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【结 构 式】 
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【药物名称】SB-235699, HEP-689 【化学名称】4-[4-(4-Fluorophenyl)-1-(4-piperidinyl)-1H-imidazol-5-yl]pyridine 【CA登记号】180869-32-3 【 分 子 式 】C19H19FN4 【 分 子 量 】322.38848 |
【开发单位】GlaxoSmithKline (Originator), Leo (Licensee) 【药理作用】Antipsoriatics, Atopic Dermatitis, Agents for, DERMATOLOGIC DRUGS, Topical Antiinflammatory Agents, p38 Protein Kinase Inhibitors |
合成路线1
Condensation between p-fluorobenzaldehyde (I), p-toluenesulfinic acid (II) and formamide in the presence of camphorsulfonic acid afforded 4-fluorophenyltosylmethyl formamide (III). Subsequent dehydration of (III) by means of POCl3 and Et3N produced isonitrile (IV). Imine (VII) was prepared by condensation of pyridine-4-carboxaldehyde (V) with 1-Boc-4-aminopiperidine (VI) using MgSO4 as the dehydrating reagent. Dipolar cycloaddition of this imine with the anion of tosyl isonitrile (IV) generated the trisubstituted imidazole (VIII). Finally, acid cleavage of the Boc protecting group furnished the title compound.
| 【1】 Adams, J.L.; Gallagher, T.F.; Garigipati, R.S.; Boehm, J.C.; Sisko, J.; Peng, Z.-Q.; Lee, J.C.-L. (SmithKline Beecham plc); Certain 1,4,5-tri-substd. imidazole cpds. useful as cytokine. EP 0809499; JP 1998512555; US 5593992; WO 9621452 . |
| 【2】 Garigipati, R.S.; Adams, J.L.; Boehm, J.C. (SmithKline Beecham Corp.); Pyridyl imidazole cpds. and compsns.. US 5670527 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 16598 | Formamide | 75-12-7 | CH3NO | 详情 | 详情 | |
| (I) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (II) | 25593 | 4-methylbenzenesulfinic acid | C7H8O2S | 详情 | 详情 | |
| (III) | 25594 | (4-fluorophenyl)[(4-methylphenyl)sulfonyl]methylformamide | C15H14FNO3S | 详情 | 详情 | |
| (IV) | 25595 | 4-Fluoro-alpha-(4-methylphenylsulfonyl)benzyl isocyanide | C15H12FNO2S | 详情 | 详情 | |
| (V) | 17203 | 4-Pyridinecarboxaldehyde; isonicotinaldehyde | 872-85-5 | C6H5NO | 详情 | 详情 |
| (VI) | 28414 | 4-Amino-1-N-Boc-piperidine; tert-butyl 4-amino-1-piperidinecarboxylate; N-Boc-4-aminopiperidine | 87120-72-7 | C10H20N2O2 | 详情 | 详情 |
| (VII) | 34886 | tert-butyl 4-[[(Z)-4-pyridinylmethylidene]amino]-1-piperidinecarboxylate | C16H23N3O2 | 详情 | 详情 | |
| (VIII) | 34887 | tert-butyl 4-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-1-yl]-1-piperidinecarboxylate | C24H27FN4O2 | 详情 | 详情 |