合成路线:The condensation of the amine (I) with the chloride of 3(R)-(1-naphthyl)glutaric acid monomethyl ester (II) by means of triethylamine in hot toluene gives the glutaramic ester (III),which is finally hydrolyzed with NaOH in methanol/methylene chloride/water.The intermediates (I) and (II) have been obtained as follows:1) Intermediate (I) is obtained by condensation of 3,5-dimethylisatoic acid anhydride (IV) with 8-azabicyclo[4.5]decane (V) by means of triethylamine in refluxing toluene.2) Intermediate (II) is obtained by reaction of 3-(1-naphthyl)glutaric anhydride (VI) with methanol,yielding the racemic monomethyl ester,which without isolation is submitted to optical resolution with cinchonine,thus obtaining the 3(R)-monoester (VII).Finally,this compound is treated with SOCl2 in refluxing ethyl ether.
参考文献标题:Anthranilic acid diamides derivs.,their preparation and pharmaceutical use as antigastrin agents
文献作者:Makovec,F.; Peris,W.; Rovati,L.C.; Rovati,L.A.(Rotta Research Laboratorium SpA)
参考来源:EP 0918754; WO 9800404
合成路线:The condensation of the amine (I) with the chloride of 3(R)-(1-naphthyl)glutaric acid monomethyl ester (II) by means of triethylamine in hot toluene gives the glutaramic ester (III),which is finally hydrolyzed with NaOH in methanol/methylene chloride/water.The intermediates (I) and (II) have been obtained as follows:1) Intermediate (I) is obtained by condensation of 3,5-dimethylisatoic acid anhydride (IV) with 8-azabicyclo[4.5]decane (V) by means of triethylamine in refluxing toluene.2) Intermediate (II) is obtained by reaction of 3-(1-naphthyl)glutaric anhydride (VI) with methanol,yielding the racemic monomethyl ester,which without isolation is submitted to optical resolution with cinchonine,thus obtaining the 3(R)-monoester (VII).Finally,this compound is treated with SOCl2 in refluxing ethyl ether.
参考文献标题:CR-2945
文献作者:Makovec,F.; Castar,J.; Revel,L.
参考来源:Drugs Fut 1999,24(5),483
产品链接: CAS No. 201605-51-8››