新产品编号:2011231
Chemical Name: (6aR,aS)-3-Methyl-2-[6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-yl]benzonitrile
项目整合开发状态: Biological Testing
项目研究机构: ACADIA (Originator), AstraZeneca (Originator)
合成路线:Hydroxyaporphine (I) was converted to triflate (II) upon treatment with N-phenyl trifluoromethanesulfonimide (1).Suzuki coupling of triflate (II) with 2,6-dimethoxyphenylboronic acid (III) furnished the 11-aryl aporphine (IV).After cleavage of the methyl ether groups of (IV) with HBr,the resultant resorcinol derivative (V) was converted to the corresponding bis-triflate (VI) by means of N-phenyl trifluoromethanesulfonimide.Stereoselective introduction of a cyano group in (VI) was achieved by displacement of the less hindered triflate group with zinc cyanide in the presence of palladium catalyst,yielding the target (6aR,aR)-cyanide (VII) in 90% d.e.After isolation of the major isomer,the remaining triflate group of (VII) was displaced with tetramethylstannane to furnish the title compound.
📌 参考资料/链接：
参考文献标题:Atropisomeric derivatives of 2',6'-disubstituted (R)-11-phenylaporphine: Selective serotonin 5-HT7 receptor antagonist
文献作者:Linnanen,T.; Brisander,M.; Unelius,L.; Rosqvist,S.; Nordvall,G.; Hacksell,U.; Johansson,A.M.
参考来源:J Med Chem 2001,44(9),1337
📄 详细内容
合成路线:Hydroxyaporphine (I) was converted to triflate (II) upon treatment with N-phenyl trifluoromethanesulfonimide (1).Suzuki coupling of triflate (II) with 2,6-dimethoxyphenylboronic acid (III) furnished the 11-aryl aporphine (IV).After cleavage of the methyl ether groups of (IV) with HBr,the resultant resorcinol derivative (V) was converted to the corresponding bis-triflate (VI) by means of N-phenyl trifluoromethanesulfonimide.Stereoselective introduction of a cyano group in (VI) was achieved by displacement of the less hindered triflate group with zinc cyanide in the presence of palladium catalyst,yielding the target (6aR,aR)-cyanide (VII) in 90% d.e.After isolation of the major isomer,the remaining triflate group of (VII) was displaced with tetramethylstannane to furnish the title compound.
参考文献标题:
文献作者:
参考来源:J Med Chem 1996,393503-13