反应详情

To a cloudy solution of 7-acetyl-4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (45 mg, 0.092 mmol) in tetrahydrofuran (4 mL) and methanol (12 mL) at 0° C. was added sodium borohydride (17.46 mg, 0.462 mmol) in one portion. The mixture was stirred at room temperature for 20 min and then the reaction was quenched with ice cold water (15 mL). The resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum, and the residue was purified by reverse phase HPLC. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with dichloromethane (3×35 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (10.9 mg, 0.022 mmol, 23.5% yield) as a white solid. LCMS (M+H)+=490.1. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.78 (s, 1H), 8.44 (s, 1H), 8.30 (s, 1H), 8.28 (dd, J1=8.0 Hz, J2=1.4 Hz, 1H), 8.25 (s, 1H), 8.24 (s, 1H), 7.30 (m, 1H), 7.12 (m, 1H), 5.25 (s, 1H), 4.85 (m, 1H), 1.82 (s, 3H),

1. customthe reaction was quenched with ice cold water (15 mL)
2. extractionThe resulting mixture was extracted with ethyl acetate (3×30 mL)
3. extractionThe combined extract
4. washwas washed with brine (25 mL)
5. dry with materialdried over anhydrous MgSO4
6. concentrationThe organic solution was concentrated under vacuum
7. customthe residue was purified by reverse phase HPLC
8. concentrationThe correct fraction was concentrated under vacuum
9. extractionextracted with dichloromethane (3×35 mL)
10. extractionThe combined extract
11. washwas washed with brine (30 mL)
12. dry with materialdried over anhydrous MgSO4
13. customRemoval of solvent under vacuum