|
【结 构 式】 
|
【药物名称】FK-3311 【化学名称】4-Acetyl-2-(2,4-difluorophenoxy)methanesulfonanilide 【CA登记号】116686-15-8 【 分 子 式 】C15H13F2NO4S 【 分 子 量 】341.33596 |
【开发单位】Fujisawa (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Cyclooxygenase-2 Inhibitors, Non-Steroidal Antiinflammatory Drugs |
合成路线1
This compound has been obtained by two different ways: 1) The oxidation of 4'-amino-3'-chloroacetophenone (I) with NaNO2 and HCl in water gives 3'-chloro-4-nitroacetophenone (II), which is condensed with 2,4-difluorophenol (III) by means of K2CO3 in xylene yielding 3'-(2,4-difluorophenyl)-4'-nitroacetophenone (IV). The reduction of (IV) with Fe and NH4Cl in ethanol affords the corresponding 4'-amino compound (V), which is finally treated with methanesulfonyl chloride and pyridine. 2) The reaction of 4'-aminoacetophenone (VI) with methanesulfonyl chloride as before gives the corresponding sulfonamide (VII), which is brominated with Br2 in acetic acid yielding N-(4-acetyl-3-bromophenyl)methanesulfonamide (VIII). Finally, this compound is condensed with 2,4-difluorophenol (III) by means of K2CO3 and CuCl as before.
| 【1】 Zanka, A.; et al.; Process development of a novel anti-inflammatory agent. The regiospecific bromination of 4'-acetylmethanesulfonanilide. Org Process Res Dev 1998, 2, 2, 71. |
| 【2】 Tsuji, K.; et al.; Studies on antiinflammatory agents. I. Synthesis and pharmacological properties of 2'-phenoxymethanesulfonanilide derivatives. Chem Pharm Bull 1992, 40, 9, 2399. |
| 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) | 33161 | 1-(4-amino-3-chlorophenyl)-1-ethanone | C8H8ClNO | 详情 | 详情 | |
| (II) | 33162 | 1-(3-chloro-4-nitrophenyl)-1-ethanone | C8H6ClNO3 | 详情 | 详情 | |
| (III) | 21486 | 2,4-difluorophenol | 367-27-1 | C6H4F2O | 详情 | 详情 |
| (IV) | 33163 | 1-[3-(2,4-difluorophenoxy)-4-nitrophenyl]-1-ethanone | C14H9F2NO4 | 详情 | 详情 | |
| (V) | 33164 | 1-[4-amino-3-(2,4-difluorophenoxy)phenyl]-1-ethanone | C14H11F2NO2 | 详情 | 详情 | |
| (VI) | 27847 | 1-(4-aminophenyl)-1-ethanone | 99-92-3 | C8H9NO | 详情 | 详情 |
| (VII) | 33165 | N-(4-acetylphenyl)methanesulfonamide | C9H11NO3S | 详情 | 详情 | |
| (VIII) | 33166 | N-(4-acetyl-2-bromophenyl)methanesulfonamide | C9H10BrNO3S | 详情 | 详情 |