反应详情

To a solution of 500 mg of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid obtained in Example 42 in 5 ml of anhydrous tetrahydrofuran, 214 mg of 1,1′-carbonyldiimidazole was added and, after stirring at room temperature for 30 minutes, the mixture was heated at reflux for 30 minutes. After air-cooling to room temperature, 206 mg of p-toluenesulfonamide was added. After stirring for 10 minutes, 0.18 ml of 1,8-diazabicyclo[5.4.0.]undec-7-ene was added dropwise. After stirring at room temperature overnight, almost all of the solvent was evaporated under reduced pressure. The residue was combined with water and then neutralized with 1N hydrochloric acid. The reaction solution was extracted with ethyl acetate and dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 460 mg of the desired compound.

1. temperaturethe mixture was heated
2. temperatureat reflux for 30 minutes
3. temperatureAfter air-cooling to room temperature
4. stirringAfter stirring for 10 minutes
5. stirringAfter stirring at room temperature overnight
6. customalmost all of the solvent was evaporated under reduced pressure
7. extractionThe reaction solution was extracted with ethyl acetate
8. dry with materialdried over anhydrous magnesium sulfate
9. customthe solvent was evaporated under reduced pressure
10. customThe residue was purified by silica gel column chromatography