Sodium hydride → 2,5-Bis{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

HRID 341070Notes

Reaction equation

HRID 341070 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]3[C:22]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:16]4=[N:23][NH:24][C:25](=[O:26])[C:15]4=[CH:14]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[H-].[Na+].Br[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]2[CH:41]=[CH:40][CH:39]=[N:38]2)=[CH:33][CH:32]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[N:37]1([C:34]2[CH:35]=[CH:36][C:31]([CH2:30][N:24]3[C:25](=[O:26])[C:15]4=[CH:14][N:13]([CH2:12][C:9]5[CH:10]=[CH:11][C:6]([N:1]6[CH:5]=[CH:4][CH:3]=[N:2]6)=[CH:7][CH:8]=5)[C:22]5[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=5[C:16]4=[N:23]3)=[CH:32][CH:33]=2)[CH:41]=[CH:40][CH:39]=[N:38]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 27764791-[4-(Bromomethyl)Phenyl]-1H-PyrazoleHCID 681538295-{[4-(1H-Pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Product 1

HCID 681764272,5-Bis{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-{[4-(1H-Pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 406, 71 mg, 0.21 mmol) was suspended in degassed N,N-dimethylformamide (3 mL), cooled to 0° C. and sodium hydride (17 mg, 0.42 mmol, 2 equiv, 60% dispersion in mineral oil) was added. After stirring for 10 minutes at 0° C., the mixture was warmed to ambient temperature and stirred for 45 minutes. 1-[4-(Bromomethyl)phenyl]-1H-pyrazole (74 mg, 0.31 mmol, 1.5 equiv) was added, the mixture as stirred for 2 hours and then poured into sodium bicarbonate (30 mL, aqueous saturated) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 88:12; dichloromethane:methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.09 (1H, s), 8.45-8.44 (2H, m), 8.15 (1H, d, J=7.8 Hz), 7.82-7.78 (4H, m), 7.75-7.72 (2H, m), 7.57 (1H, t, J=7.8 Hz), 7.48 (1H, t, J=7.7 Hz), 7.45-7.40 (4H, m), 6.52 (2H, s), 5.75 (2H, s), 5.14 (2H, s) ppm; high resolution mass spectrometry (ES+) m/z 498.2063 [(M+H)+; calculated for C30H24N7O: 498.2037].

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for 45 minutes
  3. stirringthe mixture as stirred for 2 hours
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. dry with materialThe combined organic extracts were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel gradient chromatography (100:0 to 88:12; dichloromethane:methanol)

Sources & evidence

ORD record
ord-92fcd118639a44628eac8e73f6b4ce4f
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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