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