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【结 构 式】 
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【药物名称】PAC-20030, SC-0030, JYL-1421 【化学名称】N-[4-[3-(4-tert-Butylbenzyl)thioureidomethyl]-2-fluorophenyl]methanesulfonamide 【CA登记号】401907-26-4 【 分 子 式 】C20H26FN3O2S2 【 分 子 量 】423.57552 |
【开发单位】Schwarz (Proprietary), AmorePacific (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, RENAL-UROLOGIC DRUGS, Urinary Incontinence Therapy, Vanilloid VR1 Receptor Antagonists |
合成路线1
Acylation of 2-fluoro-4-iodoaniline (I) with methanesulfonyl chloride affords the corresponding sulfonamide (II). Subsequent iodide displacement in (II) with zinc cyanide in the presence of palladium catalyst furnishes benzonitrile (III), which is further reduced to the benzylic amine (IV) by catalytic hydrogenation over Pd/C. Treatment of 4-(tert-butyl)benzylamine (V) with di-2-pyridyl thionocarbonate leads to the isothiocyanate (VI). This is finally condensed with amine (IV) to provide the target N,N'-dibenzyl thiourea derivative.
| 【1】 Lee, J.W.; Kim, J.K.; Choi, J.K.; Lee, Y.S.; Park, H.G.; Kim, S.Y.; Kim, H.D.; Park, Y.H.; Suh, Y.G.; Joo, Y.H.; Lim, K.M.; Moh, J.H.; Jeong, Y.S.; Yi, J.B.; Oh, U.T.; Park, O.H.; Koh, H.J.; Oh, Y.M. (AmorePacific Corp.); Novel thiourea derivs. and the pharmaceutical compsns. containing the same. EP 1303483; EP 1311478; US 2003212140; WO 0216318; WO 0216319 . |
| 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) | 63342 | 2-fluoro-4-iodoaniline; 2-fluoro-4-iodophenylamine | 29632-74-4 | C6H5FIN | 详情 | 详情 |
| (II) | 63343 | N-(2-fluoro-4-iodophenyl)methanesulfonamide | C7H7FINO2S | 详情 | 详情 | |
| (III) | 63344 | N-(4-cyano-2-fluorophenyl)methanesulfonamide | C8H7FN2O2S | 详情 | 详情 | |
| (IV) | 63345 | N-[4-(aminomethyl)-2-fluorophenyl]methanesulfonamide | C8H11FN2O2S | 详情 | 详情 | |
| (V) | 47899 | 4-(tert-butyl)benzylamine; [4-(tert-butyl)phenyl]methanamine | 39895-55-1 | C11H17N | 详情 | 详情 |
| (VI) | 63346 | 1-(1,1-dimethylethyl)-4-(isothiocyanatomethyl)benzene; [4-(1,1-dimethylethyl)phenyl]methyl isothiocyanate | C12H15NS | 详情 | 详情 |