Cesium carbonate → (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 8-chloro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (440 mg, 1.80 mmol) in toluene (8 mL) at room temperature, was added cesium carbonate (879 mg, 2.70 mmol) and di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (458 mg, 1.079 mmol) and the mixture was degassed for 5 min. The mixture was then treated with N-Boc L-Leucinol (1160 mg, 5.39 mmol) followed by palladium(II)acetate (121 mg, 0.54 mmol) and the mixture degassed for another 10 min. The reaction mixture was sealed and heated at 80° C. After overnight stirring the reaction mixture was 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 the crude product which was purified by combi flash (gradient of ethyl acetate and petroleum ether) to afford (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (190 mg, 0.34 mmol, 19% yield) as an off-white solid. LC/MS (ESI) m/e 426.2 [(M+H)+, calcd for C24H32N3O4426.2]; LC/MS retention time (method C): tR=2.10 min.

Provenance & Evidence