反应详情

温度

120 °C

4-[(2,3-Dichloro-4-fluorophenyl)carbonyl]-2-piperazinone (I34) (0.25 g, 0.859 mmol) was dissolved in dichloromethane (DCM) (2.147 ml) and stirred under an argon atmosphere. Triethyloxonium tetrafluoroborate (0.196 g, 1.031 mmol) was added and the solution was left to stir for 40 minutes. A clear solution formed. 1,2,4-Thiadiazole-5-carbohydrazide (I80) (0.149 g, 1.031 mmol) was added and the solution was left to stir under argon for 60 minutes and then the solvent was removed under reduced pressure. 1-Butanol (2.147 ml) was added and the solution was left to reflux at 120° C. under an argon atmosphere for 5 hours. The solvent was removed under reduced pressure to afford a crude light orange solid of 0.56 g. TLC (DCM/MeOH 90:10): showed amide remained but some product had been formed. The crude material was purified by flash chromatography (Biotage SP4, 50 g cartridge) with a gradient of MeOH 0-10% in DCM. The solvent was removed under reduced pressure to afford desired product but still containing some impurities. The isolated material was then purified by MDAP and the solvent was removed under reduced pressure and transferred to a vial. The material was triturated with ether to afford desired product in 5.7 mg.

1. waitthe solution was left
2. stirringto stir for 40 minutes
3. customA clear solution formed
4. waitthe solution was left
5. stirringto stir under argon for 60 minutes
6. customthe solvent was removed under reduced pressure
7. addition1-Butanol (2.147 ml) was added
8. waitthe solution was left
9. customThe solvent was removed under reduced pressure
10. customto afford a crude light orange solid of 0.56 g
11. customsome product had been formed
12. customThe crude material was purified by flash chromatography (Biotage SP4, 50 g cartridge) with a gradient of MeOH 0-10% in DCM
13. customThe solvent was removed under reduced pressure