Method for preparing 3-trifluoromethyl chalcones

Abstract

Disclosed is a method for preparing a compound of Formula 1 wherein Q and Z are as defined in the disclosure comprising distilling water from a mixture comprising a compound of Formula 2, a compound of Formula 3, a base comprising at least one compound selected from the group consisting of alkaline earth metal hydroxides of Formula 4 wherein M is Ca, Sr or Ba, alkali metal carbonates of Formula 4a wherein M.sup.1 is Li, Na or K, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water. Also disclosed is a method for preparing a compound of Formula 2 comprising (1) forming a reaction mixture comprising a Grignard reagent derived from contacting a compound of Formula 5 wherein X is Cl, Br or I with magnesium metal or an alkylmagnesium halide in the presence of an ethereal solvent, and then (2) contacting the reaction mixture with a compound of Formula 6 wherein Y is OR.sup.11 or NR.sup.12R.sup.13, and R.sup.11, R.sup.12 and R.sup.13 are as defined in the disclosure. Further disclosed is a method for preparing a compound of Formula 7 wherein Q and Z are as defined in the disclosure, using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above or using a compound of Formula 1 prepared by the method disclosed above. ##STR00001##

Claims

1. A method for preparing a compound of Formula 1 ##STR00071## wherein Z is optionally substituted phenyl; and Q is phenyl or 1-naphthalenyl, each optionally substituted; comprising distilling water from a mixture comprising a compound of Formula 2 ##STR00072## a compound of Formula 3 ##STR00073## a base comprising an alkali metal carbonate selected from the group consisting of the alkali metal carbonates of Formula 4a
(M.sup.1).sub.2CO.sub.3 4a wherein M.sup.1 is Li, Na or K, and an aprotic solvent capable of forming a low-boiling azeotrope with water, wherein said aprotic solvent comprises acetonitrile.

2. The method of claim 1 wherein M.sup.1 is K.

3. The method of claim 1 wherein Z is phenyl optionally substituted with up to 5 substituents independently selected from R.sup.2; and Q is phenyl or 1-naphthalenyl, each optionally substituted with up to four substituents independently selected from R.sup.3; each R.sup.2 is independently halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio, C.sub.1-C.sub.6 alkylamino, C.sub.2-C.sub.6 dialkylamino, CN or NO.sub.2; each R.sup.3 is independently halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 haloalkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 haloalkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.2-C.sub.7 alkylcarbonyl, C.sub.2-C.sub.7 haloalkylcarbonyl, C.sub.1-C.sub.6 haloalkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl, N(R.sup.4)R.sup.5, C(W)N(R.sup.4)R.sup.5, C(W)OR.sup.5, CN, OR.sup.11 or NO.sub.2; or a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl, CN, NO.sub.2, N(R.sup.4)R.sup.5, C(W)N(R.sup.4)R.sup.5, C(O)OR.sup.5 and R.sup.7; each R.sup.4 is independently H, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C4-C7 alkylcycloalkyl, C4-C7 cycloalkylalkyl, C2-C7 alkylcarbonyl or C.sub.2-C.sub.7 alkoxycarbonyl; each R.sup.5 is independently H; or C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.4-C.sub.7 alkylcycloalkyl or C.sub.4-C.sub.7 cycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R.sup.6; each R.sup.6 is independently halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 alkylamino, C.sub.2-C.sub.8 dialkylamino, C.sub.3-C.sub.6 cycloalkylamino, C.sub.2-C.sub.7 alkylcarbonyl, C.sub.2-C.sub.7 alkoxycarbonyl, C.sub.2-C.sub.7 alkylaminocarbonyl, C.sub.3-C.sub.9 dialkylaminocarbonyl, C.sub.2-C.sub.7 haloalkylcarbonyl, C.sub.2-C.sub.7 haloalkoxycarbonyl, C.sub.2-C.sub.7 haloalkylaminocarbonyl, C.sub.3-C.sub.9 halodialkylaminocarbonyl, OH, NH.sub.2, CN or NO.sub.2; or Q.sup.1; each R.sup.7 is independently a phenyl ring or a pyridinyl ring, each ring optionally substituted with one or more substituents independently selected from R.sup.8; each R.sup.8 is independently halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl, C.sub.1-C.sub.6 alkylamino, C.sub.2-C.sub.6 dialkylamino, C.sub.2-C.sub.4 alkylcarbonyl, C.sub.2-C.sub.4 alkoxycarbonyl, C.sub.2-C.sub.7 alkylaminocarbonyl, C.sub.3-C.sub.7 dialkylaminocarbonyl, OH, NH.sub.2, C(O)OH, CN or NO.sub.2; each Q.sup.1 is independently a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 haloalkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 haloalkylsulfinyl, C.sub.1-C.sub.6 alkylsulfonyl, C.sub.1-C.sub.6 haloalkylsulfonyl, C.sub.1-C.sub.6 alkylamino, C.sub.2-C.sub.6 dialkylamino, CN, NO.sub.2, C(W)N(R.sup.9)R.sup.10 and C(O)OR.sup.10; each R.sup.9 is independently H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.4-C.sub.7 alkylcycloalkyl, C.sub.4-C.sub.7 cycloalkylalkyl, C.sub.2-C.sub.7 alkylcarbonyl or C.sub.2-C.sub.7 alkoxycarbonyl; each R.sup.10 is independently H; or C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.4-C.sub.7 alkylcycloalkyl or C.sub.4-C.sub.7 cycloalkylalkyl; each R.sup.11 is independently H; or C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.4-C.sub.7 alkylcycloalkyl, C.sub.4-C.sub.7 cycloalkylalkyl, C.sub.2-C.sub.7 alkylcarbonyl, C.sub.2-C.sub.7 alkoxycarbonyl, C.sub.1-C.sub.6 alkylsulfonyl or C.sub.1-C.sub.6 haloalkylsulfonyl; and each W is independently O or S.

4. The method of claim 3 wherein Z is ##STR00074## Q is ##STR00075## R.sup.2a is halogen, C.sub.1-C.sub.2 haloalkyl or C.sub.1-C.sub.2 haloalkoxy; R.sup.2b is H, halogen or cyano; R.sup.2c is H, halogen or CF.sub.3; R.sup.3 is C(O)N(R.sup.4)R.sup.5 or C(O)OR.sup.5a; R.sup.4 is H, C.sub.2-C.sub.7 alkylcarbonyl or C.sub.2-C.sub.7 alkoxycarbonyl; and R.sup.5 is C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 haloalkyl, each substituted with one substituent independently selected from hydroxy, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 alkyl sulfonyl, C.sub.2-C.sub.7 alkylaminocarbonyl, C.sub.3-C.sub.9 dialkylaminocarbonyl, C.sub.2-C.sub.7 haloalkylaminocarbonyl and C.sub.3-C.sub.9 halodialkylaminocarbonyl; and R.sup.5a is C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, each optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.2 alkoxy and phenyl optionally substituted with up to 5 substituents selected from halogen and C.sub.1-C.sub.3 alkyl.

5. The method of claim 1 wherein Z is phenyl optionally substituted with up to 5 substituents independently selected from R.sup.2; and each R.sup.2 is independently F, Cl, Br, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluoroalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluoroalkoxy, C.sub.1-C.sub.6 alkylthio or C.sub.1-C.sub.6 fluoroalkylthio; further comprising the steps of: i) preparing the compound of Formula 2 by (1) forming a reaction mixture comprising a Grignard reagent derived from a compound of Formula 5
ZX 5 wherein X is Cl, Br or I, by contacting the compound of Formula 5 with (a) magnesium metal, or (b) an alkylmagnesium halide in the presence of an ethereal solvent; and then (2) contacting the reaction mixture with a compound of Formula 6 ##STR00076## wherein Y is OR.sup.11 or NR.sup.12R.sup.13; R.sup.11 is C.sub.1-C.sub.5 alkyl; and R.sup.12 and R.sup.13 are independently C.sub.1-C.sub.2 alkyl; or R.sup.12 and R.sup.13 are taken together as CH.sub.2CH.sub.2OCH.sub.2CH.sub.2.

6. The method of claim 5 wherein Z is ##STR00077## R.sup.2a is F, Cl, Br, C.sub.1-C.sub.2 fluoroalkyl or C.sub.1-C.sub.2 fluoroalkoxy; R.sup.2b is H, F, Cl or Br; and R.sup.2c is H, F, Cl, Br or CF.sub.3.

7. The method of claim 3 wherein M.sup.1 is K.

8. A method for preparing a compound of Formula 1 ##STR00078## wherein ##STR00079## Z is ##STR00080## Q is R.sup.2a is halogen, C.sub.1-C.sub.2 haloalkyl or C.sub.1-C.sub.2 haloalkoxy, R.sup.2b is H, halogen or cyano; R.sup.2c is H, halogen or CF.sub.3; R.sup.3 is C(O)N(R.sup.4)R.sup.5 or C(O)OR.sup.5a; R.sup.4 is H, C.sub.2-C.sub.7 alkylcarbonyl or C.sub.2-C.sub.7 alkoxycarbonyl; and R.sup.5 is C.sub.1-C.sub.6 alkyl or C.sub.1-C.sub.6 haloalkyl, each substituted with one substituent independently selected from hydroxy, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkylthio, C.sub.1-C.sub.6 alkylsulfinyl, C.sub.1-C.sub.6 alkyl sulfonyl, C.sub.2-C.sub.7 alkylaminocarbonyl, C.sub.3-C.sub.9 dialkylaminocarbonyl, C.sub.2-C.sub.7 haloalkylaminocarbonyl and C.sub.3-C.sub.9 halodialkylaminocarbonyl, and R.sup.5a is C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl or C.sub.2-C.sub.6 alkynyl, each optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.2 alkoxy and phenyl optionally substituted with up to 5 substituents selected from halogen and C.sub.1-C.sub.3 alkyl, comprising distilling water from a mixture comprising a compound of Formula 2 ##STR00081## a compound of Formula 3 ##STR00082## a base comprising an alkali metal carbonate selected from the group consisting of the alkali metal carbonates of Formula 4a
(M.sup.1).sub.2CO.sub.3, 4a wherein M.sup.1 is Li, Na or K, and an aprotic solvent capable of forming a low-boiling azeotrope with water.

9. The method of claim 8 wherein M.sup.1 is K.

10. A method for preparing a compound of Formula 1 ##STR00083## wherein Z is phenyl optionally substituted with up to 5 substituents independently selected from R.sup.2; and each R.sup.2 is independently F, Cl, Br, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 fluoroalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 fluoroalkoxy, C.sub.1-C.sub.6 alkylthio or C.sub.1-C.sub.6 fluoroalkylthio; Q is phenyl or 1-naphthalenyl, each optionally substituted; the method comprising the steps of: i) preparing the compound of Formula 2 by (1) forming a reaction mixture comprising a Grignard reagent derived from a compound of Formula 5
ZX 5 wherein X is Cl, Br or I, by contacting the compound of Formula 5 with (a) magnesium metal, or (b) an alkylmagnesium halide in the presence of an ethereal solvent and then (2) contacting the reaction mixture with a compound of Formula 6 ##STR00084## wherein Y is OR.sup.11 or NR.sup.12R.sup.13; R.sup.11 is C.sub.1-C.sub.5 alkyl; and R.sup.12 and R.sup.13 are independently C.sub.1-C.sub.2 alkyl; or R.sup.12 and R.sup.13 are taken together as CH.sub.2CH.sub.2OCH.sub.2CH.sub.2, and, ii) distilling water from a mixture comprising a compound of Formula 2 ##STR00085## a compound of Formula 3 ##STR00086## a base comprising an alkali metal carbonate selected from the group consisting of the alkali metal carbonates of Formula 4a
(M.sup.1).sub.2CO.sub.3, 4a wherein M.sup.1 is Li, Na or K, and an aprotic solvent capable of forming a low-boiling azeotrope with water.

11. The method of claim 10 wherein M.sup.1 is K.

12. The method of claim 10 wherein Z is ##STR00087## R.sup.2a is F, Cl, Br, C.sub.1-C.sub.2 fluoroalkyl or C.sub.1-C.sub.2 fluoroalkoxy, R.sup.2b is H, F, Cl or Br, and R.sup.2c is H, F, Cl, Br or CF.sub.3.

13. The method of claim 12 wherein M.sup.1 is K.

14. The method of claim 4 wherein M1 is K.

15. The method of claim 5 wherein M.sup.1 is K.

16. The method of claim 6 wherein M.sup.1 is K.

Description

EXAMPLE 1

Preparation of methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

Step A: Preparation of methyl 4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalenecarboxylate

(1) A mixture of methyl 4-acetyl-1-naphthalenecarboxylate (5.36 g, 23.4 mmol), dichlorophenyl)-2,2,2-trifluoroethanone (5.68 g, 23.4 mmol), calcium hydroxide (0.172 g, 2.3 mmol), N,N-dimethylformamide (16 mL), and tert-butyl methyl ether (32 mL) was placed in a thermometer-equipped reaction vessel. The reaction vessel was connected to a ten-plate Oldershaw column, the output of which was condensed and fed into a decanter initially filled with tert-butyl methyl ether. A nitrogen atmosphere was maintained in the apparatus. The upper part of the decanter was connected to return condensate to the fifth plate of the Oldershaw column. This arrangement ensured that wet (containing dissolved water) tert-butyl methyl ether from the decanter was not returned to the reaction vessel. A drain valve at the bottom of the decanter allowed removing tert-butyl methyl ether in addition to water from the decanter. The reaction mixture was heated to distill the tert-butyl methyl ether/water azeotrope. As the decanter trap contained an amount of tert-butyl methyl ether sufficient to dissolve all of the water formed by the reaction, the condensate in the trap did not separate into layers containing predominately water and predominately tert-butyl methyl ether. Because the reaction mixture initially contained mostly tert-butyl methyl ether, the mixture boiled at a temperature not much exceeding the normal boiling point of tert-butyl methyl ether (e.g., about 65-70 C.). The reaction appeared to proceed relatively slowly at this temperature, so condensate was gradually drained from the decanter trap to remove tert-butyl methyl ether. As the concentration of tert-butyl methyl decreased in the reaction mixture, the temperature of the boiling mixture increased. Tert-butyl methyl ether was removed by draining the decanter until the temperature of the boiling reaction mixture reached about 75 to 80 C. To maintain this temperature range, tert-butyl methyl ether was added as needed to compensate for loss of solvent from the apparatus. The total time from beginning heating the reaction mixture to stopping distillation, not including a shutdown period overnight, was about 15 h. During this time period a further portion of calcium hydroxide (1.34 g, 18.1 mmol) was added to increase the reaction rate.

(2) To isolate the product, the mixture was cooled to room temperature and filtered. The collected solid was washed with tert-butyl methyl ether (10 mL). Water (100 mL) was added, and the aqueous layer was acidified with hydrochloric acid. The organic phase was washed with water (100 mL), dried, and evaporated to give the product as a yellow solid (10.1 g, 95% yield) melting at 91-91.5 C. (after recrystallization from hexanes). The following spectra were of the product recrystallized from hexanes.

(3) IR (nujol) 1723, 1670, 1560, 1280, 1257, 1230, 1186, 1171, 1132, 1098, 1022, 804 cm.sup.1. .sup.1H NMR (CDCl.sub.3) 8.78-8.76 (m, 1H), 8.32-8.30 (m, 1H) 8.02 (d, J=7.6 Hz, 1H) 7.65-7.62 (m, 3H), 7.34 (s, 1H), 7.07-7.06 (m, 1H), 6.94 (d, J=1.7 Hz, 2H), 4.03 (s, 3H).

