMSO-rf6) 6 1.0(d, 6H), 3.9 (m, IH), 7.4 (m, 2H), 7.6 (a, IH), 7.8 (m, 2H), 8.0 (d, IH), 8.1 (d, IH), 8.3 (s, IH), 10.6 (s, IH).
251 (DMSO~d6) 5 1.0 (d, 6H), 4.0 (m, IH), 7.1 (m, IH), 7A3 (in, 2H), 7.5 (m, 4H), 7.66 (in, 2H), 10.6 (s, IB).

254 (DMSO-rf6) 5 1.02 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (in, IH), 7.2 (in, IH), 7.4 (in, IH), 7.8-7.9 (in, 2H), 8.0 (d, 2H), 8.3 (s, IH), 10.3 (s, IH).
255 (DMSO-tf6) 5 1.02 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (in, IH), 7.2 (m, IH), 7.4 (in, IH), 7.8-7.9 (in, 2H), 8.0 (d, 2H), 8.3 (s, IH), 10.3 (s, IH).
256 (DMSO-flfc) 5 1.04 (d, 6H), 4.0 (m, IH).. 7.4 (m, 2H), 7.76 (s, IH), 7.7 (in, IH), 7.74 (in, IH), 7.9 (in, IH), 7.97 (d, IH), 8.07 (s, IH), 8.2 (in, IH), 10.7 (bs, IH).
271 (DMSO-cf6) 5 1.0 (d, 6H), 2.01 (s, 3H), 2.17 (s, 3H), 3.9 (m, IH), 7.3 (m,
2H), 7.3-7.4 (in, IH), 7.8-7.9 (s, IH), 7.9-8.0 (in, 2H), 8.1-8.2 (s, IH), 10.3-10.4 (s, IH).
280 (DMSO-dg) 5 1.21 (d, 6H), 2.24 (s, 3H), 4.1-4.3 (m, IH), 5.9 (d, IH), 7.02
(d, IH), 7.1-7.6 (in, 7H), 7.78 (s, IH), 10.0 (brs, IH).
281 '(DMSO-d6) 5 1.03 (d, 6H), 1.94 (s, 3H), 2.14 (s: 3H), 3.9-4.0 (m, IH),
7.1-7.4 (m, SH), 7.8 (s, IH), 7.9-8.0 (d, IH), 10.0 (s, IH).
282 (DMSQ-cfc) 8 1.04 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (in, IH), 7.2-7.4 (in, 6H),
7.4-7.6 (in, 2H), 7.9 (s, IH), 7.9-8.0 (d, IH), 10.1 (brs, IH).
285 6 1.20 (d, 6H), 2.19 (s, 3H), 4.2 (m, IH), 5.9-6.0 (4 IH), 7.1-7.5 (in, 8H),
10.4-10.5 (s, IH).
321 (DMSO-dg) 5 1.03 (d, 6H), 2.18 (s, 3H).. 3.31 (s, 3H), 3.9-4.0 (in, IH),
7.2-7.3 (m, 2H), 7.3-7.4 (in, IH), 7.81 (s, IH), 7.9 (d. IH), 8.0 (brd: IH),
8.1 (dd, IH), 8.3 (i IH), 10.3 (s, IH).
405 6 2.57 (t, 2H), 3.57 (qs 2H): 6.25 (t, IH), 7.18-7.53 (m. 8H), 9.17 (s, IH)

WO 03/015518 ' PCT/US02/25613
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Compound iHNMRData (CDClg solution unless indicated otherwise)a
406 5 1.23 (d 6H): 4.13 (m, IH), 5.92 (d IH), 7.35 (in, 1H), 7.39 (s; IH) 7.42
(in, 2H), 7.92 (A IH), S.51 (d: IH), 10.23 (br s, IH).
409 5 1.13 (d, 6H), 4.15 (ITL IH), 5.99 (d IH), 7.40 (m, IH), 7.41 (m, IH),
7.63 (in, IH), 7.80 (s, IH), 7.90 (d, IH), S.4S (d, IH), 10.2 (brs, IH).
495 5 1.22 (d 6H), 2.18 (s, 3H), 4.15 (in, IH), 4.37 (s, IH), 5.91 (d, IH), 7.20 (in, 4H), 7.30 (in, IH), 7.40 (in, IH), 7.52 (in, 2H), 7.96 (s, IH), 10.23 (s, IH).
496 (DMSO- rf6) § 1.05 (d 6H), 2.15 (s, 3H).. 3.74 (s, 2H), 3.93 (m, IH), 7.26-7.70 (in, SH), 8.05 (s, 1R), 8.35 (brs, 2H), 10.45 (s, IH).
511 5 1.20 (d, 6H), 2.01 (s, 3H), 2.72 (d, 3H), 4.13 (in, IH), 6.01 (d, IH), 6.45
(s, IH), 7.17 (in, 5H), 7.51 (in, 2H), 7.63 (in, IH), 10.41 (s, IH).
593 (DMSO- d6) 5 1.04 (4 6H), 2.32 (s, 3H), 3.91 (m, IH), 7.44-7.64 (in, 4H),
7.77 (s, IH), 8.07 (d, IH), 8.27 (d, IH), 8.42 (d, IH), 10.6 (s, IH).
597 (DMSO- 6) 5 1.03 (d, 6H), 3.88 (m, IH), 7.65 (dd, IH), 7.S8 (s: IH), 8.18 .
(s, M), S.22 (d IH), S.48-8.57 (in, 3H), 10.95 (s, IH).
599 ? 1.24 (d 6H), 4.22 (m, IH), 5.98 (br d, IH), 7.30-7.55 (m, 6H), 7.78 (d,
IH), 7.99 (d, IH), 11.15 (s, IH).
645 5 1.30 (L 3H), 2.32 (s, 3H), 3.55 (q, 2H), 6.23 (br t, IH), 7.30 (s, IH), 7.42
(dd, IH), 7.91 (d, IH), 8.20 (apparent s, 2H), 8.52 (d, IH), 10.92 (s, IH).
646 5 2.21 (s.. 3H), 2.90 (s, 3H), 3.12 (s, 3H), 7.42 (in. 2H), 7.92 (d, IH), 7.92 . (d, IH), 8.00 (d, IH), 8.50 (d, IH), 9.92 (br s, IH).
647 5 2.32 (s, 3H), 4.02 (t, 2H), 5.18-5.30 (in, 2H), 5.82-5.98 (in, IH), 7.37 (s, IH), 7.43 (dd, IH), 7.50 (br r, IH), 7.92 (d, IH), 8.17 (s, IH), 8.37 (d, IH), 8.52 (d,lH), 11.12 (brs, IH).
648 5 0.91 (t, 3H), 1.63 (m, 2H), 2.31 (s, 3H)S 3.40 (q, 2H), 6.S3 (br t IH), 7.35 (s, IH), 7.42 (dd, IH), 7.91 (d, IH), 8.17 (d, IH), 8.24 (d, IH), 8.52 (d, IH), 11.03 (s, IH).
649 '5 1.38 (d, 3H), 2.l4 (s, 3H), 2.35 (s, 3H), 2.72 (in, 2H), 4.38 (in, IH), 6.93
(bid IH), 7.33 (s; IH), 7.43 (dd, IH), 7.91 (d, IH), S.1S (d, IH), 8.28 (d, IH), 8.52 (d, IH), 10.93 (s, IH).
650 (DMSO- d6) 5 2.32 (s, 3H), 2.70 (s, 3H), 7.63 (m, 2H)} 7.78 (br s, IH).. 8.18 (brs, IH), 8.21 (d IH), S.27 (brs, IH), S.5S (ra 2H).
651 (DMSO- flg) 5 1.25 (s, 9H), 2.51 (s: 3H), 7.64 (dd IH), 7.79 (s, IH), S.03 (br s, 2H), 8.22 (d IH), 8.28 (s, IH), 8.54 (d IH), 10.62 (s, IH).
661 § 2.33 (s, 3H), 2.75 (br s, 6H), 6.9 (br s, IH), 7.33 (s, IH), 7.43 (dd, IH),
7.91 (d IH), 8.19 (brs.. IH), 8.23 (s, IK), 8.50 (d, IH), 10.70 (brs, IH).
742 £ 1.39 (d, 6H), 2.S2 (d 3H), 4.95 (m, IH), 6.59 (s, IH), 6.62 (q, IH), 7.12

