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【结 构 式】

【分子编号】20811

【品名】ethyl 2-[[4-[2-(tert-butoxy)-2-oxoethyl]-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate

【CA登记号】

【 分 子 式 】C27H36N2O5S2

【 分 子 量 】532.72532

【元素组成】C 60.88% H 6.81% N 5.26% O 15.02% S 12.04%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XIII)

1) The reduction of 2-thiophenecarboxaldehyde cyanohydrin (I) with LiAlH4 gives 2-amino-1-(2-thienyl)ethanol (II), which is N-protected with di-tert-butyl pyrocarbonate yielding 2-(tert-butoxycarbonylamino)-1-(2-thienyl)ethanol (III). The reaction of (III) with PCl5 in dichloromethane affords 2-(tert-butoxycarbonylamino)-1-chloro-1-(2-thienyl)ethane (IV), which is condensed with benzhydryl N-phthaloylcysteinate (V) by means of Na2CO3 in hot DMF giving the S-substituted cysteinate (VI). The deprotection of (VI) with trifluoroacetic acid in anisole yields S-[2-amino-1-(2-thienyl)ethyl]-N-phthaloylcysteine (VII), which is cyclized by means of diphenylphosphoryl azide (DPA) in DMF giving 6-phthalimido-2-(2-thienyl)perhydro-1,4-thiazepin-5-one (VIII). The condensation of (VIII) with tert-butyl bromoacetate (IX) by means of NaH in DMF affords tert-butyl 2-[6-phthalimido-5-oxo-2-(2-thienyl)perhydro-1,4-thiazepin-4-yl]acetate (X), which is treated with methylhydrazine in methanol-dichloromethane yielding the 6-amino derivative (XI). The condensation of (XI) with ethyl 2-bromo-4-phenylbutyrate (XII) by means of Na2CO3 in hot DMF gives the tert-butyl ester of the desired product (XIII), which is finally deprotected with trifluoroacetic acid in anisole.

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 Prous, J.; Castaner, J.; RS-5142. Drugs Fut 1989, 14, 4, 336.
3 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.
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) 20799 2-hydroxy-2-(2-thienyl)acetonitrile C6H5NOS 详情 详情
(II) 20800 2-amino-1-(2-thienyl)-1-ethanol C6H9NOS 详情 详情
(III) 20801 tert-butyl 2-hydroxy-2-(2-thienyl)ethylcarbamate C11H17NO3S 详情 详情
(IV) 20802 tert-butyl 2-chloro-2-(2-thienyl)ethylcarbamate C11H16ClNO2S 详情 详情
(V) 20803 benzhydryl 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-sulfanylpropanoate C24H19NO4S 详情 详情
(VI) 20804 benzhydryl 3-[[2-[(tert-butoxycarbonyl)amino]-1-(2-thienyl)ethyl]sulfanyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoate C35H34N2O6S2 详情 详情
(VII) 20805 3-[[2-amino-1-(2-thienyl)ethyl]sulfanyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propionic acid C17H16N2O4S2 详情 详情
(VIII) 20806 2-[5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]-1H-isoindole-1,3(2H)-dione C17H14N2O3S2 详情 详情
(IX) 17430 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate 5292-43-3 C6H11BrO2 详情 详情
(X) 20808 tert-butyl 2-[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-oxo-2-(2-thienyl)-1,4-thiazepan-4-yl]acetate C23H24N2O5S2 详情 详情
(XI) 20809 tert-butyl 2-[6-amino-5-oxo-2-(2-thienyl)-1,4-thiazepan-4-yl]acetate 112968-38-4 C15H22N2O3S2 详情 详情
(XII) 20810 ethyl 2-bromo-4-phenylbutanoate C12H15BrO2 详情 详情
(XIII) 20811 ethyl 2-[[4-[2-(tert-butoxy)-2-oxoethyl]-5-oxo-2-(2-thienyl)-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate C27H36N2O5S2 详情 详情
Extended Information