Palladium‐Catalyzed ortho ‐C–H Alkylation of Benzamides With α ‐Bromo Ketones Accessing 2‐(2‐Oxo‐2‐phenylethyl)benzamides and Their Anti‐Inflammatory Activity

ABSTRACT 2‐(2‐Oxo‐2‐phenylethyl)benzamide derivatives are prevalent in natural products and bioactive agents. The traditional synthetic route often relies on sensitive alkali metal reagents, thereby restricting substrate versatility. In this work, we report a practical method for the palladium (II)‐catalyzed, 8‐aminoquinoline‐directed ortho ‐C–H alkylation of benzamides using α ‐bromo aryl ketones. A broad range of readily accessible benzamides, α ‐bromo aryl ketones, bromoacetonitrile, and ethyl bromoacetate could be employed as coupling partners in this transformation, to afford diverse 2‐(2‐oxo‐2‐phenylethyl)benzamide derivatives. In addition, preliminary anti‐inflammatory activity evaluation revealed that the product 3j potently inhibits LPS‐induced interleukin‐6 (IL‐6) with an IC 50 value of 15.08 μM.