5-Bromo-2,4-dimethoxypyrimidine → 2,4-bis-(methyloxy)-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine

HRID 1925030Notes

Reaction equation

HRID 1925030 reaction equation
Br[C:2]1[C:3]([O:10][CH3:11])=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[CH3:12][N:13]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[N:14]1.C([O-])(O)=O.[Na+]>COCCOC.O>[CH3:9][O:8][C:5]1[N:4]=[C:3]([O:10][CH3:11])[C:2]([C:16]2[CH:15]=[N:14][N:13]([CH3:12])[CH:17]=2)=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 2557195-Bromo-2,4-dimethoxypyrimidineHCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 594483652,4-bis-(methyloxy)-5-(1-methyl-1H-pyrazol-4-yl)pyrimidine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

5-bromo-2,4-bis(methyloxy)pyrimidine (commercially available from Aldrich, 500 mg, 2.283 mmol) was dissolved in 1,2-Dimethoxyethane (DME) (5 ml). Pd(Ph3)4 (132 mg, 0.114 mmol) was added and the reaction mixture was stirred at room temperature for 15 min. 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (commercially available from Maybridge, 997 mg, 4.79 mmol) and 1M/H2O sol. of NaHCO3 (5 ml, 5.00 mmol) were added. After 2 h stirring at 90° C., the reaction mixture was cooled at room temperature, diluted with water (5 ml) and extracted with DCM (3×10 ml). The obtained residue was purified by flash chromatography first eluting with cyclohexane/EtOAc 4:1 then with 1:2 cyclohexane/EtOAc. 483.7 mg of the title compound were obtained.

Workup

  1. stirringAfter 2 h stirring at 90° C.
  2. temperaturethe reaction mixture was cooled at room temperature
  3. extractionextracted with DCM (3×10 ml)
  4. customThe obtained residue was purified by flash chromatography
  5. washfirst eluting with cyclohexane/EtOAc 4:1

Sources & evidence

ORD record
ord-3acba802381e4b178d38ae626f07c623
Source dataset
uspto-grants-2012_05
Patent number
US08178549B2

Reaction notes

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