Sodium Carbonate → N-(5-bromo-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

HRID 1431452Notes

Reaction equation

HRID 1431452 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[H-].[Na+].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=2[F:22])[N:15]=[C:14]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[C:13]=1[CH3:30].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[Br:8][C:6]1[CH:7]=[C:2]([NH:1][C:12]2[C:21]3[C:16](=[CH:17][C:18]([F:23])=[CH:19][C:20]=3[F:22])[N:15]=[C:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[C:13]=2[CH3:30])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 8176813-Amino-5-bromopyridineHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 59631407N-(5-bromo-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A dry flask containing 3-amino-5-bromopyridine (0.13 g, 0.78 mmol) in dry DMF (5.0 mL) was cooled to 0° C., then sodium hydride, 60% dispersion in mineral oil (63.6 mg, 1.59 mmol) was added carefully in portions. The mixture was stirred at 0° C. for 15 min, then 4-chloro-5,7-difluoro-3-methyl-2-(2-pyridinyl)quinoline (0.25 g, 0.86 mmol) was added in portions. Upon complete addition, the mixture was warmed to 60° C. After 18 h, the reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted five times with DCM:MeOH (90:10). The organic extraction was then washed one time with brine and dried over anhydrous magnesium sulfate. After filtration and concentration, the black residue was treated with MeOH and warmed to 45° C. After 30 min, the solid was filtered and rinsed twice with MeOH to afford a tan solid as mostly N-(5-bromo-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine.

Workup

  1. additionUpon complete addition
  2. temperaturethe mixture was warmed to 60° C
  3. waitAfter 18 h
  4. temperaturethe reaction was cooled to rt
  5. extractionThe black mixture was subsequently extracted five times with DCM:MeOH (90:10)
  6. extractionThe organic extraction
  7. washwas then washed one time with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationAfter filtration and concentration
  10. additionthe black residue was treated with MeOH
  11. temperaturewarmed to 45° C
  12. waitAfter 30 min
  13. filtrationthe solid was filtered
  14. washrinsed twice with MeOH

Sources & evidence

ORD record
ord-b47155f5e6da4aa186dec71d8260ba6a
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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