反应详情

温度

110 °C

Dissolve 1-methyl-1H-pyrazole-4-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide (0.250 g, 0.625 mmol) in DMA-H2O (or DME:H2O) (6 mL; 3:1 v/v, previously degassed with nitrogen). Add 4-cyanomethylphenyl boronic acid (0.121 g, 0.750 mmol), potassium carbonate (0.207 g, 1.500 mmol) and tetrakis(triphenylphosphine)palladium (0.036 g, 0.031 mmol). Stir the reaction mixture at 110° C. for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol. Purify by silica gel chromatography eluting with hexanes:acetone 1:1 to afford the free base of the title compound (0.214 g, 71% yield).

1. custom3:1 v/v, previously degassed with nitrogen)
2. temperatureCool
3. extractionExtract the aqueous layer with ethyl acetate
4. dry with materialDry the combined organic layers over sodium sulfate
5. filtrationfilter
6. concentrationconcentrate
7. customPurify by SCX chromatography
8. washeluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol
9. customPurify by silica gel chromatography
10. washeluting with hexanes:acetone 1:1