Phenol → HCID 86599006, compound

Participants

Reaction Steps

To a solution of 2-(4-(trifluoromethyl)benzyl)-8-(4-chlorophenyl)-7-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (17 mg, 0.039 mmol), prepared as described in Example 274 in DMF (0.5 mL) was added phenol (7.2 mg, 0.077 mmol), followed by K2CO3 (11 mg, 0.077 mmol). The reaction mixture was stirred at RT for 16 h, and then diluted with 1M aqueous NaOH (3 mL). A yellow precipitate was formed. The solid was collected by filtration and washed thoroughly with H2O. The crude product was purified by reverse phase HPLC to give the title compound, 2-(4-trifluoromethyl)benzyl)-8-(4-chlorophenyl)-7-phenoxy-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (12 mg, 62%) as a yellow solid. HPLC: 99% at 8.31 min (retention time) (Conditions: Zorbax SB C18 (4.6×75 mm); Eluted with 0% to 100% B, 8 min gradient. (A=90% H2O—10% MeOH—0.1% H3PO4 and B=10% H2O—90% MeOH—0.1% H3PO4); Flow rate at 2.5 mL/min. UV detection at 220 nm). MS (ES): m/z 497 [M+H]+; 1H NMR (CDCl3, 400 MHz): δ 5.25 (s, 2H), 6.99 (d, J=8 Hz, 2H), 7.21 (t, J=8 Hz, 1H), 7.37-7.44 (m, 4H), 7.54 (d, J=8 Hz, 2H), 7.61 (d, J=8 Hz, 2H), 7.79-7.82 (m, 2H), 7.90 (s, 1H).

Provenance & Evidence