title: Synthesis of 4,5-dianilinophthalimide and related analogues for potential treatment of Alzheimer's disease via palladium-catalyzed amination.
abstract: DAPH (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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hennessy
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000586:Amination; D002384:Catalysis; D010165:Palladium / Q000737:chemistry*; D010797:Phthalimides / Q000138:chemical synthesis*
chemical_list: D010797:Phthalimides; D010165:Palladium; C098874:4,5-dianilinophthalimide