Step B: Preparation of methyl 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

(4) Sodium hydroxide (50%, 3.50 g, 43.7 mmol) was added to a solution of hydroxylamine sulfate (1.8 g, 11.0 mmol) in water (22 mL). When the mixture had cooled to room temperature a portion of the mixture (50%) was added dropwise over 4 minutes to methyl 4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalene-carboxylate (i.e. the product of Step A) (5.00 g, 11.0 mmol) in tetrahydrofuran (55 mL) at room temperature. After 30 minutes a further portion (10%) of the aqueous mixture was added. The mixture was stirred for a further 15 minutes. The mixture was partitioned between hydrochloric acid (1 N, 50 mL) and tert-butyl methyl ether (50 mL). The organic phase was evaporated, and the solid obtained was stirred in hot methanol. The mixture was cooled and filtered to give the product as a white solid (4.50 g, 87%) melting at 137.3-138 C. (after recrystallization from methanol). The following spectra were of the product recrystallized from methanol.

(5) IR (nujol) 1716, 1569, 1518, 1433, 1332, 1309, 1288, 1251, 1192, 1167, 1139, 1114, 1102, 1027, 1006, 910, 867, 855 cm.sup.1.

(6) .sup.1H NMR (CDCl.sub.3) 8.89-8.87 (m, 1H), 8.80-8.78 (m, 1H), 8.10 (d, J=7.6 Hz, 1H), 7.69-7.66 (m, 2H), 7.56-7.53 (m, 3H), 7.46 (t, J=2 Hz, 1H), 4.27 (ABq, J=17 Hz, 1H), 4.03 (s, 3H), 3.91 (ABq, J=17 Hz, 1H).

EXAMPLE 2

Preparation of methyl 4-[5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

Step A: Preparation of methyl 4-[3-[3,5-bis(trifluoromethyl)phenyl]-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalenecarboxylate

(7) A mixture of methyl 4-acetyl-1-naphthalenecarboxylate (5.36 g, 23.5 mmol), 1-[3,5-bis(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (7.28 g, 23.5 mmol), calcium hydroxide (1.40 g, 18.9 mmol), N,N-dimethylformamide (16 mL) and tert-butyl methyl ether (32 mL) was boiled with provision of the apparatus comprising a ten-plate Oldershaw column and decanter described in Example 1, Step A for removal of the tert-butyl methyl ether/water azeotrope. As the decanter trap contained an amount of tert-butyl methyl ether sufficient to dissolve all of the water formed by the reaction, the condensate in the trap did not separate into layers containing predominately water and predominately tert-butyl methyl ether. Tert-butyl methyl ether was removed by gradually draining the decanter trap until the pot temperature was 85 C. To maintain this temperature, tert-butyl methyl ether was added as needed to compensate for loss of solvent from the apparatus. The total time from beginning heating the reaction mixture to stopping distillation, not including a shutdown period overnight, was about 10 h. During this time period no additional calcium hydroxide was added to the reaction mixture.

(8) To isolate the product, the mixture was cooled to room temperature and was filtered. The solid was washed with tert-butyl methyl ether and the filtrate was washed with water (30 mL), and diluted with tert-butyl ether. The mixture was evaporated to give the product as a yellow solid (12.1 g, 99%) melting at 91.5-92 C. (after recrystallization from hexanes). The following spectra were of the product recrystallized from hexanes.

(9) IR (nujol) 1720, 1685, 1515, 1441, 1405, 1345, 1280, 1261, 1187, 1171, 1147, 1129, 1097, 1024, 899, 856 cm.sup.1.

(10) .sup.1H NMR (CDCl.sub.3) 8.74-8.72 (m, 1H), 8.23-8.21 (m, 1H) 7.99 (d, J=7.3 Hz, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.64-7.57 (m, 3H), 7.51 (s, 2H), 7.47 (d, J=1.4 Hz, 1H), 4.04 (s, 3H).

Step B: Preparation of methyl 4-[5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

(11) Sodium hydroxide (50%, 1.53 g, 38.2 mmol) was added to hydroxylamine sulfate (1.57 g, 9.57 mmol) in water (18 mL). A portion of the solution (51%, 9.8 mmol of hydroxyl amine) was added dropwise to methyl 4-[3-[3,5-bis(trifluoromethyl)phenyl]-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalenecarboxylate (i.e. the product of Step A) (5.00 g, 9.61 mmol) in tetrahydrofuran (45 mL). After 45 min the mixture was poured into hydrochloric acid (1 N, 100 mL) and was extracted with ether (380 mL).

(12) The combined organic extracts were washed with water (80 mL), dried and evaporated. The material was stirred in hot methanol, then cooled to room temperature, collected under filtration and dried in vacuum to give the product as a white solid (4.14 g, 80% yield) melting at 130-131 C. (after recrystallization from methanol). The following spectra were of the product recrystallized from methanol.

(13) IR (nujol) 1722, 1515, 1437, 1330, 1284, 1208, 1193, 1174, 1128, 1106, 1025, 1009, 916, 903, 859, 842 cm.sup.1.

(14) .sup.1H NMR (CDCl.sub.3) 8.89-8.87 (m, 1H), 8.82-8.79 (m, 1H), 8.14-8.09 (m, 3H), 8.0 (s, 1H), 7.70-7.67 (m, 2H), 7.56 (d, J=7.6 Hz, 1H), 4.39 ( ABq, J=17.3 Hz, 1H), 4.03 (s, 3H), 3.96 ( ABq, J=17.6 Hz, 1H).

EXAMPLE 3

Alternative preparation of methyl 4-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalenecarboxylate

(15) A solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (1.42 g, 5.84 mmol) in N,N-dimethylformamide (5.5 mL) was added to calcium hydride (0.280 g, 6.66 mmol). A solution of methyl 4-acetyl-1-naphthalenecarboxylate (1.34 g, 5.88 mmol) in N,N-dimethylformamide (5.5 mL) was added to the mixture. The mixture was warmed to 45-50 C. for 8 h. The mixture was cooled to room temperature overnight. After a further 4 h at 60 C. the mixture was cooled to room temperature and was added dropwise to hydrochloric acid (1 N, 100 mL). The mixture was extracted with ethyl acetate (2100 mL), and the combined extracts were dried and evaporated to give the product (2.7 g, 102% yield), which contained a little N,N-dimethylformamide. The .sup.1H NMR spectrum of the major isomer was recorded as follows.

(16) .sup.1H NMR (CDCl.sub.3) 8.78-8.75 (m, 1H), 8.33-8.30 (m, 1H), 8.02 (d, J=7.7 Hz, 1H), 7.66-7.61 (m, 3H), 7.34 (s, 1H), 7.07-7.04 (m, 1H), 6.94 (d, J=2 Hz, 2H) 4.03 (s, 3H).

EXAMPLE 4

Preparation of 2-chloro-6-iodo-4-(trifluoromethyl)benzenamine

(17) Iodine monochloride (17.2 g, 108 mmol) in hydrochloric acid (36%, 21.4 g) and water (35 mL) was added dropwise to 2-chloro-4-(trifluoromethyl)benzenamine (20.0 g, 102 mmol) in hydrochloric acid (36%, 20.7 g) and water (140 mL). The mixture was warmed to 50 C. for a total of 8 h. Sodium hydroxide (50%, 33.5 g, 419 mmol) was added to the mixture at room temperature. The mixture was extracted with dichloromethane (2250 mL), and the extracts were dried and evaporated to give the product as an oil (31.83 g, 97% yield).

(18) .sup.1H NMR (CDCl.sub.3) 7.78 (s, 1H), 7.5 (s, 1H), 4.87 (br s, 2H).

EXAMPLE 5

Preparation of 1-chloro-3-iodo-5-(trifluoromethyl)benzene

(19) 2-Chloro-6-iodo-4-(trifluoromethyl)benzenamine (i.e. the product of Example 4) (31.8 g, 98.9 mmol) was added to hydrochloric acid (36%, 190 mL) and the mixture was warmed to 55-60 C. for 20 min. The mixture was cooled to 0 C. Sodium nitrite (13.6 g, 197 mmol) in water (36 mL) was added over 30 min. When the addition was complete the mixture was stirred at 0-5 C. for 70 min. Hypophosphorous acid (50%, 36.5 mL, 351 mmol) was added dropwise at 5-10 C. over 40 min. When the addition was complete the mixture spontaneously warmed briefly to 35 C., and was then cooled to 10-20 C. After stirring at 10-20 C. for 2 h, the mixture was stored in a refrigerator overnight. Then thee mixture was warmed to room temperature and was stirred for 1 h. The mixture was diluted with water (400 mL) and extracted with ether (2250 mL). The combined extracts were dried and evaporated. Distillation gave the product as an oil (19.93 g, 66% yield), b.p. 98-112 C. at 2.0 kPa.

(20) .sup.1H NMR (CDCl.sub.3) 7.89 (s, 1H), 7.84 (s, 1H), 7.58 (s, 1H).

EXAMPLE 6

Preparation of 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone

(21) A tetrahydrofuran solution of isopropylmagnesium chloride (2 M, 36.0 mL, 71.8 mmol) was added dropwise to a solution of 1-chloro-3-iodo-5-(trifluoromethyl)benzene (i.e. the product of Example 5) (20.0 g, 65.3 mmol) in tetrahydrofuran (30 mL) at 5 C. The mixture was stirred for 1 h at 0-5 C. Methyl trifluoroacetate (10.0 g, 78.1 mmol) was added dropwise to the mixture while maintaining the temperature 0-5 C. When the addition was complete the mixture was stirred for 90 min.

(22) Hydrochloric acid (1 N, 100 mL) was added dropwise to the mixture at 0-5 C. When the addition was complete the mixture was extracted with ether (2100 mL).

(23) The combined extracts were dried and evaporated. The oil was dissolved in toluene (55 mL), and p-toluenesulfonic acid monohydrate (0.100 g, 0.525 mmol) was added to the mixture. The mixture was boiled for 30 min, and the water/toluene methanol/toluene azeotropes were removed by distillation at atmospheric pressure. The distillation was continued at reduced pressure to give the product as an oil (12.4 g, 69% yield), b.p. 93-103 C. at 6.7 kPa.

(24) .sup.1H NMR (CDCl.sub.3) 8.21-8.19 (m, 2H), 7.95 (s, 1H).

EXAMPLE 7

Preparation of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

Step A: Preparation of 4-acetyl-1-naphthalenecarbonyl chloride

(25) Thionyl chloride (35.00 g, 0.29 mol) was added to a solution of 4-acetyl-1-naphthalenecarboxylic acid (51.70 g, 0.24 mol) in toluene (350 mL). The mixture was warmed to 90 C. for 8.5 h. After cooling to 25 C., the solvent was removed under reduced pressure to give the title product as an off-white solid (55.1 g, 98.7% yield).

(26) IR (nujol) 1758, 1681, 1515, 1352, 1282, 1245, 1218, 1190, 1117, 1053, 923, 762 cm.sup.1.

(27) .sup.1H NMR (CDCl.sub.3): 8.72-8.69 (m, 1H), 8.50 (d, J=7.6 Hz, 1H), 8.44-8.41 (m, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.76-7.65 (m, 2H), 2.77 (s, 3H).

Step B: Preparation of 4-acetyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

(28) A solution of 2-amino-N-(2,2,2-trifluoroethyl)acetamide (21.90 g, 0.14 mol) in 1,2-dichloroethane (80 mL) was added dropwise over 15 min to a solution of the product of Example 7, Step A (32.50 g, 0.14 mol) in 1,2-dichloroethane (160 mL) at a temperature of 25 to 30 C. The resulting mixture was further stirred for 10 min at 25 C. A solution of triethylamine (14.20 g, 0.14 mol) in 1,2-dichloroethane (80 mL) was then added dropwise over 44 min at 25 C., and the mixture was stirred further for 20 min at 25 C. The solvent was removed under reduced pressure, and the residue was dissolved in hot acetonitrile (50 mL). The mixture was then cooled to 25 C., and water (40 mL) was added dropwise. The mixture was further cooled to 0 C. and filtered. The isolated solid was washed with water (100 mL) and dried overnight in a vacuum oven (approximately 16-33 kPa at 50 C.) to provide the title product as an off-white solid (37 g, 75% yield) melting at 169-169 C.

(29) IR (nujol) 3303, 3233, 3072, 1698, 1683, 1636, 1572, 1548, 1447, 1279, 1241, 1186, 1159 cm.sup.1.

(30) .sup.1H NMR (CD.sub.3S(O)CD.sub.3): 8.95 (t, J=5.8 Hz, 1H), 8.72 (t, J=6.5 Hz, 1H), 8.55 (dd, J=6.5, 2 Hz, 1H), 8.37-8.33 (m, 1H), 8.13 (d, J=7.3 Hz, 1H), 7.70-7.60 (m, 3H), 4.07-3.95 (m, 4H), 2.75 (s, 3H).

Step C: Preparation of 4-[3-[3-chloro-5-(trifluoromethyl)phenyl]-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

(31) A mixture of the product of Example 7, Step B (10.00 g, 28.38 mmol), 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (9.00 g, 32.5 mmol), calcium hydroxide (1.05 g, 14.2 mmol), N,N-dimethylformamide (20 mL) and tert-butyl methyl ether (32 mL) was placed in a thermometer-equipped reaction vessel. The reaction vessel was connected to a ten-plate Oldershaw column, the output of which was condensed and fed into a decanter initially filled with tert-butyl methyl ether. A nitrogen atmosphere was maintained in the apparatus. The upper part of the decanter was connected to return condensate to the fifth plate of the Oldershaw column. This arrangement ensured that wet (containing dissolved water) tert-butyl methyl ether was not returned from the decanter to the reaction vessel. A drain valve at the bottom of the decanter allowed removing tert-butyl methyl ether in addition to water from the decanter. The reaction mixture was heated to distill the tert-butyl methyl ether/water azeotrope. As the decanter trap contained an amount of tert-butyl methyl ether sufficient to dissolve all of the water formed by the reaction, the condensate in the trap did not separate into layers containing predominately water and predominately tert-butyl methyl ether. Because the reaction mixture initially contained mostly tert-butyl methyl ether, the mixture boiled at a temperature not much exceeding the normal boiling point of tert-butyl methyl ether (e.g., about 65-70 C.). The reaction proceeded relatively slowly at this temperature, so condensate was gradually drained from the decanter trap to remove tert-butyl methyl ether. As the concentration of tert-butyl methyl ether decreased in the reaction mixture, the temperature of the boiling reaction mixture increased. Tert-butyl methyl ether was removed by draining the decanter until the temperature of the boiling reaction mixture reached about 85 C. To maintain this temperature, tert-butyl methyl ether was added as needed to compensate for loss of solvent from the apparatus. The total time from the start of heating the reaction mixture to stopping distillation, not including a shutdown period overnight, was about 6 h.

(32) To isolate the product, the mixture was cooled to room temperature and then added to a mixture of tert-butyl methyl ether (50 mL) and 1 N hydrochloric acid (100 mL). The organic phase was separated, and heptane (60 mL) was added dropwise. The mixture was filtered to provide the title product as an off-white solid mixture of isomers (14 g, 81% yield) melting at 174.5-177 C.

