The condensation of tert-butylalanine (I) with ethyl 2-bromo-4-phenylbutanoate (II) by means of triethylamine in hot DMF gives N-[1-(ethoxycarbonyl)-3-phenylpropyl]alanine tert-butyl ester (III), which is hydrolyzed with trifluoroacetic acid to the corresponding N-substituted alanine (IV). The condensation of (IV) with benzyl 1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline-3-carboxylate (V) by means of triethylamine, 1-hydroxybenzotriazole (HBT) and dicyclohexylcarbodiimide (DCC) in methylene chloride affords benzyl 2-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-6,7-di-methoxyisoquinoline-3-carboxylate (VI), which is finally debenzylated by hydrogenation with H2 over Pd/C in THF.
The condensation of alanine tert-butyl ester (I) with ethyl 2-bromo-4-phenylbutanoate (II) by means of triethylamine in hot DMF gives ethyl 2-[[1-(tert-butoxycarbonyl)ethyl]amino]-4-phenylbutanoate (III), which is partially hydrolyzed with trifluoroacetic acid yielding ethyl 2-[[1-carboxyethyl]amino]-4-phenylbutanoate (IV). The condensation of (IV) with benzyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylate (V) [prepared from the corresponding acid (VI) and benzyl alcohol (A) by means of polyphosphoric acid] by means of triethylamine and 1-hydroxybenzotriazole affords benzyl 2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in THF.
The condensation of alanine tert-butyl ester (I) with ethyl 2-bromo-4-phenylbutanoate (II) by means of triethylamine in hot DMF gives ethyl 2-[[1-(tert-butoxycarbonyl)ethyl]amino]-4-phenylbutanoate (III), which is partially hydrolyzed with trifluoroacetic acid yielding ethyl 2-[[1-carboxyethyl]amino]-4-phenylbutanoate (IV). The condensation of (IV) with tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (VIII) [prepared from the corresponding acid (VI) and isobutylene (B) by means of H2SO4] as before gives tert-butyl-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (IX), which is finally hydrolyzed partially by treatment with trifluoroacetic acid.