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

Temperature

90 °C

To a 25 mL round-bottomed flask was added N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.750 g, 3.56 mmol), bis(pinacolato)diboron (1.18 g, 4.63 mmol, Aldrich, St. Louis, Mo.), DMSO (30.0 mL, 423 mmol) and potassium acetate (1.40 g, 14.2 mmol). The mixture was carefully evacuated and backfilled with N2. To the mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.291 g, 0.356 mmol, Strem Chemical, Inc., Newburyport, Mass.). The mixture was carefully evacuated and backfilled with N2 and then was stirred at 90° C. for 2 h. The reaction was allowed to cool to rt and treated with N-(5-bromo-2-chloropyridin-3-yl)methanesulfonamide (1.00 g, 3.50 mmol), and aq sodium carbonate (5.25 mL, 10.5 mmol, 2 M). The mixture was carefully evacuated and backfilled with N2. To the mixture was added trans-dichlorobis(triphenylphosphine)palladium(II) (0.246 g, 0.350 mmol, Strem Chemical, Inc., Newburyport, Mass.). Again, the mixture was carefully evacuated and backfilled with N2 and was stirred at 90° C. for 1 h. The reaction mixture was cooled to rt and concentrated in vacuo. The residue was taken up in 10 mL DMSO and 20 mL MeOH. The solution was filtered. The filtercake was isolated and suspended in water (50 mL) and treated with pH 4.8 buffer (25 mL, Teknova, 3 M sodium acetate solution pH adjusted to 4.8). The solution was allowed to stand for 30 minutes and then filtered. The filtercake was washed with water and then dried under vacuum to afford the title compound as a tan solid (0.415 g, 31%). MS (ESI, positive ion) m/z: 381 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.12 (s, 3H), 3.17 (s, 3H), 7.85 (d, J=9.4 Hz, 1H), 8.14 (d, J=9.4 Hz, 1H), 8.34 (s, 1H), 8.43 (s, 1H), 8.89 (s, 1H), 9.92 (s, 1H), 10.95 (s, 1H).

1. customThe mixture was carefully evacuated
2. customThe mixture was carefully evacuated
3. temperatureto cool to rt
4. customThe mixture was carefully evacuated
5. customAgain, the mixture was carefully evacuated
6. stirringwas stirred at 90° C. for 1 h
7. temperatureThe reaction mixture was cooled to rt
8. concentrationconcentrated in vacuo
9. filtrationThe solution was filtered
10. customThe filtercake was isolated
11. waitto stand for 30 minutes
12. filtrationfiltered
13. washThe filtercake was washed with water
14. customdried under vacuum

ORD record

ord-a3a84b961f614fad95a5afa31c78b5c5

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07820665B2