4-(Pyridin-3-yl)pyrimidin-2-amine → N-(2-methyl-5-nitropyridin-3-yl)-4-(pyridin-3-yl)pyrimidin-2-amine

Participants

Reaction Conditions

Reaction Steps

Palladium(II) acetate (65.3 mg, 0.29 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (336 mg, 0.58 mmol) were mixed together in a reaction vessel and evacuated and purged with nitrogen 3 times. Toluene (35 ml) was added and the resulting mixture was heated to to 50°C for 45 minutes, then cooled to r.t. To this mixture at r.t was added 3-bromo-2-methyl-5-nitropyridine (694 mg, 3.20 mmol), then 4-(pyridin-3-yl)pyrimidin-2-amine (500 mg, 2.91 mmol) and cesium carbonate (1421 mg, 4.36 mmol), and the resulting mixture heated at 90 °C for 16 hours under N2. The reaction mixture was cooled to RT, 150ml EtOAc was added and the mixture was filtered. The filtrate was concentrated, diluted with EtOAc (500 mL), and washed sequentially with water (300 mL) and saturated brine (150 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product, ~2g brown wet solid. The crude product was purified by flash silica chromatography, elution gradient 0 to 4% MeOH in DCM. Pure fractions eluting at 3% were evaporated to dryness to afford N-(2-methyl-5-nitropyridin-3-yl)-4-(pyridin-3-yl)pyrimidin-2-amine (169 mg, 18.86 %) as a cream solid.

Provenance & Evidence