1: With 4-nitro-benzoic acid in acetonitrile T=80°C; 8 h; Inert atmosphere; 2: With sodium carbonate in acetonitrile Inert atmosphere; regioselective reaction;

1: L-2-aminobutyric acid ethyl ester hydrochloride With potassium carbonate in ethanol T=20°C; 1 h; Inert atmosphere; 2: 2-iodocyclohex-2-enone With toluene-4-sulfonic acid in ethanol T=75°C; 6 h; Inert atmosphere;

tris-(dibenzylideneacetone)dipalladium(0); (S,E)-N-benzhydryl-2-(N,N'-dicyclohexylcarbamimidoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide in dichloromethane T=35°C; 5 h; Inert atmosphere; enantioselective reaction;

C32H30N4O4; copper(l) chloride in dichloromethane T=0°C; 8 h; Inert atmosphereMolecular sieve; optical yield given as percent eeenantioselective reaction;

tris-(dibenzylideneacetone)dipalladium(0); (S,E)-N-benzhydryl-2-(N,N'-dicyclohexylcarbamimidoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide in dichloromethane T=35°C; 5 h; Inert atmosphere;

1: 4-Acetylaminobenzenesulfonyl Azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 0 - 20 °C 2: (S,E)-N-benzhydryl-2-(N,N'-dicyclohexylcarbamimidoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide; tris-(dibenzylideneacetone)dipalladium(0) / dichloromethane / 5 h / 35 °C / |Inert atmosphere View Scheme