An efficient synthesis of functionalized 2-pyridones by direct route or via amide/enolate ammonium salt intermediates

A number of compounds with a 2-pyridone structure 3, which have different substituents and are analogous to cardiotonic drugs like milrinone, have been synthesized in high yields from the appropriate enamino ketones 2 using different cyanomethylene active compounds (methyl cyanoacetate, benzoylacetonitrile and phenylsulfonylacetonitrile). In this synthetic route, the active role of the dimethylamine released in situ on the cyclization process has been underlined. In particular, its direct intervention, as a nucleophile or a base, was proven and intermediate amides 5 or enolate ammonium salts 6 were isolated and recognized by the analytical and spectral data.