A new route to the synthesis of pyrazole and pyrimidine C-nucleoside derivatives

Abstract

A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, which involves as the key step a metal promoted reaction of β-D-ribofuranosyl ketoesters with alkyl cyanoformates is described. 2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl cyanide 1 reacts with α-bromoesters, in the presence of zinc dust, to give β-D-ribofuranosyl-enaminoesters 2 which are hydrolysed with 1N hydrochloric acid to β-ketoesters 3. The reactions of β-ketoesters 3 with alkyl cyanoformates, in the presence of tin(IV) chloride or of catalytic amounts of metal acetylacetonates, afford β-D-ribofuranosyl enaminoketoesters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides ( 6,7).