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 1939274Notes

Reaction equation

HRID 1939274 reaction equation
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

Participants

5

Reactant 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

Product 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 AcidYield 50%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5621b9c1a922478eb5540b16dbd0e770
Source dataset
uspto-grants-1997_12
Patent number
US05696132

Reaction notes

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