Reaction #87412

Reaction equation

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

Conditions

Workup

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

Procedure

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%).

Source