ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】20843

【品名】ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate

【CA登记号】

【分子式】C₁₅H₁₁F₄NO₃

【分子量】329.2508928

【元素组成】C 54.72% H 3.37% F 23.08% N 4.25% O 14.58%

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：(IV)

The reaction of ethyl pentafluorobenzoylacetate (I) with ethyl orthoformate in refluxing acetic anhydride and then with cyclopropylamine (II) in ether gives the aminomethylene derivative (III), which is cyclized by means of NaH in THF yielding ethyl 5,6,7,8-tetrafluoro-1-cyclopropyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (IV). The reaction of (IV) with benzylamine (V) by means of K2CO3 in refluxing acetonitrile affords the benzylamino derivative (VI), which is deprotected by hydrogenation with H2 over Pd/C in ethanol giving ethyl 5-amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (VII). The hydrolysis of (VII) with hot H2SO4 yields the free acid (VIII), which is finally condensed with cis-2,6-dimethylpiperazine (IX) in DMF.

参考文献中间体

合成目标

【1】 Matsumoto, J.; Miyamoto, T.; Egawa, H.; Nakamura, S. (Dainippon Pharm. Co.; Ltd.); Novel quinoline derivatives and processes for preparation thereof. AU 8664277; EP 0221463; JP 87277362 .
【2】 Prous, J.; Castaner, J.; AT-4140. Drugs Fut 1989, 14, 5, 413.

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)	20840	ethyl 3-oxo-3-(2,3,4,5,6-pentafluorophenyl)propanoate		C₁₁H₇F₅O₃	详情	详情
(II)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(III)	20842	ethyl 2-[(cyclopropylamino)methyl]-3-oxo-3-(2,3,4,5,6-pentafluorophenyl)propanoate		C₁₅H₁₄F₅NO₃	详情	详情
(IV)	20843	ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₅H₁₁F₄NO₃	详情	详情
(V)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(VI)	20845	ethyl 5-(benzylamino)-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₂₂H₁₉F₃N₂O₃	详情	详情
(VII)	20846	ethyl 5-amino-1-cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate		C₁₅H₁₃F₃N₂O₃	详情	详情
(VIII)	19819	4-[(benzyloxy)carbonyl]-3,4-dihydro-2H-1,4-benzothiazine-7-carboxylic acid		C₁₇H₁₅NO₄S	详情	详情
(IX)	20848	(2R,6S)-2,6-dimethylpiperazine		C₆H₁₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The reaction of pentafluorobenzoylacetic acid ethyl ester (I) with triethyl orthoformate in refluxing acetic anhydride, followed by condensation with cyclopropylamine, gives 2-(pentafluorobenzoyl)-3-(cyclopropylamino)acrylic acid ethyl ester (II), which is cyclized by means of NaH in THF to yield 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III). The hydrolysis of (III) with H2SO4 /HOAc in refluxing water affords the corresponding carboxylic acid (IV), which is finally condensed with cis-2,6-dimethylpiperazine (V) in DMF to provide the target quinolone.

参考文献中间体

合成目标

【1】 Matsumoto, J.-I.; Miyamoto, T.; Egawa, H.; Nakamura, S. (Dainippon Pharmaceutical Co., Ltd.); Quinoline derivs., pharmaceutical compsn. and method of use. EP 0242789; US 4886810 .
【2】 Miyamoto, T.; Matsumoto, J.; Chiba, K.; et al.; Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency. J Med Chem 1990, 33, 6, 1645.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	20840	ethyl 3-oxo-3-(2,3,4,5,6-pentafluorophenyl)propanoate	C₁₁H₇F₅O₃	详情	详情
(II)	55231	ethyl (Z)-3-(cyclopropylamino)-2-(2,3,4,5,6-pentafluorobenzoyl)-2-propenoate	C₁₅H₁₂F₅NO₃	详情	详情
(III)	20843	ethyl 1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate	C₁₅H₁₁F₄NO₃	详情	详情
(IV)	55232	1-cyclopropyl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid	C₁₃H₇F₄NO₃	详情	详情
(V)	20848	(2R,6S)-2,6-dimethylpiperazine	C₆H₁₄N₂	详情	详情

Extended Information