Synthesis and Chemoselective N- and O-Alkylation of Thiadiazolopyrimidine Nucleosides and Uridines

Abstract

A facile and selective N- or O-alkylation of 4-β-d-ribofuranosyl[1,2,5]thiadiazolo[3,4-d]pyrmidine-5,7(4H,6H)-dione as well as uridines was accomplished via bimolecular base alkylation or bimolecular nucleophilic substitution reaction controlled by the reagents. In the presence of 18-crown-6 and anhydrous K2CO3, the highly chemoselective O-methylation was performed using dimethyl carbonate (DMC) in DMF at 22-25 ˚C, i.e. the 2′,3′-O-isopropylidene derivatives of 4-β-d-ribofurnosyl[1,2,5]thiadiazolo[3,4-d]pyrmidine-5,7(4H,6H)-dione, uridine, and 5-bromouridine, underwent only the primary alcoholic O-methylation reaction without affecting the NH group of the pyrimidne ring. The novel N-alkylated derivatives of 4-β-d-ribofurnosyl[1,2,5]thiadiazolo[3,4-d]pyrmidine-5,7(4H,6H)-dione were also prepared using the appropriate alkyl halides with a base.