Acetonitrile → 1-Cyclopropyl-7-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid

HRID 483293노트

반응식

HRID 483293 반응식
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([O:20]C)=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.I[Si](C)(C)C.Br.Br.[CH:29]12[CH2:35][CH:32]([NH:33][CH2:34]1)[CH2:31][NH:30]2.C(#N)C>ClCCl>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11]([N:30]4[CH2:31][CH:32]5[CH2:35][CH:29]4[CH2:34][NH:33]5)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:2][CH2:3]1

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 85247Trimethylsilyl iodide2회HCID 13590045Methyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylateHCID 162131472,5-Diazabicyclo[2.2.1]heptane dihydrobromide

생성물 1

HCID 4695551-Cyclopropyl-7-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid수율 92%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 1.0 g (3.4 mmole) of methyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate in 25 ml dichloromethane was added 0.6 ml (0.8 g, 4.2 mmole) of iodotrimethylsilane while stirring at room temperature under a blanket of nitrogen. The reaction was warmed to reflux and stirred overnight. An additional 0.23 ml (1.6 mmole) of iodotrimethylsilane was added and the solution was refluxed for another two hours, cooled to room temperature, and concentrated. The residue was taken up in 20 ml of acetonitrile. To this solution was added a mixture of 2.2 g (8.5 mmole) of 2,5-diazabicyclo[2.2.1]heptane, dihydrobromide, 2.7 g (17.9 mmole) 1,8-diazobicyclo[5.4.0]undec-7-ene and 20 ml acetonitrile. The reaction was refluxed for 2.5 hours then cooled to room temperature. The formed precipitate was filtered, washed with acetonitrile and ethyl ether, yielding 1.13 g (92%) of the title compound, mp 288°-290° C.

후처리

  1. temperatureThe reaction was warmed
  2. temperatureto reflux
  3. stirringstirred overnight
  4. temperaturethe solution was refluxed for another two hours
  5. temperaturecooled to room temperature
  6. concentrationconcentrated
  7. additionTo this solution was added
  8. temperatureThe reaction was refluxed for 2.5 hours
  9. temperaturethen cooled to room temperature
  10. filtrationThe formed precipitate was filtered
  11. washwashed with acetonitrile and ethyl ether

출처 및 근거

ORD 기록
ord-b9ba5e88e1da40d784731fb8887f0ffe
출처 데이터셋
uspto-grants-1986_03
특허 번호
US04578473

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