新产品编号:794673
Chemical Name: 4-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile
CAS No. 304857-74-7
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Addition of methylmagnesium bromide to methyl 2-amino-5-bromobenzoate (I) provides the tertiary alcohol (II).Subsequent ring closure of the amino carbinol (II) with acetaldehyde leads to the benzoxazine (III).Treatment of the bromobenzoxazine (III) with bis(pinacolato)diboron (IV) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride furnishes the aryl borate (V).This is finally subjected to Suzuki coupling with 5-bromo-2-thiophenecarbonitrile (VI) to produce the title benzoxazinyl thiophene derivative.
📌 参考资料/链接：
参考文献标题:Quinazolinone and benzoxazine derivs.as progesterone receptor modulators
文献作者:Jones,T.K.; Zhi,L.; Tegley,C.M.; Fensome,A.; Zhang,P.; Terefenko,E.A.; Marschke,K.B.(Ligand Pharmaceuticals,Inc.; Wyeth)
参考来源:EP 1175404; WO 0066560
📄 详细内容
合成路线:Addition of methylmagnesium bromide to methyl 2-amino-5-bromobenzoate (I) provides the tertiary alcohol (II).Subsequent ring closure of the amino carbinol (II) with acetaldehyde leads to the benzoxazine (III).Treatment of the bromobenzoxazine (III) with bis(pinacolato)diboron (IV) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride furnishes the aryl borate (V).This is finally subjected to Suzuki coupling with 5-bromo-2-thiophenecarbonitrile (VI) to produce the title benzoxazinyl thiophene derivative.
参考文献标题:Contraceptive compsns.containing quinazolinone and benzoxazine derivs.
文献作者:Jones,T.K.; Zhi,L.; Tegley,C.M.; Marschke,K.B.; Grubb,G.S.(Ligand Pharmaceuticals,Inc.; Wyeth)
参考来源:WO 0066164; WO 0066165
合成路线:Addition of methylmagnesium bromide to methyl 2-amino-5-bromobenzoate (I) provides the tertiary alcohol (II).Subsequent ring closure of the amino carbinol (II) with acetaldehyde leads to the benzoxazine (III).Treatment of the bromobenzoxazine (III) with bis(pinacolato)diboron (IV) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride furnishes the aryl borate (V).This is finally subjected to Suzuki coupling with 5-bromo-2-thiophenecarbonitrile (VI) to produce the title benzoxazinyl thiophene derivative.
参考文献标题:Potent nonsteroidal progesterone receptor agonists: Synthesis and SAR study of 6-aryl benzoxazines
文献作者:Zhang,P.; Terefenko,E.A.; Fensome,A.; Zhang,Z.; Zhu,Y.; Cohen,J.; Winneker,R.; Wrobel,J.; Yardley,J.
参考来源:Bioorg Med Chem Lett 2002,12(5),787