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

Temperature

80 °C

A mixture of 6-fluoro-4-iodopyridin-3-ylamine (1.57 g, 6.59 mmol), 2-fluoro-5-bromopyridine-3-boronic acid (2.17 g, 9.89 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.43 g, 0.53 mmol) in acetonitrile (25 mL) and 1N aqueous potassium fluoride solution (25 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 and then partitioned between ethyl acetate (100 mL) and water (75 mL). The organic layer was separated, dried over sodium sulfate, filtered and evaporated in vacuo. The resultant residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-50% ethyl acetate in cyclohexane) to afford the title compound as an brown solid (0.54 g, 29%). 1H NMR (CDCl3, 300 MHz): 8.37 (dd, J=2.5, 1.4 Hz, 1H), 7.99 (dd, J=8.1, 2.5 Hz, 1H), 7.79 (d, J=1.5 Hz, 1H), 6.74 (d, J=2.8 Hz, 1H), 3.62 (s, 2H). LCMS (Method B): RT=3.01 min, M+H+=286/288.

1. customwas degassed with nitrogen for 20 minutes
2. temperatureto cool to ambient temperature
3. custompartitioned between ethyl acetate (100 mL) and water (75 mL)
4. customThe organic layer was separated
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customevaporated in vacuo
8. customThe resultant residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-50% ethyl acetate in cyclohexane)

ORD record

ord-0deb0136a59b427781d086ab6889e837

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216980B2