N-Methylaniline → HCID 66875318, compound

Temperature

120 °C

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.

1. customin a glass reaction tube
2. customwas fitted with a septa
3. customevacuated via house vacuum
4. customflush three times
5. customto remove air from the reaction system
6. temperatureAfter this time, the reaction was cooled to 25° C. where it
7. customAfter this time, the reaction mixture was then partitioned between water (200 mL) and ethyl acetate (200 mL)
8. extractionThe aqueous layer was back extracted with ethyl acetate (100 mL)
9. dry with materialThe combined organics were dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-16a486cec86f43ad84254b3db58aced4

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258134B2