반응 #433749

반응 방정식

Sodium hydride

4-bromo-2,6-difluoroaniline

7-benzyloxy-4-chloro-6-methoxyquinazoline

→

7-benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazoline

수율 62.1%

용매

DMF

반응 조건

후처리

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGstirring
3. 3
   온도was maintained for 4 hours
4. 4
   기타The mixture was partitioned between ethyl acetate and water (200 ml)
5. 5
   기타The organic layer was separated
6. 6
   세척washed with water, brine
7. 7
   건조dried (MgSO4)
8. 8
   기타the volatiles were removed by evaporation
9. 9
   기타The residue was triturated with isopropanol
10. 10
    여과collected by filtration
11. 11
    세척washed with ether
12. 12
    기타dried under vacuum

실험 절차

Sodium hydride (60%, 612 mg, 15.3 mmol) was added to a solution of 4-bromo-2,6-difluoroaniline (2.77 g, 6.65 mmol) in DMF (80 ml). After stirring for 30 minutes at ambient temperature, 7-benzyloxy-4-chloro-6-methoxyquinazoline (2 g, 6.65 mmol), (prepared, for example, as described in WO 97/22596, Example 1, but the free base was generated prior to use), was added and stirring was maintained for 4 hours. The mixture was partitioned between ethyl acetate and water (200 ml). The organic layer was separated, washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with isopropanol, collected by filtration, washed with ether and dried under vacuum to give 7-benzyloxy-4-(4-bromo-2,6-difluoroanilino)-6-methoxyquinazoline (1.95 g, 62%).

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