反应详情

温度

80 °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) (200 mg, 0.407 mmol) and (5-methyl-2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amine (200 mg, 0.586 mmol) (Example 248, Step B) in trifluoroethanol (10 mL) was added p-toluene sulfonic acid (200 mg, 1.05 mmol), and the vial was sealed and heated to 80° C. overnight. The reaction was then cooled to rt and silica was added. The solvent was removed on a rotovap and the product purified on a 12 g ISCO column. Desired fractions were combined and rotovaped down. The resulting foam was dissolved in DCM and ether was added to provide the title compound (100 mg, 0.125 mmol, 31%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.74 (s, 1H), 9.33 (d, J=7.1 Hz, 1H), 8.32 (s, 1H), 8.23 (d, J=5.3 Hz, 1H), 8.08 (s, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.6 Hz, 1H), 7.53 (s, 1H), 7.43-7.33 (m, 2H), 7.25 (d, J=8.4 Hz, 1H), 7.15 (t, J=8.0 Hz, 2H), 6.92 (t, J=6.9 Hz, 1H), 6.71 (s, 1H), 6.56 (d, J=5.3 Hz, 1H), 4.03 (q, J=6.8 Hz, 2H), 3.95 (s, 3H), 3.36-3.25 (m, 2H), 3.03 (s, 3H), 2.86-2.78 (m, 4H), 2.74 (t, J=6.7 Hz, 2H), 2.63-2.50 (m, 4H), 2.11 (s, 3H), 1.22 (t, J=7.0 Hz, 3H). MS (ESI) m/z=398 [M+2H]+2.

1. customthe vial was sealed
2. temperatureThe reaction was then cooled to rt
3. additionsilica was added
4. customThe solvent was removed on a rotovap
5. customthe product purified on a 12 g ISCO column
6. dissolutionThe resulting foam was dissolved in DCM
7. additionether was added