Solid‐phase synthetic method for N‐alkyl‐7‐alkylamino‐2‐aryloxazolo[5,4‐d]pyrimidine‐5‐carboxamide derivatives

Abstract

AbstractOxazolo[5,4‐d]pyrimidine derivatives have been reported to exhibit interesting biological activities. Herein, we described a solid‐phase synthetic method to produce N‐alkyl‐7‐alkylamino‐2‐aryloxazolo[5,4‐d]pyrimidine‐5‐carboxamide derivatives. The strategy consists of loading the template compounds (i.e., 2‐aryl‐6,7‐dihydrooxazolo[5,4‐d]pyrimidin‐7‐one‐5‐carboxylic acids) onto aminated acid‐sensitive methoxybenzaldehyde (AMEBA) resins, the subsequent benzotriazol‐1‐yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP)‐mediated direct amination with primary/secondary amines, and the final cleavage from the solid support to afford the target compounds. The template 2‐aryl‐6,7‐dihydrooxazolo[5,4‐d]pyrimidin‐7‐one‐5‐carboxylic acids were prepared using a five‐step solution‐phase synthetic route from ethyl 2‐cyano‐2‐(hydroxyimino)acetate. BOP‐mediated direct amination conditions were optimized by a solution‐phase model study. The solid‐phase synthetic method provided the 17 target compounds in 16%–92% five‐step overall isolated yields from the Merrified resin for selected template compounds and primary/secondary amines.