反应详情

Trimethyloxonium tetrafluoroborate (138 mg, 0.887 mmol) was added under argon to a suspension of 4-[(3-chloro-4-fluoro-2-methylphenyl)carbonyl]-2-piperazinone (I59) (200 mg, 0.739 mmol) in dry dichloromethane (DCM) (3.694 ml). The reaction mixture was stirred at room temperature overnight—cloudy mixture. 1,3-thiazole-2-carbohydrazide (I51) (159 mg, 1.108 mmol) was added and the resulting mixture was stirred at room temperature 2 h—reaction mixture was in solution before that a precipitate had appeared. 1-Butanol (3.69 ml) was added—mixture went into solution—and the reaction mixture was stirred at reflux 2 h. The reaction mixture was cooled down to room temperature and DCM was removed in vacuo. The reaction mixture was heated at reflux for 2 h and left at room temperature overnight. The mixture was diluted with DCM (150 mL) and washed with sat. NaHCO3 (2×25 mL), water (25 mL) and brine (25 mL). The resulting organic layer was dried over MgSO4 and concentrated under reduced pressure. NMR: lots of butanol left. The crude product was dissolved in DCM (150 mL) and washed with water (25 mL, 50 mL) and brine (25 mL). The resulting DCM layer was dried over MgSO4 and concentrated under reduced pressure. The foam residue was triturated with Et2O to afford a yellow solid (143.3 mg). The crude product was purified by MDAP (High pH). The obtained solid was dried at 50° C. under vacuum for 1.5 days. The solid was triturated with hexane to get remove the methanol and dried under vacuum at 50° C. to afford the desired product in 75.36 mg as a cream solid.

1. stirringthe resulting mixture was stirred at room temperature 2 h—
2. customreaction mixture
3. stirringthe reaction mixture was stirred
4. temperatureat reflux 2 h
5. temperatureThe reaction mixture was cooled down to room temperature
6. customDCM was removed in vacuo
7. temperatureThe reaction mixture was heated
8. temperatureat reflux for 2 h
9. waitleft at room temperature overnight
10. additionThe mixture was diluted with DCM (150 mL)
11. washwashed with sat. NaHCO3 (2×25 mL), water (25 mL) and brine (25 mL)
12. dry with materialThe resulting organic layer was dried over MgSO4
13. concentrationconcentrated under reduced pressure
14. waitNMR: lots of butanol left
15. dissolutionThe crude product was dissolved in DCM (150 mL)
16. washwashed with water (25 mL, 50 mL) and brine (25 mL)
17. dry with materialThe resulting DCM layer was dried over MgSO4
18. concentrationconcentrated under reduced pressure
19. customThe foam residue was triturated with Et2O