-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	60473
标题:	Benzimidazo[4,5-f]isoquinolinone derivs.
作者:	Sinclair, P.J.; Goulet, J.L.; Hong, X.; Thompson, J.E.; Cubbon, R.M.; Cummings, R.T. (Merck & Co., Inc.)
来源:	WO 0311285

合成路线图解说明: 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No.	668166
标题:	Photochemical preparation of a pyridone containing tetracycle: A jak protein kinase inhibitor
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.
来源:	Bioorg Med Chem Lett 2002,12(8),1219

合成路线图解说明: 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).