Potassium Hydroxide → 4,6-Diamino-5-(2-methoxybenzyl)-2-[2-(1-piperazinyl)ethylthio]-pyrimidine fumarate

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Reaction Steps

2.99 g (9.5 mmoles) of 4,6-diamino-2-mercapto-5-(2-ethoxy-benzyl)pyrimidine are suspended in a solution of 3.37 g (60 mmoles) of potassium hydroxide in 60 ml of water, and, to the suspension obtained, a solution of 2.22 g (10 mmoles) of 1-(2-chloroethyl)piperazine dihydrochloride in 10 ml of water are added, drop by drop, at 25° C. The reaction mixture is stirred at room temperature for 2 hours, then 50 ml of water and 100 ml of methyl alcohol are added. The mixture is heated to boiling point, filtered while hot, and the filtrate is allowed to crystallize at 0° C. The substance obtained is purified by chromatography over a column filled with 130 g of Kieselgel 60 using a mixture of methyl alcohol and toluene in a ratio of 2:3. The crystalline product obtained is recrystallized from a mixture of 20 ml of methyl alcohol and 20 ml of water to obtain 2.20 g of substance that is the dihydrate of the base. This compound is dissolved in 40 ml of ethyl alcohol under heating, and the solution obtained is added to a solution of 0.64 g of fumaric acid in 15 ml of ethyl alcohol. After crystallization at room temperature, 2.56 g (53%) of the title product are obtained. M.p.: 187-189° C.

Provenance & Evidence