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【结 构 式】 
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【分子编号】47130 【品名】methyl 5-(tert-butyl)-3-nitro-1H-pyrrole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C10H14N2O4 【 分 子 量 】226.23224 【元素组成】C 53.09% H 6.24% N 12.38% O 28.29% |
合成路线1
该中间体在本合成路线中的序号：(V)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.
| 【1】 Johnson, J.S.; Dally, R.; Redman, A.M.; et al.; p38 Kinase inhibitors for the treatment of arthritis and osteoporosis: Thienyl, furyl, and pyrrolyl ureas. Bioorg Med Chem Lett 2001, 11, 1, 9. |
| 【2】 Gunn, D.; Ranges, G.; Chen, J.; Bombara, M.; Scott, W.; Rauner, D.; Redman, A.; Paulsen, H.; Smith, R.; Renick, J. (Bayer Corp.); Inhibition of p38 kinase activity by aryl ureas. WO 9852558 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 31796 | Pyrrole-2-carboxylic acid; 1H-pyrrole-2-carboxylic acid | 634-97-9 | C5H5NO2 | 详情 | 详情 |
| (II) | 45616 | methyl 1H-pyrrole-2-carboxylate | C6H7NO2 | 详情 | 详情 | |
| (III) | 47128 | 2-chloro-2-methylpropane | 507-20-0 | C4H9Cl | 详情 | 详情 |
| (IV) | 47129 | methyl 5-(tert-butyl)-1H-pyrrole-2-carboxylate | C10H15NO2 | 详情 | 详情 | |
| (V) | 47130 | methyl 5-(tert-butyl)-3-nitro-1H-pyrrole-2-carboxylate | C10H14N2O4 | 详情 | 详情 | |
| (VI) | 47131 | methyl 3-amino-5-(tert-butyl)-1H-pyrrole-2-carboxylate | C10H16N2O2 | 详情 | 详情 | |
| (VII) | 29667 | N-(2-chloroethyl)-N-[2-(3-methoxyphenyl)-1-methylethyl]-N-methylamine; N-(2-chloroethyl)-1-(3-methoxyphenyl)-N-methyl-2-propanamine | C13H20ClNO | 详情 | 详情 |