Reaction Steps
To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (100 mg, 0.20 mmol) and [2-(methyloxy)-4-(4-propyl-1-piperazinyl)phenyl]amine (Example 173, step B) (49 mg, 0.20 mmol) in 2,2,2-trifluoroethanol (1.0 mL) was added 4 M HCl in dioxane (99 μL, 0.40 mmol). The mixture was stirred and heated on a Biotage microwave at 175° C. for 35 minutes, then cooled to rt. The mixture was neutralized with 0.5M sodium methoxide in MeOH. 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 DCM, 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 (120 mg, 0.16 mmol, 85%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.75 (s, 1H), 9.36 (br s, 1H), 8.45 (s, 1H), 8.20 (d, 1H, J=5.31 Hz), 8.05 (m, 1H), 7.74 (m, 1H), 7.69 (d, 1H, J=8.97 Hz), 7.34-7.46 (m, 3H), 7.27 (d, 1H, J=8.61 Hz), 7.19 (t, 2H, J=8.06 Hz), 6.95 (t, 1H, J=6.68 Hz), 6.68 (d, 1H, J=2.01 Hz), 6.53 (d, 1H, J=5.13 Hz), 6.48 (dd, 1H, J=2.20 and 8.61 Hz), 6.24-6.30 (m, 2H), 3.80 (s, 3H), 3.11-3.16 (m, 4H), 2.45-2.54 (m, 4H), 2.28 (t, 2H, J=7.42 Hz), 1.41-1.50 (m, 4H), 0.87 (t, 3H, J=7.42 Hz). MS (ESI): 719 [M+H]+.
