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【结 构 式】 
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【药物名称】 【化学名称】2-[5-[3-Cyclopentyloxy-4-methoxyphenyl]furan-2-yl]pyridine 【CA登记号】 【 分 子 式 】C21H21NO3 【 分 子 量 】335.40642 |
【开发单位】Merck Frosst (Originator) 【药理作用】Asthma Therapy, Bronchodilators, RESPIRATORY DRUGS, Phosphodiesterase IV Inhibitors |
合成路线1
The Grignard reaction of 3-(cyclopentyloxy)-4-methoxybenzaldehyde (I) with vinylmagnesium bromide in THF gives the vinyl carbinol (II), which is oxidized with MnO2 in ethyl acetate yielding the propenone (III). The condensation of (III) with pyridine-2-carbaldehyde (IV) by means of 3-ethyl-5-(2-hydroxyethyl)-4-methyl-thiazolium bromide (ETB) and triethylamine affords the butanedione (V), which is finally cyclized to the target compound with p-toluenesulfonic acid in refluxing toluene.
| 【1】 Rasori, R.; Robichaud, A.; Girard, Y.; MacDonal, D.; Laliberté, F.; Huang, z.; Perrier, H.; Bayly, C.; Substituted furans as inhibitors of the PDE4 enzyme. Bioorg Med Chem Lett 1999, 9, 3, 323. |
| 【2】 Young, R.N.; MacDonald, D.; Bayly, C.; Perrier, H.; Han, Y.; Giroux, A. (Merck Frosst Canada Inc.); Aryl furan derivs. as PDE IV inhibitors. EP 1021429; US 6020339; WO 9918095 . |
| 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) | 16510 | 3-(cyclopentyloxy)-4-methoxybenzaldehyde | C13H16O3 | 详情 | 详情 | |
| (II) | 30022 | 1-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-propen-1-ol | C15H20O3 | 详情 | 详情 | |
| (III) | 30023 | 1-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-propen-1-one | C15H18O3 | 详情 | 详情 | |
| (IV) | 25173 | 2-pyridinecarbaldehyde | 1121-60-4 | C6H5NO | 详情 | 详情 |
| (V) | 30024 | 1-[3-(cyclopentyloxy)-4-methoxyphenyl]-4-(2-pyridinyl)-1,4-butanedione | C21H23NO4 | 详情 | 详情 |
Extended Information