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【结 构 式】 
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【分子编号】49981 【品名】ethyl 1-[(E)-3-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-3-(trifluoromethyl)phenyl]-2-propenoyl]-3-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C26H26F3NO5S 【 分 子 量 】521.5573896 【元素组成】C 59.88% H 5.02% F 10.93% N 2.69% O 15.34% S 6.15% |
合成路线1
该中间体在本合成路线中的序号：(VII)Nucleophilic substitution of 4-fluoro-3-(trifluoromethyl)benzaldehyde (II) with 6-mercaptobenzodioxan (I) afforded the sulfanyl aldehyde (III). Knoevenagel condensation of aldehyde (III) with malonic acid furnished the cinnamic acid derivative (IV), which was subsequently converted to acid chloride (V) by treatment with oxalyl chloride. Acid chloride (V) was then coupled with ethyl nipecotate (VI), yielding amide (VII). The ethyl ester group of (VII) was finally hydrolyzed using NaOH in aqueous ethanol.
| 【1】 Pei, Z.; et al.; Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Maide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides. J Med Chem 2001, 44, 18, 2913. |
| 【2】 Lynch, J.K.; Link, J.; Zhu, G.-D.; Boyd, S.A.; Winn, M.; Pei, Z.; Gunawardana, I.W.; Liu, G.; Xin, Z.; Jae, H.-S.; Freeman, J.C.; Von Geldern, T.; Staeger, M.A. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. US 6110922; WO 0039081 . |
| 【3】 Jae, H.-S.; Pei, Z.; Staeger, M.A.; Gunawardana, I.W.; Winn, M.; Freeman, J.C.; Liu, G.; Link, J.; Boyd, S.A.; Zhu, G.-D.; Von Geldern, T.W.; Xin, Z.; Lynch, J.K.; Wang, S. (Abbott Laboratories Inc.); Cell adhesion-inhibiting antiinflammatory and immune-suppressive cpds.. WO 0059880 . |
| 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) | 49976 | 2,3-dihydro-1,4-benzodioxin-6-ylhydrosulfide; 2,3-dihydro-1,4-benzodioxine-6-thiol | C8H8O2S | 详情 | 详情 | |
| (II) | 49977 | alpha,alpha,alpha,4-Tetrafluoro-m-tolualdehyde; 4-Fluoro-3-(trifluoromethyl)benzaldehyde | 67515-60-0 | C8H4F4O | 详情 | 详情 |
| (III) | 49978 | 4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-3-(trifluoromethyl)benzaldehyde | C16H11F3O3S | 详情 | 详情 | |
| (IV) | 49979 | (E)-3-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-3-(trifluoromethyl)phenyl]-2-propenoic acid | C18H13F3O4S | 详情 | 详情 | |
| (V) | 49980 | (E)-3-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-3-(trifluoromethyl)phenyl]-2-propenoyl chloride | C18H12ClF3O3S | 详情 | 详情 | |
| (VI) | 25693 | ethyl 3-piperidinecarboxylate | 5006-62-2 | C8H15NO2 | 详情 | 详情 |
| (VII) | 49981 | ethyl 1-[(E)-3-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-3-(trifluoromethyl)phenyl]-2-propenoyl]-3-piperidinecarboxylate | C26H26F3NO5S | 详情 | 详情 |