Sodium Azide → HCID 70982084, compound

Participants

Reaction Steps

3-(6-(azidomethyl)pyridazin-3-yl)-N-cyclopropyl-4-fluorobenzamide. A solution of N-cyclopropyl-4-fluoro-3-(6-methylpyridazin-3-yl)benzamide (430 mg, 1.58 mmol) in 35 mL of DCE was treated with trichloroisocyanuric acid (122 mg, 0.52 mmol) and heated at 90° C. for 1.5 h. Additional trichloroisocyanuric acid (16 mg, 0.07 mmol) was added to the reaction mixture, which was heated for another 30 min at 90° C. The reaction mixture was cooled to RT and the white solid was filtered and rinsed with 2×25 mL of DCM. The filtrate was washed with 5 mL of 0.5 N NaOH followed by 5 mL of brine. The organic layer was concentrated and the residue was purified by silica gel chromatography (35-95% EtOAc in hexanes) to give 3-(6-(chloromethyl)pyridazin-3-yl)-N-cyclopropyl-4-fluorobenzamide (228 mg, 47% yield). MS (ESI, pos. ion) m/z: 306.2 (M+1). A solution of 3-(6-(chloromethyl)pyridazin-3-yl)-N-cyclopropyl-4-fluorobenzamide (228 mg, 0.75 mmol) in 1 mL of DMF and 1 mL of acetone at RT was treated with NaN3 (68 mg, 1.04 mmol) and the mixture stirred at RT for 5 h. The reaction mixture was filtered through a fritted funnel and the solid was rinsed with 2×5 mL of EtOAc. The solid was discarded and the filtrate was concentrated. The brown residue was purified by silica gel chromatography (55-75% EtOAc in hexanes) to give 3-(6-(azidomethyl)pyridazin-3-yl)-N-cyclopropyl-4-fluorobenzamide (215 mg, 92% yield) as an off white amorphous solid. MS (ESI, pos. ion) m/z: 313.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.65 (1 H, d, J=3.7 Hz), 8.46 (1 H, dd, J=7.3, 2.1 Hz), 8.15 (1 H, dd, J=8.8, 1.8 Hz), 8.07 (1 H, m), 7.90 (1 H, d, J=8.8 Hz), 7.52 (1 H, dd, J=10.5, 8.9 Hz), 4.87 (2 H, s), 2.88 (1 H, m), 0.72 (2 H, m), 0.60 (2 H, m). 19F NMR (376 MHz, DMSO-d6) δ ppm −114.48.

Provenance & Evidence