反应详情

To a solution of (S)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (30 mg, 0.068 mmol) in MeOH (3 mL) at 0° C. was added HCl (4N in 1,4-dioxane, 3 mL, 12.00 mmol). The solution was warmed to room temperature and stirred for 2 h. The reaction mixture was then concentrated under reduced pressure and the residue dissolved in ethyl acetate (10 mL). The organic layer was washed with saturated NaHCO3 (2×10 mL) and water (20 mL); dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by preparative TLC (DCM-MeOH mixture) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (8 mg, 0.021 mmol, 31% yield) as a brown solid. LC/MS, (ESI) m/z 340.2 [(M+H)+, calcd for C20H26N3O2, 340.2]; LC/MS retention time (method B): tR=1.27 min. HPLC retention time (method A): tR=8.30 and HPLC retention time (method B): tR=8.97 min. 1H NMR (400 MHz, CD3OD) δ ppm 8.53 (d, J=5.77 Hz, 1H), 8.33 (d, J=9.54 Hz, 1H), 8.08 (d, J=5.77 Hz, 1H), 7.00-7.06 (m, 2H), 4.21 (m, 1H), 4.02 (m, 1H), 3.73 (s, 3H), 3.47-3.52 (m, 1H), 3.06 (s, 3H), 1.82-1.93 (m, 1H), 1.67-1.76 (m, 2H), 1.26-1.56 (m, 6H).

1. concentrationThe reaction mixture was then concentrated under reduced pressure
2. dissolutionthe residue dissolved in ethyl acetate (10 mL)
3. washThe organic layer was washed with saturated NaHCO3 (2×10 mL) and water (20 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by preparative TLC (DCM-MeOH mixture)