Hydrochloric Acid → 1,3-Dibutylxanthine

Participants

Reaction Steps

A mixture of 6-amino-1,3-di-n-butyl-5-nitroso-uracil (3.1 g, 11.6 mmol) and 5% Pd-C in dry DMF (30 ml) was hydrogenated at 50 psi until it became a colorless solution (about 2 h). The catalyst was filtered off through Celite pad and the filtrate was mixed with 88% formic acid (15 ml) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (1.1 g, 5.74 mmol) at 0° C. under nitrogen. The violet solution was stirred at room temperature for 3 h. DMF and formic acid were removed by rotary evaporation and the solid residue was mixed with 2N sodium hydroxide (50 ml, 100 mmol). The reaction mixture was heated at reflux for 1 h. The yellow solution was cooled and neutralized with 6N hydrochloric acid to pH 3. The solid was collected by filtration, washed with water, and dried to yield 1,3-di-n-butyl-xanthine (2.3 g, 75%), m.p. 165.5°-169° C.; 1H NMR (DMSO-d6) δ1.41-1.47 (m, 6H, 2×CH3), 1.61-1.68 (m, 4H, 2×CH2), 1.74-1.79 (m, 2H, CH2), 1.82-1.85 (m, 2H, CH2), 3.84 (t, 2H, N--CH2), 3.98 (t, 2H, N--CH2), 8.10 (s, 1H, H-8), 13.7 (br s, 1H, NH).

Provenance & Evidence