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【结 构 式】 
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【分子编号】28509 【品名】ethyl 1-(4-amino-2-fluorophenyl)-1H-pyrazole-4-carboxylate 【CA登记号】 |
【 分 子 式 】C12H12FN3O2 【 分 子 量 】249.2447032 【元素组成】C 57.83% H 4.85% F 7.62% N 16.86% O 12.84% |
合成路线1
该中间体在本合成路线中的序号：(V)Treatment of 3,4-difluoronitrobenzene (I) with hydrazine hydrate yielded the aryl hydrazine (II), which was condensed with dialdehyde (III) to give pyrazole (IV). After reduction of the nitro group of (IV) by catalytic hydrogenation, the resulting amine (V) was protected with benzyl chloroformate to afford carbamate (VI). Subsequent treatment of (VI) with (R)-glycidyl butyrate (VII) and n-butyllithium produced the chiral oxazolidinone (VIII). The alcohol group of (VIII) was converted to mesylate (IX) and then displaced with NaN3 to give azide (X), which was reduced to amine (XI) using PPh3. Acetylation of the primary amine of (XI) with Ac2O, followed by ammonolysis of the ethyl ester furnished diamide (XII). Finally, dehydration of the primary amide of (XII) with SOCl2 provided the target nitrile.
| 【1】 Genin, M.J.; et al.; Substituent effects on the antibacterial activity of novel highly potent nitrogen-bound azolylphenyl oxazolidinones. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-138. |
| 【2】 Genin, M.J.; Hutchinson, D.K.; Allwine, D.A.; Hester, J.B.; Emmert, D.E.; Garmon, S.A.; Ford, C.W.; Zurenko, G.E.; Hamel, J.C.; Schaadt, R.D.; Stapert, D.; Yagi, B.H.; Friis, J.M.; Shobe, E.M.; Adams, W.J.; Nitrogen-carbon-linked (azolylphenyl)oxazolidinones with potent antibacterial activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J Med Chem 1998, 41, 26, 5144. |
| 【3】 Anderson, D.J.; Allwine, D.A.; Genin, M.J.; et al.; Substituted effects of the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J Med Chem 2000, 43, 5, 953. |
| 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) | 17013 | 1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene | 369-34-6 | C6H3F2NO2 | 详情 | 详情 |
| (II) | 28506 | 1-(2-fluoro-4-nitrophenyl)hydrazine | C6H6FN3O2 | 详情 | 详情 | |
| (III) | 28507 | ethyl 2-formyl-3-oxopropanoate | C6H8O4 | 详情 | 详情 | |
| (IV) | 28508 | ethyl 1-(2-fluoro-4-nitrophenyl)-1H-pyrazole-4-carboxylate | C12H10FN3O4 | 详情 | 详情 | |
| (V) | 28509 | ethyl 1-(4-amino-2-fluorophenyl)-1H-pyrazole-4-carboxylate | C12H12FN3O2 | 详情 | 详情 | |
| (VI) | 28510 | ethyl 1-(4-[[(benzyloxy)carbonyl]amino]-2-fluorophenyl)-1H-pyrazole-4-carboxylate | C20H18FN3O4 | 详情 | 详情 | |
| (VII) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (VIII) | 28511 | ethyl 1-[2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl]-1H-pyrazole-4-carboxylate | C16H16FN3O5 | 详情 | 详情 | |
| (IX) | 28512 | ethyl 1-[2-fluoro-4-((5R)-5-[[(methylsulfonyl)oxy]methyl]-2-oxo-1,3-oxazolidin-3-yl)phenyl]-1H-pyrazole-4-carboxylate | C17H18FN3O7S | 详情 | 详情 | |
| (X) | 28513 | ethyl 1-[4-[(5R)-5-(azidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]-1H-pyrazole-4-carboxylate | C16H15FN6O4 | 详情 | 详情 | |
| (XI) | 28514 | ethyl 1-[4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]-1H-pyrazole-4-carboxylate | C16H17FN4O4 | 详情 | 详情 | |
| (XII) | 28515 | 1-(4-[(5S)-5-[(acetamido)methyl]-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl)-1H-pyrazole-4-carboxamide | C16H16FN5O4 | 详情 | 详情 |