A mixture of intermediate 12 (100 mg, 0.32 mmol) and NaI (95 mg, 0.64 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 61 (105 mg, 0.48 mmol) and anhydrous K2CO3 (176 mg, 1.27 mmol) were added to the mixture. The resulting mixture was heated to reflux and stirred for 4 h. Precipitated crystals were filtered off and the filtrate was evaporated under reduced pressure. The residue was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1) to give 7-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (compound 41) (115 mg, 83%). 1H NMR (300 MHz, CDCl3): δ 7.60 (s, 1H), 7.36 (d, J=8.1 Hz, 1H), 7.27 (s, 1H), 6.78 (t, J=8.1 Hz, 1H), 6.61-6.53 (m, 2H), 6.35 (d, J=8.1 Hz, 1H), 4.33-4.20 (m, 6H), 3.10 (s, 4H), 2.86 (dd, J=7.5 Hz, 2H), 2.67-2.62 (m, 6H), 2.51-2.46 (m, 2H), 1.82-1.69 (m, 6H). HPLC: 99%, RT 2.084 min. MS (ESI) m/z 439.2 [M+H]+.
