【结 构 式】 |
【药物名称】Moexipril hydrochloride, RS-10085-197, SPM-925, RS-10085(free base), CI-925, Femipres, Uniretic, Primoxil, Perdix, Univasc 【化学名称】[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 【CA登记号】82586-52-5, 103775-10-6 (free base) 【 分 子 式 】C27H35ClN2O7 【 分 子 量 】535.0422 |
【开发单位】Pfizer (Originator), Hanmi (Not Determined), Bayer (Licensee), Orgamol (Licensee), Roche (Licensee), Schwarz (Licensee), Sicar (Licensee), Sifa (Licensee) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Angiotensin-I Converting Enzyme (ACE) Inhibitors |
合成路线1
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.
【1】 Hoefle, M.L.; Klutchko, S. (Pfizer Inc.); Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids. DD 201787; EP 0049605; EP 0096157; US 4344949 . |
【2】 Prous, J.; Castaner, J.; CI-925. Drugs Fut 1986, 11, 4, 257. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 24040 | 5-amino-2,2-dimethyl-3,4-hexanedione | C8H15NO2 | 详情 | 详情 | |
(II) | 20810 | ethyl 2-bromo-4-phenylbutanoate | C12H15BrO2 | 详情 | 详情 | |
(III) | 24042 | ethyl 4-phenyl-2-[(1,4,4-trimethyl-2,3-dioxopentyl)amino]butanoate | C20H29NO4 | 详情 | 详情 | |
(IV) | 24043 | N-[1-(ethoxycarbonyl)-3-phenylpropyl]alanine | C15H21NO4 | 详情 | 详情 | |
(V) | 24044 | benzyl 6,7-dimethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate | C19H21NO4 | 详情 | 详情 | |
(VI) | 24045 | benzyl 2-(2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate | C34H40N2O7 | 详情 | 详情 |