Potassium Phosphate, Tribasic → 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Participants

Reaction Conditions

Reaction Steps

This reaction was carried out under similar conditions to those described above instep 7 of preparation of Example 6. A solution of 6-chloro-2-methyl-4-(5-((1R,5S)-3-methyl-3,8-diazabicyclo[3.2.1]-octan-8-yl)pyridin-2-ylamino)pyridazin-3(2H)-one (150 mg, 416 μmol), 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (206 mg, 416 μmol), xPhos (19.8 mg, 41.6 μmol) and potassium phosphate (221 mg, 1.04 mmol) in 10 ml of dioxane/water (9:1) was degassed with nitrogen for 10 minutes and bis(dibenzylideneacetone)palladium (0) (12.0 mg, 20.8 μmol) was added. The reaction mixture was heated to 100° C. for 2 hr. After work up, the product was purified by preparative HPLC on silica gel, using a gradient of 10% to 20% methanol/dichloromethane to afford 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(1-methyl-5-(5-(3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate as light yellow solid (69 mg, 24%). %). (M+H)+=693, 694 m/e.

Provenance & Evidence