Reaction Steps
To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (238 mg, 0.50 mmol) and 4-[1-(2-fluoroethyl)-4-piperidinyl]-2-(methyloxy)aniline (140 mg, 0.50 mmol) in iPrOH (1 mL) in a microwave vial was added p-toluenesulfonic acid monohydrate (190 mg, 1.0 mmol). The reaction was heated in a microwave at 175° C. for 1000 seconds. After cooling to rt the material was transferred to another flask, rinsing with a solution of DCM/MeOH. Silica gel was added and the solvent removed on the rotovap. The preabsorbed solids were purified by flash chromatography. The desired fractions were combined and the solvent removed on the rotovap to give product contaminated with an impurity. The material was placed under vacuum for 3 days then triturated with diethyl ether. The desired product was obtained as a white solid (23 mg, 0.033 mmol, 6.6% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.35 (d, J=6.2 Hz, 1H), 8.47 (s, 1H), 8.22 (d, J=5.1 Hz, 1H), 8.08, (s, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.71-7.60 (m, 2H), 7.42 (dd, J=8.4, 7.3 Hz, 1H), 7.35 (dd, J=7.1, 6.6 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 7.15 (dd, J=8.1, 7.9 Hz, 2H), 6.97-6.90 (m, 2H), 6.77 (d, J=8.2 Hz, 1H), 6.56 (d, J=5.1 Hz, 1H), 4.51 (dt, J=48.0, 4.8 Hz, 2H), 3.95, (s, 3H), 3.80 (s, 3H), 2.97 (d, J=11.0 Hz, 2H), 2.60 (dt, J=28.2, 4.8 Hz, 2H), 2.08 (dd, J=11.5, 8.8 Hz, 2H), 1.77-1.59 (m, 4H). MS (ESI) m/z=708 [M+1].
