Reaktionsgleichung
[NH2:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[F:12][C:13]([F:24])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:14]([O-])=O.[Na+].C[Si](OP(=O)=O)(C)C.O>CCOC(C)=O>[F:24][C:13]([F:12])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1)[C:14]1[N:6]=[C:4]([OH:5])[C:3]2[C:2](=[CH:10][C:9]([CH3:11])=[CH:8][CH:7]=2)[N:1]=1Komponenten
6
Edukt 4
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- 130 °C
Versuchsvorschrift
To a mixture of 2-amino-4-methylbenzamide (804 mg, 5.36 mmol) and sodium 2,2-difluoro-2-(5-fluoropyridin-2-yl)acetate from Example 2 Step B (1.25 g, 5.89 mmol) was added trimethylsilyl polyphosphate (ca. 10 mL) and the mixture was heated at 130° C. in a sand bath overnight. The mixture was allowed to cool to rt, and then water (75 mL) and EtOAc (75 mL) were added and the mixture was stirred at rt for 1 h. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-60% EtOAc/hexanes to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methylquinazolin-4-ol (1.09 g, 66%). LCMS (ESI) m/z 306 (M+H)+.
Aufarbeitung
- temperatureto cool to rt
- customThe organic layer was separated
- washwashed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel chromatography
- washeluting with 0-60% EtOAc/hexanes
Quellen und Nachweise
- ORD-Eintrag
- ord-1aca565682e64f6b9c259285947cf1cb
- Quelldatensatz
- uspto-grants-2014_01
- Patentnummer
- US08633207B2
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