反应详情

温度

70 °C

Intermediate 12 (85 mg, 0.27 mmol) was dissolved in CH3CN then NaI (55 mg, 0.37 mmol), Et3N (91 mg, 0.9 mmol), and intermediate 2 (102 mg, 0.36 mmol) were added. The resulting mixture was stirred at 70° C. overnight. 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-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one (compound 3) (78 mg, 63%). 1H NMR (300 MHz, CDCl3): δ 7.64 (s, 1H), 7.38 (d, J=8.1 Hz, 1H), 7.27-7.15 (m, 2H), 7.06 (d, J=8.1 Hz, 1H), 6.37 (d, J=8.1 Hz, 1H), 4.36 (t, J=6.0 Hz, 2H), 3.61-3.49 (m, 7H), 3.32-3.20 (m, 5H), 2.90-2.85 (m, 2H), 2.67-2.62 (m, 2H), 2.21-2.16 (m, 2H), 1.90-1.85 (m, 2H). HPLC: 99%, RT 2.682 min. MS (ESI) m/z 463.1 [M+H]+. mp: 110-111° C.

1. customPrecipitated crystals
2. filtrationwere filtered off
3. customthe filtrate was evaporated under reduced pressure
4. extractionThe residue was extracted with EtOAc
5. washThe combined EtOAc layers were washed with brine
6. dry with materialdried over anhydrous Na2SO4
7. concentrationconcentrated in vacuo
8. custompurified by flash chromatography on silica gel column (elution with DCM/MeOH=30:1)