反应详情

温度

-78 °C

A round bottom flask was charged with 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-N,N-diethylquinolin-2-amine (380 mg, 0.809 mmol, Intermediate 46) and (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (206 mg, 0.809 mmol, Intermediate 36, step c) and was evacuated and re-filled with argon. THF (13.5 mL) was added, and the solution was cooled in a dry ice acetone bath for 10 minutes. n-BuLi (1.6 M in hexane, 0.506 mL, 0.809 mmol), was added dropwise by syringe. The mixture was stirred at −78° C. for 30 minutes, then in an ice water bath for 30 minutes. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 50-100% EtOAc-heptanes) to provide the title compound as a white foam.

1. customwas evacuated
2. additionre-filled with argon
3. additionTHF (13.5 mL) was added
4. temperaturethe solution was cooled in a dry ice acetone bath for 10 minutes
5. waitin an ice water bath for 30 minutes
6. customThe reaction was quenched by addition of saturated aqueous NH4Cl
7. additiondiluted with water
8. extractionextracted with EtOAc (3×)
9. dry with materialThe organic phase was dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by flash column chromatography (silica gel, 50-100% EtOAc-heptanes)