Hydrochloric Acid → HCID 73213797, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl (5,5,5-trifluoro-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (150 mg, 0.322 mmol) in diethyl ether (10 mL) under nitrogen atmosphere, cooled to 0° C. was added 4M HCl in 1,4-dioxane (0.098 mL, 0.392 mmol) slowly over a period of 5 min. The light yellow reaction mixture was stirred at 0° C. for 5 min then warmed to room temperature and allowed to stir for 12 h. The solvent was removed under reduced pressure. The residual yellow oil was diluted with water (3 mL) and extracted with EtOAc (2×4 mL). The aqueous layer was separated and treated with sat. Na2CO3 solution (3 mL). The resultant aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layer s were separated and washed with water (2×5 mL), brine (1×5 mL) and dried over sodium sulfate. The filtrate was evaporated under reduced pressure and purified by SFC (CO2 and 0.5% DEA in Methanol) to afford 8-((2-amino-5,5,5-trifluoropentyl)oxy)-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (102.8 mg, 0.278 mmol, 86% yield) as a white solid. LC/MS (ESI) m/e 366.2 [(M+H)+, calcd for C18H19F3N3O2366.13]; LC/MS retention time (method C): tR=1.77 min; HPLC retention time (method A): tR=7.79 min; HPLC retention time (method B): tR=8.20 min. 1H NMR (400 MHz, MeOD) δ 9.48 (d, J=0.80 Hz, 1H), 8.78 (d, J=5.60 Hz, 1H), 8.44 (d, J=8.80 Hz, 1H), 8.27 (d, J=5.60 Hz, 1H), 7.17 (d, J=2.40 Hz, 1H), 7.12 (dd, J=2.40, 8.80 Hz, 1H), 4.17-4.20 (m, 1H), 4.09 (dd, J=6.00, 9.40 Hz, 1H), 3.82 (s, 3H), 3.28-3.28 (m, 1H), 2.33-2.49 (m, 2H), 1.92-1.99 (m, 1H), 1.73-1.80 (m, 1H).

Provenance & Evidence