GYKI-47261
4-(8-氯-2-甲基-11H-咪唑并[1,2-c][2,3]苯并二氮杂卓-6-基)苯胺二盐酸盐Chemical Name: 4-(8-Chloro-2-methyl-11H-imidazo[1,2-c][2,3]benzodiazepin-6-yl)phenylamine
CAS No. 220445-20-5
项目整合开发状态: Preclinical
项目研究机构: Institute for Drug Research (Originator)
合成路线:Condensation of 2-(4-chlorophenyl)ethanol (I) with 4-nitrobenzaldehyde (II) by means of ZnCl2 and HCl produced isochromane (III).Subsequent oxidative cleavage of (III) employing Jones reagent in acetone afforded ketoacid (IV).Conversion of (IV) to the corresponding hydrazone (V),followed by cyclization in the presence of dicyclohexylcarbodiimide yielded benzodiazepinone (VI).After conversion of (VI) to the benzodiazepine thione (VII) by treatment with P2S5,condensation with 2-(1-aminoethyl)-1,3-dioxolane (VIII) employing HgO as the desulfurizing reagent furnished (IX).Further acid-catalyzed cyclization of (IX) gave rise to the imidazobenzodiazepine (X).Finally,the nitro group of (X) was reduced by transfer hydrogenation using hydrazine and Raney Nickel.
📌 参考资料/链接：
参考文献标题:New 2,3-benzodiazepine derivs.
文献作者:Cs鷝di,E.; Ling,I.; Berzsenyi,P.; Horv醫h,K.; 羈rah醡,G.; Andr醩i,F.; H醡ori,T.; Moravcsik,I.; Simay,A.; Tarnawa,I.; Pallagi,I.; S髄yom,S.(Gyogyszerkutato Intezet Kft.)
参考来源:EP 1001956; WO 9906408
📄 详细内容
合成路线:Condensation of 2-(4-chlorophenyl)ethanol (I) with 4-nitrobenzaldehyde (II) by means of ZnCl2 and HCl produced isochromane (III).Subsequent oxidative cleavage of (III) employing Jones reagent in acetone afforded ketoacid (IV).Conversion of (IV) to the corresponding hydrazone (V),followed by cyclization in the presence of dicyclohexylcarbodiimide yielded benzodiazepinone (VI).After conversion of (VI) to the benzodiazepine thione (VII) by treatment with P2S5,condensation with 2-(1-aminoethyl)-1,3-dioxolane (VIII) employing HgO as the desulfurizing reagent furnished (IX).Further acid-catalyzed cyclization of (IX) gave rise to the imidazobenzodiazepine (X).Finally,the nitro group of (X) was reduced by transfer hydrogenation using hydrazine and Raney Nickel.
参考文献标题:New non competitive AMPA antagonists
文献作者:羈rah醡,G.; Solyom,S.; Csuazdi,E.; Berzsenyi,P.; Ling,I.; Tarnawa,I.; Hamori,T.; Pallagi,I.; Horvath,K.; Andrasi,F.; Kapus,G.; Harsing,L.G.Jr.; Kiraly,I.; Patthy,M.; Horvath,G.
参考来源:Bioorg Med Chem 2000,8(8),2127
产品链接: CAS No. 220445-20-5››