2-Amino-3-bromobenzamide → 8-Bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazolin-4-ol
反応式
[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3]([O-])=O.[Na+].[NH2:15][C:16]1[C:24]([Br:25])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19]>>[F:1][C:2]([F:13])([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][N:7]=1)[C:3]1[NH:20][C:18](=[O:19])[C:17]2[C:16](=[C:24]([Br:25])[CH:23]=[CH:22][CH:21]=2)[N:15]=1参加物
3
反応条件
- 温度
- 115 °C
実験手順
Sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (0.49 g, 2.3 mmol) and 2-amino-3-bromobenzamide (0.42 g, 1.9 mmol) were combined in trimethylsilylpolyphosphate (4.3 mL) at rt and the mixture was heated at 115° C. for 20 h with vigorous stirring. The mixture was allowed to cool to rt and then was partitioned between water (15 mL) and ethyl acetate (15 mL). The organic layer was separated and the aqueous layer (pH˜1) was extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a 1:10 to 1:1 EtOAc/hexanes to afford 2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-bromo-3H-quinazolin-4-one as an off-white solid (0.19 g, 22%).