Christian Sellier, A. Buschauer, S. Elz
Apr 13, 1992
Citations
1
Influential Citations
15
Citations
Journal
European Journal of Organic Chemistry
Abstract
Synthesis of (Z)- and (E)-3-(1H-imidazol-4-yl)-2-propenamine and Some 3-(1H-imidazol-4-yl)propanamines 3-(1H-Imidazol-4-yl)propanamine (6, homohistamine), an essential intermediate for the synthesis of potent impromidine-type histamine H2 receptor agonists, is efficiently prepared from trans-urocanic acid (1) by reduction of the methyl ester 2 and conversion to the saturated amide 4. Dehydration with thionyl chloride yields the nitrile 5 which is subsequently reduced to 6. Side-chain methylated 3-(1H-imidazol-4-yl)propanamines 12 are available from 1H-imidazole-4-carbaldehyde (7) and 1-(1H-imidazol-4-yl)ethanone (8), respectively, via unsaturated nitriles 10 and stepwise reduction. Cyclization of the appropriate 4-bromo-5-oxohexanenitriles 14α with formamidine in liquid ammonia and reduction of the obtained nitriles 15 furnishes ring-methylated amines 16. (E)-3-(1H-Imidazol-4-yl)-2-propenamine [(E)-23] is obtained in six steps from the trans-ester 2 while (Z)-23 is accessible by treating 7 with triphenyl(2-phthalimidoethyl)phosphonium bromide (17) and final deprotection. These primary amines are valuable intermediates for the synthesis of impromidine analogues.