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

HRID 510022노트

반응식

HRID 510022 반응식
[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

참가 물질

5

반응물 3

HCID 7410AcetophenoneHCID 31358DimedoneHCID 178507669HCID 178507669, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

반응 조건

온도
190 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-63b7514a2fbf41f587f173e6166f1195
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096594B2

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