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【结 构 式】 
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【药物名称】E-5110 【化学名称】3-[3,5-Di(tert-butyl)-4-hydroxybenzylidene]-1-methoxypyrrolidin-2-one 【CA登记号】107746-52-1 【 分 子 式 】C20H29NO3 【 分 子 量 】331.45903 |
【开发单位】Eisai (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Non-Steroidal Antiinflammatory Drugs |
合成路线1
The reaction of gamma-butyrolactone (I) with Br2 and PBr3 at 100 C followed by a treatment with SOCl2 gives 2,4-dibromobutanoyl chloride (II), which is condensed with O-methylhydroxylamine by means of NaOH in CHCl3 yielding N-methoxy-3-bromopyrrolidin-2-one (III). The reaction of (III) with triphenylphosphine (IV) in hot THF affords the triphenylphosphonium salt (V), which is finally condensed with 3,5-di(tert-butyl)-4-hydroxybenzaldehyde (VI) by means of triethylamine in hot ethanol.
| 【1】 Ikuta, H.; Yamagishi, Y.; Akasaka, K.; Yamatsu, I.; Kobayashi, S.; Shirota, H.; Katayamaa, K. (Eisai Co., Ltd.); 2-Pyrrolidone derivatives, process for preparing them, pharmaceutical compositions and use. AU 8656766; EP 0204964; ES 8800148; JP 1986257967; US 4833160 . |
| 【2】 Shirota, H.; Yamatsu, I.; Yamada, K.; Yomagishi, Y.; Katayama, K.; Kobayashi, S.; Ikuta, H.; Synthesis and antiinflammatory activities of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones. J Med Chem 1987, 30, 11, 1995. |
| 【3】 Prous, J.; Castaner, J.; E-5110. Drugs Fut 1989, 14, 4, 307. |
| 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) | 20576 | dihydro-2(3H)-furanone | 96-48-0 | C4H6O2 | 详情 | 详情 |
| (II) | 20577 | 2,4-dibromobutanoyl chloride | C4H5Br2ClO | 详情 | 详情 | |
| (III) | 20578 | 3-bromo-1-methoxy-2-pyrrolidinone | C5H8BrNO2 | 详情 | 详情 | |
| (V) | 20579 | (1-methoxy-2-oxo-3-pyrrolidinyl)(triphenyl)phosphonium bromide | C23H23BrNO2P | 详情 | 详情 | |
| (VI) | 14875 | 3,5-Bis(1,1-dimethylethyl)-4-hydroxybenzaldehyde; 3,5-di(tert-butyl)-4-hydroxybenzaldehyde; 3,5-Di-tert-butyl-4-hydroxybenzaldehyde | 1620-98-0 | C15H22O2 | 详情 | 详情 |