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【结 构 式】 
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【分子编号】19904 【品名】ethyl 7-chloro-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C12H9ClFNO3 【 分 子 量 】269.6595032 【元素组成】C 53.45% H 3.36% Cl 13.15% F 7.05% N 5.19% O 17.8% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate (I) with O-(2,4-dinitrophenyl)hydroxylamine (II) by means of K2CO3 in DMF gives ethyl 1-amino-6-fluoro-7-chloro-1,4-dihydro-4-oxo-3-quinolinecarboxylate (III), which is formylated with HCOOH in acetic anhydride yielding the corresponding 1-(formylamino) compound (IV). The methylation of (IV) with MeI and K2CO3 in DMF affords the 1-(formylmethylamino) compound (V), which is hydrolyzed with NaOH in refluxing water to give 7-chloro-6-fluoro-1,4-dihydro-4-oxo-1-(methylamino)quinoline-3-carboxylic acid (VI). Finally, this compound is condensed with N-methylpiperazine (VII) in refluxing pyridine.
| 【1】 Powles, R.G.; Wentland, M.P.; Wagner, R.B.; Dobson, .A.; Bailey, D.M.; Cornett, J.B.; Novel amino-substituted 3-quinolinecarboxylic acid antibacterial agents: Synthesis and stucture-activity relationships. J Med Chem 1984, 27, 9, 1103. |
| 【2】 Wentland, M.P.; Bailey, D.M. (Sterling Winthrop Inc.); New quinolone compounds and preparation thereof. EP 0090424; JP 8401468 . |
| 【3】 Castaner, J.; Serradell, M.N.; Burnie, J.; Matthews, R.; Amifloxacin. Drugs Fut 1985, 10, 3, 183. |
| 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) | 19904 | ethyl 7-chloro-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C12H9ClFNO3 | 详情 | 详情 | |
| (II) | 29034 | 1-(aminooxy)-2,4-dinitrobenzene | C6H5N3O5 | 详情 | 详情 | |
| (III) | 29035 | ethyl 1-amino-7-chloro-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C12H10ClFN2O3 | 详情 | 详情 | |
| (IV) | 29036 | ethyl 7-chloro-6-fluoro-1-(formylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C13H10ClFN2O4 | 详情 | 详情 | |
| (V) | 29037 | ethyl 7-chloro-6-fluoro-1-[formyl(methyl)amino]-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C14H12ClFN2O4 | 详情 | 详情 | |
| (VI) | 29038 | 7-chloro-6-fluoro-1-(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C11H8ClFN2O3 | 详情 | 详情 | |
| (VII) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Title compound was synthesized by condensation of ethyl 7-chloro-6-fluoro-4-quinolone-3-carboxylate (I) with cyclohexylamine (II) in pyridine at 120 C under pressure.
| 【1】 Srivastava S; Srivastava, S.K.; Shukla, A.; Chauhan, P.M.; Puri, S.K.; Bhaduri, A.P.; Pandey, V.C.; Synthesis and methemoglobin toxicity of the amides of 6/7 mono or disubstituted quinolone. Bioorg Med Chem Lett 1999, 9, 1, 25. |
合成路线3
该中间体在本合成路线中的序号：(I)Title compound was synthesized by condensation of ethyl 7-chloro-6-fluoro-4-quinolone-3-carboxylate (I) with N-methylpiperazine (II) in pyridine at 120 C under pressure.
| 【1】 Srivastava S; Srivastava, S.K.; Shukla, A.; Chauhan, P.M.; Puri, S.K.; Bhaduri, A.P.; Pandey, V.C.; Synthesis and methemoglobin toxicity of the amides of 6/7 mono or disubstituted quinolone. Bioorg Med Chem Lett 1999, 9, 1, 25. |