General procedure for the synthesis of 7-benzyl-5,6,7,8-tetrahydro-1,7-naphthyridin-2(1H)-one from 2-hydroxy-1,7-naphthyridine and benzyl bromide: 2-hydroxy-1,7-naphthyridine (423 mg, 2.89 mmol) was suspended in ethanol (10 mL) and heated for 5 min at 70 °C. Benzyl bromide (0.34 mL, 2.89 mmol) was then slowly added and the mixture was heated to reflux for 3 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and sodium borohydride (0.55 g, 14.5 mmol) was added. The mixture was stirred at 0 °C for 10 min, followed by slow warming to room temperature. 6 M hydrochloric acid (2 mL) was carefully added and stirring was continued for 90 minutes at room temperature. The reaction mixture was alkalized to pH 10 with 2 M sodium hydroxide (10 mL) followed by liquid-liquid partitioning with ethyl acetate (20 mL) and water (10 mL). The organic layer was separated and the aqueous layer was extracted with a dichloromethane/methanol mixture (95:5, 2 x 20 mL). All organic phases were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford 7-benzyl-5,6,7,8-tetrahydro-1,7-naphthyridin-2(1H)-one as a white solid in 90% yield (626 mg).1H NMR (CD3OD, 400 MHz) δ: 2.62 (m, 2H), 2.76 (m, 2H), 3.42 (s, 2H), 3.71 (s, 2H), 6.36 (d, 1H), 7.26-7.41 (m, 6H).MS APCI+ m/z 241 [MH]+.
