Potassium Phosphate, Tribasic → N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]but-2-ynamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(2-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yloxy)ethyl)but-2-ynamide 116a (224 mg, 0.45 mmol), (4-fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-triene-5-yl}-6-(tetra-methyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 108c (240 mg, 0.59 mmol), Pd(dppf)Cl2 (90 mg, 0.12 mmol) and K3PO4 (250 mg, 1.18 mmol) in acetonitrile (10 mL) and water (1 mL) was stirred at 90° C. for 3 h under N2. The mixture was filtered and the filtrate was concentrated to give N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]but-2-ynamide 106a (330 mg crude) as a brown solid. ESI-LCMS: m/z=696.8. This material was used for the next step directly

Provenance & Evidence