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【结 构 式】 
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【分子编号】26852 【品名】methyl 2-((6S)-6-[[(2S)-2-(acetylsulfanyl)-3-phenylpropanoyl]amino]-2,2-dimethyl-7-oxoazepanyl)acetate 【CA登记号】 |
【 分 子 式 】C22H30N2O5S 【 分 子 量 】434.55668 【元素组成】C 60.81% H 6.96% N 6.45% O 18.41% S 7.38% |
合成路线1
该中间体在本合成路线中的序号：(XIV)Removal of phthaloyl protecting group of (VIII) provided amine (IX), which was protected as the tert-butyl carbamate (X) with Boc2O. Alkylation at the lactam nitrogen atom of (X) was then achieved employing LiN(SiMe3)2 and ethyl bromoacetate to afford (XI), which was deprotected under acidic conditions to furnish amine (XII). Alternatively, amine (IX) could be protected using a N-trityl group. Coupling of amine (XII) with 2-(acetylthio)benzenepropanoic acid (XIII) using either BOP or EDC as the condensing reagents produced amide (XIV). Finally, both ethyl ester and acetyl thioester of (XIV) were hydrolyzed with NaOH to yield the title compound.
| 【1】 Robl, J.A.; Sulsky, R.; Sieber-McMaster, E.; Ryono DE; Cimarusti MP; Simpkins LM; Karanewsky, D.S.; Chao, S.; Asaad, M.M.; Seymour, A.A.; Fox, M.E.; Smith, P.L.; Trippodo, N.C.; Vasopeptidase inhibitors: Incorporation of geminal and spirocyclic substituted azepinones in mercaptoacyl dipeptides. J Med Chem 1999, 42, 2, 305. |
| 【2】 Karanewsky, D.S.; Barrish, J.C.; Petrillo, E.W. Jr.; Robl, J.A.; Ryono, D.E. (Bristol-Myers Squibb Co.); Dual action inhibitors. EP 0599444; US 5552397 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 26847 | 2-[(3S)-7,7-dimethyl-2-oxoazepanyl]-1H-isoindole-1,3(2H)-dione | C16H18N2O3 | 详情 | 详情 | |
| (IX) | 26848 | (3S)-3-amino-7,7-dimethyl-2-azepanone | C8H16N2O | 详情 | 详情 | |
| (X) | 26849 | tert-butyl (3S)-7,7-dimethyl-2-oxoazepanylcarbamate | C13H24N2O3 | 详情 | 详情 | |
| (XI) | 26850 | methyl 2-[(6S)-6-[(tert-butoxycarbonyl)amino]-2,2-dimethyl-7-oxoazepanyl]acetate | C16H28N2O5 | 详情 | 详情 | |
| (XII) | 26851 | methyl 2-[(6S)-6-amino-2,2-dimethyl-7-oxoazepanyl]acetate | C11H20N2O3 | 详情 | 详情 | |
| (XIII) | 22493 | (2S)-2-(acetylsulfanyl)-3-phenylpropionic acid | C11H12O3S | 详情 | 详情 | |
| (XIV) | 26852 | methyl 2-((6S)-6-[[(2S)-2-(acetylsulfanyl)-3-phenylpropanoyl]amino]-2,2-dimethyl-7-oxoazepanyl)acetate | C22H30N2O5S | 详情 | 详情 |