反应详情

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (WSC) (0.16 g, 0.85 mmol) was added to an acetonitrile solution (6 ml) of 1-ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-ylethylamino)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.3 g, 0.71 mmol), isonicotinic acid (96 mg, 0.78 mmol), and 1-hydroxybenzotriazole (HOBT) (0.138 g, 0.85 mmol), and then stirred at room temperature for 2 days. The solvent was concentrated under reduced pressure. Ethyl acetate and a sodium hydrogen carbonate aqueous solution were added to the reaction mixture, and stirred for 1 hour. Water was added to the reaction mixture, and extraction with ethyl acetate was conducted. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by medium pressure liquid chromatography (silica gel, dichloromethane:methanol=92:8). The purified product was concentrated under reduced pressure and crystallized from ethyl acetate, diethylether and n-hexane. The precipitated crystals were collected by filtration and dried to thereby obtain 0.21 g (yield: 56%) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)isonicotinamide as a white powder.

1. concentrationThe solvent was concentrated under reduced pressure
2. additionEthyl acetate and a sodium hydrogen carbonate aqueous solution were added to the reaction mixture
3. stirringstirred for 1 hour
4. additionWater was added to the reaction mixture, and extraction with ethyl acetate
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue thus obtained
8. customwas purified by medium pressure liquid chromatography (silica gel, dichloromethane:methanol=92:8)
9. concentrationThe purified product was concentrated under reduced pressure
10. customcrystallized from ethyl acetate, diethylether and n-hexane
11. filtrationThe precipitated crystals were collected by filtration
12. customdried