Reaction Steps
To 3-[3-(2-chloro-4-pyrimidinyl)-8-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)benzamide (Example 188, step A) (90 mg, 0.19 mmol) and 2-(methyloxy)-4-(4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}-1-piperidinyl)aniline (Example 60, step B) (74 mg, 0.19 mmol) in 2,2,2-trifluoroethanol (0.90 mL) was added 4 M hydrochloric acid in dioxane (94 μL, 0.38 mmol). The mixture was stirred and heated on a microwave at 175° C. for 40 minutes, then cooled to room temperature. The mixture was neutralized with 0.5M sodium methoxide in methanol. The mixture was concentrated under vacuum and the residue purified by silica gel chromatography to give a yellow oil. The oil was dissolved in minimal dichloromethane, then hexane was added until a precipitate was formed. The slurry was cooled at −10° C. for 30 minutes, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (110 mg, 0.13 mmol, 71%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ10.27 (s, 1H), 9.20 (brs, 1H), 8.52 (s, 1H), 8.34 (s, 1H), 8.24 (d, 1H, J=5.13 Hz), 8.07 (d, 1H, J=7.70 Hz), 7.83 (d, 1H, J=7.88 Hz), 7.62 (t, 1H, J=7.70 Hz), 7.34-7.45 (m, 3H), 7.21 (t, 2H, J=8.06 Hz), 6.92-6.99 (m, 1H), 6.65-6.68 (m, 1H), 6.45-6.50 (m, 2H), 3.79 (s, 3H), 3.68-3.75 (m, 2H), 3.19-3.30 (m, 2H), 3.02 (s, 3H), 2.61-2.70 (m, 6H), 2.38-2.46 (m, 6H), 2.26-2.34 (m, 1H), 1.80-1.87 (m, 2H), 1.45-1.56 (m, 2H). MS (ESI): 840 [M+H]+.
