Dimethylformamide → N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1874340

Reaction equation

HRID 1874340 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[N:16]([CH3:17])[N:15]=[C:14]([CH3:18])[CH:13]=1)=[O:11].Br[C:20]1[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[N:24][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:20]2[CH:25]=[N:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[CH:4][C:3]=1[NH:9][C:10]([C:12]1[N:16]([CH3:17])[N:15]=[C:14]([CH3:18])[CH:13]=1)=[O:11]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 8176205-Bromo-2-nitropyridineHCID 57505434N-(2-fluoro-5-hydroxyphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide

Product 1

HCID 68739416N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 59%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of N-(2-fluoro-5-hydroxyphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide (9.80 g, 39.3 mmol), 5-bromo-2-nitropyridine (7.14 g, 35.1 mmol), cesium carbonate (14.8 g, 45.3 mmol) and N,N-dimethylformamide (80 mL) was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=90/10→0/100) to give N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (7.68 g, 59%) as a white solid. To a solution of N-{2-fluoro-5-[(6-nitropyridin-3-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (7.68 g, 20.7 mmol) thus-obtained in methanol (50 mL) was added palladium carbon (50% water-containing product, 700 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature for 2 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (6.20 g, 88%) as a white solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltrated
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by column chromatography (silica gel, hexane/ethyl acetate=90/10→0/100)

Sources & evidence

ORD record
ord-fbc40d259d07416395a598c2c52c136e
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

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