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【结 构 式】 
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【分子编号】53194 【品名】ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate 【CA登记号】n/a |
【 分 子 式 】C16H14F3NO4 【 分 子 量 】341.2867096 【元素组成】C 56.31% H 4.13% F 16.7% N 4.1% O 18.75% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 2,4,5-trifluoro-3-methoxybenzoic acid (I) with SOCl2 in toluene gives the corresponding acyl chloride (II), which is condensed with 3-(dimethylamino)acrylic acid ethyl ester (III) by means of TEA to yield 3-(dimethylamino)-2-(2,4,5-trifluoro-3-methoxybenzoyl)acrylic acid ethyl ester (IV). The cyclization of (IV) with 2-fluorocyclopropylamine (V) by means of TEA and K2CO3 in DMF affords the quinolone-3-carboxylate (VI), which is hydrolyzed with HCl in HOAc to provide the carboxylic acid (VII). The reaction of (VII) with BF3/Et2O in diethyl ether gives the boronic ester (VIII), which is condensed with the spiropyrrolidine (IX) by means of TEA in ethanol. Finally, the boronic ester of (IX) is hydrolyzed with HCl to afford the target quinolone-3-carboxylic acid.
| 【1】 Kawakami, K.; et al.; DK-570k, a new 8-methoxyquinolone: Synthesis and biological evaluation of 7-[(3-amino-4-substituted)pyrrolidin-1-yl] derivatives. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-546. |
| 【2】 Suzuki, T.; Takahashi, H.; Hayakawa, I.; Takemura, M.; Ohtani, T.; Kawakami, K.; Itoh, M.; Miyauchi, R.; Sekiguchi, M. (Daiichi Pharmaceutical Co., Ltd.); Quinolonecarboxylic acid deriv.. WO 0172738 . |
| 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) | 12258 | 2,4,5-Trifluoro-3-methoxybenzoic acid | 112811-65-1 | C8H5F3O3 | 详情 | 详情 |
| (II) | 12259 | 2,4,5-Trifluoro-3-methoxybenzoyl chloride | C8H4ClF3O2 | 详情 | 详情 | |
| (III) | 16000 | ethyl (E)-3-(dimethylamino)-2-propenoate; Ethyl trans-3-dimethylaminoacrylate | 1117-37-9 | C7H13NO2 | 详情 | 详情 |
| (IV) | 53193 | ethyl (Z)-3-(dimethylamino)-2-(2,4,5-trifluoro-3-methoxybenzoyl)-2-propenoate | n/a | C15H16F3NO4 | 详情 | 详情 |
| (V) | 15146 | (1R,2S)-2-Fluorocyclopropanamine; (1R,2S)-2-Fluorocyclopropylamine | C3H6FN | 详情 | 详情 | |
| (VI) | 53194 | ethyl 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate | n/a | C16H14F3NO4 | 详情 | 详情 |
| (VII) | 53195 | 6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | n/a | C14H10F3NO4 | 详情 | 详情 |
| (VIII) | 53196 | 3-{[(difluoroboryl)oxy]carbonyl}-6,7-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4(1H)-quinolinone | n/a | C14H9BF5NO4 | 详情 | 详情 |
| (IX) | 15193 | tert-butyl N-[(7S)-5-azaspiro[2.4]hept-7-yl]carbamate | C11H20N2O2 | 详情 | 详情 | |
| (X) | 53197 | tert-butyl (7S)-5-{3-{[(difluoroboryl)oxy]carbonyl}-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydro-7-quinolinyl}-5-azaspiro[2.4]hept-7-ylcarbamate | n/a | C25H28BF4N3O6 | 详情 | 详情 |