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 degrees C. Compound 6 is prepared from nitrophenyl carbamate 14a and methylamine or directly from 5-aminoimidazole-4-carboxamide (13) and either methyl isocyanate or N-methylcarbamoyl chloride. Temozolomide (4) is also prepared from 8-cyano-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (7) by hydrolysis to the hydrochloride salt of 4 in 10 M hydrochloric acid. Compound 7is prepared from either 5-diazoimidazole-4-carbonitrile (28) and methyl isocyanate or by diazotization of 5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile (25). Attempts to cyclize 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3) with phosgene or phosgene equivalents were unsuccessful: only 2-azahypoxanthine (11) was isolated.

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Sisomicin, the principal antibiotic produced in the fermentation of Micromonospora inyoensis, has been shown to be 0-2,6-diamino-2,3,4,6-tetradeoxy-a-D-gZycero-hex-4-enopyranosyl(l-4)-0-[3-deoxy-4-C-methyl-3-(methylamino)-/?-L-arabinopyranosyl(l-6)]-2-deoxy-D-streptamine (1). Sisomicin contains a novel unsaturated sugar unit, not previously encountered in any aminocyclitol antibiotic.Submerged fermentations of Micromonospora inyoensis (NRRL 3292) produce sisomicin,1 a novel unsaturated aminocyclitol antibiotic2•3 having broad spectrum antibacterial activity.4 Sisomicin is the major component of the crude antibiotic complex, which was isolated from the fermentation broth by ion-exchange chromatography.3 Column chromatography of the crude antibiotic on silica Preparative Routes to 4-Amino-4-deoxy-D-galactose1

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