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

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (0.075 g, 0.15 mmol), 5-methyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (0.058 g, 0.15 mmol) and para-toluenesulfonic acid (0.070 g, 0.37 mmol) in i-PrOH (5 mL) was heated in a microwave at 175° C. for 25 min. The reaction mixture was concentrated onto silica gel and purified by flash chromatography. Recrystallization from DCM and diethyl ether afforded N-(2,6-difluorophenyl)-5-(3-{2-[(5-methyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide (0.038 g, 30%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.80 (s, 1H), 9.33-9.43 (m, 1H), 8.47 (s, 1H), 8.25 (d, J=5.2 Hz, 1H), 8.08-8.14 (m, 1H), 7.76-7.84 (m, 1H), 7.71 (d, J=9.0 Hz, 1H), 7.34-7.55 (m, 3H), 7.30 (d, J=8.7 Hz, 1H), 7.15-7.25 (m, 2H), 6.97 (t, J=6.8 Hz, 1H), 6.76 (s, 1H), 6.57 (d, J=5.1 Hz, 1H), 4.00 (s, 3H), 3.80 (s, 3H), 3.06-3.19 (m, 6H), 2.88 (s, 3H), 2.59-2.72 (m, 6H), 2.38-2.44 (m, 1H), 2.16 (s, 3H), 1.80-1.91 (m, 2H), 1.50-1.71 (m, 2H). MS (M+2H, ES+) 839.

Provenance & Evidence