Sodium Hydroxide → HCID 56655888, compound

Participants

Reaction Conditions

Reaction Steps

In a 15 mL microwave reaction vial was added 6-chloro-4-[5-(2-dimethylamino-ethoxy)-pyrazin-2-ylamino]-2-methyl2H-pyridazin-3-one (89 mg, 274 μmol, Eq: 1.00) in 7 mL n-butanol and 1.4 mL water. To the solution was added potassium phosphate tribasic (128 mg, 603 μmol), X-PHOS (19.6 mg, 41.1 μmol, Eq: 0.15) and acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (279 mg, 395 μmol, Eq: 1.44) with stirring and bubbling of argon. To this mixture was added bis(dibenzylideneacetone)palladium (11.8 mg, 20.6 μmol, Eq: 0.075) and the reaction was heated at 110° C. for 3 hrs. The reaction was cooled to room temperature and treated with a solution of NaOH (220 mg) in water (1.5 mL). The resultant mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with DCM (50 mL) and water (50 mL). The organic phase was separated, washed with water (30 mL) and concentrated. The residue was purified on silica gel with 0-10% (10% NH4OH in MeOH) in ( 1/1) EtOAc/Hex. The pure fractions were concentrated and dissolved in DCM. Heptane was added to precipitate the product. The liquid was decanted off to afford 81 mg (46%) of the title compound as an off white solid. mp: 185-190° C.

Provenance & Evidence