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【结 构 式】 
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【分子编号】31123 【品名】benzyl 2-((2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C32H36N2O5 【 分 子 量 】528.64832 【元素组成】C 72.7% H 6.86% N 5.3% O 15.13% |
合成路线1
该中间体在本合成路线中的序号：(VII)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.
| 【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】 Castaner, J.; Serradell, M.N.; Blancafort, P.; CI-906. Drugs Fut 1983, 8, 12, 1014. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
| (I) | 29385 | tert-butyl (2S)-2-aminopropanoate | C7H15NO2 | 详情 | 详情 | |
| (II) | 20810 | ethyl 2-bromo-4-phenylbutanoate | C12H15BrO2 | 详情 | 详情 | |
| (III) | 31121 | ethyl 2-[[(1S)-2-(tert-butoxy)-1-methyl-2-oxoethyl]amino]-4-phenylbutanoate | C19H29NO4 | 详情 | 详情 | |
| (IV) | 31124 | (2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid | C15H21NO4 | 详情 | 详情 | |
| (V) | 31122 | benzyl 1,2,3,4-tetrahydro-3-isoquinolinecarboxylate | C17H17NO2 | 详情 | 详情 | |
| (VI) | 13953 | (3S)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid; (S)-(-)-1,2,3,4-Tetrahydro-3-isoquinolinecarboxylic acid | 74163-81-8 | C10H11NO2 | 详情 | 详情 |
| (VII) | 31123 | benzyl 2-((2S)-2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate | C32H36N2O5 | 详情 | 详情 |