Dimethyl Sulfoxide → N-(6-(6-Chloro-5-(methylsulfonamido)pyridin-3-yl)-3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a 10 mL round-bottomed flask was added N-(6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)-3-iodoimidazo[1,2-b]pyridazin-2-yl)acetamide (Example 21) (0.0820 g, 0.162 mmol), DMSO (2.50 mL, 35.2 mmol), 3-fluorophenylboronic acid (0.0272 g, 0.194 mmol, Aldrich, St. Louis, Mo.), and sodium carbonate (0.405 mL, 0.809 mmol, 2 M). The mixture was carefully evacuated and backfilled with N2. To the mixture was added trans-dichlorobis(triphenylphosphine)palladium(II) (0.011 g, 0.0162 mmol, Strem Chemical, Inc., Newburyport, Mass.). Again, the mixture was carefully evacuated and backfilled with N2. The mixture was stirred at 90° C. for 40 min, allowed to cool to rt. and then directly purified by preparative HPLC (Phenomenex Gemini 5 micron (Phenomenex, Torrance, Calif.), C18, 100×30 mm, 5 to 75% CH3CN(0.1% TFA)/H2O(0.1% TFA) over 20 min then 100% CH3CN(0.1% TFA) for 3 minutes at 20 mL/min) with the fractions containing suspected product concentrated to afford the title compound as a yellow solid (0.059 g, 62%). MS (ESI, positive ion) m/z: 475 (M−TFA+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.04 (s, 3H), 3.20 (s, 3H), 7.25-7.28 (m, 1H), 7.53-7.60 (m, 1H), 7.70-7.75 (m, 1H), 7.77-7.81 (m, 1H), 8.02 (d, J=9.6 Hz, 1H), 8.32 (d, J=9.6 Hz, 1H), 8.52 (d, J=2.2 Hz, 1H), 8.95 (d, J=2.2 Hz, 1H), 9.92 (s, 1H), 10.24 (s, 1H).

Provenance & Evidence