6-bromo-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1 (2H)-one (98) (0.2 g, 0.42 mmol), diphenylmethanimine (0.076 g, 0.42 mmol) and cesium carbonate (0.275 g, 0.84 mmol) were added to dioxane (15 mL) and the system was degassed using nitrogen. To this was added diacetoxypalladium (0.019 g, 0.08 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.073 g, 0.13 mmol), the reaction was heated at 95° C. for 2 hours. The reaction mixture was quenched with water (50 mL), extracted with EtOAc (3×50 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford brown gum. This was stirred with 2.0N HCl (5.0 mL) for 1 hour, the reaction mixture was quenched with 2M NaOH (10 mL), extracted with EtOAc (3×15 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford brown gum. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (0.024 g, 13.87%); 1H NMR (500.133 MHz, DMSO) δ 1.47-1.38 (2H, m), 1.82-1.73 (2H, m), 2.89 (3H, s), 3.23-3.16 (2H, m), 3.27 (2H, s), 3.46-3.41 (1H, m), 4.13 (2H, s), 5.78 (2H, s), 6.87 (1H, d), 7.00 (1H, dd), 7.14 (1H, t), 7.22 (1H, dd), 7.38-7.34 (1H, m), 7.93 (1H, d), 11.60 (1H, s); m/z (LC-MS, ESI+), RT=1.56 (M+H 411).
