反应详情

Acetic acid 2-(6-tert-butyl-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzyl ester (0.472 mmol) was taken up in THF (7 mL) and methanol (3 mL) and water (5 mL) and then added lithium hydroxide monohydrate (40 mg, 2 eq). The resulting mixture was stirred at room temperature overnight. The next morning the reaction was complete by TLC and most of the THF and methanol was removed under reduced pressure at 55° C. Then ethyl acetate (75 mL) and water (30 mL) were added and the layers were partitioned and then separated. Next, the ethyl acetate layer was washed with water (2×30 mL), brine (1×30 mL) and then dried over magnesium sulfate, filtered and concentrated to give 286 mg of crude product. Preparative Thin Layer Chromatography purification eluting on two 20×40 cm 1000 μM plates in 6% methanol in dicholomethane afforded the title compound (99 mg) as a white powder ((M+H)+=622).

1. customwas removed under reduced pressure at 55° C
2. additionThen ethyl acetate (75 mL) and water (30 mL) were added
3. customthe layers were partitioned
4. customseparated
5. washNext, the ethyl acetate layer was washed with water (2×30 mL), brine (1×30 mL)
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customto give 286 mg of crude product
10. customPreparative Thin Layer Chromatography purification
11. washeluting on two 20×40 cm 1000 μM plates in 6% methanol in dicholomethane