合成路线:The cyclization of ethyl 2-chloro-2-(4-fluorophenylhydrazono)acetate (I) with 4-(4-chloro-beta-styryl)morpholine (II) by means of triethyiamine in refluxing CHCl3 gives ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-morpholino-4,5-dihydropyrazol-3-carboxylate (III),which is treated with HCl in refluxing dioxane yielding ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-carboxylate (IV).The reduction of (IV) with diisobutylaluminum hydride in toluene affords [4-(4-chlorophenyl)-1-(4-fluorophenyl)-3-pyrazolyl]methanol (V),which by treatment with aqueous 63% HBr at 90 C is converted to 3-(bromomethyl)-4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole (VI).The reaction of (VI) with KCN and 18-crown-6 in hot acetonitrile affords 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole-3-acetonitrile (VII),which is finally hydrolyzed with NaOH in water-DMSO at 120 C.
参考文献标题:Derivatives of antiphlogistically effective carboxylic acids,their preparation and medicinal use
文献作者:Vorbrueggen,H.(Schering AG)
参考来源:DE 3049405; EP 0054812; GB 2091251; JP 57167977; US 4391814
合成路线:The cyclization of ethyl 2-chloro-2-(4-fluorophenylhydrazono)acetate (I) with 4-(4-chloro-beta-styryl)morpholine (II) by means of triethyiamine in refluxing CHCl3 gives ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-morpholino-4,5-dihydropyrazol-3-carboxylate (III),which is treated with HCl in refluxing dioxane yielding ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-carboxylate (IV).The reduction of (IV) with diisobutylaluminum hydride in toluene affords [4-(4-chlorophenyl)-1-(4-fluorophenyl)-3-pyrazolyl]methanol (V),which by treatment with aqueous 63% HBr at 90 C is converted to 3-(bromomethyl)-4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole (VI).The reaction of (VI) with KCN and 18-crown-6 in hot acetonitrile affords 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole-3-acetonitrile (VII),which is finally hydrolyzed with NaOH in water-DMSO at 120 C.
参考文献标题:Pirazolac
文献作者:Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1986,11(4),272
合成路线:The cyclization of ethyl 2-chloro-2-(4-fluorophenylhydrazono)acetate (I) with 4-(4-chloro-beta-styryl)morpholine (II) by means of triethyiamine in refluxing CHCl3 gives ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-morpholino-4,5-dihydropyrazol-3-carboxylate (III),which is treated with HCl in refluxing dioxane yielding ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-carboxylate (IV).The reduction of (IV) with diisobutylaluminum hydride in toluene affords [4-(4-chlorophenyl)-1-(4-fluorophenyl)-3-pyrazolyl]methanol (V),which by treatment with aqueous 63% HBr at 90 C is converted to 3-(bromomethyl)-4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole (VI).The reaction of (VI) with KCN and 18-crown-6 in hot acetonitrile affords 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole-3-acetonitrile (VII),which is finally hydrolyzed with NaOH in water-DMSO at 120 C.
参考文献标题:
文献作者:Herrine,S.K.; et al.
参考来源:Eur J Drug Metab Pharmacokinet 1985,10(1),41-53
合成路线:The cyclization of ethyl 2-chloro-2-(4-fluorophenylhydrazono)acetate (I) with 4-(4-chloro-beta-styryl)morpholine (II) by means of triethyiamine in refluxing CHCl3 gives ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)-5-morpholino-4,5-dihydropyrazol-3-carboxylate (III),which is treated with HCl in refluxing dioxane yielding ethyl 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-carboxylate (IV).The reduction of (IV) with diisobutylaluminum hydride in toluene affords [4-(4-chlorophenyl)-1-(4-fluorophenyl)-3-pyrazolyl]methanol (V),which by treatment with aqueous 63% HBr at 90 C is converted to 3-(bromomethyl)-4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole (VI).The reaction of (VI) with KCN and 18-crown-6 in hot acetonitrile affords 4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole-3-acetonitrile (VII),which is finally hydrolyzed with NaOH in water-DMSO at 120 C.
参考文献标题:
文献作者:
参考来源:J Med Chem Chim Ther 1982,1727-34
产品链接: CAS No. 71002-09-0››