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

Participants

Reaction Conditions

Reaction Steps

3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (100 mg, 0.21 mmol), 2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (60 mg, 0.19 mmol), and p-toluenesulfonic acid (98 mg, 0.51 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 130° C. for 72 h. The mixture was transferred to a 50 mL round bottom and neutralized with 2 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 to give the title compound (67 mg, 0.091 mmol, 46%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.23 (s, 1H), 9.39 (d, J=2.01 Hz, 1H), 8.46 (s, 1H), 8.32 (s, 1H), 8.19 (s, 1H), 8.01-8.07 (m, 1H), 7.78-7.83 (m, 1H), 7.68-7.75 (m, 1H), 7.56-7.63 (m, 1H), 7.36-7.47 (m, 3H), 7.16-7.23 (m, 2H), 6.93-7.01 (m, 1H), 6.67 (s, 1H), 6.45 (d, J=4.40 Hz, 2H), 3.79 (s, 3H), 3.31-3.36 (m, 2H), 3.10-3.18 (m, 4H), 3.03 (s, 3H), 2.71-2.78 (m, 2H), 2.53-2.61 (m, 4H). MS (ESI): 739 [M+H]+.

Provenance & Evidence