Process for the preparation of carboxamide compounds

1. A process for preparing a 5H-dibenz[b,f]azepine-5-carboxamide of the formula:

wherein R 1 , R 2 , R 3 and R 4 are the same or different and can be hydrogen, halogen, nitro, cyano, carboxyl, R, —CO(R), —OCO(R), —O(R), —N(R) 2 , —CON(R) 2 , and —COO(R), wherein R is selected from the group consisting of C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 alkenyl, C 5 -C 10 cycloalkenyl, C 2 -C 10 alkynyl, and C 6 -C 20 aryl, and wherein the two R groups of —N(R) 2 and —CON(R) 2 can be the same or different, and wherein R 2 and R 3 can together form a bond; the process comprising reacting a 5H-dibenz[b,f]azepine of the formula

wherein R 1 , R 2 , R 3 and R 4 have the aforementioned meanings, with one or more alkali or alkaline-earth cyanates and in the presence of one or more unsaturated dicarboxylic acid.

2. The process of claim 1 , wherein R 1 , R 2 , R 3 and R 4 are the same or different and can be hydrogen, halogen, R, —CO(R), —OCO(R), —O(R), —N(R) 2 , and —CON(R) 2 , and wherein R 2 and R 3 can together form a bond.

3. The process of claim 1 , wherein R 1 is hydrogen, R 2 and R 3 together form a bond and R 4 is —O(R) wherein R is a C 1 -C 10 alkyl.

4. The process of claim 1 , wherein the reaction is performed in a solvent.

5. The process of claim 4 , wherein the solvent is selected from the group consisting of an aromatic solvent, a halogenated hydrocarbon solvent and mixtures thereof.

6. The process of claim 5 , wherein the aromatic solvent is selected from the group consisting of toluene, benzene, xylene and mixtures thereof.

7. The process according to claim 5 , wherein the halogenated hydrocarbon solvent is an aliphatic chlorinated solvent selected from the group consisting of methylene chloride, ethylene chloride, trichloroethylene, chloroform and mixtures thereof.

8. The process of claim 1 , wherein the one or more alkali or alkaline-earth cyanates are selected from the group consisting of sodium cyanate, potassium cyanate and mixtures thereof.

9. The process of claim 1 , wherein the one or more unsaturated dicarboxylic acids comprise a substituted or unsubstituted C 3 to about C 44 unsaturated dicarboxylic acid.

10. The process of claim 1 , wherein the one or more unsaturated dicarboxylic acids comprise a substituted or unsubstituted C 3 to about C 34 unsaturated dicarboxylic acid.

11. The process of claim 1 , wherein the one or more unsaturated dicarboxylic acids are selected from the group consisting of maleic acid, fumaric acid and mixtures thereof.

12. The process of claim 1 , further comprising purifying the product 5H-dibenz[b,f]azepine-5-carboxamide.

13. A process for preparing a 5H-dibenz[b,f]azepine-5-carboxamide of the formula:

wherein R 5 can be hydrogen or O(R), wherein R is selected from the group consisting of C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, C 2 -C 10 alkenyl, C 5 -C 10 cycloalkenyl, C 2 -C 10 alkynyl, and C 6 -C 20 aryl, is provided comprising reacting a 5H-dibenz[b,f]azepine of the formula:

with one or more alkali or alkaline-earth cyanates and in the presence of one or more unsaturated dicarboxylic acids.

14. The process of claim 13 , wherein the reaction is performed in a solvent.

15. The process of claim 14 , wherein the solvent is selected from the group consisting of an aromatic solvent, a halogenated hydrocarbon solvent and mixtures thereof.

16. The process of claim 13 , wherein the one or more alkali or alkaline-earth cyanates are selected from the group consisting of sodium cyanate, potassium cyanate and mixtures thereof; the one or more unsaturated dicarboxylic acids are selected from the group consisting of maleic acid, fumaric acid and mixtures thereof and the reaction is performed in a solvent.

17. The process of claim 13 , wherein R 5 is —O(R) wherein R is a C 1 -C 10 alkyl.

18. The process of claim 13 , wherein R 5 is —OCH 3 .

19. The process of claim 17 , further comprising hydrolyzing the 5H-dibenz[b,f]azepine-5 -carboxamide to produce oxcarbazepine.

20. A process for the preparation of oxcarbazepine of Formula (I):

comprising (a) reacting a 5H-dibenz[b,f]azepine of formula II:

wherein R 5 is O(R), wherein R is a C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, with one or more alkali or alkaline-earth cyanates and in the presence of one or more unsaturated dicarboxylic acids to provide a 5H-dibenz[b,f]azepine-5-carboxamide intermediate; and (b) hydrolyzing the 5H-dibenz[b,f]azepine-5-carboxamide intermediate to provide oxcarbazepine.

21. The process of claim 20 , wherein the one or more alkali or alkaline-earth cyanates are selected from the group consisting of sodium cyanate, potassium cyanate and mixtures thereof.

22. The process of claim 20 , wherein the one or more unsaturated dicarboxylic acids comprise a substituted or unsubstituted C 3 to about C 44 unsaturated dicarboxylic acid.

23. The process of claim 20 , wherein the one or more unsaturated dicarboxylic acids are selected from the group consisting of maleic acid, fumaric acid and mixtures thereof.

24. The process of claim 20 , wherein the reaction is performed in a solvent.

25. The process of claim 24 , wherein the solvent is selected from the group consisting of an aromatic solvent, a halogenated hydrocarbon solvent and mixtures thereof.

26. The process of claim 24 , wherein the solvent is selected from the group consisting of methylene chloride, ethylene chloride, trichloroethylene, chloroform and mixtures thereof.

27. The process of claim 24 , wherein the solvent is selected from the group consisting of toluene, benzene, xylene and mixtures thereof.

28. The process of claim 20 , wherein the 5H-dibenz[b,f]azepine-5-carboxamide intermediate is hydrolyzed with a dilute acid.

29. The process of claim 28 , wherein the dilute acid is dilute hydrochloric acid.

30. The process of claim 20 , further comprising purifying the oxcarbazepine.

31. The process of claim 30 , wherein the oxcarbazepine is purified by recrystallization.

32. The process of claim 20 , wherein the step of hydrolyzing comprises hydrolyzing the 5H-dibenz[b,f]azepine-5-carboxamide intermediate to oxcarbazepine in a single phase system.

33. The process of claim 20 , wherein the step of hydrolyzing comprises hydrolyzing the 5H-dibenz[b,f]azepine-5-carboxamide intermediate to oxcarbazepine in a biphasic system chosen such that the oxcarbazepine is substantially insoluble in both phases, whereas the by-products or impurities are soluble in at least one of the phases.

34. The process of claim 33 , wherein the biphasic system comprises an organic phase and an aqueous phase.