(33) IR (nujol) 3294, 1697, 1674, 1641, 1541, 1441, 1364, 1313, 1275, 1246, 1163, 1104 cm.sup.1.

(34) .sup.1H NMR (CD.sub.3S(O)CD.sub.3): (major isomer) 8.91 (t, J=6.2 Hz, 1H), 8.73 (t, J=6.4 Hz, 1H), 8.44-8.30 (m, 2H), 8.18 (d, J=7.7 Hz, 1H), 7.97-7.61 (m, 7H), 4.06-3.95 (m, 4H).

Step D: Preparation of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

(35) Aqueous sodium hydroxide (50%, 3.04 g, 38.0 mmol) was added dropwise to a stirred solution of hydroxylamine sulfate (1.48 g, 9.02 mmol) in water (28 mL) at 25 C. After this addition was complete the product of Example 7, Step C (10.00 g, 16.33 mmol) in tetrahydrofuran (60 mL) was added dropwise over 40 min. After the addition was complete the mixture was stirred further for 30 min. The solvent was removed under reduced pressure and 1 N hydrochloric acid (100 mL) was added. The mixture was extracted with ether (2100 mL), and the combined extracts were dried and evaporated. The residue was dissolved in acetonitrile (30 mL), cooled to 0 C., and filtered to afford the title product as a white solid (7.84 g, 77% yield) melting at 107-108.5 C. (after recrystallisation from acetonitrile).

(36) IR (nujol) 3312, 1681, 1642, 1536, 1328, 1304, 1271, 1237, 1173, 1116 cm.sup.1.

(37) .sup.1H NMR (CD.sub.3S(O)CD.sub.3): 8.98 (t, J=5.8 Hz, 1H), 8.82 (d, J=7.4 Hz, 1H), 8.74 (t, J=6.5 Hz, 1H), 8.40 (d, J=9.7 Hz, 1H), 8.09 (d, J=15.3 Hz, 2H), 7.93 (d, J=7.6 Hz, 2H), 7.75-7.04 (m, 3H), 4.63 (s, 2H), 4.07-3.96 (4H, m).

EXAMPLE 7A

Alternative Preparation of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

Step A: Preparation of 4-[3-[3-chloro-5-(trifluoromethyl)phenyl]-4,4,4-trifluoro-1-[oxo-2-buten-1-yl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

(38) A mixture of 4-acetyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide (100.00 g, 267.23 mmol), 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (86.92 g, 288.6 mmol) and acetonitrile (500 mL) was placed in a thermometer-equipped reaction vessel. The reaction vessel was connected to a ten-plate Oldershaw column. A nitrogen atmosphere was maintained in the apparatus. The mixture was heated to boiling, at which time the temperature of the top of the column was 82 C. Potassium carbonate was added to the reaction mixture portionwise to control the rate of reaction. Initially, 0.40 g of potassium carbonate was added, followed sequentially by individual 0.1 g additions 30, 60, 120 and 180 minutes, and 0.40 g additions 240 and 300 minutes after the initial addition of potassium carbonate. Prior to addition to the reaction mixture, the potassium carbonate was slurried in a small amount of acetonitrile (approximately 3 mL of acetonitrile was used to slurry the 0.40 g quantities of potassium carbonate, and approximately 2 mL of acetonitrile was used to slurry the 0.1 g quantities of potassium carbonate). The acetonitrile/water azeotrope (bp 76.5 C.) was continuously removed from the top of the column as it was formed. After the final potassium carbonate addition the mixture was boiled for a further 60 minutes. After a total time of 6 h from the initial addition of potassium carbonate, more acetonitrile was removed by distillation until a total of 265 mL of acetonitrile and acetonitrile/water azeotrope had been removed. The mixture was cooled to 25 C., and water (48 mL) was added to the mixture. The mixture was cooled to 0 C. over 30 minutes, held at this temperature for 60 minutes, and then filtered. The isolated solid was washed with acetonitrile:water (96 mL, 26:5 acetonitrile:water).

(39) The product was dried in a vacuum oven (approximately 16-33 kPa at 55 C.) overnight to give the product as an off-white solid (150.51 g as a mixture of isomers, 92.2% yield).

(40) The .sup.1H NMR spectrum of the major isomer was identical to the spectrum of the material prepared in Example 7, Step C.

Step B: Preparation of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

(41) A solution of sodium hydroxide (15.10 g of a 50% aqueous solution, 0.19 mmol) in water (total volume 67.5 mL) and a solution of hydroxylamine sulfate (7.75 g, 47.3 mmol) in water (total volume 67.5 mL) were added simultaneously to the product of Example 7A, Step A (51.90 g, 81.78 mmol) in tetrahydrofuran (300 mL) at 25 C. over 75 minutes. After the addition was complete, the mixture was stirred further for 180 minutes. The mixture was acidified to approximately pH 3 by addition of hydrochloric acid (concentrated, approximately 11 g). The aqueous layer was removed, and the remaining organic solution was heated to boiling. Acetonitrile was added, and the acetonitrile/tetrahydrofuran distillate was removed until the distillate temperature reached 82 C., indicating that all of the tetrahydrofuran had been removed. The mixture was allowed to cool to 25 C., and the acetonitrile was removed under reduced pressure. The residue was dissolved in acetonitrile (200 mL), cooled to 0 C., and the resulting mixture was filtered to afford the title product as a white solid (43.45 g, 84% yield).

(42) The .sup.1H NMR spectrum of the product was identical to the spectrum of the material prepared in Example 7, Step D.

EXAMPLE 7B

Alternative Preparation of 4-[3-[3-chloro-5-(trifluoromethyl)phenyl]-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide

(43) A mixture of 4-acetyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide (50.00 g, 135.1 mmol), 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (43.93 g, 145.8 mmol) and acetonitrile (250 mL) was placed in a thermometer-equipped reaction vessel. The reaction vessel was connected to a ten-plate Oldershaw column. A nitrogen atmosphere was maintained in the apparatus. The mixture was heated to boiling, at which time the temperature of the top of the column was 82 C. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was added to the reaction mixture portionwise to control the rate of reaction. Initially, 0.20 g of DBU was added, followed sequentially by individual 0.052 g additions 30, 90, 150 and 210 minutes, and 0.20 g additions 270 and 330 minutes after the initial addition of DBU. Each individual DBU portion was diluted with acetonitrile (2 mL) prior to addition to the reaction mixture. The acetonitrile/water azeotrope (bp 76.5 C.) was continuously removed from the top of the column as it was formed. After the final DBU addition the mixture was boiled for a further 60 minutes. After a total time of 6 h from the initial addition of DBU, more acetonitrile was removed by distillation until a total of 138 mL of acetonitrile and acetonitrile/water azeotrope had been removed. The mixture was cooled to 25 C., and water (24 mL) was added to the mixture. The mixture was cooled to 0 C. over 30 minutes, held at this temperature for 60 minutes, and then filtered. The isolated solid was washed with acetonitrile:water (48 mL, 26:5 acetonitrile:water).

(44) The product was dried in a vacuum oven (approximately 16-33 kPa at 55 C.) overnight to give the product as an off-white solid (76.0 g as a mixture of isomers, 92.0% yield).

(45) The .sup.1H NMR spectrum of the major isomer was identical to the spectrum of the material prepared in Example 7, Step C.

EXAMPLE 8

Preparation of methyl 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

Step A: Preparation of methyl 4-[3-[3-chloro-5-(trifluoromethyl)phenyl]-4,4,4-trifluoro-1-oxo-2-buten-1-yl]-1-naphthalenecarboxylate

(46) A mixture of methyl 4-acetyl-1-naphthalenecarboxylate (7.83 g, 34.3 mmol), 1-[3-chloro-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroethanone (10.43 g, 37.71 mmol), calcium hydroxide (1.25 g, 16.9 mmol), N,N-dimethylformamide (27 mL) and tert-butyl methyl ether (44 mL) was heated to reflux. The tert-butyl methyl ether/water azeotrope was removed as described in Example 7, Step C. As the decanter trap contained an amount of tert-butyl methyl ether sufficient to dissolve all of the water formed by the reaction, the condensate in the trap did not separate into layers containing predominately water and predominately tert-butyl methyl ether. Tert-butyl methyl ether was removed by gradually draining the decanter trap until the reaction temperature was 85 C. To maintain this temperature, tert-butyl methyl ether was added as needed to compensate for loss of solvent from the apparatus. The total time from the start of heating the reaction mixture to stopping distillation was about 4.5 h.

(47) The mixture was cooled to 25 C. and poured into a mixture of 0.5 N hydrochloric acid (100 mL) and tert-butyl methyl ether (50 mL). The mixture was acidified with concentrated hydrochloric acid and evaporated, and the residue was crystallized from hexanes (40 mL) to give the title product as a yellow solid (13.24 g, 79% yield) melting at 90-90.5 C. (after recrystallization from hexanes).

(48) IR (nujol) 3071, 1721, 1710, 1671, 1516, 1439, 1316, 1280, 1252, 1178, 1129, 1103, 1026, 888, 861 cm.sup.1.

(49) .sup.1H NMR (CDCl.sub.3): 8.77-8.73 (m, 1H), 8.28-8.25 (m, 1H), 8.0 (d, J=7.6 Hz, 1H), 7.67-7.60 (m, 3H), 7.40 (d, J=1.4 Hz, 1H), 7.32 (s, 1H), 7.23 (s, 1H), 7.20 (s, 1H), 4.02 (s, 3H).

Step B: Preparation of methyl 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate

(50) Aqueous sodium hydroxide (50%, 2.08 g, 25.5 mmol) was added dropwise to a stirred solution of hydroxylamine sulfate (1.07 g, 6.52 mmol) in water (20 mL) at 25 C. After this addition was complete the product of Example 8, Step A (5 g, 10.27 mmol) in tetrahydrofuran (20 mL) was added dropwise over 40 min. After the addition was complete the mixture was stirred further for 30 min. The organic phase was separated and added to hydrochloric acid (100 mL). The mixture was extracted with ethyl acetate (220 mL). The organic solvent was evaporated under reduced pressure. The residue was redissolved in acetic acid (16 mL) and then warmed to 100 C. Water (2 mL) was added dropwise, and the mixture was cooled to 50 C. The mixture was seeded with a small amount of previously prepared methyl 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate and then cooled to 25 C. Water (2 mL) was added and the mixture was cooled to 0 C. The mixture was filtered, and the solid was washed with acetic acid:water (8 mL:2 mL). The solid was dried in a vacuum oven to give the title product as a white solid (3.91 g, 76% yield) melting at 111.5-112 C. (after recrystallisation from acetonitrile).

(51) IR (nujol) 1716, 1328, 1306, 1287, 1253, 1242, 1197, 1173, 1137, 1114, 1028, 771 cm.sup.1.

(52) .sup.1H NMR (CDCl.sub.3): 8.90-8.87 (m, 1H), 8.82-8.79 (m, 1H), 8.10 (d, J=7.7 Hz), 7.87 (s, 1H), 7.81 (s, 1H), 7.72-7.67 (m, 3H) 7.55 (d, J=7.6 Hz, 1H), 4.34 ( ABq, J=17.3 Hz, 1H), 4.03 (s, 3H), 3.93 ( ABq, J=17.3 Hz, 1H).

(53) The following Tables 1-8 identify specific combinations of reactants, intermediates and products illustrating the methods of the present invention. These tables specifically disclose compounds as well as particular transformations. In these tables: Et means ethyl, Me means methyl, CN means cyano, Ph means phenyl, Py means pyridinyl, c-Pr means cyclopropyl, i-Pr means isopropyl, n-Pr means normal propyl, s-Bu means secondary butyl, t-Bu means tertiary butyl, SMe means methylthio, S(O).sub.2 means sulfonyl and Thz means thiazole. Concatenations of groups are abbreviated similarly; for example, S(O).sub.2Me means methylsulfonyl.

(54) Tables 1-6 relate to the method of Scheme 1 converting compounds of Formulae 2 and 3 to corresponding compounds of Formula 1. This transformation is believed to occur through the intermediacy of compounds of Formula 11.

(55) ##STR00051##
In the example transformations embodied in Tables 1-6, M is Ca, and water is distilled as an azeotrope from a reaction mixture comprising N,N-dimethylformamide as the polar aprotic solvent and text-butyl methyl ether as the aprotic solvent capable of forming a low-boiling azeotrope with water.

