反应详情

温度

85 °C

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (19.7 g, 39.9 mmol) and 2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (13.6 g, 39.9 mmol) in 2,2,2-trifluoroethanol (200 mL) was added HCl (4M in dioxane) (19.97 mL, 80 mmol). The reaction mixture was heated at 85° C. for 2 days. The reaction was determined to be complete by LCMS. The reaction was cooled and quenched with solid NaOMe. The suspension was concentrated. Purification by flash chromatography, followed by trituration with EtOH provided the title compound of Step H (18.1 g, 22.7 mmol, 57% yield). Alternatively, this reaction can be effected using microwave irradiation. Additionally, further purification of the title compound can be effected by recrystallization from equal parts DCM and EtOH. 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.37 (d, J=6.0 Hz, 1H), 8.38 (s, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.12 (s, 1H), 7.64-7.83 (m, 2H), 7.55 (s, 1H), 7.35-7.52 (m, 2H), 7.29 (d, J=8.6 Hz, 1H), 7.20 (t, J=8.0 Hz, 2H), 6.96 (t, J=6.6 Hz, 1H), 6.75 (s, 1H), 6.59 (d, J=5.0 Hz, 1H), 3.92-4.15 (m, 5H), 3.11-3.27 (m, 2H), 2.91-3.11 (m, 5H), 2.61 (t, 2H), 2.15 (s, 3H), 1.62-1.87 (m, 4H), 1.42-1.57 (m, 1H), 1.21-1.42 (m, 5H). MS (M+H, ES+) 796.

1. temperatureThe reaction was cooled
2. customquenched with solid NaOMe
3. concentrationThe suspension was concentrated
4. customPurification by flash chromatography