Benzyl Alcohol → 2-(4-(Trifluoromethyl)benzyl)-8-(benzyloxy)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Participants

Reaction Steps

To a solution of 2-(4-(trifluoromethyl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (20 mg, 46 μmol), prepared as described in Example 361, in 1-methylpyrrolidone (1 mL) in a 1 dram vial was added benzyl alcohol (10.8 mg, 100 μmol), and 1M solution of potassium t-butoxide in THF (100 uL). The reaction vessel was capped and stirred at room temperature for 16 h. Reaction mixture was quenched with 100 uL of methanol, filtered through a Whatman 0.45 μm syringe filter and the crude product was purified using preparative HPLC (Xterra MS-C18, 30×50 mm); Eluted with 10% to 100% B, 8 min gradient, (A=water+0.1% TFA and B=acetonitrile+0.1% TFA); Flow rate at 30 mL/min. UV detection at 220 nm) to give the title compound 2-(4-(Trifluoromethyl)benzyl)-8-(benzyloxy)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one. (4.9 mg, 16% yield), as a yellow crystalline solid. MS (M+H)=511; 1H NMR MeOD: δ 8.25 (1H, s), 7.60-7.7 (4H, m), 7.47-7.55 (4H, m), 7.13-7.31 (5H, m), 5.81 (2H, s), 5.39 (2H, s). Analytical HPLC purity: 99% at 2.31 min (retention time), (Xterra MS-C18, 4.6×50 mm); Eluted with 10% to 100% B, 4.5 min gradient, (A=water+0.1% TFA and B=acetonitrile+0.1% TFA); Flow rate at 2.5 mL/min. UV detection at 220 nm.

Provenance & Evidence