2-Amino-4-methoxybenzamide → 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4(3H)-one
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[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19].C[Si](OP(=O)=O)(C)C>>[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](=[CH:24][C:23]([O:25][CH3:26])=[CH:22][CH:21]=2)[N:15]=1参加物
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 (2.3 g, 10.8 mmol) and 2-amino-4-methoxybenzamide (1.5 g, 9.0 mmol) were combined with trimethylsilyl polyphosphate (15 mL) and the mixture was heated at 115° C. for 18 h with vigorous stirring. To mixture was allowed to cool to rt, and then was partitioned between were water (15 mL) and EtOAc (15 mL). The organic layer was separated and the aqueous layer (pH˜1) was extracted with EtOAc (3×30 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1:10 to 1:1 EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4(3H)-one (487 mg) as an off-white solid.
後処理
- temperatureto cool to rt
- customwas partitioned
- customThe organic layer was separated
- extractionthe aqueous layer (pH˜1) was extracted with EtOAc (3×30 mL)
- dry with materialThe combined organic layers were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel chromatography
- washeluting with 1:10 to 1:1 EtOAc/hexanes
出典と根拠
- ORDレコード
- ord-e5d2a998aa494fdb96cbfdeb51893c0e
- 出典データセット
- uspto-grants-2014_01
- 特許番号
- US08633207B2
反応ノート
読み込み中…