反应详情

温度

0 °C

A mixture of tautomers, 3-[(2-chloro-4-pyrimidinyl)acetyl]benzonitrile and 3-[(E)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]benzonitrile, (1.56 g, 6.05 mmol) was dissolved in 100 mL of DCM with stirring and cooled to 0° C. NBS (1.08 g, 6.07 mmol) was added and the reaction was allowed to warm to rt. The reaction was stirred for one hour and concentrated in vacuo. The residue was dissolved in dioxane with stirring. 2-Aminopyridine (1.71 g, 18.2 mmol) was added, and the reaction was heated to 60° C. The reaction was stirred overnight and cooled to rt. The reaction was poured into H2O and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with DCM (2×) and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography, and fractions containing product were concentrated in vacuo. The residue was triturated with diethyl ether and hexanes (˜1:1), filtered, and the solid was washed with diethyl ether and hexanes (˜1:1). The solid was collected to provide 1.50 g (75%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.35 (d, J=7.0 Hz, 1H), 8.60 (d, J=5.3 Hz, 1H), 8.14 (s, 1H), 7.98 (d, J=7.9 Hz, 1H), 7.93 (d, J=7.9 Hz, 1H), 7.81 (d, J=8.8 Hz, 1H), 7.67 (t, J=7.9 Hz, 1H), 7.59 (dd, J=6.8, 1.1 Hz, 1H), 7.31-7.17 (m, 2H).

1. temperatureto warm to rt
2. stirringThe reaction was stirred for one hour
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in dioxane
5. stirringwith stirring
6. temperaturethe reaction was heated to 60° C
7. stirringThe reaction was stirred overnight
8. temperaturecooled to rt
9. customThe layers were separated
10. washthe organic layer was washed with brine
11. extractionThe combined aqueous layers were extracted with DCM (2×) and EtOAc
12. dry with materialThe combined organic layers were dried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe residue was purified by flash chromatography, and fractions
16. additioncontaining product
17. concentrationwere concentrated in vacuo
18. customThe residue was triturated with diethyl ether and hexanes (˜1:1)
19. filtrationfiltered
20. washthe solid was washed with diethyl ether and hexanes (˜1:1)
21. customThe solid was collected