Nitrogen → 6'-Fluoro-[2,3']bipyridinyl-3-carbonitrile

HRID 645646Notes

Reaction equation

HRID 645646 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][N:12]=1.N#N.C(=O)([O-])[O-].[Cs+].[Cs+]>O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[F:10][C:11]1[N:12]=[CH:13][C:14]([C:2]2[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 810792-ChloronicotinonitrileHCID 2783397(6-Fluoropyridin-3-yl)boronic acid

Product 1

HCID 685841966'-Fluoro-[2,3']bipyridinyl-3-carbonitrileYield 84.5%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To an oven-dried, N2-purged, 250-mL, round-bottomed flask containing a magnetic stir bar were added the commercially available 2-chloro-3-cyanopyridine (1.25 g, 9.00 mmol), the commercially available 2-fluoropyridine-5-boronic acid (845 mg, 6.00 mmol), and dichlorobis(triphenylphosphine)palladium(II) (211 mg, 0.300 mmol). The flask was sealed with a septum and purged with N2 atmosphere. Anhydrous dioxane (45 mL) and a N2-purged solution of cesium carbonate (5.86 g, 18.0 mmol) in water (45 mL) were added via syringe. The reaction mixture was heated to ˜90° C. in an oil bath and stirred for 2 hours. The reaction was monitored by LC-MS. After cooling to room temperature, the solvent/volatiles were removed by rotary evaporator to give a thick brown oil. Water (75 mL) was added and the mixture was transferred to a separatory funnel. The mixture was extracted with ethyl acetate (4×30 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown solid. The product was recrystallized from ethyl acetate/hexanes to give 1.01 g (84%) of the title compound as a tan powder. MS (ESI+) m/z 200.0 (M+H)+; 1H NMR (DMSO-d6) δ 7.43 (dd, J=8.6, 2.9 Hz, 1H), 7.70 (dd, J=8.1, 5.1 Hz, 1H), 8.49 (d, J=1.7 Hz, 1H), 8.51 (d, J=1.7 Hz, 1H), 8.74 (d, J=2.7 Hz, 1H), 8.98 (dd, J=4.7, 1.7 Hz, 1H).

Workup

  1. customTo an oven-dried, N2-purged
  2. addition250-mL, round-bottomed flask containing a magnetic stir bar
  3. customThe flask was sealed with a septum
  4. custompurged with N2 atmosphere
  5. additionwere added via syringe
  6. temperatureAfter cooling to room temperature
  7. customthe solvent/volatiles were removed by rotary evaporator
  8. customto give a thick brown oil
  9. customthe mixture was transferred to a separatory funnel
  10. extractionThe mixture was extracted with ethyl acetate (4×30 mL)
  11. dry with materialThe combined organic extracts were dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated by rotary evaporator
  14. customto give a brown solid
  15. customThe product was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f8aa3773eb904f36ae19666c131f6b1d
Source dataset
uspto-grants-2010_04
Patent number
US07704997B1

Reaction notes

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