反应详情

A mixture of intermediate 44 (43.7 mg, 0.17 mmol) and NaI (51.3 mg, 0.34 mmol) in CH3CN (3 mL) was heated to reflux for 30 min and then cooled to rt. To this mixture was added intermediate 2 (57.9 mg, 0.21 mmol), followed then by DIEA (0.066 mL, 0.38 mmol). 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 ISCO to give 6-(3-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)propoxy)-1H-indazole (compound 46) (43.6 mg, 61%). 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J=0.8 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.15-7.07 (m, 2H), 7.00 (dd, J=7.4, 2.3 Hz, 1H), 6.88 (s, 1H), 6.80 (dd, J=8.8, 2.1 Hz, 1H), 4.09 (t, J=6.1 Hz, 2H), 3.43-3.37 (m, 2H), 3.29 (t, J=6.1 Hz, 2H), 3.14-3.05 (m, 4H), 3.00-2.92 (m, 2H), 2.22-2.10 (m, 4H). HPLC: 99%, RT 4.201 min. MS (ESI) m/z 419.10 [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 EtOAc
9. washThe combined EtOAc layers were washed with brine
10. dry with materialdried over anhydrous Na2SO4
11. concentrationconcentrated in vacuo
12. custompurified by ISCO