Potassium Phosphate, Tribasic → 3-Bromo-5-(1-methyl-1H-pyrazol-4-yl)pyridine

HRID 1852484Notes

Reaction equation

HRID 1852484 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:9][N:10]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=[N:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:13]2[CH:12]=[N:11][N:10]([CH3:9])[CH:14]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 693693,5-DibromopyridineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 576426663-Bromo-5-(1-methyl-1H-pyrazol-4-yl)pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

3,5-Dibromopyridine (500 mg, 2.11 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (400 mg, 1.9 mmol), 1,1′bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (172 mg, 0.211 mmol), and potassium phosphate tribasic (1.34 g, 6.33 mmol) were combined in a 20 mL microwave vial and dissolved in dioxane (9 mL) and water (1 mL). The vial was sealed and flushed with argon. The reaction mixture was stirred at 90° C. for 2 hours. The vial was then cooled to ambient temperature and diluted with ethyl acetate. The organic layer was washed with water, brine, and then dried over anhydrous magnesium sulfate. The solution was then filtered and concentrated in vacuo. The crude material was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/DCM) to afford the title compound. 1H NMR (500 MHz, CDCl3) δ 8.58 (s, 1H), 8.44 (s, 1H), 7.82 (s, 1H), 7.72 (s, 1H), 7.63 (s, 1H), 3.91 (s, 3H). LRMS (ESI) calc'd for C9H8BrN3 [M+H]+: 238. Found: 238.

Workup

  1. customThe vial was sealed
  2. customflushed with argon
  3. temperatureThe vial was then cooled to ambient temperature
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe solution was then filtered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by MPLC on silica gel (
  10. washa gradient elution of 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-296100171da64257ad06353341347653
Source dataset
uspto-grants-2015_02
Patent number
US08962608B2

Reaction notes

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