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

Abstract

Oxazolo[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.