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

HRID 341045Notes

Reaction equation

HRID 341045 reaction equation
[CH3:1][N:2](/[CH:4]=[C:5]1\[C:6](=[O:24])[N:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])[N:8]=[C:9]\1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1F)C.[N:25]1([C:30]2[CH:35]=[CH:34][C:33](CN)=[CH:32][CH:31]=2)[CH:29]=[CH:28][CH:27]=[N:26]1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[F:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[N:7]1[C:6](=[O:24])[C:5]2=[CH:4][N:2]([CH2:1][C:33]3[CH:32]=[CH:31][C:30]([N:25]4[CH:29]=[CH:28][CH:27]=[N:26]4)=[CH:35][CH:34]=3)[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:9]2=[N:8]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 27764834-Pyrazol-1-YL-benzylamine2×HCID 68153863(4Z)-4-[(Dimethylamino)methylidene]-2,5-bis(2-fluorophenyl)-2,4-dihydro-3H-pyrazol-3-one

Product 1

HCID 681542582-fluorophenyl-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

(4Z)-4-[(Dimethylamino)methylidene]-2,5-bis(2-fluorophenyl)-2,4-dihydro-3H-pyrazol-3-one (241 mg, 0.735 mmol) and 1-[4-(1H-pyrazol-1-yl)phenyl]methanamine (127 mg, 0.735 mmol, 1 equiv) were combined in dimethylsulfoxide (10 mL) and placed into a preheated oil bath at 100° C. for 1.5 hours. To the mixture was added potassium carbonate (102 mg, 0.735 mmol, 1 equiv) and the mixture was heated for an additional 1 hour at 140° C. Additional 1-[4-(1H-pyrazol-1-yl)phenyl]methanamine (127 mg, 0.735 mmol, 1 equiv) and potassium carbonate (102 mg, 0.735 mmol, 1 equiv) were added and the mixture was heated for an additional 1 hour at 140° C. The mixture was cooled to ambient temperature, poured into water (75 mL) and extracted with ethyl acetate (2×75 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 95:5; dichloromethane:methanol; then 100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound: 1H-NMR (500 MHz, d6-DMSO) δ 9.16 (1H, s), 8.46 (1H, d, J=2.4 Hz), 8.20 (1H, dd, J=7.8, 1.4 Hz), 7.82 (2H, d, J=8.7 Hz), 7.77 (1H, d, J=8.7 Hz), 7.72 (1H, d, J=14.6 Hz), 7.64-7.59 (2H, m), 7.55-7.52 (1H, m), 7.47 (2H, d, J=8.4 Hz), 7.47-7.38 (2H, m), 7.36-7.32 (1H, m), 6.53 (1H, dd, J=2.4, 1.7 Hz), 5.78 (2H, s) ppm; high resolution mass spectrometry (ES+) m/z 436.1560 [(M+H)+; calculated for C26H19FN5O: 436.1568].

Workup

  1. temperaturethe mixture was heated for an additional 1 hour at 140° C
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionextracted with ethyl acetate (2×75 mL)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 95:5

Sources & evidence

ORD record
ord-48d8b303d02641b1b9dc88be9f74b1e6
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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