反应详情

温度

100 °C

107-1. A mixture of 9-iodo-1-methyl-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (30 mg, 81 μmol) in DCE (2 mL) is treated with POCl3 (15 μL, 0.16 mmol) and heated to 100° C. for 3 h. The mixture was then allowed to cool to RT, poured onto H2O and extracted with DCM. The org. phases were dried over Na2SO4, filtered and concentrated in vacuo. The brown residue obtained was taken up in DCE (2 mL) and 4-cyclopropyl-1H-imidazole (31 mg, 0.28 mmol) and pyridine (20 μL, 0.24 mmol) were then added. The mixture was heated to 100° C. for 4.5 h, and then allowed to cool to RT, poured onto H2O and extracted with DCM. The org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. Filtration through a pad of SiO2 (AcOEt) afforded a brown solid that was purified by SFC (column: Diol 5 μm, 250×30 mm, 60A, Princeton; eluent: 13% MeOH/CO2 for 1 min, then from 13% MeOH/CO2 to 18% MeOH/CO2 in 6 min; then from 18% MeOH/CO2 to 50% MeOH/CO2 in 1 min; flow 100 mL/min; UV detection at 220 nm) to give the title compound (11 mg) as a white powder. UPLC-MS: MS 459.0 (M+H+); UPLC rt 0.98 min.

1. temperatureto cool to RT
2. additionpoured onto H2O
3. extractionextracted with DCM
4. dry with materialphases were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe brown residue obtained
8. temperatureThe mixture was heated to 100° C. for 4.5 h
9. temperatureto cool to RT
10. additionpoured onto H2O
11. extractionextracted with DCM
12. dry with materiallayers were then dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. filtrationFiltration through a pad of SiO2 (AcOEt)
16. customafforded a brown solid that
17. customwas purified by SFC (column
18. waitfrom 13% MeOH/CO2 to 18% MeOH/CO2 in 6 min
19. waitthen from 18% MeOH/CO2 to 50% MeOH/CO2 in 1 min