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Title:
ARTHROPODICIDAL ANILIDES
Document Type and Number:
WIPO Patent Application WO/1992/020682
Kind Code:
A1
Abstract:
Substituted anilides of formula (I), wherein Q is one of (Q-1), (Q-2) and (Q-3), and R?1� to R?5�, Y, Z and Z?1� are as defined in the text, arthropodicidal compositions containing such compounds; and a method for controlling arthropods by use of such compounds.

Inventors:
BARNETTE WILLIAM ELDO (US)
HARRISON CHARLES RICHARD (US)
LAHM GEORGE PHILIP (US)
PIOTROWSKI DAVID WALTER (US)
WING KEITH DUMONT (US)
Application Number:
PCT/US1992/003880
Publication Date:
November 26, 1992
Filing Date:
May 15, 1992
Export Citation:
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Assignee:
DU PONT (US)
International Classes:
A01N47/34; A01N47/38; C07C251/84; C07C281/12; C07C313/02; C07C313/08; C07D237/24; C07D237/26; C07D253/08; C07D253/10; C07D273/04; C07D285/16; C07D471/04; C07D491/04; C07D491/052; (IPC1-7): A01N43/90; A01N47/38; C07D273/04; C07D491/052
Domestic Patent References:
WO1991008207A11991-06-13
Foreign References:
EP0386892A21990-09-12
EP0377304A21990-07-11
EP0286346A21988-10-12
Attorney, Agent or Firm:
Costello, James A. (Legal/Patent Records Center 1007 Market Stree, Wilmington DE, US)
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Claims:
CLAIMS :
1. A compound of the formula wherein Q is selected from the group Q1 Q2 Q3 R1 is selected from the group Cl, Br, CF3, OCF3, OCF2H and OS0 CF3; R1 being OCF3 when Q is Q3 and Y is CH3, CH2CH2CH2CH3 or CH2Ph; R2 is selected from the group H, F, Cl, Br, CF3, OCF3, OCF H and OCH2CF3; Y is selected from the group CiCg alkyl, C2C6 alkenyl, C2C6 alkynyl, CxC3 alkylsulfonyl, C3C6 cycloalkyl, C3C5 cycloalkylalkyl, NR6R7, N=CR8R9, OR6, COR4, CO2R and CiCg alkyl substituted by a group selected from halogen, C1C3 alkoxy, CN, N02, S(0)nR4, COR8, C02R8 and phenyl, the phenyl optionally substituted by a group selected from halogen, CN, C1C2 alkyl, C1C2 alkoxy, C!C2 haloalkyl and ^02 haloalkoxy; Y being NR6R7, N=CR8R9 or OR** when Q is Q2; and Y being other than COR4 and C02R4 when Q is Q3; R3 is selected from the group C02Me, C02Et, Ph, 4F Ph, 4ClPh and CiC3 alkyl; R4 is C!C3 alkyl; R4 being C2C3 alkyl when Y is COR4 or C02R4, Q is Q1 and Z1 is 0; R5 is selected from the group H and C!C3 alkyl; R6 is selected from the group H, C1C4 alkyl, C!C4 haloalkyl, C2C4 alkenyl, C C4 alkynyl, S02NR8R9 S02R10, COR8, CONR8R9, C02R8, phenyl optionally substituted with halogen or C\Cι alkoxy, and benzyl optionally substituted with halogen; R7 is selected from the group H, C1C4 alkyl and COR8; R8 is selected from the group H, CxC4 alkyl, C1C haloalkyl and phenyl optionally substituted by a group selected from halogen, CN, N02, CF3 and OCF3; R9 is selected from the group H and C!C4 alkyl; R8 and R9 can be taken together as CH2CH2CH2, —CH2CH2CH2CH2— and —CH2CH2CH2CH2CH2—; R10 is selected from the group C1C4 alkyl and C!C4 haloalkyl; Rn is selected from the group H and C1C4 alkyl; R11 being H when Q is Q1 and Y is CH3 or C(0)CH3; Z is selected from the group CH , O, S and NR6; and Z1 is selected from the group 0 and NR11.
2. A compound according to Claim 1 wherein Q is Q1.
3. A compound according to Claim 2 wherein Y is NR6R7, N=CR8R9 or OR6.
4. A compound according to Claim 3 wherein R6 is H or C1C3 alkyl.
5. A compound according to Claim 2 wherein Y is CH3 or CH2CH3.
6. A compound according to Claim 2 wherein R3 is C02Me.
7. A compound according to Claim 4: methyl 2[[1[4 (trifluoromethyl)phenyl] hydrazino]carbonyl]2,3dihydro7 (trifluoromethyl) [1]benzopyrano[4,3 C]pyrazole3a(4H)carboxylate.
8. A compound according to Claim 6 selected from the group consisting of: methyl 2,3dihydro2[[NmethylN[4 (trifluoromethyl)phenyl]amino]carbonyl]7 (trifluoromethyl) [1]benzopyrano[4,3 c]pyrazole3a(4H)carboxylate; methyl 7chloro2,3dihydro2[ [NmethylN [4(trifluoromethyl)phenyl]amino]carbonyl] 1benzopyrano[ ,3c]pyrazole3a(4H) carboxylate; methyl 2[[N(4chlorophenyl)Nmethylamino] carbonyl]2,3dihydro7(trifluoromethyl) 1benzopyrano[4,3c]pyrazole3a(4H) carboxylate; methyl 2[[N(4bromophenyl)Nmethylamino] carbonyl]2,3dihydro7(trifluoromethyl) 1benzopyrano[ ,3c]pyrazole3a(4H) carboxylate; and methyl 2,3dihydro2[[NmethylN[4 (trifluoro ethoxy)phenyl]amino]carbonyl]7 (trifluoromethyl) [1]benzopyrano[4,3 c]pyrazole3a(4H)carboxylate.
9. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound according to any one of Claims 1 to 8 and a carrier therefor.
10. A method for controlling arthropods comprising applying to them or to their environment an arthropodicidally effective amount of a compound according to any one of Claims 1 to 8.
Description:
TITLE ARTHROPODICIDAL ANILIDES The substituted anilides of this invention are unknown in the art, with WO 90/07495 being perhaps the most relevant publication in this regard. The anilides of this invention include all geometric and stereo- isomers, arthropodicidally suitable salts thereof, arthropodicidal compositions containing them and their use to control arthropods in agronomic and nonagronomic environments. The term "compounds" includes all such isomers and salts thereof. The compounds are:

wherein

Q is selected from the group

Q-3

R 1 is selected from the group Cl, Br, CF 3 , OCF 3 , OCF 2 H and OS0 2 CF 3 ; R 1 being OCF 3 when Q is Q-3 and Y is CH 3 , CH 2 CH 2 CH 2 CH 3 or CH 2 Ph; R 2 is selected from the group H, F, Cl, Br, CF 3 , OCF 3 ,

OCF 2 H and OCH 2 CF 3 ; Y is selected from the group Ci-Cg alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 3 alkylsulfonyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkylalkyl, NR 6 R 7 , N*=CR 8 R 9 , OR 6 , COR 4 , CO2R 4 and Ci-Cg alkyl substituted by a group selected from halogen, Cχ-C3 alkoxy, CN, N0 2 , S(0) n R 4 , COR 8 , C0 2 R 8 and phenyl, the phenyl optionally substituted by a group selected from halogen, CN, C3.-C2 alkyl, c l~ c 2 alkoxy, ^-C 2 haloalkyl and 0ι~C 2 haloalkoxy; Y being NR 6 R 7 , N«CR 8 R 9 or OR 6 when Q is Q-2; and Y being other than COR 4 and C0 2 R 4 when Q is Q-3;

R3 i s selected from the group C0 2 Me, C0 2 Et, Ph, 4-F-Ph, 4-Cl-Ph and C^Cs alkyl;

R 4 is 0^0 3 alkyl; R 4 being C 2 -C 3 alkyl when Y is COR 4 or C0 2 R 4 , Q is Q-1 and Z 1 is O;

R5 is selected from the group H and ^-0 3 alkyl;

R6 is selected from the group H, C ! -C alkyl, ^-0 4 haloalkyl, C 2 -C 4 alkenyl, C -C 4 alkynyl, S0 2 NR 8 R 9 S0 2 R 10 , COR 8 , CONR 8 R 9 , C0 2 R 8 , phenyl optionally

substituted with halogen or Ci-0 alkoxy, and benzyl optionally substituted with halogen; R 7 is selected from the group H, C J .-C 4 alkyl and COR 8 ; R 8 is selected from the group H, C J -C alkyl, ^-0 4 haloalkyl and phenyl optionally substituted by a group selected from halogen, CN, N0 2 , CF 3 and

OCF 3 ; R 9 is selected from the group H and 0^0 4 alkyl; R 8 and R 9 can be taken together as -CH 2 CH 2 CH 2 -, -CH 2 CH 2 CH 2 CH 2 - and -CH 2 -H 2 CH 2 CH 2 CH 2 -;

R 10 is selected from the group ^-0 4 alkyl and ^-0 4 haloalkyl; R 11 is selected from the group H and C 2 .-C 4 alkyl; R 11 being H when Q is Q-1 and Y is CH 3 or C(0)CH 3 ; Z is selected from the group CH , 0, S and NR 6 ; and Z 1 is selected from the group 0 and NR 11 .

Preferred for reasons including greater arthropodicidal efficacy are:

A) Compounds of Formula I wherein Q is Q-1;

B) Compounds of Formula I wherein Q is Q-2;

C) Compounds of Formula I wherein Q is Q-3;

D) Compounds of Preferred A wherein Y is NR 6 R 7 , N=CR 8 R 9 or OR 6 ;

E) Compounds of Preferred D wherein R 6 is H or C 1 -C 3 alkyl;

F) Compounds of Preferred A wherein Y is CH 3 or CH2CH3; and G) Compounds of Preferred A wherein R 3 is C0 2 Me.

Specifically preferred is Compound E:

H) methyl 2-[[-1-[4 (trifluoromethyl)phenyl]- hydrazino]carbonyl]-2,3-dihydro-7-(trifluoro-

methyl) [l]benzopyrano [4,3-C]pyrazole-3a(4H)- carboxylate.

Specifically preferred are Compounds G:

I) methyl 2,3-dihydro-2-[[N-methyl-N-[4-

(trifluoromethyl)phenyl]amino]carbonyl]-7- (trifluoromethyl) [1]benzopyrano[4,3-c]pyrazole- 3a(4H)-carboxylate,

J) methyl 7-chloro-2,3-dihydro-2-[[N-methyl-N-[4- (trifluoromethyl)phenyl]amino]carbonyl] [1]benzo¬ pyrano [4,3-c]pyrazole-3a(4H)-carboxylate,

K) methyl 2-[[N-(4-chlorophenyl)-N-methylamino]- carbonyl]-2,3-dihydro-7-(trifluoromethyl)- [1]benzopyrano[4,3-c]pyrazole-3a(4H)-carboxylate,

L) methyl 2-[[N-(4-bromophenyl)-N-methylamino]- carbonyl]2,3-dihydro-7-(trifluoromethyl)-

[1]benzopyrano[4,3-c]pyrazole-3a(4H)-carboxylate, and

) methyl 2,3-dihydro-2-[[N-methyl-N[4-(trifluoro- methoxy)-phenyl]amino]carbonyl] -1-(trifluoro¬ methyl) [1]benzopyrano[4,3-c]pyrazole-3a(4H)- carboxylate.

In the above definitions, the term "alkyl", used either alone or in compound words such as "haloalkyl" includes straight chain or branched alkyl such as methyl, ethyl, n-propyl, isopropyl, butyl, pentyl or the different hexyl isomers. Alkenyl includes straight chain or branched alkenes, such as 1-propenyl, 2-propenyl, 3-propenyl and the different hexenyl isomers. Alkynyl

includes straight chain or branched chain aικynyι groups such as 1-pentynyl, 2-pentynyl, 3-pentynyl and the different hexynyl isomers. Alkoxy includes methoxy, ethoxy, n-propyloxy and isopropyloxy. The term "halogen", either alone or in compound words such as

"haloalkyl", means fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl" said alkyl can be partially or fully substituted with halogen atoms, which can be the same or different. Examples of haloalkyl include CH 2 CH 2 F, CF CF 3 and CH 2 CHFC1. The total number of carbon atoms in a substituent group is indicated by the Ci~Cj prefix where i and j are numbers from 1 to 6. For example, C 1 -C 3 alkoxy would designate methoxy through propoxy. The term "cycloalkyl" alone or in compound words such as

"cyclohaloalkyl" includes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl groups. Cycloalkylalkyl includes cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl groups. DETAILS OF THE INVENTION

The preparation of Formula I (Q-1) compounds where Y is other than NR 6 R 7 , N=CR 8 R 9 or OR 6 can be accomplished by the N-alkylation of Formula II (Q-1) derivatives. For example. Formula II (Q-1) derivatives are treated with a base such as sodium hydride, potassium hydride, potassium tert-butoxide, lithium diisopropyl amide and the like in an inert solvent such as ether, tetrahydrof ran, dioxane, dimethylformamide and dimethylsulfoxide. Subsequent treatment with an electrophilic reagent such as alkyl halides, dialkylsulfates, alkenyl halides, alkynyl halides, substituted alkyl halides, optionally substituted benzyl halides, alkylsulfonyl halides and the like will result in the formation of Formula I compounds as illustrated in Scheme 1.

SCHEME 1

11 - {_--)

Formula I compounds where Y is NR 6 R 7 can be prepared by the N-amination of Formula II derivatives. For example. Formula II derivatives are treated with a base such as sodium hydride, potassium hydride, potassium tert-butoxide, lithiumdiisopropyl amide and the like in an inert solvent such as ether, tetrahydrofuran dioxane, dimethylformamide and di ethylsulfoxide. Subsequent treatment of the anion with an electrophilic aminating reagent such as O-diphenylphosphinylhydroxylamine, hydroxylamine-O-sulfonic acid (HOSA) , 0-(2,4-dinitro- phenyl) ydroxylamine, O-mesitylenesulfonylhydroxylamine (MSH) , and the like will result in the formation of Formula I compounds where Y is NR 6 R 7 as illustrated in Scheme 2. Methods for the preparation and use of such electrophilic aminating reagents can be found in Synthesis 1977, 1. For instance, amides, imides, pyrroles and other related compounds can be aminated by aminating reagents in good yields.

II

Alternatively, Formula I compounds can be prepared by coupling of the intermediate compounds of the Formula III with a compound of Formula Ilia in the presence of phosgene or a phosgene equivalent. Typical reaction conditions involve combination of a phosgene equivalent with the Formula III compound in a solvent such as tetrahydrofuran or chloroform followed by the addition of the Formula Ilia compound. This chemistry is depicted in Scheme 3.

SCHEME 3

Compounds of Formula I where Y is NH 2 , NHR 7 or OH can be further derivatized by standard alkylation, acylation, sulfonylation and related reactions by procedures well documented in the art. Furthermore,

compounds of Formula I where Y is NH 2 can be condensed with aldehydes and ketones to form the corresponding hydrazone derivatives of Formula I. These procedures are also well documented in the art. The preparation of Formula II (Q-1) derivatives is described in WO 90/10623, WO 88/0799 and WO 91/08207. For instance, tricyclic pyrazolines of Formula III (Q-1) can be condensed with equimolar amounts of isocyanates of Formula V to give Formula II (Q-1) compounds. Compounds of Formula II (Q-2) where Z is O, S, NR 6 can be prepared by the reaction of Formula IV compounds with isocyanates of Formula V. Typical reactions involve the combination of equimolar amounts of IV and V in a conventional organic solvent such as, but not limited to, ethyl acetate, methylene chloride, chloroform, benzene or toluene. A base such as an alkali metal, tertiary a ine, alkali metal alkoxide or metal hydride can be used. Scheme 4 illustrates this transfora tion.

SCHEME 4

s 0, S, NR 6

IV where Z is O, S, NR

Alternatively, compounds of Formula II (Q-2) , where Z is O or S, can be prepared by the reaction of semicarbazones of Formula VI with paraformaldehyde or other equivalents known to those skilled in the art. Typical reactions involve the combination of an excess in

molar amounts of paraformaldehyde (1.1 equivalents to 40 equivalents) with 1 equivalent of a Formula VI compound optionally in the presence of less than one molar equivalent of an acid catalyst (0 equivalents to 0.9 equivalents) . Typical acid catalysts include alkyl or aryl sulfonic acids (such as methyl, camphor or p-toluene sulfonic) and mineral acids (such as hydrochloric or sulfuric) . Conventional polar organic solvents such as acetonitrile, dimethylformamide, tetrahydrofuran, methanol or ethanol can be used. The reaction temperature can vary from 0°C to the reflux temperature of the particular solvent being used and the rec.-.tion is usually complete in less than 24 hours. Scheme 5 illustrates this transformation. SCHEME 5

VI Z is 0 or S

Alternatively, compounds of Formula II (Q-2), where Z is 0, S or NR 6 , can be prepared by the reaction of compounds of Formula VI with compounds of Formula VII (see Scheme 6) . Typical reactions involve combination of an excess in molar amounts of a Formula VII compound (1.1 equivalents to 5.0 equivlents) with one equivalent of a Formula VI compound in the presence of a base such as a tertiary a ine (such as triethylamine, pyridine or DBϋ),an alkali metal, an alkali metal hydride or an alkali metal alkoxide or hydroxide (such as sodium

methoxide, potassium-t-butoxide, sodium hydroxide or potassium hydroxide) . Conventional polar organic solvents such as methanol, ethanol, propanol, dimethylformamide, THF, dichloromethane or acetonitrile can be used. The reaction temperatures can vary from 0°C to the reflux temperature of the particular solvent being used and the reaction is usually complete in less than 24 hours.

Alternatively, when Z is NR 6 and L 1 and L 2 are taken together as the reaction can be performed in the absence of base in aprotic solvents such as THF, dioxane and the like. Equimolar amounts of VI and VII are used and the reaction is usually complete in 72 hours.

SCHEME 6

VI + H j C 1 .- 2 *" II (Q-2) base II

wherein:

L 1 , L 2 are Cl, Br, I, imidazole, or L 1 and L 2 may be taken together to equal «=0, -S or -V {CE 3 ) jPl$

(where Z is NR 6 ) . Compounds of Formula IV can be prepared by the reaction of Formula VIII compounds with either compounds of Formula VII or a formaldehyde equivalent using methods analogous to those shown for the preparation of Formula II (Q-2) compounds in Schemes 5 and 6. The preparation of Formula IV compounds is shown in Scheme 7.

SCHEME 7

VIII Z is 0 or S

Compounds of Formula VI can be prepared by the reaction of Formula VIII compounds with isocyanates of Formula V as shown in Scheme 8. Typical reactions involve the combination of equimolar amounts of VIII and V in the presence of 1 molar equivalent of water in a polar organic solvent such as tetrahydrofuran or dimethylformamide. The reaction is usually complete in less than 24 hours.

SCHEME 8

Alternatively, Formula VI compounds can be prepared by the reaction of compounds of Formula IX with semicarbazides of Formula X. Conditions for this reaction optionally include an acid catalyst such as hydrochloric, sulfuric or p-toluene sulfonic acid. Reaction temperatures can range from 0 to 150°C with the reflux temperature of the solvent used generally preferred. Suitable solvents include, but are not

limited to, methanol, ethanol, isopropanol, tetrahydrofuran and dioxane. Scheme 9 illustrates this transformation.

SCHEME 9

The preparation of Formula VIII compounds can be accomplished by the reaction of Formula IX compounds with an excess of equivalents (1.1 to 10.0 equivalents) of hydrazine, hydrazine monohydrate, hydrazine acetate, hydrazine hydrochloride and the like. The reaction is conducted in an alcohol solvent such as methanol, ethanol, n-propanol, isopropanol, n-butanol and the like or acetic acid and the temperature is governed by the reflux temperature of the particular solvent. The reaction is generally complete in 24 hours. Scheme 10 illustrates this transformation.

SCHEME 10

NH 2 NH 2 ,

IX » VIII

NH 2 NH 2 »H 2 0 or NH 2 NH 2 *HOAc

Compounds of Formula IX where Z is O can be prepared by the α-hydroxylation of ketones of Formula XI using procedures that are well-known to one skilled in the art . See, for instance, J. Am. Chem. Soc , 1974, ££, 5944; Tetrahedron Lett . , 1988, 2__, 2835; J. Org. Chem. , 1986, L, 2402. Scheme 11 illustrates this transformation .

SCHEME 11

Numerous alternative procedures exist for the preparation of α-hydroxyketones of Formula IX (where Z is 0) including the procedure whereby the silyl enol-ether derived from XI is treated with meta-chloroperoxybenzoic acid followed by de-silylation with fluoride (Org. Synth., SA, 118) . α-Keto sulfides of Formula IX where Z is S can be prepared from ketones of Formula XI using procedures known to the art such as treatment of XI with tetramethylthiuram disulfide followed by alkaline hydrolysis fJ. Amar. Chem. Sor... 1985, 2 __1, 4175) . α-Amino ketones of Formula IX where Z is NR 6 can be prepared from ketones of Formula XI using procedures

known in the art such as treatment of ketones XI with cyclohexanespiro-3'-oxaziridine in the presence of base if necessary .Synthesis. l££i, 327) .

Compounds where Z is NHR^i©, can be prepared by the reaction of Formula XI compounds with compounds of the type XII using a procedure similar to those described in the art (Synthesis, 1991, 327) . The conditions for this reaction are the combination of equimolar amounts of Formulae XI and XII derivatives in the presence of a base as a catalyst, such as, but not limited to, DABCO, DBU, sodium hydroxide and the like. Suitable solvents include, but are not limited to, toluene, dioxane and water. Scheme 12 illustrates this transformation.

SCHEME 12

XI XII IX θ

Z is NHR°C1

The starting ketones of Formula XI are known in the art or can be obtained by methods analogous to known procedures. Those skilled in the art will recognize the Formula XI compounds to be indanones.

One skilled in the art will recognize that the transformation of Formula XI compounds into Formula IX compounds may require the use of protecting groups to prevent undesired side reactions of functionalities that may be sensitive to the reaction conditions (for example, an indoxyl nitrogen atom may require a protecting group to render it unreactive in an α-hydroxylation of the

carbonyl group) . Since numerous alternative synthetic methods for the preparations of Formula IX compounds exist, a further discussion of protecting-group chemistry will be omitted.

Semicarbazides of Formula X can be prepared using procedures well-known to those skilled in the art.

Compounds of Formula II (Q-2) where Z is CH 2 can be prepared by the reaction of Formula IV compounds with isocyanates of Formula V employing equimolar amounts of IV and V in a conventional organic solvent such as, but not limited to, ethyl acetate, methylene chloride, chloroform, benzene or toluene. A base such as an alkali metal, tertiary amine or metal hydride can be used. Scheme 13 illustrates this transformation.

SCHEME 13

IV Z is CH '

The preparation of Formula IV compounds where Z is CH 2 can be accomplished by the reaction of Formula XIII compounds with a reducing agent such as LiAlH 4 or BH 3 (see J. Org. Chem., 19733j_, 921). The typical reaction involves the combination of an excess in molar amounts of the reducing agent (1.1 equivalents to 5.0 equivalents) with 1 equivalent of a Formula XIII compound.

Conventional aprotic organic solvents such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane can be used. The reaction temperature can vary from 0°C to the

reflux temperature of the particular solvent being used and the reaction is usually complete in less than 24 hours. Scheme 14 illustrates this transformation.

SCHEME 14

XIII

.

The preparation of Formula XIII compounds can be accomplished by the reaction of Formula XIV compounds with an excess of equivalents (1.1 to 10.0 equivalents) of hydrazine, hydrazine monohydrate, hydrazine acetate, hydrazine hydrochloride and the like. The reaction is conducted in an alcohol solvent such as methanol, ethanol, a-propanol, isopropanol, n-butanol and the like or acetic acid and the temperature is governed by the reflux temperature of the particular solvent. The reaction is generally complete in 24 hours. Scheme 15 illustrates this transformation. Alternatively, Formula XIII compounds can be prepared from Formula XlVa derivatives as described for the preparation of Formula VII compounds (Scheme 15) .

SCHEME 15

J is Cl, I, Br and OS0 2 CH 3

Compounds of Formula XIV where R 3 is equal to H can be prepared by the reduction of Formula XV compounds. This transformation can be effected by catalytic hydrogenation (House, Modern Synthetic Reactions, 1972, pp. 1-44) or more conveniently through the use of an excess of equivalents (1.5 to 4.0 equivalents) of zinc in refluxing acetic acid as solvent (J. Med. Chem., 1986 29. 2181). The reaction is usually complete in 24 hours. Scheme 16 illustrates this transformation.

