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【结 构 式】 
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【药物名称】AH-7725 【化学名称】7-(2-Hydroxyethoxy)xanthone-2-carboxylic acid 【CA登记号】33459-28-8 【 分 子 式 】C16H12O6 【 分 子 量 】300.27044 |
【开发单位】Allen and Hanbury's (Originator), GlaxoSmithKline (Not Determined) 【药理作用】Antiallergy/Antiasthmatic Drugs, Antianemics, Asthma Therapy, Cognition Disorders, Treatment of, HEMATOLOGIC DRUGS, Hematopoiesis Disorders Therapy, NEUROLOGIC DRUGS, RESPIRATORY DRUGS |
合成路线1
By cleavage of the 7-methoxy-9-oxoxanthene-2-carboxylic acid (I) with AlCl3 in xylene to give 7-hydroxy-9-oxoxanthene-2-carboxylic acid (II), which is then esterified with ethanol and anhydrous HCl to the corresponding ethyl ester (III). This product is treated first with ethylene oxide (A) in DMF, and finally hydrolyzed with NaOH in ethanol-water. The condensation of 2-chloro-5-nitrobenzoic acid (IV) with 4-methoxyphenol (V) by means of K2CO3, Cu and Cu2I2 in n-pentanol gives 2-(4-methoxyphenoxy)-5-nitrobenzoic acid (VI), which is cyclized with concentrated H2SO4 to 7-methoxy-2-nitroxanthone (VII). The reduction of the nitro group of (VII) with SnCl2 in concentrated HCl yields 7-methoxy-2-aminoxanthone (VIII). Finally, this product is treated first with NaNO2 - HCl, then with NaCN and finally hydrolyzed with H2SO4 to afford 7-methoxy-9-oxoxanthene-2-carboxylic acid.
| 【1】 Castaner, J.; Blancafort, P.; AH 7725. Drugs Fut 1976, 1, 7, 313. |
| 【2】 Bays, D.E.; Xanthone derivatives.. DE 2058295; FR 2073425; GB 1312620; US 3706768 . |
| 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) | 10393 | Oxirane; Ethylene oxide | 75-21-8 | C2H4O | 详情 | 详情 |
| (I) | 40469 | 7-methoxy-9-oxo-9H-xanthene-2-carboxylic acid | C15H10O5 | 详情 | 详情 | |
| (II) | 40470 | 7-hydroxy-9-oxo-9H-xanthene-2-carboxylic acid | C14H8O5 | 详情 | 详情 | |
| (III) | 40471 | ethyl 7-hydroxy-9-oxo-9H-xanthene-2-carboxylate | C16H12O5 | 详情 | 详情 | |
| (IV) | 10198 | 4-Chlorophenyl thiocyanate | 3226-37-7 | C7H4ClNS | 详情 | 详情 |
| (V) | 32744 | 4-methoxyphenol | 150-76-5 | C7H8O2 | 详情 | 详情 |
| (VI) | 40466 | 2-(4-methoxyphenoxy)-5-nitrobenzoic acid | C14H11NO6 | 详情 | 详情 | |
| (VII) | 40467 | 2-methoxy-7-nitro-9H-xanthen-9-one | C14H9NO5 | 详情 | 详情 | |
| (VIII) | 40468 | 2-amino-7-methoxy-9H-xanthen-9-one | C14H11NO3 | 详情 | 详情 |
合成路线2
The condensation of 2-bromo-5-methoxybenzoic acid (IX) with 4-hydroxybenzonitrile (X) by means of K2CO3, Cu and Cu2I2 in n-pentanol gives 2-(4-cyanophenoxy)-5-methoxybenzoic acid (XI), which is cyclized and hydrolyzed with hot H2SO4 to give the starting product (I). Alternatively, compound (XI) can be cyclized and partially hydrolyzed with hot polyphosphoric acid giving 7-methoxy-9-oxoxanthene-2-carboxamide (XII), which is finally hydrolyzed with H2SO4.
| 【1】 Castaner, J.; Blancafort, P.; AH 7725. Drugs Fut 1976, 1, 7, 313. |
| 【2】 Bays, D.E.; Xanthone derivatives.. DE 2058295; FR 2073425; GB 1312620; US 3706768 . |