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【结 构 式】 
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【分子编号】20817 【品名】(2S,6R)-6-amino-2-(2-thienyl)-1,4-thiazepan-5-one 【CA登记号】110221-26-6 |
【 分 子 式 】C9H12N2OS2 【 分 子 量 】228.33916 【元素组成】C 47.34% H 5.3% N 12.27% O 7.01% S 28.09% |
合成路线1
该中间体在本合成路线中的序号：(XIX)2) The addition of tert-butoxycarbonyl)-L-cysteine (XIV) to 2-(2-nitroethenyl)thiophene (XV) by means of N-methylmorpholine in toluene gives S-[2-nitro-1-(2-thienyl)ethyl-N-(tert-butoxycarbonyl-L-cysteine (XVI), which is reduced with H2 over Pd/C in acetic acid yielding the corresponding amine (XVII). The cyclization of (XVII) by means of diphenyl phosphorazidate (DPN) and N-methylmorpholine in DMF affords (2RS,6R)-6-(tert-butoxycarbonylamino)-2-(2-thienyl)perhydro-1,4-thiazepine (XVIII), which by hydrolysis and fractional crystallization gives (2S,6R)-6-amino-2-(2-thienyl)perhydro-1,4-thiazepine (XIX). The condensation of (XIX) with ethyl 2(R)-(trifluoromethylsulfonyloxy)-4-phenylbutanoate (XX) by means of triethylamine in dichloromethane yields (2S,2R)-6-[1(S)-(ethoxycarbonyl)-3-phenylpropylamino]-2-(2-thienyl)- perhydro-1,4-thiazepin-5-one (XXI), which is condensed with tert-butyl bromoacetate (XXII) by means of NaH in DMF to give the precursor (XXIII). Finally, this compound is hydrolyzed with 4N-HCl-dioxane at room temperature.
| 【1】 Yanagisawa, H.; Ishihara, S.; Ando, A.; Kanazaki, T.; Koike, H.; Tsujita, Y. (Sankyo Co., Ltd.); Perhydrothiazepine derivatives, their preparation and their therapeutical use. AU 8541058; EP 0161801; ES 8702388; ES 8801229; JP 85215678; JP 86267579 . |
| 【2】 Ishihara, S.; Ando, A.; Miyamoto, S.; Kanazaki, T.; Hata, T.; Oizumi, K.; Matsushita, Y.; Koike, H.; Yanagisawa, H.; Iijima, Y.; Angiotensin-converting enzyme inhibitors: Perhydro-1,4-thiazepin-5-one derivatives. J Med Chem 1987, 30, 11, 1984. |
| 【3】 Prous, J.; Castaner, J.; RS-5142. Drugs Fut 1989, 14, 4, 336. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 20812 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-sulfanylpropionic acid | 20887-95-0 | C8H15NO4S | 详情 | 详情 |
| (XV) | 20813 | 2-[(Z)-2-nitroethenyl]thiophene | C6H5NO2S | 详情 | 详情 | |
| (XVI) | 20814 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-[[2-nitro-1-(2-thienyl)ethyl]sulfanyl]propionic acid | C14H20N2O6S2 | 详情 | 详情 | |
| (XVII) | 20815 | (2R)-3-[[2-amino-1-(2-thienyl)ethyl]sulfanyl]-2-[(tert-butoxycarbonyl)amino]propionic acid | C14H22N2O4S2 | 详情 | 详情 | |
| (XVIII) | 20816 | tert-butyl (6R)-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-ylcarbamate | C14H20N2O3S2 | 详情 | 详情 | |
| (XIX) | 20817 | (2S,6R)-6-amino-2-(2-thienyl)-1,4-thiazepan-5-one | 110221-26-6 | C9H12N2OS2 | 详情 | 详情 |
| (XX) | 20818 | ethyl (2R)-4-phenyl-2-[[(trifluoromethyl)sulfonyl]oxy]butanoate | C13H15F3O5S | 详情 | 详情 | |
| (XXI) | 20819 | ethyl (2S)-2-[[(2S,6R)-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate | C21H26N2O3S2 | 详情 | 详情 | |
| (XXII) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (XXIII) | 20821 | ethyl (2S)-2-[[(2S,6R)-4-[2-(tert-butoxy)-2-oxoethyl]-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate | C27H36N2O5S2 | 详情 | 详情 |