A concise synthetic pathway for trans-metanicotine analogues

A convenient pathway for synthesis of trans-metanicotine analogues was deve loped. trans Metanicotine, a subtype(alpha 4 beta 2)-selective ligand for n euronal nicotinic acetylcholine receptor, is under clinical phase for Alzhe imer's disease. Zn-mediated allylation of allyl bromide and acetaldehyde fo llowed by Heck reaction with 3-bromopyridine gave 5-pyridin-3-yl-pent-4-en- 3-ol (2). Tosylation of 5-pyridin-3-yl-pent-4-en-3-ol followed by substitut ion reaction with methylamine in sealed tube gave methyl-(1-methyl-4-pyridi n-3-yl-but-3-enyl)-amine (4) in good yields. Thus, trans-metanicotine analo gues modified at the alpha-position of the methylamino group with various f unctional groups can be obtained in 4 steps.