新产品编号:380189
3-[(2-羟基乙基)硫基]-6,6-二甲基-1-(1,3-噻唑-2-基)-6,7-二氢-2-苯并噻吩-4(5H)-酮Chemical Name: 3-(2-Hydroxyethylsulfanyl)-6,6-dimethyl-1-(2-thiazolyl)-4,5,6,7-tetrahydro-2-benzothiophen-4-one
CAS No. 207306-50-1
项目整合开发状态: Preclinical
项目研究机构: Merck Sharp & Dohme (Originator)
合成路线:The title compound is prepared by two related procedures.1-Cyano-6,6-dimethyl-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiopen-4-one (I) is oxidized to the corresponding sulfone (II) employing m-chloroperbenzoic acid (mCPBA).Subsequent displacement of the methylsulfonyl group of (II) with the sodium salt of 2-mercaptoethanol leads to the hydroxyethyl sulfide (III).Addition of SH2 to the nitrile (III) in the presence of Et3N and pyridine gives rise to thioamide (IV).This is finally condensed with chloroacetaldehyde in boiling EtOH to furnish the target thiazole compound.Alternatively,nitrile (I) is first treated with SH2 in Et3N/pyridine to yield thioamide (V).Then,cyclization of (V) with chloroacetaldehyde provides thiazole (VI) .The sulfide group of (VI) is further oxidized to sulfone (VII) by means of mCPBA.Finally,displacement of the methylsulfonyl group of (VII) with 2-mercaptoethanol leads to the title hydroxyethyl sulfide.
📌 参考资料/链接：
参考文献标题:Thienylcyclohexanone derivs.as ligands of the GABAA alpha5 receptor subtype
文献作者:Broughton,H.B.; Chambers,M.S.; Hobbs,S.C.; Macleod,A.M.; Reeve,A.J.(Merck Sharp & Dohme Ltd.)
参考来源:EP 0937072; JP 2001503408; US 6262103; WO 9818792
📄 详细内容
合成路线:The title compound is prepared by two related procedures.1-Cyano-6,6-dimethyl-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiopen-4-one (I) is oxidized to the corresponding sulfone (II) employing m-chloroperbenzoic acid (mCPBA).Subsequent displacement of the methylsulfonyl group of (II) with the sodium salt of 2-mercaptoethanol leads to the hydroxyethyl sulfide (III).Addition of SH2 to the nitrile (III) in the presence of Et3N and pyridine gives rise to thioamide (IV).This is finally condensed with chloroacetaldehyde in boiling EtOH to furnish the target thiazole compound.Alternatively,nitrile (I) is first treated with SH2 in Et3N/pyridine to yield thioamide (V).Then,cyclization of (V) with chloroacetaldehyde provides thiazole (VI) .The sulfide group of (VI) is further oxidized to sulfone (VII) by means of mCPBA.Finally,displacement of the methylsulfonyl group of (VII) with 2-mercaptoethanol leads to the title hydroxyethyl sulfide.
参考文献标题:6,7-Dihydro-2-benzothiophen-4(5H)-ones: A novel class of GABA-A alpha5 receptor inverse agonists
文献作者:Chambers,M.S.; Atack,J.R.; Bromidge,F.A.; Broughton,H.B.; Cook,S.; Dawson,G.R.; Hoobs,S.C.; Maubach,K.A.; Reeve,A.J.; Seabrook,G.R.; Wafford,K.; MacLeod,A.M.
参考来源:J Med Chem 2002,45(6),1176
合成路线:The title compound is prepared by two related procedures.1-Cyano-6,6-dimethyl-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiopen-4-one (I) is oxidized to the corresponding sulfone (II) employing m-chloroperbenzoic acid (mCPBA).Subsequent displacement of the methylsulfonyl group of (II) with the sodium salt of 2-mercaptoethanol leads to the hydroxyethyl sulfide (III).Addition of SH2 to the nitrile (III) in the presence of Et3N and pyridine gives rise to thioamide (IV).This is finally condensed with chloroacetaldehyde in boiling EtOH to furnish the target thiazole compound.Alternatively,nitrile (I) is first treated with SH2 in Et3N/pyridine to yield thioamide (V).Then,cyclization of (V) with chloroacetaldehyde provides thiazole (VI) .The sulfide group of (VI) is further oxidized to sulfone (VII) by means of mCPBA.Finally,displacement of the methylsulfonyl group of (VII) with 2-mercaptoethanol leads to the title hydroxyethyl sulfide.
参考文献标题:GABA-A alpha5-subtype selective inverse agonists as potential cognition-enhancing agents
文献作者:Chambers,M.S.; Atack,J.R.; Bromidge,F.A.; Broughton,H.B.; Collinson,N.; Cook,S.; Dawson,G.R.; Hobbs,S.C.; Maubach,K.A.; Reeve,A.J.; Seabrook,G.R.; Wafford,K.; MacLeod,A.M.
参考来源:Drugs Fut 2002,27(Suppl.A),
产品链接: CAS No. 207306-50-1››