p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-5-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(4-morpholinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}-2-(methyloxy)benzamide

Participants

Reaction Conditions

Reaction Steps

5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (100 mg, 0.2 mmol), 5-fluoro-2-(methyloxy)-4-[2-(4-morpholinyl)ethyl]aniline (46 mg, 0.18 mmol), and p-toluenesulfonic acid (92 mg, 0.49 mmol) were weighed into a 10 mL microwave vial. 5 mL of iPrOH was added and the mixture was heated in the microwave to 180° C. for 17 min. The mixture was transferred to a 50 mL round bottom and neutralized with 1 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography, followed by MeOH re-crystallization to give the title compound (61 mg, 0.086 mmol, 47%). 1H NMR (400 MHz, CDCl3) δ ppm 9.51 (d, J=6.97 Hz, 1H), 9.28 (s, 1H), 8.61 (d, J=2.20 Hz, 1H), 8.24-8.32 (m, 2H), 7.88 (dd, J=8.62, 2.38 Hz, 1H), 7.78 (s, 1H), 7.71 (d, J=8.80 Hz, 1H), 7.32-7.39 (m, 1H), 7.16-7.23 (m, 1H), 7.14 (d, J=8.80 Hz, 1H), 6.90-7.00 (m, 3H), 6.74 (d, J=6.60 Hz, 1H), 6.69 (d, J=5.13 Hz, 1H), 4.12 (s, 3H), 3.91 (s, 3H), 3.73-3.80 (m, 4H), 2.78-2.86 (m, 2H), 2.58-2.65 (m, 2H), 2.52-2.58 (m, 4H). MS (ESI): 710 [M+H]+.

Provenance & Evidence