Sodium hydride → 4-(4-Amino-2,5-difluorophenoxy)pyridine-2-carboxamide

HRID 872966Notes

Reaction equation

HRID 872966 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.Cl[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([C:18]([NH2:20])=[O:19])[CH:13]=1.[H-].[Na+]>CN(C=O)C.O>[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][C:12]2[CH:17]=[CH:16][N:15]=[C:14]([C:18]([NH2:20])=[O:19])[CH:13]=2)=[C:4]([F:10])[CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3035434-Chloropyridine-2-carboxamideHCID 27787624-Amino-2,5-difluorophenol

Product 1

HCID 247886284-(4-Amino-2,5-difluorophenoxy)pyridine-2-carboxamideYield 30.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-amino-2,5-difluorophenol (100 mg, 0.64 mmol), and 4-chloropicolinamide (110 mg, 0.71 mmol) in DMF (2 mL) was added NaH (80 mg, 1.3 mmol, 60% dispersed in mineral oil). The reaction mixture was microwaved at 120° C. for 1.5 hours, then cooled to rt, diluted with water (20 mL), and extracted with EtOAc (30 mL×3). The combined organic phases were washed with brine (80 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography with (EtOAc/PE (v/v)=4/1) to afford the title compound as a brown solid (52 mg, 26%).

Workup

  1. customThe reaction mixture was microwaved at 120° C. for 1.5 hours
  2. extractionextracted with EtOAc (30 mL×3)
  3. washThe combined organic phases were washed with brine (80 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography with (EtOAc/PE (v/v)=4/1)

Sources & evidence

ORD record
ord-c1a6d11d150846d98b61e03196155337
Source dataset
uspto-grants-2015_03
Patent number
US08975282B2

Reaction notes

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