Reaktion #162716

Reaktionsgleichung

(Z)-ethyl 3-((2-amino-2-oxoethyl)amino)-3-(5-chloro-2-methoxyphenyl)acrylate

trimethylsilyl isothiocyanate

→

title compound

2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide

Lösungsmittel

butyl acetate

DMF

butyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was cooled to 0-5° C.
2. 2
   FiltrationThe formed solids were filtered
3. 3
   Waschenthe filter cake was washed with butyl acetate (2×100 mL)
4. 4
   SonstigeThe solid was dried in a vacuum oven at 50° C. for 12 hours to a tan solid
5. 5
   workup.DISSOLUTIONThe solid was dissolved in a 5:1 mixture of DMF and water at room temperature
6. 6
   workup.ADDITIONadditional water was added slowly
7. 7
   Sonstigeto crystallize the material
8. 8
   TemperaturThe slurry was cooled to 10° C.
9. 9
   Filtrationfollowed by filtration
10. 10
    Waschenwashing with water
11. 11
    SonstigeThe filter cake was dried in a vacuum oven at 50° C. for 8 hours
12. 12
    workup.DISSOLUTIONThe solid was dissolved in a 1:1 mixture of methanol and water
13. 13
    Temperaturthe slurry was heated to 50° C.
14. 14
    workup.WAITheld at this temperature for 2 hours
15. 15
    TemperaturAfter cooling to 10° C. over 30 minutes
16. 16
    workup.WAITthe slurry was held at this temperature for 1 hour
17. 17
    Filtrationfiltered
18. 18
    Waschenwashed with water
19. 19
    Sonstigedried in a vacuum oven at 50° C. for 8 hours

Vorschrift

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.

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