反应详情

温度

160 °C

To 4-[5-bromo-3-(5-chloro-2-thienyl)-1-(4-methoxybenzyl)-1H-pyrazol-4-yl]pyridine and 4-[3-bromo-5-(5-chloro-2-thienyl)-1-(4-methoxybenzyl)-1H-pyrazol-4-yl]pyridine (mixture of isomers 2:1, 1 eq, 0.435 mmol) in 1 mL of N,N-dimethylformamide, were added zinc cyanide (0.65 mmol) and Tetrakis(triphenylphosphine)palladium(0) (0.09 mmol). The mixture was stirred for 5 mins at 160° C. in the microwave. After cooling to room temperature, the reaction mixture was diluted with water and ethyl acetate was added. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried over MgSO4, filtered and concentrated. The residue was dissolved in 1 mL of trifluoroacetic acid and stirred at 65° C. for 2 h. Water and ethyl acetate were added. And the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with a saturated solution of sodium hydrogen carbonate, dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica gel (dichloromethane/methanol 20:1 to 10:1) to afford 19 mg of 3-(5-chloro-2-thienyl)-4-(pyridin-4-yl)-1H-pyrazole-5-carbonitrile (15% yield).

1. temperatureAfter cooling to room temperature
2. additionwas added
3. extractionThe aqueous layer was extracted with ethyl acetate
4. dry with materialthe combined organic extracts were dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in 1 mL of trifluoroacetic acid
8. stirringstirred at 65° C. for 2 h
9. additionWater and ethyl acetate were added
10. extractionAnd the aqueous layer was extracted with ethyl acetate
11. washThe combined organic extracts were washed with a saturated solution of sodium hydrogen carbonate
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated
15. customThe residue was purified by chromatography on silica gel (dichloromethane/methanol 20:1 to 10:1)