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-[(1-methylethyl)oxy]benzamide (Intermediate Example 7) (200 mg, 0.385 mmol) and (5-methyl-2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amine (Example 248, Step B) (200 mg, 0.586 mmol) 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 (110 mg, 0.133 mmol, 35%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 9.70 (s, 1H), 9.34 (d, J=7.0 Hz, 1H), 8.35 (s, 1H), 8.27 (d, J=5.2 Hz, 1H), 8.07 (s, 1H), 7.75-7.73 (m, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.56 (s, 1H), 7.46-7.34 (m, 2H), 7.29 (d, J=8.8 Hz, 1H), 7.19 (t, J=8.0 Hz, 2H), 6.95 (t, J=7.1 Hz, 1H), 6.74 (s, 1H), 6.61 (d, J=5.2 Hz, 1H), 4.91-4.81 (m, 1H), 4.08 (q, J=7.0 Hz, 2H), 3.39-3.28 (m, 2H), 3.06 (s, 3H), 2.88-2.81 (m, 4H), 2.77 (t, J=6.8 Hz, 2H), 2.67-2.53 (m, 4H), 2.13 (s, 3H), 1.39 (d, J=5.8 Hz, 6H), 1.25 (t, J=7.0 Hz, 3H). MS (ESI) m/z=412 [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