4-Chloropyridine-2-carboxamide → 4-(4-Amino-2,3-difluorophenoxy)pyridine-2-carboxamide

HRID 870420Notes

Reaction equation

HRID 870420 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[C:3]=1[F:10].CC([O-])(C)C.[K+].Cl[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]([NH2:26])=[O:25])[CH:19]=1>CN(C=O)C.O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]([NH2:26])=[O:25])[CH:19]=2)=[C:4]([F:9])[C:3]=1[F:10]

Participants

6

Reactant 3

HCID 3035434-Chloropyridine-2-carboxamideHCID 27787664-Amino-2,3-difluorophenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 574708784-(4-Amino-2,3-difluorophenoxy)pyridine-2-carboxamideYield 41.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-amino-2,3-difluorophenol (208 mg, 1.43 mmol) in DMF (4 mL) was added t-BuOK (257 mg, 2.29 mmol). The reaction was stirred at rt for 30 minutes, then 4-chloropicolinamide (249 mg, 1.59 mmol) was added. The mixture was microwaved at 120° C. for 3 hours, then cooled to rt and diluted with 25 mL of water. The resulted mixture was extracted with EtOAc (30 mL×3), and the combined organic phases were washed with brine (30 mL×3), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=1/2) to give the title compound as an orange solid (110 mg, 41.5%).

Workup

  1. customThe mixture was microwaved at 120° C. for 3 hours
  2. temperaturecooled to rt
  3. extractionThe resulted mixture was extracted with EtOAc (30 mL×3)
  4. washthe combined organic phases were washed with brine (30 mL×3)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=1/2)

Sources & evidence

ORD record
ord-79b6455252ba4ecb94d0e98acb78d3dc
Source dataset
uspto-grants-2015_03
Patent number
US08969388B1

Reaction notes

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