1-(4-Fluorophenyl)piperazine → 6-[4-(4-Fluorophenyl)piperazin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide

Participants

Reaction Steps

To a solution of 6-chloropyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.120 g, 0.532 mmol) in DMF (2.3 mL) was treated with 1-(4-fluorophenyl)piperazine (0.117 g, 0.638 mmol) in the presence of 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) (0.23 mL, 1.54 mmol) and tetra-n-butylammonium iodide (Bu4NI) (11 mg, 0.0298 mmol). The reaction mixture was heated at 75° C. to 80° C. for 15 hours, cooled to room temperature, diluted with ethyl acetate (100 mL). The organic layer was washed with water (3×10 mL), brine (3×10 mL), dried over Na2SO4, and then concentrated in vacuo. The crude product was purified by column chromatography to give the title compound as a white powder in 74% yield (0.146 g). 1H NMR (300 MHz, CDCl3) δ 8.05-7.99 (m, 2H), 7.02-6.89 (m, 5H), 3.90 (t, J=5.2 Hz, 4H), 3.55 (m, 2H), 3.23 (t, J=5.2 Hz, 4H), 1.55-1.47 (m, 2H), 0.79-0.72 (m, 1H), 0.49-0.43 (m, 2H), 0.11-0.06 (m, 2H). MS (ES+) m/z 370.3 (M+1).

Provenance & Evidence