Triethylamine → 4-(4-fluoro-3-(4-(2-methoxyethoxy)piperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

Participants

Reaction Steps

A solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (150 mg, 0.50 mmol) in N,N-dimethylacetamide (4 mL) was treated with 4-(2-methoxyethoxy)piperidine hydrochloride (103 mg, 0.53 mmol) and triethylamine (0.210 mL, 1.51 mmol). O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (253 mg, 0.67 mmol) was added and the resulting solution was stirred at ambient temperature for 4.5 hours. The crude reaction mixture was filtered before being 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 and lyophilised to afford a gum, which was taken up in a small amount of diethyl ether and dichloromethane and allowed to evaporate before drying under vacuum, at 55° C., for 2 hours to afford the desired compound as a white solid (151 mg, 68.3% yield); 1H NMR (400.132 MHz, DMSO) δ 1.28-1.36 (1H, m), 1.40-1.49 (1H, m), 1.68-1.75 (1H, m), 1.82-1.90 (1H, m), 2.99-3.06 (1H, m), 3.25 (3H, s), 3.26-3.32 (2H, m), 3.44 (2H, t), 3.53-3.58 (3H, m), 3.90-3.98 (1H, m), 4.33 (2H, s), 7.21 (1H, t), 7.33-7.35 (1H, m), 7.39-7.43 (1H, m), 7.81-7.91 (2H, m), 7.97 (1H, d), 8.27 (1H, dd), 12.56 (1H, s); m/z (LC-MS, ESI+), RT=1.65 (M+H 440.6).

Provenance & Evidence