Copper-catalyzed amination of (bromophenyl)ethanolamine for a concise synthesis of aniline-containing analogues of NMDA NR2B antagonist ifenprodil.
An operationally simple and concise synthesis of anilinoethanolamines, as NMDA NR2B receptor antagonist ifenprodil analogues, was developed via a copper-catalyzed amination of the corresponding bromoarene. Coupling was achieved with linear primary alkylamines, alpha,omega-diamines, hexanolamine and benzophenone imine, as well as with aqueous ammonia, in good yields using CuI and N,N-diethylsalicylamide, 2,4-pentadione or 2-acetylcyclohexanone as catalytic systems. Amination with ethylene diamine was efficient even in the absence of an additive ligand, whereas no reaction occurred with ethanolamine whatever the conditions used. The anilinoethanolamines were evaluated as NR2B receptor antagonists in a functional inhibition assay. Aminoethylanilines displayed inhibition effects close to that of ifenprodil.
Bouteiller
Cédric
C
Laboratoire de Développements Méthodologiques en TEP, CEA/DSV/I2BM/CI-NAPS, UMR 6232, CNRS, Université de Caen-Basse Normandie, Cyceron, Bd Henri Becquerel, 14074 Caen Cedex, France.
Becerril-Ortega
Javier
J
Marchand
Patrice
P
Nicole
Olivier
O
Barré
Louisa
L
Buisson
Alain
A
Perrio
Cécile
C
D000586:Amination; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017605:Bromine Compounds / Q000737:chemistry; D002384:Catalysis; D002460:Cell Line; D003300:Copper / Q000737:chemistry; D019856:Ethanolamine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D010880:Piperidines / Q000737:chemistry; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D000814:Aniline Compounds; D017605:Bromine Compounds; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D019856:Ethanolamine; D003300:Copper; C010739:ifenprodil; C023650:aniline