Pyridine → 1-[4-(Piperidin-1-yl)pyrimidin-2-yl]ethanone

Temperature

0 °C

To a stirred solution of 2-acetylpyrimidin-4(3H)-one (Intermediate 51, 500 mg, 3.62 mmol) in dichloromethane (10 mL) cooled to 0° C., pyridine (860 mg, 10.87 mmol) was added and stirred for 10 min at 0° C., followed by the addition of methane sulfonyl chloride (830 mg, 7.23 mmol) at 0° C. The above reaction mixture was stirred at room temperature for overnight. The reaction mixture was washed with water (50 mL), the aqueous layer was extracted with dichloromethane (50 mL). The combined organic layer was washed with brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude residue was dissolved in acetonitrile; piperidine (616 mg, 7.24 mmol) was added and the reaction mixture was stirred for 2 h at room temperature. The reaction mixture was concentrated under reduced pressure; water (50 mL) was added and extracted with ethyl acetate (2×30 mL). The combined organic layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield the crude product, which was purified by column chromatography over silica gel (10-50% ethyl acetate/pet ether) to obtain 1-[4-(piperidin-1-yl)pyrimidin-2-yl]ethanone 200 mg (46.8%).

1. customThe above reaction mixture
2. stirringwas stirred at room temperature for overnight
3. washThe reaction mixture was washed with water (50 mL)
4. extractionthe aqueous layer was extracted with dichloromethane (50 mL)
5. washThe combined organic layer was washed with brine solution
6. dry with materialdried over anhydrous sodium sulphate
7. concentrationconcentrated under reduced pressure
8. dissolutionThe crude residue was dissolved in acetonitrile
9. stirringthe reaction mixture was stirred for 2 h at room temperature
10. concentrationThe reaction mixture was concentrated under reduced pressure
11. additionwater (50 mL) was added
12. extractionextracted with ethyl acetate (2×30 mL)
13. washThe combined organic layer was washed with brine
14. dry with materialdried over anhydrous sodium sulphate
15. concentrationconcentrated under reduced pressure
16. customto yield the crude product, which
17. customwas purified by column chromatography over silica gel (10-50% ethyl acetate/pet ether)

ORD record

ord-3f9e7b61df554e89a4df673d88b62965

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071605B2