Late‐Stage Functionalization by Chan–Lam Amination: Rapid Access to Potent and Selective Integrin Inhibitors

A late‐stage functionalization of the aromatic ring in amino acid derivatives is described. The key step is a copper‐catalysed diversification of a boronate ester by amination (Chan–Lam reaction) that can be carried out on a complex β‐aryl‐β‐amino acid scaffold. This not only considerably extends the substrate scope of amination partners, but also delivers an array of potent and selective integrin inhibitors as potential treatment agents of idiopathic pulmonary fibrosis (IPF). This versatile chemical strategy, which is amenable to high‐throughput‐array protocols, allows the installation of pharmaceutically valuable heteroaromatic fragments at a late stage by direct coupling to NH heterocycles, leading to compounds with drug‐like attributes. It thus constitutes a useful addition to the medicinal chemist's repertoire. Array synthesis: Copper‐catalysed amination of a β‐aryl‐β‐amino acid boronate delivers an array of potent integrin inhibitors by late‐stage functionalization (see scheme).