反应详情

The crude 4-(5-methyl-7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde in 1,2-dichloroethane (50 mL) is treated with 1-(2,3-dichlorophenyl)piperazine monohydrochloride (1.104 g, 4.13 mmol), followed by triethylamine (0.80 mL, 5.69 mmol) and sodium triacetoxyborohydride (0.911 g, 4.30 mmol). The cloudy yellow solution is stirred at room temperature for 1 hour. The mixture is quenched with water and saturated NaHCO3 solution and extracted with CH2Cl2. The organic extracts are washed with brine, dried over Na2SO4, filtered and concentrated under vacuum to a yellow oil. The oil is purified by column chromatography (5:95 methanol/ethyl acetate) to afford the title compound (1.08 g, 79% over 2 steps) as a white solid. Mp 53–54° C. 1H NMR (CDCl3, 400 MHz): δ 8.94 (br s, 1H), 7.83 (d, 1H), 7.18–7.13 (m, 2H), 6.98–6.94 (m, 1H), 6.62 (d, 1H), 6.38 (d, 1H), 4.38 (t, 2H), 3.16–3.02 (m, 4H), 2.76–2.60 (m, 4H), 2.55–2.46 (m, 2H), 1.90–1.82 (m, 2H), 1.77–1.64 (m, 2H). MS ES: m/z=462.72, 464.58.

1. customThe mixture is quenched with water and saturated NaHCO3 solution
2. extractionextracted with CH2Cl2
3. washThe organic extracts are washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under vacuum to a yellow oil
7. customThe oil is purified by column chromatography (5:95 methanol/ethyl acetate)