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US 10,865,209 B2Granted
Process for preparing temozolomide and an intermediary
AssigneeCristalia Produtos Quimicos Farmaceuticos Ltda.
InventorsOgari Pacheco, Vincenzo De Sio, Murilo Massoni, Leandro Camargo
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Abstract
The present invention relates to an efficient and industrially advantageous process for preparing temozolomide and the carbamoyl-AICA intermediate through the use of N-methyl carbamoylimidazole in a good overall yield and high purity.
Claims21
A process for preparing temozolomide, comprising the following steps:
- (a) Reacting AICA base with N-methyl carbamoylimidazole to provide carbamoyl-AICA;
- (b) Reacting carbamoyl-AICA with an alkali or alkaline earth metal nitrite in the presence of an acid to provide temozolomide.
A process for preparing temozolomide, comprising the following steps:
- (a) Reacting carbonyldiimidazole with methylamine hydrochloride in a mixture of acetonitrile and dimethylformamide to obtain N-methylcarbamoylimidazole;
- (b) Reacting AICA base with N-methyl carbamoylimidazole in an aprotic polar organic solvent to provide carbamoyl-AICA;
- (c) Reacting carbamoyl-AICA with sodium nitrite, added to the reaction medium in solid form, in the presence of a tartaric acid solution and, at the end of the reaction, heating the reaction mixture to 60° C. and filtering to provide temozolomide and azahypoxanthine in a ratio of 60:40;
- (d) Purifying temozolomide through a chromatographic column filled with adsorbent polymer resin containing a carbon capsule coupled to the end of the column to provide a clarified solution of temozolomide, and crystallizing temozolomide from the clarified solution.
1 more element
A process for preparing carbamoyl-AICA comprising the reaction between AICA base and N-methyl carbamoylimidazole in an aprotic polar organic solvent.
Dependencies are inferred from the claim text.