Cianopramine, Ro-112465

氰帕明Chemical Name: 5-[3-(Dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine-3-carbonitrile; 3-Cyano-N-[3-(dimethylamino)propyl]iminodibenzyl
CAS No. 66834-24-0, 66834-20-6 (HCl)
项目整合开发状态: Phase III
项目研究机构: Roche (Originator)
合成路线: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: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.