Tandem copper catalyzed regioselective -arylation-amidation: synthesis of angularly fused dihydroimidazoquinazolinones and the anticancer agent TIC10/ONC201.

Herein, we present a copper-catalyzed tandem reaction of 2-aminoimidazolines and -halo(hetero)aryl carboxylic acids that causes the regioselective formation of angularly fused tricyclic 1,2-dihydroimidazo[1,2-]quinazolin-5(4)-one derivatives. The reaction involved in the construction of the core six-membered pyrimidone moiety proceeded regioselective -arylation-condensation. The presented protocol been successfully applied to accomplish the total synthesis of TIC10/ONC201, which is an active angular isomer acting as a tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL): a sought after anticancer clinical agent.