Potassium Phosphate, Tribasic → Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-benzyl ester

Participants

Reaction Conditions

Reaction Steps

6-Chloro-2-methyl-4-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-ylamino)pyridazin-3(2H)-one (3.1 g, 8.89 mmol, Eq: 1.00), 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 (7.69 g, 15.6 mmol, Eq: 1.75), X-PHOS (424 mg, 0.89 mmol, Eq: 0.10), bis(dibenzylideneacetone)palladium (255 mg, 0.44 mmol, Eq: 0.05) and tripotassium phosphate (4.72 g, 22.2 mmol, Eq: 2.50) were added to a large microwave vial. The vial was capped and purged. N-butanol (35.5 ml) and water (9 ml) were added and the vial was purged again and backfilled with nitrogen. The reaction was heated in a sand bath at 115° C. for 2.5 hours. Water and DCM were added to the reaction and the layers were separated. The organic layer was filtered through celite, concentrated, and purified by chromatography using a gradient of 0% to 25% methanol in DCM. Fractions with and without the protecting group were combined to give a combined yield of 4.5 g (approximately 74%).

Provenance & Evidence