反应详情

温度

65 °C

Ethyl trans-4-(4-{[hydrazino(oxo)acetyl]amino}phenoxy)cyclohexanecarboxylate (Intermediate 3, 698 mg, 2.00 mmol) was added in one portion to a stirred solution of 4-(difluoromethoxy)phenyl isothiocyanate (483 mg, 2.40 mmol) in DMF (10 mL) and the reaction mixture was stirred at 65° C. for 30 mins. EDCI (461 mg, 2.40 mmol) was added in one portion and the reaction mixture was heated to 85° C. for 3 h. The mixture was cooled to ambient temperature and water (15 mL) was added and the resulting suspension was filtered to provide a cream solid. The solid was taken up in a mixture of MeOH (8 mL) and THF (4 mL) and a 2N aqueous solution of NaOH (4 mL) was added in one portion and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was acidified by the addition of a 2M aqueous solution of HCl and the resulting precipitate was filtered, washed with water (10 mL) and dried under high vacuum to leave a solid. The solid was recrystallised from refluxing glacial acetic acid to give the title compound as a white solid (392 mg, 40%).

1. temperaturethe reaction mixture was heated to 85° C. for 3 h
2. temperatureThe mixture was cooled to ambient temperature
3. filtrationthe resulting suspension was filtered
4. customto provide a cream solid
5. stirringthe reaction mixture was stirred at ambient temperature for 16 h
6. filtrationthe resulting precipitate was filtered
7. washwashed with water (10 mL)
8. customdried under high vacuum
9. customto leave a solid
10. customThe solid was recrystallised
11. temperaturefrom refluxing glacial acetic acid