反応 #10416

反応方程式

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

chlorosulfanyl isocyanate

→

title compound

収率 38.2%

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

収率 38.2%

溶媒

dichloromethane

反応条件

後処理

1. 1
   その他The solution is reacted at room temperature for 4 hours
2. 2
   その他the solvent is removed under reduced pressure
3. 3
   workup.ADDITIONis added
4. 4
   温度The solution is warmed to room temperature for 1 hour
5. 5
   ろ過the 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
   温度refluxed overnight
8. 8
   温度The reaction is cooled
9. 9
   その他the solvent removed under reduced pressure
10. 10
    workup.DISSOLUTIONdissolved in water (100 mL)
11. 11
    ろ過The resulting precipitate is collected via filtration

実験手順

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+).

出典