Water → 7-(6-methoxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

HRID 1043934Notes

Reaction equation

HRID 1043934 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:26]([CH:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[N:25]=[CH:24][C:7]=3[C:8](=[O:23])[N:9](CC3C=CC(OC)=CC=3OC)[C:10]=2[CH:11]=1.[CH3:33][O:34][C:35]1[N:40]=[C:39]([CH3:41])[C:38](B(O)O)=[C:37]([CH3:45])[CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:33][O:34][C:35]1[N:40]=[C:39]([CH3:41])[C:38]([C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[N:26]([CH:27]5[CH2:28][CH2:29][O:30][CH2:31][CH2:32]5)[N:25]=[CH:24][C:7]=4[C:8](=[O:23])[NH:9][C:10]=3[CH:11]=2)=[C:37]([CH3:45])[CH:36]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 86686327(6-Methoxy-2,4-dimethylpyridin-3-yl)boronic acidHCID 866863597-bromo-5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

Product 1

HCID 1363878097-(6-methoxy-2,4-dimethylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

7-bromo-5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one obtained in Preparation Example 1(4) (41 mg) was dissolved in DMF (2 mL). (6-methoxy-2,4-dimethylpyridin-3-yl)boronic acid obtained in Preparation Example 24 (15 mg), Pd(PPh3)4 (4.8 mg), cesium carbonate (54 mg) and water (0.5 mL) were added to the solution, and the mixture was reacted using a microwave reactor at 150° C. for two hours. The reaction mixture was returned to room temperature and then concentrated under reduced pressure. The resulting residue was dissolved in TFA (1 mL), and the mixture was stirred at 65° C. for two hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. The resulting residue was neutralized by adding a 5 N aqueous sodium hydroxide solution. The aqueous solution was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 100%) to give the title compound (3.7 mg).

Workup

  1. additionwere added to the solution
  2. customthe mixture was reacted
  3. customat 150° C.
  4. customfor two hours
  5. customwas returned to room temperature
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in TFA (1 mL)
  8. temperatureThe reaction mixture was cooled to room temperature
  9. concentrationconcentrated under reduced pressure
  10. additionby adding a 5 N aqueous sodium hydroxide solution
  11. extractionThe aqueous solution was extracted with DCM
  12. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  13. customThe desiccant was removed by filtration
  14. concentrationThe filtrate was concentrated under reduced pressure
  15. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 100%)

Sources & evidence

ORD record
ord-a87eb100cbf84870b418849af5a2c4f5
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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