Water → 1-[5-(6-Fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone

Participants

Reaction Steps

A mixture of 3-bromo-6-fluoro-imidazo[1,2-b]pyridazine (620 mg, 2.9 mmol), 5-acetyl-2-thiopheneboronic acid [206551-43-1] (634 mg, 3.7 mmol), potassium carbonate [584-08-7] (792 mg, 5.7 mmol), and bis(triphenylphosphine)palladium(II) dichloride [13965-03-2] (100 mg, 0.1 mmol) was suspended in a microwave reaction vial with a 25% (v/v) solution of water in acetonitrile (4.5 mL) then stirred and irradiated to an internal temperature of 145° C. for 15 minutes. The cooled reaction mixture was diluted with ethyl acetate, filtered, and partitioned between 1N aqueous sodium hydroxide and additional ethyl acetate. The organic extract was flash chromatographed (silica gel, eluted with 20% (v/v) ethyl acetate/hexanes) to provide 1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone as 300 mg of yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.63 (s, 3H) 7.00 (d, J=9.35 Hz, 1H) 7.75 (d, J=4.04 Hz, 1H) 7.83 (d, J=4.04 Hz, 1H) 8.13 (dd, J=9.60, 7.07 Hz, 1H) 8.21 (s, 1H). LRMS (ESI) m/z 262.1 [(M+H)]+, calc'd for C12H8FN30S: 261.28.

Provenance & Evidence