WO 1)3/015518 PCT/US02/25613
126
Compound % NMR D ata (CD CI3 solution unless indicated otherwise)a
(s, IH), 7.24 (s, IH), 7.26 (t, IH), 7.S0 (d, 1H): S.40 (d, IH), 9.56 (brs,
IH).
779 § 1.24 (d 6H), 2.22 (s, 3H), 4.20 (m, IH), 6.10 (A IH), 7.35 (s, IH), 7.44
(t, IH), 7.55 (s, 2H), 7.87 (s,' IH), 8.48 (d IH), 10.7 (s, IH).
787 5 2.91 (d 3H), 6.3 (m, IB), 6.77 (d IH), 7.3 (obscured, IH), 7.3-7.4 (m,
2H), 7.8-7.9 (d, IH), 8.5 (d, IH), 9.6-9.7 (br s, IH).
809 (DMSO- d6) 5 7.1 (d IH), 7.5-7.7 (in, 3H), 7.8 (in, 2H), 8.1-8.2 (d, IH),
8.5(d,lH), 10.5(brs, IH).
810 (DMSO- rf6) 5 1.03 (d 6H), 3.9 (m, IH), 7.1 (d, IH), 7.4-7.5 (d, IH), 7.6 (dd, IH), 7.8 (d, IH), 8.2 (d, IH), %2 (m, IH), 8.5 (d, IH), 10.5 (brs, IH).
811 5 2.78 (s, 3H), 3.04 (s, 3H), 6.9 (d IH), 7.1 (d, IH), 7.29 (d, IH), 7.3-7.4 (dd, IH), 7.8-7.9 (d, IH), 8.5 (d IH), 9.8 (br s, IH).
812 5 2.18 (s, 3H), 5.7 (brs, IH), 6.2 (brs, IH), 6.7 (d, IH), 7.3 (m, IH), 7.3-7.4 (dd IH), 7.8-7.9 (d IH), 8.4-8.5 (d, IH), 10.0 (brs, IH).
813 5 1.23 (d, 6H), 2.19 (s, 3H), 4.2 (m, IH), 5.9 (br s, IH), 6.7 (d, IH), 7.21 (d, IH), 7.26 (obscured, IH), 7.3-7.4 (dd, IH), 7.8-7.9 (d, IH), 8.4-8.5 (d, IH), 10.1 (brs, IH).
814 5 2.20 (s, 3H), 2.96 (d 3H), 6.1 (brs, 1H): 6.65 (d IH), 7.2 (d, IH), 7.26 (obscured, IH), 7.3-7.4 (dd, IH), 7.8-7.9 (d, IH), 8.4-8.5 (d, IE), 10.1 (br s, IH).
815 5 2.06 (s, 3H), 2.78 (s, 3H), 3.08 (s, 3H), 6.9 (d, IH), 7.0 (s, IH), 7.1 (s: IH), 7.3-7.4 (dd, IH), 7.8-7.9 (d, IH), 8.4-8.5 (d IH), 9.7-9.8 (brs, IH).
821 (PMSO- 8.0-8.1 (t, IH), 8.3-8.4(in, IH), 8.4(d, IH), 10.7 (brs, IH).
845 (DMSO- IH); 7.8 (s, IH), 8.0-8.1 (t, IH), 8.4 (d, IH), 10.4-10.5 (br s, IH).
846 (DMSO- d6) 5 2.18 (s, 3H), 2.66 (d, 3H), 7.35 (d, IH), 7.49 (d, IH), 7.69
'(s, IH), 7.7-7.8 (in, IH), 8.0-8.1 (t, IH), 8.3 (in, IH), 8.4 (d, IH), 10.4-
10.5 (brs, IH).
847 § 2.00 (s, 3H), 2.75 (s, 3H), 3.09 (ss3H), 6.99 (d, IH), 7.03 (s, IH), 7.4-7.5 (in. IH), 7.5-7.6 (t IH), 7.76(d, IH), 8.4 (d, IH), 10.4-10.5 (brs, IH).
848 (DMSO- rfg) p 1.02 (d 6H), 2.19 (s, 3H), 3.9 (m, IH), 7.30 (s, IH), 7.48 (d, IH), 7.6-7.8 (in, 2H), 8.0 (t, IH), S.l (d IH), 8.4 (d IH), 10.4 (brs, IH).
349 (DMSO- d6) 6 7.56 (i IH), 7.6 (s, IH), 7,7-7.8 (in, 2H): 7.9 (m, 2H). 8.0-
8.1 (t, IH), 8.4 (d IH), 10.6-10.7 (br s, IH).
S50 5 2.79 (s, 3K1 3.08 (s: 3H), 7.09 (d IH).. 7.25 (d: IH), 7.4-7.5 (in, IH),