SCHEME 16

Compounds of Formula XV can be prepared by the reaction of Formula XI derivatives with Formula XVI compounds. One skilled in the art will recognize this reaction as an Aldol condensation (House, Modern Synthetic Reactions, 1972, pp.629-733) which is a well-known transformation; see Scheme 17.

SCHEME 17

Alternatively, compounds of Formula XIV can be prepared by hydrolysis of Formula XVII compounds. One skilled in the art will recognize this transformation as conventional and well-understood. Scheme 18 illustrates this common reaction.

SCHEME 18

Formula XVII compounds can be prepared by the alkylation of Formula XI derivatives with Formula XVIII compounds. The reaction can be accomplished by the reaction of equimolar amounts of Formula XI and XVIII compounds in the presence of a base such as an alkali metal, tertiary amine, metal hydride and the like in a conventional organic solvent such as, but not limited to, ether, tetrahydrofuran, 1,2-dimethoxyethane, dimethylformamide, dimethylsulfoxide, methanol, ethanol and propanol. The reaction is usually conducted at temperatures between 0 C C and the reflux temperature of the solvent utilized. The reaction is usually complete in 48 hours. Scheme 19 (reaction A) illustrates this transformation.

Additionally, the ketone XI serves as a useful intermediate for compounds of Formula XlVa. Formula XlVa compounds can be prepared by the alkylation of Formula XI derivatives with Formula XVIIIa compounds. The reaction can be accomplished by the reaction of one equivalent of Formula XI compounds and one to ten equivalents of Formula XVIIIa compounds in the presence of a base such as an alkali metal, tertiary amine, metal hydride and the like in a conventional organic solvent such as, but not limited to, ether, tetrahydrofuran, 1,2-dimethoxyethane,

dimethylformamide, dimethylsulfoxide, methanol, ethanol and propanol. The reaction is usually conducted at temperatures between 0°C and the reflux temperature of the solvent utilized. The reaction is usually complete in 48 hours. Scheme 19 (reaction B) illustrates this transformation.

The starting ketones of Formula XI are known in the art or can be obtained by methods analogous to known procedures.

The preparation of Formula II (Q-3) derivatives is described in WO 90/07495.

The following Examples serve to further illustrate the invention.

EXAMPLE 1

Methyl 2.3-dihydro-2-..N-methyl-N-.4-(trifluoromethyl)- phenyl1amino.carbonyl1-7-(trifluoromethyl ) .11- benzopyrano.4,3-c.pyra__ole-3a(4H.-__arbo_:ylate To a mixture of 60% sodium hydride (0.19 g,

4.75 mmol) in 10 mL of dimethylformamide was added methyl 2,3-dihydro-7-(trifluoromethyl)-2-[[[4-(trifluoromethyl)- phenyl]amino]carbonyl]-[1]benzopyrano[4,3-c]pyrazole- 3a(4H)-carboxylate (1.0 g, 2.05 mmol) in one portion. The color of the reaction turned yellow and the evolution of hydrogen gas was noted. After 10 minutes, methyl iodide (0.3 mL, 4.78 mmol) was added in one portion via syringe and the mixture was then heated at 50°C for one hour. After this time, TLC showed near completion of the reaction, with only a faint trace of residual starting compound. After cooling to room temperature overnight, the mixture was partitioned between 5% aqueous sodium bicarbonate and ether, the aqueous extracts were washed with ether and the combined ether extracts were dried over magnesium sulfate and concentrated to 1.47 g of a pale green, oily solid. Chromatography on silica gel (1:1 ethyl acetate:hexane) afforded 1.12 g of a clear colorless oil which set up to a white solid. Trituration with cold methanol afforded 0.28 g of a white solid, m.p. 105-111°C. The filtrate was concentrated and triturated with cold hexane to afford a second crop of 0.38 g of white solid, m.p. 107-110°C. *H NMR of both crops were identical.

^ NMR (CDC1 3 ) δ 3.47 (s, 3H) , 3.76 (s,3H), 3.90 (d, IH), 4.09 (d, IH), 4.15 (d, IH) , 5.00 (d, IH) , 7.13 (s, 3H), 7.32 (d, 2H), 7.62 (d, 2H) .

EXAMPLE 2 Methyl 2-..-1-.4-(trifluoromethyl.phenyl .hydrazinol r.arbonyl .-2.3-r_i__ydro-7-(tri luoromethyl. TU- bengopyrano.4.3-c.pγrazole-3a (4H. -carboxylate To a mixture of 60% sodium hydride (0.16 g, 4 mmol) in 10 mL of dimethylformamide was added methyl 2,3- dihydro-7-(trifluoromethyl)2-[[[4-(trifluoromethyl)- phenyl]amino]carbonyl]-[1]benzopyrano[4,3-c]pyrazole- 3a(4H)]-carboxylate (1.0 g, 2.05 mmol) at 0°C in one portion. The color of the reaction turned yellow and the evolution of hydrogen gas was noted. The reaction was warmed to ambient temperature over 30 minutes, then O-diphenylphosphinylhydroxylamine (0.75 g, 3.20 mmol) was added in one portion resulting in a white suspension. An extra 10 ml portion of dimethylformamide was added and the reaction was stirred for one hour. After this time the mixture was partitioned between saturated aqueous sodium bicarbonate and ether, the aqueous phase was extracted with ether. The combined ether extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was purified by chromatography on silica gel (40% ethyl acetate/hexane) to afford an oily product. Trituration with ether and hexanes afforded 0.37 g of a white solid, m.p. 118-121°C. R NMR (CDC1 3 ) δ 7.64-7.50 (m, 5H) , 7.22-7.19 (m, 2H), 5.2 (bs, 2H), 5.05 (d, IH) , 4.35 (d, IH) , 4.18 (d, IH), 3.95 (d, IH), 3.79 (s, 3H) .

EXAMPLE 3 Step A: 5-Fluoro-2-(4- luorophenyl. -2.3-riJhvdro-1H-inri. n- 1-one

To a solution of 50.0 g (0.324 mol) 4-fluorophenyl- acetic acid in 68 ml of methanol was added 1.2 g (6.5 mmol) of p-toluenesulfonic acid. The solution was heated at reflux overnight and then cooled to room temperature and partitioned between dichloromethane and saturated

sodium bicarbonate. The dichloromethane layer was washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated to afford 43.7 g of a clear, colorless oil. To a solution of 5.7 g (0.14 mol) of 60% sodium hydride in 120 ml of dimethylformamide under nitrogen was added 30.0 g (0.162 mol) of the crude methyl 4-fluoro- phenylacetate dropwise such that hydrogen evolution was moderate and the temperature of the reaction was maintained at less than 50°C. Once hydrogen evolution had ceased, a solution of 33.2 g (0.162 mol) of 3-fluoro- benzylbromide in 30 ml of dimethylformamide was added very cautiously such that the reaction temperature was maintained at less than 60°C. The reaction was maintained at 50 to 60°C with stirring overnight after which time it was partitioned between 5% aqueous NaHCθ 3 and diethyl ether, the aqueous extracts were washed five times with ether and the combined organic extracts were then washed with water. The ether extracts were dried over magnesium sulfate, filtered and concentrated to afford 31.9 g of a yellow oil.

The crude product was combined with 300 ml of methanol, 40 ml of water and 20 ml of 50% aqueous sodium hydroxide and refluxed overnight. After this time, the reaction was concentrated and the crude residue partitioned between water and ether. The aqueous extracts were acidified with IM hydrochloric acid and extracted three times with ether. The ether extracts were dried over magnesium sulfate, filtered and concentrated to 28.7 g of a yellow oil.

The crude product (27.4 g, 0.104 mol) was combined with 32 ml of thionyl chloride and then heated at reflux for 3 hours. Thionyl chloride was removed by concentration at reduced pressure and then the mixture was concentrated several times from carbon tetrachloride.

The residue was combined with 130 ml of dichloroethane, cooled under nitrogen to 0°C, and 15.3 g of aluminum trichloride was then added. After stirring overnight the reaction was poured onto a mixture of ice in IN hydrochloric acid, extracted three times with ether and chromatographed on silica gel (10% ethyl acetate/hexane) to afford 8.6 g of product.

^-H NMR (CDC1 3 ) δ 7.82 (dd, IH) , 7.25-6.95 (m, 6H) , 3.90 (dd, IH), 3.68 (dd, IH), 3.21 (dd, IH) . Step B: 5-Fluoro-2-(4-fluorophenyl>-2.3-dihydro-2- hydroxy-lH-inden-1-one A solution of 7.0 g (0.029 moles) of the product obtained from Step A and 69 mL of toluene was added with stirring to a mixture of 5.7 g (0.034 moles) of triethylphosphite, 0.33 g (0.0014 moles) of benzyl- triethylammonium chloride, 344 mL of toluene and 167 L of 50% aqueous sodium hydroxide solution. A steady stream of air was introduced into the vigorously stirred reaction mixture at room temperature for 1 hour. The resulting mixture was partitioned between hexane/ether and water and the aqueous layer was extracted three times with ether. The combined organic layers were washed twice with water, three times with saturated aqueous sodium bisulfite solution, dried over magnesium sulfate and concentrated. The resulting crude product was triturated several times with hexanes to afford 2.93 g of a pale yellow solid.

^ NMR (CDCI 3 ) δ 7.83 (dd, IH), 7.32-7.15 (m, 4H) , 6.99 (apparent t, 2H) , 3.56 (s, 2H) , 3.2 (bs, IH) . Step C: 2-r5-Fluoro-2-(4-fluorophenyl.-2.3-dihyriro-?- hydroxy-lH-inden-1-ylidene1-N-r -bromoph<.ny_ 1- hydrazine-carboxamide A solution of 2.8 g (0.0108 moles) of the product obtained from Step B, 0.78 mL (0.016 moles) of hydrazine monohydrate and 15 mL of methanol was heated at reflux

for 3 hours. The resulting solution was partitioned between water and methylene chloride and the aqueous layer was extracted with methylene chloride. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated, to afford 3.0 g of a yellow solid.

A solution of 0.8 g of the above product, 0.58 g (0.0029 moles) of 4-bromophenyl isocyanate, 8 mL of tetrahydrofuran and 1 drop of water was stirred at room temperature for two hours then 50 ml of hexane was added. After 15 minutes, a precipitate formed. The solid was filtered to afford 1.17 g of a pale yellow solid, m.p. 235-237°C.

^-H NMR (d 6 -DMSO) δ 9.42 (s, IH) , 9.23 (s, IH) , 8.03 (t, IH), 7.59 (d, 2H), 7.44 (d, 2H),7.4-7.1 (m, 7H) , 3.53 (d, IH) , 3.3 (d, overlapping with DMSO, IH) . Step D: 7-Fluoro-4a-(4-fluorophenyl )-4a.5-dihydro-N-.4- b_romo_.__ei.yl1-indenpr1,2-e1-r1>3, \1o__adiazine-

2 (3H. -carboxamide A mixture of 0.80 g (0.0017 moles) of the product obtained in Step C, 0.25 g (0.0027 moles) of paraformal¬ dehyde, 50 mg of p-toluene sulfonic acid monohydrate and 45 mL of acetonitrile was refluxed for 30 minutes. The resulting mixture was partitioned between chloroform and saturated aqueous sodium bicarbonate and the aqueous layer was extracted three times with chloroform. The combined organic layers were dried over magnesium sulfate and concentrated to give a yellow solid. The solid was triturated with methanol/water, and dried under vacuum to afford 0.57 g of a yellow solid, m.p. 208-209°C.

X H NMR (CDC1 3 ) δ 8.41 (bs, IH), 7.75 (dd, IH) , 7.43 (apparent q, 4H) , 7.32-7.22 (m, 2H) , 7.15-6.92 (m, 4H) , 5.75 (d, IH) , 4.52 (d, IH) , 3.48 (ABq, 2H) .

Step E: 7-Fluoro-4a-( -fluorophenyl. -4a.5-dihydro- indenon ,2-31-.1 ,3, 1oxadia_ine-2(3H)-carboxylic acid -H-bromcpheny )hydraaide To a mixture of 60% sodium hydride (0.16 g, 4 mmol) in 10 mL of dimethylformamide was added N-(4-bromo- phenyl)-7-fluoro-4a-(4-fluorophenyl)4a,5-dihydroindeno- [1,2-e] [1,3,4]oxadiazole-2(3H)-carboxamide (1.0 g, 2.07 mmol) at 0°C in one portion. The color of the reaction turned yellow and the evolution of hydrogen was noted. The reaction was warmed to ambient temperature over 20 minutes, then 0-diphenylphosphoylhydroxylamine (0.73 g, 3.10 mmol) was added in one portion to give a heterogeneous reaction mixture. After the hour, the mixture was partitioned between saturated sodium bicarbonate and ether and the aqueous phase was extracted with ether. The combined ether extracts were washed with water and brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel (40% ethyl acetate/hexane) to give 0.43 g of a yellow solid, m.p. 175-180°C. i H NMR (CDC1 3 ) δ 7.5-6.8 (m, 11H) , 5.5 (d, IH) , 4.7 (bs, 2H), 4.65 (d, IH) , 3.4 (ABq, 2H) .

By the procedures described herein or through obvious modifications thereof, the compounds of Tables 1-23 can be prepared.

GENERAL STRUCTURES FOR COMPOUNDS OF TABLES 1-14

I_a____-

1

2

4

5

6

8

9 10 11 12 13 14

GENERAL STRUCTURES FOR TABLES 15-18

GENERAL STRUCTURES FQR TABLES 20-23

B

Cl H

Br H

CF 3 H

OCF 3 H

OS0 2 CF 3 H

Cl H

Br H

CF 3 H

OCF 3 H

OS0 2 CF 3 H

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF 3 6-C1

OS0 2 CF 3 6-C1

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF 3 6-C1

OS0 2 CF 3 6-C1

Cl 6-F

Br 6-F

CF 3 6-F

OCF 3 6-F

OS0 2 CF 3 6-F

Cl 6-F

Br 6-F

CF 3 6-F

OCF 3 6-F

OS0 2 CF 3 6-F

E 1 B Z

Cl H

Br H

CF3 H

OCF3 H

OS0 2 CF 3 H

Cl H

Br H

CF 3 H

OCF3 H

OS0 2 CF 3 H

Cl 6-C1

Br 6-C1

CF3 6-C1

OCF3 6-C1

OS0 2 CF 3 6-C1

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF3 6-C1

OS0 2 CF 3 6-C1

Cl 6-F

Br 6-F

CF 3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

Cl 6-F

Br 6-F

CF 3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

B

Cl H

Br H

CF 3 H

OCF 3 H

OS0 2 CF 3 H

Cl H

Br H

CF 3 H

OCF3 H

OS0 2 CF 3 H

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF 3 6-C1

OS0 2 CF 3 6-C1

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF 3 6-C1

OS0 2 CF 3 6-C1

Cl 6-F

Br 6-F

CF 3 6-F

OCF 3 6-F

OS0 2 CF 3 6-F

Cl 6-F

Br 6-F

CF 3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

B 1 B 2 X B 1 E 2 X

Cl 7-CF3 Me OCF3 7-CF3 (CH 2 ) 2 OMe

Br 7-CF3 Me CF3 7-CF3 CH 2 SMe

CF 3 7-CF3 Me OCF3 7-CF3 CH 2 SMe

OCF 3 7-CF3 Me CF3 7-CF3 CH 2 C0 2 Me

OS0 2 C 3 7-CF3 Me OCF3 7-CF3 CH 2 C0 2 Me

Cl 7-CF3 Et CF3 7-CF3 CH 2 Ph

Br 7-CF3 Et OCF3 7-CF3 CH 2 Ph

CF 3 7-CF3 Et CF 3 7-CF3 allyl

OCF3 7-CF3 Et OCF3 7-CF3 allyl

OS0 2 CF 3 7-CF3 Et f

CF 3 7-Cl CH 2 CN

OCF 3 7-Cl CH 2 C

CF 3 7-Cl CH 2 OMe

OCF 3 7-Cl CH 2 OMe

CF 3 7-Cl (CH 2 ) 2 OMe

OCF 3 7-Cl (CH 2 ) 2 OMe

CF 3 7-Cl CH 2 SMe

OCF 3 7-Cl CH 2 SMe

CF 3 7-Cl CH 2 C0 2 Me OCF 3 7-Cl CH 2 C0 2 Me CF 3 7-Cl CH 2 Ph OCF 3 7-Cl CH 2 Ph

CF 3 7-Cl allyl

OCF 3 7-Cl allyl

CF 3 7-CF3 CH 2 CN

OCF 3 7-CF3 CH 2 CN

CF3 7-CF3 CH 2 OMe

OCF3 7-CF3 CH 2 0Me

CF 3 7-CF3 (CH 2 ) 2 OMe

E x B Cl H Br H CF 3 H

OCF 3 H

OS0 CF 3 H

Cl H

Br H

CF 3 H

OCF 3 H

OS0 2 CF 3 H

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF3 6-C1

OS0 2 CF 3 6-C1

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF3 6-C1

OS0 2 CF 3 6-C1

Cl 6-F

Br 6-F

C 3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

Cl 6-F

Br 6-F

CF3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

E 1 E^ Cl H Br H

CF 3 H

OCF 3 H

OS0 2 CF 3 H

Cl H

Br H

CF3 H

OCF3 H

OS0 2 CF 3 H

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF3 6-C1

OS0 2 CF 3 6-C1

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF3 6-C1

OS0 2 CF 3 6-C1

Cl 6-F

Br 6-F

CF 3 6-F

OCF3 6-F

0S0 2 CF 3 6-F

Cl 6-F

Br 6-F

CF3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

E 1 Cl H Br H

C 3 H

OCF 3 H

OS0 CF 3 H

Cl H

Br H

CF 3 H

OCF3 H

OS0 2 CF 3 H

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF 3 6-C1

OS0 2 CF 3 6-C1

Cl 6-C1

Br 6-C1

CF 3 6-C1

OCF 3 6-C1

OS0 2 CF 3 6-C1

Cl 6-F

Br 6-F

CF 3 6-F

OCF3 6-F

OS0 2 CF 3 6-F

Cl 6-F

Br 6-F

∞3 6-F OCF3 6-F

OS0 2 CF3 6-F

E 1 E^ B 3 X B^ B 3 X

OCF 3 7-F C0 Me NH 2 Br 7-F C0 2 Me NHMe

OCF3 7-F C0 2 Et NH 2 Br 7-F C0 2 Et NHMe

OCF3 7-F Me NH 2 Br 7-F Me NHMe

OCF3 7-F n-Pr NH 2 Br 7-F n-Pr NHMe

OCF3 7-F i-Pr NH 2 Br 7-F i-Pr NHMe

OCF 3 7-F 4-F-Ph NH 2 Br 7-F 4-F-Ph NHMe

OCF 3 7-Cl C0 2 Me NH 2 Br 7-Cl CO^e NHMe

OCF 3 7-Cl C0 2 Et NH 2 Br 7-Cl C0 2 Et NHMe

OCF 3 7-Cl Me NH 2 Br 7-Cl Me NHMe

OCF 3 7-Cl n-Pr NH 2 Br 7-Cl n-Pr . NHMe

OCF 3 7-Cl i-Pr NH 2 Br 7-Cl i-Pr NHMe

OCF3 7-Cl 4-F-Ph NH 2 Br 7-Cl 4-F-Ph NHMe

OCF3 7-CF 3 C0 2 Me KH 2 Br 7-CF3 C0 2 Me NHMe

OCF3 7~CF 3 C0 Et NH Br 7-CF3 C0 2 Et NHMe

OCF3 7-CF 3 Me NH 2 Br 7-CF3 Me NHMe

OCF3 7-CF 3 n-Pr NH 2 Br 7-CF3 n-Pr NHMe

OCF3 7-CF 3 i-Pr NH 2 Br 7-CF3 i-Pr NHMe

OCF3 7-CF 3 4-F-Ph NH 2 Br 7-CF3 4-F-Ph NHMe

CF 3 6-F C0 2 Me NHMe OCF3 6-F C0 2 Me NHMe

CF 3 6-F C0 2 Et NHMe OCF 3 6-F C0 2 Et NHMe

CF 3 6-F Me NHMe OCF3 6-F Me NHMe

CF3 6-F n-Pr NHMe OCF 3 6-F n-Pr NHMe

CF 3 6-F i-Pr NHMe OCF 3 6-F i-Pr NHMe

CF 3 6-F 4-F-Ph NHMe OCF 3 6-F 4-F-Ph NHMe C 3 7-F C0 2 Me NHMe OCF 3 7-F C0 2 Me NHMe CF 3 7-F C0 2 Et NHMe OCF 3 7-F C0 2 Et NHMe

C 3 7-F Me NHMe OCF 3 7-F Me NHMe CF 3 7-F n-Pr NHMe OCF 3 7-F n-Pr NHMe

CF 3 7-F i-Pr NHMe OCF3 7-F i-Pr NHMe

C 3 7-F 4-F-Ph NHMe OCF3 7-F 4-F-Ph NHMe

B 1 B^ B 3 X B 1 B B J X

Br 7-F C0 2 Me NH(CO)NHMe CF 3 7-F C0 2 Me NH(CO)NHMe

Br 7-F C0 2 Et NH(CO)NHMe CF 3 7-F C0 2 Et NH(CO)NHMe

Br 7-F Me NH(CO)NHMe CF 3 7-F Me NH(CO)NHMe

Br 7-F n-Pr NH(CO)NHMe CF 3 7-F n-Pr NH(CO)NHMe

Br 7-F i-Pr NH(CO)NHMe CF3 7-F i-Pr NH(CO) HMe

Br 7-F 4-F-Ph NH(CO)NHMe CF3 7-F 4-F-Ph NH(CO)NHMe

Br 7-Cl C0 2 Me NH(CO)NHMe CF 3 7-Cl C0 2 Me NH(CO)NHMe

Br 7-Cl C0 2 Et NH(CO)MHMe CF 3 7-Cl C0 2 Et NH(CO)MHMe

Br 7-Cl Me NH(CO)MHMe CF3 7-Cl Me NH(CO)MHMe

Br 7-Cl n-Pr NH(CO)NHMe CF3 7-Cl n-Pr NH(CO) HMe

Br 7-Cl i-Pr NH(CO)NHMe CF 3 7-Cl i-Pr NH(CO) HMe

Br 7-Cl 4-F-Ph NH(CO)NHMe CF3 7-Cl 4-F-Ph NH(CO)NHMe

Br 7-CF 3 C0 2 Me NH(CO)NHMe CF 3 7-CF3 C0 2 Me NH(CO) HMe

Br 7-CF 3 C0 2 Et NH(CO) HMe CF 3 7-CF3 C0 Et NH(CO)NHMe

Br 7-CF 3 Me NH(CO)NHMe CF 3 7-CF3 Me NH(CO) HMe

Br 7-CF3 n-Pr NH(CO)NHMe CF 3 7-CF3 n-Pr NH(CO)NHMe

Br 7-CF 3 i-Pr NH(CO)NHMe CF3 7-CF3 i-Pr NH(CO)NHMe

Br 7-CF 3 4-F-Ph NH(CO)NHMe CF 3 7-CF3 4-F-Ph NH(CO)NHMe

0CF 3 6-F C0 2 Me NH(CO)NHMe Br 6-F C0 2 Me N-CH 2 OCF36-F C0 2 Et NH(CO)NHMe Br 6-F C0 2 Et N-CH 2 OCF36-F Me NH(CO)NHMe Br 6-F Me N-CH 2 OCF36-F n-Pr NH(CO)NHMe Br 6-F n-Pr N-CH 2 OCF36-F i-Pr NH(CO)NHMe Br 6-F i-Pr N«CH 2 OCF 3 6-F 4-F-Ph NH(CO)NHMe Br 6-F 4-F-Ph N-CH 2 OCF 3 7-F C0 2 Me NH(CO)NHMe Br 7-F C0 2 Me N-CH 2 OCF 3 7-F C0 2 Et NH(CO)NHMe Br 7-F C0 2 Et N-CH 2 OCF 3 7-F Me NH(CO)NHMe Br 7-F Me N-CH 2 OCF 3 7-F n-Pr NH(CO)NHMe Br 7-F n-Pr N-CH 2 OCF 3 7-F i-Pr NH(CO)NHMe Br 7-F i-Pr N-CH 2 OCF 3 7-F 4-F-Ph NH(CO)NHMe Br 7-F 4-F-Ph N-CH

