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

HRID 12695Notes

Reaction equation

HRID 12695 reaction equation
I[C:2]1[C:3]([O:10][CH3:11])=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[F:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][C:18]=1B(O)O.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:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][C:18]=1[C:2]1[C:3]([O:10][CH3:11])=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2634165-Iodo-2,4-dimethoxypyrimidineHCID 27793533-Fluoropyridine-4-boronic acid

Product 1

HCID 589941815-(3-Fluoro-pyridin-4-yl)-2,4-dimethoxy-pyrimidineYield 93%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Procedure

5-Iodo-2,4-dimethoxy-pyrimidine (commercially available from Matrix, 905 mg, 3.4 mmol) was dissolved in degassed n-PrOH (24 ml) and then 3-fluoropyridine-4-boronic acid (715 mg, 5.1 mmol), Na2CO3 (721 mg, 6.8 mmol), PPh3 (84 mg, 0.34 mmol) and Pd(OAc)2 (40 mg) were added. The suspension was stirred at reflux for 1.5 hours. 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 crude was purified by flash chromatography with DCM-MeOH 98-2 and by SCX cartridge washing with MeOH and then collecting the product with MeOH—NH4OH (95-5) to give 750 mg of the title compound (93% yield).

Workup

  1. temperatureat reflux for 1.5 hours
  2. customThe solvent was evaporated under vacuum
  3. customthe crude was partitioned between water and ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customThe crude was purified by flash chromatography with DCM-MeOH 98-2 and by SCX cartridge
  7. washwashing with MeOH
  8. customcollecting the product with MeOH—NH4OH (95-5)

Sources & evidence

ORD record
ord-da7cc571d86c471794517e072fdfd449
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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