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【结 构 式】 
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【分子编号】10044 【品名】6,7-Dichloro-3-hydroxy-2-benzofuran-1(3H)-one 【CA登记号】 |
【 分 子 式 】C8H4Cl2O3 【 分 子 量 】219.02336 【元素组成】C 43.87% H 1.84% Cl 32.37% O 21.91% |
合成路线1
该中间体在本合成路线中的序号：(I)A new synthesis for LY-134046 has been described: The reaction of 6,7-dichloro-3-hydroxyphthalide (I) with diethyl cyanomethylphosphonate (II) by means of NaH in dimethoxyethane gives 2-carboxy-3,4-dichlorocinnamonitrile (III), which is reduced with NaBH4 in refluxing isopropanol to yield 3-(2-carboxy-3,4-dichlorophenyl)propionitrile (IV). The esterification of (IV) with methyl iodide and K2CO3 affords the cyano ester (V), which is reduced with BH3 in THF giving 6-(3-aminopropyl)-2,3-dichlorobenzoic acid methyl ester (VI). The cyclization of (VI) by means of sodium methoxide in methanol yields 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one (VII), which is finally reduced with BH3 in refluxing THF.
| 【1】 Paradkar, V.M.; Grunewald, G.L.; A regioselective synthesis of 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (LY134046), a potent phenylethanolamine N-methyltransferase inhibitor. Bioorg Med Chem Lett 1991, 1, 1, 59-60. |
| 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) | 10044 | 6,7-Dichloro-3-hydroxy-2-benzofuran-1(3H)-one | C8H4Cl2O3 | 详情 | 详情 | |
| (II) | 10045 | Diethyl cyanomethylphosphonate | 2537-48-6 | C6H12NO3P | 详情 | 详情 |
| (III) | 10046 | 2,3-Dichloro-6-[(E)-2-cyanoethenyl]benzoic acid | C10H5Cl2NO2 | 详情 | 详情 | |
| (IV) | 10047 | 2,3-Dichloro-6-(2-cyanoethyl)benzoic acid | C10H7Cl2NO2 | 详情 | 详情 | |
| (V) | 10048 | methyl 2,3-dichloro-6-(2-cyanoethyl)benzoate | C11H9Cl2NO2 | 详情 | 详情 | |
| (VI) | 10049 | methyl 6-(3-aminopropyl)-2,3-dichlorobenzoate | C11H13Cl2NO2 | 详情 | 详情 | |
| (VII) | 10050 | 8,9-Dichloro-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one | C10H9Cl2NO | 详情 | 详情 |