Sodium Carbonate → HCID 16004905, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 7-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (72 mg, 0.17 mmol), 4-trifluoromethylphenylboronic acid (65 mg, 0.34 mmol), and 2.0 M aqueous sodium carbonate (0.37 mL) in toluene (1.5 mL) was added (Ph3P)4Pd (30 mg, 0.025 mmol) in one portion, and the resulting yellow mixture was vigorously stirred under argon at 100° C. for 1.5 h. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The EtOAc layer was washed with water, then saturated aqueous NaCl twice, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluted with a gradient of EtOAc (0-80%) in hexanes to afford the desired product, which was contaminated with triphenylphosphine oxide. The product was further purified by preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 50% to 90% B over 12 min (A=90% water, 10% methanol and B=90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The yellow residue was dissolved in acetonitrile, frozen and lyophilized to afford 40 mg of the title compound as a light yellow powder. HPLC/MS: retention time=2.92 min, [M+H]+=530.4.

Provenance & Evidence