APH (4,5-dianilinophthalimide) has previously been shown to reverse the formation of neurotoxic fibrils associated with Alzheimer's disease. We have developed a synthetic route to DAPH and structurally related analogues that employs palladium-catalyzed amination as the key bond-forming step. The requisite substrates are easily obtained, and their coupling with substituted anilines proceeds in generally high yields. Thus, a variety of DAPH analogues can be quickly accessed in a modular fashion. In addition, the route described herein should also be amenable to the incorporation of other classes of nucleophiles into the molecular framework.
“Synthesis of 4,5-Dianilinophthalimide and Related Analogues for Potential Treatment of Alzheimer's Disease via Palladium-Catalyzed Amination”, J. Org. Chem., 2005, 70(18), 7371-7375.