Convenient Synthesis of 3‐Deazapurine Nucleosides (3‐Deazainosine, 3‐Deazaadenosine and 3‐Deazaguanosine) Using Inosine as a Starting Material

Abstract

A convenient synthetic method for preparing 3‐deazapurine nucleosides (3‐deazainosine, 3‐deazaadenosine, and 3‐deazaguanosine) from inosine via a 5‐ethynyl‐1‐β‐D‐ribofuranosylimidazole‐4‐carboxamide (EICAR) derivative, which is a key intermediate, is described. A large‐scale synthesis of an EICAR derivative starting from inosine was achieved in six steps via dinitrophenylation at the N1 position followed by ring opening, iodination of the resulting 5‐amino group, and a palladium‐catalyzed cross‐coupling reaction. The resulting EICAR derivative was then converted into 3‐deazainosine, 3‐deazaadenosine, and 3‐deazaguanosine. This route enabled us to synthesize 3‐deazapurine nucleosides conveniently in good yields. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 5‐ethynyl‐1‐β‐D‐ribofuranosylimidazole‐4‐carboxamide (EICAR) derivative 6 Basic Protocol 2: Preparation of 3‐deazapurine nucleosides 8, 11, and 14