To a solution 8-chloro-6-isopropylbenzo[c][2,7]naphthyridin-5(6H)-one (250 mg, 0.917 mmol) in toluene (2 mL) at room temperature was added cesium carbonate (448 mg, 1.375 mmol) and di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (234 mg, 0.550 mmol) and the mixture was degassed for 5 min. The mixture was then treated with N-Boc-L-leucinol (591 mg, 2.75 mmol) followed by palladium(II)acetate (61.7 mg, 0.275 mmol) and degassed for another 10 min. The reaction mixture was sealed and heated at 80° C. The reaction mixture was then cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford crude product which was purified by combi flash (gradient of ethyl acetate and petroleum ether) afford (S)-tert-butyl (1-((6-isopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (160 mg, 0.198 mmol, 21% yield) as an off-white solid. LC/MS (ESI) m/e 454.2 [(M+H)+, calcd for C26H36N3O4 454.3]; LC/MS retention time (method C): tR=2.17 min.
