新产品编号:63789
Chemical Name: 9-Hydroxy-2-(3-methoxy-2-oxopropoxy)-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium bromide; 9-Hydroxy-2-(3-methoxy-2-oxopropoxy)ellipticinium bromide
CAS No. 153532-59-3
项目整合开发状态: Preclinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:The cyclization of 5-methoxy-1H-indole (I) with hexane-2,6-dione (II) by means of BF3 ethearate in refluxing dioxane gives 6-methoxy-1,4-dimethylcarbazole (III),which is formylated with N-methylformanilide (IV) and POCl3 in hot o-dichlorobenzene yielding the 3-formyl derivative (V).The condensation of (V) with 2-aminoacetaldehyde diethylacetal (VI) by heating at 100 C affords the expected imino derivative (VII),which is cyclized by acid (HCl) hydrolysis of the acetal group and cyclization of the resulting aldehyde by means of NaOH in water to the 9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (VIII).The oxidation of (VIII) with m-chloroperbenzoic acid (MCPBA) in acetone gives the correponding N-oxide (IX),which is treated with BBr3 in dichloromethane yielding 9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (X).Finally,this compound is treated with 1-bromo-3-methoxy-2-propanone in DMF to afford the desired quaternary salt.
📌 参考资料/链接：
参考文献标题:Synthesis and antitumor activity of quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines
文献作者:Harada,N.; Kawaguchi,T.; Inoue,I.; Ohashi,M.; Oda,K.; Hashiyama,T.; Tsujihara,K.
参考来源:Chem Pharm Bull 1997,45(1),134
📄 详细内容
合成路线:The cyclization of 5-methoxy-1H-indole (I) with hexane-2,6-dione (II) by means of BF3 ethearate in refluxing dioxane gives 6-methoxy-1,4-dimethylcarbazole (III),which is formylated with N-methylformanilide (IV) and POCl3 in hot o-dichlorobenzene yielding the 3-formyl derivative (V).The condensation of (V) with 2-aminoacetaldehyde diethylacetal (VI) by heating at 100 C affords the expected imino derivative (VII),which is cyclized by acid (HCl) hydrolysis of the acetal group and cyclization of the resulting aldehyde by means of NaOH in water to the 9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (VIII).The oxidation of (VIII) with m-chloroperbenzoic acid (MCPBA) in acetone gives the correponding N-oxide (IX),which is treated with BBr3 in dichloromethane yielding 9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (X).Finally,this compound is treated with 1-bromo-3-methoxy-2-propanone in DMF to afford the desired quaternary salt.
参考文献标题:Ellipticine derivatives
文献作者:Guthrie,R.W.; Brossi,A.; Mennona,F.A.; Mullin,J.G.; Kierstead,R.W.; Grunberg,E.
参考来源:J Med Chem 1975,18(7),755
合成路线:The cyclization of 5-methoxy-1H-indole (I) with hexane-2,6-dione (II) by means of BF3 ethearate in refluxing dioxane gives 6-methoxy-1,4-dimethylcarbazole (III),which is formylated with N-methylformanilide (IV) and POCl3 in hot o-dichlorobenzene yielding the 3-formyl derivative (V).The condensation of (V) with 2-aminoacetaldehyde diethylacetal (VI) by heating at 100 C affords the expected imino derivative (VII),which is cyclized by acid (HCl) hydrolysis of the acetal group and cyclization of the resulting aldehyde by means of NaOH in water to the 9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (VIII).The oxidation of (VIII) with m-chloroperbenzoic acid (MCPBA) in acetone gives the correponding N-oxide (IX),which is treated with BBr3 in dichloromethane yielding 9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (X).Finally,this compound is treated with 1-bromo-3-methoxy-2-propanone in DMF to afford the desired quaternary salt.
参考文献标题:
文献作者:Liu,Q.-R.; et al.
参考来源:Aust J Chem 1967,202715