反应详情

温度

100 °C

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a 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). After bubbling nitrogen through the resulting mixture for 10 minutes, tris(dibenzylideneacetone)dipalladium(0) (915 mg, 1.0 mmol) and XantPhos (579 mg, 1.0 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and 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 (3×50 mL). The combined organic layer was washed with brine (100 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 by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 115a (1.6 g, 44%) as a yellow solid. MS-ESI: [M+H]+ 323. 1H NMR (500 MHz, DMSO-d6) δ 8.21 (d, J=3.5 Hz, 1H), 8.18 (d, J=9.0 Hz, 1H), 7.45-7.43 (m, 1H), 4.34-4.33 (m, 1H), 3.92-3.99 (m, 1H), 3.80 (d, J=12.5 Hz, 2H), 3.06-3.23 (m, 3H), 1.43 (s, 9H), 1.09 (d, J=6.5 Hz, 3H).

1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customAfter bubbling nitrogen through the resulting mixture for 10 minutes
3. customflush
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 (3×50 mL)
9. washThe combined organic layer was washed with brine (100 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 by silica-gel column chromatography
14. washeluting with 30:1 dichloromethane/methanol