抗肿瘤候选药GSK2126458的合成研究

Synthesis of Antitumor Candidate GSK2126458

对GSK2126458文献的合成方法进行了改进,用丙二酸亚异丙酯(4)代替文献方法中的乙氧基亚甲基丙二酸二乙酯(7),缩短了两步合成了6-溴-4-羟基喹啉(6),6-溴-4-氯喹啉(12)先进行一次Sonagashira反应,再进行Diels-Alder反应合成了哒嗪环,避免了使用昂贵的4-哒嗪硼酸(14),节约了成本。最后suzuki偶联制备了GSK2126458(1),总收率为25.3%

The report synthesis method of GSK2126458 was improved.2,2-dimethyl-1,3-dioxane-4,6-dione（4） instead of diethyl 2-（ethoxymethylene） Malonate（7）faciliated the process to synthesize 6-bromoquinolin-4-ol（6）,the Sonagashira reaction and Diels-alder reaction were used to the formation of the ring of pyridazine,the precious pyridazin-4-yl-4-boronic acid（14） was avoided,and the Suzuki coupling reaction was used to synthesize GSK2126458（1） in 25.3% overall yield.