LFM-A12

合成路线:Title compound has been prepared by two synthetic ways:1) Condensation of the acetoacetanilide (I) with triethyl orthoformate in the presence of Ac2O provided the ethoxymethylene compound (II),which was reacted with hydroxylamine in methanol-water to afford isoxazole (III).Ring opening of the heterocycle with NaOH then gave the target cyanoacetanilide.2) In a different procedure,cyanoacetic acid (V) was coupled with 2,5-dibromoaniline (IV) in the presence of diisopropyl carbodiimide (DIC) to form cyanoacetanilide (VI),which was acylated using acetyl chloride and NaH to afford the hydroxyethylidene derivative.

合成路线:Two synthetic ways have been reported for the compound.Coupling of cyanoacetic acid (II) to 4-(trifluoromethoxy)aniline (I) in the presence of diisopropylcarbodiimide formed the cyanoacetamide (III),which was treated with NaH and then acylated with acetyl chloride to yield the title compound.

合成路线:Alternatively,aniline (I) was coupled with 5-methylisoxazole-4-carbonyl chloride (IV) to provide the isoxazolecarboxamide (V).The isoxazole ring was then opened with NaOH to furnish the target cyanopropenamide.
参考文献标题:alpha-Cyano-beta-hydroxy-beta-methyl-N-[4-(trifluoromethoxy)phenyl]propenamide: An inhibitor of the epidermal growth factor receptor tyrosine kinase with potent cytotoxic activity
文献作者:Ghosh,S.; Zheng,Y.; Jun,X.; Narla,R.K.; Mahajan,S.; Navara,C.; Mao,C.; Sudbeck,E.A.; Uckun,F.M.
参考来源:Clin Cancer Res 1998,4(11),2657