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【结 构 式】 
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【分子编号】24553 【品名】methyl 6-acetyl-1-ethyl-7-hydroxy-4-oxo-8-propyl-1,4-dihydro-2-quinolinecarboxylate 【CA登记号】69049-70-3 |
【 分 子 式 】C18H21NO5 【 分 子 量 】331.36848 【元素组成】C 65.24% H 6.39% N 4.23% O 24.14% |
合成路线1
该中间体在本合成路线中的序号：(IX)The alkylation of 4-(N-acetyl-N-ethylamino)-2-hydroxyacetophenone (I) with allyl bromide (II) by means of K2CO3 in DMF gives the allyl ether (III), which is isomerized by refluxing in diethylaniline to 4-(N-acetyl-N-ethylamino)-3-allyl-2-hydroxyacetophenone (IV) The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding propyl derivative (V), which is deacetylated with HBr in refluxing acetic acid water to 4-(ethylamino)-3-propyl-2-hydroxyacetophenone (VI). The addition of (VI) dimethyl acetylenedicarboxylate (VII) in refluxing ethanol affords the aminomaleate (VIII), which by cyclization witn polyphosphoric acid at 100 C gives methyl 1-ethyl-6-acetyl-7-hydroxy-4 oxo-8-propyl-4H-quinoline-2-carboxylate (IX). The condensation of (IX) with diethyl oxalate in DMF by means of NaH results in the ester of the final product (X), which is then hydrolyzed with NaHCO3 iin refluxing ethanol.
| 【1】 Wilkinson, D.J.; Lockley, W.J.S.; Synthesis of nedocromil sodium labelled with tritium, deuterium and carbon-14. J Label Compd Radiopharm 1985, 22, 9, 883. |
| 【2】 Caims, H.; Cox, D. (Rhone-Poulenc Rorer Ltd.); Nouvelles pyranoquinoleinones et leurs compositions pharmaceutiques. DE 2819215; ES 469391; JP 1199909; JP 53137969 . |
| 【3】 Cairns, H.; Cox, D. (Rhone-Poulenc Rorer Ltd.); 4,6-Dioxo-4H,6H-pyrano[3,2-g]quinoline-2,8-dicarbocyclic acids. GB 2022078 . |
| 【4】 Prous, J.; Castaner, J.; Nedocromil sodium. Drugs Fut 1986, 11, 9, 756. |
| 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) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
| (I) | 24545 | N-(4-acetyl-3-hydroxyphenyl)-N-ethylacetamide | C12H15NO3 | 详情 | 详情 | |
| (II) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (III) | 24547 | 3-[4-acetyl-3-(allyloxy)phenyl]-2-pentanone | C16H20O3 | 详情 | 详情 | |
| (IV) | 24548 | N-(4-acetyl-2-allyl-3-hydroxyphenyl)-N-ethylacetamide | 69049-64-5 | C15H19NO3 | 详情 | 详情 |
| (V) | 24549 | N-(4-acetyl-3-hydroxy-2-propylphenyl)-N-ethylacetamide | C15H21NO3 | 详情 | 详情 | |
| (VI) | 24550 | 1-[4-(ethylamino)-2-hydroxy-3-propylphenyl]-1-ethanone | 69049-68-9 | C13H19NO2 | 详情 | 详情 |
| (VII) | 24551 | Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester | 762-42-5 | C6H6O4 | 详情 | 详情 |
| (VIII) | 24552 | dimethyl (Z)-2-[4-acetyl(ethyl)-3-hydroxy-2-propylanilino]-2-butenedioate | 77941-04-9 | C19H25NO6 | 详情 | 详情 |
| (IX) | 24553 | methyl 6-acetyl-1-ethyl-7-hydroxy-4-oxo-8-propyl-1,4-dihydro-2-quinolinecarboxylate | 69049-70-3 | C18H21NO5 | 详情 | 详情 |
| (X) | 24554 | diethyl 9-ethyl-4,6-dioxo-10-propyl-6,9-dihydro-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate | 69049-72-5 | C23H25NO7 | 详情 | 详情 |