反应详情

温度

120 °C

Combine 3′-(4-fluoro-phenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.500 g, 1.94 mmol) with (5-methyl-pyrazol-1-yl)-acetic acid ethyl ester (0.416 g, 2.48 mmol) in ethanol (8 mL). Add acetic acid (801 μL, 14 mmol) and a 37% aqueous solution of formaldehyde (401 μL). Heat in microwave at 120° C. for 5 hr. Add acetic acid (801 μL, 14 mmol) and a 37% aqueous solution of formaldehyde (401 μL). Heat in microwave at 120° C. for 3 hr. Concentrate, add ethyl acetate and saturated aqueous sodium bicarbonate solution. Separate organic layer. Extract aqueous layer twice with ethyl acetate, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 methanol:ethyl acetate) to give {4-[3′-(4-fluoro-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-ylmethyl]-5-methyl-pyrazol-1-yl}-acetic acid ethyl ester (139 mg, 16%). MS (ES): m/z=439 [M+H]+.

1. temperatureHeat in microwave at 120° C. for 3 hr
2. concentrationConcentrate
3. additionadd ethyl acetate and saturated aqueous sodium bicarbonate solution
4. dry with materialExtract aqueous layer twice with ethyl acetate, dry (magnesium sulfate)
5. filtrationfilter
6. concentrationconcentrate
7. custompurify (silica gel chromatography
8. washeluting with 50:50 to 100:0 ethyl acetate