E B^ B 3 X B 1 B^ B 3 X

CF 3 7-CF3 C0 2 Me N-CH 2 OCF 3 7-CF3 C0 2 Me N-CH 2

CF 3 7-CF3 C0 2 Et N-CH 2 OCF3 7-CF3 C0 Et N-CH 2

CF 3 7-CF3 Me N-CH 2 OCF3 7-CF3 Me N-CH 2

CF 3 7-CF3 n-Pr N-CH 2 OCF3 7-CF3 n-Pr N-CH 2

CF 3 7-CF3 i-Pr N-CH 2 OCF3 7-CF 3 i-Pr N-CH 2

CF 3 7-CF3 4-F-Ph N-CH 2 OCF3 7-CF3 4-F-Ph N-CH 2

Br 6-F C0 Me N-Ofe CF3 6-F C0 2 Me N-CMe 2

Br 6-F C0 2 Et N-CMe 2 CF 3 6-F C0 2 Et N-CMe 2

Br 6-F Me N-CMe 2 CF 3 6-F Me N-CMe 2

Br 6-F n-Pr N-CMe 2 CF 3 6-F n-Pr N-CMe 2

Br 6-F i-Pr N-CMe 2 CF 3 6-F i-Pr N-CMe 2

Br 6-F 4-F-Ph N-CMe 2 CF3 6-F 4-F-Ph N-CMe 2

Br 7-F C0 2 Me N-CMe 2 CF3 7-F C0 2 Me N-CMe 2

Br 7-F C0 2 Et N-CMe 2 CF3 7-F C0 2 Et N-CMe 2

Br 7-F Me N « CMe 2 CF3 7-F Me N-CMe 2

Br 7-F n-Pr N-CMe 2 CF3 7-F n-Pr N«CMe 2 Br 7-F i-Pr N-CMe 2 CF3 7-F i-Pr N-CMe 2 Br 7-F 4-F-Ph N«CMe 2 CF 3 7-F 4-F-Ph N-CMe 2 Br 7-Cl C0 2 Me N-CMe CF3 7-Cl C0 2 Me N-CMe Br 7-Cl C0 2 Et N-CMe 2 CF 3 7-Cl C0 2 Et N-CMe 2 Br 7-Cl Me N-CMe CF3 7-Cl Me N-CMe 2 Br 7-Cl n-Pr N-CMe C 3 7-Cl n-Pr N-CMe 2 Br 7-Cl i-Pr N_ te 2 CF 3 7-Cl i-Pr N-CMe 2 Br 7-Cl 4-F-Ph N-CMe 2 CF3 7-Cl 4-F-Ph N-CMe 2 Br 7-CF3 C0 2 Me N-CMe 2 CF3 7-CF3 C0 2 Me N-CMe 2 Br 7-CF 3 C0 2 Et N-CMe 2 CF3 7-CF3 C0 2 Et N-CMe 2 Br 7-CF 3 Me N-CMe 2 CF 3 7-CF3 Me N-CMe 2 Br 7-CF 3 n-Pr N-CMe 2 CF3 7-CF 3 n-Pr N-CMe 2 Br 7-CF 3 i-Pr N-CMe 2 CF3 7-CF 3 i-Pr N-CMe 2 Br 7-CF 3 4-F-Ph N-0_e 2 CF3 7~CF 3 4-F-Ph N-CMe 2

B 3 X B 1 B^ B 3 X

C0 2 Me Br 6-F C0 2 Me N-CHPh

C0 Et N-CMe 2 Br 6-F C0 2 Et N-CHPh

Me N-CMe 2 Br 6-F Me N-CHPh n-Pr N-CMe 2 Br 6-F n-Pr N-CHPh i-Pr N-CMe 2 Br 6-F i-Pr N-CHPh

4-F-Ph N-CMe 2 Br 6-F 4-F-Ph N-CHPh

C0 2 Me N-CMe Br 7-F C0 2 Me N-CHPh

C0 2 Et N-CMe 2 Br 7-F C0 2 Et N-CHPh

Me N-CMe 2 Br 7-F Me N-CHPh n-Pr N-CMe 2 Br 7-F n-Pr N-CHPh i-Pr N-CMe 2 Br 7-F i-Pr N-CHPh

4-F-Ph N-CMe 2 Br 7-F 4-F-Ph N-CHPh

CO^e N-CMe 2 Br 7-Cl C0 2 Me N-CHPh

C0 2 Et N-CMe 2 Br 7-Cl C0 2 Et N-CHPh

Me N-CMe 2 Br 7-Cl Me N-CHPh n-Pr N-CMe 2 Br 7-Cl n-Pr N-CHPh i-Pr N-CMe 2 Br 7-Cl i-Pr N-CHPh

4-F-Ph N-CMe 2 Br 7-Cl 4-F-Ph N-CHPh

C0 2 Me N-CMe 2 Br 7-CF3 C0 2 Me N-CHPh

C0 2 Et N-CMe 2 Br 7-CF3 C0 2 Et N-CHPh Me N-CMe 2 Br 7-CF3 Me N-CHPh

OCF3 7-CF3 n-Pr N-CMe 2 Br 7-CF3 n-Pr N-CHPh

OCF3 7-CF3 i-Pr N«CMe 2 Br 7-CF3 i-Pr N-CHPh

OCF3 7-CF3 4-F-Ph N-CMe 2 Br 7-CF3 4-F-Ph N-CHPh

CF3 6-F C0Me N-CHPh OCF3 6-F C0 2 Me N-CHPh

CF3 6-F C0 2 Et N-CHPh OCF3 6-F C0 2 Et N-CHPh

CF 3 6-F Me N-CHPh OCF3 6-F Me N-CHPh

CF 3 6-F n-Pr N-CHPh OCF3 6-F n-Pr N-CHPh

CF 3 6-F i-Pr N-CHPh OCF3 6-F i-Pr N-CHPh

CF3 6-F 4-F-Ph N-CHPh OCF3 6-F 4-F-Ph N-CHPh

B 1 B^ B 3 X B 1 B^ B 3 X

CF 3 7-F C0 2 Me N-CHPh OCF 3 7-F C0 2 Me N-CHPh

CF 3 7-F C0 2 Et N-CHPh OCF 3 7-F C0 2 Et N-CHPh

CF3 7-F Me N-CHPh OCF3 7-F Me N-CHPh

CF 3 7-F n-Pr N-CHPh OCF3 7-F n-Pr N-CHPh

CF 3 7-F i-Pr N-CHPh OCF3 7-F i-Pr N-CHPh

CF 3 7-F 4-F-Ph N-CHPh OCF3 7-F 4-F-Ph N-CHPh

CF 3 7-Cl C0 2 Me N-CHPh OCF3 7-Cl C0 2 Me N-CHPh

CF 3 7-Cl C0 2 Et N-CHPh OCF3 7-Cl C0 2 Et N-CHPh

CF3 7-Cl Me N-CHPh CF3 7-Cl Me N-CHPh

CF 3 7-Cl n-Pr N-CHPh OCF 3 7-Cl n-Pr N-CHPh

CF 3 7-Cl i-Pr N-CHPh OCF 3 7-Cl i-Pr N-CHPh

CF 3 7-Cl 4-F-Ph N-CHPh OCF 3 7-Cl 4-F-Ph N-CHPh

CF 3 7-CF 3 C0 2 Me N-CHPh OCF 3 7-CF 3 C0 2 Me N-CHPh

CF 3 7-CF3 C0 2 Et N-CHPh OCF 3 7-CF 3 C0 Et N-CHPh

CF 3 7"CF 3 Me N-CHPh OCF 3 7-CF 3 Me N-CHPh

CF 3 7-CF3 n-Pr N-CHPh OCF 3 7-CF 3 n-Pr N-CHPh

CF 3 7-CF3 i-Pr N-CHPh OCF 3 7"CF 3 i-Pr N-CHPh

CF 3 7-CF3 4-F-Ph N-CHPh OCF 3 7-CF 3 4-F-Ph N-CHPh

Br 6-F C0 2 Me NH(CO)CF 3 CF 3 6-F C0 2 Me NH(CO)CF 3

Br 6-F C0 2 Et NH(CO)CF 3 CF 3 6-F C0 Et NH(CO)CF3

Br 6-F Me NH(CO)CF 3 CF3 6-F Me NH(CO)CF 3

Br 6-F n-Pr NH(CO)CF 3 CF 3 6-F n-Pr NH(CO)CF 3

Br 6-F i-Pr NH(CO)CF 3 CF 3 6-F i-Pr NH(CO)CF 3

Br 6-F 4-F-Ph NH(CO)CF 3 CF 3 6-F 4-F-Ph NH(CO)CF 3

Br 7-F C0 2 Me NH(CO)CF 3 CF 3 7-F C0 Me NH(CO)CF3

Br 7-F C0 2 Et NH(CO)CF 3 CF 3 7-F C0 2 Et NH(CO)CF3

Br 7-F Me NH(CO)CF 3 CF 3 7-F Me NH(CO)CF 3

Br 7-F n-Pr NH(CO)CF 3 CF 3 7-F n-Pr NH(CO)CF 3

Br 7-F i-Pr NH(CO)CF 3 C 3 7-F i-Pr NH(CO)CF 3

Br 7-F 4-F-Ph NH(CO)CF 3 CF 3 7-F 4-F-Ph NH(CO)CF3

B 1 B z B 3 X

Br 6-F C0 2 Me OMe

Br 6-F C0 2 Et OMe

Br 6-F Me OMe

Br 6-F n-Pr OMe

Br 6-F i-Pr OMe

Br 6-F 4-F-Ph OMe

Br 7-F C0 2 Me OMe

Br 7-F C0 Et OMe

Br 7-F Me OMe

Br 7-F n-Pr OMe

Br 7-F i-Pr OMe

Br 7-F 4-F-Ph OMe

Br 7-Cl C0 2 Me OMe

Br 7-Cl C0 2 Et OMe

Br 7-Cl Me OMe

Br 7-Cl n-Pr OMe

Br 7-Cl i-Pr OMe

Br 7-Cl 4-F-Ph OMe

Br 7-CF3 C0 2 Me OMe

Br 7-CF3 C0 2 Et OMe

Br 7-CF3 Me OMe

Br 7-CF3 n-Pr OMe

Br 7-CF3 i-Pr OMe

Br 7-CF3 4-F-Ph OMe

OCF 3 6-F C0 2 Me OMe

OCF 3 6-F C0 2 Et OMe

OCF 3 6-F Me OMe

OCF 3 6-F n-Pr OMe OCF 3 6-F i-Pr OMe OCF 3 6-F 4-F-Ph OMe

B 1 B^ B 3 X B B B 3 X

OCF 3 7-F C0 Me OMe Br 7-F C0 2 Me OCH 2 Ph

OCF3 7-F C0 2 Et OMe Br 7-F C0 2 Et OCH 2 Ph

OCF3 7-F Me OMe Br 7-F Me OCH Ph

OCF3 7-F n-Pr OMe Br 7-F n-Pr OCH 2 Ph

OCF3 7-F i-Pr OMe Br 7-F i-Pr OCH 2 Ph

OCF3 7-F 4-F-Ph OMe Br 7-F 4-F-Ph OCH 2 Ph

OCF3 7-Cl C0 2 Me OMe Br 7-Cl C0 2 Me OCH 2 Ph

OCF3 7-Cl C0 2 Et OMe Br 7-Cl C0 2 Et OCH 2 Ph

OCF 3 7-Cl Me OMe Br 7-Cl Me OCH 2 Ph

OCF 3 7-Cl n-Pr OMe Br 7-Cl n-Pr OCH 2 Ph

OCF 3 7-Cl i-Pr OMe Br 7-Cl i-Pr OCH 2 Ph

OCF 3 7-Cl 4-F-Ph OMe Br 7-Cl 4-F-Ph OCH 2 Ph

OCF 3 7-CF 3 C0 2 Me OMe Br 7-CF3 C0 Me OCH 2 Ph

OCF 3 7-CF 3 C0 2 Et OMe Br 7-CF3 C0 2 Et OCH 2 Ph

OCF 3 7-CF 3 Me OMe Br 7-CF3 Me OCH 2 Ph

OCF3 7-C 3 n-Pr OMe Br 7-CF3 n-Pr OCH 2 Ph

0CF 3 7-CF3 i-Pr OMe Br 7-CF3 i-Pr OCH 2 Ph

OCF 3 7-CF3 4-F-Ph OMe Br 7-CF3 4-F-Ph OCH 2 Ph

CF 3 6-F C0 Me OCH 2 Ph OCF3 6-F C0 2 Me OCH 2 Ph

CF 3 6-F C0 2 Et OCH 2 Ph OCF3 6-F C0 2 Et OCH 2 Ph

CF 3 6-F Me OCH 2 Ph OCF3 6-F Me OCH 2 Ph

CF 3 6-F n-Pr OCH 2 Ph OCF3 6-F n-Pr OCH 2 Ph

CF 3 6-F i-Pr OCH 2 Ph OCF3 6-F i-Pr OCH 2 Ph

CF 3 6-F 4-F-Ph OCH 2 Ph OCF3 6-F 4-F-Ph OCH 2 Ph

CF 3 7-F C0 2 Me OCH 2 Ph OCF3 7-F C0 Me OCH 2 Ph

CF 3 7-F C0 2 Et OCH Ph OCF3 7-F C0 2 Et OCH 2 Ph

CF 3 7-F Me OCH 2 Ph OCF3 7-F Me OCH Ph

CF 3 7-F n-Pr OCH 2 Ph OCF3 7-F n-Pr OCH Ph

CF 3 7-F i-Pr OCH 2 Ph OCF3 7-F i-Pr OCH 2 Ph

CF 3 7-F 4-F-Ph OCH 2 Ph OCF3 7-F 4-F-Ph OCH 2 Ph

B 1 B B 3 X B α B^ B 3

CF3 7-CF3 C0 2 Me NHS0 2 NH 2 CF3 7-CF3 C0 2 Me NH(4-Me0-Ph)

OCF3 7-CF3 C0 2 Me NHS0 2 NH 2 OCF3 7-CF3 C0 2 Me NH(4-MeO-Ph)

CF3 7-Cl i-Pr NHS0 2 NH 2 CF 3 7-Cl i-Pr NH(4-MeO-Ph)

OCF3 7-Cl i-Pr NHS0 NH 2 OCF3 7-Cl i-Pr NH(4-MeO-Ph)

CF 3 7-CF3 4-F-Ph NHS0 2 NH CF 3 7-CF3 4-F-Ph NH(4-MeO-Ph)

OCF3 7-CF3 4-F-Ph NHS0 2 NH 2 OCF3 7-CF3 4-F-Ph NH(4-MeO-Ph)

CF 3 7-CF3 C0 2 Me NHS0 2 NHPh CF3 7-CF3 C0 2 Me NHCH OCH

OCF3 7-CF3 C0 2 Me NHS0 2 NHPh OCF3 7-CF3 C0 2 Me NHCH C_CH

CF 3 7-Cl i-Pr NHS0 2 NHPh CF3 7-Cl i-Pr NHCH C_CH

OCF3 7-Cl i-Pr NHS0 2 NHPh OCF3 7-Cl i-Pr NHCH 2 C_CH

CF 3 7-CF3 4-F-Ph NHS0 2 NHPh CF3 7-CF3 4-F-Ph NHCH 2 OCH

OCF 7-CF3 4-F-Ph NHS0 2 NHPh OCF-a 7-CF3 4-F-Ph NHCH 2 C_CH

B 1 B 3 X B 1 B^ B 3 X

OCF 3 7-F C0 Me NH 2 Br 7-F C0 2 Me NHMe

OCF3 7-F C0 2 Et NH 2 Br 7-F C0 2 Et NHMe

OCF3 7-F Me NH 2 Br 7-F Me NHMe

OCF3 7-F n-Pr NH 2 Br 7-F n-Pr NHMe

OCF3 7-F i-Pr NH 2 Br 7-F i-Pr NHMe

OCF 3 7-F 4-F-Ph NH 2 Br 7-F 4-F-Ph NHMe

OCF 3 7-Cl C0 Me NH 2 Br 7-Cl C0 2 Me NHMe

OCF 3 7-Cl C0 2 Et NH 2 Br 7-Cl C0 2 Et NHMe

OCF 3 7-Cl Me NH 2 Br 7-Cl Me NHMe

0CF 3 7-Cl n-Pr NH 2 Br 7-Cl n-Pr , NHMe I

OCF 3 7-Cl i-Pr NH 2 Br 7-Cl i-Pr NHMe

OCF 3 7-Cl 4-F-Ph NH 2 Br 7-Cl 4-F-Ph NHMe

OCF 3 7-CF 3 C0 2 Me NH 2 Br 7-CF 3 C0 2 Me NHMe

OCF 3 7-CF 3 C0 2 Et NH 2 Br 7-CF 3 C0 2 Et NHMe

0CF 3 7-CF 3 Me NH 2 Br 7-CF 3 Me NHMe

OCF 3 7-CF 3 n-Pr NH 2 Br 7-CF 3 n-Pr NHMe

OCF 3 7-CF 3 i-Pr NH 2 Br 7-CF 3 i-Pr NHMe

OCF 3 7-CF 3 4-F-Ph NH 2 Br 7-CF 3 4-F-Ph NHMe

CF 3 6-F C0 2 Me NHMe OCF 3 6-F C0 2 Me NHMe

CF 3 6-F C0 2 Et NHMe OCF 3 6-F C0 2 Et NHMe

CF 3 6-F Me NHMe OCF 3 6-F Me NHMe

CF 3 6-F n-Pr NHMe OCF 3 6-F n-Pr NHMe

CF 3 6-F i-Pr NHMe OCF 3 6-F i-Pr NHMe

CF 3 6-F 4-F-Ph NHMe OCF 3 6-F 4-F-Ph NHMe

CF 3 7-F C0 2 Me NHMe OCF 3 7-F C0 2 Me NHMe CF 3 7-F C0 2 Et NHMe OCF 3 7-F C0 2 Et NHMe CF3 7-F Me NHMe OCF 3 7-F Me NHMe CF3 7-F n-Pr NHMe OCF 3 7-F n-Pr NHMe CF3 7-F i-Pr NHMe OCF 3 7-F i-Pr NHMe CF 3 7-F 4-F-Ph NHMe OCF 3 7-F 4-F-Ph NHMe

B 1 B B 3 X

CF 3 7-Cl C0 2 Me NHMe

CF 3 7-Cl C0 2 Et NHMe

CF 3 7-Cl Me NHMe

CF 3 7-Cl n-Pr NHMe

CF 3 7-Cl i-Pr NHMe

CF 3 7-Cl 4-F-Ph NHMe

CF 3 7-CF3 C0 2 Me NHMe

CF 3 7-CF3 C0 2 Et NHMe

CF 3 7-CF3 Me NHMe

CF 3 7-CF3 n-Pr NHMe

CF 3 7-CF3 i-Pr NHMe

C 3 7-CF3 4-F-Ph NHMe

Br 6-F C0 2 Me NHCHO

Br 6-F C0 2 Et NHCHO

Br 6-F Me NHCHO

Br 6-F n-Pr NHCHO

Br 6-F i-Pr NHCHO

Br 6-F 4-F-Ph NHCHO

Br 7-F C0 2 Me NHCHO

Br 7-F C0 2 Et NHCHO

Br 7-F Me NHCHO

Br 7-F n-Pr NHCHO

Br 7-F i-Pr NHCHO

Br 7-F 4-F-Ph NHCHO

Br 7-Cl C0 2 Me NHCHO

Br 7-Cl C0 2 Et NHCHO

Br 7-Cl Me NHCHO

Br 7-Cl n-Pr NHCHO

Br 7-Cl i-Pr NHCHO

Br 7-Cl 4-F-Ph NHCHO

B B B 3 X B 1 B* B 3 X

Br 7-CF3 C0 2 Me NHCHO CF3 7-CF3 CO^e NHCHO

Br 7-CF3 C0 2 Et NHCHO CF 3 7-CF3 C0 2 Et NHCHO

Br 7-CF3 NHCHO CF3 7-CF 3 Me NHCHO

Br 7-CF3 n-Pr NHCHO CF3 7-CF3 n-Pr NHCHO

Br 7-CF3 i-Pr NHCHO CF 3 7-CF3 i-Pr NHCHO

Br 7-CF3 4-F-Ph NHCHO CF3 7-CF3 4-F-Ph NHCHO

OCF 3 6-F C0 2 Me NHCHO Br 6-F C0 2 Me NH(CO)Me

OCF3 6-F C0 2 Et NHCHO Br 6-F C0 2 Et NH(CO)Me

OCF3 6-F Me NHCHO Br 6-F M© NH(CO)Me

OCF3 6-F n-Pr NHCHO Br 6-F n-Pr NH(CO)Me

OCF3 6-F i-Pr NHCHO Br 6-F i-Pr NH(CO)Me

OCF3 6-F 4-F-Ph NHCHO Br 6-F 4-F-Ph NH(CO)Me

OCF3 7-F C0 2 Me NHCHO Br 7-F CO^e NH(CO)Me

OCF3 7-F C0 2 Et NHCHO Br 7-F C0 Et NH(CO)Me

OCF3 7-F Me NHCHO Br 7-F Me NH(CO)Me

OCF3 7-F n-Pr NHCHO Br 7-F n-Pr NH(CO)Me

OCF3 7-F i-Pr NHCHO Br 7-F i-Pr NH(CO)Me

OCF3 7-F 4-F-Ph NHCHO Br 7-F 4-F-Ph NH(CO)Me

OCF3 7-Cl C0 2 Me NHCHO Br 7-Cl C0 2 Me NH(CO)Me

OCF3 7-Cl C0 2 Et NHCHO Br 7-Cl C0 2 Et NH(CO)Me

OCF3 7-Cl Me NHCHO Br 7-Cl Me NH(CO)Me

OCF3 7-Cl n-Pr NHCHO Br 7-Cl n-Pr NH(CO)Me

OCF3 7-Cl i-Pr NHCHO Br 7-Cl i-Pr NH(CO)Me

OCF3 7-Cl 4-F-Ph NHCHO Br 7-Cl 4-F-Ph NH(CO)Me

OCF3 7-CF3 C0 2 Me NHCHO Br 7-CF3 C0 2 Me NH(CO)Me

OCF3 7-CF3 C0 2 Et NHCHO Br 7-CF3 C0 2 Et NH(CO)Me

OCF3 7-CF3 Me NHCHO Br 7-CF3 Me NH(CO)Me

OCF3 7-CF3 n-Pr NHCHO Br 7-CF3 n-Pr NH(CO)Me

OCF3 7-CF3 i-Pr NHCHO Br 7-CF3 i-Pr NH(CO)Me

OCF3 7-CF3 4-F-Ph NHCHO Br 7-CF3 4-F-Ph NH(CO)Me

B 1 B 3 X B A B^ B 3 X

OCF 3 7-Cl C0 2 Me OMe Br 7-Cl C0 2 Me N-CHPh

OCF3 7-Cl C0 2 Et OMe Br 7-Cl C0 2 Et N-CHPh

OCF3 7-Cl Me OMe Br 7-Cl Me N-CHPh

OCF3 7-Cl n-Pr OMe Br 7-Cl n-Pr N-CHPh

OCF3 7-Cl i-Pr OMe Br 7-Cl i-Pr N-CHPh

0CF 3 7-Cl 4-F-Ph OMe Br 7-Cl 4-F-Ph N-CHPh

OCF 3 7-CF 3 C0 Me OMe Br 7-CF 3 CO jj Me N-CHPh

OCF 3 7-CF 3 C0 2 Et OMe Br 7-CF3 C0 2 Et N-CHPh

OCF 3 7-CF 3 Me OMe Br 7-CF3 Me N-CHPh

OCF 3 7-CF 3 n-Pr OMe Br 7-CF3 n-Pr N-CHPh

OCF 3 7-CF 3 i-Pr OMe Br 7-CF3 i-Pr N-CHPh

OCF 3 7-CF 3 4-F-Ph OMe Br 7-CF3 4-F-Ph N-CHPh

CF 3 6-F C0 2 Me N-CHPh OCF 3 6-F C0 2 Me N-CHPh

CF 3 6-F C0 Et N-CHPh OCF 3 6-F C0 Et N-CHPh

CF 3 6-F Me N-CHPh OCF 3 6-F Me N-CHPh

CF 3 6-F n-Pr N-CHPh OCF 3 6-F n-Pr N-CHPh

CF 3 6-F i-Pr N-CHPh OCF 3 6-F i-Pr N-CHPh

CF 3 6-F 4-F-Ph N-CHPh OCF 3 6-F 4-F-Ph N-CHPh

CF 3 7-F C0 2 Me N-CHPh OCF 3 7-F C0 2 Me N-CHPh

C 3 7-F C0 2 Et N-CHPh OCF 3 7-F C0 2 Et N-CHPh CF 3 7-F Me N-CHPh OCF 3 7-F Me N-CHPh CF 3 7-F n-Pr N-CHPh OCF 3 7-F n-Pr N-CHPh

