反应详情

温度

110 °C

A screw capped vial was charged with 2-methoxy-4-(trifluoromethyl)phenyl boronic acid (0.094 g, 0.429 mmol), 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide (0.250 g, 0.429 mmol), and potassium phosphate tribasic (0.273 ml, 1.288 mmol). Dioxane (1.72 ml) and Water (0.57 ml) were added and the vial was purged with Argon and Amphos (0.030 g, 0.043 mmol) was added. The vial was capped and heated to 110° C. After 4 hours, reaction was cooled to room temperature. The reaction was diluted with water (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel chromatography (ISCO, 40 g), eluting with 0 to 10% MeOH/DCM. The fractions were collected and the solvent was removed under reduced pressure. The resulting material was taken up in DCM (5 mL) and TFA (1 mL) was added. The reaction was stirred for 2 hours and then the solvent was removed under reduced pressure. The resulting material was taken up in DCM (30 mL) and washed with sodium bicarbonate (sat solution). The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting solid was triturated with diethyl ether (20 mL) and filtered. The solid was dried under reduced pressure to provide 0.052 g of 4-(2-methoxy-4-(trifluoromethyl)phenyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide as an off white solid. m/z (ESI) 482.1 (M+H)+.

1. customA screw capped vial
2. additionwas added
3. customThe vial was capped
4. customreaction
5. temperaturewas cooled to room temperature
6. washwas washed with ethyl acetate (20 mL×3)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe resulting material was purified via silica gel chromatography (ISCO, 40 g)
11. washeluting with 0 to 10% MeOH/DCM
12. customThe fractions were collected
13. customthe solvent was removed under reduced pressure
14. additionTFA (1 mL) was added
15. customthe solvent was removed under reduced pressure
16. washwashed with sodium bicarbonate (sat solution)
17. dry with materialThe organic layer was dried over magnesium sulfate
18. filtrationfiltered
19. concentrationconcentrated
20. customThe resulting solid was triturated with diethyl ether (20 mL)
21. filtrationfiltered
22. customThe solid was dried under reduced pressure