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【结 构 式】 
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【药物名称】Ridogrel, R-68070, Ibidel 【化学名称】(E)-5-[(3-Pyridinyl)[3-(trifluoromethyl)phenyl]methylenaminooxy]pentanoic acid 【CA登记号】110140-89-1 【 分 子 式 】C18H17F3N2O3 【 分 子 量 】366.34299 |
【开发单位】Janssen (Originator) 【药理作用】CARDIOVASCULAR DRUGS, GASTROINTESTINAL DRUGS, Hypertension, Treatment of, Inflammatory Bowel Disease, Agents for, Prostanoid TP (Thromboxane A2) Antagonists, Thromboxane Synthase Inhibitors |
合成路线1
Grignard reaction of 3-trifluoromethylbenzene-magnesium bromide (II) with 3-pyridinecarboxaldehyde (I) in THF at 15 C gives alpha-[3-(trifluoromethyl)phenyl]-3-pyridinemethanol (III). Oxidation of this compound with MnO2 in refluxing CH2Cl2 yields the corresponding ketone (IV). The oximation reaction carried out with NH2OH.HCl in isopropanol-HCl at 70 C affords (3-pyridinyl)-[3-(trifluoromethyl)phenyl]methanone oxime (V) (more than 90% of the E-isomer). The alkylation of (V) with ethyl bromovalerate in the presence of NaOH in DMF produces ethyl 5-[[[(3-pyridinyl)[3-(trifluoromethyl)phenyl]methylene]amino]oxy] pentanoate (VI). Hydrolysis of the ester with aqueous NaOH followed by HCl treatment gives, after recrystallization from diisopropylether, ridogrel.
| 【1】 Freyne, E.J.E.; Raeymaekers, A.H.; Sipido, V.; Venet, M.G. (Janssen Pharmaceutica NV); Pharmaceutical use of [[[(3-pyridinyl)methylen]amino]oxy]alkanoic acid and esters. EP 0221601; JP 1987161759; JP 1991068556; US 4746671 . |
| 【2】 Freyne, E.J.; Raeymaekers, A.H.M.; Venet, M.G.; Sipido, V.K.; De Clerck, F.; RIDOGREL. Drugs Fut 1990, 15, 5, 463. |
| 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) | 12849 | Nicotinaldehyde; 3-Pyridinecarboxaldehyde | 500-22-1 | C6H5NO | 详情 | 详情 |
| (II) | 12028 | Bromo[3-(trifluoromethyl)phenyl]magnesium | 402-26-6 | C7H4BrF3Mg | 详情 | 详情 |
| (III) | 12029 | 3-Pyridinyl[3-(trifluoromethyl)phenyl]methanol | C13H10F3NO | 详情 | 详情 | |
| (IV) | 12030 | 3-Pyridinyl[3-(trifluoromethyl)phenyl]methanone | C13H8F3NO | 详情 | 详情 | |
| (V) | 12031 | 3-Pyridinyl[3-(trifluoromethyl)phenyl]methanone oxime | C13H9F3N2O | 详情 | 详情 |