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

Participants

Reaction Steps

To a solution of ((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, 0.353 mmol) in anhydrous dichloromethane (4 mL) was added a 2 M solution of HCl in diethyl ether (0.88 mL, 1.76 mmol) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was then concentrated under reduced pressure to afford crude product which was purified by preparative HPLC (10 mM ammonium acetate in water; acetonitrile) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6-isopropylbenzo[c][2,7]naphthyridin-5(6H)-one (45 mg, 0.127 mmol, 36% yield) as an off-white solid. LC/MS (ESI) m/e 354.2 [(M+H)+, calcd for C21H28N3O2 354.2]; LC/MS retention time (method C): tR=1.81 min; HPLC retention time (method A): tR=8.85 min; HPLC retention time (method B): tR=9.50 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.43 (d, J=0.75 Hz, 1H), 8.75 (d, J=5.77 Hz, 1H), 8.42 (d, J=9.04 Hz, 1H), 8.22 (d, J=5.52 Hz, 1H), 7.30 (d, J=2.26 Hz, 1H), 7.10 (dd, J=8.78, 2.26 Hz, 1H), 5.26-5.43 (m, 1H), 4.16 (dd, J=9.16, 3.89 Hz, 1H), 3.98 (dd, J=9.29, 7.03 Hz, 1H), 3.27-3.31 (m, 1H), 1.81-1.92 (m, 1H), 1.73 (d, J=7.03 Hz, 6H), 1.41-1.51 (m, 2H), 1.02 (dd, J=9.54, 6.53 Hz, 6H).

Provenance & Evidence