Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Synthesis of ($\pm$)-Methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-amines

  • Jang, Jin-Hee (College of Pharmacy, Kangwon National University) ;
  • Sin, Kwan-Seog (College of Pharmacy, Kangwon National University) ;
  • Park, Hae-Il (College of Pharmacy, Kangwon National University)
  • Published : 2001.12.01
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Abstract

trans-Metanicotine, a subtype (${\alpha}_4{\beta}_2$)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. An efficient synthetic route for ($\pm$)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-am ices, derivatives of tracts-metanicotine, was explored. Allylation reaction of aryl aldimines with allylmagnesium bromide in THF gave ($\pm$)-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 ($\pm$)-methyl-(1-aryl-4-pyridin-3-yl-but-3-enyl)-carbamic acid tert-butyl esters. Deprotection of the N-Boc group in aqueous 1 N-HCI solution gave the titled amines in good yields. Thus, trans-metanicotine analogues modified at the ${\alpha}-position$ of the methylamino group with amyl groups were obtained in 5 steps.

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