Assembly of 4-Aminoquinolines via Palladium Catalysis:  A Mild and Convenient Alternative to S_NAr Methodology

Abstract

4-aminoquinolines, classically prepared via SNAr chemistry from an amine and 4-haloquinoline, are important scaffolds in medicinal chemistry. Interest in these compounds prompted us to explore palladium catalysis as an alternative to the existing methods for their preparation. Initial results followed by an iterative screening paradigm confirmed Pd(OAc)2/DPEphos/K3PO4 as a mild and convenient alternative for the formation of the C-N bond in 4-aminoquinolines. A description of the screen and the scope of this methodology are discussed herein.