Sodium hydride → N-(5-Bromopyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine

HRID 1431600Notes

Reaction equation

HRID 1431600 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:8])[CH:5]=[N:6][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]=[C:28]([CH3:30])[CH:27]=[CH:26][N:25]=2)[C:13]=1[CH3:31]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][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]=[C:28]([CH3:30])[CH:27]=[CH:26][N:25]=3)[C:13]=2[CH3:31])[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 8176813-Amino-5-bromopyridineHCID 596311504-Chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline

Product 1

HCID 59631283N-(5-Bromopyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)-quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A screwcap vial was charged with a solution of 5-bromopyridin-3-amine (273 mg, 1.58 mmol) in dry DMF (8 mL) under nitrogen. To this stirring solution was slowly added sodium hydride (63.0 mg, 1.58 mmol), followed 5 min later by 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (400 mg, 1.31 mmol). The reaction mixture was then stirred at rt for 6 h. Additional portions of sodium hydride (1.2 equivalents) were added after 2 and 4 h of stirring. Upon completion, the reaction was quenched with 10% aq. sodium carbonate and the product was extracted with EtOAc. The organic layer was washed with brine, dried over magnesium sulfate, and cond. The resulting crude residue was purified by flash-chromatography (silica gel, 0-60% EtOAc in hexanes) and subsequently by recrystallization in MeOH. This afforded N-(5-bromopyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=441.0 (M+1).

Workup

  1. stirringof stirring
  2. customUpon completion, the reaction was quenched with 10% aq. sodium carbonate
  3. extractionthe product was extracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate, and cond
  6. customThe resulting crude residue was purified by flash-chromatography (silica gel, 0-60% EtOAc in hexanes) and subsequently by recrystallization in MeOH

Sources & evidence

ORD record
ord-0a3a564f2a85448fb3397a203fbe8434
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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