【结 构 式】 |
【分子编号】11364 【品名】7-(tert-butyl) 8-[2-(trimethylsilyl)ethyl] (8S)-1,4-dithia-7-azaspiro[4.4]nonane-7,8-dicarboxylate 【CA登记号】 |
【 分 子 式 】C17H31NO4S2Si 【 分 子 量 】405.65498 【元素组成】C 50.34% H 7.7% N 3.45% O 15.78% S 15.81% Si 6.92% |
合成路线1
该中间体在本合成路线中的序号:(IV)A new synthesis of spirapril has been reported: The cyclization of N-benzyloxycarbonyl-4-oxo-(S)-proline (I) with ethandithiol by means of boron trifluoride ethearate in dichloromethane gives 7-(benzyloxycarbonyl)-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid (II), which is treated with concentrated HCl to yield 1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid (III). The protection of (III) with tert-butoxycarbonyl chloride and with trimethylsilylethanol in the usual manner affords N-(tert-butoxycarbonyl)-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxyli c acid 2-(trimethylsilyl)ethyl ester (IV), which is condensed with N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine (V) by a first treatment with p-toluenesulfonic acid and a condensation step with dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole (HBT), giving spirapril 2-(trimethylsilyl)ethyl ester (VI). Finally, this ester is hydrolyzed with tetrabutylammonium fluoride trihydrate in DMF.
【1】 Powell, J.R.; Cushman, D.W.; Krapcho, J.; Turk, C.; DeForrest, J.M.; Spitzmiller, E.R.; Karanewsky, D.S.; Duggan, M.; Rovnyak, G.; Schwartz, J.; et al.; Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines. J Med Chem 1988, 31, 6, 1148. |
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) | 11357 | (2S)-1-[(Benzyloxy)carbonyl]-4-oxotetrahydro-1H-pyrrole-2-carboxylic acid | C13H13NO5 | 详情 | 详情 | |
(II) | 11358 | (8S)-7-[(Benzyloxy)carbonyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid | C15H17NO4S2 | 详情 | 详情 | |
(III) | 11359 | (8S)-1,4-Dithia-7-azaspiro[4.4]nonane-8-carboxylic acid | C7H11NO2S2 | 详情 | 详情 | |
(IV) | 11364 | 7-(tert-butyl) 8-[2-(trimethylsilyl)ethyl] (8S)-1,4-dithia-7-azaspiro[4.4]nonane-7,8-dicarboxylate | C17H31NO4S2Si | 详情 | 详情 | |
(V) | 11360 | (2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid; (S)-N-(1-Ethoxycarbonyl-3-phenylpropyl)-(S)-alanine | 82717-96-2 | C15H21NO4 | 详情 | 详情 |
(VI) | 11366 | 2-(trimethylsilyl)ethyl (8S)-7-((2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylate | C27H42N2O5S2Si | 详情 | 详情 |