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

HRID 2198090Notes

Reaction equation

HRID 2198090 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.CC[N:20]([CH2:23][CH3:24])[CH2:21]C.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=C([CH:32]=[CH:33][CH:34]=1)CN.[C]=[O:38]>C1(C)C=CC=CC=1.[Cl-].[NH4+].ClCCl.[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]>[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=[C:24]([CH:32]=[CH:33][CH:34]=1)[CH2:23][NH:20][C:21]([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:38]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 759623-(Trifluoromethyl)benzylamineHCID 592784604-Bromo-1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridineHCID 178418416HCID 178418416, compound

Product 1

HCID 451380071-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid 3-trifluoromethyl-benzylamide

Reagents, catalysts & solvents 4

HCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-bromo-1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine (340 mg, 1.2 mmol), Et3N (320 μL, 2.3 mmol), 3-trifluoromethylbenzylamine (250 μL, 1.7 mmol), Pd[PhCN]2Cl2 (10 mg, 0.03 mmol), and 1,1-bis(diphenylphosphino)ferrocene (dppf) (0.04 g, 0.07 mmol) in toluene (15 mL) was sealed in a bomb with stifling, placed under 15 bars of carbon monoxide and warmed at 140° C. After 3 hours, the mixture was cooled to room temperature, returned to atmospheric pressure and opened. The reaction was monitored by HPLC-MS indicating the desired mass M+=415.43. The reaction was diluted with saturated aqueous ammonium chloride (50 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with saturated aqueous ammonium chloride (3×20 mL), brine (20 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was dissolved in dichloromethane and purified by silica gel chromatography using a gradient of 0-30% EtOAc in dichloromethane to afford partially purified material. The material from the column was triturated with ether-hexanes to afford an off-white solid. This material was dissolved in dichloromethane and passed through a pad of silica gel (15 mL funnel) eluting with a gradient of 0-40% dichloromethane in EtOAc. The material from the pad was triturated with ether to afford the title compound, mp 172-173° C.

Workup

  1. customwas sealed in a bomb with stifling
  2. temperaturethe mixture was cooled to room temperature
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic layers were washed with saturated aqueous ammonium chloride (3×20 mL), brine (20 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe crude material was dissolved in dichloromethane
  9. custompurified by silica gel chromatography
  10. customto afford partially purified material
  11. customThe material from the column was triturated with ether-hexanes
  12. customto afford an off-white solid
  13. washeluting with a gradient of 0-40% dichloromethane in EtOAc
  14. customThe material from the pad was triturated with ether

Sources & evidence

ORD record
ord-f3550177206f46b3b62178dd33178a18
Source dataset
uspto-grants-2012_12
Patent number
US08338610B2

Reaction notes

Loading…