Hydrochloric Acid → (S)-8-((2-amino-4-methylpentyl)oxy)-9-cyclopropyl-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one

Participants

Reaction Steps

To a solution of (S)-tert-butyl (1-((9-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (60 mg, 0.129 mmol) in MeOH (4 mL), at 0° C. was added a 4M solution of HCl in 1,4-dioxane (2 mL, 8 mmol). The resultant solution was stirred for 2 h at RT. The methanol was removed under reduced pressure and the residue was extracted with ethyl acetate (2×5 mL). The organic phase was washed with saturated aqueous NaHCO3 (2×5 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel column (MeOH—CHCl3) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-cyclopropyl-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (8 mg, 0.022 mmol, 17% yield) as an off-white solid. LC/MS (ESI) m/z 366.2 [(M+H)+, calcd for C22H28N3O2 366.2]; LC/MS retention time (method B): tR=1.34 min. HPLC retention time (method B): tR=4.87 min and HPLC retention time (method A): tR=9.18 min. 1H NMR (400 MHz, CDCl3) δ ppm 9.47 (s, 1H), 8.75 (d, J=5.7 Hz, 1H), 8.28 (d, J=5.7 Hz, 1H), 7.96 (s, 1H), 7.06 (s, 1H), 4.27 (m, 1H), 4.06-4.15 (m, 1H), 3.84 (s, 3H), 3.38-3.48 (m, 1H), 2.23-2.38 (m, 1H), 1.83-1.94 (m, 1H), 1.56-1.67 (m, 1H), 1.46-1.55 (m, 1H), 1.00-1.08 (m, 6H), 0.79-0.94 (m, 4H).

Provenance & Evidence