7-chloro-6-fluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】24579

【品名】7-chloro-6-fluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid

【CA登记号】

【分子式】C₁₆H₈ClF₂NO₃

【分子量】335.6939664

【元素组成】C 57.25% H 2.4% Cl 10.56% F 11.32% N 4.17% O 14.3%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

Condensation of 2,4-dichoro-5-fluoroacetophenone (I) with diethyicarbonate (II) in the presence of sodium hydride gives ethyl 2,4-dichloro-5-fluorobenzoylacetate (III). The condensation of (III) with triethylorthoformate in reftuxing acetic anhydride yields ethyl 2-(2,4-dichloro-5-fluornbenzoyl)-3-ethoxyacrylate (IV), which is treated with p-fluoroaniline in methylene chloride to yield ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(p-fluoroanilino)acrylate (V). Cyclization of (V) with sodium hydride in tetrahydrofuran followed by hydrolysis yields 7-chloro-1-(p-fluorophenyl)-8 fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (VI). Condensation of (VI) with N-methylpiperazine in 1-methyl-2-pyrrolidinone followed by treatment with hydrochloric acid yields A-56619.

参考文献中间体

合成目标

【1】 Clairbone, A.K.; Pihuleac, E.; Nordeen, C.; Fernandes, P.B.; Pernet, A.; Chu, D.T.W.; O'Donell, T.J.; A-56619 and A-56620: Synthesis and antibacterial activities of the novel aryl-fluoro-quinolones and their analogs. 24th Intersci Conf Antimicrob Agents Chemother (Oct 8-10, Washington, D.C) 1984, Abs 72.
【2】 Granneman, G.R.; Chu, D.T.W.; Fernandes, P.B.; Abbott-56619. Drugs Fut 1985, 10, 7, 543.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
	37690	4-fluorophenylamine; 4-fluoroaniline	371-40-4	C₆H₆FN	详情	详情
(I)	24574	1-(2,4-dichloro-5-fluorophenyl)-1-ethanone	704-10-9	C₈H₅Cl₂FO	详情	详情
(II)	17470	diethyl carbonate; diethylcarbonate	105-58-8	C₅H₁₀O₃	详情	详情
(III)	22096	ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate		C₁₁H₉Cl₂FO₃	详情	详情
(IV)	22098	ethyl (Z)-2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxy-2-propenoate		C₁₄H₁₃Cl₂FO₄	详情	详情
(V)	24578	ethyl (Z)-2-(2,4-dichloro-5-fluorobenzoyl)-3-(4-fluoroanilino)-2-propenoate		C₁₈H₁₃Cl₂F₂NO₃	详情	详情
(VI)	24579	7-chloro-6-fluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₁₆H₈ClF₂NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of 7-chloro-1-(p-fluorophenyl)-6-fluoro-1,4-dihydro-4-oxoquinoline-3 carboxylic acid (I) with N-carboethoxypiperazine (II) in hot 1-methyl-2-pyrrolidinone yields 7-(4-carboethoxypiperazinyl)-1-(p-fluorophenyl)-6-fluoro-1,4-dihydro-4 oxoquinoline-3-carboxylic acid (III). Hydrolysis of (III) with aqueous sodium hydroxide in ethanol followed by treatment with dilute hydrochloric acid gives A-56620.

参考文献中间体

合成目标

【1】 Clairbone, A.K.; Pihuleac, E.; Nordeen, C.; Fernandes, P.B.; Pernet, A.; Chu, D.T.W.; O'Donell, T.J.; A-56619 and A-56620: Synthesis and antibacterial activities of the novel aryl-fluoro-quinolones and their analogs. 24th Intersci Conf Antimicrob Agents Chemother (Oct 8-10, Washington, D.C) 1984, Abs 72.
【2】 Chu, D.T.W.; Fernandes, P.B.; Granneman, G.R.; Abbott-56620. Drugs Fut 1985, 10, 7, 546.

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)	24579	7-chloro-6-fluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₁₆H₈ClF₂NO₃	详情	详情
(II)	24694	N-ethoxycarbonylpiperidine; Ethyl 1-piperazinecarboxylate; N-Ethoxycarbonyl piperazine; N-Carbethoxy piperazine	120-43-4	C₇H₁₄N₂O₂	详情	详情
(III)	24695	7-[4-(ethoxycarbonyl)-1-piperazinyl]-6-fluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₂₃H₂₁F₂N₃O₅	详情	详情

Extended Information