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【结 构 式】 
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【分子编号】16738 【品名】2-[(2S)-1-([(2S)-1-[(benzylamino)carbonyl]tetrahydro-1H-pyrrol-2-yl]carbonyl)tetrahydro-1H-pyrrol-2-yl]-2-oxoethyl acetate 【CA登记号】 |
【 分 子 式 】C21H27N3O5 【 分 子 量 】401.4626 【元素组成】C 62.83% H 6.78% N 10.47% O 19.93% |
合成路线1
该中间体在本合成路线中的序号：(XV)2) The reaction of tert-butoxycarbonyl-L-proline (XI) with diazomethane and triethylamine in ether gives the diazoketone (XII), which by treatment with acetic acid at 100 C yields the acetoxyketone (XIII). The deprotection of (XIII) with trifluoroacetic acid affords the unprotected alpha-hydroxyketone (XIV), which is condensed with N-(benzylaminecarbonyl)-L-proline (VI) by means of 1-hydroxybenzotriazole (HOBT) giving the acetylated dipeptide analogue (XV). Finally, this compound is deacetylated with K2CO3 in methanol/water.
| 【1】 Wroblewski, T.; Silvestre, J.S.; Castañer, J.; JTP-4819. Drugs Fut 1998, 23, 4, 384. |
| 【2】 Kobayashi, K.; Akamatsu, M.; Yata, S.; Abe, H.; Toide, K.; Kogayu, M.; Uchida, I. (Japan Tobacco Inc.; Welfide Corporation); Cpd. with prolyl endopeptidase inhibitor activity and pharmaceutical use thereof. EP 0670309; JP 1995512967; US 5536737; WO 9412474 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 16729 | (2S)-1-[(benzylamino)carbonyl]tetrahydro-1H-pyrrole-2-carboxylic acid | C13H16N2O3 | 详情 | 详情 | |
| (XI) | 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 | |
| (XII) | 16735 | tert-butyl (2S)-2-(2-diazoacetyl)tetrahydro-1H-pyrrole-1-carboxylate | 101130-03-4 | C11H17N3O3 | 详情 | 详情 |
| (XIII) | 16736 | tert-butyl (2S)-2-[2-(acetoxy)acetyl]tetrahydro-1H-pyrrole-1-carboxylate | C13H21NO5 | 详情 | 详情 | |
| (XIV) | 16737 | 2-oxo-2-[(2S)tetrahydro-1H-pyrrol-2-yl]ethyl acetate | C8H13NO3 | 详情 | 详情 | |
| (XV) | 16738 | 2-[(2S)-1-([(2S)-1-[(benzylamino)carbonyl]tetrahydro-1H-pyrrol-2-yl]carbonyl)tetrahydro-1H-pyrrol-2-yl]-2-oxoethyl acetate | C21H27N3O5 | 详情 | 详情 |