One-Pot Etherification of Purine Nucleosides and Pyrimidines

Abstract

A one-pot synthesis of ethers derived from inosine, guanosine, 2'-deoxyguanosine, and pyrimidinones is described. Exposure of the heterocycle to 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and Cs(2)CO(3) produces a reactive intermediate, which is converted to the desired ether by subsequent addition of an appropriate alcohol or phenol and Cs(2)CO(3). Although rapid formation of HMPA from BOP can occur in the presence of an alcohol and base, as demonstrated by the reaction with methanol, under appropriate conditions these heteroaryl ethers can be efficiently synthesized.