Lithium Hydroxide → 2-tert-Butyl-4-cyclopropyl-6-{4-[3-(pyrimidin-2-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidine

Temperature

60 °C

0.4 g of 2-mercapto-pyrimidine (3.57 mmol) were dissolved in 20 ml of dimethylformamide. After addition of 0.09 g of lithium hydroxide (3.57 mmol) and 0.27 g of sodium iodide (1.78 mmol), the reaction mixture was stirred at 60° C. and 1.2 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclopropyl-pyrimidine (3.56 mmol) were added in portions. The reaction mixture was stirred at 60° C. for 1 h, and, after evaporation of dimethylformamide, the residue was partitioned between 30 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water. The aqueous phase was re-extracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was re-dissolved in 30 ml of ethyl acetate and treated with 4 N hydrochloric acid in dioxane. The precipitated hydrochloride salt was collected by filtration and dried to yield 1.66 g of the title compound.

1. stirringThe reaction mixture was stirred at 60° C. for 1 h
2. customafter evaporation of dimethylformamide
3. customthe residue was partitioned between 30 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water
4. extractionThe aqueous phase was re-extracted twice with ethyl acetate
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. dissolutionThe crude product was re-dissolved in 30 ml of ethyl acetate
9. additiontreated with 4 N hydrochloric acid in dioxane
10. filtrationThe precipitated hydrochloride salt was collected by filtration
11. customdried

ORD record

ord-ed001a914bf640f7b991be02ba25af60

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08202868B2