反应详情

温度

100 °C

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), 5-bromo-2-nitropyridine (2.0 g, 10.0 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (2.0 g, 10.0 mmol), and cesium carbonate (6.5 g, 20 mmol). See FIG. 9. After bubbling nitrogen through the resulting mixture for 30 minutes, XantPhos (579 mg, 1.0 mmol) and tris(di-benzylideneacetone)dipalladium(0) (915 mg, 1.0 mmol) were added, and the reaction mixture was heated at 100° C. for 15 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous layer was separated and extracted with ethyl acetate (150 mL×3). The combined organic layer was washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with 30:1 DCM/MeOH to afford 109a (1.6 g, 44%) as a yellow solid. MS: [M+H]+ 323. 1H NMR (500 MHz, DMSO) δ 8.21 (d, J=3.5, 1H), 8.18 (d, J=9.0, 1H), 7.43-7.45 (m, 1H), 4.33 (s, 1H), 3.92-3.99 (m, 1H), 3.80 (d, J=12.5, 2H), 3.06-3.23 (m, 3H), 1.43 (s, 9H), 1.09 (d, J=6.5, 3H).

1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. temperaturereflux condenser
3. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
4. temperatureAfter this time the reaction was cooled to room temperature
5. filtrationfiltered
6. customThe filtrate was partitioned between ethyl acetate (100 mL) and water (100 mL)
7. customThe aqueous layer was separated
8. extractionextracted with ethyl acetate (150 mL×3)
9. washThe combined organic layer was washed with brine (50 mL)
10. dry with materialdried over sodium sulfate
11. customThe drying agent was removed by filtration
12. concentrationthe filtrate was concentrated under reduced pressure
13. customThe residue was purified on flash column
14. washeluting with 30:1 DCM/MeOH