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

Abstract

2,3,5-Tri- O-benzoyl-β- d-ribofuranosyl cyanide reacts with methyl acetoacetate and diethyl malonate in the presence of stoichiometric amounts of SnCl 4 to give a β- d-ribofuranosyl-enaminoketoester and a β- d-ribofuranosyl-enaminodiester, respectively. The β- 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-β- d-ribofuranosyl)-2-acetyl propanoate obtained in good yield together with small amounts of its α-anomer. The reactions of the β-anomer with hydrazine, methyl- and phenylhydrazine, carried out under controlled experimental conditions, afforded the pyrazole C-nucleosides in good yields as β-anomers.