反应详情

The mixture of (E)- and (Z)-4-chlorobut-2-enoic acid (750 μl of the solution from step A, 0.19 mmol) together with HATU (72 mg, 0.19 mmol) and diisopropylethylamine (21.6 μl, 0.375 mmol) was stirred at room temperature for 15 minutes. 4-piperazin-1-ylquinoline (39.9 mg, 0.19 mmol) and diisopropylethylamine (10.8 μl) were added and stirring was continued for one hour. The mixture was diluted with dichloromethane, washed with 5% sodium bicarbonate solution, water, evaporated to dryness under reduced pressure and purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 20 mg (E)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (0.063 mmol, 33%) and 9 mg (Z)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (0.029 mmol, 15%).

1. stirringstirring
2. waitwas continued for one hour
3. washwashed with 5% sodium bicarbonate solution, water
4. customevaporated to dryness under reduced pressure
5. custompurified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)