【结 构 式】 |
【药物名称】 【化学名称】N-(3-tert-Butyl-1-methyl-1H-pyrazol-5-yl)-N'-[4-(pyridin-4-ylmethyl)phenyl]urea 【CA登记号】229002-15-7 【 分 子 式 】C21H25N5O 【 分 子 量 】363.4663 |
【开发单位】Bayer (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, p38 Protein Kinase Inhibitors |
合成路线1
4-(4-Pyridinylmethyl)aniline (II) was prepared by catalytic hydrogenation of the corresponding nitro derivative (I) over Pd/C. Condensation of aniline (II) with N,N'-carbonyldiimidazole produced the imidazolide (III). This was then condensed with 5-amino-3-tert-butyl-1-methylpyrazole (IV) to furnish the target urea.
【1】 Riedl, B.; Lee, W.; Lowinger, T.B.; Redman, A.; Smith, R.A.; Khire, U.; Dumas, J.; Scott, W.J.; Wood, J.E.; Johnson, J.; Paulsen, H.; Hatoum-Mokdad, H. (Bayer Corp.); Inhibition of p38 kinase activity using substd. heterocyclic ureas. WO 9932111 . |
【2】 Redman, A.; Paulsen, H.; Lowinger, T.B.; Dumas, J.; Johnson, J.; Wood, J.E.; Scott, W.J.; Khire, U.; Hatoum-Mokdad, H.; Lee, W.; Smith, R.A.; Riedl, B. (Bayer Corp.); Inhibition of raf kinase using substd. heterocyclic ureas. EP 1047418; WO 9932106 . |
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) | 51503 | 4-(4-Nitrobenzyl)pyridine; 4-(p-nitrobenzyl) pyridine | 1083-48-3 | C12H10N2O2 | 详情 | 详情 |
(II) | 51504 | 4-(4-pyridinylmethyl)aniline; 4-(4-pyridinylmethyl)phenylamine | C12H12N2 | 详情 | 详情 | |
(III) | 51505 | N-[4-(4-pyridinylmethyl)phenyl]-1H-imidazole-1-carboxamide | C16H14N4O | 详情 | 详情 | |
(IV) | 51506 | 5-Amino-3-tert-butyl-1-methylpyrazole | 118430-73-2 | C8H15N3 | 详情 | 详情 |
合成路线2
The cyclization of 2-pivaloylacetonitrile (I) with methylhydrazine (II) in refluxing ethanol gives 5-amino-3-tert-butyl-1-methylpyrazole (III), which is finally condensed with 4-(4-pyridylmethyl)aniline (IV) and carbonyldimidazole (CDI) in dichloromethane to afford the target urea. The aniline (IV) has been obtained by reduction of the corresponding nitro derivative (V) with H2 over Pd/C in ethanol.
【1】 Dumas, J.; et al.; Synthesis and pharmacological characterization of a potent, orally active p38 kinase inhibitor. Bioorg Med Chem Lett 2002, 12, 12, 1559. |
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) | 44248 | 4,4-dimethyl-3-oxopentanenitrile | 59997-51-2 | C7H11NO | 详情 | 详情 |
(II) | 12091 | 1-Methylhydrazine; Monomethyl hydrazine | 60-34-4 | CH6N2 | 详情 | 详情 |
(III) | 51506 | 5-Amino-3-tert-butyl-1-methylpyrazole | 118430-73-2 | C8H15N3 | 详情 | 详情 |
(IV) | 51504 | 4-(4-pyridinylmethyl)aniline; 4-(4-pyridinylmethyl)phenylamine | C12H12N2 | 详情 | 详情 | |
(V) | 51503 | 4-(4-Nitrobenzyl)pyridine; 4-(p-nitrobenzyl) pyridine | 1083-48-3 | C12H10N2O2 | 详情 | 详情 |