Dichloromethane → 7-(Cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbonitrile

HRID 469234Notes

Reaction equation

HRID 469234 reaction equation
ClCCl.[CH:4]1([NH:10][C:11]2[CH:20]=[C:19]3[C:14]([C:15](=[O:29])[C:16]([C:26]([NH2:28])=O)=[CH:17][N:18]3[CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:13][C:12]=2[F:30])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>O>[CH:4]1([NH:10][C:11]2[CH:20]=[C:19]3[C:14]([C:15](=[O:29])[C:16]([C:26]#[N:28])=[CH:17][N:18]3[CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:13][C:12]=2[F:30])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 666369957-(Cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxamide

Product 1

HCID 666371057-(Cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbonitrileYield 74.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 30 ml dichloromethane suspension of 3.69 g of 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxamide were added at −78° C. 7.0 ml of triethylamine and a 10 ml dichloromethane solution of 4.0 ml of trifluoroacetic anhydride. After gradually rising the temperature, it was stirred at room temperature for 2 days. After adding water, it was extracted with chloroform, followed by drying over anhydrous sodium sulfate. After filtration, the solvent was evaporated under a reduced pressure and the resulting residue was purified by silica gel column chromatography. After adding a mixed solvent of 30 ml of THF, 30 ml of methanol and 10 ml of water to the resulting solid, 2.3 g of potassium carbonate was added thereto under ice-cooling. After stirring at room temperature for 15 hours, 1.0 g of potassium carbonate was added thereto, followed by stirring at room temperature for 4 days. After evaporating the solvent under a reduced pressure, water was added, followed by extraction with chloroform. After drying over anhydrous sodium sulfate and subsequent filtration, the solvent was evaporated under a reduced pressure. By washing the resulting residue with ethyl acetate, 2.62 g of 7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carbonitrile was obtained.

Workup

  1. additionwere added at −78° C
  2. extractionwas extracted with chloroform
  3. dry with materialby drying over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. customthe solvent was evaporated under a reduced pressure
  6. customthe resulting residue was purified by silica gel column chromatography
  7. additionAfter adding a mixed solvent of 30 ml of THF, 30 ml of methanol and 10 ml of water to the resulting solid, 2.3 g of potassium carbonate
  8. additionwas added
  9. temperatureunder ice-cooling
  10. stirringAfter stirring at room temperature for 15 hours
  11. addition1.0 g of potassium carbonate was added
  12. stirringby stirring at room temperature for 4 days
  13. customAfter evaporating the solvent under a reduced pressure, water
  14. additionwas added
  15. extractionfollowed by extraction with chloroform
  16. dry with materialAfter drying over anhydrous sodium sulfate and subsequent filtration
  17. customthe solvent was evaporated under a reduced pressure
  18. washBy washing the resulting residue with ethyl acetate

Sources & evidence

ORD record
ord-cfe32ff1e6c941849e1a2a7d52e9dbb0
Source dataset
uspto-grants-2014_01
Patent number
US08629126B2

Reaction notes

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