Acetophenone → 4,7,7-trimethyl-4-phenyl-3-(trifluoromethyl)-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-b]quinolin-5(4H)-one

HRID 510022Notes

Reaction equation

HRID 510022 reaction equation
[CH3:1][C:2]1([CH3:10])[CH2:7][C:6](=O)[CH2:5][C:4](=[O:9])[CH2:3]1.[C:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=O)[CH3:12].[F:20][C:21]([F:29])([F:28])[C:22]1[CH:26]=[C:25]([NH2:27])[NH:24][N:23]=1>FC(F)(F)C(O)=O>[CH3:12][C:11]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]2[C:4](=[O:9])[CH2:3][C:2]([CH3:1])([CH3:10])[CH2:7][C:6]=2[NH:27][C:25]2=[N:24][NH:23][C:22]([C:21]([F:29])([F:28])[F:20])=[C:26]12

Participants

5

Reactant 3

HCID 7410AcetophenoneHCID 31358DimedoneHCID 178507669HCID 178507669, compound

Product 1

HCID 1362053284,7,7-trimethyl-4-phenyl-3-(trifluoromethyl)-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-b]quinolin-5(4H)-oneYield 0.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
190 °C

Procedure

In a 25 mL rb flask, 5,5-dimethylcyclohexane-1,3-dione (1402.0 mg, 10.0 mmol, 1.0 equivalent) was dissolved in trifluoroacetic acid (10.0 mL, 0.47 molar), followed by addition of acetophenone (11.44 mL, 100.0 mmol, 10.0 equivalent) in one portion. The reaction was refluxed for 3 hours at 190° C., followed by addition of 3-(trifluoromethyl)-1H-pyrazol-5-amine (1511.0 mg, 10.0 mmol, 1.5 equivalent) and continued reflux for additional 2.5 hours at 190° C. The reaction mixture was cooled and evaporated to remove TFA. The crude reaction mixture was purified by HPLC to afford the desired product as a white solid (17.0 mg). 1H NMR (300 MHz, DMSO) δ 7.24 (d, J=7.6 Hz, 2H), 7.14 (t, J=7.6 Hz, 2H), 6.99 (t, J=7.1 Hz, 1H), 2.43 (d, J=4.7 Hz, 2H), 2.01 (d, J=15.8 Hz, 1H), 1.92 (s, 3H), 1.86 (d, J=15.8 Hz, 1H), 0.99 (s, 3H), 0.92 (s, 3H). LRMS (ESI+) (M+H): 376.24, retention time 0.67 min.

Workup

  1. temperaturecontinued reflux for additional 2.5 hours at 190° C
  2. temperatureThe reaction mixture was cooled
  3. customevaporated
  4. customto remove TFA
  5. customThe crude reaction mixture
  6. customwas purified by HPLC

Sources & evidence

ORD record
ord-63b7514a2fbf41f587f173e6166f1195
Source dataset
uspto-grants-2015_08
Patent number
US09096594B2

Reaction notes

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