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【结 构 式】 
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【分子编号】19794 【品名】2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)-1-ethanone 【CA登记号】 |
【 分 子 式 】C17H15N3O3S2 【 分 子 量 】373.45652 【元素组成】C 54.67% H 4.05% N 11.25% O 12.85% S 17.17% |
合成路线1
该中间体在本合成路线中的序号：(VII)The Grignard condensation of N-methoxy-N-methylbenzamide (I) with 4-(methylsulfanyl)benzylmagnesium bromide (II) in THF gives the expected ketone (III), which is brominated with Br2 in CCl4 yielding the alpha-bromoketone (IV). The oxidation of the thioether group of (IV) with oxone (potassium peroxymonosulfate) in dichloromethane/methanol/tert-butanol/water affords the corresponding sulfone (V) (1), which is condesed with 4H-1,2,4-triazole-3-thiol (VI) in refluxing ethanol to give 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)ethanone (VII). Finally, this compound is cyclized with polyphosphoric acid (PPA) in refluxing xylene.
| 【1】 Therien, M.; et al.; Synthesis and biological evaluation of 5, 6-diarylimidazo[2.1-b]thiazole as selective COX-2 inhibitors. Bioorg Med Chem Lett 1997, 7, 1, 47. |
| 【2】 Trimble, L.A.; et al.; Characterization of the in vitro oxidative metabolites of the COX-2 selective inhibitor L-766,112. Bioorg Med Chem Lett 1997, 7, 1, 53. |
| 【3】 Roy, P.; et al.; A new series of selective COX-2 inhibitors: 5, 6-Diarylthiazolo[3,2-b][1,2,4]triazoles. Bioorg Med Chem Lett 1997, 7, 1, 57. |
| 【4】 Gauthier, J.Y.; Lau, C.K.; Leblanc, Y.; Li, C.-S.; Roy, P.; Therien, M.; Wang, Z. (Merck Frosst Canada Inc.); Aryl substd. 5,5 fused aromatic nitrogen cpds. as anti-inflammatory agents. EP 0802917; JP 1999501902; US 5552422; WO 9621667 . |
| 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) | 19788 | N-methoxy-N-methylbenzamide | C9H11NO2 | 详情 | 详情 | |
| (II) | 19789 | bromo[4-(methylsulfanyl)benzyl]magnesium | C8H9BrMgS | 详情 | 详情 | |
| (III) | 19790 | 2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone | C15H14OS | 详情 | 详情 | |
| (IV) | 19791 | 2-bromo-2-[4-(methylsulfanyl)phenyl]-1-phenyl-1-ethanone | C15H13BrOS | 详情 | 详情 | |
| (V) | 19792 | 2-bromo-2-[4-(methylsulfonyl)phenyl]-1-phenyl-1-ethanone | C15H13BrO3S | 详情 | 详情 | |
| (VI) | 19793 | 4H-1,2,4-triazol-3-ylhydrosulfide; 4H-1,2,4-triazole-3-thiol | C2H3N3S | 详情 | 详情 | |
| (VII) | 19794 | 2-[4-(methylsulfonyl)phenyl]-1-phenyl-2-(4H-1,2,4-triazol-3-ylsulfanyl)-1-ethanone | C17H15N3O3S2 | 详情 | 详情 |