反应详情

温度

0 °C

70 mg 2-(5-cyclopropyl-4-methyl-1H-pyrazol-3-yl)-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine 1-16-1 (0-217 mmol, 1.0 eq) were dissolved in 0.52 mL THF and cooled to 0° C. 10.4 mg sodiumhydride (60%, 0.261 mmol, 1.2 eq) were added. The mixture stirred for 5 minutes, then the ice bath was removed and 65.2 mg 2-(bromomethyl)-5-(difluoromethoxy)-1,3-difluorobenzene (0.239 mmol, 1.1 eq) were added. The reaction stirred at rt for 4 days. Again 5 mg sodiumhydride (60%, 0.130 mmol, 0.6 eq) and 33 mg 2-(bromomethyl)-5-(difluoromethoxy)-1,3-difluorobenzene (0.120 mmol, 0.55 eq) were added. The reaction stirred at rt for 2 hours. Water was added and the aqueous layer was extracted by ethylacetate twice. The collected organic layers were washed with brine, dried with a silicon filter and concentrated in vacuo The crude product was purified by flashcromatography and HPLC to provide 10 mg (0.02 mmol, 8%) of the analytically pure target compound.

1. customthe ice bath was removed
2. stirringThe reaction stirred at rt for 4 days
3. stirringThe reaction stirred at rt for 2 hours
4. extractionthe aqueous layer was extracted by ethylacetate twice
5. washThe collected organic layers were washed with brine
6. customdried with a silicon
7. filtrationfilter
8. concentrationconcentrated in vacuo The crude product
9. customwas purified by flashcromatography and HPLC
10. customto provide 10 mg (0.02 mmol, 8%) of the analytically pure target compound