摘要
以3-硝基-4-氯苯甲酸为原料,经酯化、硝化、水合肼还原、环合、氯化、氢化等反应得到标题化合物。整个反应过程成本低、操作简便、节约时间、符合工业化的要求。探讨了还原2,5-二硝基-4-氯苯甲酸甲酯时水合肼用量、反应温度、反应时间和催化剂的用量,氯化反应中氯化试剂、助溶剂以及温度等因素对目标产物的影响。结果表明,当n（2,5-二硝基-4-氯苯甲酸甲酯）∶n（80%水合肼）=1∶2.5、反应温度为78℃、反应时间为3 h、Fe Cl3用量为0.6 g、活性炭用量为0.15 g时,还原效果最佳;以SOCl2为氯化试剂、DMF为催化剂,80℃时,收率及纯度最高。目标产物结构通过元素分析、^（13）CNMR、IR、~1HNMR以及MS确定,为新型酪氨酸激酶抑制剂的合成提供依据。
6-Amine-7-methoxyquinazoline was synthesized from 3-nitro-4-chlorobenzene acid via esterification,nitration,hydrazine hydrate reduction,cyclization,chlorination,hydrogenation.The process is low cost,manipulation easily,and suitable for industrial production.The effects of hydrazine hydrate dosage,reaction temperature,reaction time and catalyst dosage were discussed,and the chlorination reagent,cosolvent,the reaction temperature on the target products were investigated.The optimal conditions were the molar ratio of n（2,5-dinitro-4-methyl benzoate）∶n（80%hydrazine hydrate）=1∶2.5,reaction temperature 78℃,reaction time3 h,0.6 g Fe Cl3,0.15 g activated carbon,the yield was best.When SOCl_2was used as the chlorination reagent and solvent,DMF was used as the catalyst,temperature was 80℃,the yield and purity were best.The structure of the target molecules was confirmed by elemental analysis,^（13）CNMR,IR,~1HNMR and MS,it could also provide evidence for the synthesis of tyrosine kinase inhibitors.
作者
张帅波
金岩
李振建
刘潮
冯柏成
ZHANG Shuai-bo;JIN Yan;L Zhen-jian;LIU Chao;FENG Bai-cheng(College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, Chin)
出处
《化学试剂》
CAS
北大核心
2018年第4期383-388,共6页
Chemical Reagents