(56) TABLE-US-00001 TABLE 1 R.sup.2a R.sup.2b R.sup.2c R.sup.5 Cl H Cl CH.sub.2CH.sub.3 Cl H Cl CH.sub.2i-Pr Cl H Cl CH.sub.2CH.sub.2Cl Cl H Cl CH.sub.2CH.sub.2OH Cl H Cl CH(Me)CH.sub.2OH Cl H Cl CH.sub.2CH(Me)OH Cl H Cl CH.sub.2C(Me).sub.2OH Cl H Cl CH.sub.2CH.sub.2CH.sub.2OH Cl H Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl H Cl CH.sub.2CH.sub.2CH(Me)OH Cl H Cl CH.sub.2C(O)N(H)Et Cl H Cl CH.sub.2C(O)N(H)i-Pr Cl H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl H Cl CH.sub.2CF.sub.3 Cl H Cl CH.sub.2(2-Py) Cl H Cl CH.sub.2(4-Thz) Cl H Cl CH.sub.2c-Pr Cl H Cl CH.sub.2CH.sub.2SMe Cl H Cl CH(Me)CH.sub.2SMe Cl H Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl H Cl CH.sub.2CH.sub.2S(O)Me Cl H Cl CH(Me)CH.sub.2S(O)Me Cl H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl H Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl H Cl CH(Me)CH.sub.2S(O).sub.2Me Cl H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH.sub.2CH.sub.3 Br H Br CH.sub.2i-Pr Br H Br CH.sub.2CH.sub.2Cl Br H Br CH.sub.2CH.sub.2OH Br H Br CH(Me)CH.sub.2OH Br H Br CH.sub.2CH(Me)OH Br H Br CH.sub.2C(Me).sub.2OH Br H Br CH.sub.2CH.sub.2CH.sub.2OH Br H Br CH.sub.2C(Me).sub.2CH.sub.2OH Br H Br CH.sub.2CH.sub.2CH(Me)OH Br H Br CH.sub.2C(O)N(H)Et Br H Br CH.sub.2C(O)N(H)i-Pr Br H Br CH.sub.2C(O)N(H)CH.sub.2i-Pr Br H Br CH(Me)C(O)N(H)CH.sub.2i-Pr Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Br H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Br H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Br H Br CH.sub.2CF.sub.3 Br H Br CH.sub.2(2-Py) Br H Br CH.sub.2(4-Thz) Br H Br CH.sub.2c-Pr Br H Br CH.sub.2CH.sub.2SMe Br H Br CH(Me)CH.sub.2SMe Br H Br CH.sub.2CH.sub.2CH.sub.2SMe Br H Br CH.sub.2CH.sub.2S(O)Me Br H Br CH(Me)CH.sub.2S(O)Me Br H Br CH.sub.2CH.sub.2CH.sub.2S(O)Me Br H Br CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH(Me)CH.sub.2S(O).sub.2Me Br H Br CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Br H Br CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2CH.sub.3 CF.sub.3 H H CH.sub.2i-Pr CF.sub.3 H H CH.sub.2CH.sub.2Cl CF.sub.3 H H CH.sub.2CH.sub.2OH CF.sub.3 H H CH(Me)CH.sub.2OH CF.sub.3 H H CH.sub.2CH(Me)OH CF.sub.3 H H CH.sub.2C(Me).sub.2OH CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H H CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H H CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H H CH.sub.2C(O)N(H)Et CF.sub.3 H H CH.sub.2C(O)N(H)i-Pr CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H H CH.sub.2CF.sub.3 CF.sub.3 H H CH.sub.2(2-Py) CF.sub.3 H H CH.sub.2(4-Thz) CF.sub.3 H H CH.sub.2c-Pr CF.sub.3 H H CH.sub.2CH.sub.2SMe CF.sub.3 H H CH(Me)CH.sub.2SMe CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H H CH.sub.2CH.sub.2S(O)Me CF.sub.3 H H CH(Me)CH.sub.2S(O)Me CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H H CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2CH.sub.3 CF.sub.3 H F CH.sub.2i-Pr CF.sub.3 H F CH.sub.2CH.sub.2Cl CF.sub.3 H F CH.sub.2CH.sub.2OH CF.sub.3 H F CH(Me)CH.sub.2OH CF.sub.3 H F CH.sub.2CH(Me)OH CF.sub.3 H F CH.sub.2C(Me).sub.2OH CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H F CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H F CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H F CH.sub.2C(O)N(H)Et CF.sub.3 H F CH.sub.2C(O)N(H)i-Pr CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H F CH.sub.2CF.sub.3 CF.sub.3 H F CH.sub.2(2-Py) CF.sub.3 H F CH.sub.2(4-Thz) CF.sub.3 H F CH.sub.2c-Pr CF.sub.3 H F CH.sub.2CH.sub.2SMe CF.sub.3 H F CH(Me)CH.sub.2SMe CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H F CH.sub.2CH.sub.2S(O)Me CF.sub.3 H F CH(Me)CH.sub.2S(O)Me CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H F CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2CH.sub.3 CF.sub.3 H Br CH.sub.2i-Pr CF.sub.3 H Br CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH.sub.2CH.sub.2OH CF.sub.3 H Br CH(Me)CH.sub.2OH CF.sub.3 H Br CH.sub.2CH(Me)OH CF.sub.3 H Br CH.sub.2C(Me).sub.2OH CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H Br CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H Br CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H Br CH.sub.2C(O)N(H)Et CF.sub.3 H Br CH.sub.2C(O)N(H)i-Pr CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Br CH.sub.2CF.sub.3 CF.sub.3 H Br CH.sub.2(2-Py) CF.sub.3 H Br CH.sub.2(4-Thz) CF.sub.3 H Br CH.sub.2c-Pr CF.sub.3 H Br CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH(Me)CH.sub.2SMe CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Br CH(Me)CH.sub.2S(O)Me CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Br CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2CH.sub.3 CF.sub.3 H Cl CH.sub.2i-Pr CF.sub.3 H Cl CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH.sub.2CH.sub.2OH CF.sub.3 H Cl CH(Me)CH.sub.2OH CF.sub.3 H Cl CH.sub.2CH(Me)OH CF.sub.3 H Cl CH.sub.2C(Me).sub.2OH CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H Cl CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H Cl CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H Cl CH.sub.2C(O)N(H)Et CF.sub.3 H Cl CH.sub.2C(O)N(H)i-Pr CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Cl CH(Me)C(43)N(H)CH.sub.2i-Pr CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Cl CH.sub.2CF.sub.3 CF.sub.3 H Cl CH.sub.2(2-Py) CF.sub.3 H Cl CH.sub.2(4-Thz) CF.sub.3 H Cl CH.sub.2c-Pr CF.sub.3 H Cl CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH(Me)CH.sub.2SMe CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Cl CH(Me)CH.sub.2S(O)Me CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Cl CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH(Me)OH CF.sub.3 H CF.sub.3 CH.sub.2C(Me).sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)Et CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)i-Pr CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H CF.sub.3 CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2(2-Py) CF.sub.3 H CF.sub.3 CH.sub.2(4-Thz) CF.sub.3 H CF.sub.3 CH.sub.2c-Pr CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2CH.sub.3 Cl Cl Cl CH.sub.2i-Pr Cl Cl Cl CH.sub.2CH.sub.2Cl Cl Cl Cl CH.sub.2CH.sub.2OH Cl Cl Cl CH(Me)CH.sub.2OH Cl Cl Cl CH.sub.2CH(Me)OH Cl Cl Cl CH.sub.2C(Me).sub.2OH Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2OH Cl Cl Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl Cl Cl CH.sub.2CH.sub.2CH(Me)OH Cl Cl Cl CH.sub.2C(O)N(H)Et Cl Cl Cl CH.sub.2C(O)N(H)i-Pr Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl Cl Cl CH.sub.2CF.sub.3 Cl Cl Cl CH.sub.2(2-Py) Cl Cl Cl CH.sub.2(4-Thz) Cl Cl Cl CH.sub.2c-Pr Cl Cl Cl CH.sub.2CH.sub.2SMe Cl Cl Cl CH(Me)CH.sub.2SMe Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl Cl Cl CH.sub.2CH.sub.2S(O)Me Cl Cl Cl CH(Me)CH.sub.2S(O)Me Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl Cl Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH(Me)CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2CH.sub.3 Cl F Cl CH.sub.2i-Pr Cl F Cl CH.sub.2CH.sub.2Cl Cl F Cl CH.sub.2CH.sub.2OH Cl F Cl CH(Me)CH.sub.2OH Cl F Cl CH.sub.2CH(Me)OH Cl F Cl CH.sub.2C(Me).sub.2OH Cl F Cl CH.sub.2CH.sub.2CH.sub.2OH Cl F Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl F Cl CH.sub.2CH.sub.2CH(Me)OH Cl F Cl CH.sub.2C(O)N(H)Et Cl F Cl CH.sub.2C(O)N(H)i-Pr Cl F Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl F Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl F Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl F Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl F Cl CH.sub.2CF.sub.3 Cl F Cl CH.sub.2(2-Py) Cl F Cl CH.sub.2(4-Thz) Cl F Cl CH.sub.2c-Pr Cl F Cl CH.sub.2CH.sub.2SMe Cl F Cl CH(Me)CH.sub.2SMe Cl F Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl F Cl CH.sub.2CH.sub.2S(O)Me Cl F Cl CH(Me)CH.sub.2S(O)Me Cl F Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl F Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH(Me)CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl F Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2CH.sub.3 OCF.sub.3 H Cl CH.sub.2i-Pr OCF.sub.3 H Cl CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2CH.sub.2OH OCF.sub.3 H Cl CH(Me)CH.sub.2OH OCF.sub.3 H Cl CH.sub.2CH(Me)OH OCF.sub.3 H Cl CH.sub.2C(Me).sub.2OH OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2OH OCF.sub.3 H Cl CH.sub.2C(Me).sub.2CH.sub.2OH OCF.sub.3 H Cl CH.sub.2CH.sub.2CH(Me)OH OCF.sub.3 H Cl CH.sub.2C(O)N(H)Et OCF.sub.3 H Cl CH.sub.2C(O)N(H)i-Pr OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F OCF.sub.3 H Cl CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH.sub.2(2-Py) OCF.sub.3 H Cl CH.sub.2(4-Thz) OCF.sub.3 H Cl CH.sub.2c-Pr OCF.sub.3 H Cl CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH(Me)CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2CH.sub.2S(O)Me OCF.sub.3 H Cl CH(Me)CH.sub.2S(O)Me OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me OCF.sub.3 H Cl CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH(Me)CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me

(57) TABLE-US-00002 TABLE 2 R.sup.2a R.sup.2b R.sup.2c R.sup.5 Cl H Cl CH.sub.3 Cl H Cl CH.sub.2CH.sub.3 Cl H Cl CH.sub.2i-Pr Cl H Cl n-Pr Cl H Cl i-Pr Cl H Cl s-Bu Cl H Cl t-Bu Cl H Cl (CH.sub.2).sub.5CH.sub.3 Cl H Cl CH.sub.2Ph Br H Br CH.sub.3 Br H Br CH.sub.2CH.sub.3 Br H Br CH.sub.2i-Pr Br H Br n-Pr Br H Br i-Pr Br H Br s-Bu Br H Br t-Bu Br H Br (CH.sub.2).sub.5CH.sub.3 Br H Br CH.sub.2Ph CF.sub.3 H H CH.sub.3 CF.sub.3 H H CH.sub.2CH.sub.3 CF.sub.3 H H CH.sub.2i-Pr CF.sub.3 H H n-Pr CF.sub.3 H H i-Pr CF.sub.3 H H s-Bu CF.sub.3 H H t-Bu CF.sub.3 H H (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H H CH.sub.2Ph CF.sub.3 H F CH.sub.3 CF.sub.3 H F CH.sub.2CH.sub.3 CF.sub.3 H F CH.sub.2i-Pr CF.sub.3 H F n-Pr CF.sub.3 H F i-Pr CF.sub.3 H F s-Bu CF.sub.3 H F t-Bu CF.sub.3 H F (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H F CH.sub.2Ph CF.sub.3 H Br CH.sub.3 CF.sub.3 H Br CH.sub.2CH.sub.3 CF.sub.3 H Br CH.sub.2i-Pr CF.sub.3 H Br n-Pr CF.sub.3 H Br i-Pr CF.sub.3 H Br s-Bu CF.sub.3 H Br t-Bu CF.sub.3 H Br (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H Br CH.sub.2Ph CF.sub.3 H Cl CH.sub.3 CF.sub.3 H Cl CH.sub.2CH.sub.3 CF.sub.3 H Cl CH.sub.2i-Pr CF.sub.3 H Cl n-Pr CF.sub.3 H Cl i-Pr CF.sub.3 H Cl s-Bu CF.sub.3 H Cl t-Bu CF.sub.3 H Cl (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H Cl CH.sub.2Ph CF.sub.3 H CF.sub.3 CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2i-Pr CF.sub.3 H CF.sub.3 n-Pr CF.sub.3 H CF.sub.3 i-Pr CF.sub.3 H CF.sub.3 s-Bu CF.sub.3 H CF.sub.3 t-Bu CF.sub.3 H CF.sub.3 (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2Ph Cl Cl Cl CH.sub.3 Cl Cl Cl CH.sub.2CH.sub.3 Cl Cl Cl CH.sub.2i-Pr Cl Cl Cl n-Pr Cl Cl Cl i-Pr Cl Cl Cl s-Bu Cl Cl Cl t-Bu Cl Cl Cl (CH.sub.2).sub.5CH.sub.3 Cl Cl Cl CH.sub.2Ph Cl F Cl CH.sub.3 Cl F Cl CH.sub.2CH.sub.3 Cl F Cl CH.sub.2i-Pr Cl F Cl n-Pr Cl F Cl i-Pr Cl F Cl s-Bu Cl F Cl t-Bu Cl F Cl (CH.sub.2).sub.5CH.sub.3 Cl F Cl CH.sub.2Ph OCF.sub.3 H Cl CH.sub.3 OCF.sub.3 H Cl CH.sub.2CH.sub.3 OCF.sub.3 H Cl CH.sub.2i-Pr OCF.sub.3 H Cl n-Pr OCF.sub.3 H Cl i-Pr OCF.sub.3 H Cl s-Bu OCF.sub.3 H Cl t-Bu OCF.sub.3 H Cl (CH.sub.2).sub.5CH.sub.3 OCF.sub.3 H Cl CH.sub.2Ph

(58) TABLE-US-00003 TABLE 3 R.sup.2a R.sup.2b R.sup.2c R.sup.3 Cl H Cl Cl Cl H Cl Br Cl H Cl I Cl H Cl OH Cl H Cl OMe Cl H Cl OS(O).sub.2CF.sub.3 Cl H Cl nitro Cl H Cl NH.sub.2 Cl H Cl cyano Cl H Cl Me Cl H Cl CH.sub.2Cl Cl H Cl CH.sub.2Br Cl H Cl CH.sub.2OH Cl H Cl CH.sub.2OC(O)Me Cl H Cl CO.sub.2H Cl H Cl n-Pr Br H Br Cl Br H Br Br Br H Br I Br H Br OH Br H Br OMe Br H Br OS(O).sub.2CF.sub.3 Br H Br nitro Br H Br NH.sub.2 Br H Br cyano Br H Br Me Br H Br CH.sub.2Cl Br H Br CH.sub.2Br Br H Br CH.sub.2OH Br H Br CH.sub.2OC(O)Me Br H Br CO.sub.2H Br H Br n-Pr CF.sub.3 H H Cl CF.sub.3 H H Br CF.sub.3 H H I CF.sub.3 H H OH CF.sub.3 H H OMe CF.sub.3 H H OS(O).sub.2CF.sub.3 CF.sub.3 H H nitro CF.sub.3 H H NH.sub.2 CF.sub.3 H H cyano CF.sub.3 H H Me CF.sub.3 H H CH.sub.2Cl CF.sub.3 H H CH.sub.2Br CF.sub.3 H H CH.sub.2OH CF.sub.3 H H CH.sub.2OC(O)Me CF.sub.3 H H CO.sub.2H CF.sub.3 H H n-Pr CF.sub.3 H F Cl CF.sub.3 H F Br CF.sub.3 H F I CF.sub.3 H F OH CF.sub.3 H F OMe CF.sub.3 H F OS(O).sub.2CF.sub.3 CF.sub.3 H F nitro CF.sub.3 H F NH.sub.2 CF.sub.3 H F cyano CF.sub.3 H F Me CF.sub.3 H F CH.sub.2Cl CF.sub.3 H F CH.sub.2Br CF.sub.3 H F CH.sub.2OH CF.sub.3 H F CH.sub.2OC(O)Me CF.sub.3 H F CO.sub.2H CF.sub.3 H F n-Pr CF.sub.3 H Br Cl CF.sub.3 H Br Br CF.sub.3 H Br I CF.sub.3 H Br OH CF.sub.3 H Br OMe CF.sub.3 H Br OS(O).sub.2CF.sub.3 CF.sub.3 H Br nitro CF.sub.3 H Br NH.sub.2 CF.sub.3 H Br cyano CF.sub.3 H Br Me CF.sub.3 H Br CH.sub.2Cl CF.sub.3 H Br CH.sub.2Br CF.sub.3 H Br CH.sub.2OH CF.sub.3 H Br CH.sub.2OC(O)Me CF.sub.3 H Br CO.sub.2H CF.sub.3 H Br n-Pr CF.sub.3 H Cl Cl CF.sub.3 H Cl Br CF.sub.3 H Cl I CF.sub.3 H Cl OH CF.sub.3 H Cl OMe CF.sub.3 H Cl OS(O).sub.2CF.sub.3 CF.sub.3 H Cl nitro CF.sub.3 H Cl NH.sub.2 CF.sub.3 H Cl cyano CF.sub.3 H Cl Me CF.sub.3 H Cl CH.sub.2Cl CF.sub.3 H Cl CH.sub.2Br CF.sub.3 H Cl CH.sub.2OH CF.sub.3 H Cl CH.sub.2OC(O)Me CF.sub.3 H Cl CO.sub.2H CF.sub.3 H Cl n-Pr CF.sub.3 H CF.sub.3 Cl CF.sub.3 H CF.sub.3 Br CF.sub.3 H CF.sub.3 I CF.sub.3 H CF.sub.3 OH CF.sub.3 H CF.sub.3 OMe CF.sub.3 H CF.sub.3 OS(O).sub.2CF.sub.3 CF.sub.3 H CF.sub.3 nitro CF.sub.3 H CF.sub.3 NH.sub.2 CF.sub.3 H CF.sub.3 cyano CF.sub.3 H CF.sub.3 Me CF.sub.3 H CF.sub.3 CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2Br CF.sub.3 H CF.sub.3 CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2OC(O)Me CF.sub.3 H CF.sub.3 CO.sub.2H CF.sub.3 H CF.sub.3 n-Pr Cl Cl Cl Cl Cl Cl Cl Br Cl Cl Cl I Cl Cl Cl OH Cl Cl Cl OMe Cl Cl Cl OS(O).sub.2CF.sub.3 Cl Cl Cl nitro Cl Cl Cl NH.sub.2 Cl Cl Cl cyano Cl Cl Cl Me Cl Cl Cl CH.sub.2Cl Cl Cl Cl CH.sub.2Br Cl Cl Cl CH.sub.2OH Cl Cl Cl CH.sub.2OC(O)Me Cl Cl Cl CO.sub.2H Cl Cl Cl n-Pr Cl F Cl Cl Cl F Cl Br Cl F Cl I Cl F Cl OH Cl F Cl OMe Cl F Cl OS(O).sub.2CF.sub.3 Cl F Cl nitro Cl F Cl NH.sub.2 Cl F Cl cyano Cl F Cl Me Cl F Cl CH.sub.2Cl Cl F Cl CH.sub.2Br Cl F Cl CH.sub.2OH Cl F Cl CH.sub.2OC(O)Me Cl F Cl CO.sub.2H Cl F Cl n-Pr OCF.sub.3 H Cl Cl OCF.sub.3 H Cl Br OCF.sub.3 H Cl I OCF.sub.3 H Cl OH OCF.sub.3 H Cl OMe OCF.sub.3 H Cl OS(O).sub.2CF.sub.3 OCF.sub.3 H Cl nitro OCF.sub.3 H Cl NH.sub.2 OCF.sub.3 H Cl cyano OCF.sub.3 H Cl Me OCF.sub.3 H Cl CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2Br OCF.sub.3 H Cl CH.sub.2OH OCF.sub.3 H Cl CH.sub.2OC(O)Me OCF.sub.3 H Cl CO.sub.2H OCF.sub.3 H Cl n-Pr

