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

HRID 12699Notes

Reaction equation

HRID 12699 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.[Cl:12][C:13]1[C:18](B(O)O)=[CH:17][C:16]([F:22])=[CH:15][N:14]=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]>[Cl:12][C:13]1[C:18]([C:2]2[C:3]([O:10][CH3:11])=[N:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=2)=[CH:17][C:16]([F:22])=[CH:15][N:14]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2634165-Iodo-2,4-dimethoxypyrimidineHCID 249017742-Chloro-5-fluoropyridine-3-boronic acid

Product 1

HCID 589942395-(2-Chloro-5-fluoro-pyridin-3-yl)-2,4-dimethoxy-pyrimidineYield 27%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Procedure

5-Iodo-2,4-dimethoxy-pyrimidine (868 mg, 3.3 mmol) was dissolved in degassed n-PrOH (30 ml) and then 2-chloro-5-fluoropyridine-3-boronic acid (858 mg, 4.9 mmol), Na2CO3 (700 mg, 6.6 mmol), PPh3 (88 mg, 0.33 mmol) and Pd(OAc)2 (90 mg) were added. The suspension was stirred at reflux for 4 hours. The solvent was evaporated under vacuum and the crude was partitioned between brine and ethyl acetate. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with ethyl acetate-petroleum ether 2-8 affording 240 mg of the title compound (27% yield).

Workup

  1. temperatureat reflux for 4 hours
  2. customThe solvent was evaporated under vacuum
  3. customthe crude was partitioned between brine and ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-5d2ba8741cdc4601a6f678054ff65ceb
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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