反应详情

温度

80 °C

A mixture of methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (33 mg, 0.068 mmol), ethylamine HCl (11.06 mg, 0.136 mmol), and Hunig's base (47.4 μl, 0.271 mmol) in N,N-Dimethylformamide (DMF) (631 μl) was degassed with N2 for 8 min, and then treated with Pd(OAc)2 (1.5 mg, 6.78 μmol) and 1,3-bis(diphenylphosphino)propane (2.80 mg, 6.78 μmol). The reaction was placed under vacuum, filled and purged with N2 3×, followed by CO 3×. The reaction was stirred at 50 psi (CO) at 80° C. overnight. Additional DMF (1 mL), ethylamine HCl (11.06 mg, 0.136 mmol), and Hunig's base (47.4 μl, 0.271 mmol) were added, the reaction was degassed with N2 for 5 min, treated with Pd(OAc)2 (1.523 mg, 6.78 μmol) and 1,3-bis(diphenylphosphino)propane (2.80 mg, 6.78 μmol), filled and purged with N2 3×, CO 3×, and stirred at 80° C. under 50 psi of CO for 5 hours. The mixture was filtered, extracted with EtOAc, washed with water, brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (0-100% EtOAc/Hexane, followed with 0-20% MeOH/DCM) to afford methyl [(1,1-dimethylethyl)oxy]{4-(3,4-dimethylphenyl)-7-[(ethylamino)carbonyl]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl}acetate (9.3 mg, 0.019 mmol, 28.6% yield); LC/MS (m/z) ES+=479 (M+1).

1. customwas degassed with N2 for 8 min
2. additionfilled
3. custompurged with N2 3×
4. customthe reaction was degassed with N2 for 5 min
5. additionfilled
6. custompurged with N2 3×, CO 3×
7. stirringstirred at 80° C. under 50 psi of CO for 5 hours
8. filtrationThe mixture was filtered
9. extractionextracted with EtOAc
10. washwashed with water, brine
11. dry with materialdried with Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was purified by column chromatography (0-100% EtOAc/Hexane, followed with 0-20% MeOH/DCM)