2-Fluoropyridine-3-boronic acid → HCID 58266636, compound

HRID 1505859Notes

Reaction equation

HRID 1505859 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4](I)[CH:3]=1.[F:10][C:11]1[C:16](B(O)O)=[CH:15][CH:14]=[CH:13][N:12]=1>C(#N)C.[F-].[K+]>[Br:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:16]2[C:11]([F:10])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:3]=1

Participants

5

Reactant 2

HCID 27832702-Fluoropyridine-3-boronic acidHCID 58266485HCID 58266485, compound

Product 1

HCID 58266636HCID 58266636, compoundYield 39.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 6-bromo-4-iodo-pyridin-3-ylamine (10.0 g, 33.4 mmol), 2-fluoropyridine-3-boronic acid (5.2 g, 36.8 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (2.73 g, 3.34 mmol) in acetonitrile (150 mL) and 1N aqueous potassium fluoride solution (150 mL) was degassed with nitrogen for 20 minutes. The reaction mixture was heated at 70° C. for 2.5 h, allowed to cool to ambient temperature and then partitioned between ethyl acetate (400 mL) and water (150 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The resultant solid residue was triturated with dichloromethane: methanol (1:1, 100 mL), collected by filtration and washed with diethyl ether (50 mL) to furnish the title compound as a brown solid (3.5 g, 39%). The filtrate was evaporated and purified by passing the resultant residue through a pad of silica eluting with ethyl acetate: cyclohexane (1:1). Collection of the appropriate fractions and evaporation to dryness afforded a solid that was then triturated with diethyl ether to afford the title compound as a brown solid (3.7 g, 42%) (combined yield—7.22 g, 81%). 1H NMR (CDCl3, 300 MHz): 8.34 (ddd, J=4.9, 2.0, 1.2 Hz, 1H), 7.99 (s, 1H), 7.85 (ddd, J=9.4, 7.4, 2.0 Hz, 1H), 7.37 (ddd, J=7.4, 4.9, 2.0 Hz, 1H), 7.22 (s, 1H), 3.75 (s, 2H). LCMS (Method B): RT=2.78 min, M+H+=268/270.

Workup

  1. customwas degassed with nitrogen for 20 minutes
  2. temperatureto cool to ambient temperature
  3. custompartitioned between ethyl acetate (400 mL) and water (150 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resultant solid residue was triturated with dichloromethane: methanol (1:1, 100 mL)
  9. filtrationcollected by filtration
  10. washwashed with diethyl ether (50 mL)

Sources & evidence

ORD record
ord-73c380819727469986edc1a5bafe1aae
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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