(59) TABLE-US-00004 TABLE 4 R.sup.2a R.sup.2b R.sup.2c R.sup.1 R.sup.3 Cl H Cl CF.sub.3 H Cl H Cl CF.sub.3 Me Cl Cl CN CF.sub.3 CN CF.sub.3 H H CF.sub.3 H CF.sub.3 H Me CF.sub.3 Me CF.sub.3 H H CF.sub.3 CN CF.sub.3 H Cl CF.sub.3 H CF.sub.3 H Cl CF.sub.3 Me CF.sub.3 H Cl CF.sub.3 CN Cl Cl Cl CF.sub.3 H Cl Cl Cl CF.sub.3 CN Cl Cl Cl CF.sub.3 Me Cl H Cl CF.sub.2Cl H Cl H Cl CF.sub.2Cl CN Cl H Cl CCl.sub.2F H Cl H Cl CCl.sub.2F CN Br H Br CF.sub.3 H Br H Br CF.sub.3 Me Br H Br CF.sub.3 CN CF.sub.3 H F CF.sub.3 H CF.sub.3 H F CF.sub.3 Me CF.sub.3 H F CF.sub.3 CN CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 H CF.sub.3 CF.sub.3 Me CF.sub.3 H CF.sub.3 CF.sub.3 CN Cl F Cl CF.sub.3 H Cl F Cl CF.sub.3 CN Cl F Cl CF.sub.3 Me Cl H Cl CF.sub.2CF.sub.2H H Cl H Cl CF.sub.2CF.sub.2H CN Cl H Cl CF.sub.2CF.sub.3 H Cl H Cl CF.sub.2CF.sub.3 CN

(60) TABLE-US-00005 TABLE 5 R.sup.2a R.sup.2b R.sup.2c R.sup.1 R.sup.3 Cl H Cl CF.sub.3 H Cl H Cl CF.sub.3 Me Cl Cl CN CF.sub.3 CN CF.sub.3 H H CF.sub.3 H CF.sub.3 H Me CF.sub.3 Me CF.sub.3 H H CF.sub.3 CN CF.sub.3 H Cl CF.sub.3 H CF.sub.3 H Cl CF.sub.3 Me CF.sub.3 H Cl CF.sub.3 CN Cl Cl Cl CF.sub.3 H Cl Cl Cl CF.sub.3 CN Cl Cl Cl CF.sub.3 Me Cl H Cl CF.sub.2Cl H Cl H Cl CF.sub.2Cl CN Cl H Cl CCl.sub.2F H Cl H Cl CCl.sub.2F CN Br H Br CF.sub.3 H Br H Br CF.sub.3 Me Br H Br CF.sub.3 CN CF.sub.3 H F CF.sub.3 H CF.sub.3 H F CF.sub.3 Me CF.sub.3 H F CF.sub.3 CN CF.sub.3 H CF.sub.3 CF.sub.3 H CF.sub.3 H CF.sub.3 CF.sub.3 Me CF.sub.3 H CF.sub.3 CF.sub.3 CN Cl F Cl CF.sub.3 H Cl F Cl CF.sub.3 CN Cl F Cl CF.sub.3 Me Cl H Cl CF.sub.2CF.sub.2H H Cl H Cl CF.sub.2CF.sub.2H CN Cl H Cl CF.sub.2CF.sub.3 H Cl H Cl CF.sub.2CF.sub.3 CN

(61) TABLE-US-00006 TABLE 6 R.sup.2a R.sup.2b R.sup.2c R.sup.v R.sup.3 Cl H Cl Br H Cl H Cl Br Me Cl Cl Cl Br CN CF.sub.3 H H Br H CF.sub.3 H H Br Me CF.sub.3 H H Br CN CF.sub.3 H Cl Br H CF.sub.3 H Cl Br Me CF.sub.3 H Cl Br CN Cl Cl Cl Br H Cl Cl Cl Br CN Cl Cl Cl Br Me Br H Br Br H Br H Br Br Me Br H Br Br CN CF.sub.3 H F Br H CF.sub.3 H F Br Me CF.sub.3 H F Br CN CF.sub.3 H CF.sub.3 Br H CF.sub.3 H CF.sub.3 Br Me CF.sub.3 H CF.sub.3 Br CN Cl F Cl Br H Cl F Cl Br CN Cl F Cl Br Me

(62) Tables 7-9 relate to the method of Scheme 1a converting compounds of Formulae 2 and 3 to corresponding compounds of Formula 1. This transformation is believed to occur through the intermediacy of compounds of Formula 11.

(63) ##STR00059##
In the example transformations embodied in Tables 7-9, M.sup.1 is K (i.e. the base is potassium carbonate), and water is distilled as an azeotrope from a reaction mixture comprising acetonitrile as the aprotic solvent capable of forming a low-boiling azeotrope with water.

(64) TABLE-US-00007 TABLE 7 0 R.sup.2a R.sup.2b R.sup.2c R.sup.5 Cl H Cl CH.sub.2CH.sub.3 Cl H Cl CH.sub.2i-Pr Cl H Cl CH.sub.2CH.sub.2Cl Cl H Cl CH.sub.2CH.sub.2OH Cl H Cl CH(Me)CH.sub.2OH Cl H Cl CH.sub.2CH(Me)OH Cl H Cl CH.sub.2C(Me).sub.2OH Cl H Cl CH.sub.2CH.sub.2CH.sub.2OH Cl H Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl H Cl CH.sub.2CH.sub.2CH(Me)OH Cl H Cl CH.sub.2C(O)N(H)Et Cl H Cl CH.sub.2C(O)N(H)i-Pr Cl H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl H Cl CH.sub.2CF.sub.3 Cl H Cl CH.sub.2(2-Py) Cl H Cl CH.sub.2(4-Thz) Cl H Cl CH.sub.2c-Pr Cl H Cl CH.sub.2CH.sub.2SMe Cl H Cl CH(Me)CH.sub.2SMe Cl H Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl H Cl CH.sub.2CH.sub.2S(O)Me Cl H Cl CH(Me)CH.sub.2S(O)Me Cl H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl H Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl H Cl CH(Me)CH.sub.2S(O).sub.2Me Cl H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH.sub.2CH.sub.3 Br H Br CH.sub.2i-Pr Br H Br CH.sub.2CH.sub.2Cl Br H Br CH.sub.2CH.sub.2OH Br H Br CH(Me)CH.sub.2OH Br H Br CH.sub.2CH(Me)OH Br H Br CH.sub.2C(Me).sub.2OH Br H Br CH.sub.2CH.sub.2CH.sub.2OH Br H Br CH.sub.2C(Me).sub.2CH.sub.2OH Br H Br CH.sub.2CH.sub.2CH(Me)OH Br H Br CH.sub.2C(O)N(H)Et Br H Br CH.sub.2C(O)N(H)i-Pr Br H Br CH.sub.2C(O)N(H)CH.sub.2i-Pr Br H Br CH(Me)C(O)N(H)CH.sub.2i-Pr Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Br H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Br H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Br H Br CH.sub.2CF.sub.3 Br H Br CH.sub.2(2-Py) Br H Br CH.sub.2(4-Thz) Br H Br CH.sub.2c-Pr Br H Br CH.sub.2CH.sub.2SMe Br H Br CH(Me)CH.sub.2SMe Br H Br CH.sub.2CH.sub.2CH.sub.2SMe Br H Br CH.sub.2CH.sub.2S(O)Me Br H Br CH(Me)CH.sub.2S(O)Me Br H Br CH.sub.2CH.sub.2CH.sub.2S(O)Me Br H Br CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH(Me)CH.sub.2S(O).sub.2Me Br H Br CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Br H Br CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2CH.sub.3 CF.sub.3 H H CH.sub.2i-Pr CF.sub.3 H H CH.sub.2CH.sub.2Cl CF.sub.3 H H CH.sub.2CH.sub.2OH CF.sub.3 H H CH(Me)CH.sub.2OH CF.sub.3 H H CH.sub.2CH(Me)OH CF.sub.3 H H CH.sub.2C(Me).sub.2OH CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H H CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H H CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H H CH.sub.2C(O)N(H)Et CF.sub.3 H H CH.sub.2C(O)N(H)i-Pr CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H H CH.sub.2CF.sub.3 CF.sub.3 H H CH.sub.2(2-Py) CF.sub.3 H H CH.sub.2(4-Thz) CF.sub.3 H H CH.sub.2c-Pr CF.sub.3 H H CH.sub.2CH.sub.2SMe CF.sub.3 H H CH(Me)CH.sub.2SMe CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H H CH.sub.2CH.sub.2S(O)Me CF.sub.3 H H CH(Me)CH.sub.2S(O)Me CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H H CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2CH.sub.3 CF.sub.3 H F CH.sub.2i-Pr CF.sub.3 H F CH.sub.2CH.sub.2Cl CF.sub.3 H F CH.sub.2CH.sub.2OH CF.sub.3 H F CH(Me)CH.sub.2OH CF.sub.3 H F CH.sub.2CH(Me)OH CF.sub.3 H F CH.sub.2C(Me).sub.2OH CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H F CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H F CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H F CH.sub.2C(O)N(H)Et CF.sub.3 H F CH.sub.2C(O)N(H)i-Pr CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H F CH.sub.2CF.sub.3 CF.sub.3 H F CH.sub.2(2-Py) CF.sub.3 H F CH.sub.2(4-Thz) CF.sub.3 H F CH.sub.2c-Pr CF.sub.3 H F CH.sub.2CH.sub.2SMe CF.sub.3 H F CH(Me)CH.sub.2SMe CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H F CH.sub.2CH.sub.2S(O)Me CF.sub.3 H F CH(Me)CH.sub.2S(O)Me CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H F CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2CH.sub.3 CF.sub.3 H Br CH.sub.2i-Pr CF.sub.3 H Br CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH.sub.2CH.sub.2OH CF.sub.3 H Br CH(Me)CH.sub.2OH CF.sub.3 H Br CH.sub.2CH(Me)OH CF.sub.3 H Br CH.sub.2C(Me).sub.2OH CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H Br CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H Br CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H Br CH.sub.2C(O)N(H)Et CF.sub.3 H Br CH.sub.2C(O)N(H)i-Pr CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Br CH.sub.2CF.sub.3 CF.sub.3 H Br CH.sub.2(2-Py) CF.sub.3 H Br CH.sub.2(4-Thz) CF.sub.3 H Br CH.sub.2c-Pr CF.sub.3 H Br CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH(Me)CH.sub.2SMe CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Br CH(Me)CH.sub.2S(O)Me CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Br CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2CH.sub.3 CF.sub.3 H Cl CH.sub.2i-Pr CF.sub.3 H Cl CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH.sub.2CH.sub.2OH CF.sub.3 H Cl CH(Me)CH.sub.2OH CF.sub.3 H Cl CH.sub.2CH(Me)OH CF.sub.3 H Cl CH.sub.2C(Me).sub.2OH CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H Cl CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H Cl CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H Cl CH.sub.2C(O)N(H)Et CF.sub.3 H Cl CH.sub.2C(O)N(H)i-Pr CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Cl CH.sub.2CF.sub.3 CF.sub.3 H Cl CH.sub.2(2-Py) CF.sub.3 H Cl CH.sub.2(4-Thz) CF.sub.3 H Cl CH.sub.2c-Pr CF.sub.3 H Cl CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH(Me)CH.sub.2SMe CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Cl CH(Me)CH.sub.2S(O)Me CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Cl CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH(Me)OH CF.sub.3 H CF.sub.3 CH.sub.2C(Me).sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)Et CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)i-Pr CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H CF.sub.3 CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2(2-Py) CF.sub.3 H CF.sub.3 CH.sub.2(4-Thz) CF.sub.3 H CF.sub.3 CH.sub.2c-Pr CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2CH.sub.3 Cl Cl Cl CH.sub.2i-Pr Cl Cl Cl CH.sub.2CH.sub.2Cl Cl Cl Cl CH.sub.2CH.sub.2OH Cl Cl Cl CH(Me)CH.sub.2OH Cl Cl Cl CH.sub.2CH(Me)OH Cl Cl Cl CH.sub.2C(Me).sub.2OH Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2OH Cl Cl Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl Cl Cl CH.sub.2CH.sub.2CH(Me)OH Cl Cl Cl CH.sub.2C(O)N(H)Et Cl Cl Cl CH.sub.2C(O)N(H)i-Pr Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl Cl Cl CH(Me)C()N(H)CH.sub.2i-Pr Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl Cl Cl CH.sub.2CF.sub.3 Cl Cl Cl CH.sub.2(2-Py) Cl Cl Cl CH.sub.2(4-Thz) Cl Cl Cl CH.sub.2c-Pr Cl Cl Cl CH.sub.2CH.sub.2SMe Cl Cl Cl CH(Me)CH.sub.2SMe Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl Cl Cl CH.sub.2CH.sub.2S(O)Me Cl Cl Cl CH(Me)CH.sub.2S(O)Me Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl Cl Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH(Me)CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2CH.sub.3 Cl F Cl CH.sub.2i-Pr Cl F Cl CH.sub.2CH.sub.2Cl Cl F Cl CH.sub.2CH.sub.2OH Cl F Cl CH(Me)CH.sub.2OH Cl F Cl CH.sub.2CH(Me)OH Cl F Cl CH.sub.2C(Me).sub.2OH Cl F Cl CH.sub.2CH.sub.2CH.sub.2OH Cl F Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl F Cl CH.sub.2CH.sub.2CH(Me)OH Cl F Cl CH.sub.2C(O)N(H)Et Cl F Cl CH.sub.2C(O)N(H)i-Pr Cl F Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl F Cl CH(Me)C()N(H)CH.sub.2i-Pr Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl F Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl F Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl F Cl CH.sub.2CF.sub.3 Cl F Cl CH.sub.2(2-Py) Cl F Cl CH.sub.2(4-Thz) Cl F Cl CH.sub.2c-Pr Cl F Cl CH.sub.2CH.sub.2SMe Cl F Cl CH(Me)CH.sub.2SMe Cl F Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl F Cl CH.sub.2CH.sub.2S(O)Me Cl F Cl CH(Me)CH.sub.2S(O)Me Cl F Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl F Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH(Me)CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl F Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2CH.sub.3 OCF.sub.3 H Cl CH.sub.2i-Pr OCF.sub.3 H Cl CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2CH.sub.2OH OCF.sub.3 H Cl CH(Me)CH.sub.2OH OCF.sub.3 H Cl CH.sub.2CH(Me)OH OCF.sub.3 H Cl CH.sub.2C(Me).sub.2OH OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2OH OCF.sub.3 H Cl CH.sub.2C(Me).sub.2CH.sub.2OH OCF.sub.3 H Cl CH.sub.2CH.sub.2CH(Me)OH OCF.sub.3 H Cl CH.sub.2C(O)N(H)Et OCF.sub.3 H Cl CH.sub.2C(O)N(H)i-Pr OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F OCF.sub.3 H Cl CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH.sub.2(2-Py) OCF.sub.3 H Cl CH.sub.2(4-Thz) OCF.sub.3 H Cl CH.sub.2c-Pr OCF.sub.3 H Cl CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH(Me)CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2CH.sub.2S(O)Me OCF.sub.3 H Cl CH(Me)CH.sub.2S(O)Me OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me OCF.sub.3 H Cl CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH(Me)CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me

