新产品编号:2327631
Chemical Name: 2-tert-Butyl-9-fluoro-6,7-dihydro-3H-benzo[h]imidazo[4,5-f]isoquinolin-7-one
项目整合开发状态: Biological Testing
项目研究机构: Merck & Co. (Originator)
合成路线:Condensation of 2-fluoro-4-methylpyridine (I) with ethyl 4-fluorobenzoate (II) by means of sodium bis(trimethylsilyl)amide provides the diaryl ethanone (III).Subsequent nitrosation of ketone (III) with tert-butyl nitrite under acidic conditions furnishes oxime (IV).Cyclization of keto oxime (IV) with trimethylacetaldehyde (V) in the presence of ammonium acetate in boiling AcOH proceeds with concomitant hydrolysis of the fluoro group to produce the N-hydroxy imidazole (VI).Reduction of (VI) employing TiCl3 gives imidazole (VII).Finally,the photochemical cyclization of diarylimidazole (VII) leads to the target tetracyclic compound (1,2).
📌 参考资料/链接：
参考文献标题:Benzimidazo[4,5-f]isoquinolinone derivs.
文献作者:Sinclair,P.J.; Goulet,J.L.; Hong,X.; Thompson,J.E.; Cubbon,R.M.; Cummings,R.T.(Merck & Co.,Inc.)
参考来源:WO 0311285
📄 详细内容
合成路线:Condensation of 2-fluoro-4-methylpyridine (I) with ethyl 4-fluorobenzoate (II) by means of sodium bis(trimethylsilyl)amide provides the diaryl ethanone (III).Subsequent nitrosation of ketone (III) with tert-butyl nitrite under acidic conditions furnishes oxime (IV).Cyclization of keto oxime (IV) with trimethylacetaldehyde (V) in the presence of ammonium acetate in boiling AcOH proceeds with concomitant hydrolysis of the fluoro group to produce the N-hydroxy imidazole (VI).Reduction of (VI) employing TiCl3 gives imidazole (VII).Finally,the photochemical cyclization of diarylimidazole (VII) leads to the target tetracyclic compound (1,2).
参考文献标题:Photochemical preparation of a pyridone containing tetracycle: A jak protein kinase inhibitor
文献作者:Thompson,J.E.; Cubbon,R.M.; Cummings,R.T.; Wicker,L.S.; Franksun,R.; Cunningham,B.R.; Cameron,P.M.; Meinke,P.T.; Liverton,N.; Weng,Y.; DeMartino,J.A.
参考来源:Bioorg Med Chem Lett 2002,12(8),1219