Synthesis of (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines.

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Jang J, Sin KS, Park H

Synthesis of (+/-)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines.

Arch Pharm Res. 2001 Dec;24(6):503-7.

PubMed ID
11794523 [ View in PubMed
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Abstract

trans-Metanicotine, a subtype (alpha4beta2)-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 aryl 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-HCI solution gave the titled amines in good yields. Thus, trans-metanicotine analogues modified at the a-position of the methylamino group with aryl groups were obtained in 5 steps.

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