36070-80-1

33332-25-1

36070-80-1

Example 29: Synthesis of 5-[2(R)-(3-chloro-4-methylsulfonyl-phenyl)-3-cyclopentylpropylamino]-pyrazine-2-carboxylic acid hydroxylamides [000197] General steps: 1. dissolve methyl 5-chloropyrazine-2-carboxylate (30.00 g, 0.17 mol) in tetrahydrofuran (87 mL). 2. a solution of potassium carbonate (72.08 g, 0.52 mol) in water (261 mL) was added to the above solution. 3. The reaction mixture was stirred at 25 °C for 42 h. 4. 4. Upon completion of the reaction, the reaction mixture was acidified to a pH of about 2 with concentrated hydrochloric acid. 5. The reaction mixture was diluted with saturated aqueous sodium chloride solution (300 mL). 6. Extracted successively with ethyl acetate (4 L total) until no product was detected in the aqueous layer. 7. The organic layers were combined, dried over sodium sulfate and filtered. 8. The filtrate was concentrated in vacuum to give 5-chloropyrazine-2-carboxylic acid (26.54 g, 96% yield) as an off-white solid. Physical properties: melting point 150-151°C; EH-HRMS m/e calculated value C5H3ClN2O2 (M+) 157.9883, measured value 157.9877.