Chlorosuccinimide → 7-(But-2-YN-1-YL)-8-chloro-3-methyl-3,7-dihydro-1H-purine-2,6-dione

Participants

Reaction Steps

3-Methylxanthine (1.1 g) was dissolved in N,N-dimethylformamide (15 ml), and potassium carbonate (1.0 g) and 1-bromo-2-butyne (0.64 ml) were added thereto. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate, and washed with water. Insoluble white solid was collected by filtration, and washed with ethyl acetate to give 1.3 g of 7-(2-butynyl)-3-methyl-3,7-dihydropurine-2,6-dione. Then, the resulting 7-(2-butynyl)-3-methyl-3,7-dihydropurine-2,6-dione (1.3 g) was dissolved in N,N-dimethylformamide (15 ml), and N-chlorosuccinimide (0.89 g) was added while cooling on ice. After stirring at room temperature for 3 hours, the reaction mixture was diluted with ethyl acetate, and washed with water. Insoluble white solid was collected by filtration, and washed with ethyl acetate to give 1.1 g of 7-(2-butynyl)-8-chloro-3-methyl-3,7-dihydropurine-2,6-dione. The resulting 7-(2-butynyl)-8-chloro-3-methyl-3,7-dihydropurine-2,6-dione (1.4 g) and 1-piperazine carboxylic acid tert-butyl ester (2.8 g) were stirred at 150° C. for 1 hour. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate, then the organic layer was washed with water and saturate brine, and was dried over anhydrous magnesium sulfate. The solvent was removed by distillation at reduced pressure. The residue was purified by silica gel column chromatography to obtain 1.1 g of the title compound from a fraction eluted with hexane-ethyl acetate (1:4).

Provenance & Evidence