| 摘要 |
1. A process for making compounds of Formula 5 R<1> is selected from the group consisting of (a) CH3, (b) NH2, (c) NHC(O)CF3, (d) NHCH3; and Ar is a mono-, di-, or trisubstituted phenyl or pyridinyl (or the N-oxide thereof), wherein the substituents are chosen from the group consisting of (a) hydrogen, (b) halo, (c) C1-4alkoxy, (d) C1-4alkylthio, (e) CN, (f) C1-4alkyl, (g) C1-4fluoroalkyl, the process comprising: reacting a compound of formula 13 wherein X is a halogen belonging to the group consisting of iodine, chlorine, bromine and fluorine, with a compound of formula 9 to yield a compound of formula 15 and oxidizing the compound of formula 15 using an oxidizing agent, and optionally a catalyst and an acid to yield a compound of formula 5. 2. A process according to Claim 1 wherein the oxidizing agent belongs to the group consisting of hydrogen peroxide, oxone, and hydrogen peroxide/acetic acid and the acid is acetic, propionic, methanesulfonic acid or sulfuric acid. 3. A process according to Claim 1 wherein the catalyst is Na2WO4. 4. A process according to Claim 2 wherein the oxidizing agent is oxone or hydrogen peroxide and the acid is sulfuric acid. 5. A process according to Claim 1 wherein Ar is a mono- or di-, trisubstituted 3-pyridinyl. 6. A process according to Claim 1 wherein R<1> is CH3 or NH2. 7. A process according to Claim 1 wherein Ar is a mono- or di-substituted 3-pyridinyl and the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (c) C1-3alkoxy, (d) C1-3alkylthio, (e) C1-3alkyl, (f) CF3, and (g) CN. 8. A process for making a compound of formula 13a wherein X is a halogen belonging to the group consisting of iodide, chloride, bromide and fluoride; comprising reacting a compound of formula 12a with magnesium in the presence of a solvent/co-solvent mixture to yield a compound of formula 13a. 9. A process according to Claim 8 wherein X is chloride. 10. A process according to Claim 8 wherein the solvent/co-solvent mixture is selected from the group consisting of toluene/tetrahydrofuran, tetrahydrofuran/diethylether, toluene/diethylether, tetrahydrofuran/methyl-tert-butylether, toluene/methyl-tert-butylether, toluene/dioxane and tetrahydrofuran/dioxane. 11. A process according to Claim 10 wherein the solvent/co-solvent mixture is toluene/tetrahydrofuran. 12. A process according to Claim 8 wherein the molar ratio of solvent to co-solvent is from about 0.5:4 to about 1:1. 13. A process according to Claim 12 wherein the molar ratio of solvent to co-solvent is from about 1:2 to about 1:1. 14. A process for making a compound of formula I wherein: R<1> is selected from the group consisting of (a) CH3, (b) NH2, (c) NHC(O)CF3, (d) NHCH3; Ar is a mono-, di-, or trisubstituted phenyl or pyridinyl (or the N-oxide thereof), wherein the substituents are chosen from the group consisting of (a) hydrogen, (b) halo, (c) Cl-4alkoxy, (d) C l-4alkylthio, (e) CN, (f) C l-4alkyl, (g) C l-4fluoroalkyl, and R<2> is chosen from the group consisting of (a) F, Cl, Br, I, (b) CN, (c) azide comprising reacting a compound of formula 12 wherein X is a halogen belonging to the group consisting of iodide, chloride, bromide and fluoride; with magnesium in the presence of a solvent/co-solvent mixture to yield a compound of formula 13 reacting the compound of formula 13 with a compound of formula 9 to yield a compound of formula 15 and oxidizing the compound of formula 15 using an oxidizing agent and optionally a catalyst under acid conditions to yield a compound of formula condensing a compound of formula A1 or A2 under acidic conditions, and optionally in the presence of a non-reactive solvent and in the presence of an ammonium reagent, with compound 5 to yield a compound of Formula I. 15. A process according to Claim 14 wherein the oxidizing agent belongs to the group consisting of hydrogen peroxide, oxone, and hydrogen peroxide/acetic acid and the acid is acetic, propionic, methanesulfonic acid or sulfuric acid. 16. A process according to Claim 14 wherein the catalyst is Na2WO4. 