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Compound *H NMR Data (CDCh solution unless indicated otherwise)a
7.5-7.6 ft IH), 7.7S (is. IH), U (± IH), 10.5 (brs, IB). '
851 (DMSO- ^6) & 101 (^ 6H)> 3-q Cm, IH), 7.46 (d, IE), 7.7 (ra, 1H), 7.8 (s,
IH), 7.S5 (d IH), 8.0 ft 1H), 8.2-8J (d IH), 8.4 (d IH), 10.6-10.7 Cbrs:
IH).
852 (DMS(>^^7.39(s>lH),7J5(dJlH),7.4(s,IH),7.4-7J(i^lB),7.8
(s, IH), 7.85 (d, IH), S.O ft IH), 8.4 (d, IH), 10.5 (hrs, IB).
853 (DMSO- rf6) 6 2.66 (d, 3H), 7.40 (s, IH), 7.51 (d, IH), 7.6-7.7 (in, IH),
7.84 (d, IH), 8.0 ft IH), 8.3-8.4 (in. IH), 8.4 (d, IH), 10.5-10.6 (brs, IH).
854 6 2.80 (s, 3H), 3.07 (s, 3H), 7.10 (s, IH), 7.31 (d, IH), 7.35 (s, IH), 7.4 (m:
IH), 7.5-7.6 ft IH), 8.4 (d, IH), 9.5 (brs, IH).
855 (DMSO- rfg) 5 1.02 (d, 856 (DMSO- d6) 5 2.17 (s, 3H), 7.33 (s, IH), 7.4 (d, IH), 7.5 (m, 2H), 7.6-7.7 (HI, IH), 7.9 (s, IH), 8.0 ft IH), 8.4 (d, IH), 10.3 (br s, IH).
857 (DMSO- rfg) 5 2.17 (s, 3H), 2.67 (d, 3H), 7.3-7.4 (in, 2H), 7.5 (d, IH), 7.6-7.7 (in, IH), 8.0 ft IH), 8.2-8.3 (m, IH), 8.4 (d, IH), 10.3 (br s, IH).
858 5 2.08 (s,3H), 2.79 (s,3H), 3.09 (s,3H), 6.99 (MH), 7.11 (srlH),7.2S (d, IH), 7.4 (m, IH), 7.5-7.6 (t, IH), 8.3-S.4 (d, IH), 9.8 (br s, IH).
859 (DMSO- a H NMR data are in ppm du wnfield from tetrainethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-hiplet, (q)-quartet, (mj-multiplet, (dd)-doublet of doublets, (dt)-doubIet of triplets, (brs)-bro ad singlet.
BIOLOGICAL EXAMPLES OF THE INVENTION
TESTA
For evaluating control of fall armyworm (Spodoptemfmgiperda) the test unit consisted of a small open container with a 4-5-day-old com (maize) plant inside. This was pre-infested with 10-15 1 -day-old larvae on a piece of insect diet by us e of a core sampler to remove a plug from a sheet of hardened insect diet having many larvae growing on it and transfer the plug containing lan-'ae and diet to the test unit. The larvae moved onto the test plant as the diet plug dried out.
Test compounds were formulated using a solution containing 10% acetone, 90?/Q water and 300 ppm X-77© Spreader Lo-Foam Formula non-ionic surfactant containing alkylarylpolyoxyethylene. free fatty acids, glycols and isopropanol (Loveland Industries. Inc.). unless otherwise indicated. 'The formulated compounds were applied in 1 mL of liquid

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through a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying S3'3tems Co.) positioned 1.27 cm (0.5 inches) above the top of each test unit. AH experimental compounds in this screen were sprayed at 50 ppm and replicated three times. After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour and then a black, screened cap was placed on top. The test units were held for 6 days in a growth chamber at 25 °C and 70% relative humidity. Plant feeding damage was then visually assessed.
Of the compounds tested, the following provided excellent levels of plant protection (10% or less feeding damage): 5, 11, IB, 19, 24, 2B, 30,. 32, 33, 34, 37, 38, 39, 40,45, 46, 47, 48, 56, 57, 58, 59, 63, 64, 75, 76, 77, 78, 79, 84, 85, 86, 87, 91,93, 94, 95, 96, 97, 98, 99, 108, 113., 114, 116, 115, 117,118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 133, 135, 136, 141, 142, 143, 144, 145, 147, 148, 149, 150, 151, 153, 154, 155, 156, 157, 158, 160, 161, 164, 165,166, 168, 169,170, 174, 176,177, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 1SS, 189, 190,191,192,193,194,195, 196, 197, 198,199, 200, 201, 202, 207, 208, 209, 210, 211, 212,213,214, 218, 219,220, 221, 222,224,229, 230, 231,232,233, 234, 236,237, 238,244,246,247, 250, 257,258, 259, 267, 268,270, 271, 272, 273, 275, 276, 277, 278, 279,280, 281, 282, 283, 284,287, 288,289,290,291,292, 293,294,295,297,298,299,300,301,302, 305,306, 307, 309, 313, 314,315, 316, 319, 320, 321, 322, 324, 325, 326,327, 328,329, 330, 335, 336, 338, 339, 341, 344,345, 346, 347, 348, 349, 351, 352, '156,364, 365, 366,367,370, 371, 372, 373, 374, 376, 377, 3S4, 387, 388, 390, 391, 392, 393,394, 395, 396, 401,402, 404, 405, 406, 407, 409,410, 411, 412, 413, 414, 415, 416, 417,418, 419,420, 421, 422, 423,424, 426, 428, 429, 430, 431, 432, 433, 434, 446, 449, 453,454, 456, 457, 458, 459, 460,461, 462, 463, 468,469, 470, 471, 472, 473, 474,475, 476,477, 478, 479,481,482, 483,484, 486, 487,488,489, 494, 497, 499, 500, 501, 502, 505, 506, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 526, 527, 528, 529, 530, 531, 532,533,534, 535,536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 611, 612, 613, 615, 616, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639,'640, 641, 642, 643, 644, 645, 647, 648, 649, 650, 651, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668,-669, 671, 672, 673, 674, 675, 676, 677, 678, 679, 6S0: 681, 682, 683, 684, 685, 6S6, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 701, 702: 703, 704, 705, 706, 707, 708, 709, 710, 711, 713, 714, 715, 716, 717, 718, 719, 720, 721, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 759, 762, 763, 766, 767, 768, 769, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 787, 790, 791, 792, 793, 794, 795, 796, 797, 798, 801,

