反应详情

The crude 5-bromo-6-hydroxy-2H-isoquinolin-1-one (93 mg) was mixed with (R)-3-methanesulphonyloxypiperidine-1-carboxylic acid tert-butyl ester (500 mg, 4.3 mol eq), potassium carbonate (700 mg, 12 mol eq) and N, N-dimethylformamide (2 ml). The mixture was microwaved at 150° C. for 20 minutes. Water was added to the mixture and the crude product extracted out into ethyl acetate. The organic phase was washed with brine and dried (MgSO4). The organics were concentrated in vacuo then purified by prep-HPLC. Dichloromethane and trifluoroacetic acid (3:1, 2 ml) were added and the mixture stirred for 1 h then concentrated in vacuo to give a residue. The residue was loaded onto a pre-acidified SCX column using methanol and eluted with 2M ammonia in methanol to afford (S)-5-bromo-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one. The residue was purified by prep-HPLC (1.8 mg), El-MS: m/z=323.5 and 323.5 [M+H]+

1. customThe mixture was microwaved at 150° C. for 20 minutes
2. extractionthe crude product extracted out into ethyl acetate
3. washThe organic phase was washed with brine
4. dry with materialdried (MgSO4)
5. concentrationThe organics were concentrated in vacuo
6. customthen purified by prep-HPLC
7. additionDichloromethane and trifluoroacetic acid (3:1, 2 ml) were added
8. concentrationthen concentrated in vacuo
9. customto give a residue
10. washeluted with 2M ammonia in methanol