反应详情

To a mixture of (R,S)-[4-[2-amino-4-oxo-4-[4-(pyridin-4-yl)piperazin-1-yl]butyryl]-3-methoxy-carbonylmethyl-2-oxopiperazin-1-yl]acetic acid trifluoroacetic acid salt (0.25 g) produced in Working Example 21, an aqueous solution of sodium hydrogen carbonate (0.15 g), water (2.5 ml) and 1,4-dioxane (2.5 ml) was added 4-fluorobenzoyl chloride (0.051 ml) and the solution was stirred for 1 hour at room temperature. The pH of the reaction solution was adjusted to 3 with 1N hydrochloric acid and the solution was concentrated under reduced pressure. The concentrate was purified by means of CHP-20 column chromatography (eluent:H2O→15% acetonitrile aqueous solution→20% acetonitrile aqueous solution→25% acetonitrile aqueous solution→30% acetonitrile aqueous solution). The objected fraction was concentrated and subjected to lyophilization to give the titled compound (0.10 g) as a white amorphous powdery product.

1. customproduced in Working Example 21
2. concentrationthe solution was concentrated under reduced pressure
3. customThe concentrate was purified by means of CHP-20 column chromatography (eluent:H2O→15% acetonitrile aqueous solution→20% acetonitrile aqueous solution→25% acetonitrile aqueous solution→30% acetonitrile aqueous solution)
4. concentrationThe objected fraction was concentrated