新产品编号:448215
Chemical Name: 5-tert-Butyl-3-(2,3-dichlorophenylureido)-1H-pyrrole-2-carboxylic acid methyl ester
CAS No. 216573-65-8
项目整合开发状态: Biological Testing
项目研究机构: Bayer (Originator)
合成路线:Esterification of pyrrole-2-carboxylic acid (I) by treatment with TMSCl in MeOH yields methyl carboxylate (II),which is then condensed with tert-butyl chloride (III) by means of AlCl3 in 1,2-dichloroethane to provide methyl 5-tert-butyl pyrrole-2-carboxylate (IV).Nitration of pyrrolic derivative (IV) by reaction with HNO3/H2SO4 affords a mixture of compounds from which 3-nitropyrrole derivative (V) is cromatographically separated.Hydrogenation of (V) over Pd/C in MeOH allows conversion of the nitro group into an amino group to furnish methyl 3-amino-5-tert-butylpyrrole-2-carboxylate (VI),which is finally coupled to 2,3-dichlorophenyl isocyanate (VII) in dichloromethane to afford the desired compound.
📌 参考资料/链接：
参考文献标题:Inhibition of p38 kinase activity by aryl ureas
文献作者:Gunn,D.; Ranges,G.; Chen,J.; Bombara,M.; Scott,W.; Rauner,D.; Redman,A.; Paulsen,H.; Smith,R.; Renick,J.(Bayer Corp.)
参考来源:WO 9852558
📄 详细内容
合成路线:Esterification of pyrrole-2-carboxylic acid (I) by treatment with TMSCl in MeOH yields methyl carboxylate (II),which is then condensed with tert-butyl chloride (III) by means of AlCl3 in 1,2-dichloroethane to provide methyl 5-tert-butyl pyrrole-2-carboxylate (IV).Nitration of pyrrolic derivative (IV) by reaction with HNO3/H2SO4 affords a mixture of compounds from which 3-nitropyrrole derivative (V) is cromatographically separated.Hydrogenation of (V) over Pd/C in MeOH allows conversion of the nitro group into an amino group to furnish methyl 3-amino-5-tert-butylpyrrole-2-carboxylate (VI),which is finally coupled to 2,3-dichlorophenyl isocyanate (VII) in dichloromethane to afford the desired compound.
参考文献标题:p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: Thienyl,furyl,and pyrrolyl ureas
文献作者:Redman,A.M.; Johnson,J.S.; Dally,R.; Swartz,S.; Wild,H.; Paulsen,H.; Caringal,Y.; Gunn,D.; Renick,J.; Osterhout,M.; Kingery-Wood,J.; Smith,R.A.; Lee,W.; Dumas,J.; Wilhelm,S.M.; Housley,T.J.; Bhargava,A.; Ranges,G.E.; et al.
参考来源:Bioorg Med Chem Lett 2001,11(1),9