p-Toluenesulfonic acid → N-(2,6-difluorophenyl)-2-(methyloxy)-5-{3-[2-({2-(methyloxy)-4-[3-(1-piperidinyl)propyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}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) (120 mg, 0.24 mmol), 2-(methyloxy)-4-[3-(1-piperidinyl)propyl]aniline (Example 139, step D) (55 mg, 0.22 mmol), and p-toluenesulfonic acid (111 mg, 0.59 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 120° C. for 40 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 (54 mg, 0.077 mmol, 35%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.77 (s, 1H), 9.36 (s, 1H), 8.49 (s, 1H), 8.24 (s, 1H), 8.10 (s, 1H), 7.76 (s, 1H), 7.68 (s, 1H), 7.63 (s, 1H), 7.34-7.45 (m, J=17.58 Hz, 2H), 7.27 (s, 1H), 7.12-7.21 (m, 2H), 6.91-6.98 (m, 2H), 6.74 (s, 1H), 6.59 (s, 1H), 3.97 (s, 3H), 3.81 (s, 3H), 2.51-2.59 (m, 2H), 2.19-2.31 (m, 6H), 1.67-1.77 (m, 2H), 1.42-1.50 (m, 4H), 1.30-1.39 (m, 2H). MS (ESI): 704 [M+H]+.

Provenance & Evidence