反应详情

温度

117.5 °C

A slurry of (Z)-ethyl 3-((2-amino-2-oxoethyl)amino)-3-(5-chloro-2-methoxyphenyl)acrylate (20 g, 63 mmol) in a mixture of butyl acetate (140 mL) and DMF (38 mL) was treated with trimethylsilyl isothiocyanate (16.8 g, 125 mmol) and the mixture was heated at 115-120° C. for 5-6 hours. The mixture was cooled to 0-5° C., butyl acetate (100 mL) was added and the mixture was slurried for 8 hours. The formed solids were filtered, and the filter cake was washed with butyl acetate (2×100 mL). The solid was dried in a vacuum oven at 50° C. for 12 hours to a tan solid. The solid was dissolved in a 5:1 mixture of DMF and water at room temperature and additional water was added slowly to crystallize the material. The slurry was cooled to 10° C. and stirred for 8 hours, followed by filtration and washing with water. The filter cake was dried in a vacuum oven at 50° C. for 8 hours. The solid was dissolved in a 1:1 mixture of methanol and water and the slurry was heated to 50° C. and held at this temperature for 2 hours. After cooling to 10° C. over 30 minutes, the slurry was held at this temperature for 1 hour, filtered and washed with water and dried in a vacuum oven at 50° C. for 8 hours to give the title compound as a white solid.

1. temperatureThe mixture was cooled to 0-5° C.
2. filtrationThe formed solids were filtered
3. washthe filter cake was washed with butyl acetate (2×100 mL)
4. customThe solid was dried in a vacuum oven at 50° C. for 12 hours to a tan solid
5. dissolutionThe solid was dissolved in a 5:1 mixture of DMF and water at room temperature
6. additionadditional water was added slowly
7. customto crystallize the material
8. temperatureThe slurry was cooled to 10° C.
9. filtrationfollowed by filtration
10. washwashing with water
11. customThe filter cake was dried in a vacuum oven at 50° C. for 8 hours
12. dissolutionThe solid was dissolved in a 1:1 mixture of methanol and water
13. temperaturethe slurry was heated to 50° C.
14. waitheld at this temperature for 2 hours
15. temperatureAfter cooling to 10° C. over 30 minutes
16. waitthe slurry was held at this temperature for 1 hour
17. filtrationfiltered
18. washwashed with water
19. customdried in a vacuum oven at 50° C. for 8 hours