|
【结 构 式】 
|
【药物名称】Ciprofloxacin hydrochloride, Bay-o-9867 monohydrate, Septocipro, Ciprenit, Velmonit, Cipro XR, Ciproxan, Sarf, Cetraxal, Ciprobay, Ciloxan, Ciflox, Cipro, Eni, Ciproxin, Oftacilox 【化学名称】1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride hydrate 【CA登记号】86393-32-0, 85721-33-1 (free base, anhydrous) 【 分 子 式 】C17H21ClFN3O4 【 分 子 量 】385.82602 |
【开发单位】Bayer (Originator), Alcon (Licensee), Esteve (Licensee), Salvat (Licensee), Vita (Licensee), National Institutes of Health (Codevelopment) 【药理作用】Antibacterial Drugs, Antibacterial Ophthalmic Drugs, ANTIINFECTIVE THERAPY, Cystic Fibrosis, Treatment of , Ocular Antiinflammatory and Antiinfective Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, RESPIRATORY DRUGS, DNA Gyrase Inhibitors, DNA Topoisomerase IV Inhibitors, Quinolones |
合成路线1
The condensation of 2,4-dichloro-5-fluorobenzoyl chloride (I) with diethyl malonate (II) by means of magnesium ethoxide in ether gives diethyl 2,4-dichloro-5-fluorobenzoylmalonate (III), which is partially hydrolyzed and decarboxylated with p-toluenesulfonic acid water yielding ethyl 2,4-dichloro-5-fluorobenzoylacetate (IV). The condensation of (IV) with triethyl orthoformate (V) in refluxing acetic anhydride affords ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate (VI), which is treated with cyclopropylamine (VII) in ethanol to give ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-cyclopropylaminoacrylate (VIII). The cyclization of (VIII) with NaH in refluxing dioxane yields 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (IX), which is finally condensed with piperazine (X) in hot DMSO.
| 【1】 Reddy, P.G.; Baskaran, S.; Microwave assisted amination of quinolone carboxylic acids: An expeditious synthesis of fluoroquinolone antibacterials. Tetrahedron Lett 2001, 42, 38, 6775. |
| 【2】 Grohe, K.; Zeiler, H. J.; Metzger, K.G. (Bayer AG); 1-Cyclopropyl-6-fluoro-1,4-dihidro-4-oxo-7-piperazino-quinoline-3-carboxilic acids, process for their preparation and antibacterial agents containing them. EP 0078362; JP 4253963; JP 58074667 . |
| 【3】 Serradell, M.N.; Castaner, J.; Ciprofloxacin. Drugs Fut 1984, 9, 3, 179. |
| 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) | 30340 | ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | 86483-54-7 | C15H13ClFNO3 | 详情 | 详情 |
| (X) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |