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【结 构 式】 
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【分子编号】56644 【品名】ethyl 8-chloro-1-{3,5-difluoro-6-[(4-methoxybenzyl)amino]-2-pyridinyl}-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C25H18ClF4N3O4 【 分 子 量 】535.8820528 【元素组成】C 56.03% H 3.39% Cl 6.62% F 14.18% N 7.84% O 11.94% |
合成路线1
该中间体在本合成路线中的序号：(X)Reaction of 2,3,5,6-tetrafluoropyridine (I) with benzylamine (II) in refluxing acetonitrile gives 2-(benzyl-amino)-3,5,6-trifluoropyridine (III), which is debenzylated with H2 over Pd/C in methanol to yield 3,5,6-trifluoropyridine-2-amine (IV). Reaction of amine (IV) with 4-methoxybenzylamine (V) in N-methylpyrrolidone at 140 C affords 3,5-difluoro-6-(4-methoxybenzylamino)pyridine-2-amine (VI), which is cyclized with 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxyacrylic acid ethyl ester (VII) obtained by condensation of 2-(3-chloro-2,4,5-trifluorobenzoyl)acetic acid ethyl ester (VIII) with triethyl orthoformate (IX) by means of acetic anhydride in hot DMF in the presence of K2CO3 to provide the N-protected aminoquinolone derivative (X). Reaction of quinolone (X) with HCl in refluxing acetic acid gives 4-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (XI), which is finally condensed with 3-hydroxyazetidine (XII) by means of N-methylpyrrolidine in refluxing acetonitrile.
| 【2】 Yazaki, A.; Niino, Y.; Ohshita, Y.; Hirao, Y.; Amano, H.; Hayashi, N.; Kuramoto, Y. (Wakunaga Pharmaceutical Co., Ltd.); Novel pyridonecarboxylic acid derivs. or their salts and antibacterial agent comprising the same as the active ingredient. EP 0911327; EP 0992501; JP 1999322715; JP 2000136191; US 5998436; US 6133284; WO 9711068 . |
| 【1】 Mealy, N.E.; Castaner, J.; ABT-492. Drugs Fut 2002, 27, 11, 1033. |
| 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) | 56640 | 2,3,5,6-Tetrafluoropyridine | 2875-18-5 | C5HF4N | 详情 | 详情 |
| (II) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (III) | 56641 | N-benzyl-3,5,6-trifluoro-2-pyridinamine; N-benzyl-N-(3,5,6-trifluoro-2-pyridinyl)amine | C12H9F3N2 | 详情 | 详情 | |
| (IV) | 56642 | 3,5,6-trifluoro-2-pyridinamine; 3,5,6-trifluoro-2-pyridinylamine | C5H3F3N2 | 详情 | 详情 | |
| (V) | 15098 | 4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine | 2393-23-9 | C8H11NO | 详情 | 详情 |
| (VI) | 56643 | N-(6-amino-3,5-difluoro-2-pyridinyl)-N-(4-methoxybenzyl)amine; 3,5-difluoro-N~2~-(4-methoxybenzyl)-2,6-pyridinediamine | C13H13F2N3O | 详情 | 详情 | |
| (VII) | 11682 | ethyl (Z)-2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxy-2-propenoate | C14H12ClF3O4 | 详情 | 详情 | |
| (VIII) | 11681 | ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate | 101987-86-4 | C11H8ClF3O3 | 详情 | 详情 |
| (IX) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
| (X) | 56644 | ethyl 8-chloro-1-{3,5-difluoro-6-[(4-methoxybenzyl)amino]-2-pyridinyl}-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C25H18ClF4N3O4 | 详情 | 详情 | |
| (XI) | 56645 | 1-(6-amino-3,5-difluoro-2-pyridinyl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid | C15H6ClF4N3O3 | 详情 | 详情 | |
| (XII) | 31397 | 3-azetidinol | C3H7NO | 详情 | 详情 |