反应详情

温度

175 °C

To 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (100 mg, 0.22 mmol) and [2-(methyloxy)-4-(4-propyl-1-piperazinyl)phenyl]amine (54 mg, 0.22 mmol) in 2,2,2-trifluoroethanol (1.1 mL) was added 4 M HCl in dioxane (108 μL, 0.43 mmol). The mixture was stirred and heated on a Biotage microwave at 175° C. for 35 min, 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 min, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (103 mg, 0.15 mmol, 70%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ10.24 (s, 1H), 9.40 (brs, 1H), 8.46 (s, 1H), 8.33 (s, 1H), 8.20 (d, 1H, J=5.13 Hz), 8.05 (d, 1H, J=7.69 Hz), 7.82 (d, 1H, J=7.69 Hz), 7.73 (d, 1H, J=8.97 Hz), 7.61 (t, 1H, J=7.78 Hz), 7.36-7.49 (m, 3H), 7.21 (t, 2H, J=8.15 Hz), 6.98 (t, 1H, J=6.87 Hz), 6.68 (d, 1H, J=2.20 Hz), 6.45-6.50 (m, 2H), 3.80 (s, 3H), 3.12-3.17 (m, 4H), 2.45-2.55 (m, 4H), 2.28 (t, 2H, J=7.42 Hz), 1.47 (q, 2H, J=7.39 Hz), 0.87 (T, 3H, J=7.32 Hz). MS (ESI): 675 [M+H]+.

1. temperaturecooled to rt
2. concentrationThe mixture was concentrated under vacuum
3. customthe residue purified by silica gel chromatography
4. customto give a yellow oil
5. customwas formed
6. temperatureThe slurry was cooled at −10° C. for 30 min
7. filtrationfilter
8. washwashing the solids with cold hexanes
9. customThe solids were dried under vacuum