Reaction Steps
O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (509 mg, 1.34 mmol) was added, in one portion, to 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (200 mg, 0.67 mmol) and triethylamine (0.206 mL, 1.48 mmol) in N,N-dimethylformamide (2.5 mL), at 25° C. under an air atmosphere. The resulting solution was stirred at 25° C. for 10 minutes. A solution of 4-((tetrahydrofuran-2-yl)methoxy)piperidine hydrochloride (164 mg, 0.74 mmol) and triethylamine (0.206 mL, 1.48 mmol) in N,N-dimethylformamide (1 mL) was then added dropwise and the resulting solution stirred at 25° C. for 10 hours. The crude mixture was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 30 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 compound as a solid (238 mg, 76%); 1H NMR (400.132 MHz, DMSO) δ 1.01 (2H, dt), 1.31-1.37 (1H, m), 1.43-1.50 (1H, m), 1.51-1.58 (1H, m), 1.68-1.73 (1H, m), 1.74-1.93 (4H, m), 3.00-3.07 (1H, m), 3.17-3.18 (1H, m), 3.39 (2H, d), 3.53-3.59 (1H, m), 3.70-3.75 (1H, m), 3.90 (2H, ddd), 4.33 (2H, s), 7.21 (1H, t), 7.33-7.35 (1H, m), 7.39-7.43 (1H, m), 7.83 (1H, td), 7.89 (1H, td), 7.97 (1H, d), 8.27 (1H, dd), 12.56 (1H, s) m/z (LC-MS, ESI+), RT=1.71 (M+H 466.5).
