SYNTHESIS OF 6-AMINO-1-(BETA-D-RIBOFURANOSYL)-1H-PYRAZOLO[3,4-D]-1,3-OXAZIN-4-ONE, AN ISOSTERE OF OXANOSINE, AND THE GUANOSINE ANALOG 6-AMINO-1-(BETA-D-RIBOFURANOSYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4(5H)-ONE VIA RING-CLOSURE OF PYRAZOLE-5-THIOUREIDO INTERMEDIATES

6‐Amino‐1‐(β‐D‐ribofuranosyl)‐1H‐pyrazolo[3,4‐d]‐1,3‐oxazin‐4‐one (4), an isostere of the nucleoside antibiotic oxanosine has been synthesized from ethyl 5‐amino‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)pyrazole‐4‐carboxylate (6). Treatment of 6 with ethoxycarbonyl isothiocyanate in acetone gave the 5‐thioureido derivative 7, which on methylation with methyl iodide afforded ethyl 1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)‐5‐[(N'‐ethoxycarbonyl‐S‐methylisothiocarbamoyl)amino]pyrazole‐4‐carboxylate (8). Ring closure of 8 under alkaline media furnished 6‐amino‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)‐1H‐pyrazolo[3,4‐d]‐1,3‐oxazin‐4‐one (10), which on deisopropylidenation afforded 4 in good yield. 6‐Amino‐1‐(β‐D‐ribofuranosyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (5) has also been synthesized from the AICA riboside congener 5‐amino‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)pyrazole‐4‐carboxamide (12). Treatment of 12 with benzoyl isothiocyanate, and subsequent methylation of the reaction product with methyl iodide gave 1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)‐5‐[(N'‐benzoyl‐S‐methylisothiocarbamoyl)amino]pyrazole‐4‐carboxamide (15). Base mediated cyclization of 15 gave 6‐amino‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (14). Deisopropylidenation of 14 with aqueous trifluoroacetic acid afforded 5 in good yield. Compound 4 was devoid of any significant antiviral or antitumor activity in culture. Copyright © 1990 Journal of Heterocyclic Chemistry