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

HRID 1043938Notes

Reaction equation

HRID 1043938 reaction equation
[CH3:1][O:2][C:3]1[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=[CH:35][C:4]=1[CH2:5][N:6]1[C:15]2[CH:14]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:12]=[CH:11][C:10]=2[C:9]2[N:25]([CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[N:26]=[CH:27][C:8]=2[C:7]1=[O:34].Br[C:42]1[C:43]([O:49][CH3:50])=[N:44][CH:45]=[CH:46][C:47]=1[CH3:48].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.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>[CH3:1][O:2][C:3]1[CH:38]=[C:37]([O:39][CH3:40])[CH:36]=[CH:35][C:4]=1[CH2:5][N:6]1[C:15]2[CH:14]=[C:13]([C:42]3[C:43]([O:49][CH3:50])=[N:44][CH:45]=[CH:46][C:47]=3[CH3:48])[CH:12]=[CH:11][C:10]=2[C:9]2[N:25]([CH:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[N:26]=[CH:27][C:8]=2[C:7]1=[O:34]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 219528033-Bromo-2-methoxy-4-methylpyridineHCID 866863605-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one

Product 1

HCID 866863665-(2,4-dimethoxybenzyl)-7-(2-methoxy-4-methylpyridin-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 312751,4-DioxaneSolvent

Procedure

5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (100 mg) obtained in Preparation Example 1(5) was dissolved in 1,4-dioxane (4 mL). 3-bromo-2-methoxy-4-methylpyridine obtained in Preparation Example 37 (2) (55.6 mg), Pd(PPh3)4 (10.6 mg), cesium carbonate (179 mg) and water (1 mL) were added to the solution, and the mixture was reacted using a microwave reactor at 130° C. for three hours. The reaction mixture was returned to room temperature and then partitioned by adding ethyl acetate. The organic layer was washed with brine and then dried over magnesium sulfate. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 30% to 50% to 80%) to give 5-(2,4-dimethoxybenzyl)-7-(2-methoxy-4-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (78 mg). The 5-(2,4-dimethoxybenzyl)-7-(2-methoxy-4-methylpyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (78 mg) 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 saturated aqueous sodium bicarbonate 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 70% to 80% to 100%) to give the title compound (30 mg).

Workup

  1. additionwere added to the solution
  2. customthe mixture was reacted
  3. customat 130° C.
  4. customfor three hours
  5. customwas returned to room temperature
  6. custompartitioned
  7. additionby adding ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. customThe desiccant was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/n-heptane, 30% to 50% to 80%)

Sources & evidence

ORD record
ord-8e2e59ca8a3c4870a1aea4724ec5d8f2
Source dataset
uspto-grants-2013_10
Patent number
US08563565B2

Reaction notes

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