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• Synthesis

  The carbonyl precursor of n-(4-Chloro-3-cyano-7-ethoxy-6-quinolinyl) acetamide (61 g, 0.22 mol) and N,N-dimethylpyridine (0.85 g, 5 mol%) were suspended in ethyl acetate (565 mL). The mixture was stirred at room temperature. Triphosphine oxychloride (60 mL, 0.65 mol) was slowly added to the mixture over 1 hour. The mixture was heated under reflux for 2 hours to obtain a clear solution, and then cooled to room temperature.

  The reaction solution was slowly poured into ice water (900 mL) and stirred for 1 hour. The resulting solid was washed with water (80 mL x 2) and dried. The crude product (60 g) was suspended in DMF (180 mL) and stirred at room temperature for 1 hour. The solid was filtered, and the filtrate was washed with ethyl acetate (39 mL x 3). The product was dried at 50 °C to obtain the target product n-(4-Chloro-3-cyano-7-ethoxy-6-quinolinyl) acetamide.

  

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