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【结 构 式】 
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【药物名称】 【化学名称】3-(3,4-Difluorophenoxy)-5,5-dimethyl-4-[4-(methylsulfonyl)phenyl]furan-2(5H)-one 【CA登记号】 【 分 子 式 】C19H16F2O5S 【 分 子 量 】394.39717 |
【开发单位】Merck Frosst (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Antiarthritic Drugs, Non-Opioid Analgesics, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Cyclooxygenase-2 Inhibitors, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The Friedel Crafts condensation of thioanisole (I) with isobutyryl chloride (II) by means of AlCl3 gives the propiophenone (III), which is alpha hydroxylated by means of Aliquant 336 and NaOH yielding the alpha hydroxy ketone (IV). The oxidation of the methylsulfanyl group of (IV) with magnesium monoperoxyphthalate (MMPP) affords the corresponding sulfone (V), which is finally cyclized with 2-(3,4-difluorophenoxy)acetic acid (VI) by means of 1-cyclohexyl-3-[2-(4-morpholinyl)ethyl]carbodiimide metho-p-toluenesulfonate (CMC), DMAP and DBU to furnish the target furanone.
| 【1】 Brideau, C.; Li, C.-S.; Chan, C.C.; Black, W.C.; et al.; A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett 1999, 9, 22, 3181. |
| 【2】 Belley, M.; Gauthier, J.Y.; Grimm, E.; Leblanc, Y.; Li, C.-S.; Therien, M.; Lau, C.-K.; Prasit, P.; Roy, P. (Merck Frosst Canada Inc.); (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors. EP 0863891; JP 1999500146; US 5981576; WO 9714691 . |
| 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) | 19722 | 2-[(3aR,5S,7S,7aS)-7-hydroxy-7-(2-methoxyphenyl)octahydro-1H-isoindol-5-yl]acetonitrile | C17H22N2O2 | 详情 | 详情 | |
| (II) | 14932 | isobutyryl chloride; 2-methylpropanoyl chloride | 79-30-1 | C4H7ClO | 详情 | 详情 |
| (III) | 36573 | 2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone | C11H14OS | 详情 | 详情 | |
| (IV) | 36574 | 2-hydroxy-2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone | C11H14O2S | 详情 | 详情 | |
| (V) | 36575 | 2-hydroxy-2-methyl-1-[4-(methylsulfonyl)phenyl]-1-propanone | C11H14O4S | 详情 | 详情 | |
| (VI) | 18826 | 2-(3,4-difluorophenoxy)acetic acid | C8H6F2O3 | 详情 | 详情 |