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804, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 820, 821, 822, 823, 824, 825, S26,
829,830, 831. 832 and 833.
TESTB
For evaluating control of tobacco budworm (Heliothis virescens) the test unit consisted
5 of a small open container with a 6-7 day old cotton plant inside. This was pre-infested with
S 2-day-oH larvae on a piece of insect diet by use of a core sampler as described for Test A.
Test-compounds were formulated and sprayed at 50 ppm as described for Test A. The
applications were replicated three times. After spraying, the test units were maintained in a'
growth chamber and then visually rated as described for Test A.
10 Of the compounds tested, the following provided excellent levels of plant protection
(10% or less feeding damage): 8, 11, 18, 24, 28, 30, 32, 33, 34, 37, 39, 46, 47, 48, 53, 56,
51, 58, 59, 60, 74, 75, 76, 77, 78, 79, 80, 82, 84, 85, 86,-87, 88, 91, 93, 94, 95, 96, 113, 114,
115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 141, 142, 143, 145, 147, 150,
151, 153, 154, 155, 156, 158, 160, 161, 164, 165, 166, 168, 169, 170, 171, 174, 176, 177,
15 17S, 179, 180, 181, 182, 183, 184, 185, 186, 187, 189,, 190, 191, 192, 193, 194, 195, 196,
197, 198, 199, 200, 201, 202, 207, 208, 209, 210, 211, 212, 213, 214, 216, 218, 219, 220,
221, 222, 223, 224, 229, 230, 231, 232, 233, 234, 236, 237, 23S, 239, 240, 244, 246, 247,
250, 257, 258, 267, 270, 271, 272; 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283,
284, 285, 2S6, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298,.299, 300, 301,
20 302, 304, 305, 306, 307, ?09, 313, 314, 315, 316, 319, 320, 321, 322, 324, 325, 326, 327,
328, 336, 338, 339, 341, \45, 346, 348, 353, 356, 357, 364, 366, 367, 370, 371, 372, 373,
374, 377, 381, 383, 384, 385, 387, 388, 390, 391, 392, 393, 394, 395, 397, 399, 401, 402,
404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422,
423, 424, 428, 429, 430, 431, 432, 433, 434, 444, 445, 446, 447, 449, 453, 454, 456, 457,
25 458, 459, 460, 461, 462, 468, 469, 470, 471, 472, 474, 473, 475, 476, 477, 478, 479, 481,
482, 483, 484, 486, 487, 488, 489, 494, 497, 499, 500, 501, 502, 506, 511, 512, 513, 514,
515, 516, 517, 518, M9, 520, 521, 522, 523, 524, 526, 527, 528, 529, 530, 531, 532, 533,
534, 535, 536, 537. 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551,
552, 553, 554, 555, 556, 557, 55S, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569,
30 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587,
588, 589, 590: 591, 592, 593, 594, 595, 596, 597, 598, 600, 601, 602, 603, 605, 608, 609,
611, 612, 613,, 614, 615, 616, 619, 620, 621, 624, 625, 626, 627, 628, 629, 630, 631, 632,
633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 647, 648, 649, 650, 651,
655.. 656, 657, 65S, 659, 660, 661, 662, 663, 664, 665, 666, 667, 66%., 669, 670, 671, 672,
35 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690,
691, 692, 693, 694, 695, 696, 697, 698, 699, 701, 702, 703, 704, 705, 706, 707, 70S, 709,
710, 711, 713, 714, 715, 716, 717, 71S, 719, 720, 721, 724, 725, 726, 727, 72S, 729, 730,

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731, 732: 733, 734, 735, 736, 737, 738, 739, 740, 742; 743, 745, 746, 747, 74S, 749, 750,
751, 752, 753, 754 and 755.
TEST C
For evaluating control of beet aimyworm (Spodopiera exigua) the test unit consisted of
5 a small open container with, a 4-5-day-old com (maize) plant inside. This was pre-infested
with 10-15 1-day-old larvae on a piece of insect diet by use of a core sampler as described
for Test A.
Test compounds were formulated and sprayed at 50 ppm as described for Test A* The
applications were replicated three times. After spraying, the test units were maintained in a
10 growth chamber and then visually rated as described for Test A.
Of the compounds tested, the following provided excellent levels of plant protection
(10% or less feeding damage): 5,8,11, 18, 19, 24, 28, 30, 32, 33, 34, 37, 38, 39, 46,47, 48,
53, 56, 57, 58, 59, 60, 63, 64, 74, 75, 76, 77, 78, 79, 84, 85, S6, 87, 88, 91, 92, 93, 94, 95, 96,
97, 98, 99, 101, 102, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,
15 127, 128, 129, 130, 133, 135, 136, 137, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,
151, 153, 154, 155, 156, 157, 15S, 160, 161, 164, 165, 166, 168, 169, 170, 174, 176, 177,
178, 179, 180, 182, 183, .184, 185, 186, 187, 188, 189, 190, 191, 192, 195, 196, 197, 198,
199, 201, 202, 207, 208, 209, 210, 211, 212, 214, 218, 219, 221, 224, 229, 230, 231, 232,
233, 234, 236, 237, 238, 239, 240, 244, 246, 247, 250, 257, 258, 267, 270, 271, 272, 273,
20 274, 275, 276, 277, 27S, 279, 280, 281, 282, 283, 284, 286, 287, 288, 289, 290, 291, 292,
293, 294, 295, 297, 298, 299, 300, 301, 302, 304, 305, 307, 309, 313, 314, 315, 316, 319,
320, 321, 322, 324, 325, 326, 327, 328, 330, 336, 338, 339, 341, 343, 344, 345, 346, 347,
348, 351, 352, 356, 364, 365, 366, 367, 370, 371, 372, 373, 374, 376, 377, 380, 384, 385,
387, 388, 389, 390, 391, 392, 393, 394, 395, 401, 402, 404, 405, 406, 407, 409, 410, 413,
25 414, 418, 420, 422, 423, 424, 428, 429, 430, 431, 432, 433, 434, 449, 453, 454, 456, 457,
458, 459, 460, 461, 462, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 481,
4S2, 483, 484, 486, 487, 488, 494, 497, 499, 500, 501, 502, 506, 512, 5.13, 514, 515, 516,
517, 518, 519, 520, 521, 522, 523, 524, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535,
536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553,
30 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 561, 568, 569, 570, 571,
572, 573, 574, 575, 576, 577, 578, 579, 580, 5S-1, 582, 583, 584,^585, 586, 587, 588, 589,
590, 591, 592, 593, 595, 596, 597, 598, 600, 601, 603, 605, 606, 607, 608, 609, 611, 612,
613, 614, 616, 619, 620, 621, 624, 625, 626, 627, 62S, 629, 630, 631, 632, 633, 634, 635,
636/637, 638, 639, 640, 641, 642, 643, 644, 645, 647, 648, 650, 651,. 655, 656, 657, 658,
35 659, 660, 661, 662, 663, 664, 665, 666, 667, 669, 671, 672, 673, 674, 676, 677, 678, 679,
680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697,
698, 699, 701, 702, 703, 704, 705, 706, 707, 70S, 709, 710, 711, 713, 714, 715, 719, 720,

