Dimethylformamide → N-(6-(2-(2-Fluorophenylthio)pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

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Reaction Conditions

Reaction Steps

To a 10-mL, round-bottomed flask was added N-(6-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (Example 3) (0.034 g, 0.13 mmol), DMF (2.0 mL), 2-fluorothiophenol (0.045 mL, 0.42 mmol, Aldrich, St. Louis, Mo.), and sodium hydride (17 mg, 0.45 mmol, 60% dispersion in mineral oil, Aldrich, St. Louis, Mo.). The mixture was stirred at 110° C. for 42 h. The mixture was poured into water and extracted with EtOAc (3×30 mL). The combined extracts were washed with water (2×30 mL) and brine (30 mL) then dried (Na2SO4), and concentrated onto silica. Purification by silica gel chromatography (0 to 3.5% MeOH (2 M in NH3)/CH2Cl2), followed by further purification by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 2 to 100% CH3CN/H2O, 0.1% TFA, over 15 min) (Phenomenex, Torrance, Calif.) and conversion to the free base by elution of the isolated material through an SCX cartridge (Radleys Discovery Technologies, Essex, UK) with MeOH (2 M in NH3)/CH2Cl2 afforded the title compound as a yellow solid. MS (ESI positive ion) m/z: 380 (M+1). 1H NMR (400 MHz, DMSO-d6): δ ppm 10.99 (s, 1H), 8.53 (d, J=5.0 Hz, 1H), 8.28 (s, 1H), 8.13 (d, J=9.5 Hz, 1H), 7.82-7.84 (m, 3H), 7.71 (t, J=7.3 Hz, 1H), 7.62 (q, J=6.7 Hz, 1H), 7.43 (t, J=8.8 Hz, 1H), 7.35 (t, J=7.5 Hz, 1H), 2.11 (s, 3H).

Provenance & Evidence