反应详情

To a solution of 4-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-7-(2-oxoethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide (178 mg, 85% purity, 0.300 mmol) in tetrahydrofuran (10 mL) at 0° C. was added methylmagnesium bromide (0.707 mL, 2.121 mmol). The mixture was stirred at rt for 20 min. Additional methylmagnesium bromide (0.50 mL, 1.50 mmol) was added. The mixture was stirred at room temperature for another 20 min and then the reaction was quenched with water (20 mL). The resulting mixture was extracted with ethyl acetate (3×40 mL). The combined extract was washed with brine (30 mL) and dried over anhydrous MgSO4. After solvent was removed under vacuum, the residue was purified by reverse phase HPLC. The correct fractions were combined and concentrated under vacuum, basified with saturated NaHCO3 solution, and extracted with ethyl acetate (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 (7.6 mg, 0.014 mmol, 4.9% yield) as a yellow solid. LCMS (M+H)+=520.21. 1H NMR (500 MHz, DMSO-d6) (recognizable peaks for the major atropisomer) δ: 11.68 (s, 1H), 8.44 (s, 1H), 8.21 (s, 1H), 7.36 (s, 1H), 4.01 (m, 1H), 3.92-3.84 (m, 2H), 1.81 (s, 3H).

1. stirringThe mixture was stirred at room temperature for another 20 min
2. customthe reaction was quenched with water (20 mL)
3. extractionThe resulting mixture was extracted with ethyl acetate (3×40 mL)
4. extractionThe combined extract
5. washwas washed with brine (30 mL)
6. dry with materialdried over anhydrous MgSO4
7. customAfter solvent was removed under vacuum
8. customthe residue was purified by reverse phase HPLC
9. concentrationconcentrated under vacuum
10. extractionextracted with ethyl acetate (3×35 mL)
11. extractionThe combined extract
12. washwas washed with brine (30 mL)
13. dry with materialdried over anhydrous MgSO4
14. customRemoval of solvent under vacuum