Cesium carbonate → 3-Fluoro-4-(pyrimidin-5-yl)picolinonitrile

HRID 871164Notes

Reaction equation

HRID 871164 reaction equation
[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[CH:6][C:7]=1I.[N:11]1[CH:16]=[C:15](B(O)O)[CH:14]=[N:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[F:1][C:2]1[C:3]([C:9]#[N:10])=[N:4][CH:5]=[CH:6][C:7]=1[C:15]1[CH:16]=[N:11][CH:12]=[N:13][CH:14]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 210758673-Fluoro-4-iodopyridine-2-carbonitrile

Product 1

HCID 867304123-Fluoro-4-(pyrimidin-5-yl)picolinonitrileYield 68.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A vial containing a mixture of 3-fluoro-4-iodopicolinonitrile (1.25 g, 5.04 mmol), pyrimidin-5-ylboronic acid (1.249 g, 10.08 mmol), and cesium carbonate (3.45 g, 10.58 mmol) in dioxane (Ratio: 2.0, Volume: 10.18 ml) and water (Ratio: 1.000, Volume: 5.09 ml) was degassed with N2 for 5 min, then PdCl2(dppf)-CH2Cl2Adduct (0.218 g, 0.267 mmol) was added. The solution was heated at 85° C. for 17 hr, and then allowed to cool to room temperature. The reaction was quenched with water. The reaction mixture was diluted with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried over Na2SO4, filtered, and concentrated to afford a brown residue. The crude material was purified by MPLC (80 g column, 60 mL/min, 30-100% EtOAc in hexanes) to give the title compound (695 mg, 3.44 mmol, 68.2% yield) as a pink solid. ESI MS (M+H)+=201.1.

Workup

  1. additionA vial containing
  2. customwas degassed with N2 for 5 min
  3. temperatureto cool to room temperature
  4. customThe reaction was quenched with water
  5. additionThe reaction mixture was diluted with EtOAc
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted with EtOAc (3×)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a brown residue
  12. customThe crude material was purified by MPLC (80 g column, 60 mL/min, 30-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c97d298ee16c49e08adf76fd10f1e8d0
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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