CF 3 7-F i-Pr N-CHPh OCF 3 7-F i-Pr N-CHPh CF 3 7-F 4-F-Ph N-CHPh OCF 3 7-F 4-F-Ph N-CHPh CF 3 7-Cl C0 2 Me N-CHPh OCF 3 7-Cl C0 2 Me N-CHPh CF 3 7-Cl C0 2 Et N-CHPh OCF 3 7-Cl C0 2 Et N-CHPh CF 3 7-Cl Me N-CHPh OCF 3 7-Cl Me N-CHPh CF 3 7-Cl n-Pr N-CHPh OCF 3 7-Cl n-Pr N-CHPh CF 3 7-Cl i-Pr N-CHPh OCF 3 7-Cl i-Pr N-CHPh CF 3 7-Cl 4-F-Ph N-CHPh OCF 3 7-Cl 4-F-Ph N-CHPh

B 1 B B 3 X B 1 # B- 3 X

CF 3 7-Cl C0 2 Me Et CO^e Et

CF 3 7-Cl C0 2 Et Et C0 2 Et Et

CF 3 7-Cl Me Et Me Et

CF3 7-Cl n-Pr Et n-Pr Et

CF 3 7-Cl i-Pr Et i-Pr Et

C 3 7-Cl 4-F-Ph Et 4-F-Ph Et CF 3 7-CF3 C0 2 Me Et C0 2 Me Et CF 3 7-CF3 C0 2 Et Et C0 2 Et Et CF 3 7-CF3 Me Et Me Et CF 3 7-CF3 n-Pr Et n-Pr f.t CF 3 7-CF3 i-Pr Et i-Pr Et

CF 3 7-CF3 4-F-Ph Et 4-F-Ph Et

Br 6-F C0 2 Me -CH 2 OCH 3 C0 Me -CH 2 OCH 3

Br 6-F C0 2 Et -CH 2 OCi_3 CF3 6-F C0 2 Et -CH 2 OCH 3

Br 6-F Me -CH 2 OCH 3 CF3 6-F Me -CH 2 OCH 3

Br 6-F n-Pr -CH 2 OCH 3 CF3 6-F n-Pr -CH 2 OCH 3

Br 6-F i-Pr -CH 2 OCH 3 CF3 6-F i-Pr —CH 2 OCH 3

Br 6-F 4-F-Ph -CH 2 OCH 3 CF3 6-F 4-F-Ph -CH 2 OCH 3

Br 7-F C0 2 Me -CH 2 OCH 3 CF3 7-F C0Me -CH 2 OCH 3

Br 7-F C0 2 Et -CH 2 OCH 3 CF3 7-F C0 2 Et -CH 2 OCH 3

Br 7-F Me -CH 2 OCH 3 CF 3 7-F Me -CH 2 OCH 3

Br 7-F n-Pr -CH 2 OCH 3 CF 3 7-F n-Pr -CH 2 OCH 3

Br 7-F i-Pr -CH 2 OCH 3 CF 3 7-F i-Pr -CH 2 OCH 3

Br 7-F 4-F-Ph -CH 2 OCH 3 CF 3 7-F 4-F-Ph -CH 2 OCH 3

Br 7-Cl C0 2 Me -CH 2 OCH 3 CF 3 7-Cl C0 2 Me -CH 2 OCH 3

Br 7-Cl C0 2 Et -CH 2 OCH 3 CF 3 7-Cl C0 2 Et -CH 2 OCH 3

Br 7-Cl Me -CH 2 OCH 3 CF 3 7-Cl Me -CH 2 OCH 3

Br 7-Cl n-Pr -CH 2 OCH 3 CF 3 7-Cl n-Pr -CH 2 OCH 3

Br 7-Cl i-Pr -CH 2 OCH 3 CF 3 7-Cl i-Pr -CH 2 OCH 3

Br 7-Cl 4-F-Ph -CH 2 OCH 3 CF 3 7-Cl 4-F-Ph —CH 2 OCH 3

8 Q Q O Q O O Q Q Q O O Q Q O O O Q Q Q O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω co co co co co co co oo oo co co co co oo co oo co oo oo oo c

-4 s4 sJ -4 -4 sj _J ^l -j •4 s ~ •sl s j sJ -4 -sl -sl Ol OI I I I I I I I I I I I I I I I I I I I I Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω tn tΛ tΛ tn ππ tn In i

. .. . . . . H H H H co co oo co co oo

I I I I I I I I I I I I I I I I I a .- Oa Ωa Ωa Ωa Ωa Ωa Ωa Ωa Ωa Ωa Ωa Ωa Ω O Ω Ω Ω Ω Ω

M M M M M M M M M M M M M Ma Ma Ma Ma Ma Ma Ma

8 a 8a 8a 8a 8a 88 88 8 co co co co co cao ca 8 o ca 8 o ca 8 o ca 8 o ωa 8 ca 8 888 8 o cao cao ωa oao cao cao cao cao

I I I I I I I I I I I I I I I I I I I I Oa Ωa Ωa Ωa Ωa Oa Ωa Ωa Ω Ω Ω Ω Ω

M M M M M M M M Ma Ma Ω Ma Ma Ω Ma Ω Ω Ω Ω Ω Ma Ma Ma Ma Ma Ma Ma

888 a 8 a 8888 a 88 a 8 a 88 a 88 a 8 a 88 a 88 a

B 1 B^ B J X 1 B B 3 X

Br 7-CF3 C0 2 Me -CH 2 0_CH CF3 7-CF3 CO^e -CH 2 C_CH

Br 7-C 3 C0 2 Et -CH 2 C_CH CF3 7-CF3 C0 2 Et -CH 2 C_CH

Br 7-CF3 Me -CH 2 0_CH CF3 7-CF3 Me -CH 2 C_CH

Br 7-CF3 n-Pr -CH 2 C_CH CF3 7-CF3 n-Pr -CH 2 0_CH

Br 7-CF3 Pr -CH 2 C_CH CF3 7-CF3 i-Pr -CH 2 0_CH

Br 7-CF3 4-F-Ph -CH OCH CF3 7-CF3 4-F-Ph -CH C_CH

OCF 3 6-F C0 2 Me -CH 2 Q-CH Br 6-F C0 2 Me -CH 2 CH=CH 2

OCF3 6-F C0 Et -CH 2 *CH Br 6-F C0 2 Et -CH 2 CH=CH 2

OCF3 6-F Me -CH C-CH Br 6-F Me -CH 2 CH_CH 2

OCF3 6-F n-Pr -CH 2 C_CH Br 6-F n-Pr -CH 2 CH=CH 2

OCF3 6-F Pr -CH 2 C_CH Br 6-F Pr -CH 2 CH=CH 2

OCF3 6-F 4-F-Ph -CH 2 C_CH Br 6-F 4-F-Ph -CH 2 CH=CH 2

OCF3 7-F C0 2 Me -CH 2 OCH Br 7-F C0 2 Me —CH 2 CH— H 2

OCF3 7-F C0 2 Et -CH 2 C_CH Br 7-F C0 2 Et -CH 2 CH=CH 2

OCF3 7-F Me -CH 2 0_CH Br 7-F Me -CH 2 CH=CH 2

OCF3 7-F n-Pr -CH 2 C«CH Br 7-F n-Pr -CH 2 CH=CH

OCF 3 7-F Pr -CH 2 C-CH Br 7-F Pr -CH 2 CH=CH 2

OCF 3 7-F 4-F-Ph -CH 2 C_CH Br 7-F 4-F-Ph -CH 2 CH=CH 2

CF 3 7-F C0 2 Me -CH 2 C_CH OCF3 7-Cl C0 2 Me -CH 2 C_CH

CF 3 7-F C0 Et -CH 2 OCH OCF3 7-Cl C0 2 Et -CH 2 C_CH

CF 3 7-F Me -CH 2 C_CH OCF3 7-Cl Me -CH 2 C-CH

CF 3 7-F n-Pr -CH 2 C_CH OCF3 7-Cl n-Pr -CH 2 C_CH

CF 3 7-F i-Pr -CH 2 C_CH OCF3 7-Cl Pr -CH 2 C«CH

CF 3 7-F 4-F-Ph -CH 2 C_CH OCF3 7-Cl 4-F-Ph -CH 2 C_CH

CF 3 7-Cl CO^e -CH 2 CβCH OCF3 7-CF3 C0 2 Me -CH 2 CβCH

CF3 7-Cl C0 2 Et -CH C_CH OCF3 7-CF3 C0 2 Et -CH C_CH

CF3 7-Cl Me -CH 2 C_CH OCF3 7-CF3 Me -CH 2 OCH

CF3 7-Cl n-Pr -CH 2 C_CH OCF3 7-CF3 n-Pr -CH CβCH

CF3 7-Cl i-Pr -CH 2 C_CH OCF3 7-CF3 Pr -CH 2 C_CH

CF3 7-Cl 4-F-Ph -CH 2 C_CH OCF3 7-CF3 4-F-Ph -CH 2 C*CH

B 1 B^ B 3 B 1 B^ B 3

CF 3 6-F C0 2 Me -CH 2 CH=CH 2 OCF 3 6-F C0 2 Me -CH 2 CH=CH 2

CF 3 6-F C0 2 Et -CH 2 CH=CH OCF 3 6-F C0 2 Et -CH 2 CH=CH 2

CF 3 6-F Me -CH 2 CH=CH 2 OCF 3 6-F Me -CH 2 CH=CH 2

CF 3 6-F n-Pr -CH 2 CH=CH 2 OCF 3 6-F n-Pr -CH 2 CH=CH 2

CF 3 6-F Pr -CH CH=CH 2 OCF 3 6-F Pr -CH 2 CH=CH 2

CF 3 6-F 4-F-Ph -CH 2 CH=CH 2 OCF 3 6-F 4-F-Ph -CH 2 CH=CH 2 F 3 7-F C0 2 Me -CH 2 CH=CH 2 OCF 3 7-F C0 2 Me -CH CH=CH 2 CF 3 7-F C0 Et -CH 2 CH-CH 2 OCF 3 7-F CO z Et -CH 2 CH=CH 2

CF 3 7-F Me -CH 2 CH=CH 2 OCF3 7-F Me -CH 2 CH=CH 2

CF 3 7-F n-Pr -CH CH=CH 2 OCF3 7-F n-Pr CH 2 CH=CH 2

CF 3 7-F Pr -CH 2 CH=CH 2 OCF3 7-F Pr -CH 2 CH=CH 2

C 3 7-F 4-F-Ph -CH 2 CH=CH 2 OCF3 7-F 4-F-Ph -CH 2 CH=CH 2

CF3 7-Cl Cθ 2 Me -CH CH=CH 2 OCF3 7-Cl C0 2 Me -CH 2 CH=CH 2

CF 3 7-Cl C0 2 Et -CH 2 CH=CH 2 OCF3 7-Cl C0 2 Et -CH 2 CH=CH 2

CF 3 7-Cl Me -CH 2 CH=CH 2 OCF3 7-Cl Me -CH 2 CH=CH 2

CF 3 7-Cl n-Pr -CH 2 CH=CH 2 OCF3 7-Cl n-Pr —CH 2 CH—CH 2

C 3 7-Cl Pr -CH 2 CH=CH 2 OCF3 7-Cl Pr -CH 2 CH=CH 2

CF 3 7-Cl 4-F-Ph -CH 2 CH=CH 2 OCF3 7-Cl 4-F-Ph -CH 2 CH=CH 2

Br 7-Cl C0 2 Me -CH 2 CH-CH 2 CF 3 7-CF3 C0 2 Me —CH 2 CH_CH 2

Br 7-Cl C0 2 Et -CH 2 CH=CH 2 CF 3 7-CF3 C0 2 Et -CH 2 CH=CH 2

Br 7-Cl Me -CH 2 CH_CH 2 CF3 7-CF3 Me —CH 2 CH—CH 2

Br 7-Cl n-Pr -CH 2 CH=CH 2 CF3 7-CF3 n-Pr —CH 2 CH_CH 2

Br 7-Cl Pr -CH CH=CH 2 CF 3 7-CF3 Pr -CH 2 CH_CH 2

Br 7-Cl 4-F-Ph -CH 2 CH=CH 2 CF 3 7-CF3 4-F-Ph -CH 2 CH=CH 2

Br 7-CF 3 C0 2 Me -CH 2 CH=CH 2 OCF3 7-CF3 C0 2 Me -CH 2 CH_CH 2

Br 7-CF 3 C0 2 Et -CH 2 CH=CH 2 OCF3 7-CF3 C0 2 Et —CH 2 CH—CH 2

Br 7"CF 3 Me -CH CH=CH 2 OCF3 7-CF3 Me -CH CH=CH 2

Br 7-CF 3 n-Pr -CH 2 CH=CH 2 OCF3 7-CF3 n-Pr -CH 2 CH=CH

Br 7-CF 3 Pr -CH 2 CH=CH 2 OCF3 7-CF3 Pr -CH 2 CH=CH 2

Br 7-CF 3 4-F-Ph -CH 2 CH=CH 2 OCF3 7-CF3 4-F-Ph -CH 2 CH=CH 2

R x ^ B J X B B^ B 3 X

Br 6-F C0 2 Me NHMe CF 3 7-Cl C0 2 Me NHMe

Br 6-F C0 2 Et NHMe CF 3 7-Cl C0 Et NHMe

Br 6-F i-Pr NHMe CF 3 7-Cl i-Pr NHMe

Br 6-F Me NHMe CF 3 7-Cl Me NHMe

Br 6-F 4-F-Ph NHMe CF 3 7-CΪ 4-F-Ph NHMe

Br 7-F C0 2 Me NHMe CF 3 7-CF 3 C0 Me NHMe

Br 7-F C0 2 Et NHMe CF 3 7-CF 3 C0 2 Et NHMe

Br 7-F i-Pr NHMe CF 3 7-CF 3 i-Pr NHMe

Br 7-F Me NHMe CF 3 7-CF 3 Me NHMe

Br 7-F 4-F-Ph NHMe CF 3 7-CF 3 4-F-Ph NHMe

Br 7-Cl C0 2 Me NHMe OCF 3 6-F C0 2 Me NHMe

Br 7-Cl C0 Et NHMe OCF 3 6-F C0 2 Et NHMe

Br 7-Cl i-Pr NHMe OCF 3 6-F i-Pr NHMe

Br 7-Cl Me NHMe OCF 3 6-F Me NHMe

Br 7-Cl 4-F-Ph NHMe OCF 3 6-F 4-F-Ph NHMe

Br 7-CF 3 C0 2 Me NHMe OCF 3 7-F C0 Me NHMe

Br 7-CF 3 C0 2 Et NHMe OCF 3 7-F C0 2 Et NHMe

Br 7-CF 3 i-Pr NHMe OCF 3 7-F i-Pr NHMe

Br 7-CF 3 Me NHMe OCF 3 7-F Me NHMe

Br 7~CF 3 4-F-Ph NHMe OCF 3 7-F 4-F-Ph NHMe

CF 3 6-F C0 2 Me NHMe OCF 3 7-Cl C0 Me NHMe

CF 3 6-F C0 2 Et NHMe OCF 3 7-Cl C0 2 Et NHMe

CF 3 6-F i-Pr NHMe OCF 3 7-Cl i-Pr NHMe

CF 3 6-F Me NHMe OCF 3 7-Cl Me NHMe

CF 3 6-F 4-F-Ph NHMe OCF 3 7-Cl 4-F-Ph NHMe

CF 3 7-F C0 2 Me NHMe OCF 3 7-CF 3 C0 2 Me NHMe

CF 3 7-F C0 2 Et NHMe OCF 3 7-CF 3 C0 2 Et NHMe

CF 3 7-F i-Pr NHMe OCF 3 7-CF 3 i-Pr NHMe

CF 3 7-F Me NHMe OCF 3 7"CF 3 Me NHMe

C 3 7-F 4-F-Ph NHMe OCF 3 7-CF 3 4-F-Ph NHMe

B B < = B J X B 1 B^ B 5 X

Br 6-F C0 2 Me NH.CO . Me CF3 7-Cl C0 2 Me NH(CO)Me

Br 6-F C0 2 Et NH(CO)Me CF 3 7-Cl C0 2 Et NH(CO)Me

Br 6-F i-Pr NH(CO)Me CF 3 7-Cl i-Pr NH(C )Me

Br 6-F Me NH(CO)Me CF 3 7-Cl Me NH.CO.Me

Br 6-F 4-F-Ph NH(CO)Me CF 3 7-Cl 4-F-Ph NH.CO.Me

Br 7-F C0 2 Me NH(CO)Me CF3 7-CF3 C0 2 Me NH.CO . Me

Br 7-F C0 2 Et NH(CO)Me CF 3 7-CF3 C0 2 Et NH(CO) e

Br 7-F i-Pr NH(CO)Me CF3 7-CF3 i-Pr NH(CO)Me

Br 7-F Me NH(CO)Me CF 3 7-CF3 Me NH.CO.Me

Br 7-F 4-F-Ph NH(CO)Me CF3 7-CF3 4-F-Ph NH.CO.Me

Br 7-Cl C0 2 Me NH(CO)Me OCF3 6-F C0 2 Me NH(CO)Me

Br 7-Cl C0 2 Et NH(CO)Me OCF3 6-F C0 2 Et NH(CO)Me

Br 7-Cl i-Pr NH(CO)Me OCF3 6-F i-Pr NH(CO)Me

Br 7-Cl Me NH(CO)Me OCF3 6-F Me NH(CO)Me

Br 7-Cl 4-F-Ph NH(CO)Me OCF3 6-F 4-F-Ph NH(CO)Me

Br 7-CF3 C0 2 Me NH(CO)Me OCF3 7-F C0 2 Me NH(CO)Me

Br 7-CF3 C0 2 Et NH(CO)Me OCF3 7-F C0 2 Et NH(CO)Me

Br 7-CF3 i-Pr NH.CO.Me OCF3 7-F i-Pr NH.CO.Me

Br 7-CF3 Me NH(CO)Me OCF3 7-F Me NH.CO.Me

Br 7-CF3 4-F-Ph NH(CO)Me OCF3 7-F 4-F-Ph NH(CO)Me

C 3 6-F C0 2 Me NH(CO)Me OCF3 7-Cl C0 2 Me NH(CO)Me CF 3 6-F C0 Et NH(CO)Me OCF3 7-Cl C0 2 Et NH(CO)Me

C 3 6-F i-Pr NH(CO)Me OCF3 7-Cl i-Pr NH(CO)Me CF 3 6-F Me NH(CO)Me OCF3 7-Cl Me NH(CO)Me

CF 3 6-F 4-F-Ph NH(CO)Me OCF3 7-Cl 4-F-Ph NH(CO)Me CF 3 7-F C0 2 Me NH(CO)Me OCF3 7-CF3 C0 2 Me NH(CO)Me CF 3 7-F C0 2 Et NH(CO)Me OCF3 7-CF3 C0 2 Et NH(CO)Me CF 3 7-F i-Pr NH(CO)Me OCF3 7-CF3 i-Pr NH(CO)Me

CF 3 7-F Me NH(CO)Me OCF3 7-CF3 Me NH(CO)Me CF 3 7-F 4-F-Ph NH(CO)Me OCF3 7-CF3 4-F-Ph NH(CO)Me

B x B B 3 X B 1 B z B 3 X

Br 6-F C0 2 Me NH(CO)NHMe C 3 7-Cl C0 2 Me NH(CO)NHMe

Br 6-F C0 2 Et NH(CO)NHMe CF3 7-Cl C0 2 Et NH(CO)NHMe

Br 6-F i-Pr NH(CO) HMe CF3 7-Cl i-Pr NH(CO)NHMe

Br 6-F Me NH(CO)NHMe CF3 7-Cl Me NH(CO)NHMe

Br 6-F 4-F-Ph NH(CO)NHMe CF3 7-Cl 4-F-Ph NH(CO)NHMe

Br 7-F CO jj Me NH(CO)NHMe CF3 7-CF3 O0Me NH(CO)NHMe

Br 7-F C0 2 Et NH(CO)NHMe CF3 7-CF3 C0 Et NH(CO)NHMe

Br 7-F i-Pr NH(CO)NHMe CF 3 7-CF3 i-Pr NH(CO)NHMe

Br 7-F Me NH(CO)NHMe CF3 7-CF3 Me NH(CO)NHMe

Br 7-F 4-F-Ph NH(CO)NHMe CF3 7-CF3 4-F-Ph NH(CO)NHMe

Br 7-Cl C0 2 Me NH(CO)NHMe OCF 3 6-F C0 2 Me NH(CO)NHMe

Br 7-Cl C0 2 Et NH(CO) HMe OCF 3 6-F C0 2 Et NH(CO)NHMe

Br 7-Cl i-Pr NH(CO)NHMe OCF 3 6-F i-Pr NH(CO)NHMe

Br 7-Cl Me NH(CO)NHMe OCF 3 6-F Me NH(CO)NHMe

Br 7-Cl 4-F-Ph NH(CO)NHMe OCF 3 6-F 4-F-Ph NH(CO)NHMe

Br 7-CF3 C0 2 Me NH(CO)NHMe OCF 3 7-F CO^e NH(CO)NHMe

Br 7-CF3 C0 2 Et NH(CO)NHMe OCF 3 7-F C0 2 Et NH(CO)NHMe

Br 7-CF3 i-Pr NH(CO) HMe OCF 3 7-F i-Pr NH(CO)NHMe

Br 7-CF3 Me NH(CO)NHMe OCF 3 7-F Me NH(CO)NHMe

Br 7-CF3 4-F-Ph NH(CO)NHMe OCF 3 7-F 4-F-Ph NH(CO)NHMe

CF 3 6-F C0 2 Me NH(CO)NHMe OCF 3 7-Cl C0 2 Me NH(CO)NHMe C 3 6-F C0 2 Et NH(CO)NHMe OCF 3 7-Cl C0 2 Et NH(CO)NHMe CF 3 6-F i-Pr NH(CO)NHMe OCF 3 7-Cl i-Pr NH(CO)NHMe CF 3 6-F Me NH(CO)NHMe OCF 3 7-Cl Me NH(CO)NHMe CF 3 6-F 4-F-Ph NH(CO)NHMe OCF 3 7-Cl 4-F-Ph NH(CO)NHMe CF 3 7-F CO^e NH(CO)NHMe OCF 3 7-CF3 CO«>Me NH(CO)NHMe CF 3 7-F C0 2 Et NH(CO)NHMe OCF3 7-CF3 C0 2 Et NH(CO)NHMe CF3 7-F i-Pr NH(CO)NHMe OCF3 7-CF3 i-Pr NH(CO)NHMe CF 3 7-F Me NH(CO) HMe OCF3 7-CF3 Me NH(CO)NHMe CF 3 7-F 4-F-Ph NH(CO)NHMe OCF3 7-CF3 4-F-Ph NH(CO)NHMe

