反应详情

To a clear solution of Dess-Martin reagent (1.40 g, 3.3 mmol, 1.3 equiv) in CH2Cl2 (200 mL) was added 7-(4-hydroxy-butoxy)-6-methyl-3,4-dihydro-1H-[1,8]naphthyridin-2-one (0.55 g, 2.2 mmol, 1.0 equiv) and the mixture was stirred at room temperature for 4 hours. TLC confirmed the completion of the reaction. The reaction mixture was diluted with CH2Cl2 and poured into a saturated solution of NaHCO3 containing Na2S2O3 (3.0 g). The mixture was stirred and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2×30 mL) and the combined organic layer was dried over Na2SO4 and concentrated. The crude aldehyde was dissolved in DCE and 1-naphthalen-1-yl-piperazine monohydrochloride (0.76 g, 3.08 mmol, 1.4 equiv), Et3N (0.5 mL, 1.7 equiv) and NaBH(OAc)3 (0.65 g, 3.08 mmol, 1.4 equiv) were added. The reaction mixture was stirred for 1 hour, diluted with CH2Cl2 and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated. Purification of the residue by column chromatography (5% MeOH/EtOAc) gave the title compound as a white solid (0.40 g, 41%). mp: 76–78° C.; 1H NMR: (400 MHz, CDCl3) δ 8.22 (d, 1H), 7.85 (d, 1H), 7.58–7.38 (m, 5H), 7.25 (s, 1H), 7.05 (d, 1H), 4.25 (t, 2H), 3.30–3.10 (br s, 4H), 2.82–2.65 (m, 4H), 2.65–2.45 (m, 4H), 2.15 (s, 3H), 1.88–1.35 (m, 6H). MS: ES+ 445.41 (M+H)+, exact mass: 444.25.

1. customthe completion of the reaction
2. stirringThe mixture was stirred
3. customthe organic layer was separated
4. extractionThe aqueous layer was extracted with CH2Cl2 (2×30 mL)
5. dry with materialthe combined organic layer was dried over Na2SO4
6. concentrationconcentrated
7. dissolutionThe crude aldehyde was dissolved in DCE
8. stirringThe reaction mixture was stirred for 1 hour
9. washwashed with saturated NaHCO3 and brine
10. dry with materialThe organic layer was dried over Na2SO4
11. concentrationconcentrated
12. customPurification of the residue by column chromatography (5% MeOH/EtOAc)