The present invention relates to a process for preparing temozolomide.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an X-ray powder diffraction pattern of temozolomide prepared according to Example 5.
FIG. 2 is a differential scanning calorimetry curve of temozolomide prepared according to Example 5.
FIG. 3 is an infrared absorption spectrum of temozolomide prepared according to Example 5.
Claims
1. A process for preparing temozolomide, comprising pyrolyzing N′-methyl-N,N-diphenyl urea to form a vapor comprising methyl isocyanate, and reacting formed methyl isocyanate with 5-diazo-5H-imidazole-4-carboxylic acid amide.
2. The process of claim 1, wherein a vapor comprising methyl isocyanate is condensed into a solution comprising 5-diazo-5H-imidazole-4-carboxylic acid amide.
3. The process of claim 1, wherein 5-diazo-5H-imidazole-4-carboxylic acid amide is in a solution comprising dimethylsulfoxide, N,N-dimethylformamide, or N,N-dimethylacetamide as a solvent.
4. The process of claim 1, wherein pyrolyzing occurs at temperatures between about 200° C. to about 300° C.
5. The process of claim 1, wherein a weight of N′-methyl-N,N-diphenyl urea that is pyrolyzed is about 3 to about 8 times the weight of 5-diazo-5H-imidazole-4-carboxylic acid amide.
6. Temozolomide obtained according to the process of claim 1, containing less than about 0.15% by weight of any one or more of:
7. Temozolomide obtained according to the process of claim 1, having D10 less than about 10 microns; D50 less than about 20 microns; and D90 less than about 100 microns.
8. A process for preparing temozolomide, comprising pyrolyzing N′-methyl-N,N-diphenyl urea to form a vapor comprising methyl isocyanate, and reacting condensed methyl isocyanate with a solution comprising 5-diazo-5H-imidazole-4-carboxylic acid amide and dimethylsulfoxide, N,N-dimethylformamide, or N,N-dimethylacetamide as a solvent.
9. The process of claim 8, wherein pyrolyzing occurs at temperatures between about 200° C. to about 300° C.
10. The process of claim 8, wherein a weight of N′-methyl-N,N-diphenyl urea that is pyrolyzed is about 3 to about 8 times the weight of 5-diazo-5H-imidazole-4-carboxylic acid amide.
11. The process of claim 8, wherein reacting occurs at temperatures about 0° C. to about 100° C.
12. The process of claim 8, wherein reacting occurs at temperatures about 25° C. to about 35° C.
13. A process for preparing N′-methyl-N,N-diphenyl urea, comprising reacting diphenyl carbomyl chloride with methylamine in the presence of water.
14. The process of claim 13, wherein methylamine is provided in the form of an aqueous solution.
15. The process of claim 13, wherein methylamine is provided in an aqueous solution at a concentration about 30 to about 45 percent by weight.
16. The process of claim 13, wherein reacting occurs at temperatures between about 70° C. and about 80° C.
Patent Application
20070225496
