Antitumour imidazotetrazines. Part 12. Reactions of mitozolomide and its 3-alkyl congeners with oxygen, nitrogen, halogen, and carbon nucleophiles
Abstract
Mitozolomide (1) and its 3-alkyl congeners ring-open in aqueous sodium carbonate to form 5-(3-alkyltriazen-1-yl)imidazole-4-carboxamides. The 3-methyl and 3-ethyl analogues of mitozolomide decompose in alcohols to form 2-azahypoxanthine and 5-amino-1-alkoxycarbonylimidazole-4-carboxamides. In hydrazine hydrate mitozolomide yields, principally, 5-azidoimidazole-4-carboxamide, whereas the 3-alkyl-derivatives form 5-amino-4-carbamoylimidazole-1-carbohydrazide.
5-Diazoimidazole-4-carboxamide, generated by thermolysis of mitozolomide in acetic acid or pyridine, can be trapped by reactive methylenic ketones, nitriles or esters to afford imidazo[1,2,4]triazines.