反应详情

To a solution of sodium hydride (60 wt % in mineral oil, 0.772 g, 19.3 mmol) in tetrahydrofuran (92 ml) was added tert-butyl 4-hydroxy-piperidine-1-carboxylate (3.70 g, 18.4 mmol) at 0° C. The mixture was stirred at room temperature for one hour, then 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (4.09 g, 18.4 mmol) was added. The mixture was stirred overnight. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was dissolved into dichloromethane (37 ml), and trifluoroacetic acid (41.9 g, 368 mmol) was added to the solution. The mixture was stirred at room temperature for 5 hours. After concentration under reduced pressure, the residue was dissolved into water. The aqueous solution was washed with ethyl acetate and basified with potassium carbonate. Extraction with chloroform was performed three times. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4′]bipyrimidinyl-6-one as a pale yellow solid (2.48 g, 8.63 mmol, 47%). This compound was used for the next reaction without further purification.

1. stirringThe mixture was stirred overnight
2. customThe mixture was partitioned between water and ethyl acetate
3. washThe organic layer was washed with brine
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated in vacuo
6. additionwas added to the solution
7. stirringThe mixture was stirred at room temperature for 5 hours
8. concentrationAfter concentration under reduced pressure
9. dissolutionthe residue was dissolved into water
10. washThe aqueous solution was washed with ethyl acetate
11. extractionExtraction with chloroform
12. dry with materialThe organic layer was dried over sodium sulfate
13. concentrationconcentrated in vacuo