Mild and Catalyst-Free Microwave-Assisted Synthesis of 4,6-Disubstituted 2-Methylthiopyrimidines – Exploiting Tetrazole as an Efficient Leaving Group

Abstract

Typically, 4,6-disubstituted 2-thiomethylpyrimidines are synthesized starting from 4,6-dichloro-2-thiomethylpyrimidine or an amino-substituted precursor. However, these reactions take several hours up to days and require multiple steps. Herein, we report a novel, easy, and quick-to-prepare synthetic intermediate, namely 2-(methylthio)-4,6-di(1H-tetrazol-1-yl)pyrimidine, for the synthesis of these interesting target compounds. The intermediate can be transformed within minutes into desired substituted pyrimidines under mild conditions with moderate to excellent yields. The reaction can be conducted in an automated microwave system, at room temperature or by conventional heating. Furthermore, we demonstrate the robustness of the method in a one-pot procedure.

Keywords

tetrazole - pyrimidine - combinatorial chemistry - medicinal chemistry - nucleophilic aromatic substitution

• References and Notes

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