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【结 构 式】 
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【药物名称】Amfenac sodium, AHR-5850D, Fenazox, Fenamate 【化学名称】2-Amino-3-benzoylbenzeneacetic acid sodium salt monohydrate 【CA登记号】61618-27-7, 51579-82-9 (free acid) 【 分 子 式 】C15H14NNaO4 【 分 子 量 】295.27293 |
【开发单位】Meiji Seika (Originator) 【药理作用】Non-Steroidal Antiinflammatory Drugs |
合成路线1
The reaction of 1-aminoindolin-2-one (I) with phenylacetone (A) by means of acetic acid in refluxing ethanol gives 1-(alpha-methylphenethylidiene-imino)indolin-2-one (II), which by reaction with refluxing ethanolic hydrogen chloride affords ethyl alpha-(2-methyl-3-phenylindol-7-yl)acetate (III). The ozonolysis of (III) in acetic acid yields ethyl 2-acetamido-3-benzoylphenyl-acetate (IV), which is cyclized by refluxing with HCl in acetic acid to give 7-benzoylindolin-2-one (V). Finally, of the ester (III) with KOH in refluxing water affords the corresponding acid (this compound is hydrolyzed with NaOH in refluxing water). The hydrolysis of the ester (III) with KOH in refluxing water affords the corresponding acid (VI), which can be ozonolyzed as before yielding 2-acetamido-3-benzoylphenylacetic acid (VII). This acid can be cyclized to (V) by refluxing with HCl in acetic acid as before.
| 【1】 Welstead, W.J.Jr.; Moran, H.W (A.H. Robins Co. Inc.); Anti-inflammatory methods using 2-amino-3-(5- and 6-)benzoylphenyl acetic acids, esters and metal salts thereof and the compounds. CA 1012979; DE 2324768; FR 2184934; GB 1521097; US 4045576 . |
| 【2】 Hillier, K.; Castaner, J.; Amfenac. Drugs Fut 1978, 3, 5, 340. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 23143 | 1-Phenylacetone; Methyl benzyl ketone; Benzyl methyl ketone; phenylacetone; Phenyl-2-propanone | 103-79-7 | C9H10O | 详情 | 详情 |
| (I) | 33494 | 1-Aminoindolin-2-one; 1-Amino-1,3-dihydro-2H-indol-2-one | 36149-75-4 | C8H8N2O | 详情 | 详情 |
| (II) | 33495 | 1-(alpha-Methylphenethylidiene-imino)indolin-2-one; 1-[[(Z)-1-Methyl-2-phenylethylidene]amino]-1,3-dihydro-2H-indol-2-one | C17H16N2O | 详情 | 详情 | |
| (III) | 33496 | Ethyl 2-(2-methyl-3-phenyl-1H-indol-7-yl)acetate; Ethyl alpha-(2-methyl-3-phenylindol-7-yl)acetate | C19H19NO2 | 详情 | 详情 | |
| (IV) | 33497 | Ethyl 2-acetamido-3-benzoylphenyl-acetate; Ethyl 2-[2-(acetamido)-3-benzoylphenyl]acetate | C19H19NO4 | 详情 | 详情 | |
| (V) | 33498 | 7-Benzoyl-1,3-dihydro-2H-indol-2-one; 7-Benzoylindolin-2-one | C15H11NO2 | 详情 | 详情 | |
| (VI) | 33499 | 2-(2-methyl-3-phenyl-1H-indol-7-yl)acetic acid | C17H15NO2 | 详情 | 详情 | |
| (VII) | 33500 | 2-[2-(acetamido)-3-benzoylphenyl]acetic acid; 2-Acetamido-3-benzoylphenylacetic acid | C17H15NO4 | 详情 | 详情 |