Synthesis of isoindolinones: Intramolecular [4+2] cycloaddition/retro [4+2] of pyridone propiolamides

A new synthesis of isoindolinones was discovered during a screening campaign aimed at the development of novel methods for the synthesis of pyridone-EZH2 inhibitor analogues. The reaction proceeds via an intramolecular [4+2] cycloaddition of a pyridone with a tethered propiolamide moiety followed by extrusion of isocyanic acid. The discovery, optimization, and scope of the methodology are described.     

Synthesis and spectroscopic studies of 3-carbamoylisonicotinic acid derivatives

An unusual example of the selective hydrolysis of a cyano group to the corresponding carboxyl group under mild reaction conditions in the presence of a carboxamide group is reported. The reaction resulted in the formation of a rare combination of vicinal carboxamide and carboxyl groups on a pyridone ring. The structure of the synthesized products was thoroughly studied using one- and two-dimensional NMR experiments and the reaction pathway was monitored fluorometrically.