Into a 100 mL round-bottomed flask was added 1-(6-(6-(2,4-difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanone (1.04 g, 2.73 mmol) and THF (20 mL) to give an off-white suspension. The reaction suspension was cooled to about −30° C. Then methylmagnesium chloride (3 M in THF, 3.65 mL, 10.9 mmol) was added over about 5 min. The reaction was stirred at about −30° C. for about 30 min. A saturated solution of NH4Cl (50 mL) was slowly added to the reaction suspension, followed by the addition of DCM (50 mL). The layers were partitioned and the aqueous solution was extracted with DCM (2×50 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and the solvents removed under reduced pressure to give the title compound (0.86 g, 79%). The product was combined with other product from additional reactions (7.5 g total) and the material was purified by flash chromatography (40 g RediSep® silica gel; DCM/MeOH 1:0 to 9:1) to give an off-white solid. The material was dissolved in DMSO (35 mL) at about 80° C. and then cooled to about 0° C. Then water (200 mL) was added to form a precipitate that was collected by filtration. The filter pad was washed with water and then triturated with 1-propanol using sonication and the solid collected by filtration. The solid was further triturated with 1-propanol using sonication and the solid collected by filtration and then dried in a vacuum oven at about 80° C. to give the title compound (5.05 g, 67% recovery). LC/MS (Table 1, Method g) Rt=1.78 min; MS m/z: 398.2 (M+M)+. 1H NMR (DMSO-d6) δ 8.53 (d,), 8.26 (m, 2H), 7.76 (m, 1H), 7.55-7.24 (m, 2H), 6.93 (m, 1H), 5.77 (s, 1H), 2.58-2.50 (m, 4H), 1.79 (s, 6H). mp 258-260° C.; Anal. calcd. for C19H14F2N6O2: C, 57.58; H, 3.56; N, 21.20; F, 9.59. found C, 57.42; H, 3.36; N, 21.22; F, 9.28.
