Water → HCID 22640014, compound

Participants

Reaction Steps

A solution of 73.4 g (0.465 mol) of 4-amino-5-chloro-2,6-dimethylpyrimidine in 370 ml of anhydrous N-methylpyrrolidone is added dropwise over 45 min under a nitrogen atmosphere at room temperature to a suspension of 19.5 g (0.49 mol) of sodium hydride (60% suspension in liquid paraffin) in 80 ml of anhydrous N-methylpyrrolidone. The mixture is stirred at room temperature for 1 h and then cooled to 4° C. Then a solution of 111.0 g (0.465 mol) of 4-benzyloxybenzyl chloride in anhydrous N-methylpyrrolidone is added dropwise, with vigorous stirring, at a rate such that the internal temperature does not rise higher than 5° C. (about 1 h). Thereafter, the mixture is warmed to room temperature and stirred for 1 h. The solution is subsequently poured into 4 l of water and extracted with ethyl acetate (3×1 l). The combined organic extracts are washed with water (2 l), dried over sodium sulfate and concentrated. The oil (180 g) which remains is dissolved in 400 ml of isopropanol and is admixed dropwise with stirring with 100 ml of saturated ethereal hydrochloric acid. Thereafter, further ethyl acetate is added and the mixture is stirred at room temperature for 1 h for complete precipitation of the hydrochloride. The precipitate is filtered off with suction, washed with ethyl acetate (500 ml) and dried in a vacuum drying cabinet at 40° C. 114.8 g (63%) of the title compound are isolated as a beige solid. m.p.: 227° C.

Provenance & Evidence