Reaktionsgleichung
[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]=1Komponenten
Reaktionsbedingungen
- Temperatur
- 115 °C
Versuchsvorschrift
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.
Aufarbeitung
- 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
Quellen und Nachweise
- ORD-Eintrag
- ord-e5d2a998aa494fdb96cbfdeb51893c0e
- Quelldatensatz
- uspto-grants-2014_01
- Patentnummer
- US08633207B2
Verknüpfte Notizen
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