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721, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740,
741. 742, 743, 745. 746, 747, 74S, 749, 750, 751, 752, 753, 754 and 755.
TESTD
For evaluating control of green peach aphid (Myzus persicae) through contact and/or
5 systemic means, the test unit consisted of a small open container with a 12-15-day-old
radish plant inside. This was pre-infested by placing on a leaf of the test plant 30-40 insects
on a piece of leaf excised from a culture plant (cut-leaf method). The larvae moved onto the
■ test plant as the leaf piece desiccated. After pre-infestation, the soil of the test unit was
covered with a layer of sand.
10 Test compounds were formulated using a solution containing 10% acetone, 90% water
and 300 ppm X-77® Spreader Lo-Foarn Formula non-ionic surfactant containing
alkylarylpolyoxyethylene, free fatty acids, glycols and isopropanol (Loveland Industries,
Inc.), unless otherwise indicated. The formulated compounds were applied in 1 mL of liquid
through a SUJ2 atomizer nozzle with 1/8 JJ custom body (Spraying Systems Co.) positioned
.15 1.27 cm (0.5 inches) above the top of each test unit. All experimental compounds in this
screen were sprayed at 250 ppm and replicated three times. After spraying of the formulated
test compound, each test unit was allowed to dry for 1 hour and then a black, screened cap
was placed on top. The test units were held for 6 days in a growth chamber at 19-21 °C and
50-70%'relative humidity. Each test unit was then visually assessed for insect mortality.
20 Of the compounds tested, the following resulted in at least 80% mortality: 283,297,
370, 371, 372, 388, 431, 434, 469, 470, 472, 473, 474, 476, 479, 486, 494, 497, 499, 500, 501, 502, 506, 512, 514, 515, 516, 517, 518, 520, 530, 531, 532, 533, 534, 536, 537, 538, 539, 540, 542, 543, 544, 546, 548, 549, 550, 551, 553, 554, 555, 557, 559, 560, 561, 562, 563, 564, 565, 566, 567, 569, 571, 575, 576, 577, 578, 579, 580, 582, 584, 590, 596, 597, 25 601, 602, 603, 604, 609, 611, 614, 619, 620, 621, 624, 625, 626, 627, 629, 630, 631, 633, 638, 639, 640, 641, 642, 643, 644, 645, 650, 651, 655, 656, 657, 661, 664, 669, 671, 672, 673, 674, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 691, 698, 699, 703, 70S, 709, 710, 711, 719, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 771, 776, 779, 780, 781, 783,
30 7S4, 787, 793, 809, 810, 811, 812, 821, 822, 823, 824, 825, 826, 830, 831, 832 and 833.
TESTE
For evaluating control of cotton melon aphid (Aphis gossypii) through contact and/or
systemic means, the test unit consisted of a small open container with a 6-7-day-old cotton
plant inside. This was pre-infested with 30-40 insects on a piece of leaf according to the
35 cut-leaf method described for Test D. and the soil of the test unit was covered with a layer of
sand.

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Test compounds were formulated and sprayed at 250 ppm as described for Test D. The applications were replicated three times. After spraying, the test units were maintained in a growth chamber and then visually rated as described for Test D.
Of the compounds tested, the following resulted in at least 80% mortality: 370, 371. 5 372, 388, 431, 470, 472, 474, 476, 486, 494, 497, 500, 501, 506, 512, 514, 515, 516, 517, 51S, 520, 530, 531, 532, 533, 534, 536, 537, 538, 539, 540, 542, 543, 544, 546, 548, 549, 550, 551, 553, 554, 555, 557, 559, 560, 561, 562, 563, 564, 566, 567, 568, 575, 576, 577, 57S, 579, 5S2, 596, 601, 602, 603, 604, 609, 611, 620, 621, 624, 625, 626, 627, 628, 629, 630, 631, 638, 639, 640, 641, 642, 643, 644, 655, 656, 657, 661, 672, 673, 679, 681, 686, 10 687, 691, 698, 699, 703, 704, 706, 708, 709, 710, 711, 719, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 743, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 771, 774, 776, 777, 779, 780, 783, 784, 787, 791, 793, 794, 809, 811, 812, 821, 822, 823, 825 and 826.
15 TESTF
For evaluating control of com planthopper (Peregiinus maidis) through contact and/or systemic means, the test, unit consisted of a small open container with a 3-4 day old corn (maize) plant (spike) inside. White sand was added to the top of the soil prior to application. Test compounds were formulated and sprayed at 250 ppm and replicated three times as
20 described for Test D. After spraying, the test units were allowed to dry for 1 hour before
they were post-infested with 10-20 corn planthoppers (18 to 20 day old) nymphs) by
sprinkling them onto the sand with a salt shaker. A black, screened cap was placed on the
top of the cylinder. The test imits were held for 6 days in a growth chamber at 19-21 °C and
50-70% relative humidity. Each test unit was then visually assessed for insect mortality.
25 Of the compounds tested, the following resulted in at least 80% mortality: 370, 371,
372, 388, 431, 469, 470, 472, 474, 476, 486, 489, 494, 497, 500, 501, 506, 512, 514, 515,
516, 517, 518, 520, 530, 531, 532, 533, 534, 536, 537, 538, 539, 540, 542, 543, 544, 546,
548, 549, 550, 551, 553, 554, 555, 551, 559, 560, 561, 562, 563, 564, 566, 567, 568, 575,
576, 577, 578, 57.9, 582, 596, 601, 602, 603, 604, 609, 611, 620, 621, 624, 625, 626, 627,
30 628, 629, 630, 631, 638, 639, 640, 641, 642, 643, 644, 655, 656, 657, 661, 672, 673, 679,
681, 686, 687, 691, 698, 699, 703, 704, 706, 708, 709, 710, 71L 719, 725, 726, 727, 728,
729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 743, 745, 746, 747, 748, 749, 750,
751, 752, 753, 754, 755, 771, 774, 776, 777, 779, 780, 781, 783, 784, 787, 79L 793, 794,
809, 811, 812, 814, 821, 822, 823, 825 and 826.
35 TESTG
For evaluating control of potato leafhopper (Empoasca fabae Harris) through contact
and'or systemic means, the test unit consisted of a small open container with a 5-6 day old
Longio bean plant (primary leaves emerged) inside. 'White sand was added to the top of the

