Dimethylformamide → 7-(1,4-Diazabicyclo[3.2.1]octan-4-yl)-6-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

HRID 1939274노트

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HRID 1939274 반응식
CN(C)C=O.[F:6][C:7]1[C:8]([CH3:26])=[C:9]2[C:14](=[CH:15][C:16]=1F)[N:13]([C@@H:18]1[CH2:20][C@@H:19]1[F:21])[CH:12]=[C:11]([C:22]([OH:24])=[O:23])[C:10]2=[O:25].Cl.Cl.[N:29]12[CH2:36][CH:33]([CH2:34][CH2:35]1)[NH:32][CH2:31][CH2:30]2>C(N(CC)CC)C>[N:29]12[CH2:36][CH:33]([CH2:34][CH2:35]1)[N:32]([C:16]1[CH:15]=[C:14]3[C:9]([C:10](=[O:25])[C:11]([C:22]([OH:24])=[O:23])=[CH:12][N:13]3[C@@H:18]3[CH2:20][C@@H:19]3[F:21])=[C:8]([CH3:26])[C:7]=1[F:6])[CH2:31][CH2:30]2

참가 물질

5

반응물 3

HCID 6228DimethylformamideHCID 123740781,4-Diazabicyclo[3.2.1]octane dihydrochlorideHCID 228799656,7-Difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

생성물 1

HCID 228799677-(1,4-Diazabicyclo[3.2.1]octan-4-yl)-6-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid수율 50%

시약·촉매·용매 1

HCID 8471Triethylamine용매

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온도
100 °C

실험 절차

To 6 ml of dried N,N-dimethylformamide were added 200 mg of 6,7-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 372 mg of 1,4-diazabicyclo[3.2.1]octane dihydrochloride, and 2 ml of triethylamine, and the mixture was stirred at 100° C. for 1 hour. After allowing to cool, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a 1N sodium hydroxide aqueous solution under cooling with ice. The solution was neutralized with 1N hydrochloric acid and extracted with chloroform. The extract was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The resulting crude crystals were recrystallized from a mixed solvent of ethanol and 28% aqueous ammonia, and the crystals were collected by filtration, washed with diethyl ether, and dried at 60° C. under reduced pressure overnight to yield 131 mg of the titled compound as a yellow powder.

후처리

  1. temperatureto cool
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in a 1N sodium hydroxide aqueous solution
  4. temperatureunder cooling with ice
  5. extractionextracted with chloroform
  6. dry with materialThe extract was dried over anhydrous sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe resulting crude crystals were recrystallized from a mixed solvent of ethanol and 28% aqueous ammonia
  9. filtrationthe crystals were collected by filtration
  10. washwashed with diethyl ether
  11. customdried at 60° C. under reduced pressure overnight

출처 및 근거

ORD 기록
ord-5621b9c1a922478eb5540b16dbd0e770
출처 데이터셋
uspto-grants-1997_12
특허 번호
US05696132

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