-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	48349
标题:	Inhibition of p38 kinase activity by aryl ureas
作者:	Gunn, D.; Ranges, G.; Chen, J.; Bombara, M.; Scott, W.; Rauner, D.; Redman, A.; Paulsen, H.; Smith, R.; Renick, J. (Bayer Corp.)
来源:	WO 9852558

合成路线图解说明: 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No.	605028
标题:	p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: Thienyl, furyl, and pyrrolyl ureas
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.
来源:	Bioorg Med Chem Lett 2001,11(1),9

合成路线图解说明: 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.