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【结 构 式】 
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【分子编号】33214 【品名】3-(cyclopentyloxy)-4-methoxybenzoic acid 【CA登记号】 |
【 分 子 式 】C13H16O4 【 分 子 量 】236.26764 【元素组成】C 66.09% H 6.83% O 27.09% |
合成路线1
该中间体在本合成路线中的序号：(IV)The alkylation of isovanillin (I) with cyclopentyl bromide (II) by means of K2CO3 in refluxing ethanol (or hot DMF) gives the 4-cyclopentyloxy-3-methoxybenzaldehyde (III), which is oxidized with H2O2 and NaOH (or NaClO2 in AcOH/water) yielding the carboxylic acid (IV). The reaction of (IV) with SOCl2 and DMF in refluxing toluene affords the acyl chloride (V), which is finally condensed with 3,5-dichloropyridine-4-amine (VI) by means of potassium tert-butoxide in toluene or NaH in THF or by heating at the melting point. The intermediate 3,5-dichloropyridine-4-amine (VI) is obtained by chlorination of pyridine-4-amine (VII) with HCl and H2O2 at 70 C.
| 【1】 Ashton, M.J.; Cook, D.C.; Fenton, G.; Hills, S.J.; Mcfarlane, I.M.; Palfreyman, M.N.; Ratcliffe, A.J.; Vicker, N. (Aventis Pharma SA); Benzamides. EP 0497564; EP 0569414; JP 1994504782; WO 9212961 . |
| 【2】 Cook, D.C.; Walton, J.B.; Pemberton, C.; Jones, R.H.; McFarlane, I.M.; Thompson, D.M.; Thatcher, A.A.; Kabir, H.; Lythgoe, D.J.; Process development of the PDE IV inhibitor 3-(cyclopentyloxy)-N-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide. Org Process Res Dev 1998, 2, 3, 157. |
| 【3】 Ashton, M.J.; et al.; Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues. J Med Chem 1994, 37, 11, 1696. |
| 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) | 18455 | 3-hydroxy-4-methoxybenzaldehyde; Isovanillin | 621-59-0 | C8H8O3 | 详情 | 详情 |
| (II) | 10972 | 1-Bromocyclopentane; Cyclopentyl bromide | 137-43-9 | C5H9Br | 详情 | 详情 |
| (III) | 16510 | 3-(cyclopentyloxy)-4-methoxybenzaldehyde | C13H16O3 | 详情 | 详情 | |
| (IV) | 33214 | 3-(cyclopentyloxy)-4-methoxybenzoic acid | C13H16O4 | 详情 | 详情 | |
| (V) | 33213 | 3-(cyclopentyloxy)benzoyl chloride | C12H13ClO2 | 详情 | 详情 | |
| (VI) | 25135 | 3,5-dichloro-4-pyridinamine; 4-amino-3,5-dichloropyridine | 22889-78-7 | C5H4Cl2N2 | 详情 | 详情 |
| (VII) | 25661 | 4-pyridinamine; 4-aminopyridine | 5044-74-5 | C5H6N2 | 详情 | 详情 |