Water → 3-Methyl-1-(2-pyridinyl)-1,9-dihydro-4H-pyrazolo[3,4-b]quinolin-4-one

HRID 498014Notes

Reaction equation

HRID 498014 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH3:15][C:16]1[CH:20]=[C:19]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=2[C:24]([OH:26])=O)[N:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[N:17]=1.O.[OH-].[Na+]>C(OCC)(=O)C.CO.CS(O)(=O)=O>[CH3:15][C:16]1[C:20]2[C:24](=[O:26])[C:23]3[C:22](=[CH:30][CH:29]=[CH:28][CH:27]=3)[NH:21][C:19]=2[N:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[N:17]=1

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 223201402-[[3-Methyl-1-(2-pyridinyl)-1H-pyrazol-5-yl]amino]benzoic acid

Product 1

HCID 1358480443-Methyl-1-(2-pyridinyl)-1,9-dihydro-4H-pyrazolo[3,4-b]quinolin-4-oneYield 67%

Reagents, catalysts & solvents 3

HCID 6395Methanesulfonic AcidCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methanesulfonic acid (120 mL, 1.85 mmol) and phosphorus pentoxide (24.0 g, 0.17 mol) was heated to 100° C. To the mixture stirred at the same temperature, powdery 2-[[3-methyl-1-(2-pyridinyl)-1H-pyrazole-5-yl]amino]benzoic acid (24.0 g, 82 mmol) was added gradually in small portions. The mixture was heated and stirred at the same temperature for 15 minutes. After the solution was allowed to cool to room temperature, iced water was added to the solution. The solution was made basic by the addition of an aqueous 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 basic silica gel column chromatography (chloroform). The crystals thus obtained we dissolved in a hot mixture of ethyl acetate (300 mL) and methanol (300 mL), and the solution was heated under reflux for 30 minutes in the presence of activated carbon (2.5 g). The hot solution was filtered and the solvents were evaporated under reduced pressure. The residue was recrystallized from ethyl acetate to give the title compound (15.1 g, 67% yield).

Workup

  1. additionwas added gradually in small portions
  2. temperatureThe mixture was heated
  3. temperatureto cool to room temperature
  4. extractionthe organic matter was extracted with chloroform
  5. washThe extract was washed with saturated brine and water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by basic silica gel column chromatography (chloroform)
  10. customThe crystals thus obtained we
  11. temperaturethe solution was heated
  12. temperatureunder reflux for 30 minutes in the presence of activated carbon (2.5 g)
  13. filtrationThe hot solution was filtered
  14. customthe solvents were evaporated under reduced pressure
  15. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-1a2d643259894bd9868d72eb56644bc0
Source dataset
uspto-grants-2005_09
Patent number
US06949648B2

Reaction notes

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