Hydrochloric Acid → 4,5-difluoro-2-[[3-ethyl-1-(2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid

HRID 498060Notes

Reaction equation

HRID 498060 reaction equation
[CH2:1]([C:3]1[CH:7]=[C:6]([NH2:8])[N:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[N:4]=1)[CH3:2].Cl[C:16]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:17]=1[C:18]([OH:20])=[O:19].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.O>[F:25][C:23]1[C:22]([F:26])=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[C:16]([NH:8][C:6]2[N:5]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=3)[N:4]=[C:3]([CH2:1][CH3:2])[CH:7]=2)[CH:24]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 7371712-Chloro-4,5-difluorobenzoic acidHCID 337836213-Ethyl-1-(2-pyridinyl)-1H-pyrazol-5-ylamine

Product 1

HCID 223201384,5-difluoro-2-[[3-ethyl-1-(2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acidYield 66%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-ethyl-1-(2-pyridinyl)-1H-pyrazol-5-ylamine (9.41 g, 50.0 mmol), 2-chloro-4,5-difluorobenzoic acid (9.63 g, 50.0 mmol), copper acetate (II) (0.908 g, 5.00 mmol) and potassium carbonate (6.91 g, 50.0 mmol) in N,N-dimethylformamide (50 mL) was heated under reflux under an argon atmosphere for 2 hours. The solution was allowed to cool to room temperature, and poured into water. The solution was made weakly acidic by the addition of 1N hydrochloric acid, and the resulting crude crystals were collected by filtration. The crystals were washed with water and air dried to give crude 4,5-difluoro-2-[[3-ethyl-1-(2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid (11.3 g, 66% yield). A solution of the compound (11.0 g, 31.9 mmol) in phosphorous oxychloride (15 mL, 161 mmol) was heated under reflux for 2 hours. The solution was allowed to cool to room temperature, and poured into iced water. The solution was neutralized by the addition of a sodium hydroxide solution, and the organic matter was extracted with chloroform. The extract was washed with saturated brine and water, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (chloroform) to give the title compound (5.50 g, 50% yield).

Workup

  1. temperatureunder reflux under an argon atmosphere for 2 hours
  2. filtrationthe resulting crude crystals were collected by filtration
  3. washThe crystals were washed with water and air
  4. customdried

Sources & evidence

ORD record
ord-e7dadffad4b44fc285af54ee3f66cf6f
Source dataset
uspto-grants-2005_09
Patent number
US06949648B2

Reaction notes

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