N-Methylaniline → HCID 66875318, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (2.0 g, 8.02 mmol) (Intermediate 20), sodium tert-butoxide (0.93 g, 9.67 mmol), tris(dibenzylideneacetone)dipalladium(0) (19 mg, 0.02 mmol) and N-phenyl-2-(di-tert-butylphosphino)indole (27.4 mg, 0.08 mmol) in a glass reaction tube was fitted with a septa and then evacuated via house vacuum followed by a nitrogen flush three times to remove air from the reaction system. The reaction was then treated with anhydrous toluene (8 mL, 1.0M) and N-methylaniline (1.05 mL, 9.69 mmol). The reaction was heated to 120° C. for 4 d. After this time, the reaction was cooled to 25° C. where it stirred for an additional 1 d. After this time, the reaction mixture was then partitioned between water (200 mL) and ethyl acetate (200 mL). The aqueous layer was back extracted with ethyl acetate (100 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 115 g, 10-40% ethyl acetate/hexanes gradient) afforded 4-chloro-5-(methyl-phenyl-amino)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (277.2 mg, 11%) as an orange/red oil.

Provenance & Evidence