新产品编号:709245

合成路线:Alkylation of vanillic acid methyl ester (V) with 3-chloropropyl tosylate (VI) in the presence of K2CO3 and Aliquat 336 gives the chloropropyl ether (VII).Subsequent electrophilic nitration of (VII) in hot HOAc affords the ortho-nitrobenzoate (VIII),which is further reduced to the amino benzoate analogue (IX) employing Fe/NH4Cl.Condensation of amino ester (IX) with dimethylformamide dimethylacetal provides adduct (X).This is then converted to the key quinoline derivative (XI) upon condensation with acetonitrile in the presence of butyllithium.Chlorination of (XI) with boiling POCl3 leads to the 4-chloroquinoline (XII).This is then coupled with the (imidazolylsulfanyl)aniline (IV) using pyridinium chloride in refluxing ethoxyethanol to furnish the anilino quinoline adduct (XIII).Finally,displacement of the chloride group of (XIII) with morpholine (XIV) in DMF provides the title compound.

参考文献标题:Substd.3-cyanoquinolines
文献作者:Frost,P.; Floyd,M.B.Jr.; Wissner,A.; Hamann,P.R.; Zhang,N.; Tsou,H.-R.; Berger,D.M.; Salvati,M.E.(Wyeth)
参考来源:US 6288082


合成路线:Condensation of 3-chloro-4-fluoronitrobenzene (I) with the sodium derivative of 2-mercapto-1-methylimidazole (II) affords the diaryl sulfide (III).Subsequent nitro group reduction in (III) using iron dust and ammonium chloride provides the intermediate aniline (IV).

合成路线:Alkylation of vanillic acid methyl ester (V) with 3-chloropropyl tosylate (VI) in the presence of K2CO3 and Aliquat 336 gives the chloropropyl ether (VII).Subsequent electrophilic nitration of (VII) in hot HOAc affords the ortho-nitrobenzoate (VIII),which is further reduced to the amino benzoate analogue (IX) employing Fe/NH4Cl.Condensation of amino ester (IX) with dimethylformamide dimethylacetal provides adduct (X).This is then converted to the key quinoline derivative (XI) upon condensation with acetonitrile in the presence of butyllithium.Chlorination of (XI) with boiling POCl3 leads to the 4-chloroquinoline (XII).This is then coupled with the (imidazolylsulfanyl)aniline (IV) using pyridinium chloride in refluxing ethoxyethanol to furnish the anilino quinoline adduct (XIII).Finally,displacement of the chloride group of (XIII) with morpholine (XIV) in DMF provides the title compound.
参考文献标题:Synthesis and evaluation of 4-anilino substituted 3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade
文献作者:Dutia,M.; Powell,D.W.; Berger,D.M.; et al.
参考来源:224th ACS Natl Meet (Aug 18 2002,Boston) 2002,Abst MEDI 105