B B < = B J X B 1 B B J X

Br 6-F C0 2 Me N-CH 2 C 3 7-Cl C0 2 Me N-CH 2

Br 6-F C0 2 Et N-CH 2 CF 3 7-Cl C0 2 Et N-CH 2

Br 6-F i-Pr N—CH 2 CF 3 7-Cl i-Pr N-CH 2

Br 6-F Me N—CH 2 CF 3 7-Cl Me N"CH 2

Br 6-F 4-F-Ph N*"CH 2 CF 3 7-Cl 4-F-Ph N« :H 2

Br 7-F C0 2 Me N CH CF 3 7-CF3 C0 Me N-CH 2

Br 7-F C0 Et N_CH 2 CF 3 7-CF3 C0 Et N-CH 2

Br 7-F i-Pr N-CH 2 CF 3 7-CF3 i-Pr N-CH 2

Br 7-F Me N-CH 2 CF 3 7-CF3 Me N-CH 2

Br 7-F 4-F-Ph N-CH 2 CF 3 7-CF3 4-F-Ph N-CH

Br 7-Cl C0 2 Me N-CH 2 OCF 3 6-F C0 2 Me N-CH 2

Br 7-Cl C0 2 Et N-CH 2 OCF3 6-F C0 2 Et N-CH 2

Br 7-Cl i-Pr N-CH 2 OCF3 6-F i-Pr N-CH 2

Br 7-Cl Me N-CH 2 OCF3 6-F Me N-CH 2

Br 7-Cl 4-F-Ph N-CH 2 OCF3 6-F 4-F-Ph N-CH

Br 7~CF 3 C0 2 Me N-CH 2 OCF3 7-F C0 2 Me N-CH 2

Br 7-CF 3 C0 2 Et N-CH OCF3 7-F C0 2 Et N-CH 2

Br 7-CF 3 i-Pr N-CH 2 OCF3 7-F i-Pr N-CH 2

Br 7-CF 3 Me N-CH 2 OCF3 7-F Me N-CH

Br 7"CF 3 4-F-Ph N-CH 2 OCF3 7-F 4-F-Ph N-CH 2

CF 3 6-F C0 2 Me N-CH 2 OCF3 7-Cl C0 2 Me N-CH 2

CF 3 6-F C0 2 Et N-CH OCF3 7-Cl C0 Et N-CH 2

CF 3 6-F i-Pr N-CH 2 OCF3 7-Cl i-Pr N-CH 2

CF 3 6-F Me N-CH 2 OCF3 7-Cl Me N-CH 2

CF 3 6-F 4-F-Ph N-CH 2 OCF3 7-Cl 4-F-Ph N-CH 2

CF 3 7-F C0 2 Me N-CH 2 OCF3 7-CF3 CO^e N- H 2

CF 3 7-F C0 2 Et N-CH 2 OCF3 7-CF3 C0 2 Et N-CH 2

CF 3 7-F i-Pr N-CH 2 OCF3 7-CF3 i-Pr N-CH 2

CF 3 7-F Me N-CH 2 OCF 3 7-CF3 Me N-CH 2

CF 3 7-F 4-F-Ph N-CH 2 OCF 3 7-CF3 4-F-Ph N-CH 2

B x B^ B J X B 1 B < = B J X

Br 6-F C0 Me OCH 2 Ph CF 3 7-Cl C0 2 Me OCH Ph

Br 6-F C0 2 Et OCH 2 Ph CF 3 7-Cl C0 2 Et OCH 2 Ph

Br 6-F i-Pr OCH 2 Ph CF 3 7-Cl i-Pr OCH 2 Ph

Br 6-F Me OCH 2 Ph CF 3 7-Cl Me OCH 2 Ph

Br 6-F 4-F-Ph OCH 2 Ph CF 3 7-Cl 4-F-Ph OCH 2 Ph

Br 7-F C0 2 Me OCH 2 Ph CF 3 7-CF3 C0 2 Me OCH Ph

Br 7-F C0 2 Et OCH 2 Ph CF 3 7-CF3 C0 2 Et OCH 2 Ph

Br 7-F i-Pr OCH 2 Ph CF 3 7-CF3 i-Pr 0CH 2 Ph

Br 7-F Me OCH 2 Ph CF 3 7-CF3 Me OCH Ph

Br 7-F 4-F-Ph OCH 2 Ph CF 3 7-CF3 4-F-Ph OCH 2 Ph

Br 7-Cl C0 2 Me OCH Ph OCF 3 6-F C0 2 Me OCH 2 Ph

Br 7-Cl C0 Et OCH 2 Ph OCF3 6-F C0 2 Et OCH 2 Ph

Br 7-Cl i-Pr OCH 2 Ph OCF3 6-F i-Pr OCH 2 Ph

Br 7-Cl Me OCH 2 Ph OCF3 6-F Me OCH 2 Ph

Br 7-Cl 4-F-Ph OCH 2 Ph OCF3 6-F 4-F-Ph OCH 2 Ph

Br 7-CF 3 C0 2 Me OCH Ph OCF3 7-F C0 2 Me OCH 2 Ph

Br 7-CF 3 C0 Et OCH 2 Ph OCF3 7-F C0 2 Et OCH 2 Ph

Br 7-CF 3 i-Pr OCH 2 Ph OCF3 7-F i-Pr OCH 2 Ph

Br 7~CF 3 Me OCH 2 Ph OCF3 7-F Me OCH 2 Ph

Br 7"CF 3 4-F-Ph OCH 2 Ph OCF3 7-F 4-F-Ph OCH 2 Ph

CF 3 6-F C0 2 Me OCH 2 Ph OCF3 7-Cl C0 2 Me OCH 2 Ph

CF 3 6-F C0 2 Et OCH 2 Ph OCF3 7-Cl C0 2 Et OCH Ph

CF 3 6-F i-Pr OCH 2 Ph OCF3 7-Cl i-Pr OCH 2 Ph CF 3 6-F Me OCH 2 Ph OCF3 7-Cl Me OCH 2 Ph CF 3 6-F 4-F-Ph OCH 2 Ph OCF3 7-Cl 4-F-Ph OCH 2 Ph CF 3 7-F C0 2 Me OCH 2 Ph OCF3 7-CF3 C0 2 Me OCH 2 Ph CF 3 7-F C0 2 Et OCH Ph OCF3 7-CF3 C0 Et OCH 2 Ph CF 3 7-F i-Pr OCH 2 Ph OCF3 7-CF3 i-Pr OCH 2 Ph CF 3 7-F Me OCH 2 Ph OCF3 7-CF3 Me OCH 2 Ph CF 3 7-F 4-F-Ph OCH 2 Ph OCF3 7-CF3 4-F-Ph OCH 2 Ph

B 1 B^ B J X B 1 B^ B J X

Br 6-F C0 2 Me NHMe CF 3 7-Cl C0 Me NHMe

Br 6-F C0 2 Et NHMe C 3 7-Cl C0 2 Et NHMe

Br 6-F i-Pr NHMe CF 3 7-Cl i-Pr NHMe

Br 6-F Me NHMe CF 3 7-Cl Me NHMe

Br 6-F 4-F-Ph NHMe CF 3 7-Cl 4-F-Ph NHMe

Br 7-F C0 2 Me NHMe CF 3 7-CF 3 C0 2 Me NHMe

Br 7-F C0 2 Et NHMe CF 3 7-CF 3 C0 Et NHMe

Br 7-F i-Pr NHMe CF 3 7-CF 3 i-Pr NHMe

Br 7-F Me NHMe CF 3 7-CF 3 Me NHMe

Br 7-F 4-F-Ph NHMe CF 3 7-CF 3 4-F-Ph NHMe

Br 7-Cl C0 2 Me NHMe OCF 3 6-F C0 Me NHMe

Br 7-Cl C0 2 Et NHMe OCF 3 6-F C0 2 Et NHMe

Br 7-Cl i-Pr NHMe OCF 3 6-F i-Pr NHMe

Br 7-Cl Me NHMe OCF 3 6-F Me NHMe

Br 7-Cl 4-F-Ph NHMe OCF 3 6-F 4-F-Ph NHMe

Br 7-CF 3 C0 2 Me NHMe OCF 3 7-F C0 Me NHMe

Br 7-CF 3 C0 2 Et NHMe OCF 3 7-F C0 2 Et NHMe

Br 7-CF 3 i-Pr NHMe OCF 3 7-F i-Pr NHMe

Br 7-CF 3 Me NHMe OCF 3 7-F Me NHMe

Br 7-CF 3 4-F-Ph NHMe OCF 3 7-F 4-F-Ph NHMe

CF 3 6-F C0 2 Me NHMe OCF 3 7-Cl C0 2 Me NHMe

C 3 6-F C0 2 Et NHMe OCF 3 7-Cl C0 2 Et NHMe CF 3 6-F i-Pr NHMe OCF 3 7-Cl i-Pr NHMe CF 3 6-F Me NHMe OCF 3 7-Cl Me NHMe CF 3 6-F 4-F-Ph NHMe OCF 3 7-Cl 4-F-Ph NHMe CF 3 7-F C0 Me NHMe OCF 3 7-CF 3 C0 Me NHMe CF 3 7-F C0 2 Et NHMe OCF 3 7~CF 3 C0 2 Et NHMe CF 3 7-F i-Pr NHMe OCF 3 7-CF 3 i-Pr NHMe CF 3 7-F Me NHMe OCF 3 7-CF 3 Me NHMe CF 3 7-F 4-F-Ph NHMe OCF 3 7-CF 3 4-F-Ph NHMe

B A B < = B J X B 1 B < = B J X

Br 6-F C0 2 Me N-CH 2 CF3 7-Cl C0 2 Me N-CH 2

Br 6-F C0 Et N-CH CF3 7-Cl C0 2 Et N»CH 2

Br 6-F i-Pr N™CH 2 CF3 7-Cl i-Pr N-CH

Br 6-F Me N-CH 2 CF 3 7-Cl Me N«-CH 2

Br 6-F 4-F-Ph CF3 7-Cl 4-F-Ph N-CH 2

Br 7-F C0 2 Me N-CH 2 CF3 7-CF3 C0 2 Me N-CH 2

Br 7-F C0 2 Et N-CH 2 CF3 7-CF3 C0 2 Et N-CH 2

Br 7-F i-Pr N-CH 2 CF 3 7-CF3 i-Pr N-CH 2

Br 7-F Me N-CH 2 CF3 7-CF3 Me N-CH 2

Br 7-F 4-F-Ph N-CH 2 CF3 7-CF3 4-F-Ph N-CH 2

Br 7-Cl C0 2 Me N-CH 2 OCF3 6-F C0 2 Me N-CH 2

Br 7-Cl C0 2 Et N-CH 2 OCF3 6-F C0 Et N-CH 2

Br 7-Cl i-Pr N-CH 2 OCF3 6-F i-Pr N-CH 2

Br 7-Cl Me N-CH 2 OCF3 6-F Me N-CH 2

Br 7-Cl 4-F-Ph N-CH 2 OCF3 6-F 4-F-Ph N-CH 2

Br 7-CF3 C0 Me N-CH 2 OCF3 7-F C0 Me N-CH 2

Br 7-CF3 C0 2 Et N-CH 2 OCF3 7-F C0 2 Et N-CH 2

Br 7-CF3 i-Pr N-CH 2 OCF3 7-F i-Pr N-CH 2

Br 7-CF3 Me N-CH 2 OCF3 7-F Me N-CH 2

Br 7-CF3 4-F-Ph N-CH 2 OCF3 7-F 4-F-Ph N-CH 2

CF 3 6-F C0 2 Me N-CH 2 OCF3 7-Cl C0 2 Me N-CH 2

CF 3 6-F C0 2 Et N-CH 2 OCF3 7-Cl C0 2 Et N-CH 2

CF 3 6-F i-Pr N-CH 2 OCF3 7-Cl i-Pr N-CH 2

CF3 6-F Me N-CH 2 OCF3 7-Cl Me N-CH 2

CF3 6-F 4-F-Ph N-CH 2 OCF3 7-Cl 4-F-Ph N-CH 2

CF 3 7-F C0 2 Me N-CH 2 OCF3 7-CF3 C0 2 Me N-CH 2

CF 3 7-F C0 2 Et N-CH 2 OCF3 7-CF3 C0 Et N-CH 2

CF3 7-F i-Pr N«CH OCF3 7-CF3 i-Pr N-CH 2

CF3 7-F Me N-CH 2 OCF3 7-CF3 Me N-CH 2

CF 3 7-F 4-F-Ph N-CH 2 OCF3 7-CF3 4-F-Ph N-CH 2

B 1 B* B 3 X B 1 B B 3 X

Br 6-F CO^e N-CMe 2 CF 3 7-Cl C0 2 Me N-CMe 2

Br 6-F C0 2 Et N-CMe 2 CF3 7-Cl C0 2 Et N-CMe 2

Br 6-F i-Pr N-CMe 2 CF 3 7-Cl i-Pr N-CMe

Br 6-F Me N-CMe 2 CF3 7-Cl Me N_CMe 2

Br 6-F 4-F-Ph N-CMe 2 CF3 7-Cl 4-F-Ph N-CMe 2

Br 7-F C0 2 Me CF3 7-CF3 C0 2 Me N-CMe 2

Br 7-F C0 2 Et CF3 7-CF3 C0 2 Et N β CM 2

Br 7-F i-Pr CF3 7-CF3 i-Pr N"*CMe 2

Br 7-F Me N- fe 2 CF 3 7-CF3 Me N-CMe 2

Br 7-F 4-F-Ph N-CMe CF 3 7-CF3 4-F-Ph N-CMe 2

Br 7-Cl C0 2 Me N-CMe OCF3 6-F C0 2 Me N-CMe 2

Br 7-Cl C0 2 Et N-CMe 2 OCF3 6-F C0 Et N-CMe 2

Br 7-Cl i-Pr N-CMe 2 i-Pr N-CMe 2

Br 7-Cl Me N-CMe 2 Me N-CMe 2

Br 7-Cl 4-F-Ph N-CMe 2 4-F-Ph N-CMe 2

Br 7-CF3 CO^e N-CMe 2 CO^e N-CMe 2

Br 7-CF3 C0 2 Et N-CMe 2 C0 2 Et N-CMe 2

Br 7-CF3 i-Pr N-CMe 2 i-Pr N-CMe 2

Br 7-CF3 Me N-CMe 2 Me N-CMe 2

Br 7-CF3 4-F-Ph N-CMe 2 OCF3 7-F 4-F-Ph N-CMe 2

CF 3 6-F CO^e N-CMe 2 OCF3 7-Cl CO^e N-CMe 2

CF 3 6-F C0 2 Et N-CMe OCF3 7-Cl C0 2 Et N-CMe 2

CF 3 6-F i-Pr N-CMe 2 OCF3 7-Cl i-Pr N CMe 2

CF 3 6-F Me N«CMe 2 OCF3 7-Cl Me N-CMe 2

CF 3 6-F 4-F-Ph N-CMe 2 OCF3 7-Cl 4-F-Ph KM_Me 2

CF 3 7-F C0 2 Me OCF3 7-CF3 C0 2 Me N-CMe 2

CF 3 7-F C0 2 Et OCF3 7-CF3 C0 2 Et N-CMe 2

CF 3 7-F i-Pr N-CMe 2 OCF3 7-CF3 i-Pr N-CMe 2

CF 3 7-F Me N-CMe 2 OCF3 7-CF3 Me N-CMe 2

CF _, 7-F 4-F-Ph N-CMe 2 OCF3 7-CF3 4-F-Ph N-CMe 2

B 1 B B 3 X B 1 B 3 X

Br 6-F C0 Me N-CHPh CF 3 7-Cl C0 2 Me N-CHPh

Br 6-F C0 2 Et N-CHPh CF 3 7-Cl C0 2 Et N-CHPh

Br 6-F i-Pr N-CHPh CF 3 7-Cl i-Pr N-CHPh

Br 6-F Me N-CHPh CF 3 7-Cl Me N-CHPh

Br 6-F 4-F-Ph N-CHPh CF 3 7-Cl 4-F-Ph N-CHPh

Br 7-F C0 2 Me N-CHPh CF 3 7-CF3 C0 2 Me N-CHPh

Br 7-F C0 Et N-CHPh CF 3 7-CF3 C0 2 Et N-CHPh

Br 7-F i-Pr N-CHPh CF 3 7-CF3 i-Pr N-CHPh

Br 7-F Me N-CHPh CF 3 7-CF3 Me N-CHPh

Br 7-F 4-F-Ph N-CHPh CF 3 7-CF3 4-F-Ph f -CHPh

Br 7-Cl C0 2 Me N-CHPh OCF 3 6-F C0 2 Me N-CHPh

Br 7-Cl C0 2 Et N-CHPh OCF3 6-F C0 2 Et N-CHPh

Br 7-Cl i-Pr N-CHPh OCF3 6-F i-Pr N-CHPh

Br 7-Cl Me N-CHPh OCF3 6-F Me N-CHPh

Br 7-Cl 4-F-Ph N-CHPh OCF3 6-F 4-F-Ph N-CHPh

Br 7-CF 3 C0 2 Me N-CHPh OCF3 7-F C0 2 Me N-CHPh

Br 7-CF 3 C0 2 Et N-CHPh OCF3 7-F C0 2 Et N-CHPh

Br 7-CF 3 i-Pr N-CHPh OCF3 7-F i-Pr N-CHPh

Br 7-CF 3 Me N-CHPh OCF3 7-F Me N-CHPh

Br 7-CF 3 4-F-Ph N-CHPh OCF3 7-F 4-F-Ph N-CHPh

CF 3 6-F C0 2 Me N-CHPh OCF3 7-Cl C0 2 Me N-CHPh

CF 3 6-F C0 2 Et N-CHPh OCF3 7-Cl C0 2 Et N-CHPh

CF 3 6-F i-Pr N-CHPh OCF3 7-Cl i-Pr N-CHPh

CF 3 6-F Me N-CHPh OCF3 7-Cl Me N-CHPh

CF 3 6-F 4-F-Ph N-CHPh OCF3 7-Cl 4-F-Ph N-CHPh

CF 3 7-F C0 2 Me N-CHPh OCF3 7-CF3 C0 2 Me N-CHPh

CF 3 7-F C0 Et N-CHPh OCF3 7-CF 3 C0 Et N-CHPh

CF 3 7-F i-Pr N-CHPh OCF3 7-CF 3 i-Pr N-CHPh

CF 3 7-F Me N-CHPh OCF3 7-CF 3 Me N-CHPh

CF 3 7-F 4-F-Ph N-CHPh OCF3 7-CF 3 4-F-Ph N-CHPh

B A B B 3 X

Br 6-F C0 2 Me OMe

Br 6-F C0 2 Et OMe

Br 6-F i-Pr OMe

Br 6-F Me OMe

Br 6-F 4-F-Ph OMe

Br 7-F CO^e OMe

Br 7-F C0 2 Et OMe

Br 7-F i-Pr OMe

Br 7-F Me OMe

Br 7-F 4-F-Ph OMe

Br 7-Cl C0 2 Me OMe

Br 7-Cl C0 2 Et OMe

Br 7-Cl i-Pr OMe

Br 7-Cl Me OMe

Br 7-Cl 4-F-Ph OMe

Br 7-CF3 C0 2 Me OMe

Br 7-CF3 C0 2 Et OMe

Br 7-CF3 i-Pr OMe

Br 7-CF3 Me OMe

Br 7-CF3 4-F-Ph OMe

CF 3 6-F C0 2 Me OMe

CF 3 6-F C0 2 Et OMe

CF 3 6-F i-Pr OMe

CF 3 6-F Me OMe

CF 3 6-F 4-F-Ph OMe

C 3 7-F C0 2 Me OMe

CF 3 7-F C0 2 Et OMe

CF 3 7-F i-Pr OMe

CF 3 7-F Me OMe

CF 3 7-F 4-F-Ph OMe

B 1 X B 1 B z B X

Br 6-F C0 2 Me OCH 2 Ph CF 3 7-Cl C0 2 Me OCH 2 Ph

Br 6-F C0 2 Et OCH Ph CF 3 7-Cl C0 2 Et OCH 2 Ph

Br 6-F i-Pr OCH 2 Ph CF 3 7-Cl i-Pr OCH 2 Ph

Br 6-F Me OCH 2 Ph CF 3 7-Cl Me OCH 2 Ph

Br 6-F 4-F-Ph OCH 2 Ph CF3 7-Cl 4-F-Ph OCH Ph

Br 7-F C0 2 Me OCH 2 Ph CF 3 7-CF3 C0 2 Me OCH 2 Ph

Br 7-F C0 2 Et OCH 2 Ph CF 3 7-CF3 C0 Et OCH 2 Ph

Br 7-F i-Pr OCH 2 Ph CF 3 7-CF3 i-Pr OCH 2 Ph

Br 7-F Me OCH Ph CF 3 7-CF3 Me OCH 2 Ph

Br 7-F 4-F-Ph OCH 2 Ph CF 3 7-CF3 4-F-Ph OCH 2 Ph

Br 7-Cl C0 2 Me OCH 2 Ph OCF 3 6-F C0 Me OCH Ph

Br 7-Cl C0 Et OCH 2 Ph OCF3 6-F C0 2 Et OCH 2 Ph

Br 7-Cl i-Pr OCH 2 Ph OCF3 6-F i-Pr OCH 2 Ph

Br 7-Cl Me OCH 2 Ph OCF3 6-F Me OCH 2 Ph

Br 7-Cl 4-F-Ph OCH 2 Ph OCF3 6-F 4-F-Ph OCH 2 Ph

Br 7-CF 3 C0 Me OCH 2 Ph OCF3 7-F C0 2 Me OCH 2 Ph

Br 7-CF 3 C0 2 Et OCH 2 Ph OCF3 7-F C0 2 Et OCH 2 Ph

Br 7-CF 3 i-Pr OCH 2 Ph OCF3 7-F i-Pr OCH 2 Ph

Br 7-CF 3 Me OCH 2 Ph OCF3 7-F Me OCH 2 Ph

Br 7-CF 3 4-F-Ph OCH 2 Ph OCF3 7-F 4-F-Ph OCH 2 Ph

CF 3 6-F C0 2 Me OCH 2 Ph OCF3 7-Cl C0 2 Me OCH 2 Ph

CF 3 6-F C0 2 Et OCH 2 Ph OCF3 7-Cl C0 2 Et OCH 2 Ph

CF 3 6-F i-Pr OCH 2 Ph OCF3 7-Cl i-Pr OCH 2 Ph

<= 3 6-F Me OCH 2 Ph OCF3 7-Cl Me OCH Ph CF 3 6-F 4-F-Ph OCH 2 Ph OCF3 7-Cl 4-F-Ph OCH 2 Ph CF 3 7-F C0 2 Me OCH Ph OCF3 7-CF3 C0 2 Me OCH 2 Ph CF 3 7-F C0 2 Et OCH 2 Ph OCF3 7-CF3 C0 Et OCH 2 Ph CF 3 7-F i-Pr OCH 2 Ph OCF3 7-CF3 i-Pr OCH 2 Ph CF 3 7-F Me OCH 2 Ph OCF3 7-CF3 Me OCH 2 Ph CF 3 7-F 4-F-Ph OCH 2 Ph OCF3 7-CF3 4-F-Ph OCH Ph

