Antitumor imidazotetrazines. 35. New synthetic routes to the antitumor drug temozolomide

…, T Chan, D DiBenedetto, Z Ding, D Gala…

Index: Wang, Yongfeng; Stevens, Malcolm F. G.; Chan, Tze-Ming; DiBenedetto, Donald; Ding, Zhe-Xing; Gala, Dinesh; Hou, Donald; Kugelman, Max; Leong, William; Kuo, Shen-Chun; Mas, Janet L.; Schumacher, Doris P.; Shutts, Bruce P.; Smith, Lyman; Zhan, Zheng-Yun J.; Thomson, William T. Journal of Organic Chemistry, 1997 , vol. 62, # 21 p. 7288 - 7294

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Citation Number: 31

Abstract

Three new pathways to the antitumor drug temozolomide (4) have been explored via intermediates 3, 6, and 7. The key intermediate 5-amino-1-(N-methylcarbamoyl) imidazole-4- carboxamide (6) has been successfully converted to 4 in 45% yield by employing sodium nitrite in aqueous tartaric acid at 0-5° C. Compound 6 is prepared from nitrophenyl carbamate 14a and methylamine or directly from 5-aminoimidazole-4-carboxamide (13) ...