Hydrochloric Acid → HCID 73213873, compound

Participants

Reaction Steps

An ambient temperature suspension of (S)-tert-butyl (1-cyclopropyl-3-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (50 mg, 0.114 mmol) (prepared as described in Example 16 using (S)-tert-butyl (1-cyclopropyl-3-hydroxypropan-2-yl)carbamate (0.287 g, 1.334 mmol) in Part H) in diethyl ether (1 mL) was treated with HCl (4M in 1,4-dioxane) (0.571 mL, 2.286 mmol) and stirred for 1 h. The resulting mixture was concentrated under reduced pressure to a 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). Fractions containing product were concentrated under reduced pressure. The resulting residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The layers were separated and the aqueous was extracted twice more with ethyl acetate. The pooled organics were washed once with brine, dried over magnesium sulfate, filtered, and concentrated to afford (S)-8-(2-amino-3-cyclopropylpropoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (9.0 mg, 0.025 mmol, 22% yield for the final step) as a white solid. LC/MS, (ESI) m/z 338.2 [(M+H)+, calcd for C20H24N3O2 338.2]; HPLC retention time (method C): tR=13.05 min; HPLC retention time (method D): tR=13.88 min; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.65 (d, J=5.8 Hz, 1H), 8.16 (d, J=8.8 Hz, 1H), 7.83 (d, J=5.5 Hz, 1H), 6.92 (dd, J=8.9, 2.4 Hz, 1H), 6.87 (d, J=2.3 Hz, 1H), 4.15 (dd, J=8.9, 3.9 Hz, 1H), 3.97 (dd, J=8.8, 7.0 Hz, 1H), 3.75 (s, 3H), 3.48-3.35 (m, 1H), 3.17 (s, 3H), 1.59-1.42 (m, 2H), 0.87-0.74 (m, 1H), 0.64-0.47 (m, 2H), 0.25-0.17 (m, 1H), 0.16-0.10 (m, 1H).

Provenance & Evidence