Z B B- 3 X

Br 6-F C0 2 Me NHCHO

Br 6-F C0 2 Et NHCHO

Br 6-F i-Pr NHCHO

Br 6-F Me NHCHO

Br 6-F 4-F-Ph NHCHO

Br 7-F CO^e NHCHO

Br 7-F C0 2 Et NHCHO

Br 7-F i-Pr NHCHO

Br 7-F Me NHCHO

Br 7-F 4-F-Ph NHCHO

Br 7-Cl C0 2 Me NHCHO

Br 7-Cl C0 2 Et NHCHO

Br 7-Cl i-Pr NHCHO

Br 7-Cl Me NHCHO

Br 7-Cl 4-F-Ph NHCHO

Br 7-CF 3 C0 Me NHCHO

Br 7-CF 3 C0 2 Et NHCHO

Br 7-CF 3 i-Pr NHCHO

Br 7-CF 3 Me NHCHO

Br 7-CF 3 4-F-Ph NHCHO

CF 3 6-F C0 2 Me NHCHO

CF 3 6-F C0 2 Et NHCHO

CF 3 6-F i-Pr NHCHO

CF 3 6-F Me NHCHO

CF 3 6-F 4-F-Ph NHCHO

CF 3 7-F C0 2 Me NHCHO

CF 3 7-F C0 Et NHCHO

CF 3 7-F i-Pr NHCHO

C 3 7-F Me NHCHO CF 3 7-F 4-F-Ph NHCHO

B 1 B < = B J X B 1 B^ B X

Br 6-F C0 2 Me NH(CO)Me CF 3 7-Cl C0 2 Me NH(CO)Me

Br 6-F C0 2 Et NH(CO)Me CF 3 7-Cl C0 2 Et NH(CO)Me

Br 6-F i-Pr NH(CO)Me CF 3 7-Cl i-Pr NH(CO)Me

Br 6-F Me NH(CO)Me CF 3 7-Cl Me NH(CO)Me

Br 6-F 4-F-Ph NH(CO)Me CF 3 7-Cl 4-F-Ph NH(CO)Me

Br 7-F C0 2 Me NH(CO)Me CF 3 7-CF3 C0 2 Me NH(CO)Me

Br 7-F C0 2 Et NH(CO)Me CF 3 7-CF3 C0 2 Et NH(CO)Me

Br 7-F i-Pr NH(CO)Me CF 3 7-CF3 i-Pr NH(CO)Me

Br 7-F Me NH(CO)Me CF 3 7-CF3 Me NH(CO)Me

Br 7-F 4-F-Ph NH(CO)Me CF 3 7-CF3 4-F-Ph NH(CO)Me

Br 7-Cl C0 2 Me NH(CO)Me OCF 3 6-F C0 2 Me NH(CO)Me

Br 7-Cl C0 2 Et NH(CO)Me OCF3 6-F C0 2 Et NH(CO)Me

Br 7-Cl i-Pr NH(CO)Me OCF3 6-F i-Pr NH(CO)Me

Br 7-Cl Me NH(CO)Me OCF3 6-F Me NH(CO)Me

Br 7-Cl 4-F-Ph NH(CO)Me OCF3 6-F 4-F-Ph NH(CO)Me

Br 7-CF 3 C0 2 Me NH(CO)Me OCF3 7-F C0 2 Me NH(CO)Me

Br 7-CF 3 C0 2 Et NH(CO)Me OCF3 7-F C0 2 Et NH(CO)Me

Br 7-CF 3 i-Pr NH(CO)Me OCF3 7-F i-Pr NH(CO)Me

Br 7-CF 3 Me NH(CO)Me OCF3 7-F Me NH(CO)Me

Br 7~CF 3 4-F-Ph NH(CO)Me OCF3 7-F 4-F-Ph NH(CO)Me

CF 3 6-F C0 2 Me NH(CO)Me OCF3 7-Cl C0 Me NH(CO)Me

CF 3 6-F C0 2 Et NH(CO)Me OCF3 7-Cl C0 2 Et NH(CO)Me

CF 3 6-F i-Pr NH(CO)Me OCF3 7-Cl i-Pr NH(CO)Me

CF 3 6-F Me NH(CO)Me OCF3 7-Cl Me NH(CO)Me

CF 3 6-F 4-F-Ph NH(CO)Me OCF3 7-Cl 4-F-Ph NH(CO)Me

CF 3 7-F C0 2 Me NH(CO)Me OCF3 7-CF3 C0 2 Me NH(CO)Me

CF 3 7-F C0 2 Et NH(CO)Me OCF3 7-CF3 C0 2 Et NH.CO.Me

CF 3 7-F i-Pr NH(CO)Me OCF3 7-CF3 i-Pr NH(CO)Me

CF 3 7-F Me NH(CO)Me OCF3 7-CF3 Me NH(CO)Me

CF 3 7-F 4-F-Ph NH(CO)Me OCF3 7-CF3 4-F-Ph NH(CO)Me

B x B* B J X B 1 B B J X

Br 6-F C0 Me N-CMe 2 CF 3 7-Cl C0 2 Me N-CMe 2

Br 6-F C0 Et N-CMe 2 CF3 7-Cl C0 2 Et N-CMe 2

Br 6-F i-Pr _*_CMe 2 CF3 7-Cl i-Pr N-CMe 2

Br 6-F Me w CMe 2 CF3 7-Cl Me N-α e 2

Br 6-F 4-F-Ph N-CMe CF 3 7-Cl 4-F-Ph N-CMe 2

Br 7-F CO2M& N-CMe 2 CF3 7-CF3 C0 2 Me N-CMe 2

Br 7-F C0 2 Et N-CMe 2 CF3 7-CF3 C0 2 Et

Br 7-F i-Pr N-CMe 2 CF 3 7-CF3 i-Pr N-CMe 2

Br 7-F Me N-CMe 2 CF3 7-CF3 Me N-CMe 2

Br 7-F 4-F-Ph N _Me 2 CF3 7-CF3 4-F-Ph N-CMe 2

Br 7-Cl C0 2 Me N-CMe 2 OCF3 6-F C0 2 Me N _Me

Br 7-Cl C0 2 Et N-CMe 2 OCF3 6-F C0 2 Et N-CMe

Br 7-Cl i-Pr N-CMe 2 OCF3 6-F i-Pr N-CMe 2

Br 7-Cl Me N- _e 2 OCF3 6-F Me N-CMe

Br 7-Cl 4-F-Ph N«CMe 2 OCF3 6-F 4-F-Ph N-CMe 2

Br 7-CF 3 C0 2 Me N-CMe 2 OCF3 7-F C0 2 Me N-CMe 2

Br 7-CF 3 C0 Et N-CMe OCF3 7-F C0 2 Et N-CMe 2

Br 7-CF 3 i-Pr N-CMe OCF3 7-F i-Pr N-CMe 2

Br 7-CF 3 Me N-CMe 2 OCF3 7-F Me N-CMe 2

Br 7-CF 3 4-F-Ph N-CMe OCF3 7-F 4-F-Ph N-CMe 2

CF 3 6-F C0 2 Me N>"CMe 2 OCF3 7-Cl C0 2 Me N-CMe 2

C 3 6-F C0 2 Et N-CMe 2 OCF3 7-Cl C0 2 Et N-CMe 2

CF 3 6-F i-Pr N«CMe 2 OCF3 7-Cl i-Pr N«»CMe 2

CF 3 6-F Me N-CMe 2 OCF3 7-Cl Me N-CMe 2

CF 3 6-F 4-F-Ph N-CMe 2 OCF3 7-Cl 4-F-Ph NK_Me 2

CF 3 7-F C0 2 Me N-CMe 2 OCF3 7-CF3 CO^e !W_Me 2

CF 3 7-F C0 2 Et N-CMe 2 OCF3 7-CF3 C0 2 Et N 3_e 2

CF 3 7-F i-Pr N-CMe 2 OCF 3 7-CF3 i-Pr »M31e 2

CF 3 7-F Me N-CMe 2 OCF 3 7-CF3 Me N-CMe 2

CF 3 7-F 4-F-Ph N_CMe 2 OCF 3 7-CF3 4-F-Ph N-CMe 2

B 1 B* B J X x B* B 3 X

Br 6-F C0 Me N-CHPh CF 3 7-Cl C0 2 Me N-CHPh

Br 6-F C0 2 Et N-CHPh CF 3 7-Cl C0 2 Et N-CHPh

Br 6-F i-Pr N-CHPh CF3 7-Cl i-Pr N-CHPh

Br 6-F Me N-CHPh CF3 7-Cl Me N-CHPh

Br 6-F 4-F-Ph N-CHPh CF 3 7-Cl 4-F-Ph N-CHPh

Br 7-F C0 2 Me N-CHPh CF 3 7-CF3 C0 2 Me N-CHPh

Br 7-F C0 2 Et N-CHPh CF 3 7-CF3 C0 2 Et N-CHPh

Br 7-F i-Pr N-CHPh CF3 7-CF3 i-Pr N-CHPh

Br 7-F Me N-CHPh CF3 7-CF3 Me N-CHPh

Br 7-F 4-F-Ph N-CHPh CF3 7-CF3 4-F-Ph N-CHPh

Br 7-Cl C0 2 Me N-CHPh OCF3 6-F C0 2 Me N-CHPh

Br 7-Cl C0 2 Et N-CHPh OCF3 6-F C0 2 Et N-CHPh

Br 7-Cl i-Pr N-CHPh OCF3 6-F i-Pr N-CHPh

Br 7-Cl Me N-CHPh OCF3 6-F Me N-CHPh

Br 7-Cl 4-F-Ph N-CHPh OCF3 6-F 4-F-Ph N-CHPh

Br 7-CF3 C0 2 Me N-CHPh OCF3 7-F C0 Me N-CHPh

Br 7-CF3 C0 2 Et N-CHPh OCF3 7-F C0 2 Et N-CHPh

Br 7-CF3 i-Pr N-CHPh OCF3 7-F i-Pr N-CHPh

Br 7-CF3 Me N-CHPh OCF3 7-F Me N-CHPh

Br 7-CF3 4-F-Ph N-CHPh OCF3 7-F 4-F-Ph N-CHPh

CF 3 6-F C0 2 Me N-CHPh OCF3 7-Cl C0 2 Me N-CHPh

CF 3 6-F C0 Et N-CHPh OCF3 7-Cl C0 2 Et N-CHPh

CF 3 6-F i-Pr N-CHPh OCF3 7-Cl i-Pr N-CHPh

CF 3 6-F Me N-CHPh OCF3 7-Cl Me N-CHPh

CF 3 6-F 4-F-Ph N-CHPh OCF3 7-Cl 4-F-Ph N-CHPh CF 3 7-F C0 2 Me N-CHPh OCF3 7-CF3 C0 2 Me N-CHPh

CF 3 7-F C0 2 Et N-CHPh OCF3 7-CF3 C0 2 Et N-CHPh

CF 3 7-F i-Pr N-CHPh OCF3 7-CF3 i-Pr N-CHPh

CF 3 7-F Me N-CHPh OCF3 7-CF3 Me N-CHPh

CF 3 7-F 4-F-Ph N-CHPh OCF3 7-CF3 4-F-Ph N-CHPh

x B z B 3 X B 1 B < = B 3 X

Br 6-F CO^e OMe CF 3 7-Cl C0 Me OMe

Br 6-F C0 2 Et OMe CF 3 7-Cl C0 2 Et OMe

Br 6-F i-Pr OMe CF 3 7-Cl i-Pr OMe

Br 6-F Me OMe CF 3 7-Cl Me OMe

Br 6-F 4-F-Ph OMe CF 3 7-Cl 4-F-Ph OMe

Br 7-F CO^e OMe CF 3 7-CF3 C0 2 Me OMe

Br 7-F C0 2 Et OMe CF 3 7-CF3 C0 2 Et OMe

Br 7-F i-Pr OMe CF 3 7-CF3 i-Pr OMe

Br 7-F Me OMe CF 3 7-CF3 Me OMe

Br 7-F 4-F-Ph OMe CF 3 7-CF3 4-F-Ph { OMe

Br 7-Cl Cθ 2 Me OMe OCF3 6-F Cθ 2 Me OMe

Br 7-Cl C0 2 Et OMe OCF3 6-F C0 2 Et OMe

Br 7-Cl i-Pr OMe OCF3 6-F i-Pr OMe

Br 7-Cl Me OMe OCF3 6-F Me OMe

Br 7-Cl 4-F-Ph OMe OCF3 6-F 4-F-Ph OMe

Br 7-CF3 C0 Me OMe OCF3 7-F C0 2 Me OMe

Br 7-CF3 C0 Et OMe OCF3 7-F C0 2 Et OMe

Br 7-CF3 i-Pr OMe OCF3 7-F i-Pr OMe

Br 7-CF3 Me OMe OCF3 7-F Me OMe

Br 7-CF3 4-F-Ph OMe OCF3 7-F 4-F-Ph OMe

CF 3 6-F C0 2 Me OMe OCF3 7-Cl C0 2 Me OMe CF 3 6-F C0 2 Et OMe OCF3 7-Cl C0 2 Et OMe CF 3 6-F i-Pr OMe OCF3 7-Cl i-Pr OMe CF 3 6-F Me OMe OCF3 7-Cl Me OMe CF 3 6-F 4-F-Ph OMe OCF3 7-Cl 4-F-Ph OMe

CF 3 7-F C0 2 Me OMe OCF3 7-CF3 C0 2 Me OMe CF 3 7-F C0 2 Et OMe OCF3 7-CF3 C0 Et OMe CF 3 7-F i-Pr OMe OCF3 7-CF3 i-Pr OMe CF 3 7-F Me OMe OCF3 7-CF3 Me OMe CF 3 7-F 4-F-Ph OMe OCF3 7-CF3 4-F-Ph OMe

B A B J X B 1 B Z B J X

Br 6-F C0 2 Me OCH 2 Ph CF 3 7-Cl C0 2 Me OCH 2 Ph

Br 6-F C0 2 Et OCH 2 Ph CF 3 7-Cl C0 2 Et OCH 2 Ph

Br 6-F . i-Pr OCH 2 Ph CF 3 7-Cl i-Pr OCH 2 Ph

Br 6-F Me OCH 2 Ph CF 3 7-Cl Me OCH Ph

Br 6-F 4-F-Ph OCH 2 Ph CF 3 7-Cl 4-F-Ph OCH 2 Ph

Br 7-F C0 2 Me OCH 2 Ph CF 3 7-CF 3 C0 2 Me OCH 2 Ph

Br 7-F C0 2 Et OCH 2 Ph CF 3 7-CF 3 C0 2 Et OCH Ph

Br 7-F i-Pr OCH 2 Ph CF 3 7-CF 3 i-Pr OCH 2 Ph

Br 7-F Me OCH 2 Ph CF 3 7-CF 3 Me OCH Ph

Br 7-F 4-F-Ph OCH 2 Ph CF 3 7-CF 3 4-F-Ph OCH 2 Ph

Br 7-Cl C0 2 Me OCH 2 Ph OCF 3 6-F C0 2 Me OCH 2 Ph

Br 7-Cl C0 2 Et OCH 2 Ph OCF 3 6-F C0 2 Et OCH 2 Ph

Br 7-Cl i-Pr OCH 2 Ph OCF 3 6-F i-Pr OCH Ph

Br 7-Cl Me OCH 2 Ph CF 3 6-F Me OCH 2 Ph

Br 7-Cl 4-F-Ph OCH 2 Ph OCF 3 6-F 4-F-Ph OCH 2 Ph

Br 7-CF 3 C0 2 Me OCH 2 Ph OCF 3 7-F C0 2 Me OCH 2 Ph

Br 7-CF 3 C0 2 Et OCH 2 Ph OCF 3 7-F C0 2 Et OCH 2 Ph

Br 7-CF 3 i-Pr OCH 2 Ph OCF 3 7-F i-Pr OCH 2 Ph

Br 7-CF 3 Me OCH 2 Ph OCF 3 7-F Me OCH 2 Ph

Br 7-CF 3 4-F-Ph OCH Ph OCF 3 7-F 4-F-Ph OCH 2 Ph

CF 3 6-F C0 2 Me OCH 2 Ph OCF 3 7-Cl C0 2 Me OCH 2 Ph

C 3 6-F C0 2 Et OCH 2 Ph OCF 3 7-Cl C0 2 Et OCH 2 Ph CF 3 6-F i-Pr OCH 2 Ph OCF 3 7-Cl i-Pr OCH 2 Ph CF 3 6-F Me OCH 2 Ph OCF 3 7-Cl Me OCH 2 Ph CF 3 6-F 4-F-Ph OCH 2 Ph OCF 3 7-Cl 4-F-Ph OCH 2 Ph CF 3 7-F C0 2 Me OCH 2 Ph OCF 3 7-CF 3 C0 2 Me OCH 2 Ph CF 3 7-F C0 2 Et OCH 2 Ph OCF 3 7-CF 3 C0 2 Et OCH 2 Ph CF 3 7-F i-Pr OCH Ph OCF 3 7-CF 3 i-Pr OCH 2 Ph CF 3 7-F Me OCH 2 Ph OCF 3 7~CF 3 Me OCH 2 Ph CF 3 7-F 4-F-Ph OCH 2 Ph OCF 3 7-CF 3 4-F-Ph OCH 2 Ph

B 1 B B J X B 1 B^ B J X

Br 6-F C0 2 Me NHMe CF 3 7-Cl C0 2 Me NHMe

Br 6-F C0 2 Et NHMe CF 3 7-Cl C0 Et NHMe

Br 6-F i-Pr NHMe CF 3 7-Cl i-Pr NHMe

Br 6-F Me NHMe CF 3 7-Cl Me NHMe

Br 6-F 4-F-Ph NHMe CF 3 7-Cl 4-F-Ph NHMe

Br 7-F C0 2 Me NHMe C 3 7-CF3 C0 2 Me NHMe

Br 7-F C0 2 Et NHMe CF 3 7-CF3 C0 2 Et NHMe

Br 7-F i-Pr NHMe CF 3 7-CF3 i-Pr NHMe

Br 7-F Me NHMe CF3 7-CF3 Me NHMe

Br 7-F 4-F-Ph NHMe CF3 7-CF3 4-F-Ph NHMe

Br 7-Cl C0 2 Me NHMe OCF3 6-F C0 2 Me NHMe

Br 7-Cl C0 2 Et NHMe OCF3 6-F C0 Et NHMe

Br 7-Cl i-Pr NHMe OCF3 6-F i-Pr NHMe

Br 7-Cl Me NHMe OCF3 6-F Me NHMe

Br 7-Cl 4-F-Ph NHMe OCF3 6-F 4-F-Ph NHMe

Br 7-CF 3 C0 2 Me NHMe OCF3 7-F C0 2 Me NHMe

Br 7-CF 3 C0 2 Et NHMe OCF3 7-F C0 2 Et NHMe

Br 7-CF 3 i-Pr NHMe OCF3 7-F i-Pr NHMe

Br 7-CF 3 Me NHMe OCF3 7-F Me NHMe

Br 7-CF 3 4-F-Ph NHMe OCF3 7-F 4-F-Ph NHMe

CF 3 6-F C0 2 Me NHMe OCF3 7-Cl C0 2 Me NHMe

CF 3 6-F C0 2 Et NHMe OCF3 7-Cl C0 Et NHMe

CF 3 6-F i-Pr NHMe OCF3 7-Cl i-Pr NHMe

CF 3 6-F Me NHMe OCF3 7-Cl Me NHMe

CF 3 6-F 4-F-Ph NHMe OCF3 7-Cl 4-F-Ph NHMe

CF 3 7-F C0 2 Me NHMe OCF3 7-CF3 C0 2 Me NHMe CF 3 7-F C0 2 Et NHMe OCF3 7-CF3 C0 2 Et NHMe CF 3 7-F i-Pr NHMe OCF3 7-CF3 i-Pr NHMe CF 3 7-F Me NHMe OCF3 7-CF3 Me NHMe CF 3 7-F 4-F-Ph NHMe OCF3 7-CF3 4-F-Ph NHMe

B B < = B 3 X B 1 B < = B J X

Br 6-F C0 2 Me NH.CO.Me CF 3 7-Cl C0 2 Me NH(CO)Me

Br 6-F C0 2 Et NH(CO)Me CF3 7-Cl C0 2 Et NH(CO)Me

Br 6-F i-Pr NH(CO)Me CF 3 7-Cl i-Pr NH(CO)Me

Br 6-F Me NH(CO)Me CF 3 7-Cl Me NH(CO)Me

Br 6-F 4-F-Ph NH(CO)Me CF3 7-Cl 4-F-Ph NH(CO)Me

Br 7-F C0 Me NH(CO)Me CF3 7-CF3 CO^e NH(CO)Me

Br 7-F C0 2 Et NH(CO)Me CF3 7-CF3 C0 2 Et NH(CO)Me

Br 7-F i-Pr NH(CO)Me CF3 7-CF3 i-Pr NH(CO)Me

Br 7-F Me NH(CO)Me CF 3 7-CF3 Me NH(CO)Me

Br 7-F 4-F-Ph NH(CO)Me CF3 7-CF3 4-F-Ph NH(CO)Me

Br 7-Cl C0 2 Me NH(CO)Me OCF3 6-F C0 2 Me NH(CO)Me

Br 7-Cl C0 2 Et NH(CO)Me OCF3 6-F C0 2 Et NH(CO)Me

Br 7-Cl i-Pr NH(CO)Me OCF3 6-F i-Pr NH(CO)Me

Br 7-Cl Me NH(CO)Me OCF3 6-F Me NH(CO)Me

Br 7-Cl 4-F-Ph NH(CO)Me OCF3 6-F 4-F-Ph NH(CO)Me

Br 7-CF3 C0 2 Me NH(CO)Me OCF3 7-F C0 2 Me NH(CO)Me

Br 7-CF3 C0 2 Et NH(CO)Me OCF3 7-F C0 2 Et NH(CO)Me

Br 7-CF3 i-Pr NH(CO)Me OCF3 7-F i-Pr NH(CO)Me

Br 7-CF3 Me NH(CO)Me OCF3 7-F Me NH(CO)Me

Br 7-CF3 4-F-Ph NH(CO)Me OCF3 7-F 4-F-Ph NH(CO)Me

CF 3 6-F C0 2 Me NH(CO)Me OCF3 7-Cl C0 2 Me NH(CO)Me

CF 3 6-F C0 2 Et NH(CO)Me OCF3 7-Cl C0 2 Et NH(CO)Me

CF 3 6-F i-Pr NH(CO)Me OCF3 7-Cl i-Pr NH(CO)Me

CF 3 6-F Me NH(CO)Me OCF3 7-Cl Me NH(CO)Me

CF 3 6-F 4-F-Ph NH(CO)Me OCF3 7-Cl 4-F-Ph NH(CO)Me

CF 3 7-F C0 2 Me NH(CO)Me OCF3 7-CF3 C0 Me NH(CO)Me

CF 3 7-F C0 Et NH(CO)Me OCF3 7-CF3 C0 2 Et NH(CO)Me

CF 3 7-F i-Pr NH(CO)Me OCF3 7-CF3 i-Pr NH(CO)Me

CF 3 7-F Me NH(CO)Me OCF3 7-CF3 Me NH(CO)Me

CF 3 7-F 4-F-Ph NH(CO)Me OCF3 7-CF3 4-F-Ph NH(CO)Me

B x B B J X B 1 B J -X

Br 6-F C0 Me N-CH 2 CF 3 7-Cl C0 2 Me N-CH 2

Br 6-F C0 2 Et N-CH 2 CF 3 7-Cl C0 2 Et N-CH 2

Br 6-F i-Pr CF3 7-Cl i-Pr N-CH 2

Br 6-F Me N™CH9 CF 3 7-Cl Me N-CH 2

Br 6-F 4-F-Ph N-CH 2 CF3 7-Cl 4-F-Ph N-CH 2

Br 7-F C0 2 Me N-CH 2 CF3 7-CF3 C0 Me "CH 2

Br 7-F C0 2 Et N-CH 2 CF 3 7-CF3 C0 2 Et N—CH 2

Br 7-F i-Pr N-CH 2 CF 3 7-CF3 i-Pr N-CH 2

Br 7-F Me N :H 2 CF 3 7-CF3 Me N-CH

Br 7-F 4-F-Ph N-CH CF 3 7-CF3 4-F-Ph N«CH

Br 7-Cl C0 Me N-CH 2 OCF 3 6-F C0 2 Me N-CH 2

Br 7-Cl C0 2 Et N-CH 2 OCF3 6-F C0 Et N-CH 2

Br 7-Cl i-Pr N-CH 2 OCF3 6-F i-Pr N-CH 2

Br 7-Cl Me N-CH 2 OCF3 6-F Me N-CH 2

Br 7-Cl 4-F-Ph N-CH 2 OCF3 6-F 4-F-Ph N-CH 2

Br 7"CF 3 C0Me N-CH 2 OCF3 7-F C0 2 Me N-CH 2

Br 7-CF 3 C0 2 Et N-CH 2 OCF3 7-F C0 2 Et N-CH 2

Br 7-CF 3 i-Pr N-CH 2 OCF3 7-F i-Pr N-CH 2

Br 7"CF 3 Me N-CH 2 OCF3 7-F Me N-CH 2

Br 7"CF 3 4-F-Ph N-CH OCF3 7-F 4-F-Ph N-CH 2

CF3 6-F C0 2 Me N"CH 2 OCF3 7-Cl C0 2 Me N-CH 2

CF 3 6-F C0 2 Et N-CH 2 OCF3 7-Cl C0 Et N-CH 2

CF 3 6-F i-Pr N-CH 2 OCF3 7-Cl i-Pr N-CH 2

CF 3 6-F Me N-CH 2 OCF3 7-Cl Me N-CH 2

CF 3 6-F 4-F-Ph N-CH 2 OCF3 7-Cl 4-F-Ph N-CH 2

CF 3 7-F C0 2 Me N-CH 2 OCF3 7-CF3 C0 2 Me N-CH 2

CF 3 7-F C0 2 Et N-CH 2 OCF3 7-CF3 C0 2 Et N-CH 2

CF 3 7-F i-Pr N-CH OCF3 7-CF3 i-Pr N-CH 2

CF 3 7-F Me N-CH 2 OCF3 7-CF3 Me N-CH 2

CF 3 7-F 4-F-Ph N-CH 2 OCF3 7-CF3 4-F-Ph N-CH

B 1 B J X

Br 6-F C0 2 Me N-CHPh

Br 6-F C0 2 Et N-CHPh

Br 6-F i-Pr N-CHPh

Br 6-F Me N-CHPh

Br 6-F 4-F-Ph N-CHPh

Br 7-F C0 Me N-CHPh

Br 7-F C0 2 Et N-CHPh

Br 7-F i-Pr N-CHPh

Br 7-F Me N-CHPh

Br 7-F 4-F-Ph N-CHPh

Br 7-Cl C0 2 Me N-CHPh

Br 7-Cl C0 2 Et N-CHPh

Br 7-Cl i-Pr N-CHPh

Br 7-Cl Me N-CHPh

Br 7-Cl 4-F-Ph N-CHPh

Br 7-CF 3 C0 2 Me N-CHPh

Br 7-CF 3 C0 2 Et N-CHPh

Br 7-CF 3 i-Pr N-CHPh

Br 7-CF 3 Me N-CHPh

Br 7-CF 3 4-F-Ph N-CHPh

CF 3 6-F C0 2 Me N-CHPh

CF 3 6-F C0 Et N-CHPh CF 3 6-F i-Pr N-CHPh CF 3 6-F Me N-CHPh CF 3 6-F 4-F-Ph N-CHPh CF 3 7-F C0 2 Me N-CHPh CF 3 7-F C0 2 Et N-CHPh CF 3 7-F i-Pr N-CHPh CF 3 7-F Me N-CHPh CF 3 7-F 4-F-Ph N-CHPh

