反应详情

温度

150 °C

A stirred solution of 5-bromo-N-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-4-(trifluoromethyl)-1,2-benzenediamine (D55) (0.34 mmol) in tetrahydrofuran (8 ml) at room temperature under argon was treated with diisopropylethylamine (0.12 ml, 0.68 mmol) followed by ethyl chloroformate (40 mg, 0.38 mmol) and then heated under reflux for 2 hrs. The mixture was concentrated under vacuum and the residue dissolved in dimethylformamide, treated with more diisopropylethylamine (0.12 ml) and heated at 150° C. for 0.75 hr. The solution was then concentrated under vacuum and the residue treated with 10% Na2CO3 solution and extracted with ethyl acetate. The extract was dried and concentrated under vacuum. The residue was triturated with diethyl ether to afford 6-bromo-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one as a beige solid. This was converted to its HCl salt as a beige solid (55 mg, 33%). MH+=448, 450.

1. temperatureheated
2. temperatureunder reflux for 2 hrs
3. concentrationThe mixture was concentrated under vacuum
4. dissolutionthe residue dissolved in dimethylformamide
5. additiontreated with more diisopropylethylamine (0.12 ml)
6. concentrationThe solution was then concentrated under vacuum
7. additionthe residue treated with 10% Na2CO3 solution
8. extractionextracted with ethyl acetate
9. customThe extract was dried
10. concentrationconcentrated under vacuum
11. customThe residue was triturated with diethyl ether