1,3-Dioxane → 6-(Benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline

HRID 1473372

반응식

HRID 1473372 반응식
[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](Cl)=[N:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCCOC1>O>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]([C:23]1[CH:24]=[CH:25][C:26]([C:28]([F:31])([F:30])[F:29])=[CH:27][C:22]=1[O:21][CH3:20])=[N:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 104501,3-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 866874176-(Benzylthio)-1-chloroisoquinoline

생성물 1

HCID 866874186-(Benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline수율 97%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A round-bottom flask was charged with 6-(benzylthio)-1-chloroisoquinoline (3.101 g, 10.85 mmol)-(2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (2.86 g, 13.02 mmol), Pd(AmPhos)2Cl2 (0.384 g, 0.543 mmol), potassium phosphate (6.91 g, 32.6 mmol), 1,3-dioxane (27.1 ml), and water (9.04 ml). The vial was flushed with Ar (g), fitted with a reflux condenser, and placed in a 100° C. heating bath for 45 min. The mixture was cooled to room temperature, then diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (120-g, 10 to 40% EtOAc/Heptane) to give 6-(benzylthio)-1-(2-methoxy-4-(trifluoromethyl)phenyl)isoquinoline (4.47 g, 10.51 mmol, 97% yield) as a light-yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.58 (d, J=5.8 Hz, 1H), 7.66 (d, J=1.8 Hz, 1H), 7.56-7.47 (m, 3H), 7.45-7.26 (m, 8H), 4.31 (s, 2H), 3.76 (s, 3H); m/z (ESI) 426.2 (M+H)+.

후처리

  1. customThe vial was flushed with Ar (g)
  2. customfitted with a reflux condenser
  3. customplaced in a 100° C.
  4. temperatureheating bath for 45 min
  5. additiondiluted with water
  6. extractionextracted with EtOAc (2×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography on silica gel (120-g, 10 to 40% EtOAc/Heptane)

출처 및 근거

ORD 기록
ord-ecba7d8ae2c44cdcae577a79775b1192
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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