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【结 构 式】 
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【分子编号】23316 【品名】3-methylbenzenesulfonyl chloride 【CA登记号】1899-93-0 |
【 分 子 式 】C7H7ClO2S 【 分 子 量 】190.65008 【元素组成】C 44.1% H 3.7% Cl 18.6% O 16.78% S 16.82% |
合成路线1
该中间体在本合成路线中的序号：(II)Preparation of intermediate (IV) is illustrated in Scheme 25654801a: Methyl N3-Boc-(S)-2,3-diaminopropionate (I) was condensed with m-toluenesulfonyl chloride (II) to provide sulfonamide (III). The Boc group was then deprotected with HCl in dioxan to give amine (IV).
| 【1】 Wityak, J.; Xue, C.-B.; Sielecki-Dzurdz, T.M.; Olson, R.E.; Degrado, W.F.; Cain, G.A. (DuPont Pharmaceuticals Co.); Novel isoxazoline and isoxazole fibrinogen receptor antagonists. EP 0730590; EP 0832076; JP 1997505590; JP 1999504651; US 5849736; WO 9514683; WO 9638426 . |
| 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) | 25095 | methyl (2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate | C9H18N2O4 | 详情 | 详情 | |
| (II) | 23316 | 3-methylbenzenesulfonyl chloride | 1899-93-0 | C7H7ClO2S | 详情 | 详情 |
| (III) | 28132 | methyl (2S)-3-[(tert-butoxycarbonyl)amino]-2-[[(3-methylphenyl)sulfonyl]amino]propanoate | C16H24N2O6S | 详情 | 详情 | |
| (IV) | 28133 | methyl (2S)-3-amino-2-[[(3-methylphenyl)sulfonyl]amino]propanoate | C11H16N2O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Treatment of (R)-2-pyrrolidine methanol (I) with di-tert-butyl dicarbonate and K2CO3 gave carbamate (II), which was converted to mesylate (III) using methanesulfonyl chloride and Et3N. Subsequent reaction of (III) with NaCN in DMF provided nitrile (IV). The catalytic hydrogenation of this nitrile in the presence of 4-methylpiperidine (V) furnished the (piperidinylethyl)pyrrolidine (VI). After Boc deprotection of (VI) with trifluoroacetic acid in refluxing CH2Cl2, the resulting pyrrolidine (VII) was finally condensed with m-toluenesulfonyl chloride (VIII) to give the target sulfonamide.
| 【1】 King, F.D.; Forbes, I.T.; Rahman, S.K. (SmithKline Beecham plc); Sulphonamide derivs. and their use in the treatment of CNS disorders. WO 9748681 . |
| 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) | 23309 | (2R)pyrrolidinylmethanol | 68832-13-3 | C5H11NO | 详情 | 详情 |
| (II) | 23310 | tert-butyl (2R)-2-(hydroxymethyl)-1-pyrrolidinecarboxylate | C10H19NO3 | 详情 | 详情 | |
| (III) | 23311 | tert-butyl (2R)-2-[[(methylsulfonyl)oxy]methyl]-1-pyrrolidinecarboxylate | C11H21NO5S | 详情 | 详情 | |
| (IV) | 23312 | tert-butyl (2R)-2-(cyanomethyl)-1-pyrrolidinecarboxylate | C11H18N2O2 | 详情 | 详情 | |
| (V) | 10192 | 4-Methylpiperidine; gamma-Pipecoline | 626-58-4 | C6H13N | 详情 | 详情 |
| (VI) | 23314 | tert-butyl (2R)-2-[2-(4-methyl-1-piperidinyl)ethyl]-1-pyrrolidinecarboxylate | C17H32N2O2 | 详情 | 详情 | |
| (VII) | 23315 | 4-methyl-1-[2-[(2R)pyrrolidinyl]ethyl]piperidine | C12H24N2 | 详情 | 详情 | |
| (VIII) | 23316 | 3-methylbenzenesulfonyl chloride | 1899-93-0 | C7H7ClO2S | 详情 | 详情 |