Phosphorus oxychloride → 4-Chloro-3-methyl-1-(2-pyridinyl)-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]quinoline

HRID 498026Notes

Reaction equation

HRID 498026 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:8]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:9]=2[C:10](O)=O)[N:4]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[N:3]=1.P(Cl)(Cl)([Cl:29])=O>>[Cl:29][C:10]1[C:9]2[C:8](=[CH:16][CH:15]=[C:14]([C:17]([F:19])([F:18])[F:20])[CH:13]=2)[N:7]=[C:5]2[N:4]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[N:3]=[C:2]([CH3:1])[C:6]=12

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 223201712-[[3-Methyl-1-(2-pyridinyl)-1H-pyrazol-5-yl]amino]-5-(trifluoromethyl)benzoic acid

Product 1

HCID 223202634-Chloro-3-methyl-1-(2-pyridinyl)-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]quinolineYield 50.5%

Procedure

A solution of 2-[[3-methyl-1-(2-pyridinyl)-1H-pyrazol-5-yl]amino]-5-(trifluoromethyl)benzoic acid (14.0 g, 38.6 mmol) in phosphorous oxychloride (27.4 mL, 294 mmol) was heated under reflux for 1 hour. The solution was allowed to cool to room temperature, and the reaction solvent was evaporated under reduced pressure, 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 was purified by silica gel column chromatography (hexane:chloroform=1:1 to chloroform) to give the title compound (7.07 g, 50% yield).

Workup

  1. temperatureunder reflux for 1 hour
  2. customthe reaction solvent was evaporated under reduced pressure
  3. additionthe residue was poured into iced water
  4. additionThe solution was neutralized by the addition of a sodium hydroxide solution
  5. extractionthe organic matter was extracted with chloroform
  6. washThe extract was washed with saturated brine and water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:chloroform=1:1 to chloroform)

Sources & evidence

ORD record
ord-2d0d751bd20e4e8e8d661b27a89621ae
Source dataset
uspto-grants-2005_09
Patent number
US06949648B2

Reaction notes

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