(65) TABLE-US-00008 TABLE 8 R.sup.2a R.sup.2b R.sup.2c R.sup.5 Cl H Cl CH.sub.3 Cl H Cl CH.sub.2CH.sub.3 Cl H Cl CH.sub.2i-Pr Cl H Cl n-Pr Cl H Cl i-Pr Cl H Cl s-Bu Cl H Cl t-Bu Cl H Cl (CH.sub.2).sub.5CH.sub.3 Cl H Cl CH.sub.2Ph Br H Br CH.sub.3 Br H Br CH.sub.2CH.sub.3 Br H Br CH.sub.2i-Pr Br H Br n-Pr Br H Br i-Pr Br H Br s-Bu Br H Br t-Bu Br H Br (CH.sub.2).sub.5CH.sub.3 Br H Br CH.sub.2Ph CF.sub.3 H H CH.sub.3 CF.sub.3 H H CH.sub.2CH.sub.3 CF.sub.3 H H CH.sub.2i-Pr CF.sub.3 H H n-Pr CF.sub.3 H H i-Pr CF.sub.3 H H s-Bu CF.sub.3 H H t-Bu CF.sub.3 H H (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H H CH.sub.2Ph CF.sub.3 H F CH.sub.3 CF.sub.3 H F CH.sub.2CH.sub.3 CF.sub.3 H F CH.sub.2i-Pr CF.sub.3 H F n-Pr CF.sub.3 H F i-Pr CF.sub.3 H F s-Bu CF.sub.3 H F t-Bu CF.sub.3 H F (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H F CH.sub.2Ph CF.sub.3 H Br CH.sub.3 CF.sub.3 H Br CH.sub.2CH.sub.3 CF.sub.3 H Br CH.sub.2i-Pr CF.sub.3 H Br n-Pr CF.sub.3 H Br i-Pr CF.sub.3 H Br s-Bu CF.sub.3 H Br t-Bu CF.sub.3 H Br (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H Br CH.sub.2Ph CF.sub.3 H Cl CH.sub.3 CF.sub.3 H Cl CH.sub.2CH.sub.3 CF.sub.3 H Cl CH.sub.2i-Pr CF.sub.3 H Cl n-Pr CF.sub.3 H Cl i-Pr CF.sub.3 H Cl s-Bu CF.sub.3 H Cl t-Bu CF.sub.3 H Cl (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H Cl CH.sub.2Ph CF.sub.3 H CF.sub.3 CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2i-Pr CF.sub.3 H CF.sub.3 n-Pr CF.sub.3 H CF.sub.3 i-Pr CF.sub.3 H CF.sub.3 s-Bu CF.sub.3 H CF.sub.3 t-Bu CF.sub.3 H CF.sub.3 (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2Ph Cl Cl Cl CH.sub.3 Cl Cl Cl CH.sub.2CH.sub.3 Cl Cl Cl CH.sub.2i-Pr Cl Cl Cl n-Pr Cl Cl Cl i-Pr Cl Cl Cl s-Bu Cl Cl Cl t-Bu Cl Cl Cl (CH.sub.2).sub.5CH.sub.3 Cl Cl Cl CH.sub.2Ph Cl F Cl CH.sub.3 Cl F Cl CH.sub.2CH.sub.3 Cl F Cl CH.sub.2i-Pr Cl F Cl n-Pr Cl F Cl i-Pr Cl F Cl s-Bu Cl F Cl t-Bu Cl F Cl (CH.sub.2).sub.5CH.sub.3 Cl F Cl CH.sub.2Ph OCF.sub.3 H Cl CH.sub.3 OCF.sub.3 H Cl CH.sub.2CH.sub.3 OCF.sub.3 H Cl CH.sub.2i-Pr OCF.sub.3 H Cl n-Pr OCF.sub.3 H Cl i-Pr OCF.sub.3 H Cl s-Bu OCF.sub.3 H Cl t-Bu OCF.sub.3 H Cl (CH.sub.2).sub.5CH.sub.3 OCF.sub.3 H Cl CH.sub.2Ph

(66) TABLE-US-00009 TABLE 9 R.sup.2a R.sup.2b R.sup.2c R.sup.3 Cl H Cl Cl Cl H Cl Br Cl H Cl I Cl H Cl OH Cl H Cl OMe Cl H Cl OS(O).sub.2CF.sub.3 Cl H Cl nitro Cl H Cl NH.sub.2 Cl H Cl cyano Cl H Cl Me Cl H Cl CH.sub.2Cl Cl H Cl CH.sub.2Br Cl H Cl CH.sub.2OH Cl H Cl CH.sub.2OC(O)Me Cl H Cl CO.sub.2H Cl H Cl n-Pr Br H Br Cl Br H Br Br Br H Br I Br H Br OH Br H Br OMe Br H Br OS(O).sub.2CF.sub.3 Br H Br nitro Br H Br NH.sub.2 Br H Br cyano Br H Br Me Br H Br CH.sub.2Cl Br H Br CH.sub.2Br Br H Br CH.sub.2OH Br H Br CH.sub.2OC(O)Me Br H Br CO.sub.2H Br H Br n-Pr CF.sub.3 H H Cl CF.sub.3 H H Br CF.sub.3 H H I CF.sub.3 H H OH CF.sub.3 H H OMe CF.sub.3 H H OS(O).sub.2CF.sub.3 CF.sub.3 H H nitro CF.sub.3 H H NH.sub.2 CF.sub.3 H H cyano CF.sub.3 H H Me CF.sub.3 H H CH.sub.2Cl CF.sub.3 H H CH.sub.2Br CF.sub.3 H H CH.sub.2OH CF.sub.3 H H CH.sub.2OC(O)Me CF.sub.3 H H CO.sub.2H CF.sub.3 H H n-Pr CF.sub.3 H F Cl CF.sub.3 H F Br CF.sub.3 H F I CF.sub.3 H F OH CF.sub.3 H F OMe CF.sub.3 H F OS(O).sub.2CF.sub.3 CF.sub.3 H F nitro CF.sub.3 H F NH.sub.2 CF.sub.3 H F cyano CF.sub.3 H F Me CF.sub.3 H F CH.sub.2Cl CF.sub.3 H F CH.sub.2Br CF.sub.3 H F CH.sub.2OH CF.sub.3 H F CH.sub.2OC(O)Me CF.sub.3 H F CO.sub.2H CF.sub.3 H F n-Pr CF.sub.3 H Br Cl CF.sub.3 H Br Br CF.sub.3 H Br I CF.sub.3 H Br OH CF.sub.3 H Br OMe CF.sub.3 H Br OS(O).sub.2CF.sub.3 CF.sub.3 H Br nitro CF.sub.3 H Br NH.sub.2 CF.sub.3 H Br cyano CF.sub.3 H Br Me CF.sub.3 H Br CH.sub.2Cl CF.sub.3 H Br CH.sub.2Br CF.sub.3 H Br CH.sub.2OH CF.sub.3 H Br CH.sub.2OC(O)Me CF.sub.3 H Br CO.sub.2H CF.sub.3 H Br n-Pr CF.sub.3 H Cl Cl CF.sub.3 H Cl Br CF.sub.3 H Cl I CF.sub.3 H Cl OH CF.sub.3 H Cl OMe CF.sub.3 H Cl OS(O).sub.2CF.sub.3 CF.sub.3 H Cl nitro CF.sub.3 H Cl NH.sub.2 CF.sub.3 H Cl cyano CF.sub.3 H Cl Me CF.sub.3 H Cl CH.sub.2Cl CF.sub.3 H Cl CH.sub.2Br CF.sub.3 H Cl CH.sub.2OH CF.sub.3 H Cl CH.sub.2OC(O)Me CF.sub.3 H Cl CO.sub.2H CF.sub.3 H Cl n-Pr CF.sub.3 H CF.sub.3 Cl CF.sub.3 H CF.sub.3 Br CF.sub.3 H CF.sub.3 I CF.sub.3 H CF.sub.3 OH CF.sub.3 H CF.sub.3 OMe CF.sub.3 H CF.sub.3 OS(O).sub.2CF.sub.3 CF.sub.3 H CF.sub.3 nitro CF.sub.3 H CF.sub.3 NH.sub.2 CF.sub.3 H CF.sub.3 cyano CF.sub.3 H CF.sub.3 Me CF.sub.3 H CF.sub.3 CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2Br CF.sub.3 H CF.sub.3 CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2OC(O)Me CF.sub.3 H CF.sub.3 CO.sub.2H CF.sub.3 H CF.sub.3 n-Pr Cl Cl Cl Cl Cl Cl Cl Br Cl Cl Cl I Cl Cl Cl OH Cl Cl Cl OMe Cl Cl Cl OS(O).sub.2CF.sub.3 Cl Cl Cl nitro Cl Cl Cl NH.sub.2 Cl Cl Cl cyano Cl Cl Cl Me Cl Cl Cl CH.sub.2Cl Cl Cl Cl CH.sub.2Br Cl Cl Cl CH.sub.2OH Cl Cl Cl CH.sub.2OC(O)Me Cl Cl Cl CO.sub.2H Cl Cl Cl n-Pr Cl F Cl Cl Cl F Cl Br Cl F Cl I Cl F Cl OH Cl F Cl OMe Cl F Cl OS(O).sub.2CF.sub.3 Cl F Cl nitro Cl F Cl NH.sub.2 Cl F Cl cyano Cl F Cl Me Cl F Cl CH.sub.2Cl Cl F Cl CH.sub.2Br Cl F Cl CH.sub.2OH Cl F Cl CH.sub.2OC(O)Me Cl F Cl CO.sub.2H Cl F Cl n-Pr OCF.sub.3 H Cl Cl OCF.sub.3 H Cl Br OCF.sub.3 H Cl I OCF.sub.3 H Cl OH OCF.sub.3 H Cl OMe OCF.sub.3 H Cl OS(O).sub.2CF.sub.3 OCF.sub.3 H Cl nitro OCF.sub.3 H Cl NH.sub.2 OCF.sub.3 H Cl cyano OCF.sub.3 H Cl Me OCF.sub.3 H Cl CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2Br OCF.sub.3 H Cl CH.sub.2OH OCF.sub.3 H Cl CH.sub.2OC(O)Me OCF.sub.3 H Cl CO.sub.2H OCF.sub.3 H Cl n-Pr

(67) Tables 10-12 relate to the method of Scheme 1b converting compounds of Formulae 2 and 3 to corresponding compounds of Formula 1. This transformation is believed to occur through the intermediacy of compounds of Formula 11.

(68) ##STR00063##
In the example transformations embodied in Tables 10-12, the base is 1,8-diazabicyclo[5.4.0]undec-7-ene, and water is distilled as an azeotrope from a reaction mixture comprising acetonitrile as the aprotic solvent capable of forming a low-boiling azeotrope with water.

