【药物名称】Cianopramine, Ro-112465
化学结构式(Chemical Structure):
参考文献No.47483
标题:3-Cyano-N-(N,N-dimethylaminopropyl)-iminodibenzyl and salts thereof
作者:Dostert, P. (Hoffmann-La Roche, Inc.)
来源:US 4138482
合成路线图解说明:

1) The acetylation of iminodibenzyl (I) with acetyl chloride (A) in refluxing toluene gives N-acetyl-iminodibenzyl (II), which by a Friedel-Kraft's reaction with methyl oxalyl chloride (B) and AlCl3 in CH2Cl2 or CS2 is converted to N-acetyl-3-(methyloxalyl)iminodibenzyl (III). The hydrolysis of (III) with NaOH in methanol-water yields N-acetyl-5-oxalyliminodibenzyl (IV), which by treatment with NaOH in water-ethanol at high temperature affords 3-oxalyliminodibenzyl (V). The reaction of (V) with hydroxylamine and acetic acid gives 3-hydroxylaminooxalyliminodibenzyl (VI), which by heating at 100 C in water is converted into 3-cyanoiminodibenzyl (VII). Finally, this compound is condensed with 3-(dimethylamino)propyl chloride (VIII) by means of NaH in DMF. 2) Compound (VII) can also be condensed with dimethylaminopropyl N,N-dimethylcarbamate (IX) by heating at 250 C. 3) The reaction of (VII) with phosgene gives N-chlorocarbonyl-3-cyanoiminodibenzyl (X), which is condensed with 3-dimethylaminopropanol (XI) to afford 3-cyanoiminodibenzyl-N-carboxylic acid 3-dimethylaminopropyl ester (XII). Finally, this compound is heated at 250 C under reduced pressure.

合成路线图解说明:

The reaction of 3-bromoiminodibenzyl (XIII) with 3-(dimethylamino)propyl chloride (VIII) at 100 C gives N-(3-dimethylaminopropyl)-3-bromoiminodibenzyl (XIV), which is treated with cuprous cyanide in refluxing DMF.

参考文献No.62044
标题:RO-11-2465
作者:Blancafort, P.; Casta馿r, J.; Owen, R.T.; Serradell, M.N.
来源:Drugs Fut 1981,6(1),41
合成路线图解说明:

1) The acetylation of iminodibenzyl (I) with acetyl chloride (A) in refluxing toluene gives N-acetyl-iminodibenzyl (II), which by a Friedel-Kraft's reaction with methyl oxalyl chloride (B) and AlCl3 in CH2Cl2 or CS2 is converted to N-acetyl-3-(methyloxalyl)iminodibenzyl (III). The hydrolysis of (III) with NaOH in methanol-water yields N-acetyl-5-oxalyliminodibenzyl (IV), which by treatment with NaOH in water-ethanol at high temperature affords 3-oxalyliminodibenzyl (V). The reaction of (V) with hydroxylamine and acetic acid gives 3-hydroxylaminooxalyliminodibenzyl (VI), which by heating at 100 C in water is converted into 3-cyanoiminodibenzyl (VII). Finally, this compound is condensed with 3-(dimethylamino)propyl chloride (VIII) by means of NaH in DMF. 2) Compound (VII) can also be condensed with dimethylaminopropyl N,N-dimethylcarbamate (IX) by heating at 250 C. 3) The reaction of (VII) with phosgene gives N-chlorocarbonyl-3-cyanoiminodibenzyl (X), which is condensed with 3-dimethylaminopropanol (XI) to afford 3-cyanoiminodibenzyl-N-carboxylic acid 3-dimethylaminopropyl ester (XII). Finally, this compound is heated at 250 C under reduced pressure.

合成路线图解说明:

The reaction of 3-bromoiminodibenzyl (XIII) with 3-(dimethylamino)propyl chloride (VIII) at 100 C gives N-(3-dimethylaminopropyl)-3-bromoiminodibenzyl (XIV), which is treated with cuprous cyanide in refluxing DMF.

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us