Triethylamine → 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid ethyl ester

HRID 1698123Notes

Reaction equation

HRID 1698123 reaction equation
Br[C:2]1[CH: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(CC)CC.[C]=O.[CH3:27][CH2:28][O:29][C:30](C)=[O:31]>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH2:28]([O:29][C:30]([C:2]1[C:3]2[CH:10]=[N:9][N:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=2[CH:5]=[N:6][CH:7]=1)=[O:31])[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 592784604-Bromo-1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridineHCID 178418416HCID 178418416, compound

Product 1

HCID 592784101-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 702EthanolSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-bromo-1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine (3.5 g, 12 mmol), Et3N (3.5 mL, 25 mmol), Pd[PhCN]2Cl2 (105 mg, 0.273 mmol), and dppf (418 mg, 0.754 mmol) in absolute ethanol (90 mL) was placed in a sealed bomb with stifling and placed under 15 bars of carbon monoxide and warmed to 140° C. for 4 hours. The mixture was then cooled to room temperature, returned to atmospheric pressure and opened. The reaction was monitored by TLC (EtOAc-hexanes 4:6 and EtOAc) indicating the starting material was consumed. The reaction was diluted with water (300 mL) and the solid was collected by filtration washing with water. The filtrate was diluted with water (200 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (2×100 mL). The still moist filter cake was dissolved in EtOAc and combined with the extracted organic layers, dried over magnesium sulfate, treated with activated carbon) and filtered through a pad of diatomaceous earth and a layer of silica gel. The material from the pad was dissolved in dichloromethane and passed through a pad of silica gel eluting with dichloromethane to afford 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid ethyl ester.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. customwas consumed
  3. additionThe reaction was diluted with water (300 mL)
  4. filtrationthe solid was collected by filtration
  5. washwashing with water
  6. additionThe filtrate was diluted with water (200 mL)
  7. extractionextracted with EtOAc (2×100 mL)
  8. washThe combined organic layers were washed with brine (2×100 mL)
  9. dissolutionThe still moist filter cake was dissolved in EtOAc
  10. dry with materialdried over magnesium sulfate
  11. additiontreated with activated carbon) and
  12. filtrationfiltered through a pad of diatomaceous earth
  13. dissolutionThe material from the pad was dissolved in dichloromethane

Sources & evidence

ORD record
ord-82d0a148b8e94a468af7b369ede6510a
Source dataset
uspto-grants-2012_04
Patent number
US08163918B2

Reaction notes

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