7-[(7S)-7-(carboxyamino)-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】15132

【品名】7-[(7S)-7-(carboxyamino)-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid

【CA登记号】

【分子式】C₂₀H₁₈ClF₂N₃O₅

【分子量】453.8296464

【元素组成】C 52.93% H 4% Cl 7.81% F 8.37% N 9.26% O 17.63%

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：(VIII)

The condensation of 3-chloro-2,4,5-trifluorobenzoylacetic acid ethyl ester (I) with (1R,2S)-N-(tert-butoxycarbonyl)-2-fluorocyclopropylamine (III) and ethyl orthoformate (II) in hot acetic anhydride gives (1R,2S)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-(2-fluorocyclopropylamino)acrylic acid ethyl ester (IV). The cyclization of (IV) by means of NaH yields the quinolone (V), which is hydrolyzed with HCl to the free acid (VI). The condensation of (VI) with 7(S)-(tert-butoxycarbonylamino)-5-azaspiro[2.4]heptane (VII) by means of triethylamine in refluxing acetonitrile affords the protected final product (VIII), which is finally deprotected with trifluoroacetic acid and anisole.

参考文献中间体

合成目标

【1】 Hayakawa, I.; Kimura, Y. (Daiichi Pharmaceutical Co., Ltd.); Optically active pyridone carboxylic acid derivs. AU 8933702; EP 0341493; JP 1990231475; JP 1995300416; JP 1999124367; JP 1999124380; US 5587386; US 5767127 .
【2】 Castaner, J.; Graul, A.; Prous, J.; DU-6859. Drugs Fut 1994, 19, 9, 827.

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)	11681	ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate	101987-86-4	C₁₁H₈ClF₃O₃	详情	详情
(II)	11927	5-Sulfanyl-1,3,4-thiadiazol-2-ylhydrosulfide; 1,3,4-Thiadiazole-2,5-dithiol	1072-71-5	C₂H₂N₂S₃	详情	详情
(III)	15127	tert-butyl N-[(1R,2S)-2-fluorocyclopropyl]carbamate	127199-16-0	C₈H₁₄FNO₂	详情	详情
(IV)	15128	ethyl (E)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-[[(1R,2S)-2-fluorocyclopropyl]amino]-2-propenoate		C₁₅H₁₂ClF₄NO₃	详情	详情
(V)	15129	ethyl 8-chloro-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₅H₁₁ClF₃NO₃	详情	详情
(VI)	15130	8-chloro-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid	127199-27-3	C₁₃H₇ClF₃NO₃	详情	详情
(VII)	15131	N-[(7S)-5-azaspiro[2.4]hept-7-yl]carbamic acid tert-butyl ester	127199-45-5	C₁₁H₂₀N₂O₂	详情	详情
(VIII)	15132	7-[(7S)-7-(carboxyamino)-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid		C₂₀H₁₈ClF₂N₃O₅	详情	详情

Extended Information