C-nucleoside studies. Part 20. Synthesis of some pyrazolo[4,3-d]pyrimidine acyclonucleosides related to (S)-(2,3-dihydroxypropyl)adenine; a direct method for double functionalization of the pyrazole ring

Abstract

Treatment of 3(5)-alkylpyrazoles with ammonium nitrate and trifluoroacetic anhydride in trifluoroacetic acid gives 3-alkyl-1,4-dinitropyrazoles directly. This procedure, in conjunction with cine-substitution, offers a direct route for double functionalisation of the pyrazole ring.

3(5)-Cyano-5(3)-[(S)-2,3-diacetoxypropyl]-4-nitropyrazole (13), prepared in this way, was elaborated into 5-amino-3-[(S)-2,3-dihydroxypropyl]-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (5), 7-amino-3-[(S)-2,3-dihydroxypropyl]-1H-6-methylpyrazolo[4,3-d]pyrimidin-5(6H)-one (6), its Ndemethyl analogue (7), and 4-amino-5-carbamoyl-3-[(S)-2,3-dihydroxypropyl]pyrazole (8), all of which are C-nucleoside analogues of the antiviral agent (S)-9-(2,3-dihydroxypropyl)adenine (4).