反应详情

温度

-78 °C

A 2.5M n-butyl lithium in tetrahydrofuran solution (0.16 ml, 0.40 mmol) was added dropwise to a solution of tert-butyl 4-(3-bromoisoquinolin-1-yl)-1,4-diazepane-1-carboxylate (155 mg, 0.38 mmol) in tetrahydrofuran (8 ml), cooled to −78° C. The reaction mixture was stirred at that temperature for 10 minutes. A solution of 2-fluoro-N-methoxy-N-methylnicotinamide (70 mg, 0.38 mmol) in tetrahydrofuran (3 ml) was added dropwise. The reaction mixture was allowed to warm up to room temperature and was stirred for 2 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride and extracted into ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound as a yellow solid (78 mg, 46% yield).

1. temperatureto warm up to room temperature
2. stirringwas stirred for 2 hours
3. customThe reaction was quenched with a saturated aqueous solution of ammonium chloride
4. extractionextracted into ethyl acetate
5. dry with materialThe organic phase was dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified on silica gel by flash column chromatography