p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-3-(3-{2-[(5-methyl-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) (90 mg, 0.195 mmol), 5-methyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (57 mg, 0.175 mmol), and p-toluenesulfonic acid (89 mg, 0.47 mmol) were weighed into a 20 mL vial. 10 mL of iPrOH was added and the mixture was heated to 120° C. for 48 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 (65 mg, 0.086 mmol, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.22 (s, 1H), 9.39 (s, 1H), 8.46 (s, 1H), 8.32 (s, 1H), 8.22 (d, J=5.31 Hz, 1H), 8.04 (d, J=7.69 Hz, 1H), 7.80 (d, J=7.87 Hz, 1H), 7.72 (d, J=8.97 Hz, 1H), 7.59 (t, J=7.69 Hz, 1H), 7.42-7.51 (m, 2H), 7.34-7.42 (m, 1H), 7.13-7.23 (m, 2H), 6.97 (t, J=6.68 Hz, 1H), 6.75 (s, 1H), 6.48 (d, J=5.31 Hz, 1H), 3.79 (s, 3H), 3.30-3.35 (m, 2H), 3.05 (s, 3H), 2.82-2.90 (m, 4H), 2.76 (t, J=6.68 Hz, 2H), 2.53-2.64 (m, 4H), 2.13 (s, 3H). MS (ESI): 753 [M+H]+.

Provenance & Evidence