Moexipril hydrochloride, RS-10085-197, SPM-925, RS-10085(free base), CI-925, Femipres, Uniretic, Primoxil, Perdix, Univasc

盐酸莫昔普利 莫西卜里 Chemical Name: [3S-[2R*,(R*),3R*]]-2-[2-[[1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid monohydrochloride; L-(S)-2-[N-[1-(Ethoxycarbonyl)-3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline-3-carboxylic acid monohydrochloride; (3S)-2-[(2S)-N-[(1S)-1-Carboxy-3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid,2-ethyl ester monohydrochloride
CAS No. 82586-52-5, 103775-10-6 (free base)
项目整合开发状态: Launched-1995
项目研究机构: Pfizer (Originator), Hanmi (Not Determined), Bayer (Licensee), Orgamol (Licensee), Roche (Licensee), Schwarz (Licensee), Sicar (Licensee), Sifa (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.