Ridogrel, R-68070, Ibidel
利多格雷Chemical Name: (E)-5-[(3-Pyridinyl)[3-(trifluoromethyl)phenyl]methylenaminooxy]pentanoic acid; (E)-5-[[[alpha-3-Pyridyl-m-(trifluoromethyl)benzylidene]amino]oxy]valeric acid
CAS No. 110140-89-1
项目整合开发状态: Phase III
项目研究机构: Janssen (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Pharmaceutical use of [[[(3-pyridinyl)methylen]amino]oxy]alkanoic acid and esters
文献作者:Freyne,E.J.E.; Raeymaekers,A.H.; Sipido,V.; Venet,M.G.(Janssen Pharmaceutica NV)
参考来源:EP 0221601; JP 1987161759; JP 1991068556; US 4746671
📄 详细内容
合成路线: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.
参考文献标题:RIDOGREL
文献作者:Freyne,E.J.; Raeymaekers,A.H.M.; Venet,M.G.; Sipido,V.K.; De Clerck,F.
参考来源:Drugs Fut 1990,15(5),463
产品链接: CAS No. 110140-89-1››