(69) TABLE-US-00010 TABLE 10 R.sup.2a R.sup.2b R.sup.2c R.sup.5 Cl H Cl CH.sub.2CH.sub.3 Cl H Cl CH.sub.2i-Pr Cl H Cl CH.sub.2CH.sub.2Cl Cl H Cl CH.sub.2CH.sub.2OH Cl H Cl CH(Me)CH.sub.2OH Cl H Cl CH.sub.2CH(Me)OH Cl H Cl CH.sub.2C(Me).sub.2OH Cl H Cl CH.sub.2CH.sub.2CH.sub.2OH Cl H Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl H Cl CH.sub.2CH.sub.2CH(Me)OH Cl H Cl CH.sub.2C(O)N(H)Et Cl H Cl CH.sub.2C(O)N(H)i-Pr Cl H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl H Cl CH.sub.2CF.sub.3 Cl H Cl CH.sub.2(2-Py) Cl H Cl CH.sub.2(4-Thz) Cl H Cl CH.sub.2c-Pr Cl H Cl CH.sub.2CH.sub.2SMe Cl H Cl CH(Me)CH.sub.2SMe Cl H Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl H Cl CH.sub.2CH.sub.2S(O)Me Cl H Cl CH(Me)CH.sub.2S(O)Me Cl H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl H Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl H Cl CH(Me)CH.sub.2S(O).sub.2Me Cl H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH.sub.2CH.sub.3 Br H Br CH.sub.2i-Pr Br H Br CH.sub.2CH.sub.2Cl Br H Br CH.sub.2CH.sub.2OH Br H Br CH(Me)CH.sub.2OH Br H Br CH.sub.2CH(Me)OH Br H Br CH.sub.2C(Me).sub.2OH Br H Br CH.sub.2CH.sub.2CH.sub.2OH Br H Br CH.sub.2C(Me).sub.2CH.sub.2OH Br H Br CH.sub.2CH.sub.2CH(Me)OH Br H Br CH.sub.2C(O)N(H)Et Br H Br CH.sub.2C(O)N(H)i-Pr Br H Br CH.sub.2C(O)N(H)CH.sub.2i-Pr Br H Br CH(Me)C(O)N(H)CH.sub.2i-Pr Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Br H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Br H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Br H Br CH.sub.2CF.sub.3 Br H Br CH.sub.2(2-Py) Br H Br CH.sub.2(4-Thz) Br H Br CH.sub.2c-Pr Br H Br CH.sub.2CH.sub.2SMe Br H Br CH(Me)CH.sub.2SMe Br H Br CH.sub.2CH.sub.2CH.sub.2SMe Br H Br CH.sub.2CH.sub.2S(O)Me Br H Br CH(Me)CH.sub.2S(O)Me Br H Br CH.sub.2CH.sub.2CH.sub.2S(O)Me Br H Br CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH(Me)CH.sub.2S(O).sub.2Me Br H Br CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Br H Br CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Br H Br CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Br H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2CH.sub.3 CF.sub.3 H H CH.sub.2i-Pr CF.sub.3 H H CH.sub.2CH.sub.2Cl CF.sub.3 H H CH.sub.2CH.sub.2OH CF.sub.3 H H CH(Me)CH.sub.2OH CF.sub.3 H H CH.sub.2CH(Me)OH CF.sub.3 H H CH.sub.2C(Me).sub.2OH CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H H CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H H CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H H CH.sub.2C(O)N(H)Et CF.sub.3 H H CH.sub.2C(O)N(H)i-Pr CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H H CH.sub.2CF.sub.3 CF.sub.3 H H CH.sub.2(2-Py) CF.sub.3 H H CH.sub.2(4-Thz) CF.sub.3 H H CH.sub.2c-Pr CF.sub.3 H H CH.sub.2CH.sub.2SMe CF.sub.3 H H CH(Me)CH.sub.2SMe CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H H CH.sub.2CH.sub.2S(O)Me CF.sub.3 H H CH(Me)CH.sub.2S(O)Me CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H H CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H H CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H H CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2CH.sub.3 CF.sub.3 H F CH.sub.2i-Pr CF.sub.3 H F CH.sub.2CH.sub.2Cl CF.sub.3 H F CH.sub.2CH.sub.2OH CF.sub.3 H F CH(Me)CH.sub.2OH CF.sub.3 H F CH.sub.2CH(Me)OH CF.sub.3 H F CH.sub.2C(Me).sub.2OH CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H F CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H F CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H F CH.sub.2C(O)N(H)Et CF.sub.3 H F CH.sub.2C(O)N(H)i-Pr CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H F CH.sub.2CF.sub.3 CF.sub.3 H F CH.sub.2(2-Py) CF.sub.3 H F CH.sub.2(4-Thz) CF.sub.3 H F CH.sub.2c-Pr CF.sub.3 H F CH.sub.2CH.sub.2SMe CF.sub.3 H F CH(Me)CH.sub.2SMe CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H F CH.sub.2CH.sub.2S(O)Me CF.sub.3 H F CH(Me)CH.sub.2S(O)Me CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H F CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H F CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H F CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2CH.sub.3 CF.sub.3 H Br CH.sub.2i-Pr CF.sub.3 H Br CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH.sub.2CH.sub.2OH CF.sub.3 H Br CH(Me)CH.sub.2OH CF.sub.3 H Br CH.sub.2CH(Me)OH CF.sub.3 H Br CH.sub.2C(Me).sub.2OH CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H Br CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H Br CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H Br CH.sub.2C(O)N(H)Et CF.sub.3 H Br CH.sub.2C(O)N(H)i-Pr CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Br CH.sub.2CF.sub.3 CF.sub.3 H Br CH.sub.2(2-Py) CF.sub.3 H Br CH.sub.2(4-Thz) CF.sub.3 H Br CH.sub.2c-Pr CF.sub.3 H Br CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH(Me)CH.sub.2SMe CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Br CH(Me)CH.sub.2S(O)Me CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Br CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Br CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H Br CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2CH.sub.3 CF.sub.3 H Cl CH.sub.2i-Pr CF.sub.3 H Cl CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH.sub.2CH.sub.2OH CF.sub.3 H Cl CH(Me)CH.sub.2OH CF.sub.3 H Cl CH.sub.2CH(Me)OH CF.sub.3 H Cl CH.sub.2C(Me).sub.2OH CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H Cl CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H Cl CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H Cl CH.sub.2C(O)N(H)Et CF.sub.3 H Cl CH.sub.2C(O)N(H)i-Pr CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H Cl CH.sub.2CF.sub.3 CF.sub.3 H Cl CH.sub.2(2-Py) CF.sub.3 H Cl CH.sub.2(4-Thz) CF.sub.3 H Cl CH.sub.2c-Pr CF.sub.3 H Cl CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH(Me)CH.sub.2SMe CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Cl CH(Me)CH.sub.2S(O)Me CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H Cl CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH(Me)OH CF.sub.3 H CF.sub.3 CH.sub.2C(Me).sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2C(Me).sub.2CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH(Me)OH CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)Et CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)i-Pr CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2i-Pr CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CF.sub.3 H CF.sub.3 CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2(2-Py) CF.sub.3 H CF.sub.3 CH.sub.2(4-Thz) CF.sub.3 H CF.sub.3 CH.sub.2c-Pr CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2S(O)Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH(Me)CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CF.sub.3 H CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2CH.sub.3 Cl Cl Cl CH.sub.2i-Pr Cl Cl Cl CH.sub.2CH.sub.2Cl Cl Cl Cl CH.sub.2CH.sub.2OH Cl Cl Cl CH(Me)CH.sub.2OH Cl Cl Cl CH.sub.2CH(Me)OH Cl Cl Cl CH.sub.2C(Me).sub.2OH Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2OH Cl Cl Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl Cl Cl CH.sub.2CH.sub.2CH(Me)OH Cl Cl Cl CH.sub.2C(O)N(H)Et Cl Cl Cl CH.sub.2C(O)N(H)i-Pr Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl Cl Cl CH.sub.2CF.sub.3 Cl Cl Cl CH.sub.2(2-Py) Cl Cl Cl CH.sub.2(4-Thz) Cl Cl Cl CH.sub.2c-Pr Cl Cl Cl CH.sub.2CH.sub.2SMe Cl Cl Cl CH(Me)CH.sub.2SMe Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl Cl Cl CH.sub.2CH.sub.2S(O)Me Cl Cl Cl CH(Me)CH.sub.2S(O)Me Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl Cl Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH(Me)CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl Cl Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl Cl Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2CH.sub.3 Cl F Cl CH.sub.2i-Pr Cl F Cl CH.sub.2CH.sub.2Cl Cl F Cl CH.sub.2CH.sub.2OH Cl F Cl CH(Me)CH.sub.2OH Cl F Cl CH.sub.2CH(Me)OH Cl F Cl CH.sub.2C(Me).sub.2OH Cl F Cl CH.sub.2CH.sub.2CH.sub.2OH Cl F Cl CH.sub.2C(Me).sub.2CH.sub.2OH Cl F Cl CH.sub.2CH.sub.2CH(Me)OH Cl F Cl CH.sub.2C(O)N(H)Et Cl F Cl CH.sub.2C(O)N(H)i-Pr Cl F Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr Cl F Cl CH(Me)C(O)N(H)CH.sub.2i-Pr Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl Cl F Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F Cl F Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F Cl F Cl CH.sub.2CF.sub.3 Cl F Cl CH.sub.2(2-Py) Cl F Cl CH.sub.2(4-Thz) Cl F Cl CH.sub.2c-Pr Cl F Cl CH.sub.2CH.sub.2SMe Cl F Cl CH(Me)CH.sub.2SMe Cl F Cl CH.sub.2CH.sub.2CH.sub.2SMe Cl F Cl CH.sub.2CH.sub.2S(O)Me Cl F Cl CH(Me)CH.sub.2S(O)Me Cl F Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me Cl F Cl CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH(Me)CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 Cl F Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe Cl F Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2CH.sub.3 OCF.sub.3 H Cl CH.sub.2i-Pr OCF.sub.3 H Cl CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2CH.sub.2OH OCF.sub.3 H Cl CH(Me)CH.sub.2OH OCF.sub.3 H Cl CH.sub.2CH(Me)OH OCF.sub.3 H Cl CH.sub.2C(Me).sub.2OH OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2OH OCF.sub.3 H Cl CH.sub.2C(Me).sub.2CH.sub.2OH OCF.sub.3 H Cl CH.sub.2CH.sub.2CH(Me)OH OCF.sub.3 H Cl CH.sub.2C(O)N(H)Et OCF.sub.3 H Cl CH.sub.2C(O)N(H)i-Pr OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2i-Pr OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2i-Pr OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2F OCF.sub.3 H Cl CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH.sub.2(2-Py) OCF.sub.3 H Cl CH.sub.2(4-Thz) OCF.sub.3 H Cl CH.sub.2c-Pr OCF.sub.3 H Cl CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH(Me)CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2CH.sub.2S(O)Me OCF.sub.3 H Cl CH(Me)CH.sub.2S(O)Me OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O)Me OCF.sub.3 H Cl CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH(Me)CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2CH.sub.2CH.sub.2S(O).sub.2Me OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH(Me)C(O)N(H)CH.sub.2CF.sub.3 OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe OCF.sub.3 H Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2S(O).sub.2Me

(70) TABLE-US-00011 TABLE 11 R.sup.2a R.sup.2b R.sup.2c R.sup.5 Cl H Cl CH.sub.3 Cl H Cl CH.sub.2CH.sub.3 Cl H Cl CH.sub.2i-Pr Cl H Cl n-Pr Cl H Cl i-Pr Cl H Cl s-Bu Cl H Cl t-Bu Cl H Cl (CH.sub.2).sub.5CH.sub.3 Cl H Cl CH.sub.2Ph Br H Br CH.sub.3 Br H Br CH.sub.2CH.sub.3 Br H Br CH.sub.2i-Pr Br H Br n-Pr Br H Br i-Pr Br H Br s-Bu Br H Br t-Bu Br H Br (CH.sub.2).sub.5CH.sub.3 Br H Br CH.sub.2Ph CF.sub.3 H H CH.sub.3 CF.sub.3 H H CH.sub.2CH.sub.3 CF.sub.3 H H CH.sub.2i-Pr CF.sub.3 H H n-Pr CF.sub.3 H H i-Pr CF.sub.3 H H s-Bu CF.sub.3 H H t-Bu CF.sub.3 H H (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H H CH.sub.2Ph CF.sub.3 H F CH.sub.3 CF.sub.3 H F CH.sub.2CH.sub.3 CF.sub.3 H F CH.sub.2i-Pr CF.sub.3 H F n-Pr CF.sub.3 H F i-Pr CF.sub.3 H F s-Bu CF.sub.3 H F t-Bu CF.sub.3 H F (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H F CH.sub.2Ph CF.sub.3 H Br CH.sub.3 CF.sub.3 H Br CH.sub.2CH.sub.3 CF.sub.3 H Br CH.sub.2i-Pr CF.sub.3 H Br n-Pr CF.sub.3 H Br i-Pr CF.sub.3 H Br s-Bu CF.sub.3 H Br t-Bu CF.sub.3 H Br (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H Br CH.sub.2Ph CF.sub.3 H Cl CH.sub.3 CF.sub.3 H Cl CH.sub.2CH.sub.3 CF.sub.3 H Cl CH.sub.2i-Pr CF.sub.3 H Cl n-Pr CF.sub.3 H Cl i-Pr CF.sub.3 H Cl s-Bu CF.sub.3 H Cl t-Bu CF.sub.3 H Cl (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H Cl CH.sub.2Ph CF.sub.3 H CF.sub.3 CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2i-Pr CF.sub.3 H CF.sub.3 n-Pr CF.sub.3 H CF.sub.3 i-Pr CF.sub.3 H CF.sub.3 s-Bu CF.sub.3 H CF.sub.3 t-Bu CF.sub.3 H CF.sub.3 (CH.sub.2).sub.5CH.sub.3 CF.sub.3 H CF.sub.3 CH.sub.2Ph Cl Cl Cl CH.sub.3 Cl Cl Cl CH.sub.2CH.sub.3 Cl Cl Cl CH.sub.2i-Pr Cl Cl Cl n-Pr Cl Cl Cl i-Pr Cl Cl Cl s-Bu Cl Cl Cl t-Bu Cl Cl Cl (CH.sub.2).sub.5CH.sub.3 Cl Cl Cl CH.sub.2Ph Cl F Cl CH.sub.3 Cl F Cl CH.sub.2CH.sub.3 Cl F Cl CH.sub.2i-Pr Cl F Cl n-Pr Cl F Cl i-Pr Cl F Cl s-Bu Cl F Cl t-Bu Cl F Cl (CH.sub.2).sub.5CH.sub.3 Cl F Cl CH.sub.2Ph OCF.sub.3 H Cl CH.sub.3 OCF.sub.3 H Cl CH.sub.2CH.sub.3 OCF.sub.3 H Cl CH.sub.2i-Pr OCF.sub.3 H Cl n-Pr OCF.sub.3 H Cl i-Pr OCF.sub.3 H Cl s-Bu OCF.sub.3 H Cl t-Bu OCF.sub.3 H Cl (CH.sub.2).sub.5CH.sub.3 OCF.sub.3 H Cl CH.sub.2Ph

