Sodium Carbonate → 5-(2-Fluoro-5-methylpyridin-3-yl)-2,4-dimethoxy-pyrimidine

HRID 12722

Reaction equation

HRID 12722 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6](B(O)O)=[CH:5][N:4]=1.[F:14][C:15]1[C:20](Br)=[CH:19][C:18]([CH3:22])=[CH:17][N:16]=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(O)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:14][C:15]1[C:20]([C:6]2[C:7]([O:9][CH3:10])=[N:8][C:3]([O:2][CH3:1])=[N:4][CH:5]=2)=[CH:19][C:18]([CH3:22])=[CH:17][N:16]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acidHCID 218165633-Bromo-2-fluoro-5-methylpyridine

Product 1

HCID 589941695-(2-Fluoro-5-methylpyridin-3-yl)-2,4-dimethoxy-pyrimidineYield 33.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Procedure

2,4-Dimethoxy-pyrimidine-5-boronic acid (842 mg, 4.60 mmol) was dissolved in degassed n-PrOH (55 ml) and then 2-fluoro-3-bromo-5-methylpyridine (800 mg, 4.21 mmol), Na2CO3 (1.46 g, 13.77 mmol), PPh3 (348 mg, 1.33 mmol) and Pd(OAc)2 (101 mg, 0.45 mmol) were added. The suspension was stirred at reflux for 2 hours. After cooling, the solvent was evaporated under vacuum and the crude was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4) and evaporated. The residue was triturated with Et2O to give 350 mg of the title compound as a gray powder (31% yield).

Workup

  1. temperatureat reflux for 2 hours
  2. temperatureAfter cooling
  3. customthe solvent was evaporated under vacuum
  4. customthe crude was partitioned between water and ethyl acetate
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customevaporated
  7. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-12f4a5822159455fbcc84489de49ee47
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Linked notes

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