Into a 25-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed 6-[bis(4-chlorophenyl)methyl]-4-bromoquinolin-2-ol (300 mg, 0.65 mmol, 1.00 equip, 99%), ethyl 4-(4-aminopiperidin-1-yl)-4-oxobutanoate (295.1 mg, 0.97 mmol, 1.50 equip), Pd2(dba)3 (60 mg, 0.06 mmol, 0.10 equip, 99%), dppf (126.7 mg, 0.23 mmol, 0.35 equip, 99%), Cs2CO3 (532.7 mg, 1.62 mmol, 2.50 equip, 99%), t-BuOK (146.4 mg, 1.29 mmol, 2.00 equip, 99%), and 1,4-dioxane (9 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting solution was diluted with water (80 mL). The resulting solution was extracted with ethyl acetate (3×80 mL) and the organic layers combined. The resulting mixture was washed with water (1×80 mL) and brine (1×80 mL). The resulting mixture was dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The resulting residue was purified by Prep-HPLC with the following conditions: Column, Sunfire Prep C18 OBD 5 μm, 19×150 mm; mobile phase, Phase A: water (0.05% NH4HCO3), Phase B:CH3CN (20% CH3CN up to 80% in 8 min, up to 100% for 0.1 min, hold 100% in 1.9 min, down to 20% in 0.1 min, hold 20% in 1.9 min); Detector, UV 220 & 254 nm to yield ethyl 4-[4-([6-[bis(4-chlorophenyl)methyl]-2-hydroxyquinolin-4-yl]amino)piperidin-1-yl]-4-oxobutanoate as a white solid.
