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【结 构 式】 
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【分子编号】32846 【品名】5-bromo-1-indolinecarbothioamide 【CA登记号】 |
【 分 子 式 】C9H9BrN2S 【 分 子 量 】257.15394 【元素组成】C 42.04% H 3.53% Br 31.07% N 10.89% S 12.47% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Condensation of 5-bromoindoline (XV) with KSCN produced thiourea (XVI). Subsequent cyclization of (XVI) with 1-chloro-2-decanone (XVII) generated the 4-n-octylthiazole system (XVIII). Lithium-bromine exchange in (XVIII) with butyllithium at -78 C, followed by reaction with SO2 afforded sulfinic acid (XIX), which was then oxidized with N-chlorosuccinimide to the sulfonyl chloride (XX). The condensation of sulfonyl chloride (XX) with carbamate (VII) in the presence of pyridine in CH2Cl2 gave rise to sulfonamide (XXI). Finally, the Boc protecting group of (XXI)) was cleaved by treatment with trifluoroacetic acid.
| 【1】 Tota, L.; Barritta, A.M.; Fisher, M.H.; Mathvink, R.J.; Cascieri, M.A.; Deng, L.; Candelore, M.R.; Weber, A.E.; Wyvratt, M.J.; Strader, C.D.; Potent, selective human beta3 adrenergic receptor agonists containing a substituted indoline-5-sulfonamide pharmacophore. Bioorg Med Chem Lett 1999, 9, 13, 1869. |
| 【2】 Fisher, M.H.; Naylor, E.M.; Ok, D.; Weber, A.E.; Shih, T.; Ok, H. (Merck & Co., Inc.); Substd. sulfonamides as selective beta3 agonists for the treatment of diabetes and obesity. EP 0757674; JP 1997512275; US 5541197; US 5561142; WO 9529159 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 26653 | tert-butyl (3S,4S)-1-benzyl-4-methoxypyrrolidinyl(methyl)carbamate | C18H28N2O3 | 详情 | 详情 | |
| (XV) | 32845 | 5-bromoindoline | 22190-33-6 | C8H8BrN | 详情 | 详情 |
| (XVI) | 32846 | 5-bromo-1-indolinecarbothioamide | C9H9BrN2S | 详情 | 详情 | |
| (XVII) | 32851 | 1-chloro-2-decanone | C10H19ClO | 详情 | 详情 | |
| (XVIII) | 32847 | 5-bromo-1-(4-octyl-1,3-thiazol-2-yl)indoline | C19H25BrN2S | 详情 | 详情 | |
| (XIX) | 32848 | 1-(4-octyl-1,3-thiazol-2-yl)-5-indolinesulfinic acid | C19H26N2O2S2 | 详情 | 详情 | |
| (XX) | 32849 | 1-(4-octyl-1,3-thiazol-2-yl)-5-indolinesulfonyl chloride | C19H25ClN2O2S2 | 详情 | 详情 | |
| (XXI) | 32850 | tert-butyl (2R)-2-hydroxy-2-(3-pyridinyl)ethyl[4-([[1-(4-octyl-1,3-thiazol-2-yl)-2,3-dihydro-1H-indol-5-yl]sulfonyl]amino)phenethyl]carbamate | C39H51N5O5S2 | 详情 | 详情 |