AG-1296
6,7-二甲氧基-2-苯基喹喔啉Chemical Name: 6,7-Dimethoxy-2-phenylquinoxaline
CAS No. 146535-11-7
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator)
合成路线:Leflunomide can be obtained by several related ways:1) The reaction of diketene (I) with 4-(trifluoromethyl)-aniline (II) in hot acetonitrile gives N-[4-(trifluoro-methyl) phenyl]acetoacetamide (III) ,which by reaction with triethyl orthoformate (IV) in refluxing acetic anhydride yields the corresponding ethoxymethylene derivative (V).Finally,this compound is cyclized with hydroxylamine in refluxing ethanol/water.2) The reaction of ethyl acetoacetate (VI) with triethyl orthoformate (IV) as before gives the corresponding ethoxymethylene derivative (VII),which by cyclization with hydroxylamine as before affords 5-methylisoxazole-4-carboxylic acid ethyl ester (VIII).The hydrolysis of (VIII) under acidic conditions yields the free acid (IX),which is converted into the acid chloride (X) by standard methods.Finally,this compound is condensed with 4-(trifluoro-methyl)aniline (II) by means of triethylamine in acetonitrile.3) The formation of leflunomide from acid (IX) or its derivatives such as ethyl (VIII) or other esters can also be performed through other standard procedures of amide formation.4) The N-[4-(trifluoromethyl)phenyl]acetoacetamide (III) can also be obtained by reaction of 4-(trifluoro-methyl) aniline (II) with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (XI) in refluxing xylene.
合成路线:Treatment of veratrole (I) with aqueous HNO3 and H2SO4 yields 1,2-dinitrobenzene derivative (II),which is then converted into diamine (III) by hydrogenation over Pd/C in HOAc/EtOH or over PtO2.Finally,reaction of diamine (III) with phenyl glyoxal (IV) in EtOH and HOAc or HCl affords the desired product.
📌 参考资料/链接：
参考文献标题:Treatment of platelet derived growth factor related disorders such as cancers using inhibitors of platelet derived growth receptor
文献作者:Levitzki,A.; Mann,E.; Bajor,T.; Lammers,R.; Kabbinavar,F.F.; Hirth,K.P.; Orfi,L.; Slamon,D.J.; et al.(Max-Planck-Gesellschaft zur Fderung der Wissenschaften e.V.; Sugen,Inc.; The Hebrew University; Yissum Research Development Co.)
参考来源:EP 1000617; US 5700823; WO 9519169
📄 详细内容
合成路线:Treatment of veratrole (I) with aqueous HNO3 and H2SO4 yields 1,2-dinitrobenzene derivative (II),which is then converted into diamine (III) by hydrogenation over Pd/C in HOAc/EtOH or over PtO2.Finally,reaction of diamine (III) with phenyl glyoxal (IV) in EtOH and HOAc or HCl affords the desired product.
参考文献标题:Treatment of platelet derived growth factor related disorders such as cancers
文献作者:Levitzki,A.; Hirth,K.P.; Schwartz,D.P.; Tang,P.C.; Ullrich,A.; Haimichael,J.; Shawver,L.K.; Szekely,I.; Mann,E.; Orfi,L.; Slamon,D.; Keri,G.; Kabbinavar,F.F.; Gazit,A.; Bajor,T.; Lammers,R.(Sugen,Inc.)
参考来源:US 5990141
合成路线:Treatment of veratrole (I) with aqueous HNO3 and H2SO4 yields 1,2-dinitrobenzene derivative (II),which is then converted into diamine (III) by hydrogenation over Pd/C in HOAc/EtOH or over PtO2.Finally,reaction of diamine (III) with phenyl glyoxal (IV) in EtOH and HOAc or HCl affords the desired product.
参考文献标题:Tyrphostins.5.Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: Structure-activity relationships in quinoxalines,quinolines,and indole tyrphostins
文献作者:Gazit,A.; App,H.; McMahon,G.; Chen,J.; Levitzki,A.; Bohmer,F.D.
参考来源:J Med Chem 1996,39(11),2170
产品链接: CAS No. 146535-11-7››