网站主页>>>项目整合精选>>>项目整合精选>>>Cizolirtine citrate, E-3710 citrate, E-4018, E-4961((S)-isomer), E-4960((R)-isomer)

Cizolirtine citrate, E-3710 citrate, E-4018, E-4961((S)-isomer), E-4960((R)-isomer)

乙氨酸,N-二甲基-2-[(1-甲基-1羟基-5-基)苯甲氧基]-,2-羟基-1,2,2,-3-丙烷三羧酸酯 乙胺,N-二甲基-2-[(1-甲基-1H-吡咯唑-5-基)苯甲氧基]-,2-羟基-1,2,3-丙烷三羧酸盐(1:1) Chemical Name: (?-O-[2-(Dimethylamino)ethyl]-1-methyl-alpha-phenyl-1H-pyrazol-5-methanol citrate; (?-5-[alpha-[2-(Dimethylamino)ethoxy]benzyl]-1-methyl-1H-pyrazole citrate; (?-N,N-Dimethyl-2-[1-(1-methyl-1H-pyrazol-5-yl)-1-phenylmethoxy]ethanamine citrate
CAS No. 142155-44-0, 251375-82-3 ((1:1) salt), 148981-63-9 ((R)-isomer), 148981-65-1 ((S)-isomer), 142155-43-9 (free base), 148981-64-0 (free base, (S)-isomer)
项目整合开发状态: Phase III
项目研究机构: Esteve (Originator)
合成路线:The key compound 5-(alpha-hydroxybenzyl)-1-methyl-1H-pyrazole [(?-I] was obtained by two related ways: 1) by condensation of N-methylpyrazole with benzonitrile and butyl lithium in tetrahydrofuran and reduction of the obtained ketone with sodium borohydride in methanol or 2) by condensation of N-methylpyrazole with benzaldehyde and butyl lithium in THF/toluene.The alkylation of [(?-I] with 2-(dimethylamino)ethyl chloride hydrochloride was carried out using phase transfer conditions and reaction with citric acid using propanone as solvent.
📌 参考资料/链接:
参考文献标题:Aryl-heteroaryl-carbinol derivs.having an analgesic activity
文献作者:Colombo,A.; Par閟,J.; Frigola,J.(Laboratorios del Dr.Esteve,SA)
参考来源:EP 0289380; FR 2613720; JP 1988267761; US 5017596

📄 详细内容


合成路线:Asymmetric reduction of ketone (III) with catecholborane or borane璵ethyl sulfide complex and CBS-oxazaborolidene as catalyst afforded [(R)-(+)-I] or [(S)-(?-I].

参考文献标题:Process for obtaining enantiomers of cizolirtine
文献作者:Frigola-Constansa,J.; Torrens-Jover,A.(Laboratorios del Dr.Esteve,SA)
参考来源:EP 1029852; ES 2130083; US 6118009; WO 9907684


合成路线:The transesterification of [(?-I] with vinyl acetate enzymatically catalyzed (lipase) allowed the selective recovery of the enatiomer [(R)-(+)-I] and the hydrolysis and racemization of the undesired enantiomer [(S)-(?-II] with hydrochloric acid.

参考文献标题:Method for separating carbinols
文献作者:Frigola Constansa,J.; Cuberes Altisent,M.R.; Berrocal Romero,J.M.; Gotor Santamaria,V.(Laboratorios del Dr.Esteve,SA)
参考来源:ES 2128959; FR 2742147; US 5849931; WO 9720817


合成路线:The optical resolution of (?-cizolirtine was accomplished by recrystallizing diastereoisomeric salts formed with the antipodes of di-p-toluoyltartaric acid in isopropanol.

参考文献标题:Resolution of amines
文献作者:Frigola-Constansa,J.; Torrens-Jover,A.(Laboratorios del Dr.Esteve,SA)
参考来源:EP 1024137; ES 2130079; US 6187930; WO 9902500


合成路线:The key compound 5-(alpha-hydroxybenzyl)-1-methyl-1H-pyrazole [(?-I] was obtained by two related ways: 1) by condensation of N-methylpyrazole with benzonitrile and butyl lithium in tetrahydrofuran and reduction of the obtained ketone with sodium borohydride in methanol or 2) by condensation of N-methylpyrazole with benzaldehyde and butyl lithium in THF/toluene.The alkylation of [(?-I] with 2-(dimethylamino)ethyl chloride hydrochloride was carried out using phase transfer conditions and reaction with citric acid using propanone as solvent.

合成路线:The optical resolution of (?-cizolirtine was accomplished by recrystallizing diastereoisomeric salts formed with the antipodes of di-p-toluoyltartaric acid in isopropanol.

合成路线:Resolution of alcohol [(?-I] as its diastereomeric O-acetylmandelate esters and saponification of each of them in ethanol in the presence of catalytic amounts of sodium cyanide yielded the enantiomerically pure alcohols [(R)-(+)-I] and [(S)-(?-I].

合成路线:The transesterification of [(?-I] with vinyl acetate enzymatically catalyzed (lipase) allowed the selective recovery of the enatiomer [(R)-(+)-I] and the hydrolysis and racemization of the undesired enantiomer [(S)-(?-II] with hydrochloric acid.

合成路线:Asymmetric reduction of ketone (III) with catecholborane or borane璵ethyl sulfide complex and CBS-oxazaborolidene as catalyst afforded [(R)-(+)-I] or [(S)-(?-I].

合成路线:Ethyl (R)-mandelate [(R)-IV] was protected as its tert-butyldimethylsilyl ether and reduced with DIBAL to [(R)-V],which was treated with ethoxycarbonylmethyl-enetriphenylphosphorane,followed by reduction to give [(R)-VI].Subsequent oxidation to [(R)-VII] and cyclization by reaction with methylhydrazine afforded a mixture of pyrazolines [(R)-VIII].Oxidation to pyrazole and deprotection yielded [(R)-(+)-I].

参考文献标题:Cizolirtine Citrate
文献作者:Farr? A.J.; Frigola,J.
参考来源:Drugs Fut 2002,27(8),721


合成路线:Resolution of alcohol [(?-I] as its diastereomeric O-acetylmandelate esters and saponification of each of them in ethanol in the presence of catalytic amounts of sodium cyanide yielded the enantiomerically pure alcohols [(R)-(+)-I] and [(S)-(?-I].

合成路线:Ethyl (R)-mandelate [(R)-IV] was protected as its tert-butyldimethylsilyl ether and reduced with DIBAL to [(R)-V],which was treated with ethoxycarbonylmethyl-enetriphenylphosphorane,followed by reduction to give [(R)-VI].Subsequent oxidation to [(R)-VII] and cyclization by reaction with methylhydrazine afforded a mixture of pyrazolines [(R)-VIII].Oxidation to pyrazole and deprotection yielded [(R)-(+)-I].
参考文献标题:Preparation of the enantiomers of the analgesic E-3710
文献作者:Hueso,J.; Frigola,J.; Farr? A.; Berrocal,J.; Gutierrez,B.
参考来源:Bioorg Med Chem Lett 1993,3(2),269


产品链接: CAS No. 142155-44-0››

产品链接: CAS No.251375-82-3››