Direct Chemoselective Synthesis of N-3-Substituted Pyrimidinones in a Microwave-Assisted Method

Abstract

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.

GRAPHICAL ABSTRACT

Keywords:

• Lewis acid
• microwave and DNA damages
• nucleobases
• pyrimidine

ACKNOWLEDGMENT

The Central Instrumental Facility (CIF), IIT Guwahati, is hereby acknowledged for recording NMR.

SUPPLEMENTARY INFORMATION

General experimental methods, full characterization of compounds, ORTEP presentations, details of crystallographic data, and copies of ¹H NMR,¹³C NMR, and HRMS spectra for this article can be accessed on the publisher’s website.