反应详情

0.755 g of (R)-3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-2-methyl-propan-1-ol (2.18 mmol) were stirred in 7.6 ml of dimethylformamide under argon. 0.105 g of 60% sodium hydride (2.6 mmol) were added and stirred for 10 min. A solution of 0.275 g of 2-chloro-pyrimidine (2.4 mmol) in 2.4 ml of dimethylformamide was added. The reaction mixture was stirred for 16 h, followed by the addition of 30 ml of water and 40 ml of ethyl acetate. The organic layer was separated and the aqueous phase extracted with a further portion of ethyl acetate. The combined extracts were concentrated to dryness and the crude product purified by flash column chromatography eluting with ethyl acetate. The fractions containing the product were combined and evaporated under reduced pressure to give a pale yellow oil. The oil was dissolved in tert-butyl methylether and 4 N hydrochloric acid in dioxan was added to the solution. A white solid separated. The precipitate was collected by filtration, washed with tert-butyl methyl ether and dried in a vacuum oven to yield 0.42 g of the title compound.

1. stirringThe reaction mixture was stirred for 16 h
2. customThe organic layer was separated
3. extractionthe aqueous phase extracted with a further portion of ethyl acetate
4. concentrationThe combined extracts were concentrated to dryness
5. customthe crude product purified by flash column chromatography
6. washeluting with ethyl acetate
7. additionThe fractions containing the product
8. customevaporated under reduced pressure
9. customto give a pale yellow oil
10. customA white solid separated
11. filtrationThe precipitate was collected by filtration
12. washwashed with tert-butyl methyl ether
13. customdried in a vacuum oven