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【结 构 式】 
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【分子编号】11909 【品名】5-Chloro-2-nitrophenylhydrosulfide; 5-Chloro-2-nitrobenzenethiol 【CA登记号】 |
【 分 子 式 】C6H4ClNO2S 【 分 子 量 】189.622 【元素组成】C 38.01% H 2.13% Cl 18.7% N 7.39% O 16.88% S 16.91% |
合成路线1
该中间体在本合成路线中的序号：(I)A new synthesis of racemic TA-3090 has been reported: The condensation of 5-chloro-2-nitrothiophenol (I) with 4-methoxybenzyl chloride (II) by means of sodium ethoxide in ethanol gives the thioether (III), which is reduced with SnCl2 in hot ethanol to afford 4-chloro-2-(4-methoxybenzylthio)aniline (IV). The acylation of (IV) with ethoxalyl chloride (V) by means of NaHCO3 in dichloromethane - water yields the oxamate (VI), which is condensed with 2-(dimethylamino)ethyl chloride (VII) by means of K2CO3 and 18-crown-6 in hot acetonitrile to afford the alkylated oxamate compound (VIII). The cyclization of (VIII) by means of lithium diisopropylamide in THF gives 8-chloro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiaze pine-3,4(2H,5H)-dione (IX), which is reduced with NaBH4 in aqueous ethanol to cis-8-chloro-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one (X). Finally, this compound is acetylated in the usual manner.
| 【1】 Takeda, M.; Takamura, N.; Oh-ishi, T.; Harada, T.; Morimoto, M.; Inoue, H.; Nagasawa, M.; A new synthetic route to 1,5-benzothiazepines. Synthesis of derivatives of diltiazem. Chem Pharm Bull 1992, 40, 8, 1986. |
| 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) | 11909 | 5-Chloro-2-nitrophenylhydrosulfide; 5-Chloro-2-nitrobenzenethiol | C6H4ClNO2S | 详情 | 详情 | |
| (II) | 11910 | 4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether | 824-94-2 | C8H9ClO | 详情 | 详情 |
| (III) | 11911 | 4-[[(5-Chloro-2-nitrophenyl)sulfanyl]methyl]phenyl methyl ether; 4-Chloro-2-[(4-methoxybenzyl)sulfanyl]-1-nitrobenzene | C14H12ClNO3S | 详情 | 详情 | |
| (IV) | 11912 | 4-Chloro-2-[(4-methoxybenzyl)sulfanyl]phenylamine; 4-Chloro-2-[(4-methoxybenzyl)sulfanyl]aniline | C14H14ClNOS | 详情 | 详情 | |
| (V) | 11043 | Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride | 4755-77-5 | C4H5ClO3 | 详情 | 详情 |
| (VI) | 11914 | ethyl 2-[4-chloro-2-[(4-methoxybenzyl)sulfanyl]anilino]-2-oxoacetate | C18H18ClNO4S | 详情 | 详情 | |
| (VII) | 11907 | Dimethylaminoethyl chloride; 2-Dimethylaminoethyl chloride; 2-Chloro-N,N-dimethyl-1-ethanamine; N-(2-Chloroethyl)-N,N-dimethylamine | 107-99-3 | C4H10ClN | 详情 | 详情 |
| (VIII) | 11916 | ethyl 2-[4-chloro[2-(dimethylamino)ethyl]-2-[(4-methoxybenzyl)sulfanyl]anilino]-2-oxoacetate | C22H27ClN2O4S | 详情 | 详情 | |
| (IX) | 11917 | (2S)-8-Chloro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione | C20H21ClN2O3S | 详情 | 详情 | |
| (X) | 11908 | (2S,3S)-8-Chloro-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C20H23ClN2O3S | 详情 | 详情 |