B 3 X

Br 6-F C0 2 Me OMe

Br 6-F C0 2 Et OMe

Br 6-F i-Pr OMe

Br 6-F Me OMe

Br 6-F 4-F-Ph OMe

Br 7-F C0 2 Me OMe

Br 7-F C0 2 Et OMe

Br 7-F i-Pr OMe

Br 7-F Me OMe

Br 7-F 4-F-Ph OMe

Br 7-Cl C0 2 Me OMe

Br 7-Cl C0 2 Et OMe

Br 7-Cl i-Pr OMe

Br 7-Cl Me OMe

Br 7-Cl 4-F-Ph OMe

Br 7-CF 3 C0 2 Me OMe

Br 7-CF 3 C0 2 Et OMe

Br 7-CF 3 i-Pr OMe

Br 7~CF 3 Me OMe

Br 7-CF 3 4-F-Ph OMe

CF 3 6-F C0 2 Me OMe

CF 3 6-F C0 2 Et OMe

C 3 6-F i-Pr OMe

CF 3 6-F Me OMe

CF 3 6-F 4-F-Ph OMe

CF 3 7-F CO^e OMe

CF 3 7-F C0 2 Et OMe

CF 3 7-F i-Pr OMe

C 3 7-F Me OMe

CF, 7-F 4-F-Ph OMe

B 1 B^ J X B x B 3 X

Br 6-F C0 2 Me OCH 2 Ph CF 3 7-Cl C0 2 Me OCH 2 Ph

Br 6-F C0 2 Et OCH 2 Ph CF 3 7-Cl C0 2 Et OCH 2 Ph

Br 6-F i-Pr OCH 2 Ph CF 3 7-Cl i-Pr OCH 2 Ph

Br 6-F Me OCH 2 Ph CF 3 7-Cl Me OCH 2 Ph

Br 6-F 4-F-Ph OCH 2 Ph CF 3 7-Cl 4-F-Ph OCH 2 Ph

Br 7-F C0 2 Me OCH 2 Ph CF 3 7-CF3 C0 Me OCH 2 Ph

Br 7-F C0 Et OCH 2 Ph CF 3 7-CF3 C0 2 Et OCH 2 Ph

Br 7-F i-Pr OCH 2 Ph CF 3 7-CF3 i-Pr OCH 2 Ph

Br 7-F Me OCH 2 Ph CF 3 7-CF3 Me OCH 2 Ph

Br 7-F 4-F-Ph OCH 2 Ph CF 3 7-CF3 4-F-Ph I)CH 2 Ph

Br 7-Cl C0 2 Me OCH 2 Ph OCF 3 6-F C0 2 Me OCH 2 Ph

Br 7-Cl C0 2 Et OCH 2 Ph OCF 3 6-F C0 2 Et OCH 2 Ph

Br 7-Cl i-Pr OCH 2 Ph OCF 3 6-F i-Pr OCH 2 Ph

Br 7-Cl Me OCH 2 Ph OCF 3 6-F Me OCH 2 Ph

Br 7-Cl 4-F-Ph OCH 2 Ph OCF 3 6-F 4-F-Ph OCH 2 Ph

Br 7-CF 3 C0 2 Me OCH 2 Ph OCF 3 7-F C0 2 Me OCH 2 Ph

Br 7-CF 3 C0 2 Et OCH 2 Ph OCF 3 7-F C0 2 Et OCH 2 Ph

Br 7-CF 3 i-Pr OCH 2 Ph OCF 3 7-F i-Pr OCH 2 Ph

Br 7-CF 3 Me OCH 2 Ph OCF 3 7-F Me OCH 2 Ph

Br 7-CF 3 4-F-Ph OCH 2 Ph OCF 3 7-F 4-F-Ph OCH 2 Ph

CF 3 6-F C0 Me OCH 2 Ph OCF 3 7-Cl C0 Me OCH 2 Ph

CF 3 6-F C0 2 Et OCH 2 Ph OCF 3 7-Cl C0 2 Et OCH 2 Ph

C 3 6-F i-Pr OCH 2 Ph OCF 3 7-Cl i-Pr OCH 2 Ph CF 3 6-F Me OCH 2 Ph OCF 3 7-Cl Me OCH Ph CF 3 6-F 4-F-Ph OCH 2 Ph OCF3 7-Cl 4-F-Ph OCH 2 Ph CF 3 7-F C0 2 Me OCH 2 Ph OCF3 7-CF3 C0 2 Me OCH 2 Ph CF 3 7-F C0 2 Et OCH 2 Ph OCF3 7-CF3 C0 2 Et OCH 2 Ph CF 3 7-F i-Pr OCH 2 Ph OCF3 7-CF3 i-Pr OCH 2 Ph C 3 7-F Me OCH 2 Ph OCF3 7-CF3 Me OCH 2 Ph C 3 7-F 4-F-Ph OCH 2 Ph OCF3 7-CF3 4-F-Ph OCH 2 Ph

B 1 B* B J X B 1 B B 3 X Br 7-F 4-F-Ph NHC0 2 Me Br 7-F 4-F-Ph NHS0 2 NHMe

CF 3 7-F 4-F-Ph NHCO^e CF 3 7-F 4-F-Ph NHS0 2 NHMe

OCF3 7-F 4-F-Ph NHC0 2 Me OCF3 7-F 4-F-Ph NHS0 2 NHMe

CF3 7-Cl C0 2 Me HCO^e CF3 7-Cl CO j gMe NHS0 2 NHMe

OCF3 7-Cl CO^e NHC0 2 Me OCF3 7-Cl C0 Me NHS0 2 NHMe

OCF3 7-Cl C0 2 Et NHC0 Me OCF3 7-Cl C0 2 Et NHS0 2 NHMe

Br 7-F 4-F-Ph NHC0 2 Et Br 7-F 4-F-Ph NH(4-F-Ph) CF 3 7-F 4-F-Ph NHC0 2 Et CF 3 7-F 4-F-Ph NH(4-F-Ph)

OCF3 7-F 4-F-Ph NHC0 2 Et OCF3 7-F 4-F-Ph NH(4-F-Ph)

CF3 7-Cl C0 2 Me NHC0 2 Et CF 3 7-Cl CO^e NH(4-F-Ph)

OCF3 7-Cl C0 2 Me NHC0 2 Et OCF3 7-Cl C0 2 Me NH(4-F-Ph)

OCF3 7-Cl C0 Et NHC0 2 Et OCF3 7-Cl C0 2 Et NH(4-F-Ph)

Br 7-F 4-F-Ph NHS0 NH 2 Br 7-F 4-F-Ph NH(4-MeO-Ph)

CF 3 7-F 4-F-Ph NHS0 2 NH 2 CF 3 7-F 4-F-Ph NH(4-MeO-Ph) OCF3 7-F 4-F-Ph NHS0 NH 2 OCF3 7-F 4-F-Ph NH(4-MeO-Ph)

CF 3 7-Cl C0 2 Me NHS0 2 NH 2 CF3 7-Cl C0 2 Me NH(4-MeO-Ph)

OCF3 7-Cl C0 2 Me NHS0 2 NH 2 OCF3 7-Cl C0 2 Me NH(4-MeO-Ph) OCF3 7-Cl C0 2 Et NHS0 2 NH 2 OCF3 7-Cl C0 2 Et NH(4-MeO-Ph)

