Sorafenib, BAY-43-9006

合成路线:Reaction of picolinic acid (I) with hot thionyl chloride in DMF gives 4-chloropyridine-2-carbonyl chloride (II),which is treated with methanol to give ester (III).Subsequent displacement of the methyl ester function withmethylamine provides amide (IV).Alternatively,acid chloride (II) is directly converted into amide (IV) by reaction with a cold solution of methylamine.In a different synthetic procedure,amide (IV) can be obtained from 4-chloropyridine (V) via the Menisci reaction using N-methylformamide and hydrogen peroxide in the presence of FeSO4 and H2SO4.Coupling of the amide (IV) with potassium 4-aminophenolate (VI) -obtained by treatment of 4-aminophenol (VII) with potassium tert-butoxide- in hot DMF yields the pyridyloxyaniline (VIII).Aniline (VIII) isfinally condensed with either 4-chloro-3-(trifluoromethyl)phenyl isocyanate (IX) in CH2Cl2 or 4-chloro-3-(trifluoromethyl)aniline (X) by means of CDI in CH2Cl2.

参考文献标题:omega-Carboxy aryl substd.diphenyl ureas as p38 kinase inhibitors
文献作者:Smith,R.A.; Monahan,M.-K.; Riedl,B.; Scott,W.J.; Khire,U.; Lowinger,T.B.; Natero,R.; Sibley,R.N.; Wood,J.E.; Renick,J.; Dumas,J.(Bayer Corp.)
参考来源:WO 0041698


合成路线:Reaction of picolinic acid (I) with hot thionyl chloride in DMF gives 4-chloropyridine-2-carbonyl chloride (II),which is treated with methanol to give ester (III).Subsequent displacement of the methyl ester function withmethylamine provides amide (IV).Alternatively,acid chloride (II) is directly converted into amide (IV) by reaction with a cold solution of methylamine.In a different synthetic procedure,amide (IV) can be obtained from 4-chloropyridine (V) via the Menisci reaction using N-methylformamide and hydrogen peroxide in the presence of FeSO4 and H2SO4.Coupling of the amide (IV) with potassium 4-aminophenolate (VI) -obtained by treatment of 4-aminophenol (VII) with potassium tert-butoxide- in hot DMF yields the pyridyloxyaniline (VIII).Aniline (VIII) isfinally condensed with either 4-chloro-3-(trifluoromethyl)phenyl isocyanate (IX) in CH2Cl2 or 4-chloro-3-(trifluoromethyl)aniline (X) by means of CDI in CH2Cl2.

参考文献标题:A scaleable synthesis of BAY 43-9006: A potent Raf kinase inhibitor for the treatment of cancer
文献作者:Monahan,M.-K.; Sibley,R.; Natero,R.; Dumas,J.; Bankston,D.; Riedl,B.
参考来源:Org Process Res Dev 2002,6(6),777


合成路线:Reaction of picolinic acid (I) with hot thionyl chloride in DMF gives 4-chloropyridine-2-carbonyl chloride (II),which is treated with methanol to give ester (III).Subsequent displacement of the methyl ester function withmethylamine provides amide (IV).Alternatively,acid chloride (II) is directly converted into amide (IV) by reaction with a cold solution of methylamine.In a different synthetic procedure,amide (IV) can be obtained from 4-chloropyridine (V) via the Menisci reaction using N-methylformamide and hydrogen peroxide in the presence of FeSO4 and H2SO4.Coupling of the amide (IV) with potassium 4-aminophenolate (VI) -obtained by treatment of 4-aminophenol (VII) with potassium tert-butoxide- in hot DMF yields the pyridyloxyaniline (VIII).Aniline (VIII) isfinally condensed with either 4-chloro-3-(trifluoromethyl)phenyl isocyanate (IX) in CH2Cl2 or 4-chloro-3-(trifluoromethyl)aniline (X) by means of CDI in CH2Cl2.
参考文献标题:BAY-43-9006
文献作者:Sorbera,L.A.; Castar,J.; Bozzo,J.; Leeson,P.A.
参考来源:Drugs Fut 2002,27(12),1141


产品链接: CAS No. 284461-73-0››