反应详情

The crude 4-(5,6-dimethyl-7-oxo-7,8-dihydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde (100 mg, 0.38 mmol) is dissolved in dichloroethane (7 mL) and 1-(2,3-dichlorophenyl)piperazine monohydrochloride (112 mg, 0.42 mmol) is added, followed by triethylamine (39 mg, 0.05 mL, 1.14 mmol). The mixture is stirred for 5 minutes and NaBH(OAc)3 (81 mg, 0.38 mmol) is added. The mixture is stirred at room temperature for 1 hour and water (5 mL) is added. The organic layer is separated, washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under vacuum. The crude solid is purified by column chromatography (1:9 methanol/ethyl acetate) to yield the title compound (123 mg, 68%) as a white solid. mp 161–163° C., 1H NMR (400 MHz, CDCl3) δ 8.98 (br s, 1H), 7.80 (d, 1H), 7.20–7.10 (m, 2H), 7.00–6.90 (m, 1H), 6.60 (d, 1H), 4.20 (t, 2H), 3.15–3.00 (m, 4H), 2.75–2.60 (m, 4H), 2.50 (t, 2H), 2.40 (s, 3H), 2.20 (s, 3H), 1.85–1.60 (m, 4H), MS ES+ 474.76 (M)+ (Exact Mass: 474.16).

1. stirringThe mixture is stirred at room temperature for 1 hour
2. customThe organic layer is separated
3. washwashed with brine (10 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customThe crude solid is purified by column chromatography (1:9 methanol/ethyl acetate)