Hydrochloric Acid → 2-[[3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid

HRID 498069Notes

Reaction equation

HRID 498069 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)[N:3]=1.I[C:16]1[CH:24]=[CH:23][CH:22]=[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>[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:16]2[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=2[C:18]([OH:20])=[O:19])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)[N:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 69412-Iodobenzoic acidHCID 11430Potassium CarbonateHCID 574177003-Methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-ylamine

Product 1

HCID 223202242-[[3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acidYield 92.2%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-ylamine (7.03 g, 37.3 mmol), 2-iodobenzoic acid (10.2 g, 41.0 mmol), copper acetate (II) (0.745 g, 4.10 mmol) and potassium carbonate (5.67 g, 41.0 mmol) in N,N-dimethylformamide (30 mL) was heated under reflux under an argon atmosphere for 2 hours. The reaction solution was allowed to cool to room temperature, and the reaction mixture was 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 2-[[3-methyl-1-(6-methyl-2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid (10.6 g, 92% yield). A solution of the compound (9.5 g, 30.8 mmol) in phosphorous oxychloride (15 mL, 161 mmol) was heated under reflux for 1 hour. The reaction solution was allowed to cool to room temperature, and the residue was 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 (2.37 g, 25% 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-9a83c4d93a1f4395903bb2a8821244f8
Source dataset
uspto-grants-2005_09
Patent number
US06949648B2

Reaction notes

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