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【结 构 式】 
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【分子编号】29361 【品名】methyl (2R)-2-(acetamido)-3-(2-oxocyclopentyl)propanoate 【CA登记号】 |
【 分 子 式 】C11H17NO4 【 分 子 量 】227.26032 【元素组成】C 58.14% H 7.54% N 6.16% O 28.16% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of 1-cyclopentenylpyrrolidino (I) with methyl 2-acetylamino-3-chloropropionate (II) in DMF gives methyl 2-acetylamino-3-(2-oxocyclopentyl)propionate (III), which is cyclized in refluxing concentrated HCl and reduced with H2 over Pd/C in acetic acid yielding cis,endo-2-azabicyclo[3.3.0]octan-3-carboxylic acid (IV). Esterification of (IV) with SOCl2 and benzyl alcohol affords the corresponding benzyl ester (V), which is condensed with N-(1-ethoxycarbonyl-3-phenylpropyl)alanine (VI) by means of dicyclohexylcarbodiirnide (DCC) in DMF affording benzyl N-(1-ethoxycarbonyl-3-phenylpropyl)alanyl-cis,endo-2-azabicyclo[3.3.0]octan-3-carboxylate (VII). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol.
| 【1】 Teetz, V.; et al. (Aventis Pharma AG); Method for making 2-azabicyclo[3.3.0]octane-3-carboxylic acids. DE 3226768; EP 0079022; EP 0150263; JP 2104526; JP 2104573; JP 4217949; US 4727160; US 5053519 . |
| 【2】 Mannhold, R.; Serradell, M.N.; Castaner, J.; Ramipril. Drugs Fut 1985, 10, 5, 400. |
| 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) | 29359 | 1-(1-cyclopenten-1-yl)pyrrolidine | 7148-07-4 | C9H15N | 详情 | 详情 |
| (II) | 29360 | methyl (2S)-2-(acetamido)-3-chloropropanoate | C6H10ClNO3 | 详情 | 详情 | |
| (III) | 29361 | methyl (2R)-2-(acetamido)-3-(2-oxocyclopentyl)propanoate | C11H17NO4 | 详情 | 详情 | |
| (IV) | 29362 | (2S,3aS,6aS)octahydrocyclopenta[b]pyrrole-2-carboxylic acid | C8H13NO2 | 详情 | 详情 | |
| (V) | 29363 | benzyl (2S,3aS,6aS)octahydrocyclopenta[b]pyrrole-2-carboxylate | 93779-31-8 | C15H19NO2 | 详情 | 详情 |
| (VI) | 11360 | (2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid; (S)-N-(1-Ethoxycarbonyl-3-phenylpropyl)-(S)-alanine | 82717-96-2 | C15H21NO4 | 详情 | 详情 |
| (VII) | 29364 | benzyl (2S,3aS,6aS)-1-((2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)octahydrocyclopenta[b]pyrrole-2-carboxylate | C30H38N2O5 | 详情 | 详情 |