In a sealed tube containing 8-chloro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (30 mg, 0.123 mmol) and (S)-tert-butyl (4,4-difluoro-1-hydroxypentan-2-yl)carbamate (35.2 mg, 0.147 mmol) was added toluene (3 mL). Di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (31.2 mg, 0.074 mmol) and cesium carbonate (59.9 mg, 0.184 mmol) were added to the reaction mixture followed by palladium (II)acetate (8.26 mg, 0.037 mmol). The reaction mixture was then heated at 85° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and filtered through diatomaceous earth (Celite®), eluting with ethyl acetate. The filtrate was evaporated under reduced pressure and the crude product was purified by silica gel chromatography to afford (S)-tert-butyl (4,4-difluoro-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (12 mg, 0.027 mmol, 22% yield) as yellow solid. LC/MS (ESI) m/e 448.3 [(M+H)+, calcd for C23H28F2N3O4 448.2]; LC/MS retention time (method E): tR=0.96 min.
