Synthesis of Potent Bicyclic Bisarylimidazole c-Jun N-Terminal Kinase Inhibitors by Catalytic C−H Bond Activation

Abstract
The efficient preparation of the privileged bicyclic bisarylimidazole kinase inhibitor scaffold was accomplished using rhodium-catalyzed C−H activation and intramolecular alkylation. The key C−H activation/alkylation step represents one of the first evaluations of diastereocontrol in catalyzed C−H activation/olefin alkylation processes. Several inhibitors of JNK3 were prepared using this sequence, with the most potent inhibitor having an IC50 value of 1.6 nM.