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【结 构 式】 
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【药物名称】SB-399885 【化学名称】N-(3,5-Dichloro-2-methoxyphenyl)-4-methoxy-3-(1-piperazinyl)benzenesulfonamide 【CA登记号】402713-80-8, 402713-82-0 (4-methylbenzenesulfonate), 402713-81-9 (hydrochloride) 【 分 子 式 】C18H21Cl2N3O4S 【 分 子 量 】446.35577 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antidepressants, Anxiolytics, Cognition Disorders, Treatment of, Mood Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, 5-HT6 Antagonists |
合成路线1
N-(2-Methoxyphenyl)piperazine (I) is protected as the trichloroacetamide (II) using trichloroacetyl chloride and diisopropylethylamine. Then, chlorosulfonation of (II) in cold CH2Cl2 furnishes sulfonyl chloride (III)
| 【1】 Bromidge, S.M.; Moss, S.F. (GlaxoSmithKline plc); N-(3,5-Dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-yl-benzenesulfonamide. EP 1313720; WO 0218358 . |
| 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) | 11882 | 1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine | 35386-24-4 | C11H16N2O | 详情 | 详情 |
| (II) | 48007 | 2,2,2-trichloro-1-[4-(2-methoxyphenyl)-1-piperazinyl]-1-ethanone | C13H15Cl3N2O2 | 详情 | 详情 | |
| (III) | 48008 | 4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride | C13H14Cl4N2O4S | 详情 | 详情 |
合成路线2
Alkylation of 2,4-dichloro-6-nitrophenol (IV) with iodomethane in the presence of K2CO3 provides the methyl ether (V). Subsequent nitro group reduction in (V) employing iron powder and NH4Cl leads to aniline (VI). This is then acylated by sulfonyl chloride (III) to form sulfonamide (VII). The N-trichloroacetyl group of (VII) is finally removed by alkaline hydrolysis to provide the title compound
| 【1】 Bromidge, S.M.; Moss, S.F. (GlaxoSmithKline plc); N-(3,5-Dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-yl-benzenesulfonamide. EP 1313720; WO 0218358 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 48008 | 4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonyl chloride | C13H14Cl4N2O4S | 详情 | 详情 | |
| (IV) | 60881 | 2,4-dichloro-6-nitrophenol | C6H3Cl2NO3 | 详情 | 详情 | |
| (V) | 60882 | 2,4-dichloro-6-nitrophenyl methyl ether; 1,5-dichloro-2-methoxy-3-nitrobenzene | C7H5Cl2NO3 | 详情 | 详情 | |
| (VI) | 60883 | 3,5-dichloro-2-methoxyaniline; 3,5-dichloro-2-methoxyphenylamine | C7H7Cl2NO | 详情 | 详情 | |
| (VII) | 60884 | N-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-[4-(2,2,2-trichloroacetyl)-1-piperazinyl]benzenesulfonamide | C20H20Cl5N3O5S | 详情 | 详情 |