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【结 构 式】 
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【药物名称】 【化学名称】1-(3-Fluorophenyl)-1-[6-[4-(methylsulfonyl)phenyl]-1,3-benzodioxol-5-yl]methanone 【CA登记号】445039-17-8 【 分 子 式 】C21H15FO5S 【 分 子 量 】398.4131 |
【开发单位】NitroMed (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 |
合成路线1
Piperonal (I) is brominated by means of Br2 in AcOH to produce (II). Subsequent Suzuki coupling of aryl bromide (II) with 4-(methylsulfanyl)benzeneboronic acid (III) furnishes adduct (IV). Addition of 3-fluorophenylmagnesium bromide (V) to aldehyde (IV) leads to carbinol (VI). The sulfide group is further oxidized to sulfone (VII) employing oxone in aqueous MeOH. Finally, oxidation of alcohol (VII) with pyridinium chlorochromate provides the target ketone. (1,2)
| 【1】 Ezawa, M.; Khanapure, S.P.; Garvey, D.S.; Young, D.; Earl, R.; Gaston, R.; Fang, F.; Marek, P.; Shumway, M.; Trocha, M.; Tam, S.W.; Janero, D.R.; Letts, L.G.; Design and synthesis of novel benzo-dioxolane cyclooxygenase (COX-2) selective inhibitors. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 243. |
| 【2】 Earl, R.A.; Garvey, D.S.; Khanapure, S.P.; Gaston, R.D.; Fang, X.; Ezawa, M. (NitroMed Inc.); Substd. aryl cpds. as novel cyclooxygenase-2 selective inhibitors, compsns. and methods of use. US 2002119977; WO 0260378 . |
| 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) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |
| (II) | 46376 | ethyl 3-(3-[2-[[(6-bromo-1,3-benzodioxol-5-yl)methyl](2-ethoxy-2-oxoacetyl)amino]phenyl]-3-oxopropyl)benzoate | C30H28BrNO8 | 详情 | 详情 | |
| (III) | 18561 | 4-(methylsulfanyl)phenylboronic acid | 98546-51-1 | C7H9BO2S | 详情 | 详情 |
| (IV) | 64023 | 6-[4-(methylsulfanyl)phenyl]-1,3-benzodioxole-5-carbaldehyde | C15H12O3S | 详情 | 详情 | |
| (V) | 35384 | bromo(3-fluorophenyl)magnesium | C6H4BrFMg | 详情 | 详情 | |
| (VI) | 64024 | (3-fluorophenyl){6-[4-(methylsulfanyl)phenyl]-1,3-benzodioxol-5-yl}methanol | C21H17FO3S | 详情 | 详情 | |
| (VII) | 64025 | (3-fluorophenyl){6-[4-(methylsulfonyl)phenyl]-1,3-benzodioxol-5-yl}methanol | C21H17FO5S | 详情 | 详情 |