Pyrimidine-5-carboxylic acid → Pyrimidine-5-carboxylic acid {4-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-amide

Participants

Reaction Steps

0.1 g of pyrimidine-5-carboxylic acid (0.805 mmol) and 0.28 g of 4-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butylamine (0.805 mmol) were dissolved in 10 ml of dichloromethane. 0.46 g of diisopropylethylamine (3.17 mmol), 0.054 g of hydroxybenzotriazole (HOBt, 0.4 mmol), and 0.17 g of N-ethyl-N′-(3-dimethylamino-propyl)-carbodiimide hydrochloride (EDCl, 0.88 mmol) were added at 0° C. The reaction mixture was stirred for 16 h at room temperature. Then, 0.085 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride were added and the reaction mixture was stirred for 4 h. The solvent was evaporated and the residue partitioned between and ethyl acetate and saturated aqueous sodium chloride. 4 ml of acetone were added to improve phase separation. The organic phase was dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using ethyl acetate and ethyl acetate-methanol (5-10%). Evaporation of the solvent yielded 0.16 g of the title compound as a white solid.

Provenance & Evidence