反应详情

温度

60 °C

A tautomeric mixture of 5-[(2-Chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide and 5-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (1.26 g, 3.02 mmol) was dissolved in 60 mL of DCM with stirring. NBS (0.538 g, 3.02 mmol) was added in a single portion. The reaction was stirred for 20 minutes and concentrated in vacuo. The residue was dissolved in 60 mL of dioxane with stirring, and 2-aminopyridine (0.853 g, 9.06 mmol) was added in a single portion. The reaction was heated at 60° C. with an oil bath for 24 hours and cooled to rt. The reaction was stirred at rt for an additional 40 hours. The reaction was poured into half-saturated NaHCO3 solution and EtOAc, and the layers were separated. The organic layer was washed with brine, and the combined aqueous layers were extracted twice with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography. Impure fractions were concentrated and further purified by flash chromatography. The combined clean fractions (by TLC) from both runs were combined and concentrated in vacuo to afford 1.07 g (72%) of the desired product. 1H NMR (400 MHz, DMSO-d6): δ 9.80 (s, 1H), 9.40 (d, J=7.0 Hz, 1H), 8.57 (d, J=5.1 Hz, 1H), 8.10 (d, J=1.5 Hz, 1H), 7.84-7.77 (m, 2H), 7.57 (m, 1H), 7.39 (m, 1H), 7.33-7.26 (m, 2H), 7.24-7.14 (m, 3H), 3.99 (s, 3H).

1. stirringThe reaction was stirred for 20 minutes
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in 60 mL of dioxane
4. stirringwith stirring
5. temperaturecooled to rt
6. stirringThe reaction was stirred at rt for an additional 40 hours
7. customthe layers were separated
8. washThe organic layer was washed with brine
9. extractionthe combined aqueous layers were extracted twice with EtOAc
10. dry with materialThe combined organic layers were dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude product was purified by flash chromatography
14. concentrationImpure fractions were concentrated
15. customfurther purified by flash chromatography
16. concentrationconcentrated in vacuo