5-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride) → 5-Bromo-6'-chloro-2-fluoro-[3,4']bipyridinyl-3'-ylamine

HRID 1505863Notes

Reaction equation

HRID 1505863 reaction equation
[Cl: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][C:14]([Br:20])=[CH:13][N:12]=1>C(#N)C.[F-].[K+]>[Br:20][C:14]1[CH:15]=[C:16]([C:4]2[CH:3]=[C:2]([Cl:1])[N:7]=[CH:6][C:5]=2[NH2:8])[C:11]([F:10])=[N:12][CH:13]=1

Participants

5

Reactant 2

HCID 27832425-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride)HCID 184070406-Chloro-4-iodopyridin-3-amine

Product 1

HCID 582665005-Bromo-6'-chloro-2-fluoro-[3,4']bipyridinyl-3'-ylamineYield 49%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 522689Potassium FluorideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-chloro-4-iodo-pyridin-3-ylamine (2.37 g, 9.31 mmol), 2-fluoro-5-bromopyridine-3-boronic acid (2.64 g, 12.0 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.76 g, 0.93 mmol) in acetonitrile (35 mL) and 1N aqueous potassium fluoride solution (35 mL) was degassed with nitrogen for 20 minutes. The reaction mixture was heated at 80° C. for 3 h, allowed to cool to ambient temperature then partitioned between ethyl acetate (100 mL) and water (75 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The resultant solid residue was triturated using 1:1 DCM/methanol, collected by filtration, washed with diethyl ether and ethyl acetate to afford the title compound as a tan solid (1.37 g, 49%). The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-40% ethyl acetate in pentane) to afford further title compound as a brown solid (0.73 g, 26%). 1H NMR (DMSO-D6, 300 MHz): 8.46 (dd, J=2.5, 1.3 Hz, 1H), 8.24 (dd, J=8.3, 2.5 Hz, 1H), 7.88 (s, 1H), 7.19 (s, 1H), 5.57 (s, 2H). LCMS (Method B): RT=3.21 min, M+H+=304.

Workup

  1. customwas degassed with nitrogen for 20 minutes
  2. temperatureto cool to ambient temperature
  3. customthen partitioned between ethyl acetate (100 mL) and water (75 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
  9. filtrationcollected by filtration
  10. washwashed with diethyl ether and ethyl acetate

Sources & evidence

ORD record
ord-f5e12727cff047269efb1d3a73c43265
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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