Reaction Steps
To 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (120 mg, 0.25 mmol) and 4-(1,4′-bipiperidin-1′-yl)-2-(methyl)aniline (68 mg, 0.25 mmol) in iPrOH (2 mL) in a microwave vial was added p-toluenesulfonic acid monohydrate (110 mg, 0.60 mmol). The reaction was heated in a microwave at 175° C. for 800 seconds. After cooling to rt, the solvent was removed on a rotovap and the residue taken up in DCM. 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 dissolved in DCM, and ether was added until the solution just turned cloudy. After two days, the solids were collected by vacuum filtration and washed with diethyl ether. The yellow crystals were separated from the beige powder using tweezers. The desired product was obtained as yellow crystals (23 mg, 0.033 mmol, 13% yield). 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.35 (br s, 1H), 8.81 (s, 1H), 8.32 (s, 1H), 8.16 (d, J=5.4 Hz, 1H), 8.06 (d, J=7.9 Hz, 1H), 7.82 (d, J=7.7 Hz, 1H), 7.71 (d, J=9.0 Hz, 1H), 7.62 (dd, J=7.9, 7.7 Hz, 1H), 7.48-7.34 (m, 2H), 7.25-7.14 (m, 3H), 6.85 (br s, 1H), 6.85 (s, 1H), 6.79 (dd, J=8.6, 2.6 Hz, 1H), 6.43 (d, J=5.3 Hz, 1H), 3.72 (d, J=12.5 Hz, 2H), 2.62 (dd, J=12.1, 10.6 Hz, 2H), 2.52-2.27 (m, 5H), 2.17 (s, 3H), 1.78 (d, J=11.8 Hz, 2H), 1.60-1.34 (m, 8H). MS (ESI) m/z=699 [M+1].
