Ethanol → HCID 68345601, compound

HRID 1423019Notes

Reaction equation

HRID 1423019 reaction equation
Cl[C:2]1[N:7]=[N:6][CH:5]=[C:4]2[N:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:9]=[CH:10][C:3]=12.CCN([CH:24]([CH3:26])C)C(C)C.[C]=[O:28].[CH2:29]([OH:31])C>[Cl-].[NH4+].[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2]>[CH2:24]([O:28][C:29]([C:2]1[N:7]=[N:6][CH:5]=[C:4]2[N:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:9]=[CH:10][C:3]=12)=[O:31])[CH3:26]

Participants

7

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 86672829HCID 86672829, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 68345601HCID 68345601, compound

Reagents, catalysts & solvents 2

HCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 4-chloro-1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyridazine (510 mg, 2.1 mmol), DIPEA (700 μL, 4 mmol)), Pd[PhCN]2Cl2 (24 mg, 0.063 mmol), and 1,1-bis(diphenylphosphino)ferrocene (dppf) (48 mg, 0.087 mmol) in absolute ethanol (15 mL) is placed in a sealed pressure reactor with stirring and placed under 15 bars of carbon monoxide and warmed at 85° C. After 18 hours, the sealed pressure reactor is cooled to room temperature, returned to atmospheric pressure and opened. The reaction mixture is diluted with saturated aqueous ammonium chloride (30 mL) and extracted with EtOAc (3×20 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (2×15 mL) and brine (2×15 mL), dried over magnesium sulfate, filtered and concentrated. The crude product is passed through a pad of silica gel eluting using a gradient of 10-40% EtOAc in hexanes to afford 1-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid ethyl ester as a solid.

Workup

  1. customis placed in a sealed pressure reactor
  2. temperaturethe sealed pressure reactor is cooled to room temperature
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic layers are washed with saturated aqueous ammonium chloride (2×15 mL) and brine (2×15 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c213779ec9b041d2842b137233b3ff62
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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