17. A process according to Claim 15 wherein the oxidizing agent is oxone or hydrogen peroxide and the acid is sulfuric acid. 18. A process according to Claim 14 wherein Ar is a mono-, di-, or trisubstituted 3-pyridinyl. 19. A process according to Claim 1 wherein R<1> is CH3 or NH2 and R<2> is F, Br or Cl. 20. A process according to Claim 14 wherein Ar is a mono- or di-substituted 3-pyridinyl and the substituents are selected from the group consisting of (a) hydrogen, (b) halo, (c) C1-3alkoxy, (d) C1-3alkylthio, (e) C1-3alkyl, (f) CF3, and (g) CN. 21. A process according to Claim 14 wherein X is chloride. 22. A process according to Claim 14 wherein the solvent/co-solvent mixture is selected from the group consisting of toluene/tetrahydrofuran, tetrahydrofuran/diethylether, toluene/diethylether, tetrahydrofuran/methyl-tert-butylether, toluene/methyl-tert-butylether, toluene/dioxane and tetrahydrofuran/dioxane. 23. A process according to Claim 22 wherein the solvent/co-solvent mixture is toluene/tetrahydrofuran. 24. A process according to Claim 14 wherein the molar ratio of solvent to co-solvent is from about 0.5:4 to about 1:1. 25. A process according to Claim 24 wherein the molar ratio of solvent to co-solvent is from about 1:2 to about 1:1. 26. A process according to Claim 14 employing A1 wherein the acidic condition consists of the addition of acetic or propionic acid, the non-reactive solvent is tetrahydrofuran, dioxane, C1-6alkanol, or toluene and the ammonium reagent is ammonia, ammonium acetate and ammonium propionate. 27. A process according to 14 employing A2 wherein the acidic condition consists of the addition of acetic acid, methanesulfonic acid or propionic acid or a mixture thereof, the non-reactive solvent is tetrahydrofuran, dioxane, C1-6alkanol, or toluene and the ammonium reagent is ammonia, ammonium acetate, ammonium hydroxide and ammonium propionate. 28. A process according to 27 wherein the acidic condition consists of the addition of a mixture of propionic acid and methanesulfonic acid and the ammonium reagent is ammonium hydroxide. 29. A process for making a compound of formula II comprising reacting a compound of formula 12a wherein X is a halogen belonging to the group consisting of iodide, chloride, bromide and fluoride; with magnesium in the presence of a solvent/co-solvent mixture to yield a compound of formula 13a reacting the compound of formula 13a with a compound of formula 9a to yield a compound of formula 15a and oxidizing the compound of formula 15a using an oxidizing agent and optionally a catalyst under acid conditions to yield a compound of formula condensing a compound of formula A1 or A2 wherein R<2> is Cl, under acidic conditions, and optionally in the presence of a non-reactive solvent and in the presence of an ammonium reagent, with compound 5a to yield a compound of Formula II. 30. A process according to Claim 29 wherein X is chloride. 31. A process according to Claim 29 employing A1 wherein the acidic condition consists of the addition of acetic or propionic acid, the non-reactive solvent is tetrahydrofuran, dioxane, C1-6alkanol, or toluene and the ammonium reagent is ammonia, ammonium acetate and ammonium propionate. 32. A process according to 29 employing A2 wherein the acidic condition consists of the addition of acetic acid, methanesulfonic acid or propionic acid or a mixture thereof, the non-reactive solvent is tetrahydrofuran, dioxane, C1-6alkanol, or toluene and the ammonium reagent is ammonia, ammonium acetate, ammonium hydroxide and ammonium propionate. |
