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【结 构 式】 
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【药物名称】 【化学名称】4-[3-(4-Fluorophenyl)-2-oxo-2,3-dihydrooxazol-4-yl]benzenesulfonamide 【CA登记号】197240-09-8 【 分 子 式 】C15H11FN2O4S 【 分 子 量 】334.32832 |
【开发单位】Almirall Prodesfarma (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Cyclooxygenase-2 Inhibitors |
合成路线1
The synthesis of the title compound has been reported by two related procedures. Cyclization of phenacyl N-(4-fluorophenyl)carbamate (I) in boiling HOAc gave rise to oxazolone (II). Chlorosulfonation of (II), followed by treatment of the resulting sulfonyl chloride (III) with ammonia, yielded the title sulfonamide.
| 【1】 Puig Duran, C.; Pujol Noguera, F.; Fernandez Forner, D. (Almirall Prodesfarma, SA); 2-(3H)-Oxazolone derivs. and their use as COX-2 inhibitors. EP 0888316; ES 2125161; JP 2000506876; WO 9734882 . |
合成路线2
In an alternative procedure, sodium 4-acetylbenzenesulfonate (IV) was refluxed with POCl3 and subsequently treated with dibenzylamine to afford sulfonamide (V). Bromination of (V) in chloroform yielded the bromo ketone (VI), which was hydrolyzed to phenacyl alcohol (VII) by treatment with ethanolic betaine, followed by aqueous NaHCO3. Addition of 4-fluorophenyl isocyanate (VIII) to (VII) and then cyclization in refluxing HOAc yielded the oxazolone (IX). Final debenzylation was achieved with concentrated H2SO4 to give the target sulfonamide.
| 【1】 Godessart, N.; Crespo, M.I.; Puig, C.; et al.; Synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active cyclooxygenase-2 inhibitors. J Med Chem 2000, 43, 2, 214. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 44956 | sodium 4-acetylbenzenesulfonate | 61827-67-6 | C8H7NaO4S | 详情 | 详情 |
| (V) | 44957 | 4-acetyl-N,N-dibenzylbenzenesulfonamide | C22H21NO3S | 详情 | 详情 | |
| (VI) | 44958 | N,N-dibenzyl-4-(2-bromoacetyl)benzenesulfonamide | C22H20BrNO3S | 详情 | 详情 | |
| (VII) | 44959 | N,N-dibenzyl-4-glycoloylbenzenesulfonamide | C22H21NO4S | 详情 | 详情 | |
| (VIII) | 17977 | 1-Fluoro-4-isocyanatobenzene; 4-Fluorophenyl isocyanate | 1195-45-5 | C7H4FNO | 详情 | 详情 |
| (IX) | 44960 | N,N-dibenzyl-4-[3-(4-fluorophenyl)-2-oxo-2,3-dihydro-1,3-oxazol-4-yl]benzenesulfonamide | C29H23FN2O4S | 详情 | 详情 |