反应详情

温度

-78 °C

2-(Azetidin-1-yl)-6-bromo-4-chloro-3-(4-(trifluoromethyl)benzyl)quinoline (1.00 g, 2.19 mmol, Intermediate 69: step a) was dissolved in THF (20 mL) in a dry round bottom flask under an N2 atmosphere, then cooled to −78° C. in dry ice acetone bath. n-BuLi (1.6 M in hexanes, 1.74 mL, 2.79 mmol) was then added dropwise via syringe over approximately 5 minutes. The contents were stirred at −78° C. for approximately 10 minutes, then a solution of 1,2-dimethyl-1H-imidazole-5-carbaldehyde (0.30 g, 2.4 mmol) in THF (20 mL) was added via cannula and the resulting mixture stirred for 10 minutes at −78° C. The dry ice bath was then removed and replaced with an ice water bath and the mixture stirred at 0° C. for approximately one hour. The reaction was then quenched with a saturated, aqueous NH4Cl solution, then transferred to a separatory funnel with EtOAc. The organic phase was extracted with a saturated, aqueous NH4Cl solution and deionized water, then separated and dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH3 MeOH in DCM) to provide the title compound.

1. stirringthe resulting mixture stirred for 10 minutes at −78° C
2. customThe dry ice bath was then removed
3. customreplaced with an ice water bath
4. stirringthe mixture stirred at 0° C. for approximately one hour
5. customThe reaction was then quenched with a saturated, aqueous NH4Cl solution
6. customtransferred to a separatory funnel with EtOAc
7. extractionThe organic phase was extracted with a saturated, aqueous NH4Cl solution
8. customseparated
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH3 MeOH in DCM)