Sodium Carbonate → HCID 59631297, compound

HRID 1431551Notes

Reaction equation

HRID 1431551 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH3:15])=[N:6][CH:7]=1.[H-].[Na+].Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([F:31])=[CH:27][C:28]=2[F:30])[N:23]=[C:22]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[C:21]=1[CH3:38].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:16][C:20]2[C:29]3[C:24](=[CH:25][C:26]([F:31])=[CH:27][C:28]=3[F:30])[N:23]=[C:22]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[C:21]=2[CH3:38])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH3:15])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 59631125HCID 59631125, compound

Product 1

HCID 59631297HCID 59631297, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A dry flask containing 5-bromo-2-(2-methoxyphenyl)pyridin-3-amine (194.5 mg, 0.7 mmol) in dry DMF (5 mL) was cooled to 0° C., then sodium hydride, 60% dispersion in mineral oil (90.8 mg, 2.27 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-(pyridin-2-yl)quinoline (308.7 mg, 1.06 mmol) was added in portions. Upon complete addition, the mixture was warmed to 70° C. After 3 h, the reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted 5 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 residue was purified on basic alumina (0-35% EtOAc in hexanes) to afford a yellow residue as mostly N-(5-bromo-2-(2-methoxyphenyl)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine that was used without further purification.

Workup

  1. additionUpon complete addition
  2. temperaturethe mixture was warmed to 70° C
  3. waitAfter 3 h
  4. temperaturethe reaction was cooled to rt
  5. extractionThe black mixture was subsequently extracted 5 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. customthe residue was purified on basic alumina (0-35% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c6165b8537444a27b54049d67ff136e7
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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