Br 7-F 4-F-Ph NHS0 NHPh Br 7-F 4-F-Ph NHCH 2 C_CH

CF 3 7-F 4-F-Ph NHS0 2 NHPh CF3 7-F 4-F-Ph NHCH 2 C-CH

OCF3 7-F 4-F-Ph NHS0 2 NHPh OCF3 7-F 4-F-Ph NHCH 2 C_CH

CF3 7-Cl C0 2 Me NHS0 2 NHPh CF 3 7-Cl C0 2 Me NHCH 2 C_CH

OCF3 7-Cl C0 2 Me NHS0 2 NHPh OCF3 7-Cl C0 2 Me NHCH 2 C_CH

OCF3 7-Cl C0 2 Et NHS0 NHPh OCF3 7-Cl C0 Et NHCH 2 C«CH

TABLE 20

B 1 B J X B B^ B 3 X

CF 3 6-F 4-F-Ph NH 2 CF 3 6-F 4-F-Ph NHMe

CF 3 6-F Me NH 2 CF 3 6-F Me NHMe

CF3 6-F Et NH 2 CF 3 6-F Et NHMe

CF 3 6-F i-Pr NH 2 CF 3 6-F i-Pr NHMe

CF 3 7-F 4-F-Ph NH 2 CF 3 7-F 4-F-Ph NHMe

CF 3 7-F Me NH 2 CF 3 7-F Me NHMe

CF 3 7-F Et NH 2 CF 3 7-F Et NHMe

CF 3 7-F i-Pr NH 2 CF 3 7-F i-Pr NHMe

CF 3 7-Cl 4-F-Ph NH 2 CF 3 7-Cl 4-F-Ph NHMe

CF 3 7-Cl Me NH 2 CF 3 7-Cl Me NHMe

CF 3 7-Cl Et NH 2 CF 3 7-Cl Et NHMe

CF 3 7-Cl i-Pr NH 2 CF 3 7-Cl i-Pr NHMe

OCF 3 6-F 4-F-Ph NH 2 OCF 3 6-F 4-F-Ph NHMe

OCF3 6-F Me NH 2 OCF 3 6-F Me NHMe

OCF3 6-F Et NH 2 OCF 3 6-F Et NHMe

OCF3 6-F i-Pr NH 2 OCF 3 6-F i-Pr NHMe

OCF3 7-F 4-F-Ph NH 2 OCF 3 7-F 4-F-Ph NHMe

OCF3 7-F Me NH 2 OCF 3 7-F Me NHMe

OCF 3 7-F Et NH 2 OCF 3 7-F Et NHMe

OCF 3 7-F i-Pr NH 2 OCF 3 7-F i-Pr NHMe

OCF 3 7-Cl 4-F-Ph NH 2 OCF 3 7-Cl 4-F-Ph NHMe

OCF 3 7-Cl Me NH 2 OCF 3 7-Cl Me NHMe

OCF 3 7-Cl Et NH 2 OCF 3 7-Cl Et NHMe

OCF 3 7-Cl i-Pr NH 2 OCF 3 7-Cl i-Pr NHMe

B 1 B^ B 3 B 1 B z B 3 X

C 3 6-F 4-F-Ph NH(CO)NHMe CF 3 6-F 4-F-Ph NHC0 2 Me

CF 3 6-F Me NH(CO)NHMe CF 3 6-F Me NHC0 2 Me

CF 3 6-F Et NH(CO)NHMe CF 3 6-F Et NHC0 2 Me

CF 3 6-F i-Pr NH(CO)NHMe CF 3 6-F i-Pr NHC0 2 Me

CF 3 7-F 4-F-Ph NH(CO)NHMe CF 3 7-F 4-F-Ph NHC0 2 Me

CF 3 7-F Me NH(CO)NHMe CF 3 7-F Me NHC0 2 Me

CF 3 7-F Et NH(CO)NHMe CF 3 7-F Et NHC0 2 Me

CF 3 7-F i-Pr NH(CO)NHMe CF 3 7-F i-Pr NHC0 2 Me

CF 3 7-Cl 4-F-Ph NH(CO)NHMe CF 3 7-Cl 4-F-Ph NHC0 2 Me

CF 3 7-Cl Me NH(CO)NHMe CF 3 7-Cl Me NHC0 Me

CF 3 7-Cl Et NH(CO)NHMe CF 3 7-Cl Et NHC0 Me

CF 3 7-Cl i-Pr NH(CO)NHMe CF 3 7-Cl i-Pr NHC0 2 Me

OCF 3 6-F 4-F-Ph NH(CO)NHMe OCF 3 6-F 4-F-Ph NHC0 2 Me

OCF 3 6-F Me NH(CO)NHMe OCF3 6-F Me NHC0 2 Me

OCF 3 6-F Et NH(CO)NHMe OCF3 6-F Et NHCO^e

OCF 3 6-F i-Pr NH(CO)NHMe OCF3 6-F i-Pr NHC0 2 Me

OCF 3 7-F 4-F-Ph NH(CO)NHMe OCF3 7-F 4-F-Ph NHC0 2 Me

OCF 3 7-F Me NH(CO)NHMe OCF3 7-F Me NHC0 2 Me

OCF 3 7-F Et NH(CO)NHMe OCF3 7-F Et NHC0 2 Me

OCF 3 7-F i-Pr NH(CO)NHMe OCF3 7-F i-Pr NHC0 2 Me

OCF 3 7-Cl 4-F-Ph NH(CO)NHMe OCF3 7-Cl 4-F-Ph NHC0 2 Me

OCF 3 7-Cl Me NH(CO)NHMe OCF3 7-Cl Me NHC0 2 Me

OCF 3 7-Cl Et NH(CO)NHMe OCF3 7-Cl Et NHC0 2 Me

OCF 3 7-Cl i-Pr NH(CO)NHMe OCF3 7-Cl i-Pr NHC0 2 Me

B 1 B 3 X B 1 B^ B 3 X

CF 3 6-F 4-F-Ph N-CHPh CF 3 6-F 4-F-Ph OH

CF 3 6-F Me N-CHPh CF 3 6-F Me OH

CF 3 6-F Et N-CHPh CF 3 6-F Et OH

CF 3 6-F i-Pr N-CHPh CF 3 6-F i-Pr OH

CF 3 7-F 4-F-Ph N-CHPh CF 3 7-F 4-F-Ph OH

CF 3 7-F Me N-CHPh C 3 7-F Me OH

CF 3 7-F Et N-CHPh CF 3 7-F Et OH

CF 3 7-F i-Pr N-CHPh CF 3 7-F i-Pr OH

CF 3 7-Cl 4-F-Ph N-CHPh CF 3 7-Cl 4-F-Ph OH

CF 3 7-Cl Me N-CHPh CF 3 7-Cl Me OH

CF 3 7-Cl Et N-CHPh CF 3 7-Cl Et OH

CF 3 7-Cl i-Pr N-CHPh CF 3 7-Cl i-Pr OH

OCF 3 6-F 4-F-Ph N-CHPh OCF 3 6-F 4-F-Ph OH

OCF 3 6-F Me N-CHPh OCF 3 6-F Me OH

OCF 3 6-F Et N-CHPh OCF 3 6-F Et OH

OCF 3 6-F i-Pr N-CHPh OCF 3 6-F i-Pr OH

OCF 3 7-F 4-F-Ph N-CHPh OCF 3 7-F 4-F-Ph OH

OCF 3 7-F Me N-CHPh OCF 3 7-F Me OH

OCF 3 7-F Et N-CHPh OCF 3 7-F Et OH

OCF 3 7-F i-Pr N-CHPh OCF 3 7-F i-Pr OH

OCF 3 7-Cl 4-F-Ph N-CHPh OCF 3 7-Cl 4-F-Ph OH

OCF 3 7-Cl Me N-CHPh OCF 3 7-Cl Me OH

OCF 3 7-Cl Et N-CHPh OCF 3 7-Cl Et OH

OCF 3 7-Cl i-Pr N-CHPh OCF 3 7-Cl i-Pr OH

B x B 3 X

CF 3 6-F 4-F-Ph OMe

CF 3 6-F Me OMe

CF 3 6-F Et OMe

CF 3 6-F i-Pr OMe

CF 3 7-F 4-F-Ph OMe

CF 3 7-F Me OMe

C 3 7-F Et OMe CF 3 7-F i-Pr OMe

CF 3 7-Cl 4-F-Ph OMe

CF 3 7-Cl Me OMe

CF 3 7-Cl Et OMe

CF 3 7-Cl i-Pr OMe

OCF 3 6-F 4-F-Ph OMe

OCF 3 6-F Me OMe

OCF 3 6-F Et OMe

OCF 3 6-F i-Pr OMe

OCF 3 7-F 4-F-Ph OMe

OCF 3 7-F Me OMe

OCF 3 7-F Et OMe

OCF 3 7-F i-Pr OMe

OCF 3 7-Cl 4-F-Ph OMe

OCF 3 7-Cl Me OMe

OCF 3 7-Cl Et OMe

OCF-_ . 7-Cl i-Pr OMe

B 1 B^ B J B 1 B^ B J X CF 3 6-F 4-F-Ph NH(CO)NHMe CF 3 6-F 4-F-Ph NHC0 2 Me

C 3 6-F Me NH(CO)NHMe CF 3 6-F Me NHC0 2 Me

CF 3 6-F Et NH(CO)NHMe CF 3 6-F Et NHC0 2 Me

CF 3 6-F i-Pr NH(CO)NHMe CF 3 6-F i-Pr NHC0 2 Me

CF 3 7-F 4-F-Ph NH(CO)NHMe CF 3 7-F 4-F-Ph NHC0 2 Me

CF 3 7-F Me NH(CO)NHMe CF 3 7-F Me NHC0 2 Me

CF 3 7-F Et NH(CO)NHMe CF 3 7-F Et NHC0 2 Me

CF 3 7-F i-Pr NH(CO)NHMe CF 3 7-F i-Pr NHC0 Me

CF 3 7-Cl 4-F-Ph NH(CO)NHMe CF 3 7-Cl 4-F-Ph NHC0 Me

CF 3 7-Cl Me NH(CO)NHMe CF 3 7-Cl Me NHC0 Me

CF 3 7-Cl Et NH(CO)NHMe CF 3 7-Cl Et NHC0 Me

CF 3 7-Cl i-Pr NH(CO)NHMe CF 3 7-Cl i-Pr NHC0 2 Me

OCF 3 6-F 4-F-Ph NH(CO)NHMe OCF 3 6-F 4-F-Ph NHC0 2 Me

OCF 3 6-F Me NH(CO)NHMe OCF 3 6-F Me NHC0 2 Me

OCF 3 6-F Et NH(CO)NHMe OCF 3 6-F Et NHC0 2 Me

OCF 3 6-F i-Pr NH(CO)NHMe OCF 3 6-F i-Pr NHC0 2 Me

OCF 3 7-F 4-F-Ph NH(CO)NHMe OCF 3 7-F 4-F-Ph NHC0 2 Me

OCF 3 7-F Me NH(CO)NHMe OCF 3 7-F Me NHC0 2 Me

OCF 3 7-F Et NH(CO)NHMe OCF 3 7-F Et NHC0 2 Me

OCF 3 7-F i-Pr NH(CO)NHMe OCF 3 7-F i-Pr NHC0 2 Me

OCF 3 7-Cl 4-F-Ph NH(CO)NHMe OCF 3 7-Cl 4-F-Ph NHC0 2 Me

OCF 3 7-Cl Me NH(CO)NHMe OCF 3 7-Cl Me NHC0 2 Me

OCF 3 7-Cl Et NH(CO)NHMe OCF 3 7-Cl Et NHC0 2 Me

OCF 7-Cl i-Pr NH(CO)NHMe OCF 3 7-Cl i-Pr NHC0 2 Me

B x ^ B 3 X B- 1 B^ B 3 X CF 3 6-F 4-F-Ph N-CH 2 CF 3 6-F 4-F-Ph N-CMe 2

CF 3 6-F Me N^CH 2 CF 3 6-F Me N-CMe 2

CF 3 6-F Et N-CH 2 CF 3 6-F Et N-CMe 2

CF 3 6-F i-Pr N-CH 2 CF 3 6-F i-Pr N-CMe 2

CF 3 7-F 4-F-Ph N-CH 2 C 3 7-F 4-F-Ph N-CMe 2

CF 3 7-F Me N-CH 2 CF 3 7-F Me N-CMe 2

CF 3 7-F Et N—CH 2 CF 3 7-F Et N—CMe 2

CF 3 7-F i-Pr N-CH 2 CF 3 7-F i-Pr N-CMe 2

CF 3 7-Cl 4-F-Ph N-CH 2 CF 3 7-Cl 4-F-Ph N-CMe 2

CF 3 7-Cl Me N«CH 2 CF 3 7-Cl Me N-CMe 2

CF 3 7-Cl Et N-CH 2 CF 3 7-Cl Et N-CMe

CF 3 7-Cl i-Pr N-CH 2 CF 3 7-Cl i-Pr N-CMe 2

OCF 3 6-F 4-F-Ph N-CH 2 OCF 3 6-F 4-F-Ph N-CMe 2

OCF 3 6-F Me N-CH 2 OCF 3 6-F Me N-CMe 2

OCF 3 6-F Et N-CH 2 OCF 3 6-F Et N-CMe 2

OCF 3 6-F i-Pr N-CH 2 OCF 3 6-F i-Pr N-CMe 2

OCF 3 7-F 4-F-Ph N-CH 2 OCF 3 7-F 4-F-Ph N-CMe 2

OCF 3 7-F Me N-CH 2 OCF 3 7-F Me N-CMe 2

OCF 3 7-F Et N-CH 2 OCF 3 7-F Et N-CMe 2

OCF 3 7-F i-Pr N-CH 2 OCF 3 7-F i-Pr N-CMe 2

OCF 3 7-Cl 4-F-Ph N-CH 2 OCF 3 7-Cl 4-F-Ph N-CMe 2

OCF 3 7-Cl Me N-CH 2 OCF 3 7-Cl Me N-CMe 2

OCF 3 7-Cl Et N-CH 2 OCF 3 7-Cl Et N-CMe 2

OCF 3 7-Cl i-Pr N-CH 2 OCF_ 7-Cl i-Pr N-CMe 2

B 1 B B 3 X B 1 B^ B 3 X

CF 3 6-F 4-F-Ph N-CHPh CF 3 6-F 4-F-Ph OH

CF 3 6-F Me N-CHPh CF 3 6-F Me OH

CF 3 6-F Et N-CHPh CF 3 6-F Et OH

CF 3 6-F i-Pr N-CHPh CF 3 6-F i-Pr OH

CF 3 7-F 4-F-Ph N-CHPh CF 3 7-F 4-F-Ph OH

CF 3 7-F Me N-CHPh CF 3 7-F Me OH

CF 3 7-F Et N-CHPh CF 3 7-F Et OH

CF 3 7-F i-Pr N-CHPh CF 3 7-F i-Pr OH

CF 3 7-Cl 4-F-Ph N-CHPh CF 3 7-Cl 4-F-Ph OH

CF 3 7-Cl Me N-CHPh CF 3 7-Cl Me OH

CF 3 7-Cl Et N-CHPh CF 3 7-Cl Et OH CF 3 7-Cl i-Pr N-CHPh CF 3 7-Cl i-Pr OH

OCF 3 6-F 4-F-Ph N-CHPh OCF 3 6-F 4-F-Ph OH

OCF 3 6-F Me N-CHPh OCF3 6-F Me OH

OCF 3 6-F Et N-CHPh OCF3 6-F Et OH

OCF 3 6-F i-Pr N-CHPh OCF3 6-F i-Pr OH

OCF 3 7-F 4-F-Ph N-CHPh OCF3 7-F 4-F-Ph OH

OCF 3 7-F Me N-CHPh OCF3 7-F Me OH

OCF 3 7-F Et N-CHPh OCF3 7-F Et OH

OCF 3 7-F i-Pr N-CHPh OCF3 7-F i-Pr OH

OCF 3 7-Cl 4-F-Ph N-CHPh OCF3 7-Cl 4-F-Ph OH

OCF 3 7-Cl Me N-CHPh OCF3 7-Cl Me OH

OCF 3 7-Cl Et N-CHPh OCF3 7-Cl Et OH

OCF 3 7-Cl i-Pr N-CHPh OCF3 7-Cl i-Pr OH

B x ^ X

CF 3 6-F 4-F-Ph OMe

CF 3 6-F Me OMe

CF 3 6-F Et OMe

CF 3 6-F i-Pr OMe

CF 3 7-F 4-F-Ph OMe

CF3 7-F Me OMe

CF 3 7-F Et OMe

CF 3 7-F i-Pr OMe

CF 3 7-Cl 4-F-Ph OMe

CF 3 7-Cl Me OMe

CF 3 7-Cl Et OMe

CF 3 7-Cl i-Pr OMe

OCF 3 6-F 4-F-Ph OMe

OCF 3 6-F Me OMe

OCF 3 6-F Et OMe

OCF 3 6-F i-Pr OMe

OCF 3 7-F 4-F-Ph OMe

OCF 3 7-F Me OMe

OCF 3 7-F Et OMe

OCF 3 7-F i-Pr OMe

OCF 3 7-Cl 4-F-Ph OMe

OCF 3 7-Cl Me OMe

OCF 3 7-Cl Et OMe

OCF 3 7-Cl i-Pr OMe

B 1 B^ B 3 X B B^ B 3 X

CF 3 6-F 4-F-Ph -CH 2 OCH 3 CF 3 6-F 4-F-Ph -CH 2 C0 2 Me

CF 3 6-F Me -CH 2 OCH 3 CF 3 6-F Me -CH 2 C0Me

CF 3 6-F Et —CH 2 OCH 3 CF 3 6-F Et -CH 2 C0Me

CF 3 6-F i-Pr -CH 2 OCH 3 CF 3 6-F i-Pr -CH 2 C0 2 Me

CF 3 7-F 4-F-Ph -CH 2 OCH 3 CF 3 7-F 4-F-Ph -CH 2 C0 2 Me

CF 3 7-F Me -CH 2 OCH 3 CF 3 7-F Me -CH 2 C0Me

CF 3 7-F Et -CH OCH 3 CF 3 7-F Et -CH 2 C0 Me

CF 3 7-F i-Pr -CH 2 OCH 3 CF 3 7-F i-Pr -CH 2 C0 2 Me

CF 3 7-Cl 4-F-Ph -CH 2 OCH 3 C 3 7-Cl 4-F-Ph -CJ^CO^e

CF 3 7-Cl Me -CH 2 OCH 3 CF 3 7-Cl Me -CH 2 C0 2 Me

CF 3 7-Cl Et -CH 2 OCH 3 CF3 7-Cl Et -CH 2 C0 2 Me

CF 3 7-Cl i-Pr -CH 2 OCH 3 CF 3 7-Cl i-Pr -CH C0 2 Me

OCF 3 6-F 4-F-Ph -CH 2 OCH 3 OCF3 6-F 4-F-Ph -CH 2 C0 2 Me

OCF 3 6-F Me -CH 2 OCH 3 OCF3 6-F Me -CH 2 C0 2 Me

OCF 3 6-F Et -CH 2 OCH 3 OCF3 6-F Et -CH 2 C0 2 Me

OCF 3 6-F i-Pr -CH 2 OCH 3 OCF3 6-F i-Pr -CH 2 C0Me

OCF 3 7-F 4-F-Ph -CH 2 OCH 3 OCF3 7-F 4-F-Ph -CH 2 C0 2 Me

OCF 3 7-F Me -CH 2 OCH 3 OCF3 7-F Me -CH 2 C0 2 Me

OCF 3 7-F Et -CH 2 OCH 3 OCF3 7-F Et -CH 2 C0 2 Me

OCF 3 7-F i-Pr -CH 2 OCH 3 OCF3 7-F i-Pr -CH 2 C0 2 Me

OCF 3 7-Cl 4-F-Ph -CH 2 OCH 3 OCF3 7-Cl 4-F-Ph -CH 2 C0 2 Me

OCF 3 7-Cl Me -CH 2 OCH 3 OCF3 7-Cl Me -CH 2 C0 2 Me

OCF 3 7-Cl Et -CH 2 OCH 3 OCF3 7-Cl Et -CH 2 C0 2 Me

OCF 3 7-Cl i-Pr -CH 2 OCH 3 OCF3 7-Cl i-Pr -CH 2 C0 2 Me

E x B J X B 1 B^ B 3 X

CF 3 6-F 4-F-Ph —CH 2 OCH 3 CF 3 6-F 4-F-Ph -CH 2 C0 2 Me

CF 3 6-F Me -CH 2 OCH 3 CF 3 6-F Me -CH 2 C0 Me

CF 3 6-F Et -CH 2 OCH 3 CF 3 6-F Et -CH 2 C0 2 Me

CF 3 6-F i-Pr —CH 2 OCH 3 CF 3 6-F i-Pr -CH 2 C0 2 Me

CF 3 7-F 4-F-Ph -CH OCH 3 CF 3 7-F 4-F-Ph -CH 2 C0 2 Me

CF 3 7-F Me -CH 2 OCH 3 CF 3 7-F Me -CH 2 C0 2 Me

CF 3 7-F Et -CH 2 OCH 3 CF 3 7-F Et -CH 2 C0 2 Me

CF 3 7-F i-Pr -CH 2 OCH 3 CF 3 7-F i-Pr -CH 2 C0 2 Me

CF 3 7-Cl 4-F-Ph -CH 2 OCH 3 CF 3 7-Cl 4-F-Ph -CH C0 2 Me

CF 3 7-Cl Me -CH 2 OCH 3 CF 3 7-Cl Me -CH 2 C0 2 Me

CF 3 7-Cl Et —CH 2 OCH 3 CF 3 7-Cl Et -CH 2 C0 Me

CF 3 7-Cl i-Pr -CH 2 OCH 3 CF 3 7-Cl i-Pr -CH 2 C0 2 Me

OCF 3 6-F 4-F-Ph -CH 2 OCH 3 OCF 3 6-F 4-F-Ph -CH 2 C0 2 Me

OCF 3 6-F Me -CH 2 OCH 3 OCF 3 6-F Me -CH 2 C0 2 Me

OCF 3 6-F Et -CH 2 OCH 3 OCF 3 6-F Et -CH 2 C0 Me

OCF 3 6-F i-Pr —CH 2 OCH 3 OCF 3 6-F i-Pr -CH 2 C0 2 Me

OCF 3 7-F 4-F-Ph -CH 2 OCH 3 OCF 3 7-F 4-F-Ph -CH 2 C0 2 Me

OCF 3 7-F Me -CH 2 OCH 3 OCF 3 7-F Me -CH 2 C0 2 Me

OCF 3 7-F Et -CH 2 OCH 3 OCF 3 7-F Et -CH 2 C0 Me

OCF 3 7-F i-Pr -CH 2 OCH 3 OCF 3 7-F i-Pr -CH 2 C0 2 Me

OCF 3 7-Cl 4-F-Ph -CH 2 OCH 3 OCF 3 7-Cl 4-F-Ph -CH 2 C0 2 Me

OCF 3 7-Cl Me -CH 2 OCH 3 OCF 3 7-Cl Me -CH 2 C0 2 Me

OCF 3 7-Cl Et -CH 2 OCH 3 OCF 3 7-Cl Et -CH 2 C0 2 Me

OCF 3 7-Cl i-Pr -CH 2 OCH 3 OCF 3 7-Cl i-Pr -CH 2 C0 2 Me

Formulation and Use

The compounds of this invention will generally be used in formulation with an agriculturally suitable carrier comprising a liquid or solid diluent or an organic solvent. Useful formulations of the compounds of Formula I can be prepared in conventional ways. They include dusts, granules, baits, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Many of these can be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain from less than about 1% to 99% by weight of active ingredient(s) and at least one of a) about 0.1% to 20% surfactant(s) and b) about 5% to 99% solid or liquid diluent(s) . More specifically, they will contain effective amounts of these ingredients in the following approximate proportions:

Percent by Weight

Active Ingre ien Diluent. I s ) Surfant-ant....ι

Wettable Powders 25-90 0-74 1-10

Oil Suspensions, 5-50 40-95 0-15 Emulsions, Solutions, (including Emulsifiable Concentrates)

Lower or higher levels of active ingredient can, of course, be present depending on the intended use and the physical properties of the compound. Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mixing.

Typical solid diluents are described in Watkins, et al., "Handbook of nsecticide Dust Diluents and Carriers", 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, "Solvents Guide," 2nd Ed., Interscience, New York, 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0°C. "McCutcheon's Detergents and Emulsifiers 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, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.

The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer or fluid energy mill. Suspensions are prepared by wet milling

(see, for example, U.S. 3,060,084). Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See J. E. Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pages 147 and

following, and "Perry's Chemical Engineer's Handbook", 4th Ed., McGraw-Hill, New York, 1963, pages 8 to 59 and following.

Example _

Emulsifiable Concentrate

Methyl 2,3-dihydro-2-[[N-methyl-N-[4-(trifluoro¬ methyl)phenyl]amino]carbonyl]-7-(trifluoro¬ methyl) [1]benzopyrano-[4,3-c]pyrazole-3a(4H)- carboxylate 20% blend of oil soluble sulfonates and polyoxyethylene ethers 10% isophorone 70%

The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filter is included in the packaging operation to insure the absence of any extraneous undissolved material in the product.

Example B Wettable Powder

Methyl 7-chloro-2,3-dihydro-2-[[N-methyl-N-[4- (trifluoromethyl)phenyl]amino]carbonyl]- [1]benzopyrano[4,3-c]pyrazole-3a(4H)- carboxylate 30% sodium alkylnaphthalenesulfonate 2% sodium ligninsulfonate 2% synthetic amorphous silica 3% kaolinite 63%

The active ingredient is mixed with the inert materials in a blender. After grinding in a hammer-mill, the material is re-blended and sifted through a 50 mesh screen.

Example C __________

Wettable powder of Example B 10% pyrophyllite (powder) 90% The wettable powder and the pyrophyllite diluent are thoroughly blended and then packaged. The product is suitable for use as a dust.

Example D Granule

Methyl 2-[[N-(4-chlorophenyl)-N-methylamino]- carbonyl]2,3-dihydro-7-(trifluoromethyl) [1]- * benzopyrano[4,3-c]-pyrazole-3a(4H)-carboxylate 10% attapulgite granules (low volative matter, 0.71/0.30 mm; U.S.S. No.

25-50 sieves) 90%

The active ingredient is dissolved in a volatile solvent such as acetone and sprayed upon dedusted and pre-warmed attapulgite granules in a double cone blender. The acetone is then driven off by heating. The granules are then allowed to cool and are packaged.

Example E Granule Wettable powder of Example B 15% gypsum 69% potassium sulfate 16%

The ingredients are blended in a rotating mixer and water sprayed on to accomplish granulation. When most of the material has reached the desired range of 0.1 to 0.42 mm (U.S.S. No. 18 to 40 sieves), the granules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range. These granules contain 4.5% active ingredient.

Example F

Solution

Methyl 2-[ [N-(4-bromophenyl)-N-methylamino]- carbonyl]2,3-dihydro-7-(trifluoromethyl)-[1]- benzopyrano[4,3-c]pyrazole-3a(4H)-carboxylate 25% N-methyl-pyrrolidone 75%

The ingredients are combined and stirred to produce a solution suitable for direct, low volume application.

Example G

Aqueous Suspension

Methyl 2,3-dihydro-2-[[N-methyl-N-[4-(trifluoro- methoxy)phenyl]amino]carbonyl]-7-(trifluoro¬ methyl) [1]benzopyrano[4,3-c]pyrazole- 3a(4H)-carboxylate 40% polyacrylic acid thickener 0.3% dodecyclophenol polyethylene glycol 0.5% disodium phosphate 1.0% monosodium phosphate 0.5% polyvinyl alcohol 1.0% water 56.7%

The ingredients are blended and ground together in a sand mill to produce particles substantially all under 5 microns in size.

Example H Oil Suspension

Methyl 2,3-dihydro-2-[[N-methyl-N-[4-(trifluoro¬ methyl)phenyl]amino]carbonyl]-7-(trifluoro- methyl) [1]benzopyrano[4,3-c]-pyrazole-3a(4H)- carboxylate 35.0% blend of polyalcohol carboxylic 6.0% esters and oil soluble petroleum sulfonates xylene range solvent 59.0%

The ingredients are combined and ground together in a sand mill to produce particles substantially all below 5 microns. The product can be used directly, extended with oils, or emulsified in water.

Example I Bait Granules

Methyl 2,3-dihydro-2-[[N-methyl-N-[ (trifluoro¬ methyl)phenyl]amino]carbonyl]-7-(trifluoro- methyl) [1]benzopyrano[4,3-c]-pyrazole-3a(4H)- carboxylate 3.0% blend of polyethoxylated nonyl- 9.0% phenols and sodium dodecylbenzene sulfonates ground up corn cobs 88.0%

The active ingredient and surfactant blend are dissolved in a suitable solvent such as acetone and sprayed onto the ground corn cobs. The granules are then dried and packaged. Compounds of Formula I can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of effective agricultural protection. Examples of other agricultural protectants with which compounds of this invention can be formulated are:

Insecticides: 3-hydroxy-N-methylcrotonamide(dimethyIphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-dimethyl-

7-benzof ranol (carbofuran) 0-[2,4,5-trichloro-α-(chloromethyl)benzyl]phosphoric acid, O',0'-dimethyl ester (tetrachlorvinphos)

2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester ( alathion) phosphorothioic acid, 0,0-dimethyl, O-p-nitrophenyl ester (methyl parathion) methylcarbamic acid, ester with a-naphthol (carbaryl) methyl O-(methylcarbamoyl)thiolacetohydroxamate

(methomyl) N'-(4-chloro-o_-tolyl)-N,N-dimethylform__midine (chlordimeform) 0,0-diethyl-0-2-isopropyl-4-methyl-6-pyrimidylphos- phorothioate (diazinon) octachlorocamphene (toxaphene)

O-ethyl-0-p-nitrophenyl phenylphosphonothioate (EPN) (S)-α-cyano-m-phenoxybenzyl(1R,3R)-3-(2,2-dibromovinyl)- 2,2-dimethylcyclopropanecarboxylate (deltamethrin)

Methyl-N',N'-dimethyl-N-[ (methylcarbamoyl)oxy]-1-thioox amimidate (oxamyl) cyano(3-phenoxyphenyl)-methyl-4-chloro-α-(1-methyl- ethy1)benzeneacetate (fenvalerate) (3-phenoxyphenylJmethyl ( +T-cis r rans-3-(2 f 2-dichloro ethenyl)-2,2-dimethylcyclopropanecarboxylate (permethrin) α-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylate (cypermethrin) O-ethyl-S-(p-chlorophenyl)ethylphosphonodithioate (profenofos) O-ethyl-O-[4-(methylthio)-phenyl]-S-n-propyl ester (sulprofos) .

Additional insecticides are listed hereafter by their common names: triflumuron, diflubenzuron, methoprene, buprofezin, thiodicarb, acephate, azinphosmethyl, chlorpyrifos, dimethoate, fonophos, isofenphos, methidathion, methamidiphos, monocrotphos, phosmet, phosphamidon, phosalone, pirimicarb, phorate,

terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, etaldehyde and rotenone.

Fungicides: methyl 2-benzimidazolecarbamate (carbendazim) tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (maneb) l-4-dichloro-2,5-dimethoxybenzene (chloroneb) methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate

(benomyl) l-[2-(2,4-dichlorophenyl)-4-propyl-l,3-dioxolan-2- ylmethyl]-1H-1,2,4-triazole (propiconazole) 2-cyano-N-ethylcarbamoyl-2-methoxyiminoacetamide (cymoxanil) 1-(4-chlorophenoxy)-3,3-dimethyl-l-(1H-1,2,4-triazol-l- yl)-2-butanone (triadimefon) N-(trichloromethylthio)tetrahydrophthalimide (captan) N-(trichloromethylthio)phthalimide (folpet) l-[[[bis(4-fluorophenyl)] [methyl]silyl]methyl]-1H-1,2,4- triazole (flusilazol)

Nematocides: S-methyl 1-(dimethylcarbamoyl)-N-(methylcarbamoyloxy)- thioformimidate S-methyl 1-carbamoyl-N-(methylcarbamoyloxy)- thioformimidate N-isopropylphosphoramidic acid O-ethyl 0'-[4-(methyl- thio)-m-tolyl]diester (fenamiphos)

Baπtericides: tribasic copper sulfate streptomycin sulfate

Aπaricides: senecioic acid, ester with 2-sec-butyl-4 r 6-dinitro-phenol

(binapacryl) 6-methyl-l,3-cithiolo[4,5-β]quinoxalin-2-one (oxythioquinox) ethyl 4,4'-dichlorobenzilate (chlorobenzilate) 1,1-bis (p-chlorophenyl ) -2, 2,2-trichloroethanol (dicofol) bis(pentachloro-2,4-cyclopentadien-l-yl) (dienochlor) tricyclohexyltin hydroxide (cyhexatin) trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2-oxo- thiazolidine-3-carboxamide (hexythiazox) amitraz propargite fenbutatin-oxide

Biological

Bacillus thuringiensis

Avermectin B.

Utility

The compounds of this invention are characterized by favorable metabolic and soil residual patterns and exhibit activity against a wide spectrum of foliar and soil-inhabiting arthropods which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will recognize that not all compounds are equally effective against all pests but the compounds of this invention display activity against economically important agronomic, forestry, greenhouse, ornamental food and fiber product, stored product, domestic structure, and nursery pests, such as:

larvae of the order Lepidoptera including fall and beet armyworm and other Spodoptera ≤pp., tobacco budworm, corn earworm and other Heliothis ≤pp., European corn borer, navel 5 orangeworm, stalk/stem borers and other pyralids, cabbage and soybean loopers and other loopers, codling moth, grape berry moth and other tortricids, black cutworm, spotted cutworm, other cutworms and other noctuids, 10 diamondback moth, green cloverworm, velvetbean caterpillar, green cloverworm, pink bollworm, gypsy moth, and spruce budworm;

foliar feeding larvae and adults of the order 15 Coleoptera including Colorado potato beetle,

Mexican bean beetle, flea beetle, Japanese beetles, and other leaf beetles, boll weevil, rice water weevil, granary weevil, rice weevil and other weevil pests, and soil inhabiting 20 insects such as Western corn rootworm and other

Diabrotica ≤pp.., Japanese beetle, European chafer and other coleopteran grubs, and wireworms;

25 adults and larvae of the orders Hemipt ra and

Homopt ra including tarnished plant bug and other plant bugs .miridaei , aster leafhopper and other leafhoppers .cicadellidae) , rice planthopper, brown planthopper, and other

30 planthoppers (fulgoroidea) f psylids, whiteflies

(aleurodidae) , aphids (__j22_i_____) , scales (coccidae and diaspididae) , lace bugs

(tingidae), stink bugs (pentatomidae) , cinch bugs and other seed bugs .lygaeidaeϊ , cicadas 35 (Cicadidae) , spittlebugs .cercopidBΪ , squash

bugs (-oreidae) , red bugs and cotton stainers (pyrrhocorida ) ;

adults and larvae of the order acari (mites) including European red mite, two spotted spider mite, rust mites, McDaniel mite, and foliar feeding mites;

adults and immatures of the order Orthoptera including grasshoppers;

adults and immatures of the order Diptera including leafminers, midges, fruit flies (tephritidae) , and soil maggots;

adults and immatures of the order Thysanoptera including onion thrips and other foliar feeding thrips.

The compounds are also active against economically important livestock, household, public and animal health pests such as:

insect pests of the order Hymenoptera including carpenter ants, bees, hornets, and wasps;

insect pests of the order Diptera including house flies, stable flies, face flies, horn flies, blow flies, and other muscoid fly pests, horse flies, deer flies and other Brachycera f mosquitoes, black flies, biting midges, sand flies, sciarids, and other Nematocera

insect pests of the order Orthoptera including cockroaches and crickets;

insect pests of the order Isoptera including the Eastern subterranean termite and other termites;

insect pests of the order Mallophaga and

Anoplura including the head louse, body louse, chicken head louse and other sucking and chewing parasitic lice that attack man and animals;

insect pests of the order Siphonoptera including the cat flea, dog flea and other fleas.

The specific species for which control is exemplified are: fall armyworm, Spodoptera fruigiperda: tobacco budworm, H liothis virescens. boll weevil, __nthenemus grandis; aster leafhopper, Macrosteles fascifrons; black bean aphid, .Aphis Fabaei ; southern corn rootworm, Diabroti__a undeci punct t . The pest control protection afforded by the compounds of the present invention is not limited, however, to these species. The compounds of this invention may also be utilized as rodenticides.

Application Arthropod pests are controlled and protection of agronomic crops, animal and human health is achieved by applying one or more of the 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. Because of the diversity of habitat and behavior of these arthropod pest species, many different methods of application are employed. A preferred method of application is by spraying with equipment that distributes the compound in the

environment of the pests, on the foliage, animal, person, or premise, in the soil or animal, to the plant part that is infested or needs to be protected. Alternatively, granular formulations of these toxicant compounds can be applied to or incorporated into the soil. Other methods of application can also be employed including direct and residual sprays, aerial sprays, baits, eartags, boluses, foggers, aerosols, and many others. The compounds can be incorporated into baits that are consumed by the arthropods or in devices such as traps and the like which entice them to ingest or otherwise contact the compounds.

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 (including 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 concentrations, and synergists such as piperonyl butoxide often enhance the efficacy of the compounds of this invention.

The rate of application of the compounds required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, etc. In general, application rates of 0.01 to 2 kg of active ingredient per hectare are sufficient to provide large-scale effective control of pests in agronomic ecosystems under normal circumstances, but as little as 0.001 kg/hectare or as much as 8 kg hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as

about 0.1 mg/square meter or as much as 150 mg/square meter may be required.

The following Tests demonstrate the control efficacy of compounds of Formula I on specific pests; see Index Tables A and B for compound descriptions.

INDEX TABLE __

INDEX TABLE B

TEST A

Fall Armyworm

Test units, each consisting of an 8-ounce (230 mL) plastic cup containing a layer of wheat germ diet, approximately 0.5 cm thick, were prepared. Ten third- instar larvae of fall armyworm .Spodoptera frugiperdai were placed into a cup. Solutions of each of the test compounds (acetone/distilled water 75/25 solvent) were sprayed into the cup. Spraying was accomplished by passing the cup, on a conveyer belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.5 pounds of active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i. (207 kPa) . The cup was then covered and held at 27°C and 50% relative humidity for 48 hours, after which time readings were taken. Of the compounds tested, the following resulted in greater than or equal to 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 9*, 10*, 11*, 12*, 13, 14**, 15, 16, 17, 18, 19, 20, 21, 22,

23, 25, 26, 2, 28, 29, 30, 31, 32, 33, 34, 35, 36, 40, 41, 43, 44, 45* and 46*

_IE___J______

Tf.haf.r.r» Budworm

The test procedure of Test 1 was repeated for efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) . Of the compounds tested, the following resulted in greater than or equal to 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 9*, 10*, 11*, 12*, 13, 14**, 15, 17, 19, 20, 21, 25, 28, 29, 30, 31, 32, 33, 34, 35, 36, 40, 41, 42, 43, 44, 45*, 46 and 47*. TEST C

Southern Ccrn Rcp orm

Test units, each consisting of an 8-ounce (230 mL) plastic cup containing 1 sprouted corn seed, were prepared. The test unit was sprayed as described in Test A with individual solutions of the test compounds. After

the spray on the cup had dried, five third-instar larvae of the southern corn rootworm (Diabrotica undecimpunetata howardi) were placed into the cup. A moistened dental wick was inserted into the cup to prevent drying and the cup was then covered. The cup was then held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested, the following resulted in greater than or equal to 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 9*, 10*, 11*, 12*, 13, 15, 16, 19, 20, 21, 23, 24, 25, 27, 28, 30, 31, 32, 33, 35, 36, 40, 41, 42, 43, 44, 46 and 47*.

TEST D Aster Leafhopper

Test units were prepared from a 12-ounce (350 mL) cup containing oat (Avena sativa) seedlings in a 1-inch (2.54 cm) layer of sterilized soil. The test unit was sprayed as described in Test A with individual solutions of the below-listed compounds. After the oats had dried from the spraying, between 10 and 15 adult aster leafhoppers (__-5<-;rn..___ _ fascifronsϊ were aspirated into the covered cup. The cup was held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings wre taken. Of the compounds tested, the following resulted in greater than or equal to 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 9*, 10*, 11*, 12*, 13, 14**, 15, 16, 17, 20, 21, 27, 28, 29, 30, 31, 32, 33, 35, 36, 40, 43 and 45*.

TEST E Boll Weevil Five adult boll weevils (Anthonomus σrandis ς_ran_ii..i were placed into each of a 9 ounce (260 mL) cup. The test procedure employed was then otherwise the same as in Test A with one cup per treatment. Mortality readings were taken 48 hours after treatment. Of the compounds tested, the following resulted in greater than or equal

to 80% mortality: 1, 2, 3, 4, 5, 6, 7, 8, 9*, 11*, 12*, 13, 16, 17, 20, 25, 27, 28, 29, 31, 33, 36, 40, 41, 42, 43, 44, 46 and 47*.

*Tested at 250 ppm **Tested at 50 ppm