4-propan-2-yloxypiperidine;hydrochloride

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-isopropoxypiperidine hydrochloride (192 mg, 1.07 mmol) and triethylamine (0.327 mL, 2.35 mmol) in N,N-dimethylformamide (3 mL) was added in one portion to a stirred solution of 4-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)picolinic acid (5)(300 mg, 1.07 mmol), triethylamine (0.327 mL, 2.35 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (607 mg, 1.60 mmol) in DMF (3 mL) at 25° C. 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, 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 and lyophilised to afford the desired compound as a solid (257 mg, 59.3%); 1H NMR (400.132 MHz, DMSO) δ 1.08 (6H, dd), 1.28-1.46 (2H, m), 1.65-1.74 (1H, m), 1.78-1.87 (1H, m), 3.12 (1H, ddd), 3.23-3.31 (1H, m), 3.42-3.51 (1H, m), 3.62 (1H, m), 3.69 (1H, quintet), 3.91-4.00 (1H, m), 4.40 (2H, s), 7.39 (1H, dd), 7.49 (1H, d), 7.83-7.97 (3H, m), 8.28 (1H, dd), 8.46-8.49 (1H, m), 12.60 (1H, s); m/z (LC-MS, ESI+), RT=1.54 (M+H 407). The crude mixture was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 30 mm diameter, 100 mm length) Fractions containing the desired compound were evaporated to dryness

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-isopropoxypiperidine hydrochloride (120 mg, 0.67 mmol) and triethylamine (0.206 mL, 1.48 mmol), in N,N dimethylformamide (2 mL) was added in one portion to a stirred solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (200 mg, 0.67 mmol), triethylamine (0.206 mL, 1.48 mmol) and O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (381 mg, 1.01 mmol) in N,N dimethylformamide (2 mL) at 25° C. The resulting solution was stirred at 25° C. for 4 hours. The crude product 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 (172 mg, 60.6% yield); 1H NMR (399.902 MHz, DMSO) δ 1.06-1.11 (6H, m), 1.21-1.46 (2H, m), 1.61-1.87 (2H, m), 3.04 (1H, t), 3.62 (2H, td), 3.70 (1H, quintet), 3.92-4.01 (1H, m), 4.07 (1H, q), 4.33 (2H, s), 7.19-7.25 (1H, m), 7.32-7.37 (1H, m), 7.38-7.44 (1H, m), 7.81-7.92 (2H, m), 7.96-8.00 (1H, m), 8.26-8.29 (1H, m), 12.58 (1H, s); m/z (LC-MS, ESI+), RT=1.98 (M+H 424.6). The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 30 mm diameter, 100 mm length) Fractions containing the desired compound were evaporated to dryness

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-isopropoxypiperidine hydrochloride (192 mg, 1.07 mmol) and triethylamine (0.327 mL, 2.35 mmol) in N,N-dimethylformamide (3 mL) was added in one portion to a stirred solution of 4-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)picolinic acid (5)(300 mg, 1.07 mmol), triethylamine (0.327 mL, 2.35 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (607 mg, 1.60 mmol) in DMF (3 mL) at 25° C. 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, 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 and lyophilised to afford the desired compound as a solid (257 mg, 59.3%); 1H NMR (400.132 MHz, DMSO) δ 1.08 (6H, dd), 1.28-1.46 (2H, m), 1.65-1.74 (1H, m), 1.78-1.87 (1H, m), 3.12 (1H, ddd), 3.23-3.31 (1H, m), 3.42-3.51 (1H, m), 3.62 (1H, m), 3.69 (1H, quintet), 3.91-4.00 (1H, m), 4.40 (2H, s), 7.39 (1H, dd), 7.49 (1H, d), 7.83-7.97 (3H, m), 8.28 (1H, dd), 8.46-8.49 (1H, m), 12.60 (1H, s); m/z (LC-MS, ESI+), RT=1.54 (M+H 407). The crude mixture was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 30 mm diameter, 100 mm length) Fractions containing the desired compound were evaporated to dryness

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-isopropoxypiperidine hydrochloride (120 mg, 0.67 mmol) and triethylamine (0.206 mL, 1.48 mmol), in N,N dimethylformamide (2 mL) was added in one portion to a stirred solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (200 mg, 0.67 mmol), triethylamine (0.206 mL, 1.48 mmol) and O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (381 mg, 1.01 mmol) in N,N dimethylformamide (2 mL) at 25° C. The resulting solution was stirred at 25° C. for 4 hours. The crude product 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 (172 mg, 60.6% yield); 1H NMR (399.902 MHz, DMSO) δ 1.06-1.11 (6H, m), 1.21-1.46 (2H, m), 1.61-1.87 (2H, m), 3.04 (1H, t), 3.62 (2H, td), 3.70 (1H, quintet), 3.92-4.01 (1H, m), 4.07 (1H, q), 4.33 (2H, s), 7.19-7.25 (1H, m), 7.32-7.37 (1H, m), 7.38-7.44 (1H, m), 7.81-7.92 (2H, m), 7.96-8.00 (1H, m), 8.26-8.29 (1H, m), 12.58 (1H, s); m/z (LC-MS, ESI+), RT=1.98 (M+H 424.6). The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 30 mm diameter, 100 mm length) Fractions containing the desired compound were evaporated to dryness