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

HRID 510022ノート

反応式

HRID 510022 の反応式
[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

参加物

5

反応物 3

HCID 7410AcetophenoneHCID 31358DimedoneHCID 178507669HCID 178507669、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
190 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-63b7514a2fbf41f587f173e6166f1195
出典データセット
uspto-grants-2015_08
特許番号
US09096594B2

反応ノート

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