新产品编号:663367
Chemical Name: 3-[6-Oxo-9-(trifluoromethyl)-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepin-2-yl]propanenitrile
CAS No. 252894-30-7
项目整合开发状态: Biological Testing
项目研究机构: CNRS (Originator), National Cancer Institute (Originator), Universit鋞 Hamburg (Originator)
合成路线:5-Iodoanthranilic acid (I) was converted to ethyl ester (II) (1),which was subsequently reacted with ethoxysuccinyl chloride (III) to furnish the amide (IV).Dieckmann cyclization of (IV) using KH produced ketoester (V),and further dealkoxycarbonylation by heating in wet DMSO gave rise to benzazepinedione (VI).After formation of the corresponding hydrazone (VIII) with 4-(trifluoromethyl)phenylhydrazine (VII),Fisher indole synthesis yielded the paulone system (IX).The Heck reaction of (IX) with acrylonitrile in the presence of palladium catalyst gave adduct (X).The target saturated analogue was finally prepared by refluxing the acrylonitrile derivative (X) with Mg in MeOH.
📌 参考资料/链接：
参考文献标题:Fused azepinone cyclin dependent kinase inhibitors
文献作者:Gussio,R.; Zaharevitz,D.W.; Sausville,E.A.; Jalluri,R.K.(US Department of Health & Human Services)
参考来源:WO 9965910
📄 详细内容
合成路线:5-Iodoanthranilic acid (I) was converted to ethyl ester (II) (1),which was subsequently reacted with ethoxysuccinyl chloride (III) to furnish the amide (IV).Dieckmann cyclization of (IV) using KH produced ketoester (V),and further dealkoxycarbonylation by heating in wet DMSO gave rise to benzazepinedione (VI).After formation of the corresponding hydrazone (VIII) with 4-(trifluoromethyl)phenylhydrazine (VII),Fisher indole synthesis yielded the paulone system (IX).The Heck reaction of (IX) with acrylonitrile in the presence of palladium catalyst gave adduct (X).The target saturated analogue was finally prepared by refluxing the acrylonitrile derivative (X) with Mg in MeOH.
参考文献标题:2-Substituted paullones: CDK1/cyclin B-inhibiting property and in vitro antiproliferative activity
文献作者:Kunick,C.; Schultz,C.; Lemdke,T.; Zaharevitz,D.W.; Gussio,R.; Jalluri,R.K.; Sausville,E.A.; Leost,M.; Meijer,L.
参考来源:Bioorg Med Chem Lett 2000,10(6),567