Fleroxacin, Ro-23-6240/000, Ro-236240, AM-833, Megalocin, Megalosin, Megalone, Quinodis, -Drug Synthesis Database

【结构式】

【药物名称】Fleroxacin, Ro-23-6240/000, Ro-236240, AM-833, Megalocin, Megalosin, Megalone, Quinodis

【化学名称】6,8-Difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

【CA登记号】79660-72-3, 79660-53-0 (monoHCl)

【分子式】C₁₇H₁₈F₃N₃O₃

【分子量】369.34651

【开发单位】Kyorin (Originator), Roche (Licensee)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Quinolones

合成路线1 合成路线2

合成路线1

A new synthesis of fleroxacin, labeled with fluorine-18, has been described: The reaction of 6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (I) with 2-bromoethanol (II) gives 6,7,8-trifluoro-1-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is condensed with N-methylpiperazine (IV), yielding 6,8-difluoro-1-(2-hydroxyethyl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (V). The reaction of (V) with methanesulfonyl chloride affords the corresponding mesylate (VI), which is treated with [18F]-KF in dichloromethane at 80 C to give 6,8-difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII). Finally, this compound is hydrolyzed with NaOH.

参考文献中间体

【1】 Liu, Y.Y.; Cleeland, R.; Livni, E.; Rubin, R.H.; Thom, E.; Strauss, H.W.; Fischman, A.J.; Fleroxacin, a quinolone antibacterial agent. Labeling with fluorine-18 for pharmacokinetic studies. J Label Compd Radiopharm 1993, 32, 576.

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)	10058	ethyl 6,7,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate	79660-46-1	C₁₂H₈F₃NO₃	详情	详情
(II)	10059	Ethylene bromohydrin; 2-Bromo-1-ethanol	540-51-2	C₂H₅BrO	详情	详情
(III)	10060	ethyl 6,7,8-trifluoro-1-(2-hydroxyethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₄H₁₂F₃NO₄	详情	详情
(IV)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(V)	10062	ethyl 6,8-difluoro-1-(2-hydroxyethyl)-7-(4-methylpiperazino)-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₉H₂₃F₂N₃O₄	详情	详情
(VI)	10063	ethyl 6,8-difluoro-7-(4-methylpiperazino)-1-[2-[(methylsulfonyl)oxy]ethyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₂₀H₂₅F₂N₃O₆S	详情	详情
(VII)	10064	ethyl 6,8-difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazino)-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₉H₂₂F₃N₃O₃	详情	详情
(VII)	44571	ethyl 6,8-difluoro-1-(2-fluoroethyl)-7-(4-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₉H₂₂F₃N₃O₃	详情	详情

合成路线2

The reaction of 6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (I) with 1-bromo-2-fluoroethane (II) by means of NaI in hot DMF gives 6,7,8-trifluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (III), which is then condensed with N-methylpiperazine (IV) in refluxing pyridine.

参考文献中间体

【1】 Irikura, T.; Koga, H.; Murayama, S. (Kyorin Pharmaceutical Co., Ltd.); Quinoline carboxylic acid derivatives and process for the preparation. BE 0887574; DE 3106013; FR 2499990; FR 2507183; US 4398029 .
【2】 Serradell, M.N.; Castaner, J.; AM-833. Drugs Fut 1984, 9, 4, 246.

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)	30588	6,7,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₁₀H₄F₃NO₃	详情	详情
(II)	28769	1-bromo-2-fluoroethane	762-49-2	C₂H₄BrF	详情	详情
(III)	30589	1,4-dihydro-1-(2-fluoroethyl)-4-oxo-6,7,8-trifluoro-3-quinolinecarboxylic acid; 6,7,8-trifluoro-1-(2-fluoroethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₁₂H₇F₄NO₃	详情	详情
(IV)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情

Extended Information