Reaktion #506764
ord-d46a025a3b96464794878b8753d9a269
Reaktionsgleichung
Edukte
Reagenzien
Lösungsmittel
Reaktionsbedingungen
Aufarbeitung
- 1Einengenconcentrated under vacuum to a foam like solid
- 2workup.DISSOLUTIONThe solid was dissolved in dioxane (23 mL)
- 3workup.STIRRINGThe reaction was stirred under N2
- 4workup.STIRRINGstirred for approximately 16 h
- 5Temperaturcooled to rt
- 6SonstigeThe organic layer was separated
- 7Waschenwashed with brine
- 8ExtraktionThe combined aqueous layers were extracted with EtOAc (2×)
- 9TrocknenThe combined organic layers were dried over MgSO4
- 10Filtrationfiltered
- 11Einengenconcentrated under vacuum
- 12SonstigeThe residue was purified by silica gel chromatography
Vorschrift
To a stirred solution of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-4-(methyloxy)benzamide (Intermediate Example 2, step E) (0.950 g, 2.28 mmol) in dichloromethane (23 mL) at rt under N2 was added NBS (0.426 g, 2.39 mmol). The reaction was stirred approximately 30 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (23 mL) and 4-fluoro-2-pyridinamine (Example 194, step A) (0.765 g, 6.83 mmol) was added. The reaction was stirred under N2, heated to 80° C., and stirred for approximately 16 h, then cooled to rt. The reaction was diluted with EtOAc and half-saturated aqueous NaHCO3. The organic layer was separated and washed with brine. The combined aqueous layers were extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography to give the title compound of step A (0.700 g, 1.37 mmol, 61%) as a light tan solid. MS (ESI): 510 [M+H]+.