【结 构 式】 |
【分子编号】37486 【品名】(2R,3S)-3-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one 【CA登记号】 |
【 分 子 式 】C19H21NO2S2 【 分 子 量 】359.51328 【元素组成】C 63.48% H 5.89% N 3.9% O 8.9% S 17.84% |
合成路线1
该中间体在本合成路线中的序号:(VI)The reaction of 2-aminothiophenol (I) with diethyl benzylidenemalonate (II) by heating at 90 C gives diethyl 2-(2-aminophenylthio)-2-phenylethane-1,1-dicarboxylate (III), which is cyclized by heating at 180 C with triethylamine hydrochloride yielding 2,3-dihydro-3-ethoxycarbonyl-2-phenyl-1,5-benzothiazepin-4(5H)-one (IV). The reduction of (IV) with LiAlH4 in THF affords 2,3-dihydro-3-hydroxymethyl-2-phenyl-1,5-benzothiazepin-4(5H)-one (V), which by reaction with SOCl2 in refluxing benzene is converted into 2,3-dihydro-3-chloromethyl-2-phenyl-1,5-benzothiazepin-4(5H)-one (VII). Finally, this compound is treated with N-methylpiperazine at reflux temperature, and acidified with HCl. An alternative way is the reaction of (V) with methanesulfonyl chloride in pyridine affording 2,3-dihydro-3-methanesulfonyloxymethyl-2-phenyl-1,5-benzothiazepin-4(5H)-one (VI), which is then treated with N-methylpiperazine and HCl as before.
【1】 Izumi, K.; et al.; FR 2416890 . |
【2】 Hillier, K.; Castaner, J.; BTM-1042. Drugs Fut 1981, 6, 9, 534. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
(I) | 25182 | 2-aminobenzenethiol | 137-07-5 | C6H7NS | 详情 | 详情 |
(II) | 37482 | diethyl 2-benzylidenemalonate | 5292-53-5 | C14H16O4 | 详情 | 详情 |
(III) | 37483 | diethyl 2-[[(2-aminophenyl)sulfanyl](phenyl)methyl]malonate | C20H23NO4S | 详情 | 详情 | |
(IV) | 37484 | ethyl (2R,3R)-4-oxo-2-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepine-3-carboxylate | C18H17NO3S | 详情 | 详情 | |
(V) | 37485 | (2R,3S)-3-(hydroxymethyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C16H15NO2S | 详情 | 详情 | |
(VI) | 37486 | (2R,3S)-3-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C19H21NO2S2 | 详情 | 详情 | |
(VII) | 37487 | (2R,3S)-3-(chloromethyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C16H14ClNOS | 详情 | 详情 |