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【结 构 式】 
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【分子编号】22101 【品名】7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid 【CA登记号】86393-33-1 |
【 分 子 式 】C13H9ClFNO3 【 分 子 量 】281.6705032 【元素组成】C 55.43% H 3.22% Cl 12.59% F 6.74% N 4.97% O 17.04% |
合成路线1
该中间体在本合成路线中的序号：(IX)1) The condensation of 2,4-dichloro-5-fluoro-benzoyl chloride (I) with diethyl malonate (II) by means of magnesium ethoxide gives diethyl 2,4-dichloro-5-fluorobenzoylmalonate (III), which is partially decarboxylated with p-toluenesulfonic acid yielding ethyl 2,4-dichloro-5-fluorobenzoylacetate (IV). The condensation of (IV) with triethyl orthoformate (V) by means of refluxing acetic anhydride affords ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate (VI), which is treated with cyclopropylamine (VII) in ethanol giving ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(cyclopropylamino)acrylate (VII). The cyclization of (VII) by means of NaH in refluxing dioxane yields 1-cyclopropyl-7-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (IX), which is finally condensed with N-ethylpiperazine (X) by heating at 140 C in DMSO.
| 【1】 Grohe, K.; Klimetzek, V.; Metzger, K.G.; Stunkel, K.G.; Zeiler, H.-J. (Bayer AG); Immunostimulant agent. AU 8542762; DE 3420116; EP 0165474; ES 8607020; JP 1985258163; US 4659603 . |
| 【2】 Grohe, K.; Petersen, U.; Kuck, K.-H. (Bayer AG); Antimicrobial agent of quinolone-carboxylic acid b. DE 3248507; US 4563459 . |
| 【3】 Castaner, J.; Prous, J.; Enrofloxacin. Drugs Fut 1988, 13, 4, 305. |
| 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) | 22093 | 2,4-dichloro-5-fluorobenzoyl chloride | 86393-34-2 | C7H2Cl3FO | 详情 | 详情 |
| (II) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (III) | 22095 | diethyl 2-(2,4-dichloro-5-fluorobenzoyl)malonate | C14H13Cl2FO5 | 详情 | 详情 | |
| (IV) | 22096 | ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate | C11H9Cl2FO3 | 详情 | 详情 | |
| (V) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
| (VI) | 22098 | ethyl (Z)-2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxy-2-propenoate | C14H13Cl2FO4 | 详情 | 详情 | |
| (VII) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |
| (VIII) | 22100 | ethyl (E)-3-(cyclopropylamino)-2-(2,4-dichloro-5-fluorobenzoyl)-2-propenoate | C15H14Cl2FNO3 | 详情 | 详情 | |
| (IX) | 22101 | 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | 86393-33-1 | C13H9ClFNO3 | 详情 | 详情 |
| (X) | 14213 | N-Ethylpiperazine; 1-Ethylpiperazine | 5308-25-8 | C6H14N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)2) The condensation of quinoline (IX) with piperazine (XI) by heating at 140 C as before gives 1-cyclopropyl-6-fluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-3-carboxylic acid (XII), which is finally treated with ethyl iodide and triethylamine in hot DMF.
| 【1】 Grohe, K.; Petersen, U.; Kuck, K.-H. (Bayer AG); Antimicrobial agent of quinolone-carboxylic acid b. DE 3248507; US 4563459 . |
| 【2】 Grohe, K.; Klimetzek, V.; Metzger, K.G.; Stunkel, K.G.; Zeiler, H.-J. (Bayer AG); Immunostimulant agent. AU 8542762; DE 3420116; EP 0165474; ES 8607020; JP 1985258163; US 4659603 . |
| 【3】 Castaner, J.; Prous, J.; Enrofloxacin. Drugs Fut 1988, 13, 4, 305. |
| 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) | 10925 | Iodoethane;ethyl iod | 75-03-6 | C2H5I | 详情 | 详情 |
| (IX) | 22101 | 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | 86393-33-1 | C13H9ClFNO3 | 详情 | 详情 |
| (XI) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
| (XII) | 22103 | 1-cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4-dihydro-3-quinolinecarboxylic acid | 85721-33-1 | C17H18FN3O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IX)3) The condensation of 2,4-dichloro-5-fluorobenzoyl chloride (I) with methyl 3-(cyclopropylamino)acrylate (XIII) gives methyl 2-(2,4-dichloro-5-fluoro-benzoyl)-3-(cyclopropylamino)acrylate (XIV), which is first cyclized with t-BuOK and then hydrolyzed to give compound (IX).
| 【1】 Grohe, K.; Petersen, U.; Kuck, K.-H. (Bayer AG); Antimicrobial agent of quinolone-carboxylic acid b. DE 3248507; US 4563459 . |
| 【2】 Grohe, K.; Klimetzek, V.; Metzger, K.G.; Stunkel, K.G.; Zeiler, H.-J. (Bayer AG); Immunostimulant agent. AU 8542762; DE 3420116; EP 0165474; ES 8607020; JP 1985258163; US 4659603 . |
| 【3】 Castaner, J.; Prous, J.; Enrofloxacin. Drugs Fut 1988, 13, 4, 305. |
| 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) | 22093 | 2,4-dichloro-5-fluorobenzoyl chloride | 86393-34-2 | C7H2Cl3FO | 详情 | 详情 |
| (IX) | 22101 | 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | 86393-33-1 | C13H9ClFNO3 | 详情 | 详情 |
| (XIII) | 22104 | methyl (E)-3-(cyclopropylamino)-2-propenoate | C7H11NO2 | 详情 | 详情 | |
| (XIV) | 22105 | methyl (E)-3-(cyclopropylamino)-2-(2,4-dichloro-5-fluorobenzoyl)-2-propenoate | C14H12Cl2FNO3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)The title adduct is prepared by condensation between the piperazinyl oxazolidinone derivative (I) and chloroquinoline (II) in hot N-methylpyrrolidinone.
| 【1】 Locher, H.H.; Specklin, J.; Borer, Y.; Brohammer, S.; Schroeder, S.; Sigwalt, C.; Hubschwerlen, C.; Synthesis and antibacterial action of novel quinolone-linked oxazolidinones. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1317. |
| 【2】 Barbachyn, M.R.; Patel, D.V.; Gage, J.R.; Gordeev, M.F. (Pharmacia Corp.); Antimicrobial quinolone derivs. and use of the same to treat bacterial infections. WO 0259116 . |