Hydrochloric Acid → HCID 73213877, compound

Participants

Reaction Steps

An ambient temperature solution of (S)-tert-butyl (1-cyclopropyl-3-((4,6,9-trimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (41 mg, 0.091 mmol) in methanol (0.5 mL) was treated with HCl (4M in 1,4-dioxane) (0.454 mL, 1.816 mmol) and stirred for 1 h. The resulting mixture was concentrated under reduced pressure to yellow solid. The crude material was purified by reverse phase high performance liquid chromatography (Phenomenex Luna C18 30×100 mm 10 micron; water/methanol/TFA gradient elution). Product containing fractions were neutralized with saturated aqueous sodium bicarbonate and concentrated under reduced pressure. The resulting residue was partitioned between water and ethyl acetate and the layers were separated. The aqueous was extracted twice more with ethyl acetate and the pooled organics were dried over magnesium sulfate, filtered, and concentrated to afford (S)-8-(2-amino-3-cyclopropylpropoxy)-4,6,9-trimethylbenzo[c][2,7]naphthyridin-5(6H)-one (10.7 mg, 0.028 mmol, 93% yield) as a colorless solid. LC/MS, (ESI) m/z 352.2 [(M+H)+, calcd for C21H26N3O2 352.2]; HPLC retention time (method C): tR=13.71 min; HPLC retention time (method D): tR=14.29 min; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.63 (d, J=5.5 Hz, 1H), 7.98 (s, 1H), 7.84 (d, J=5.8 Hz, 1H), 6.74 (s, 1H), 4.15 (dd, J=8.8, 4.0 Hz, 1H), 4.00 (dd, J=8.7, 6.9 Hz, 1H), 3.76 (s, 3H), 3.50-3.37 (m, 1H), 3.17 (s, 3H), 2.37 (s, 3H), 1.61-1.44 (m, 2H), 1.02-0.74 (m, 1H), 0.68-0.45 (m, 2H), 0.30-0.06 (m, 2H).

Provenance & Evidence