反应详情

温度

80 °C

In a 10 mL vial with septum cap, 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.200 g, 0.395 mmol), 5-chloro-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (0.165 g, 0.474 mmol) were taken up in iPrOH (3 mL) and pyridinium p-toluenesulfonate (0.238 g, 0.949 mmol) was added. The vial was sealed and heated to 80° C. overnight. When reaction was complete by MS, it was cooled to rt, neutralized with 7N ammonia in MeOH, absorbed onto silica gel and flash chromatographed. Fractions containing the desired product were concentrated and the resulting solid was triturated with diethyl ether, filtered and air dried to give the title compound (0.12 g, 0.15 mmol, 37%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.71 (s, 1H), 9.38 (dd, J=4.4, 1.1 Hz, 1H), 8.53 (s, 1H), 8.25 (d, J=5.3 Hz, 1H), 8.02 (d, J=0.4 Hz, 1H), 7.87 (s, 1H), 7.63-7.79 (m, 2H), 7.28-7.50 (m, 2H), 7.10-7.28 (m, 3H), 6.97 (t, J=6.9 Hz, 1H), 6.82 (s, 1H), 6.60 (d, J=5.2 Hz, 1H), 4.23 (q, J=6.7 Hz, 2H), 3.83 (s, 3H), 3.27-3.34 (m, 2H), 3.03 (s, 3H), 2.93-3.01 (m, 4H), 2.75 (t, J=6.6 Hz, 2H), 2.51-2.64 (m, 4H), 1.40 (t, J=6.8 Hz, 3H). MS (M+H, ES+) 817.

1. customIn a 10 mL vial with septum cap
2. customThe vial was sealed
3. customWhen reaction
4. temperaturewas cooled to rt
5. customabsorbed onto silica gel and flash
6. customchromatographed
7. additionFractions containing the desired product
8. concentrationwere concentrated
9. customthe resulting solid was triturated with diethyl ether
10. filtrationfiltered
11. customair dried