【药物名称】Retelliptine, NSC-D-626717-W, BD-84, SR-95325B(diHCl), SR-95325A(dimaleate), Peliptil
化学结构式(Chemical Structure):
参考文献No.8642
标题:Substd. ellipticines in position 1 by a polyaminated chain, their synthesis and medicaments containing them
作者:Bisagni, E.; Ducrocq, C.; Rivalle, C.; Tambourin, P.; Wendling, F.; Civier, A.; Montagnier, L.; Chermann, J.-C.; Gruest, J.; Lidereau, R. (ANVAR (Agence Natl. Valor. Rech.))
来源:EP 0010029
合成路线图解说明:

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No.236325
标题:Retelliptine
作者:Casta馿r, J.; Hoshi, A.
来源:Drugs Fut 1994,19(2),122
合成路线图解说明:

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No.236748
标题:Structure-activity relationships in a series of newly synthesized 1-aminosubstituted ellipticine derivatives
作者:Ducrocq, C.; Wendling, F.; Tourbez-Perrin, M.; Rivalle, C.; Tambourin, P.; Pochon, F.; Bisagni, E.; Chermann, J.C.
来源:J Med Chem 1980,231212
合成路线图解说明:

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No.801724
标题:Synthesis of 1-substituted ellipticines by a new route to pyrido[4,3-b]carbazoles
作者:Lhoste, J.-M.; Bisagni, E.; Rivalle, C.; Ducrocq, C.; Civier, A.
来源:J Chem Soc - Perkins Trans I 1979,1706
合成路线图解说明:

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).

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