Palladium-catalyzed N-arylation of 2-aminobenzothiazole-4-carboxylates/carboxamides: Facile synthesis of PARP14 inhibitors

We have developed a palladium-catalyzed N-arylation of the biologically interesting, but synthetically rather challenging 2-arylaminobenzothiazoles bearing multiple functionalities. This protocol was successfully used to readily synthesize our initial PARP14 inhibitor followed by a limited structural optimization. A more potent PARP14 inhibitor with an IC₅₀ value of 1.69 μM was identified, and the interaction was ascertained by the X-ray co-crystal structure of the catalytic domain of PARP14 in complex with compound 8.