Reacción #10416

Ecuación de reacción

2-cyclopropylamino-4,5-difluorobenzoic acid ethyl ester

chlorosulfanyl isocyanate

→

title compound

Rendimiento 38.2%

1-Cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione

Rendimiento 38.2%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solution is reacted at room temperature for 4 hours
2. 2
   Otrothe solvent is removed under reduced pressure
3. 3
   workup.ADDITIONis added
4. 4
   TemperaturaThe solution is warmed to room temperature for 1 hour
5. 5
   Filtraciónthe solid is collected by filtration
6. 6
   workup.ADDITIONThe dry solid is added to a solution of triethylamine (5 mL) in THF (250 mL)
7. 7
   Temperaturarefluxed overnight
8. 8
   TemperaturaThe reaction is cooled
9. 9
   Otrothe solvent removed under reduced pressure
10. 10
    workup.DISSOLUTIONdissolved in water (100 mL)
11. 11
    FiltraciónThe resulting precipitate is collected via filtration

Procedimiento

To a solution of 2-cyclopropylamino-4,5-difluorobenzoic acid ethyl ester (Example 22) (5.0 g, 22.0 mmol) in dry dichloromethane (120 mL) under a N2 atmosphere is added chlorosulfanyl isocyanate (3.11 g, 22 mmol). The solution is reacted at room temperature for 4 hours, and the solvent is removed under reduced pressure. The residue is cooled to −20° C., and a cold brine solution (100 mL) buffered with NaHCO3 is added. The solution is warmed to room temperature for 1 hour. The volume is reduced by half with a stream of air, and the solid is collected by filtration. The dry solid is added to a solution of triethylamine (5 mL) in THF (250 mL) and refluxed overnight. The reaction is cooled, the solvent removed under reduced pressure, dissolved in water (100 mL), and acidified to pH 1–2 with 1.0 M hydrochloric acid. The resulting precipitate is collected via filtration to afford 2.0 g of the title compound. MS CI: m/z 239 (MH+).

Fuente