Reaction Steps
A round bottom flask equipped with a drying tube was charged with 4-piperidin-4-yl-morpholine (0.21 g, 1.2 mmol), cupric acetate (0.34 g, 1.9 mmol), 4-bromobenzeneboronic acid (0.50 g, 2.5 mmol), pyridine (0.20 mL, 2.5 mmol) and dichloromethane (5 mL, 80 mmol). The blue suspension was stirred open to the air for 6 days at room temperature. Water (25 mL) was added to the green-brown suspension and stirred for 10 minutes. The mixture was extracted with ethyl acetate (3×25 mL). The combined organic layer was washed with saturated aqueous sodium chloride (25 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified via chromatography using silica gel column (40 g) and 0%→8% methanol: dichloromethane solvent gradient. 4-[1-(4-Bromo-phenyl)-piperidin-4-yl]-morpholine was isolated as a tan solid (0.168 g, 41%). MP=146-149° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.32 (d, J=7.5 Hz, 2H), 6.79 (d, J=7.8 Hz, 2H), 3.76-3.71 (m, 4H), 3.68 (d, J=12.8 Hz, 2H), 2.71 (t, J=12.3 Hz, 2H), 2.60-2.54 (m, 4H), 2.37-2.27 (m, 1H), 1.93 (d, J=11.3 Hz, 2H), 1.69-1.58 (m, 2H). MS=325, 327 (MH)+. 49b) [8-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-amine was prepared from 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (50.0 mg, 0.173 mmol) and 4-[1-(4-bromo-phenyl)-piperidin-4-yl]-morpholine (65.0 mg, 0.200 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (20.0 mg, 0.0366 mmol) as the ligand in a manner analogous to Step 2d. The title compound was isolated as a yellow solid (0.044 g, 48%). MP=253-254° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.47 (d, J=6.3 Hz, 1H), 8.23 (d, J=7.5 Hz, 2H), 8.08 (d, J=8.2 Hz, 2H), 7.63 (d, J=7.3 Hz, 1H), 7.47 (d, J=7.1 Hz, 2H), 7.01-6.95 (m, 3H), 6.68 (s, 1H), 3.77-3.72 (m, 4H), 3.69-3.62 (m, 2H), 3.10 (s, 3H), 2.74-2.65 (m, 2H), 2.62-2.57 (m, 4H), 2.36-2.28 (m, 1H), 1.98-1.92 (m, 2H), 1.75-1.63 (m, 2H). MS=533 (MH)+.
