Potassium Carbonate → HCID 66690188, compound

HRID 592295Notes

Reaction equation

HRID 592295 reaction equation
Cl[C:2]1[C:3]2[N:4]([CH:15]=[N:16][N:17]=2)[CH:5]=[C:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:7]=1.[CH3:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)CC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:3]3[N:4]([CH:15]=[N:16][N:17]=3)[CH:5]=[C:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:7]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 66690797HCID 66690797, compound

Product 1

HCID 66690188HCID 66690188, compoundYield 16.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of tert-butyl 8-chloro[1,2,4]triazolo[4,3-a]pyridine-6-carboxylate (1.7 g, 6.7 mmol) in n-propanol (53.6 mL) and water (13.4 mL) were added (4-methylphenyl)boronic acid (1.37 g, 10.1 mmol), tetrakistriphenylphosphinepalladium (0) (0.39 g, 0.34 mmol) and potassium carbonate (2.78 g, 20.1 mmol). The mixture was purged with nitrogen and heated to 85° C. After 18 h, the mixture was cooled to ambient temperature and filtered with Celite. The filtrate was concentrated to remove n-propanol. The aqueous mixture was extracted with ethyl acetate (3×). The combined organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol). The product obtained was purified again by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.025% trifluoroacetic acid) gave the title compound (0.35 g): LC-MS [M+1]=310.2.

Workup

  1. customThe mixture was purged with nitrogen
  2. temperaturethe mixture was cooled to ambient temperature
  3. filtrationfiltered with Celite
  4. concentrationThe filtrate was concentrated
  5. customto remove n-propanol
  6. extractionThe aqueous mixture was extracted with ethyl acetate (3×)
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by silica gel chromatography (100% dichloromethane→95% dichloromethane/methanol)
  12. customThe product obtained
  13. customwas purified again by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.025% trifluoroacetic acid)

Sources & evidence

ORD record
ord-6f343d63a2014290b80f4ed088a69eee
Source dataset
uspto-grants-2016_01
Patent number
US09238647B2

Reaction notes

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