Synthesis of pyrazole C-nucleosides via Tin(IV) chloride-promoted reactions of beta-D-ribofuranosyl cyanide with beta-dicarbonyl compounds

2,3,5-Tri-O-benzoyl-beta-D-ribofuranosyl cyanide reacts with methyl acetoacetate and diethyl malonate in the presence of stoichiometric amounts of SnCl4 to give a beta-D-ribofuranosyl-enaminoketoester and a beta-D-ribofuranosyl-enaminodiester, respectively. The beta-D-ribofuranosyl-enaminoketoester was debenzoylated, treated with 2,2-dimethoxypropane and tert-butyl-dimethylsilyl chloride to give the methyl 3-amino-3-(5'-O-tert-butyldimethylsilyl-2',3'-O-isopropylidene-beta-D-ribofuranosyl)-2-acetyl propanoate obtained in good yield together with small amounts of its alpha-anomer. The reactions of the beta-anomer with hydrazine, methyl- and phenylhydrazine carried out under controlled experimental conditions, afforded the pyrazole C-nucleosides in good yields as beta-anomers. (C) 2002 Elsevier Science Ltd. All rights reserved.