反应详情

To a suspension of 4-[(2-chloro-4-fluorophenyl)carbonyl]-2-piperazinone (I3)(0.78 g, 3.04 mmol) in Dichloromethane (DCM) (7.60 ml) was added triethyloxonium tetrafluoroborate (0.606 g, 3.19 mmol) and the mixture was stirred at room temperature under argon. After 5-10 minutes it turned to a yellow solution. TLC showed the formation of the imidate (some unreacted starting material always present due to instability of imidate on TLC). After 1 hour 2-pyrazinecarbohydrazide (0.504 g, 3.65 mmol, commercially available) was added but it was insoluble. After 15 minutes the solvent was evaporated in vacuo and the residue taken in n-butanol (7.60 ml) and heated at reflux (120° C.). After 2 hours LCMS showed a main peak which is consistent with the desired product. It was concentrated in vacuo and the residue was purified by flash chromatography (Biotage SP4, 40+M cartridge) with a gradient of 2M ammonia in MeOH 0 to 10% in DCM. The crude product was then dissolved in EtOAc (50 mL), the precipitate filtered off (50 mg of impurity by LCMS) and the solution washed with sat. NH4Cl (30 mL), water (30 mL) and brine (30 mL) and finally dried over MgSO4 to afford an off-white solid that was fruther purified by MDAP to isolate the desired product in 310 mg as a white solid.

1. additioncommercially available) was added
2. customAfter 15 minutes the solvent was evaporated in vacuo
3. temperatureheated
4. temperatureat reflux (120° C.)
5. waitAfter 2 hours LCMS showed
6. concentrationIt was concentrated in vacuo
7. customthe residue was purified by flash chromatography (Biotage SP4, 40+M cartridge) with a gradient of 2M ammonia in MeOH 0 to 10% in DCM
8. dissolutionThe crude product was then dissolved in EtOAc (50 mL)
9. filtrationthe precipitate filtered off (50 mg of impurity by LCMS)
10. washthe solution washed with sat. NH4Cl (30 mL), water (30 mL) and brine (30 mL)
11. dry with materialfinally dried over MgSO4
12. customto afford an off-white solid
13. customthat was fruther purified by MDAP