LFM-A13-F(oral formulation), LFM-A13
(2Z)-2-氰基-N-(2,5-二溴苯基)-3-羟基-2-丁烯酰胺 2-氰基-N-(2,5-二溴苯基)-3-羟基-2-丁烯酰胺 Chemical Name: (Z)-2-Cyano-N-(2,5-dibromophenyl)-3-hydroxy-2-butenamide
CAS No. 244240-24-2, 62004-35-7 (undefined stereoch.)
项目整合开发状态: Preclinical
项目研究机构: Parker Hughes Institute (Originator)
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.
📌 参考资料/链接：
参考文献标题:Cyano acetic acid anilide derivs.,process for their manufacture and compsns.containing these cpds.
文献作者:Ertel,H.; Wolf,E.; Heubach,G.(Aventis SA)
参考来源:DE 2524929; US 4061767
📄 详细内容
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
产品链接: CAS No. 244240-24-2›› 产品链接: CAS No.62004-35-7››