2,5-Diamino-4,6-dichloropyrimidine → 6-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine

Participants

Reaction Steps

2,5-diamino-4,6-dichloropyrimidine (6 g, 33.5 mmol), 4-aminotetrahydropyran (3.39 g, 33.5 mmol, 1 equiv.), sodium bicarbonate (9.85 g, 117.2 mmol, 3.5 equiv.) and 1-butanol (120 mL) were heated together at 150° C. in a sealed tube. After 3 days, when the reaction appeared to be complete (by HPLC), the reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was purified by flash chromatography (silica gel, gradual elution with 95/5 methylene chloride/methanol to 90/10 methylene chloride/methanol) to give 7.1 g (87% yield) of the desired product as a pink solid. In an alternative procedure, water (300 mL) was added to the residue (before chromatographic purification) and the mixture stirred for 30 min at room temperature. Filtration under vacuum, thorough washing of the precipitate with water, followed by thorough drying of the pink solid in vacuum oven at 60° C., provided high purity desired product in 78% yield. 1H NMR (300 MHz, CD3OD) δ, ppm: 4.21-4.12 (m, 1H), 4.01-3.96 (m, 2H), 3.53 (td, J=11.7, 2.2 Hz, 2H), 2.01-1.96 (m, 2H), 1.60 (tdd, J=12.1, 11.7, 4.6 Hz, 2H); MS (EI) m/z 244.3 (MH)+.

Provenance & Evidence