Reaktion #87412

Reaktionsgleichung

2-(2-{[3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]amino}-6-[(2,2,2-trifluoroethoxy)-methyl]pyrimidin-4-yl)acetamide

Phosphorus oxychloride

dimethylaniline

→

title compound

2-[2-[3-Methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe layers were separated
2. 2
   Extraktionthe aqueous layer was extracted twice with dichloromethane
3. 3
   TrocknenThe combined organic layers were dried over sodium sulfate
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe residue was purified on a silica gel cartridge
6. 6
   Wascheneluting with a gradient of methanol, DCM and EtOAc
7. 7
   SonstigeThe residue was further purified on a C18 reverse phase cartridge
8. 8
   Wascheneluting with 30% to 70% MeOH/H2O containing 0.05% TFA

Vorschrift

2-(2-{[3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]amino}-6-[(2,2,2-trifluoroethoxy)-methyl]pyrimidin-4-yl)acetamide (68 mg, 0.15 mmol, 1.0 eq) was added to a solution of Phosphorus oxychloride (4 mL) and dimethylaniline (0.033 mL, 0.26 mmol, 1.75 eq). The reaction mixture was immersed in a pre-heated oil bath at 120° C. for 10 min. The reaction mixture, still hot, was rapidly poured into ice/DCM slurry and stirred for 16 h. The layers were separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified on a silica gel cartridge eluting with a gradient of methanol, DCM and EtOAc. The residue was further purified on a C18 reverse phase cartridge eluting with 30% to 70% MeOH/H2O containing 0.05% TFA to give the title compound, 8 mg (12%).

Quelle