抗肿瘤药VLX600的合成

来源 :中国医药工业杂志 | 被引量 : 0次 | 上传用户:newbitcom
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
以邻甲基苯胺(2)为起始原料,经Sandmeyer法合成7-甲基靛红(4)。4在β-环糊精(β-CD)的催化下与氨基硫脲在水中经环合制得6-甲基-5H-1,2,4-三嗪并[5,6-b]吲哚-3-硫醇(5);后处理简便,β-CD经过滤回收可重复利用,收率也由文献的<30%增至77.9%。再以异丙醇代替毒性较大的水合肼为溶剂,回流条件下5与水合肼反应,反应完毕,直接冷却即可析出纯度较高(93.8%)的3-肼基-6-甲基-5H-1,2,4-三嗪并[5,6-b]吲哚(6)。以异丙醇代替水为溶剂,在乙酸催化下使6与2-乙酰吡啶(7)反应,粗品经乙酸乙酯重结晶,便可得纯度99.3%的VLX600(1),总收率17.0%(以2计)。 Using o-methylaniline (2) as the starting material, 7-methylisatin (4) was synthesized by Sandmeyer method. 4 was cyclized with thiosemicarbazone in water under the catalysis of β-cyclodextrin (β-CD) to prepare 6-methyl-5H-1,2,4-triazino [5,6-b] 3-mercaptan (5). The post-treatment was simple and the β-CD was recovered by filtration. The yield of β-CD was also increased from <30% to 77.9%. Then the isopropanol instead of the more toxic hydrazine hydrate as the solvent, under reflux conditions 5 and hydrazine hydrate reaction, the reaction is completed, the direct cooling can precipitate higher purity (93.8%) 3-hydrazino-6-methyl- 5H-1,2,4-triazolo [5,6-b] indole (6). Using isopropanol instead of water as solvent, 6 and 2-acetylpyridine (7) were reacted under the catalysis of acetic acid. The crude product was recrystallized from ethyl acetate to obtain VLX600 (1) with purity of 99.3%. The total yield was 17.0% (2).
其他文献
针对张家口发电厂一期DQ2400/3000*35型斗轮堆取料机.上部金属结构铰轴卡涩问题,详细介绍了施工措施及更换方案,供同行参考.
期刊
期刊
目的探索微创治疗与DC-CIK细胞治疗肝癌原发性肝癌患者24例确诊病例治疗的临床应用价值。方法对确诊为原发性肝癌患者24例进行TACE,术后1个月,行冷冻消融,术后一个半月应用DC
期刊
期刊
期刊
期刊
期刊
目的 探讨冠心病多支病变,择期行非体外循环冠脉搭桥术的麻醉与管理.方法 采用非体外循环(OPCABG)冠状动脉搭桥.结果 24例患者中,3例术中出现血压骤降,2例患者冠脉搭桥后出现