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【结 构 式】

【药物名称】SB-258741

【化学名称】4-Methyl-1-[2-[1-(3-methylphenylsulfonyl)pyrrolidin-2(R)-yl]ethyl]piperidine

【CA登记号】201038-58-6

【 分 子 式 】C19H30N2O2S

【 分 子 量 】350.52715

【开发单位】GlaxoSmithKline (Originator)

【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, 5-HT7 Antagonists

合成路线1

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
Extended Information