6,7-二取代喹唑啉类抗肿瘤药物中间体的合成

Synthesis of 6,7-disubstituted quinazoline antitumor drug intermediates

为了探讨化合物(2a～2c)合成工艺的影响因素,以6,7-二取代的喹唑啉酮(1a～1c)为起始原料,在催化剂(大孔树脂和三乙烯二胺)存在下,与等摩尔的二氯亚砜为氯代试剂反应得到目标产物;将目标产物粗品在乙酸乙酯和石油醚中重结晶纯化,得到2a～2c,产物结构通过1H NMR及ESI-MS进行了表征。结果表明:通过重结晶纯化后得到的2a～2c的收率大于90%,色谱纯度大于99%;实验所采用的合成方法操作简单,满足"原子经济学"的要求,经济环保,适合工业化生产。

In order to investigate the factors which affect the synthesis process of 2a^2c,the 6,7-disubstituted quinazolinone(1a^1c)was used as the starting material in the presence of catalyst(macroporous resin and triethylenediamine),and reacted with equal molor dichlorosulfoxide which was used as chlorinated reagent;The crude product was recrystallized from ethyl acetate and petroleum ether to obtain 2a^2c.The structures of the product were confirmed by 1H NMR and ESI-MS.The results showed that the yield of 2a^2c was over 90%and the purity was over 99%after recrystallization.The operation of this synthetic route is simple,and meets the requirements of“atomic economics”and environmental protection;it is also suitable for industrial manufacture.