5-chloropyrazine-2-carboxamide

Synthesis

33332-25-1

21279-64-1

General procedure for the synthesis of 5-chloropyrazine-2-carboxamide from methyl 5-chloropyrazine-2-carboxylate: Step 1: Ammonium chloride (558 mg, 10.4 mmol) was suspended in benzene (5 mL), and a toluene solution of 2M trimethylaluminum (5.2 mL, 10.4 mmol) was added slowly and dropwise at 0 °C. After stirring for 1 h, a solution of methyl 5-chloropyrazine-2-carboxylate (600 mg, 3.48 mmol) in benzene (5 mL) was added. The reaction mixture was heated to 50 °C and stirred overnight. After the reaction was completed and cooled to room temperature, the reaction mixture was poured into water and neutralized with saturated aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol = 100:0 → 98:2) to afford 5-chloropyrazine-2-carboxamide (236 mg, 43% yield) as a white solid.

References