Claims
- 1. Ondansetron hydrochloride dihydrate having a purity of at least 99.0%.
- 2. Ondansetron hydrochloride dihydrate having a purity of at least 99.5%.
- 3. Ondansetron hydrochloride dihydrate having a purity of at least 99.9%.
- 4. A process for preparing dimethylamino-methyl-carbazolone comprising the steps of:
a) preparing a solution of methyl-carbazolone having the formula: 4b) heating the solution in the presence of dimethylamine hydrochloride and paraformaldehyde; c) basifying the solution to form a precipitate; d) separating the precipitate from the solution; e) drying the precipitate.
- 5. The process according to claim 4, wherein R is methyl.
- 6. The process according to claim 4, wherein the heating step is performed at a temperature of about 70° C. to about 100° C.
- 7. The process according to claim 4, wherein the heating step is performed at a temperature of about 80° C. to about 90° C.
- 8. The process according to claim 4, wherein the heating step is performed for about 6 to about 24 hours.
- 9. The process according to claim 4, wherein the heating step is performed for about 6 to about 12 hours.
- 10. The process according to claim 4, wherein the heating step is performed in acetic acid.
- 11. The process according to claim 4, wherein about one equivalent methyl-carbazolone is heated in the presence of about 1.1 to about 1.5 equivalents of dimethylamine hydrochloride and paraformaldehyde.
- 12. The process according to claim 4, wherein about one equivalent methyl-carbazolone is heated in the presence of about 1.2 equivalents of dimethylamine hydrochloride and formaldehyde.
- 13. The process according to claim 4, wherein about one equivalent methyl-carbazolone is heated in the presence of about 1.1 to about 1.5 equivalents of dimethylamine hydrochloride and formaldehyde.
- 14. The process according to claim 4, wherein about one equivalent methyl-carbazolone is heated in the presence of about 1.2 equivalents of dimethylamine hydrochloride and formaldehyde.
- 15. The process according to claim 4, wherein about one equivalent methyl-carbazolone is heated in the presence of about 4 to about 6 volumes of acetic acid.
- 16. The process according to claim 4, wherein about one equivalent methyl-carbazolone is heated in the presence of about 4 volumes of acetic acid.
- 17. The process according to claim 4, wherein the solution of methyl-carbazolone is basified by about 45% sodium hydroxide.
- 18. The process according to claim 17, wherein the solution is basified to a pH of about 13 to about 14.
- 19. The process according to claim 17 or 18, wherein the basifying step is performed in the presence of 10% celite.
- 20. A process for preparing ondansetron base, comprising the steps of:
a) preparing a solution of methyl-imidazole and dimethylamino-methyl-carbazolone of the formula 5b) heating the solution; c) removing a precipitate containing ondasetron base from the solution; d) washing the precipitate; e) drying precipitate to obtain ondansetron base.
- 21. The process according to claim 20, wherein the solution is prepared by adding about 4 to about 6 equivalents methyl-imidazole to one equivalent dimethylamino-methyl-carbazolone.
- 22. The process according to claim 20, wherein the solution is prepared by adding about 5 equivalents methyl-imidazole to one equivalent dimethylamino-methyl-carbazolone.
- 23. The process according to claim 20, wherein the solution is prepared in the presence of 10% celite.
- 24. The process according to claim 20, further comprising the step of:
recrystallizing ondansetron base.
- 25. The process according to claim 24, wherein the recrystallizing step is performed in the presence of activated carbon and methanol.
- 26. A process of preparing pure ondansetron hydrochloride dihydrate comprising the steps of:
a) preparing a solution of ondansetron base; b) acidifying the solution with hydrogen chloride to form a precipitate; c) washing the precipitate; and d) crystallizing pure ondansetron hydrochloride dihydrate.
- 27. The process according to claim 26 wherein about 3 to about 7 volumes of water is added to ondansetron base to prepare a solution of ondansetron base.
- 28. The process according to claim 26 wherein about 5 volumes of water is added to ondansetron base to prepare a solution of ondansetron base.
- 29. The process according to claim 26 wherein about 1.0 to about 1.4 equivalents of about 32% (v:v) hydrochloric acid is added to acidify the solution to induce precipitation.
- 30. The process according to claim 26 wherein about 1.1 equivalents of about 32% (v:v) hydrochloric acid is added to acidify the solution to induce precipitation.
- 31. The process of claims 29 or 30, wherein the solution is acidified to a pH about 1 to about 4.
- 32. The process of claims 29 or 30, wherein the solution is acidified to a pH about 3.
- 33. The process according to claim 26, wherein the precipitate is washed with about 5 to about 15 ml of isopropanol.
- 34. The process according to claim 26, wherein the precipitate is washed with about 10 ml of isopropanol.
- 35. The process according to claim 26, wherein the crystallizing step is achieved by adding about 3 to about 5 volumes of water to induce crystallization.
- 36. The process according to claim 26, wherein the crystallizing step is achieved by adding about 4 volumes of water to induce crystallization.
- 37. The process according to claim 26, wherein the crystallization step is repeated two times.
- 38. The process according to claim 26, wherein the crystallizing step is achieved in the presence of activated carbon.
- 39. The process according to claim 36, wherein the activated carbon is selected from the group consisting of SX-2, CA-1, CXV and SX-1.
- 40. The process according to claim 39, wherein the activated carbon is about 5 to about 15% SX-1.
- 41. The process according to claim 39, wherein the activated carbon is about 5 to about 10% SX-1.
- 42. Ondansetron hydrochloride dihydrate as prepared in accordance with a process of claim 26, wherein the ondansetron hydrochloride dihydrate has a purity of at least about 99.0%.
- 43. Ondansetron hydrochloride dihydrate as prepared in accordance with a process of claim 26, wherein the ondansetron hydrochloride dihydrate have a purity of at least about 99.5%.
- 44. Ondansetron hydrochloride dihydrate as prepared in accordance with a process of claim 26, wherein the ondansetron hydrochloride dihydrate has a purity of at least about 99.9%.
- 45. A pharmaceutical formulation comprising ondansetron hydrochloride dihydrate as prepared in accordance with a process of claim 26, wherein the ondansetron hydrochloride dihydrate has a purity of at least about 99.0%.
- 46. A pharmaceutical formulation comprising ondansetron hydrochloride dihydrate as prepared in accordance with a process of claim 26, wherein the ondansetron hydrochloride dihydrate has a purity of at least about 99.5%.
- 47. A pharmaceutical formulation comprising ondansetron hydrochloride dihydrate as prepared in accordance with a process of claim 26, wherein the ondansetron hydrochloride dihydrate has a purity of at least about 99.9%.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of Provisional Application Ser. No. 60/261,051, filed Jan. 11, 2001, the disclosure of which is incorporated by reference in its entirety herein.
Provisional Applications (1)
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Number |
Date |
Country |
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60261051 |
Jan 2001 |
US |