To a suspension of Dess-Martin periodinane (0.419 g, 0.99 mmol, 1.2 eq) in CH2Cl2 (20 mL) was added a solution of 7-(4-hydroxy-butoxy)-3-(2,2,2-trifluoro-ethyl)-1H-[1,8]naphthyridin-2-one (0.26 g, 0.82 mmol) in THF (8 mL). The mixture was stirred at room temperature for 1 h. Et2O (100 mL) was added to dilute the reaction mixture. The reaction was quenched with aqueous NaHCO3 (20 mL) containing Na2S2O3 (0.91 g, 5.74 mmol, 7 eq). After extraction with Et2O (3×50 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 crude aldehyde in 1,2-dichloroethane (20 mL) was added 1-naphthalen-1-yl-piperazine monohydrochloride (0.286 g, 1.15 mmol, 1.4 eq), Et3N (0.21 mL, 1.56 mmol, 1.9 eq) and NaBH(OAc)3 (0.241 g, 1.15 mmol, 1.4 eq). The mixture was stirred at room temperature for 1 h. The reaction was 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 (2% MeOH/CH2Cl2) to give the title compound (200 mg, 50% in two steps). 1H NMR (400 MHz, δ ppm): 9.05 (br s, 1H), 8.20 (d, J=6.2 Hz, 1H), 7.80 (d, J=6.0 Hz, 1H), 7.75 (m, 2H), 7.58 (d, J=6.3 Hz, 1H), 7.50 (m, 2H), 7.40 (t, J=6.3 Hz, 1H), 7.10 (d, J=5.3 Hz, 1H), 6.40 (d, J=6.5 Hz, 1H), 4.40 (t, J=4.2 Hz, 2H), 3.50 (q, J=7.5 Hz, 2H), 3.20 (br s, 4H), 2.80 (br s, 4H), 2.60 (m, 2H), 1.90 (m, 2H), 1.72 (m, 2H). 19F NMR: −65.6 ppm. MS: 511 (M+). Elemental Analysis calculated for C28H29F3N4O2: C, 65.88; H, 5.69; N, 10.98. Found: C, 66.08; H, 5.89; N, 10.67.
