Sodium Carbonate → 3-(2,4-Dimethoxy-5-pyrimidinyl)-2-pyridinecarbonitrile

HRID 12726

Reaction equation

HRID 12726 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.[C:14]([C:16]1[C:21](Br)=[CH:20][CH:19]=[CH:18][N:17]=1)#[N:15].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]>[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6]([C:21]2[C:16]([C:14]#[N:15])=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 8176943-Bromopyridine-2-carbonitrileHCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acid

Product 1

HCID 589942323-(2,4-Dimethoxy-5-pyrimidinyl)-2-pyridinecarbonitrileYield 79.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Procedure

2,4-Dimethoxy-pyrimidine-5-boronic acid (1 g, 5.46 mmol) was dissolved in degassed n-PrOH (30 ml) and then 2-cyano-3-bromopyridine (950 mg, 5.19 mmol), Na2CO3 (1.65 g, 15.56 mmol), PPh3 (393 mg, 1.5 mmol) and Pd(OAc)2 (114 mg, 0.51 mmol) were added. The suspension was stirred at reflux for 3 hours. After cooling, the solvent was evaporated under vacuum and the crude was partitioned between water and ethyl acetate. The organic phase washed with brine, dried (Na2SO4) and evaporated. The residue was triturated with iPrOH to give 1 g of the title compound as a white powder (76% yield).

Workup

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

Sources & evidence

ORD record
ord-479b3529179947c7ae9108e5afb47566
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Linked notes

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