Metal-Free Tandem Approach to Structurally Diverse N-Heterocycles: Synthesis of 1,2,4-Oxadiazoles and Pyrimidinones

Abstract

A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2,4-oxadiazoles and 2,6 disubstituted pyrimidin-4-ones is described via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids. The reactions occur at room temperature forming N-acylamidines which undergo tandem nucleophilic addition / deamination / intramolecular cyclisation to give the corresponding heterocyclic compounds in good to excellent yields. This one pot approach has led to the successful synthesis of drug lead molecule, ataluren, (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl) benzoic acid in two steps.