Reaction #87424

Reaction equation

2-Chloro-4-((cyclopropylmethoxy)methyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine

3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline

2-(dicyclohexylphosphino)-biphenyl

→

title compound

4-((Cyclopropylmethoxy)methyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Solvents

dioxane

Conditions

Workup

1. 1
   OtherThe vial was capped
2. 2
   Otherevacuated
3. 3
   Otherflushed with nitrogen
4. 4
   FiltrationThe mixture was filtered through a pad of silica
5. 5
   Washthe pad was washed with 10% methanol in ethyl acetate
6. 6
   OtherThe solvents were evaporated
7. 7
   Otherthe residue was purified by preparative HPLC

Procedure

2-Chloro-4-((cyclopropylmethoxy)methyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (approximately 50% pure, 33 mg, 0.11 mmol), 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (26 mg, 0.13 mmol), palladium (II) acetate (4 mg, 0.02 mmol), 2-(dicyclohexylphosphino)-biphenyl (6 mg, 0.02 mmol) cesium carbonate (69 mg, 0.21 mmol) and dioxane (2 mL) were mixed in a vial. The vial was capped, evacuated and flushed with nitrogen. The mixture was heated by microwave irradiation at 120° C. for 1.5 h. The mixture was filtered through a pad of silica, the pad was washed with 10% methanol in ethyl acetate. The solvents were evaporated and the residue was purified by preparative HPLC to give the title compound as a dry film, 15 mg (28%).

Source