반응 #10423

반응 방정식

2,4-dinitrophenylhydroxylamine

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

tetrahydrofuran

sodium hydride

→

3-amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione

용매

N,N-dimethylformamide

dioxane

반응 조건

후처리

1. 1
   온도the resulting solution is cooled to room temperature
2. 2
   온도The mixture is heated at 60° C. to 80° C. for 30 minutes
3. 3
   온도cooled
4. 4
   기타the dioxane removed reduced pressure
5. 5
   workup.ADDITIONThe residue is poured into ice water
6. 6
   추출extracted with ethyl acetate
7. 7
   세척washed with brine
8. 8
   건조dried with Na2SO4
9. 9
   농축concentrated in vacuo
10. 10
    기타The residue is purified by flash column chromatography (ethyl acetate/hexanes)

실험 절차

To a solution of a 1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione (Example 23) in 1:1 dry tetrahydrofuran or dioxane and dry N,N-dimethylformamide is added portionwise sodium hydride (1.1 eq., 60% mineral oil dispersion) at room temperature. After stirring at 50° C. for 20 to 30 minutes, the resulting solution is cooled to room temperature and 2,4-dinitrophenylhydroxylamine (4 eq.) is added. The mixture is heated at 60° C. to 80° C. for 30 minutes, cooled, and the dioxane removed reduced pressure. The residue is poured into ice water and extracted with ethyl acetate. The organic layers are combined, washed with brine, dried with Na2SO4, and concentrated in vacuo. The residue is purified by flash column chromatography (ethyl acetate/hexanes) to afford a 3-amino-1-cyclopropyl-6,7-difluoro-1H-quinazoline-2,4-dione.

출처