Dimethyl Sulfoxide → HCID 44125612, Verbindung

Beteiligte Stoffe

Reaktionsschritte

Following the procedure described for N-(6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (Example 19), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.132 g, 0.627 mmol) was reacted with bis(pinacolato)diboron (0.207 g, 0.815 mmol), DMSO (6.00 mL, 84.5 mmol) and potassium acetate (0.246 g, 2.51 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.050 g, 0.062 mmol, Strem Chemical, Inc., Newburyport, Mass.) for 6 h. This was followed by treatment with 5-bromo-2,3-dimethoxypyridine (0.136 g, 0.624 mmol), aq sodium carbonate (0.312 mL, 0.624 mmol, 2 M) and trans-dichlorobis(triphenylphosphine)palladium(II) (0.0438 g, 0.0624 mmol, Strem). Purification by preparative HPLC (Phenomenex Gemini 5 micron (Phenomenex, Torrance, Calif.), C18, 100×30 mm, 5 to 65% CH3CN(0.1% TFA)/H2O(0.1% TFA) over 20 min then 100% CH3CN(0.1% TFA) for 3 minutes at 20 mL/min) followed by conversion to the free base by loading the purified material onto a 1000 mg SCX (cation exchange resin, Radleys Discovery Technology, Essex, UK) cartridge and elution with MeOH(2M NH3)/CH2Cl2 which, after concentration, afforded the title compound (0.0318 g, 16%) as a yellow solid. MS (ESI, positive ion) m/z: 314 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.11 (s, 3H), 3.92 (s, 3H), 3.95 (s, 3H), 7.83 (d, J=9.6 Hz, 1H), 7.87 (d, J=2.0 Hz, 1H), 8.05 (d, J=9.6 Hz, 1H), 8.29 (s, 1H), 8.41 (d, J=2.0 Hz, 1H), 10.89 (s, 1H).

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