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

作　　者：方舒慧 薛斌[1] 李善柱 刘勇 刘景 方立文 葛新颖 侯玲[1] 于大伟[1] 赵蓉 王志明[1] 蔡志强[1] 李帅 马启朋 FANG Shu-hui;XUE Bin;LI Shan-zhu;LIU Yong;LIU Jing;FANG Li-wen;GE Xin-ying;HOU Ling;YU Da-wei;ZHAO Rong;WANG Zhi-ming;CAI Zhi-qiang;LI Shuai;MA Qi-peng(School of Petrochemical Engineering, Shenyang University of Technology, Liaoyang 111003, China;Shenyang Photosensitive Chemical Research Institute Co.Ltd., Shenyang 110141, China;Key Laboratory for Chemical Drug Research of Shandong Province, Instiitute of Phamaceutical Sciences of Shandong Province, Jinan 250101, China;Lucky(Shenyang)Technological Industries Co., Itd.,Shenyang 110141, China;Petrochina Fushun Petrochemical Company, Fushun 113008, China)

机构地区：[1]沈阳工业大学石油化工学院,辽宁辽阳111003 [2]沈阳感光化工研究院有限公司,辽宁沈阳110141 [3]乐凯(沈阳)科技产业有限责任公司,辽宁沈阳110141 [4]山东省药学科学院化学药物重点实验室,山东济南250101 [5]中国石油天然气股份有限公司抚顺石化分公司,辽宁抚顺113008

出　　处：《广西大学学报（自然科学版）》2018年第6期2419-2424,共6页Journal of Guangxi University（Natural Science Edition）

基　　金：国家自然科学基金资助项目(51203091);辽宁省自然科学基金资助项目(20180550016);辽宁省教育厅科学研究一般项目(L2015383);沈阳市科技计划项目(18-004-4-32)。

摘　　要：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.

关 键 词：抗肿瘤 喹唑啉 药物中间体 合成 

分 类 号：O626.3[理学—有机化学] R914.5[理学—化学]