Quinapril hydrochloride, PD-109522, CI-906, Accuretic, Lidaltrin, Ectren, Conan, Accupril, Korec, Quinazil, Acequin, Accupro, Accuprin

盐酸喹那普利 喹那普利 Chemical Name: [3S-[2[R*(R*),3R*]]-2-[2-[[1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid monohydrochloride; (S)-2-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 1-ethyl ester monohydrochloride; 2-[N-[1(S)-(Ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-1,2,3,4-tetrahydroisoquinoline-3(S)-carboxylic acid monohydrochloride
CAS No. 82586-55-8, 85441-61-8 (free base), 90243-99-5 (monohydrate), 82768-84-1 (undefined stereoch.)
项目整合开发状态: Launched-1989
项目研究机构: Pfizer (Originator), Japan Tobacco (Licensee), Lacer (Licensee), Malesci (Licensee), Menarini (Licensee), Mitsubishi Pharma (Licensee), Recordati (Licensee), Sankyo (Licensee)
合成路线: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.

合成路线: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.

合成路线: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.