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

HRID 1360433

反応式

HRID 1360433 の反応式
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.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

参加物

9

反応物 4

HCID 10311-PropanolHCID 10340Sodium Carbonate2 回HCID 164270902-Aminophenylboronic acid hydrochloride2 回HCID 669586364-(4-bromo-5-cyano-2-ethyl-2H-pyrazol-3-yl)butyl acetate

生成物 1

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

試薬・触媒・溶媒 4

HCID 11776Triphenylphosphine触媒2 回HCID 167845palladium(II) acetate触媒2 回HCID 962Water溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
100 °C

実験手順

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 (II) 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.

後処理

  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

出典と根拠

ORDレコード
ord-af667354e3ac42068c581e94423e56b5
出典データセット
uspto-grants-2011_02
特許番号
US07879849B2

関連ノート

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