反应详情

A mixture of intermediate 15 (70 mg, 0.24 mmol) and NaI (70 mg, 0.48 mmol) in CH3CN was heated to reflux for 30 min and then cooled to rt. Intermediate 61 (78 mg, 0.36 mmol) and anhydrous K2CO3 (162 mg, 0.96 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 EtOA. 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)quinolin-2(1H)-one (compound 42) (52 mg, 50%). 1H NMR (300 MHz, CDCl3): δ 11.65 (brs, 1H), 7.72 (d, J=9.6 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 6.82-6.75 (m, 3H), 6.61-6.52 (m, 3H), 4.33-4.26 (m, 4H), 4.12-4.08 (m, 2H), 3.12 (br, 4H), 2.70 (br, 4H), 2.52 (br, 2H), 2.04-1.68 (m, 6H). HPLC: 99%, RT 2.167 min. MS (ESI) m/z 436.0 [M+H]+.

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