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【结 构 式】 
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【药物名称】 【化学名称】4-[2-(4-Chlorophenyl)-4-(2,4-dibutoxyphenyl)-1H-imidazol-5-yl]pyridine 【CA登记号】208188-17-4 (tautomer) 【 分 子 式 】C28H30ClN3O2 【 分 子 量 】476.0232 |
【开发单位】Merck & Co. (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Glucagon Antagonists |
合成路线1
The reaction of 3,5-dihydroxybenzoic acid (I) with N,O-dimethylhydroxylamine (II) by means of EDC and NMM in dichloromethane gives the N,O-dimethylbenzamide (III), which is alkylated with butyl bromide (IV) and K2CO3 in hot DMF to yield the dibutoxybenzamide (V). The condensation of (V) with 4-methylpyridine (VI) by means of LDA in THF affords 1-(2,4-dibutoxyphenyl)-2-(4-pyridyl)ethanone (VII), which is oxidized with SeO2 in hot acetic acid to provide the dione (VIII). Finally, this compound is cyclized with 4-chlorobenzaldehyde (IX) and ammonium acetate in refluxing acetic acid to furnish the target imidazole.
| 【1】 Chang, L.L.; et al.; Substituted imidazoles as gluagon receptor antagonists. Bioorg Med Chem Lett 2001, 11, 18, 2549. |
| 【2】 de Laszlo, S.; O'Keefe, S.; Li, B.; MacCoss, M.; Rolando, A.; mantlo, N.; Koch, G.; Cascieri, M.A.; Hagmann, W.K.; Chang, L.L.; Pang, M.; Sidler, K.L.; Selective, non-peptide antagonists for the glucagon receptor: Substituted imidazoles. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 237. |
| 【3】 Chang, L.L. (Merck & Co., Inc.); Triaryl substd. imidazoles as glucagon antagonists. EP 0959886; JP 2000514088; US 5880139; WO 9822109 . |
| 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) | 48820 | 2,4-Dihydroxybenzenecarboxylic acid; 2,4-Dihydroxybenzoic acid; beta-Resorcylic acid; Resorcinol-4-carboxylic acid | 89-86-1 | C7H6O4 | 详情 | 详情 |
| (II) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
| (III) | 48821 | 2,4-dihydroxy-N-methoxy-N-methylbenzamide | C9H11NO4 | 详情 | 详情 | |
| (IV) | 28721 | 1-bromobutane | 109-65-9 | C4H9Br | 详情 | 详情 |
| (V) | 48822 | 2,4-dibutoxy-N-methoxy-N-methylbenzamide | C17H27NO4 | 详情 | 详情 | |
| (VI) | 31150 | 4-methylpyridine | 108-89-4 | C6H7N | 详情 | 详情 |
| (VII) | 48823 | 1-(2,4-dibutoxyphenyl)-2-(4-pyridinyl)-1-ethanone | C21H27NO3 | 详情 | 详情 | |
| (VIII) | 48824 | 1-(2,4-dibutoxyphenyl)-2-(4-pyridinyl)-1,2-ethanedione | C21H25NO4 | 详情 | 详情 | |
| (IX) | 29029 | 4-chlorobenzaldehyde | 104-88-1 | C7H5ClO | 详情 | 详情 |