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

A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, which involves as the key step a metal promoted reaction of beta-D-ribofuranosyl ketoesters with alkyl cyanoformates is described. 2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl cyanide 1 reacts with alpha-bromoesters, in the presence of zinc dust, to give beta-D-ribofuranosyl-enaminoesters 2 which are hydrolysed with IN hydrochloric acid to beta-ketoesters 3. The reactions of beta-ketoesters 3 with alkyl cyanoformates, in the presence of tin(IV) chloride or of catalytic amounts of metal acetylacetonates, afford beta-D-ribofuranosyl enaminoketoesters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides (6,7). (C) 1999 Elsevier Science Ltd. All rights reserved.