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

Participants

Reaction Steps

To a solution of (S)-tert-butyl (1-((6-cyclopropyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (100 mg, 0.221 mmol) in anhydrous dichloromethane (2 mL) was added a 2 M solution of HCl in diethyl ether (0.176 mL, 0.353 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 (0.1% TFA in water) to afford (S)-6-allyl-8-((2-amino-4-methylpentyl)oxy)benzo[c][2,7]naphthyridin-5(6H)-one (8 mg, 22.76 mmol, 10% yield) as a yellow solid. LC/MS (ESI) m/e 352.2 [(M+H)+, calcd for C21H26N3O2 352.2]; LC/MS retention time (method C): tR=1.80 min; HPLC retention time (method A): tR=8.06 min; HPLC retention time (method B): tR=9.21 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.56 (s, 1H), 8.85 (d, J=6.27 Hz, 1H), 8.55 (d, J=9.04 Hz, 1H), 8.48 (d, J=6.27 Hz, 1H), 7.20 (dd, J=8.91, 2.38 Hz, 1H), 7.14 (d, J=2.26 Hz, 1H), 6.08 (dd, J=17.32, 10.54 Hz, 1H), 5.28 (dd, J=10.54, 1.00 Hz, 1H), 5.18 (dd, J=17.32, 1.25 Hz, 1H), 5.09-5.13 (m, 2H), 4.44 (dd, J=10.54, 3.26 Hz, 1H), 4.27 (dd, J=10.42, 6.40 Hz, 1H), 3.77 (dd, J=6.78, 3.51 Hz, 1H), 1.64-1.88 (m, 3H), 1.07 (dd, J=6.40, 4.89 Hz, 6H).

Provenance & Evidence