合成路线:The nitrosation of p-anisidine (I) with NaNO2 and HCl in water gives 4-methoxyphenyldiazonium chloride (II),which is condensed with 4-(4-methyl-1-cyclohexenyl)morpholine (III) yielding 2-(4-methoxyphenylhydrazono)-4-methylcyclohexanone (IV).The cyclization of (IV) by means of H2SO4 in refluxing ethanol affords 6-methoxy-4-methyl-1,2,3,4-tetrahydro-9H-carbazol-1-one (V),which is condensed with refluxing ethyl formate and NaH to give the corresponding 2-(hydroxymethylene) derivative (VI).The alkylation of (VI) with isopropyl iodide and K2CO3 yields the corresponding 2-(isopropoxymethylene) derivative (VII),which is methylated with CH3Li in ether to afford 6-methoxy-1,4-dimethyl-3,4-dihydrocarbazole-2-carboxaldehyde (VIII).The aromatization of (VIII) with MnO2 in refluxing benzene gives the corresponding carbazole (IX),which is condensed with malonic acid by means of piperidine in refluxing pyridine to afford 3-(6-methoxy-1,4-dimethylcarbazol-2-yl)-2-propenoic acid (X).The reaction of (X) with ethylchloroformate and sodium azide and acetone gives the corresponding azide (XI),which is cyclized by means of tributylamine in diphenyl ether at 250 C yielding 9-methoxy-5,11-dimethyl-1,2-dihydro-6H-pyrido[4,3-b]carbazol-1-one (XII).The reaction of (XII) with refluxing POCl3 affords 1-chloro-9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (XIII),which is finally treated with refluxing 2-(diethylamino)propylamine (XIV).
参考文献标题:Retelliptine
文献作者:Castar,J.; Hoshi,A.
参考来源:Drugs Fut 1994,19(2),122
合成路线:The nitrosation of p-anisidine (I) with NaNO2 and HCl in water gives 4-methoxyphenyldiazonium chloride (II),which is condensed with 4-(4-methyl-1-cyclohexenyl)morpholine (III) yielding 2-(4-methoxyphenylhydrazono)-4-methylcyclohexanone (IV).The cyclization of (IV) by means of H2SO4 in refluxing ethanol affords 6-methoxy-4-methyl-1,2,3,4-tetrahydro-9H-carbazol-1-one (V),which is condensed with refluxing ethyl formate and NaH to give the corresponding 2-(hydroxymethylene) derivative (VI).The alkylation of (VI) with isopropyl iodide and K2CO3 yields the corresponding 2-(isopropoxymethylene) derivative (VII),which is methylated with CH3Li in ether to afford 6-methoxy-1,4-dimethyl-3,4-dihydrocarbazole-2-carboxaldehyde (VIII).The aromatization of (VIII) with MnO2 in refluxing benzene gives the corresponding carbazole (IX),which is condensed with malonic acid by means of piperidine in refluxing pyridine to afford 3-(6-methoxy-1,4-dimethylcarbazol-2-yl)-2-propenoic acid (X).The reaction of (X) with ethylchloroformate and sodium azide and acetone gives the corresponding azide (XI),which is cyclized by means of tributylamine in diphenyl ether at 250 C yielding 9-methoxy-5,11-dimethyl-1,2-dihydro-6H-pyrido[4,3-b]carbazol-1-one (XII).The reaction of (XII) with refluxing POCl3 affords 1-chloro-9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (XIII),which is finally treated with refluxing 2-(diethylamino)propylamine (XIV).
参考文献标题:Structure-activity relationships in a series of newly synthesized 1-aminosubstituted ellipticine derivatives
文献作者:Ducrocq,C.; Wendling,F.; Tourbez-Perrin,M.; Rivalle,C.; Tambourin,P.; Pochon,F.; Bisagni,E.; Chermann,J.C.
参考来源:J Med Chem 1980,231212
合成路线:The nitrosation of p-anisidine (I) with NaNO2 and HCl in water gives 4-methoxyphenyldiazonium chloride (II),which is condensed with 4-(4-methyl-1-cyclohexenyl)morpholine (III) yielding 2-(4-methoxyphenylhydrazono)-4-methylcyclohexanone (IV).The cyclization of (IV) by means of H2SO4 in refluxing ethanol affords 6-methoxy-4-methyl-1,2,3,4-tetrahydro-9H-carbazol-1-one (V),which is condensed with refluxing ethyl formate and NaH to give the corresponding 2-(hydroxymethylene) derivative (VI).The alkylation of (VI) with isopropyl iodide and K2CO3 yields the corresponding 2-(isopropoxymethylene) derivative (VII),which is methylated with CH3Li in ether to afford 6-methoxy-1,4-dimethyl-3,4-dihydrocarbazole-2-carboxaldehyde (VIII).The aromatization of (VIII) with MnO2 in refluxing benzene gives the corresponding carbazole (IX),which is condensed with malonic acid by means of piperidine in refluxing pyridine to afford 3-(6-methoxy-1,4-dimethylcarbazol-2-yl)-2-propenoic acid (X).The reaction of (X) with ethylchloroformate and sodium azide and acetone gives the corresponding azide (XI),which is cyclized by means of tributylamine in diphenyl ether at 250 C yielding 9-methoxy-5,11-dimethyl-1,2-dihydro-6H-pyrido[4,3-b]carbazol-1-one (XII).The reaction of (XII) with refluxing POCl3 affords 1-chloro-9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (XIII),which is finally treated with refluxing 2-(diethylamino)propylamine (XIV).
参考文献标题:Synthesis of 1-substituted ellipticines by a new route to pyrido[4,3-b]carbazoles
文献作者:Lhoste,J.-M.; Bisagni,E.; Rivalle,C.; Ducrocq,C.; Civier,A.
参考来源:J Chem Soc - Perkins Trans I 1979,1706
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