Water → Ethyl 1-[(6-methyl-2,3'-bipyridin-5-yl)methyl]-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

Participants

Reaction Steps

Ethyl 1-[(6-chloropyridin-3-yl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate [(Example 5, Step 3), 335 mg, 0.972 mmol] was dissolved in tetrahydrofuran (15 mL), treated with an aqueous solution (3 mL) of cesium carbonate (792 mg, 2.43 mmol, 2.5 equiv), copper(I) chloride (96.0 mg, 0.972 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (333 mg, 2.43 mmol, 2.5 equiv) and bis(tri-tert-butylphosphine)palladium(0) (99.0 mg, 0.194 mmol, 0.2 equiv). The mixture was placed into a preheated oil bath at 70° C. for 2 hours, cooled to ambient temperature, poured into sodium bicarbonate (50 mL, aqueous saturated) and water (100 mL) and then extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 10% methanol), providing the titled compound as a light yellow solid.

Provenance & Evidence