Ethyl Acetate → 5-Aminopyrazine-2-carbonitrile

Participants

Reaction Steps

A mixture of Example 1A (19.29 g, 105 mmol), freshly powdered KCN (16.9 g, 260 mmol), CuI (49.5 g, 260 mmol), 18-crown-6 (2.08 g, 7.8 mmol), and (PPh3)4Pd (1.8 g, 1.57 mmol) in N,N-dimethylformamide (600 mL) was stirred at room temperature for 30 minutes and heated to reflux in an oil bath preheated to about 200° C. The solution was stirred at reflux for 3 hours, cooled to room temperature, poured into ethyl acetate (1 L), filtered through diatomaceous earth (Celite®), treated with silica gel (100 g), and concentrated. The concentrate was purified by flash column chromatography on silica gel with 60% ethyl acetate/hexanes to provide 11.9 g (94.4%) of the desired product. MS (APCI(+)) m/z 121 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 8.40 (d, J=0.7 Hz, 1H), 7.90 (d, J=0.7 Hz, 1H), 7.47–7.69 (br s, 2H).

Provenance & Evidence