A FACILE SYNTHESIS OF CERTAIN 4-SUBSTITUTED AND 4,5-DISUBSTITUTED 1-BETA-D-RIBOFURANOSYLPYRAZOLES

A number of pyrazole ribonucleosides, structurally related to AICA riboside and ribavirin have been prepared and evaluated for their biological activity in vitro. Deisopropylidenation of 5‐amino‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (6) with aqueous trifluoroacetic acid gave 5‐amino‐1‐(β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (7). Conventional transformation of the carbonitrile function of 7 gave the AICA riboside congener (2) and related 5‐amino‐1‐(β‐D‐ribofuranosyl)‐pyrazoles (8–10). Acetylation of 7 at low temperature gave the versatile intermediate 5‐amino‐1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (15). Non‐aqueous diazotization of 15 with isoamylnitrite in dibromomethane or diiodomethane gave the corresponding C5‐bromo 13 and C5‐iodo 16 derivatives. Compounds 13 and 16 were subsequently transformed into 5‐bromo‐1‐(β‐D‐ribofuranosyl)pyrazole‐4‐carboxamide (11) and the 5‐iodo analog 25. However, a similar nonaqueous diazotization of 15 in dichloromethane afforded the deaminated product 1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (22). Treatment of 22 with ammonium hydroxide/hydrogen peroxide gave the ribavirin congener 1‐(β‐D‐ribofuranosyl)pyrazole‐4‐carboxamide (18). Similar treatment of 22 with hydrogen sulfide in pyridine or hydroxylamine in ethanol gave the 4‐thiocarboxamide 19 and 4‐carboxamidoxime 20 derivatives, respectively. Catalytic hydrogenation of 20 afforded 1[β‐D‐ribofuranosyl)pyrazole‐4‐carboxamidine (21). These pyrazole nucleosides are devoid of any significant antiviral or antitumor activity in vitro. Copyright © 1990 Journal of Heterocyclic Chemistry