The Use of Chloroformamidine Hydrochloride as a Reagent for the Synthesis of Guanidines from Electron Deficient Aromatic Amines

In efforts to optimize a manufacturing process for an internal development compound, a clean, efficient approach to guanidine synthesis using chloroformamidine hydrochloride was identified. To investigate the general utility of this methodology towards electron-deficient aromatic amines, a set of favorable conditions were developed from a series of screens, and the scope of the reaction was probed. The successful application of this chemistry to a variety of pyridines, anilines, and heterocyclic compounds highlights its use as an improved, alternative guanylation method for this often challenging set of aromatic amines.