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【结 构 式】 
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【分子编号】64268 【品名】2-oxo-2-((2S)-1-{[(2S)-1-(4-phenylbutanoyl)pyrrolidinyl]carbonyl}pyrrolidinyl)ethyl acetate 【CA登记号】 |
【 分 子 式 】C23H30N2O5 【 分 子 量 】414.50168 【元素组成】C 66.65% H 7.3% N 6.76% O 19.3% |
合成路线1
该中间体在本合成路线中的序号：(VII)L-Proline (I) is protected as its N-Boc derivative (II) with Boc2O/NaOH in a two-phase system. N-Boc-Proline (II) is further converted into diazo ketone (III) via activation with ethyl chloroformate, followed by condensation with diazomethane. Subsequent treatment of diazo ketone (III) with AcOH leads to the acetoxy ketone (IV). Then, acidic N-Boc group cleavage in (IV) furnishes amine (V). On the other side, L-proline (I) is acylated by 4-phenylbutyryl chloride to produce the corresponding amide (VI). Coupling between 2-(acetoxyacetyl)pyrrolidine (V) and N-(phenylbutyryl)proline (VI) via activation with pivaloyl chloride leads to the amide adduct (VII). Finally, methanolysis of the acetate ester group of (VII) provides the target hydroxyacetyl compound.
| 【1】 Wallén, E.A.; Christiaans, J.A.M.; Saario, S.M.; Forsberg, M.M.; Venalainen, J.I.; Paso, H.M.; Mannisto, P.T.; Gynther, J.; 4-Phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines as prolyl oligopeptidase inhibitors. Bioorg Med Chem 2002, 10, 7, 2199. |
| 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) | 16131 | methyl 4-(butyrylamino)-3-methylbenzoate | C13H17NO3 | 详情 | 详情 | |
| (II) | 16734 | (2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid | C10H17NO4 | 详情 | 详情 | |
| (III) | 64266 | (L)-2-Diazoacetyl-pyrrolidine-1-carboxylic acid tertiary-butyl ester (L)-2-Diazoacetyl-pyrrolidine-1-carboxylic acid tertiary-butyl ester (L)-2-Diazoacetyl-pyrrolidine-1-carboxylic acid tertiary-butyl ester | 101130-03-4 | C11H17N3O3 | 详情 | 详情 |
| (IV) | 16736 | tert-butyl (2S)-2-[2-(acetoxy)acetyl]tetrahydro-1H-pyrrole-1-carboxylate | C13H21NO5 | 详情 | 详情 | |
| (V) | 16737 | 2-oxo-2-[(2S)tetrahydro-1H-pyrrol-2-yl]ethyl acetate | C8H13NO3 | 详情 | 详情 | |
| (VI) | 64267 | (2S)-1-(4-phenylbutanoyl)-2-pyrrolidinecarboxylic acid | C15H19NO3 | 详情 | 详情 | |
| (VII) | 64268 | 2-oxo-2-((2S)-1-{[(2S)-1-(4-phenylbutanoyl)pyrrolidinyl]carbonyl}pyrrolidinyl)ethyl acetate | C23H30N2O5 | 详情 | 详情 |