Late-stage amination of drug-like benzoic acids: Access to anilines and drug conjugates via directed iridium-catalyzed C-H activation

Chemistry. 2021 Oct 21. doi: 10.1002/chem.202103510. Online ahead of print.ABSTRACTFunctionalization of C-H bonds, ubiquitous in drugs and drug-like molecules, represents an important synthetic strategy with a 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 herein presented method 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 for 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, as well as probes for chemical biology. The 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.PMID:34672032 | DOI:10.1002/chem.202103510

Source: Chemistry - October 21, 2021 Category: Chemistry Authors: Bel én Martín-Matute Erik Weis Magnus J Johansson Source Type: research