Potassium Carbonate → 2-(2-fluorophenyl)-5-[(2-oxo-1-phenylpiperidin-4-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

HRID 341055Notes

Reaction equation

HRID 341055 reaction equation
CN(/[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.[NH2:25][CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:29](=[O:39])[CH2:28]1.C(=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>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:25]([CH2:26][CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:29](=[O:39])[CH2:28]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 11430Potassium Carbonate2×HCID 516892Sodium BicarbonateHCID 671114354-(Aminomethyl)-1-phenylpiperidin-2-one2×HCID 68153863(4Z)-4-[(Dimethylamino)methylidene]-2,5-bis(2-fluorophenyl)-2,4-dihydro-3H-pyrazol-3-one

Product 1

HCID 681541852-(2-fluorophenyl)-5-[(2-oxo-1-phenylpiperidin-4-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

(4Z)-4-[(Dimethylamino)methylidene]-2,5-bis(2-fluorophenyl)-2,4-dihydro-3H-pyrazol-3-one (0.12 g, 0.37 mmol), 4-(aminomethyl)-1-phenylpiperidin-2-one (76 mg, 0.37 mmol, 1 equiv) and potassium carbonate (0.15 g, 1.1 mmol, 3 equiv) were combined in degassed dimethylsulfoxide (5 mL) and placed into a preheated oil bath at 100° C. open to the air for 1 hour. Additional 4-(aminomethyl)-1-phenylpiperidin-2-one (0.15 g, 0.74 mmol, 2 equiv) and potassium carbonate (0.15 g, 1.1 mmol, 3 equiv) were added and the mixture was heated at 100° C. for an additional 2 hours. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (40 mL, aqueous saturated) 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 0:100 hexanes:ethyl acetate containing 5% methanol; then eluted with chloroform containing 15% methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 8.93 (1H, s), 8.23 (1H, dd, 7.8, 1.4 Hz), 8.06 (1H, d, J=8.7 Hz), 7.79-7.75 (1H, m), 7.63-7.57 (2H, m), 7.47-7.30 (5H, m), 7.27-7.21 (3H, m), 4.49 (2H, d, J=7.1 Hz), 3.66-3.53 (2H, m), 2.68-2.58 (1H, m), 2.47-2.30 (2H, m), 1.89 (1H, br d, J=12.5 Hz), 1.85-1.73 (1H, m) ppm; low resolution mass spectrometry (ES+) m/z 466.97 [(M+H)+; calculated for C28H24FN4O2: 467.18].

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionextracted with ethyl acetate (2×75 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100 hexanes
  7. washthen eluted with chloroform containing 15% methanol),

Sources & evidence

ORD record
ord-599cc6ae27c94c69bf85d070aca1c9cb
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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