Zur Synthese von (Z)‐ und (E)‐3‐(1H‐Imidazol‐4‐yl)‐2‐propenamin und einigen 3‐(1H‐Imidazol‐4‐yl)propanaminen

Abstract

Synthesis of (Z)‐ and (E)‐3‐(1H‐imidazol‐4‐yl)‐2‐propenamine and Some 3‐(1H‐imidazol‐4‐yl)propanamines3‐(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.