反应详情

温度

-30 °C

9-bromo-4-iodo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.100 mmol) was dissolved in THF and cooled to −30° C. Phenylmagnesium chloride (2M in THF) (105 μl, 0.210 mmol) was added dropwise, then stirred for 30 minutes before allowing to warm to room temperature by removing cooling baths and stirring an additional 30 minutes. Then, isopropylmagnesium chloride (2M in ether) (60.0 μl, 0.120 mmol) was added dropwise and stirred for 1 h. Then, cyclopropanecarboxaldehyde (29.9 μl, 0.400 mmol) was added and the reaction mixture was stirred for 30 minutes before quenching with saturated NH4Cl (10 mL). The reaction was then diluted with brine and extracted with ethyl acetate. The organic extract was then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Then, the residue was purified by preparative HPLC reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA, to give the title compound as a pale yellow solid as an approximate 1:1 mixture of diastereomers. LRMS (ESI) calc'd for (C22H27BrN3O2) [M+H]+ 444.1; found 444.1.

1. temperatureto warm to room temperature
2. customby removing
3. temperaturecooling baths
4. stirringstirring an additional 30 minutes
5. stirringstirred for 1 h
6. stirringthe reaction mixture was stirred for 30 minutes
7. custombefore quenching with saturated NH4Cl (10 mL)
8. additionThe reaction was then diluted with brine
9. extractionextracted with ethyl acetate
10. extractionThe organic extract
11. dry with materialwas then dried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customThen, the residue was purified by preparative HPLC reverse phase (C-18)
15. washeluting with Acetonitrile/Water+0.05% TFA