4-Fluorobenzaldehyde → HCID 46893453, compound

Participants

Reaction Steps

(Polystyrylmethyl)trimethylammonium cyanoborohydride (4.1 mmol/g, 125 mg, 0.510 mmol) was added to 6-(piperazin-1-yl)-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine (100 mg, 0.365 mmol) and 4-fluorobenzaldehyde (63 mg, 0.510 mmol) in 10% acetic acid in DCM (2.2 mL). The resulting mixture was stirred at ambient temperature for 16 hours, then the resin removed by filtration and the solvents evaporated. The crude product was 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% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to give 6-[4-(4-fluorobenzyl)piperazin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (85 mg, 61%) as a solid. 1H NMR (399.9 MHz, DMSO-d6) δ 2.44 (4H, m), 2.88 (2H, t), 3.13 (2H, t), 3.52 (6H, m), 7.16 (2H, m), 7.36 (2H, m); m/z=383 [M+H]+.

Provenance & Evidence