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soil and one of the primary leaves was excised prior to application. Test compounds were
formulated and sprayed at 250 ppm and replicated three times as described for Test D. After
spraying, the-test units were allowed to dry for 1 hour before they were post-infested with
5 potato leafhoppers (18 to 21 day old) adults). A black, screened cap is placed on the top of
the cylinder. The test units were held for 6 days in a growth chamber at 19-21 °C and 50-
70% relative humidity. Each test -unit was then visually assessed for insect mortality.
Of the compounds tested, the following resulted in at least 80% mortality: 200, 233,
236, 283, 313, 316, 324, 370, 371, 372, 434, 456, 457, 469, 470, 471, 472, 473, 474, 475,
476, 482, 486, 494, 497, 499, 500, 501, 502, 506, 512, 514, 515, 516, 517, 51S, 519, 520,
530, 531, 533, 534, 536, 537, 538, 539, 542, 543, 544, 549, 550, 551, 553, 554, 555, 551,
558, 559, 560, 561, 562, 563, 564, 566, 567, 568, 575, 576, 577, 578, 579, 582, 584, 601,
603, 609, 611, 614, 619, 621, 625, 626, 629, 630, 631, 632, 633, 634, 639, 640, 641, 643,
644, 655, 656, 657, 662, 664, 672, 678, 679, 680, 681, 682, 683, 685, 686, 687, 703, 706,
70S, 710, 719, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 742, 743,
744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 766, 771, 776, 777, 779, 780,
781, 784, 787, 793, 794, 796, 809, 810, 811, 812, 814, 821, 822, 824, 825, 826, S2S, 831,
832 and 833.
TESTH
For evaluating control of silverleaf whitefly (Bemisia tabaci), the test unit consisted of a 14-21-day-old cotton plant grown in Redi-earth® media (Scotts Co.) with at least two true leaves infested with 2nd and 3rd instar nymphs on the underside of the leaves.
Test compounds were formulated in no more than 2 mL of acetone and then diluted with water to 25-30 mL. The formulated compounds were applied using a flat fan air- ■ assisted nozzle (Spraying Systems 122440) at 10 psi (69 kPa). Plants were sprayed to run¬off on a turntable sprayer. All experimental compounds in this screen were sprayed at 250 ppm and replicated three times. After spraying of the test compound, the test units were held for 6 days in a growth chamber at 50-60'% relative humidity and 28 °C daytime and 24 °C nighttime temperature. Then the leaves were removed and the dead and live nymphs were counted to calculate percent mortality.
Of the compounds tested, the following resulted in at least 80% mortality: 494, 497, 499, 500, 501, 502, 506, 512, 513, 514, 515, 516, 517, 51S, 520, 523, 530, 531, 532, 533, 534, 535, 536, 537, 538, 540, 542, 543, 544, 549, 550, 551, 553, 554, 555, 557, 560, 575, 576; 577; 578', 579, 601, 620, 625, 629; 641\ 673, 686. 691 and 703. *
TEST I For evaluating soil systemic control of tobacco budworm {Heliothis virescens), cotton plants were grown in sassafras soil in 15-cm pots in aluminum trays. When the plants reached square stage (bud formation on the plant) the plants were treated with the test compounds.

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Test compounds were formulated in 0.25 mL of acetone and then diluted with, water to provide solutions of 10 ppm. Ten mL of the treatment solutions was added to the pots weekly for four weeks, with four replicates of each treatment rate. One day after the second, third and fourth treatments. 35-50 first instar Heliothis virescens larvae were brushed on 5 each plant with paintbrushes and placed on the terminal area, squares, and bolls. Five days after the last infestation with larvae the plants were rated for damage. Of the compounds tested, the following provided excellent levels of plant protection at 10 ppm (10% or less feeding damage) with excellent protection of squares and bolls including no or minimal
sepal demage: 214, 283 and 520.
10 TEST J
Test H followed an alternative protocol for evaluating soil systemic control of tobacco
budworm (Heliothis virescens). Cotton plants were grown in sassafras soil in 15-cm pots
under greenhouse conditions. When the plants reached square stage (bud formation on the
plant) the soil surface was treated with the test compounds.
15 Test compounds were formulated in 0.25 mL of acetone and then diluted with water.
Ten mL of treatment solution containing 3 mg of compound was added to the soil surface of each pot. The plants were watered the next day and each day following as needed. At 1, 2 and 4 days after treatment, leaves were excised for evaluation. Two sets of leaves were selected from each plant: upper leaves at approximately second node from terminal and with 20 area greater than 25 cm2 and lower leaves at approximately third node from bottom and with area greater than 25 cm-: The excised leaves were cut into 3 cm x 2 cm sections and placed into test trays made of nigh-impact styrene consisting of sixteen contiguous wells, each 6 cm wide, 4 cm long and 3 cm deep, with a clear plastic lid molded so that it locked into each well by friction. Solidified agar was placed into the bottom of each well to maintain 25 moisture for plant material. One second instar tobacco budwoim was placed into each well with plant material; wells were sealed and held at 25 °C and provided with 16 hours of light per day
Of the compounds tested, the following compounds provided excellent levels of mortality (greater than 70% mortality) on upper leaves excised at 4 da)'s after treatment at 30 the test rate; 497, 530 and 543.
TEST K
For evaluating soil systemic control of fall armyworm (Spodoptera fnigiperda), com
(maize) plants (Pioneer #3394) were grown in small pots for 5 days until they were at least 4
cm tall and the first leaf was unfurling.
3^ Test compounds were dissolved in 0.25 mL of acetone and diluted with water provide
solutions of 1. 10. 50 and 200 ppm. One mL of the test solution was applied by pipette to the surface of the soil in each pot. with eight plants for each compoundaate. The pots were covered and held at 25 °C with 16 hours of light per day. The plants were watered the next

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ay and each dav following as needed After 6 daj^s. the plant matter above the first leaf was excised and cut into 3-cm lengths. Each test unit was a high-impact styrene tray (Supplier: Clearpack Company. 11610 Copenhagen Court Franklin Park TL 60131) consisting of sixteen contiguous wells each 6 cm wide. 4 cm long and 3 cm deep, with a clear plastic lid molded so that it locks into each well by friction. Solidified agar (2 to 4 mL) was placed onto the bottom of each well to maintain moisture in the wells during the test. Each 3-cm length of corn plant matter was placed into a fray such that the plant matter was contained within two wells. One second-instar fall arnryworm (Spodopterafnigiperdd) larva was placed in each well, the tray was covered and then the test units were held at at 25 °C with 16 hours of light per day. Moztality was observed after four days.
LC90 concentrations (test compound concentrations giving 90% kill of the larvae) were calculated based on probit analysis (log linear regression) using a general linearized model (GLIM) of the SAS statistical computer analysis product of SAS Institute (Cary, NC, U.S.A.). Of the compounds tested, the following provided excellent levels of mortality, with
LCOQ values of 10 PPm or less: 20°. 202» 313> 494> 497> 50°. 513> 515> 516> 518> 520' 531> 533, 535, 538, 542, 543 and544.
TESTL
For evaluating soil systemic control of Colorado potato beetle (Leptinotarsa decemlineata), transplanted tomato plants were grown in 6-cm pots for 5 days until they were at the two true leaf stage.
Test compounds were dissolved in 0.25 mL of acetone and diluted with water provide solutions of 5 ppm. Five mL of the appropriate test solution was applied by pipette to the surface of the soil in each pot, followed by 5 mL of water, with eight plants for each compound/rate. The pots were covered and held at 25 °C with 16 hours of light per day. The plants were watered the next day and each day following as needed. After 4 days, one leaf from each plant was excised and placed into a well of a test tray as described in Test H. One 5-day old Colorado potato beetle {Leptinotarsa decemlineata) was placed in each well, the tray was covered and then the test units were hejd at at 25 °C with 16 hours of light per day. Mortality was observed after four days.
Of the compounds tested, the following provided excellent levels of mortality and feeding inhibition at 5 ppm: 214.
TEST M For evaluating control of boll weevil (Anthonomus g. grandis), samples of the test compounds were dissolved in 1 mL of acetone. This solution was then diluted to 100 mL total volume using an aqueous 500 ppm solution of Oriho X-77™ surfactant. Serial dilutions were made to obtain 50 mL of 50 ppm concentration.

