Sodium Carbonate → 2-(4-(isoxazol-5-yl)benzyl)-7-(4-chlorophenyl)-8-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Participants

Reaction Steps

To a stirred solution of 2-(4-(isoxazol-5-yl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (100 mg, 0.23 mmol), prepared as described in Example 355 in toluene (2 mL) in a round bottomed flask was added Pd(PPh3)4 (16 mg, 0.014 mmol) under bubbling argon. Phenyl boronic acid (36 mg, 0.3 mmol) was added subsequently. Under vigorous stirring, Na2CO3 (97 mg, 0.91 mmol) pre-dissolved in water (0.25 mL) was added to the suspension. Argon was bubbled through this suspension for 10 min before the flask was placed in an oil bath preheated at 120° C. The reaction was stirred at reflux for 6 days. The reaction was then allowed to cool to RT. After this time, the reaction mixture was poured into water (10 mL). The resultant solution was extracted with EtOAc (3×10 mL). The combined organic layers were washed with water (2×10 mL) followed by saturated aqueous NaCl (2×5 mL). The organic layer was dried (MgSO4), filtered and concentrated to obtain crude product. This crude product was purified by reverse phase HPLC to give the title compound, 2-(4-(isoxazol-5-yl)benzyl)-7-(4-chlorophenyl)-8-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, (15.5 mg, 14%) as pale yellow solid. HPLC: 3.68 min; MS, M+H=480; 1H NMR (CDCl3), ppm: 8.31 (1H, d, J=2.0 Hz), 8.22 (1H, s), 7.77 (2H, d, J=10.0 Hz), 7.51 (2H, d, J=10.0 Hz), 7.26-7.42 (7H, m), 7.09 (2H, d, J=10.0 Hz), 6.54 (1H, d, J=5.0 Hz), 5.29 (2H, s).

Provenance & Evidence