(71) TABLE-US-00012 TABLE 12 R.sup.2a R.sup.2b R.sup.2c R.sup.3 Cl H Cl Cl Cl H Cl Br Cl H Cl I Cl H Cl OH Cl H Cl OMe Cl H Cl OS(O).sub.2CF.sub.3 Cl H Cl nitro Cl H Cl NH.sub.2 Cl H Cl cyano Cl H Cl Me Cl H Cl CH.sub.2Cl Cl H Cl CH.sub.2Br Cl H Cl CH.sub.2OH Cl H Cl CH.sub.2OC(O)Me Cl H Cl CO.sub.2H Cl H Cl n-Pr Br H Br Cl Br H Br Br Br H Br I Br H Br OH Br H Br OMe Br H Br OS(O).sub.2CF.sub.3 Br H Br nitro Br H Br NH.sub.2 Br H Br cyano Br H Br Me Br H Br CH.sub.2Cl Br H Br CH.sub.2Br Br H Br CH.sub.2OH Br H Br CH.sub.2OC(O)Me Br H Br CO.sub.2H Br H Br n-Pr CF.sub.3 H H Cl CF.sub.3 H H Br CF.sub.3 H H I CF.sub.3 H H OH CF.sub.3 H H OMe CF.sub.3 H H OS(O).sub.2CF.sub.3 CF.sub.3 H H nitro CF.sub.3 H H NH.sub.2 CF.sub.3 H H cyano CF.sub.3 H H Me CF.sub.3 H H CH.sub.2Cl CF.sub.3 H H CH.sub.2Br CF.sub.3 H H CH.sub.2OH CF.sub.3 H H CH.sub.2OC(O)Me CF.sub.3 H H CO.sub.2H CF.sub.3 H H n-Pr CF.sub.3 H F Cl CF.sub.3 H F Br CF.sub.3 H F I CF.sub.3 H F OH CF.sub.3 H F OMe CF.sub.3 H F OS(O).sub.2CF.sub.3 CF.sub.3 H F nitro CF.sub.3 H F NH.sub.2 CF.sub.3 H F cyano CF.sub.3 H F Me CF.sub.3 H F CH.sub.2Cl CF.sub.3 H F CH.sub.2Br CF.sub.3 H F CH.sub.2OH CF.sub.3 H F CH.sub.2OC(O)Me CF.sub.3 H F CO.sub.2H CF.sub.3 H F n-Pr CF.sub.3 H Br Cl CF.sub.3 H Br Br CF.sub.3 H Br I CF.sub.3 H Br OH CF.sub.3 H Br OMe CF.sub.3 H Br OS(O).sub.2CF.sub.3 CF.sub.3 H Br nitro CF.sub.3 H Br NH.sub.2 CF.sub.3 H Br cyano CF.sub.3 H Br Me CF.sub.3 H Br CH.sub.2Cl CF.sub.3 H Br CH.sub.2Br CF.sub.3 H Br CH.sub.2OH CF.sub.3 H Br CH.sub.2OC(O)Me CF.sub.3 H Br CO.sub.2H CF.sub.3 H Br n-Pr CF.sub.3 H Cl Cl CF.sub.3 H Cl Br CF.sub.3 H Cl I CF.sub.3 H Cl OH CF.sub.3 H Cl OMe CF.sub.3 H Cl OS(O).sub.2CF.sub.3 CF.sub.3 H Cl nitro CF.sub.3 H Cl NH.sub.2 CF.sub.3 H Cl cyano CF.sub.3 H Cl Me CF.sub.3 H Cl CH.sub.2Cl CF.sub.3 H Cl CH.sub.2Br CF.sub.3 H Cl CH.sub.2OH CF.sub.3 H Cl CH.sub.2OC(O)Me CF.sub.3 H Cl CO.sub.2H CF.sub.3 H Cl n-Pr CF.sub.3 H CF.sub.3 Cl CF.sub.3 H CF.sub.3 Br CF.sub.3 H CF.sub.3 I CF.sub.3 H CF.sub.3 OH CF.sub.3 H CF.sub.3 OMe CF.sub.3 H CF.sub.3 OS(O).sub.2CF.sub.3 CF.sub.3 H CF.sub.3 nitro CF.sub.3 H CF.sub.3 NH.sub.2 CF.sub.3 H CF.sub.3 cyano CF.sub.3 H CF.sub.3 Me CF.sub.3 H CF.sub.3 CH.sub.2Cl CF.sub.3 H CF.sub.3 CH.sub.2Br CF.sub.3 H CF.sub.3 CH.sub.2OH CF.sub.3 H CF.sub.3 CH.sub.2OC(O)Me CF.sub.3 H CF.sub.3 CO.sub.2H CF.sub.3 H CF.sub.3 n-Pr Cl Cl Cl Cl Cl Cl Cl Br Cl Cl Cl I Cl Cl Cl OH Cl Cl Cl OMe Cl Cl Cl OS(O).sub.2CF.sub.3 Cl Cl Cl nitro Cl Cl Cl NH.sub.2 Cl Cl Cl cyano Cl Cl Cl Me Cl Cl Cl CH.sub.2Cl Cl Cl Cl CH.sub.2Br Cl Cl Cl CH.sub.2OH Cl Cl Cl CH.sub.2OC(O)Me Cl Cl Cl CO.sub.2H Cl Cl Cl n-Pr Cl F Cl Cl Cl F Cl Br Cl F Cl I Cl F Cl OH Cl F Cl OMe Cl F Cl OS(O).sub.2CF.sub.3 Cl F Cl nitro Cl F Cl NH.sub.2 Cl F Cl cyano Cl F Cl Me Cl F Cl CH.sub.2Cl Cl F Cl CH.sub.2Br Cl F Cl CH.sub.2OH Cl F Cl CH.sub.2OC(O)Me Cl F Cl CO.sub.2H Cl F Cl n-Pr OCF.sub.3 H Cl Cl OCF.sub.3 H Cl Br OCF.sub.3 H Cl I OCF.sub.3 H Cl OH OCF.sub.3 H Cl OMe OCF.sub.3 H Cl OS(O).sub.2CF.sub.3 OCF.sub.3 H Cl nitro OCF.sub.3 H Cl NH.sub.2 OCF.sub.3 H Cl cyano OCF.sub.3 H Cl Me OCF.sub.3 H Cl CH.sub.2Cl OCF.sub.3 H Cl CH.sub.2Br OCF.sub.3 H Cl CH.sub.2OH OCF.sub.3 H Cl CH.sub.2OC(O)Me OCF.sub.3 H Cl CO.sub.2H OCF.sub.3 H Cl n-Pr

(72) Tables 13-14 relate to the method of Scheme 2 converting compounds of Formula 5 to Grignard reagents, which are contacted with compounds of Formula 6 to prepare compounds of Formula 2. X.sup.1 can be the same as or different than X, as explained in the description of the method of Scheme 2.

(73) ##STR00067##
In the example transformations embodied in these tables the solvent comprises tetrahydrofuran.

(74) TABLE-US-00013 TABLE 13 R.sup.2a R.sup.2b R.sup.2c X Y Cl H Cl I OMe Cl H Cl I OEt Cl H Cl I Oi-Pr Cl H Cl I O(CH.sub.2).sub.4CH.sub.3 Cl H Cl I N(CH.sub.3).sub.2 Cl H Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) Cl H Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl H Cl Br OMe Cl H Cl Br OEt Cl H Cl Br Oi-Pr Cl H Cl Br O(CH.sub.2).sub.4CH.sub.3 Cl H Cl Br N(CH.sub.3).sub.2 Cl H Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) Cl H Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H Br I OMe CF.sub.3 H Br I OEt CF.sub.3 H Br I Oi-Pr CF.sub.3 H Br I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H Br I N(CH.sub.3).sub.2 CF.sub.3 H Br I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H Br I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H H I OMe CF.sub.3 H H I OEt CF.sub.3 H H I Oi-Pr CF.sub.3 H H I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H H I N(CH.sub.3).sub.2 CF.sub.3 H H I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H H I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H H Br OMe CF.sub.3 H H Br OEt CF.sub.3 H H Br Oi-Pr CF.sub.3 H H Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H H Br N(CH.sub.3).sub.2 CF.sub.3 H H Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H H Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H H Cl OMe CF.sub.3 H H Cl OEt CF.sub.3 H H Cl Oi-Pr CF.sub.3 H H Cl O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H H Cl N(CH.sub.3).sub.2 CF.sub.3 H H Cl N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H H Cl NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H F I OMe CF.sub.3 H F I OEt CF.sub.3 H F I Oi-Pr CF.sub.3 H F I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H F I N(CH.sub.3).sub.2 CF.sub.3 H F I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H F I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H F Br OMe CF.sub.3 H F Br OEt CF.sub.3 H F Br Oi-Pr CF.sub.3 H F Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H F Br N(CH.sub.3).sub.2 CF.sub.3 H F Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H F Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H F Cl OMe CF.sub.3 H F Cl OEt CF.sub.3 H F Cl Oi-Pr CF.sub.3 H F Cl O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H F Cl N(CH.sub.3).sub.2 CF.sub.3 H F Cl N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H F Cl NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H Cl I OMe CF.sub.3 H Cl I OEt CF.sub.3 H Cl I Oi-Pr CF.sub.3 H Cl I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H Cl I N(CH.sub.3).sub.2 CF.sub.3 H Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H Cl Br OMe CF.sub.3 H Cl Br OEt CF.sub.3 H Cl Br Oi-Pr CF.sub.3 H Cl Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H Cl Br N(CH.sub.3).sub.2 CF.sub.3 H Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H CF.sub.3 I OMe CF.sub.3 H CF.sub.3 I OEt CF.sub.3 H CF.sub.3 I Oi-Pr CF.sub.3 H CF.sub.3 I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H CF.sub.3 I N(CH.sub.3).sub.2 CF.sub.3 H CF.sub.3 I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H CF.sub.3 I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H CF.sub.3 Br OMe CF.sub.3 H CF.sub.3 Br OEt CF.sub.3 H CF.sub.3 Br Oi-Pr CF.sub.3 H CF.sub.3 Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H CF.sub.3 Br N(CH.sub.3).sub.2 CF.sub.3 H CF.sub.3 Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H CF.sub.3 Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H CF.sub.3 Cl OMe CF.sub.3 H CF.sub.3 Cl OEt CF.sub.3 H CF.sub.3 Cl Oi-Pr CF.sub.3 H CF.sub.3 Cl O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H CF.sub.3 Cl N(CH.sub.3).sub.2 CF.sub.3 H CF.sub.3 Cl N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H CF.sub.3 Cl NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl Cl Cl I OMe Cl Cl Cl I OEt Cl Cl Cl I Oi-Pr Cl Cl Cl I O(CH.sub.2).sub.4CH.sub.3 Cl Cl Cl I N(CH.sub.3).sub.2 Cl Cl Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) Cl Cl Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl Cl Cl Br OMe Cl Cl Cl Br OEt Cl Cl Cl Br Oi-Pr Cl Cl Cl Br O(CH.sub.2).sub.4CH.sub.3 Cl Cl Cl Br N(CH.sub.3).sub.2 Cl Cl Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) Cl Cl Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl F Cl I OMe Cl F Cl I OEt Cl F Cl I Oi-Pr Cl F Cl I O(CH.sub.2).sub.4CH.sub.3 Cl F Cl I N(CH.sub.3).sub.2 Cl F Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) Cl F Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl F Cl Br OMe Cl F Cl Br OEt Cl F Cl Br Oi-Pr Cl F Cl Br O(CH.sub.2).sub.4CH.sub.3 Cl F Cl Br N(CH.sub.3).sub.2 Cl F Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) Cl F Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2

(75) TABLE-US-00014 TABLE 14 R.sup.2a R.sup.2b R.sup.2c X Y Cl H Cl I OMe Cl H Cl I OEt Cl H Cl I Oi-Pr Cl H Cl I O(CH.sub.2).sub.4CH.sub.3 Cl H Cl I N(CH.sub.3).sub.2 Cl H Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) Cl H Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl H Cl Br OMe Cl H Cl Br OEt Cl H Cl Br Oi-Pr Cl H Cl Br O(CH.sub.2).sub.4CH.sub.3 Cl H Cl Br N(CH.sub.3).sub.2 Cl H Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) Cl H Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H Br I OMe CF.sub.3 H Br I OEt CF.sub.3 H Br I Oi-Pr CF.sub.3 H Br I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H Br I N(CH.sub.3).sub.2 CF.sub.3 H Br I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H Br I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H H I OMe CF.sub.3 H H I OEt CF.sub.3 H H I Oi-Pr CF.sub.3 H H I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H H I N(CH.sub.3).sub.2 CF.sub.3 H H I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H H I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H H Br OMe CF.sub.3 H H Br OEt CF.sub.3 H H Br Oi-Pr CF.sub.3 H H Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H H Br N(CH.sub.3).sub.2 CF.sub.3 H H Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H H Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H H Cl OMe CF.sub.3 H H Cl OEt CF.sub.3 H H Cl Oi-Pr CF.sub.3 H H Cl O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H H Cl N(CH.sub.3).sub.2 CF.sub.3 H H Cl N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H H Cl NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H F I OMe CF.sub.3 H F I OEt CF.sub.3 H F I Oi-Pr CF.sub.3 H F I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H F I N(CH.sub.3).sub.2 CF.sub.3 H F I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H F I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H F Br OMe CF.sub.3 H F Br OEt CF.sub.3 H F Br Oi-Pr CF.sub.3 H F Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H F Br N(CH.sub.3).sub.2 CF.sub.3 H F Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H F Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H F Cl OMe CF.sub.3 H F Cl OEt CF.sub.3 H F Cl Oi-Pr CF.sub.3 H F Cl O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H F Cl N(CH.sub.3).sub.2 CF.sub.3 H F Cl N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H F Cl NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H Cl I OMe CF.sub.3 H Cl I OEt CF.sub.3 H Cl I Oi-Pr CF.sub.3 H Cl I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H Cl I N(CH.sub.3).sub.2 CF.sub.3 H Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H Cl Br OMe CF.sub.3 H Cl Br OEt CF.sub.3 H Cl Br Oi-Pr CF.sub.3 H Cl Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H Cl Br N(CH.sub.3).sub.2 CF.sub.3 H Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H CF.sub.3 I OMe CF.sub.3 H CF.sub.3 I OEt CF.sub.3 H CF.sub.3 I Oi-Pr CF.sub.3 H CF.sub.3 I O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H CF.sub.3 I N(CH.sub.3).sub.2 CF.sub.3 H CF.sub.3 I N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H CF.sub.3 I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H CF.sub.3 Br OMe CF.sub.3 H CF.sub.3 Br OEt CF.sub.3 H CF.sub.3 Br Oi-Pr CF.sub.3 H CF.sub.3 Br O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H CF.sub.3 Br N(CH.sub.3).sub.2 CF.sub.3 H CF.sub.3 Br N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H CF.sub.3 Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 CF.sub.3 H CF.sub.3 Cl OMe CF.sub.3 H CF.sub.3 Cl OEt CF.sub.3 H CF.sub.3 Cl Oi-Pr CF.sub.3 H CF.sub.3 Cl O(CH.sub.2).sub.4CH.sub.3 CF.sub.3 H CF.sub.3 Cl N(CH.sub.3).sub.2 CF.sub.3 H CF.sub.3 Cl N(CH.sub.3)(CH.sub.2CH.sub.3) CF.sub.3 H CF.sub.3 Cl NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl Cl Cl I OMe Cl Cl Cl I OEt Cl Cl Cl I Oi-Pr Cl Cl Cl I O(CH.sub.2).sub.4CH.sub.3 Cl Cl Cl I N(CH.sub.3).sub.2 Cl Cl Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) Cl Cl Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl Cl Cl Br OMe Cl Cl Cl Br OEt Cl Cl Cl Br Oi-Pr Cl Cl Cl Br O(CH.sub.2).sub.4CH.sub.3 Cl Cl Cl Br N(CH.sub.3).sub.2 Cl Cl Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) Cl Cl Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl F Cl I OMe Cl F Cl I OEt Cl F Cl I Oi-Pr Cl F Cl I O(CH.sub.2).sub.4CH.sub.3 Cl F Cl I N(CH.sub.3).sub.2 Cl F Cl I N(CH.sub.3)(CH.sub.2CH.sub.3) Cl F Cl I NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2 Cl F Cl Br OMe Cl F Cl Br OEt Cl F Cl Br Oi-Pr Cl F Cl Br O(CH.sub.2).sub.4CH.sub.3 Cl F Cl Br N(CH.sub.3).sub.2 Cl F Cl Br N(CH.sub.3)(CH.sub.2CH.sub.3) Cl F Cl Br NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2

(76) The following compounds of Formula 3 defined in Table 15 are of particular note as intermediates for preparing the corresponding compounds of Formula 1 as shown in Schemes 1, 1a and 1b by the procedures described herein together with methods known in the art.

(77) TABLE-US-00015 TABLE 15 0 R.sup.5 CH.sub.2CH.sub.3 CH.sub.2i-Pr CH.sub.2CH.sub.2Cl CH.sub.2CH.sub.2OH CH(Me)CH.sub.2OH CH.sub.2CH(Me)OH CH.sub.2C(Me).sub.2OH CH.sub.2CH.sub.2CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH CH.sub.2CH.sub.2CH(Me)OH CH.sub.2C(O)N(H)Et CH.sub.2C(O)N(H)i-Pr CH.sub.2C(O)N(H)CH.sub.2i-Pr CH(Me)C(O)N(H)CH.sub.2i-Pr CH.sub.2C(O)N(H)CH.sub.2CH.sub.2Cl CH(Me)C(O)N(H)CH.sub.2CH.sub.2Cl CH.sub.2C(O)N(H)CH.sub.2CH.sub.2F CH(Me)C(O)N(H)CH.sub.2CH.sub.2F CH.sub.2CF.sub.3 CH.sub.2(2-Py) CH.sub.2(4-Thz) CH.sub.2c-Pr CH.sub.2CH.sub.2SMe CH(Me)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2SO.sub.2Me CH(Me)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2C(O)N(H)CH.sub.2CF.sub.3 CH(Me)C(O)N(H)CH.sub.2CF.sub.3 CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SMe CH.sub.2C(O)N(H)CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et) CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(s-Bu) CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3 CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3 CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3