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【结 构 式】 
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【药物名称】 【化学名称】1-(2,5-Dimethoxybenzyl)-4-(4-methoxyphenyl)-2-oxo-1,2-dihydrobenzofuro[3,2-b]pyridine-3-carboxylic acid 【CA登记号】 【 分 子 式 】C28H23NO7 【 分 子 量 】485.49801 |
【开发单位】Merck KGaA (Originator) 【药理作用】Endothelin ETA Receptor Antagonists, Endothelin ETB Receptor Antagonists |
合成路线1
2-Cyanophenol (I) was condensed with 2-bromo-4'-methoxyacetophenone (II) in the presence of K2CO3 in acetone to give aminobenzofuran (III). This was acylated with trifluoroacetic anhydride, and the resulting trifluoroacetamide (IV) was alkylated with 2,5-dimethoxybenzyl chloride (V) under phase-transfer conditions to afford monobenzylated compound (VI). The benzofuro[3,2-b]pyridine nucleus was formed by acylation of the secondary amine group of (VI) with ethyl malonyl chloride (VII) to give (VIII) followed by an intramolecular Knoevenagel condensation over silica gel in refluxing CH2Cl2 to give (IX). Alkaline hydrolysis of the ester function of (IX) then provided the corresponding carboxylic acid.
| 【1】 Mederski, W.K.R.; Wilm, C.; Schmitges, C.-J.; Oswald, M.; Dorsch, D.; Christadler, M.; Benzofuro[3,2-b]pyridines as mixed ETA/ETB and selective ETB endothelin receptor antagonists. Bioorg Med Chem Lett 1999, 9, 4, 619. |
| 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) | 21990 | 2-hydroxybenzonitrile | 611-20-1 | C7H5NO | 详情 | 详情 |
| (II) | 21991 | 2-Methoxyphenacyl bromide; 2-bromo-1-(4-methoxyphenyl)-1-ethanone | 2632-13-5 | C9H9BrO2 | 详情 | 详情 |
| (III) | 21992 | (3-amino-1-benzofuran-2-yl)(4-methoxyphenyl)methanone | C16H13NO3 | 详情 | 详情 | |
| (IV) | 21993 | 2,2,2-trifluoro-N-[2-(4-methoxybenzoyl)-1-benzofuran-3-yl]acetamide | C18H12F3NO4 | 详情 | 详情 | |
| (V) | 21994 | 2-(chloromethyl)-4-methoxyphenyl methyl ether; 2-(chloromethyl)-1,4-dimethoxybenzene | 3840-27-5 | C9H11ClO2 | 详情 | 详情 |
| (VI) | 21995 | [3-[(2,5-dimethoxybenzyl)amino]-1-benzofuran-2-yl](4-methoxyphenyl)methanone | C25H23NO5 | 详情 | 详情 | |
| (VII) | 13188 | ethyl 3-chloro-3-oxopropanoate; 2-Ethoxycarbonylacetyl chloride; Ethyl malonyl chloride | 36239-09-5 | C5H7ClO3 | 详情 | 详情 |
| (VIII) | 21997 | ethyl 3-[(2,5-dimethoxybenzyl)[2-(4-methoxybenzoyl)-1-benzofuran-3-yl]amino]-3-oxopropanoate | C30H29NO8 | 详情 | 详情 | |
| (IX) | 21998 | ethyl 1-(2,5-dimethoxybenzyl)-4-(4-methoxyphenyl)-2-oxo-1,2-dihydro[1]benzofuro[3,2-b]pyridine-3-carboxylate | C30H27NO7 | 详情 | 详情 |