反应详情

温度

110 °C

A mixture of 6-chloro-2-methyl-4-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (1.06 g, 3.18 mmol), potassium (2-(acetoxymethyl)-3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)phenyl)trifluoroborate (1.51 g, 3.18 mmol), xPhos (227 mg, 476 μmol) and potassium phosphate (1.48 g, 6.99 mmol) in 60 ml of butanol/water (5:1) was degassed with nitrogen for 10 minutes and bis(dibenzylideneacetone)palladium (0) (137 mg, 238 mmol) was added. The reaction mixture was heated to 110° C. for 3 hr. The crude reaction mixture was extracted with DCM, washed with water, dried over Na2SO4, filtered and concentrated to form a solid during concentration. This solid was triturated with ether to afford 1.67 g of crude product. Combined with 300 mg of crude material from a previous batch and purified by silica chromatography to afford 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (1.6 g) as a white solid.

1. customwas degassed with nitrogen for 10 minutes
2. customThe crude reaction mixture
3. extractionwas extracted with DCM
4. washwashed with water
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto form a solid
9. concentrationduring concentration
10. customThis solid was triturated with ether
11. customto afford 1.67 g of crude product
12. custompurified by silica chromatography