Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs

Authors: Rui Feng, Yong-Qi Zhen, Dongbo Wu, Lian Sun, Jin-Bu Xu, Xiaohuan Li, Lan Zhang, Feng Gao

Published: 2024-03-08

DOI: 10.1126/sciadv.adl0026

Source: Full article

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Abstract

Achieving regioselective synthesis in complex molecules with multiple reactive sites remains a tremendous challenge in synthetic chemistry. Regiodivergent palladium-catalyzed C─H arylation of complex antitumor drug osimertinib with various aryl bromides via the late-stage functionalization strategy was demonstrated here. This reaction displayed a switch in regioselectivity under complete base control. Potassium carbonate (K