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Ethyl 4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate (1.00 g, 4.56 mmol) and 2-chloro-5-(chloromethyl)pyridine (813 mg, 5.02 mmol, 1.1 equiv) were combined in degassed N,N-dimethylformamide and cooled to 0° C. Sodium hydride (219 mg, 5.47 mmol, 1.2 equiv) was added portionwise over 5 minutes and the mixture was stirred for an additional 1 hour at 0° C. The mixture was warmed to ambient temperature, stirred for 1 hour and poured into sodium bicarbonate (150 mL, aqueous saturated). The aqueous layer was extracted with ethyl acetate (2×150 mL) and 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), providing the titled compound as a white solid.

1. temperatureThe mixture was warmed to ambient temperature
2. stirringstirred for 1 hour
3. extractionThe aqueous layer was extracted with ethyl acetate (2×150 mL)
4. dry with materialthe combined organic extracts were dried with sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)