7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】15231

【品名】7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid

【CA登记号】

【分子式】C₁₅H₆ClF₃N₂O₃

【分子量】354.6722296

【元素组成】C 50.8% H 1.71% Cl 10% F 16.07% N 7.9% O 13.53%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(IV)

Treatment of ethyl 2,6-dichloro-5-fluoronicotinylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with 2,4-difluoroaniline in methylene chloride at room temperature gives the enaminoketo ester derivative (II). Cyclization of (II) with sodium hydride in THF gives ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (III). Hydrolysis of (III) with hydrochloric acid yields 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (IV). Condensation of (IV) with 3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidine (V) in pyridine yields 7-(3-tert-butoxycarbonyl-L-norvalyl-L-norvalylaminopyrrolidin-1-yl)- 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (VI). Hydrolysis of (VI) in trifluoroacetic acid gives A-70826.

参考文献中间体

合成目标

【1】 Chu, D.T.W.; A-70826. Drugs Fut 1992, 17, 3, 179.
【2】 Chu, D.T.W.; Pernet, A.G.; Plattner, J.J.; Hallas, R.; Shipkowitz, N.; Marsh, K.C.; Synthesis and biological properties of A-70826: A prodrug of tosufloxacin. 31st Intersci Conf Antimicrob Agents Chemother (Sept 29-Oct 2, Chicago) 1991, Abst 1440.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	19462	2,4-difluoroaniline; 2,4-difluorophenylamine；2,4-Difluoro-benzenamine;1-Amino-2,4-difluorobenzene	367-25-9	C₆H₅F₂N	详情	详情
(I)	15228	ethyl 3-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-oxopropanoate		C₁₀H₈Cl₂FNO₃	详情	详情
(II)	15229	ethyl (Z)-2-[(2,6-dichloro-5-fluoro-3-pyridinyl)carbonyl]-3-(2,4-difluoroanilino)-2-propenoate		C₁₇H₁₁Cl₂F₃N₂O₃	详情	详情
(III)	15230	ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate		C₁₇H₁₀ClF₃N₂O₃	详情	详情
(IV)	15231	7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid		C₁₅H₆ClF₃N₂O₃	详情	详情
(V)	15232	tert-butyl N-[(1S)-1-[([(1S)-1-[(tetrahydro-1H-pyrrol-3-ylamino)carbonyl]butyl]amino)carbonyl]butyl]carbamate		C₁₉H₃₆N₄O₄	详情	详情
(VI)	15233	7-(3-[[(2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]pentanoyl]amino)pentanoyl]amino]-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic acid		C₃₄H₄₁F₃N₆O₇	详情	详情

Extended Information