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The diluted solutions of the test compounds were sprayed to run-off on three-week-old cotton plants. The plants were placed on a rotating turntable sprayer (10 rpm). Test solutions were applied using a flat fan air-assisted nozzle (Spraying Systems 122440) at 10 psi (69 kPa). Sprayed and dried plants were incased in a plastic cylinder. Twenty weevils were placed in each cylinder containing a whole cotton plant. At three days after infestation a feeding damage rating was taken.
Of the compounds tested, the following provided excellent levels of plant protection at 50pprn (10% or less feeding damage): 530 and 531.
TESTN For evaluating control of thrips (Frahkliniella sp.), samples of the test compounds . were dissolved in 1 rnL of acetone. This solution was then diluted to 100 mL total volume using an aqueous 500 ppm solution of Ortho X-77™ surfactant. Serial dilutions were made to obtain 50 mL of 10 ppm concentration.
The diluted solutions of the test compounds were sprayed to run-off on three-week-old cotton or soybean plants infested with thrips. The plants were placed on a rotating turntable sprayer (10 rpm). Test solutions were applied using a flat fan air-assisted nozzle (Spraying Systems 122440) at 10 psi (69 kPa). Sprayed and dried plants were incased in a plastic cylinder. At four days after application the total number of dead thrips was recorded.
• Of the compounds tested, the following resulted in at least 90% mortality at 10 ppm: 542.
TESTO Test O followed an alternative protocol for evaluating control of Colorado potato beetle (Leptinotarsa decemlineate). Several hours prior to spraying, 5 mg (100% active ingredient, ai) of the test compounds were dissolved in 1 mL of acetone. Using the aqueous solution of 500 ppm of Ortho X-77™, the sample bottle was rinsed and added to the test compounds. This sample solution was then brought to 100 mL with the aqueous solution. Serial dilutions are made to obtain 50 mL of 10 ppm.
Formulated experimental compounds were sprayed to run-off on three week old potato or tomato plants. The plants were placed on a rotating turntable sprayer (10 rpm). Test solutions were applied using a flat fan air-assisted nozzle (Spraying Systems 122440) at 10 psi (69 KPa). Once the plants were dried, leaves were excised from the treated plant. The leaves were cut, and then the pieces were placed singly into a 5.5 cm-by-3.5 cm cell of a sixteen-well plastic tray. Each cell contained a 2.5 square of moistened chromatography paper to prevent desiccation. One second instar larvae was placed in each cell. At three days after infestation total number of dead Colorado potato beetles was recorded.
Of the compounds tested., the following resulted in at least 90% mortality at 10 ppm: 497: 500; 530: 543: 544, 558, 562 and 684.

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TESTP Seventy-eight cotton plants were grown in the greenhouse with natural lighting in Sassafras soil in six inch pots. When six true leaves were on the plant (approximately 36 cm tall) the soil was drenched with a solution of Compound 497:500, 530: 531 or 543. Each of the 5 compounds was dissolved in 2 mL of acetone, and distilled water was added to make 300 ppm solutions of each of the compounds. The pots were divided into six groups (13 plants / treatment), and 10 mL of each solution was applied over the soil surface of each group with one group left untreated. The plants were arranged in the greenhouse in a randomized block design. Each treatment was divided into three groups for sampling at 24, 48, and 96 hours.
Leaves were taken from the base and tenninal of the plants. The leaves from the third node and the terminal leaves greater than 15 cm2 were sampled per plant. One clipped leaf from each plant was cut into four pieces and each piece was placed into an well with one second-ktstar larvae of Heliothis yirescens (tobacco budworra). Larval mortality (%M) was recorded 96 hours after sampling. The percentage of leaf feeding (%FF) was also recorded. Consumption of the leaf in the well was reported as 0 - 100% (0 equals no feeding). Results are listed in Table P.
TABLEP
Percent Larval Mortality and Feeding of Cotton Leaves Over Time

Compound Leaf position 24 h 48 h 96 h


% M % FF %M %FF %M %FF
497 terminal base 29 50 13 80 65 50 46 300 81 10 59 20
500 terminal base 4 60 4 SO 38 60 54 SO 30 30 30 30
530 tenninal base 46 50 33 SO 79 20 63 50 96 5 70 5
531 terminal base 25 40 13 60 42 40
33 80 55 10. 29 20
543 terminal base 46 20 33 30 J 63 20 5S 30 74 5 17 5
Untreated terminal base 0 90 1 0 90 0 90 | 0 100 0 100 0 95
TEST- Q For evaluating german cockroach {Blatetta germanicd). Compound 531 was mixed with water, and then blended into a slurry with equal amounts (by weight) of peanut butter. The mixture was air dried leaving a peanut butter bait with final concentration of the test

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substance as indicated in the following table. Approximately 1 gram of bait was placed into each test cage. Ten German cockroaches (Blatella germanica) were then placed into each cage, and provided water via a saturated cotton ball. The cages were held indoors, with indirect sunlight and temperatures ranging from 22 to 31 °C. Four test replicates were set up per rate. Evaluations were conducted 1, 2. 3, 5, and 7 days after treatment (DAT) by counting and removing the killed roaches found in each cage.
TABLE 0 German Cockroach Bait Test

Average of Killed Cockroaches
Rate 1DAT 2 DAT 3 DAT 5 DAT 7 DAT
untreated 0.3 0.3 0.3 1 2
400 ppm 3.8 5.8 6.3 7 7
2000 ppm 6.3 8 8.8 9 9
10000 ppm 9.5 9.5 9.5 9.5 9.5
TESTR For evaluating control of fire ant (Solenopsis xy/ora'), Compound 531 was mixed with water and then mixed into a slurry with equal amounts (by weight) of Niban granular bait with no active ingredient (supplied by Nisus Corp.). The mixture was air dried, leaving a dry granular bait with final concentration of the test substance as indicated in the following table. The baits were uniformly sprinkled onto the sand substrate in each test cage. Fifty field-collected southeni fire ants (Solenopsis xyloni) were then placed into each cage and provided water via a saturated cotton ball. The cages were held indoors with indirect sunlight and temperatures ranging from 22 to 31 °C. Four test replicates were set up per rate. Evaluations were conducted at 1,3, 7,10, and 14 days after treatment (DAT) by counting and removing the killed ants found in each cage.
TABLER Fire Ant Bait Test

