Reaction Steps
To 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (260 mg, 0.57 mmol) and 4-{4-[(1S,4S)-5-(2-fluoroethyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-piperidinyl}-2-(methyloxy)aniline (200 mg, 0.57 mmol) in trifluoroethanol (2 mL) was added concentrated HCl (0.14 mL, 1.7 mmol). The reaction was heated in a sealed-tube at 85° C. for two days. After cooling to rt 0.5 N sodium methoxide in MeOH (4 mL) was added to the reaction. The solvent was removed under vacuum. DCM and silica gel were added, and the solvent removed under vacuum. The material was purified by flash chromatography. The desired fractions were combined and the solvent removed on the rotovap to give product. The material was dissolved in DCM then diethyl ether was added until the solution just turns cloudy. The solution was placed in the refrigerator. The title compound was obtained as yellow crystals which were collected by vacuum filtration, washing with ether. (120 mg, 0.15 mmol, 27% yield). 1H NMR (400 MHz, DMSO-d6) δ10.16 (s, 1H), 9.31 (brs, 1H), 8.38 (s, 1H), 8.25 (s, 1H), 8.12 (d, J=5.1 Hz, 1H), 7.97 (d, J=7.7 Hz, 1H), 7.73 (d, J=7.5 Hz, 1H), 7.64 (d, J=9.0 Hz, 1H), 7.53 (dd, J=7.9, 7.7 Hz, 1H), 7.42-7.25 (m, 3H), 7.12 (dd, J=8.1, 8.1 Hz, 2H), 6.89 (dd, J=6.6, 6.6 Hz, 1H), 4.34 (dt, J=47.6, 4.9 Hz, 2H), 3.71 (s, 3H), 3.52 (d, J=11.7 Hz, 2H), 3.39 (s, 1H), 3.17 (s, 1H), 2.82-2.54 (m, 6H), 2.51 (d, J=9.3 Hz, 1H), 2.42-2.30 (m under DMSO peak, 2H), 1.78 (d, J=11.9 Hz, 1H), 1.69 (d, J=11.9 Hz, 1H), 1.50 (d, J=8.8 Hz, 1H), 1.42 (d, J=8.8 Hz, 1H), 1.38-1.25 (m, 2H).
