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【结 构 式】 
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【药物名称】L-766112 【化学名称】5-[4-(Methylsulfonyl)phenyl]-6-phenylimidazo[2,1-b]thiazole 【CA登记号】 【 分 子 式 】C18H14N2O2S2 【 分 子 量 】354.45248 |
【开发单位】Merck Frosst (Originator) 【药理作用】Cyclooxygenase-2 Inhibitors, Non-Steroidal Antiinflammatory Drugs |
合成路线1
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 finally cyclocondesed with thiazol-2-amine (VI) in refluxing ethanol or isopentanol.
| 【1】 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) | 19789 | bromo[4-(methylsulfanyl)benzyl]magnesium | C8H9BrMgS | 详情 | 详情 | |
| (II) | 19788 | N-methoxy-N-methylbenzamide | C9H11NO2 | 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) | 19795 | 2-Thiazolamine; 1,3-thiazol-2-amine; 1,3-thiazol-2-ylamine | 96-50-4 | C3H4N2S | 详情 | 详情 |
Extended Information