DIRECT CHEMOSELECTIVE SYNTHESIS OF N-3-SUBSTITUTED PYRIMIDINONES IN A MICROWAVE-ASSISTED METHOD

Synthesis of selectively N-3-substituted pyrimidine nucleobases or pyrimidinones has always been a challenge because of poor regioselectivity and chemoselectivity. In this article we demonstrate a single-step, de novo synthesis of selectively N-3-substituted modified pyrimidinones. We have developed a microwave-assisted methodology for direct, chemoselective alkylation, benzylation, and arylation of C-5 and C-6 substituted pyrimidine nucleobases selectively at the N-3 position. The reactions were found to proceed, with high efficiency, without the requirement of solvent and were complete within 10-15 min of irradiation. The efficiency of the method was further improved by addition of a Lewis acid, which not only increases the yield significantly but also accelerates the reaction rate.