反应详情

To a suspension of Dess-Martin periodinane (0.79 g, 1.86 mmol, 1.2 eq) in CH2Cl2 (20 mL) was added a solution of 3-fluoro-7-(4-hydroxy-butoxy)-1H-[1,8]naphthyridin-2-one (0.39 g, 1.5 mmol) in THF (6 mL)/DMSO (2 mL). The mixture was stirred at room temperature for 1.5 h. The reaction mixture was diluted with Et2O (100 mL) and quenched with aqueous NaHCO3 (20 mL) containing Na2S2O3 (1.66 g, 10.5 mmol, 7 eq). After extraction with Et2O (3×40 mL), the combined organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated to give the crude aldehyde as a pale yellow solid. To a solution of the aldehyde in 1,2-dichloroethane (20 mL) was added 1-naphthalen-1-yl-piperazine monohydrochloride (0.522 g, 2.1 mmol, 1.4 eq), Et3N (0.38 mL, 2.85 mmol, 1.9 eq) and NaBH(OAc)3 (0.445 g, 2.1 mmol, 1.4 eq). The mixture was stirred at room temperature for 1 h and quenched with water and saturated NaHCO3. After extraction with CH2Cl2 (3×50 mL), the combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography (3% MeOH/CH2Cl2) to give the title compound (430 mg, 62% in two steps). 1H NMR (400 MHz, δ ppm): 12.60 (br s, 1H), 8.10 (d, J=6.0 Hz, 1H), 8.00 (d, J=7.2 Hz, 1H), 7.85 (m, 2H), 7.60 (d, J=6.0 Hz, 1H), 7.50 (m, 2H), 7.40 (d, J=6.0 Hz, 1H), 7.10 (d, J=6.0 Hz, 1H), 6.75 (d, J=7.0 Hz, 1H), 4.35 (t, J=4.0 Hz, 2H), 3.00 (br s, 4H), 2.60 (br s, 4H), 2.40 (t, J=3.8 Hz, 2H), 1.80 (m, 2H), 1.60 (m, 2H); 19F NMR: −140 ppm; MS: 447 (M+H)+ (Exact Mass: 446.21).

1. customquenched with aqueous NaHCO3 (20 mL)
2. extractionAfter extraction with Et2O (3×40 mL)
3. washthe combined organic layer was washed with brine (20 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated
6. customto give the crude aldehyde as a pale yellow solid
7. stirringThe mixture was stirred at room temperature for 1 h
8. customquenched with water and saturated NaHCO3
9. extractionAfter extraction with CH2Cl2 (3×50 mL)
10. dry with materialthe combined organic layer was dried over Na2SO4
11. concentrationconcentrated
12. customThe residue was purified by column chromatography (3% MeOH/CH2Cl2)