新产品编号:581103
Chemical Name: N-[2-(1H-Indol-3-yl)ethyl]-7,8-dihydroisoquinoline-6-carboxamide hydrochloride
CAS No. 227199-46-4 (free base)
项目整合开发状态: Preclinical
项目研究机构: Shire BioChem (Originator)
合成路线:Oxidation of 5-hydroxy-5,6,7,8-tetrahydroisoquinoline (I) using CrO3 in pyridine produced the corresponding ketone (II).Subsequent condensation of (II) with methyl cyanoformate (A) in the presence of lithium hexamethyldisilazide gave ketoester (III),which was reduced to hydroxyester (IV) by means of catalytic hydrogenation.Dehydration of (IV) to the unsaturated ester (V) was achieved by treatment with methanesulfonyl chloride and triethylamine,followed by basic elimination with DBU.Saponification of the ester group of (V) produced carboxylic acid (VI).After activation of (VI) as the mixed anhydride (VII) with isopropyl chloroformate (B),coupling with tryptamine (VIII) furnished the title amide,which was finally isolated as the hydrochloride salt.
合成路线:Treatment of 2-isopropoxyphenylamine (I) with triphosgene (II) and DIEA in dichloromethane affords isocyanate (III),which is then converted into the desired urea derivative by treatment with amine (IV) in refluxing acetonitrile.
📌 参考资料/链接：
参考文献标题:Antiviral cpds.
文献作者:Bedard,J.; Rando,R.; Falardeau,G.; Lavallee,J.-F.(BioChem Pharma Inc.)
参考来源:WO 9929318
📄 详细内容
合成路线:Oxidation of 5-hydroxy-5,6,7,8-tetrahydroisoquinoline (I) using CrO3 in pyridine produced the corresponding ketone (II).Subsequent condensation of (II) with methyl cyanoformate (A) in the presence of lithium hexamethyldisilazide gave ketoester (III),which was reduced to hydroxyester (IV) by means of catalytic hydrogenation.Dehydration of (IV) to the unsaturated ester (V) was achieved by treatment with methanesulfonyl chloride and triethylamine,followed by basic elimination with DBU.Saponification of the ester group of (V) produced carboxylic acid (VI).After activation of (VI) as the mixed anhydride (VII) with isopropyl chloroformate (B),coupling with tryptamine (VIII) furnished the title amide,which was finally isolated as the hydrochloride salt.
参考文献标题:Design and evaluation of dihydroisoquinolines as potent and orally bioavailable human cytomegalovirus inhibitors
文献作者:Chan,L.; Stefanac,T.; Turcotte,N.; Hu,Z.; Chen,Y.; B閐ard,J.; May,S.; Jin,H.
参考来源:Bioorg Med Chem Lett 2000,10(13),1477