Synthesis of (±)-Methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines

초록

trans-Metanicotine, a subtype (α<inf>4</inf>β<inf>2</inf>)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. An efficient synthetic route for (±)-methyl- (1-aryl-4-pyridin-3-yl-but-3-enyl)-amines, derivatives of trans-metanicotine, was explored. Allylation reaction of aγl aldimines with allylmagnesium bromide in THF gave (±)-methyl-(1-aryl- but-3-enyl)-amines. Protection of the amines with the Boc group and following Heck reaction of the N-Boc amines with 3-bromopyridine gave (±)-methyl-(1-aryl-4-pyridin-3-yl-but-3- enyl)-carbamic acid tert-butyl esters. Deprotection of the N-Boc group in aqueous 1N-HCl solution gave the titled amines in good yields. Thus, trans-metanicotine analogues modified at the α-position of the methylamino group with aryl groups were obtained in 5 steps.

키워드