Hydrazine → HCID 178510603, compound

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Reaction Steps

Methyl 1,2,4-triazole-3-carboxylate and 3-cyano-1,2,4-triazole are precursors in alternative synthetic routes to 1,2,4-triazole nucleosides of the invention. The former compound can be conventionally prepared by oxidation of 3-methyl-1,2,4-triazole followed by esterification of the resulting acid according to the procedure of Cipens and Grinsteins' Latvijas PSR Zinatnu Akad. Vestis., Kim. Ser. (1965) (2) 204-08 (see C.A. 63, 13243, 1965). 3-cyano-1,2,4-triazole is prepared by a multi-step synthesis reported by Cipens et al., supra, or more conveniently, by the addition reaction of cyanogen and hydrazine to form 1-cyanoformimidic acid hydrazide, followed by acid-catalyzed ring closure in triethylorthoformate to the 3-cyano compound. By one route, the trimethylsilyl derivative of the methyl 1,2,4-triazole-3-carboxylate is formed in quantitative yield by reaction with hexamethyldisilazane under reflux and reacted with an appropriate O-acylated halo sugar GX to form, for example, a mixture of O-benzoylated 1-(β -D-ribofuranosyl)-1,2,4-triazole-3-carboxylic acid methyle ester and 5-carboxylic acid methyl ester, i.e.: ##STR4## wherein Bz is benzoyl. The 3-carboxylic acid methyl ester is separated by fractional crystallization or, preferably, by column chromatography over silica gel. Debenzoylation and aminolysis gives the 1-(β -D-ribofuranosyl)-1,2,4-triazole-3-carboxamide.

Provenance & Evidence