1-Cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid → 7-(4-Amino-2-isoindolinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 1494725Notes

Reaction equation

HRID 1494725 reaction equation
[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]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[NH2:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][NH:25][CH2:26]2>CN(C=O)C>[NH2:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][N:25]([C:11]1[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5][N:4]3[CH:1]3[CH2:2][CH2:3]3)=[CH:9][C:10]=1[F:16])[CH2:26]2

Participants

4

Reactant 2

HCID 5354141-Cyclopropyl-6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acidHCID 14795861Isoindolin-4-amine

Product 1

HCID 147957557-(4-Amino-2-isoindolinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 64.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 136 mg of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 180 mg of 4-aminoisoindoline, and 1.5 ml of anhydrous DMF was heated at 120° C. for 1.5 hours while stirring. The resulting reaction mixture was evaporated under reduced pressure to dryness. 20 ml of chloroform and 10 ml of 5% acetic acid was added to the residue, and the mixture was stirred. Deposited crystals were collected by filtration, washed with water and ethanol. The chloroform layer was separated, washed with brine, dried over anhydrous sodium sulfate, and condensed. The residue was crystallized by the addition of hot ethanol. After cooling the mixture, the crystals were collected by filtration. These crystals were combined with those collected above and were recrystallized from a mixed solvent of chloroform, methanol, and ethanol to obtain 123 mg of the target compound.

Workup

  1. customThe resulting reaction mixture
  2. customwas evaporated under reduced pressure to dryness
  3. addition20 ml of chloroform and 10 ml of 5% acetic acid was added to the residue
  4. stirringthe mixture was stirred
  5. filtrationDeposited crystals were collected by filtration
  6. washwashed with water and ethanol
  7. customThe chloroform layer was separated
  8. washwashed with brine
  9. dry with materialdried over anhydrous sodium sulfate, and condensed
  10. customThe residue was crystallized by the addition of hot ethanol
  11. temperatureAfter cooling the mixture
  12. filtrationthe crystals were collected by filtration
  13. customthose collected above and
  14. customwere recrystallized from a mixed solvent of chloroform, methanol, and ethanol

Sources & evidence

ORD record
ord-6dcdbc3925a3461abc722ae03543d663
Source dataset
uspto-grants-1991_06
Patent number
US05026856

Reaction notes

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