Pyrazolopyrimidine nucleosides. Part III. Synthesis of 1- and 2-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidines from pyrazole nucleo-side derivatives

Abstract

The trimethylsilyl derivative (6) of 3-(3,3-dimethyl-1-triazeno)pyrazole-4-carboxamide (4) was condensed with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide (7) to give a mixture of nucleosides that were subsequently established as isomers rather than anomers. Removal of the blocking groups from one of the isomers furnished 5-(3,3-di-methyl-1-triazeno)-1-(β-D-ribofuranosyl)pyrazole-4-carboxamide (12) which was catalytically hydrogenated to afford the pyrazole analogue, 5-amino-1-(β-D-ribofuranosyl)pyrazole-4-carboxamide (13), of AICA riboside. Ring closure of (13) with formic acid-acetic anhydride followed by treatment with base furnished a mixture of nucleosides which were separated and characterized as 1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (16; allopurinol riboside) and 6-methyl-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (17). The other isomer (8) furnished 3-(3,3-dimethyl-1-triazeno)-1-(β-D-ribofuranosyl)pyrazole-4-carboxamide (11) which was converted by a similar series of reactions into 2-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (15).