Triethylamine → 4-[[4-fluoro-3-(4-methoxy-4-methylpiperidine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one

Participants

Reaction Conditions

Reaction Steps

O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.597 g, 1.57 mmol) was added in one portion to 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (0.188 g, 0.63 mmol) and triethylamine (0.193 mL, 1.39 mmol) in N,N-dimethylformamide (2 mL) at ambient temperature under an air atmosphere. The resulting solution was stirred at 25° C. for 15 minutes. A solution of 4-methoxy-4-methylpiperidine (23) (89.5 mg, 0.69 mmol) in N,N-dimethylformamide (1 mL) was added dropwise and the resulting solution was stirred at 25° C. for 4 hours. The crude mixture was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 21 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 the desired compound as a solid (0.110 g, 42.7%); 1H NMR (400.132 MHz, DMSO) δ 1.11 (3H, s), 1.25-1.34 (1H, m), 1.42 (1H, td), 1.56 (1H, d), 1.75 (1H, dd), 3.10-3.18 (4H, m), 4.09 (3H, q), 4.32 (2H, s), 7.21 (1H, t), 7.31 (1H, dd), 7.39-7.43 (1H, m), 7.83 (1H, td), 7.88 (1H, td), 7.96 (1H, dd), 8.27 (1H, dd), 12.57 (1H, s); m/z (LC-MS, ESI+), RT=1.79 (M+H 409).

Provenance & Evidence