Synthesis of β‐D‐ribo‐ and 2′‐deoxy‐β‐D‐ribofuranosyl derivatives of 6‐aminopyrazolo[4,3‐c]pyridin‐4(5H)‐one by a ring closure of pyrazole nucleoside precursors

Abstract

Abstract6‐Amino‐1‐(2‐deoxy‐β‐D‐erthro‐pentofuranosyl)pyrazolo[4,3‐c]pyridin‐4(5H)‐one (5), as well as 2‐(β‐D‐ribofuranosyl)‐ and 2‐(2‐deoxy‐β‐D‐ribofuranosyl)‐ derivatives of 6‐aminopyrazolo[4,3‐c]pyridin‐4(5H)‐one (18 and 22, respectively) have been synthesized by a base‐catalyzed ring closure of pyrazole nucleoside precursors. Glycosylation of the sodium salt of methyl 3(5)‐cyanomethylpyrazole‐4‐carboxylate (6) with 1‐chloro‐2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythro‐pentofuranose (8) provided the corresponding N‐1 and N‐2 glycosyl derivatives (9 and 10, respectively). Debenzoylation of 9 and 10 with sodium methoxide gave deprotected nucleosides 14 and 16, respectively. Further ammonolysis of 14 and 16 afforded 5(or 3)‐cyanomethyl‐1‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)pyrazole‐4‐carboxamide (15 and 17, respectively). Ring closure of 15 and 17 in the presence of sodium carbonate gave 5 and 22, respectively. By contrast, glycosylation of the sodium salt of 6 with 2,3,5‐tri‐O‐benzoyl‐D‐ribofuranosyl bromide (11) or the persilylated 6 with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose gave mainly the N‐2 glycosylated derivative 13, which on ammonolysis and ring closure furnished 18. Phosphorylation of 18 gave 6‐amino‐2‐β‐D‐ribofuranosylpyrazolo[4,3‐c]pyridin‐4(5H)‐one 5′‐phosphate (19). The site of glycosylation and the anomeric configuration of these nucleosides have been assigned on the basis of 1H nmr and uv spectral characteristics and by single‐crystal X‐ray analysis of 16.