Abstract

A straightforward, cost effective and eco-friendly protocol for the Biginelli reaction relying on the use of readily available hypophosphorous acid is presented. The methodology developed displays improvements compared to existing methods, is high-yielding, robust and was applied to a panel of dihydropyrimidines and thio-derivatives with various substituents. Related urea derivatives such as guanidines, benzimidazoles and benzothiazoles also reacted efficiently to afford more complex scaffolds. Thus, this rapid and convenient catalysis allows access to a wide diversity of structures including original biologically relevant heterocycles.

1. Introduction

3,4-Dihydropyrimidin-2(1H)-one (DHPM) is a biologically relevant heterocycle with great interest thanks to its anticancer [1], antifungal [2], anti-hypertensive [3], antimalarial [4], antiHIV [5] and anti-tubercular activities [6]. It is found in several drug candidates such as monastrol [7], an effective nontubulin-interacting mitosis inhibitor, SQ-32926 [8], a calcium channel antagonist with antihypertensive activity, or Bay 41– 4109 [9], a potent human hepatitis B virus (HBV) inhibitor with an IC50 of 53 nM (Fig. 1).