Averase of Killed Fire Ants
P.ate 1DAT 3 DAT 7 DAT 10 DAT 14 DAT
untreated O.S 1.3 3.5 5.5 8.5
400 ppm 0.5 1.3 40.5 50 50
2,000 ppm 1 1 n 43 49.8 50
10:000ppm 0 2.3 ' 42.8 50 50

We claim:
1. A benzoxazinone compound of Formula 10

wherein R R5 is H. Ci-C6 alkyl, CrC6 haloalkyl, CrC4 alkoxyalkyl, d- C4 hydroxvalkyl, C(0)R10, C02R10, C(0)NR1(5Ru, halogen, C1-C4 alkoxy, Cr C4 haloalkoxy, NR1^ N(Ru)C(0)R10, N(Ru)C02R10 or S(0)„R12; R6 is H. Ci-Ce alkyl, Ci-C6 haloalkyl, halogen, CN, d-C4 allcoxy or C1-C4 haloalkoxy; 10 R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6~haloalkynyl or C3- C$ halocycloalkyl; or 117 is a phenyl ring, a benzyl ring, a 5- or 6- membered heteroaromatic ring, a naphthyl ring system or an aromatic 8-, 9- or 10-membered fused heterobicyclic ring system, each ring or ring system optionally substituted with one to three substituents independently selected from R9; R8 is H. Ci-Ce alkyl, Ci-Q haloalkyl, halogen, Ct-C4 alkoxy or Q-Q haloalkoxy; each R9 is independently Ci-C4 alkyl, C2-C4 allcenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 halocycloalkyl, halogen, CN, NO2, CrC4 alkoxy, Ci-C4 haloalkoxy' CrC4 alkylthio, C1-C4 alkylsulfmyl, Ci-C4 alkylsulfonyl, C,-C4 alkylamino, C2-Cg dialkylamino, C3.Ce cycloalkylamino, C4-C8 (alkyl) (cycloalkyl)amino, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl or C3-C6 trialkylsilyl;
R10 is H. C1-C4 alkyl or CrC4 haloalkyl;
R"isHorCi-C4alkyl;
R12 is C1-C4 alkyl or CrC4 haloalkyl; and n is 0, 1 or 2.
\\Vulcan\patent data\geeta\l 3386(p-l)div.doc

provided that (a) when R4 attached at position 2 is CH3, F, CI or Br, R5 attached at position 4 is halgen of CF3, R6 is CF3, CI, Br or OCH2CHF3 and R8 is H, then R7 is other than 3-Cl-2-pyridinyl or 3-Br-2-prydinyl;
(b) when R4,R5 and R8 are H and R6 is CI, then R7 is other than methyl.
2. The compound as claimed in Claim 1 wherein R7 is a phenyl ring or a 5- or 6-membered heteroaromatic ring selected from the group 30 consisting of
M J-2 J-3 J-4
each ring optionally substituted with one to three substituents independently selected fromR ;
Q is O, S, NH or NR9; and
W. X, Y and Z are independently N, CH or CR9, provided that in J-3 and J-4 at least 5 one of W, X, Y or Z is N.
3. The compound as claimed in Claim 2 wherein
R8isH;
R4 group is attached at position 2;
R4 is CH3, CF3, OCF3, OCHF2, CN or halogen;
R5 is H. CH3 or halogen;
R6 is CH3, CF3 or halogen; and
R7 is phenyl or 2- pyridinyl, each optionally substituted.
4. The compound as claimed in Claim 3 wherein R is CF3.
\\VulcaJ)Vatent data\geeta\l 3386(p-1 )div.doc

Documents:

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438-mumnp-2005-claims(granted)-(17-5-2005).doc

438-mumnp-2005-claims(granted)-(17-5-2005).pdf

438-mumnp-2005-claims.doc

438-mumnp-2005-claims.pdf

438-mumnp-2005-correspondence 1(1-3-2007).pdf

438-mumnp-2005-correspondence 2(2-11-2007).pdf

438-mumnp-2005-correspondence(ipo)-(12-3-2007).pdf

438-mumnp-2005-correspondence-others.pdf

438-mumnp-2005-correspondence-received-ver-041005.pdf

438-mumnp-2005-correspondence-received-ver-160505.pdf

438-mumnp-2005-correspondence-received-ver-270207.pdf

438-mumnp-2005-descripiton (complete).pdf

438-mumnp-2005-form 1(17-5-2005).pdf

438-mumnp-2005-form 18(6-10-2005).pdf

438-mumnp-2005-form 2(granted)-(17-5-2005).doc

438-mumnp-2005-form 2(granted)-(17-5-2005).pdf

438-mumnp-2005-form 3(17-5-2005).pdf

438-mumnp-2005-form 3(2-11-2007).pdf

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438-mumnp-2005-form-3.pdf

438-mumnp-2005-form-5.pdf

438-mumnp-2005-form-pct-ipea-409(17-5-2005).pdf

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438-mumnp-2005-form-pct-separate sheet-409.pdf

438-mumnp-2005-pct-search report.pdf


Patent Number 213274
Indian Patent Application Number 438/MUMNP/2005
PG Journal Number N/A
Publication Date 15-Mar-2007
Grant Date 26-Dec-2007
Date of Filing 17-May-2005
Name of Patentee E.I. DU PONT DE NEMOURS AND COMPANY
Applicant Address 1007 MARKET STREET, WILMINGTON, DELAWARE 19898, U.S.A.
Inventors:
# Inventor's Name Inventor's Address
1 LAHM, GEORGE PHILIP 148, FAIRHILL DRIVE, WILMINGTON, DE 19808, U.S.A.
2 MCCANN STEPHAN FREDERICK 11 Old Stable Lane, Newark, DE 19711.
3 PATEL KANU MAGANBHAI 149 Fairhill Drive, Wilmington, DE 19808.
4 SELBY THOMAS PAUL 116 Hunter Court, Wilmington, DE 19808.
5 STEVENSON THOMAS MARTIN 103 Iroquois Court, Newark, DE 19702.
PCT International Classification Number A 01N 43/56
PCT International Application Number PCT/US02/25613
PCT International Filing date 2002-08-13
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60/324,173 2001-09-21 U.S.A.
2 60/311,919 2001-08-13 U.S.A.