反应详情

(±)-4-(4-(4-Chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)butyric acid (0.50 g) and 1-hydroxybenzotriazole (0.17 g) are added to dry dimethylformamide (20 ml) and the mixture is stirred under ice-cooling. Thereto is added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.25 g), and then triethylamine (0.24 g) and aniline (0.11 g) are added. The mixture is stirred at room temperature for 4 days. After the completion of the reaction, water (100 ml) is added and the mixture is extracted with ethyl acetate. The organic layer is washed with 6N hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (ethyl acetate:methanol=10:l) and crystallized from ethyl acetate and isopropyl ether to give 0.29 g of (±)-N-phenyl-4-(4-(4-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo-[4,3-a][1,4]diazepin-6-yl)butaneamide as white powdery crystals, melting point 238°-240° C.

1. temperaturecooling
2. stirringThe mixture is stirred at room temperature for 4 days
3. additionis added
4. extractionthe mixture is extracted with ethyl acetate
5. washThe organic layer is washed with 6N hydrochloric acid
6. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue is purified by silica gel column chromatography (ethyl acetate:methanol=10:l)
9. customcrystallized from ethyl acetate and isopropyl ether