Sodium hydride → 2-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyrimidin-2-yloxy)-propyl]-piperazin-1-yl}-pyrimidine hydrochloride

Participants

Reaction Steps

0.31 g of sodium hydride (7.8 mmol; 60% in paraffin) was washed oil-free with pentane before 1.3 g of 3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-propan-1-ol (3.91 mmol) dissolved in 20 ml of dioxane were added. The reaction was heated to reflux for 1 h. After cooling, 0.7 g of 2-chloro-pyrimidine (6.11 mmol) dissolved in 10 ml of dioxane were added. The reaction mixture was heated under reflux for 2 h. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, the solvent evaporated, and the residue re-dissolved in isopropanol and treated with hydrochloric acid in diethyl ether. After removing most of the organic phase, the residue was treated with isopranol/diisopropyl ether, which, after cautious evaporation, yielded 1.6 g of the title compound.

Provenance & Evidence