1-Propanol → 4-(4-amino-2-ethyl-2H-pyrazolo[3,4-c]quinolin-1-yl)butan-1-ol

HRID 2283758

반응식

HRID 2283758 반응식
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(O)CC.C([O:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]1[N:31]([CH2:38][CH3:39])[N:32]=[C:33]([C:36]#[N:37])[C:34]=1Br)(=O)C>[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[NH2:37][C:36]1[C:33]2=[N:32][N:31]([CH2:38][CH3:39])[C:30]([CH2:29][CH2:28][CH2:27][CH2:26][OH:25])=[C:34]2[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[N:2]=1

참가 물질

10

반응물 4

HCID 10311-PropanolHCID 10340Sodium Carbonate2회HCID 164270902-Aminophenylboronic acid hydrochloride2회HCID 669586364-(4-bromo-5-cyano-2-ethyl-2H-pyrazol-3-yl)butyl acetate

생성물 1

HCID 577175274-(4-amino-2-ethyl-2H-pyrazolo[3,4-c]quinolin-1-yl)butan-1-ol수율 32.6%

시약·촉매·용매 5

HCID 11776Triphenylphosphine촉매2회HCID 23938Palladium촉매HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
100 °C

실험 절차

Triphenylphosphine (21 mg, 0.082 mmol), 2-aminophenylboronic acid hydrochloride (710 mg, 4.1 mmol), 2 M aqueous sodium carbonate (4.1 mL), n-propanol (4.8 mL), and water (1 mL) were added to 4-(4-bromo-5-cyano-2-ethyl-2H-pyrazol-3-yl)butyl acetate (0.86 mg, 2.7 mmol), and the flask was evacuated and backfilled with nitrogen five times before the addition of palladium (II) acetate (6.0 g, 0.027 mmol). The reaction was evacuated and backfilled with nitrogen three more times and then heated overnight at 100° C. An analysis by HPLC indicated that the reaction was incomplete. Additional triphenylphosphine (10 mg, 0.038 mmol), 2-aminophenylboronic acid hydrochloride (300 mg, 1.73 mmol), solid sodium carbonate (500 mg), and palladium (H) acetate (3.0 g, 0.013 mmol) were added at ambient temperature, and the reaction was heated at reflux for three hours and allowed to cool to ambient temperature. The reaction was diluted with brine and extracted with chloroform. The combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. Methanol (10 mL) and sodium methoxide (2.2 mL of a 47% solution in methanol) were added to the resulting dark oil. The reaction was heated at reflux for three hours, allowed to cool to ambient temperature, and concentrated under reduced pressure. The residue was diluted with water and extracted with chloroform. The combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (40+M cartridge, eluting with chloroform/CMA in a gradient from 100:0 to 75:25) to provide an oil. The oil was crystallized from acetonitrile and recrystallized from acetonitrile to provide 250 mg of 4-(4-amino-2-ethyl-2H-pyrazolo[3,4-c]quinolin-1-yl)butan-1-ol as gold-colored crystals, mp 159-160° C.

후처리

  1. customthe flask was evacuated
  2. customThe reaction was evacuated
  3. temperaturethe reaction was heated
  4. temperatureat reflux for three hours
  5. temperatureto cool to ambient temperature
  6. extractionextracted with chloroform
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. additionMethanol (10 mL) and sodium methoxide (2.2 mL of a 47% solution in methanol) were added to the resulting dark oil
  11. temperatureThe reaction was heated
  12. temperatureat reflux for three hours
  13. temperatureto cool to ambient temperature
  14. concentrationconcentrated under reduced pressure
  15. additionThe residue was diluted with water
  16. extractionextracted with chloroform
  17. dry with materialThe combined extracts were dried over sodium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated under reduced pressure
  20. customThe crude product was purified by chromatography on a HORIZON HPFC system (40+M cartridge
  21. washeluting with chloroform/CMA in a gradient from 100:0 to 75:25)
  22. customto provide an oil
  23. customThe oil was crystallized from acetonitrile
  24. customrecrystallized from acetonitrile

출처 및 근거

ORD 기록
ord-9fde09251860475fb7cb8c6a43e7aca1
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09145410B2

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