C-nucleoside studies. Part 14. A new synthesis of pyrazofurin

Abstract

Treatment of 3-cyano-4-nitro-5-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (4) with benzyl bromide and triethylamine gave as major product the 1-benzyl-5-cyano-isomer (5), whilst similar treatment of 5-cyano-3-methyl-4-nitropyrazole (7) gave exclusively 1-benzyl-3-cyano-5-methyl-4-nitropyrazole (8). This was converted into 4-amino-1-benzyl-3-carboxamido-5-methylpyrazole (10); attempts to convert (10) into a 4-hydroxypyrazole via the diazonium salt were unsuccessful, but photolysis of the diazonium salt (11) in aqueous trifluoroacetic acid–dioxan gave 1-benzyl-3-carboxamido-5-methylpyrazole (13) in 67% yield.

Treatment of 4-amino-3-cyano-5-methylpyrazole (14) with nitrous acid and subsequent neutralisation gave a diazopyrazole which on photolysis in aqueous acetone yielded 3-cyano-4-hydroxy-5-methylpyrazole (16) in 79% overall yield. Application of the same sequence to 4-amino-3-cyano-5-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-pyrazole (2) gave the 4-hydroxy-compound (17)(87% overall), which was converted in two steps into pyrazofurin (1).