反应详情

Triethyloxonium tetrafluoroborate (330 mg, 1.738 mmol) was added to a suspension of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37) (460 mg, 1.580 mmol) in dry Dichloromethane (DCM) (3.9 ml). The reaction mixture was stirred at room temperature 45 mins—mixture became clear. 4-Methyl-1,2,3-thiadiazole-5-carbohydrazide (300 mg, 1.896 mmol, commercially available) was added and the resulting reaction mixture was stirred at room temperature 2 h 10 min. The solvent was evaporated under reduced pressure. The residue was dissolved in 1-butanol (3.90 ml) and the reaction mixture was stirred at reflux for 17 h. The reaction mixture was diluted in ethyl acetate (150 mL) and washed with water (2×25 mL), sat. NaHCO3 (25 mL) and brine (2×25 mL). The resulting organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by MDAP (basic method). The resulting residue was triturated with ether (5×2 mL) and then dried under vacuum at 50° C. to afford the desired product in 117.4 mg as a cream powder.

1. customthe resulting reaction mixture
2. stirringwas stirred at room temperature 2 h 10 min
3. customThe solvent was evaporated under reduced pressure
4. dissolutionThe residue was dissolved in 1-butanol (3.90 ml)
5. stirringthe reaction mixture was stirred
6. temperatureat reflux for 17 h
7. additionThe reaction mixture was diluted in ethyl acetate (150 mL)
8. washwashed with water (2×25 mL), sat. NaHCO3 (25 mL) and brine (2×25 mL)
9. dry with materialThe resulting organic layer was dried over MgSO4
10. concentrationconcentrated under reduced pressure
11. customThe crude product was purified by MDAP (basic method)
12. customThe resulting residue was triturated with ether (5×2 mL)
13. customdried under vacuum at 50° C.