Dimethylformamide → 7-(1,4-Diazabicyclo[3.2.1]octan-4-yl)-6,8-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

HRID 1939275노트

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HRID 1939275 반응식
CN(C)C=O.[F:6][C:7]1[C:8]([CH3:27])=[C:9]2[C:14](=[C:15]([F:18])[C:16]=1F)[N:13]([C@@H:19]1[CH2:21][C@@H:20]1[F:22])[CH:12]=[C:11]([C:23]([OH:25])=[O:24])[C:10]2=[O:26].Cl.Cl.[N:30]12[CH2:37][CH:34]([CH2:35][CH2:36]1)[NH:33][CH2:32][CH2:31]2>C(N(CC)CC)C>[N:30]12[CH2:37][CH:34]([CH2:35][CH2:36]1)[N:33]([C:16]1[C:15]([F:18])=[C:14]3[C:9]([C:10](=[O:26])[C:11]([C:23]([OH:25])=[O:24])=[CH:12][N:13]3[C@@H:19]3[CH2:21][C@@H:20]3[F:22])=[C:8]([CH3:27])[C:7]=1[F:6])[CH2:32][CH2:31]2

참가 물질

5

반응물 3

HCID 6228DimethylformamideHCID 123740781,4-Diazabicyclo[3.2.1]octane dihydrochlorideHCID 228799641-[(1R,2S)-2-Fluorocyclopropyl]-6,7,8-trifluoro-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

생성물 1

HCID 228799667-(1,4-Diazabicyclo[3.2.1]octan-4-yl)-6,8-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid수율 62.3%

시약·촉매·용매 1

HCID 8471Triethylamine용매

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온도
100 °C

실험 절차

To 5 ml of dried N,N-dimethylformamide were added 211 mg of 6,7,8-trifluoro-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 while cooling with ice. After neutralizing with 1N hydrochloric acid, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resulting crude crystals were recrystallized from a mixed solvent of ethanol and 28% aqueous ammonia. The precipitated crystals were collected by filtration, washed with diethyl ether, and dried at 60° C. in vacuo overnight to yield 170 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. temperaturewhile cooling with ice
  5. extractionthe mixture was extracted 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 precipitated crystals were collected by filtration
  10. washwashed with diethyl ether
  11. customdried at 60° C. in vacuo overnight

출처 및 근거

ORD 기록
ord-bb02766707044c7ea1b8c73623a4ff8d
출처 데이터셋
uspto-grants-1997_12
특허 번호
US05696132

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