Late‐Stage Amination of Drug‐Like Benzoic Acids: Access to Anilines and Drug Conjugates through Directed Iridium‐Catalyzed C−H Activation

Abstract The functionalization of C−H bonds, ubiquitous in drugs and drug‐like molecules, represents an important synthetic strategy with the potential to streamline the drug‐discovery process. Late‐stage aromatic C−N bond–forming reactions are highly desirable, but despite their significance, accessing aminated analogues through direct and selective amination of C−H bonds remains a challenging goal. The method presented herein enables the amination of a wide array of benzoic acids with high selectivity. The robustness of the system is manifested by the large number of functional groups tolerated, which allowed the amination of a diverse array of marketed drugs and drug‐like molecules. Furthermore, the introduction of a synthetic handle enabled expeditious access to targeted drug‐delivery conjugates, PROTACs, and probes for chemical biology. This rapid access to valuable analogues, combined with operational simplicity and applicability to high‐throughput experimentation has the potential to aid and considerably accelerate drug discovery.