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[1]陈金芳,朱冬斌,王亚,等.多韦替尼乳酸盐的合成[J].武汉工程大学学报,2014,(05):1-4.[doi:103969/jissn16742869201405001]
　CHEN Jin fang,ZHU Dong bin,WANG Ya,et al.Synthesis of dovtinib lactic acid salt[J].Journal of Wuhan Institute of Technology,2014,(05):1-4.[doi:103969/jissn16742869201405001]
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多韦替尼乳酸盐的合成(/HTML)
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
期数:
2014年05期
页码:
1-4
栏目:
化学与化学工程
出版日期:
2014-05-31

文章信息/Info

Title:
Synthesis of dovtinib lactic acid salt
文章编号:
16742869(2014)05000104
作者:
陈金芳1; 朱冬斌2; 王亚2; 徐启明3
1.绿色化工过程教育部重点实验室(武汉工程大学)，湖北 武汉 430074；2.武汉工程大学化工与制药学院，湖北 武汉 430074；3.新型反应器与绿色化学工艺湖北省重点实验室（武汉工程大学），湖北 武汉 430074
Author(s):
CHEN Jinfang1; ZHU Dongbin2; WANG Ya2; XU Qiming3
1.Key Laboratory of Green Chemical Process(Wuhan Institute of Technology),Ministry of Education,Wuhan 430074,China;2.Schoool of Chemical Engineeing and Pharmacy,Wuhan Institute of Technology,Wuhan 430074,China;3.Hubei Key Laboratory of Novel Chemical Reactor &Green Chemical Technology(Wuhan Institute of Technology),Wuhan 430074,China
关键词:
多韦替尼; 抗肿瘤; 合成
Keywords:
dovitinib; antitumor; synthesis
分类号:
R914.5
DOI:
103969/jissn16742869201405001
文献标志码:
A
摘要:
为了解决多韦替尼乳酸盐合成工艺中操作比较繁琐的问题，以5氯2硝基苯胺和N甲基哌嗪为原料，经取代、还原、在酸性条件下与3乙氧基3亚胺基丙酸乙酯盐酸盐回流成环，最后在碱性条件下与2氨基6氟苯腈进行环合得到多韦替尼，与乳酸成盐，得到终产品多韦替尼乳酸盐.通过对反应过程中的每步反应工艺条件研究，得到各步工艺条件：取代反应不采用溶剂，n(5氯2硝基苯胺)∶n（N甲基哌嗪）=1∶2.5，产率可达97.8%；在氨取代反应中2氟6胺基苯腈的产率为85%；在还原的过程中，选择在80 ℃时钯碳催化加氢；在40 ℃下采用六甲基硅胺钾作为碱合成多韦替尼，最终产率达到44.5%.
Abstract:
To solve the problem of complicated production process conditions of synthizing dovtinib lactic acid salt,5chloro2nitroaniline and 2amino6fluorobenzonitrile were applied as starting materials to prepare dovtinib lactic acid salt.via substitution,cyclization with ethylβethoxyβimino propanoate hydrochloride was refluxed under acidic conditions,cyclization with 2amino6fluorobenzonitrile under base conditions,and then lactic acid was carried out.The results show that the yield is 97.8% when the molar of (5chloro2nitroaniline)∶(1methylpiperazine) is 1∶2.5 in substitution;the yield of 2amino6fluorobenzonitrile is 85% when the temperature is 90 ℃ in substitution of NH3;the optimum conditions of the reduction reaction are demonstrated at 80 ℃ for 6 h through catalytic hydrogenation of Pd/C;the total yield is 44.5% after using the base of lithium bistrimethylsililyl)amide at 40 ℃ to synthize the dovtinib.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期：20140317作者简介：陈金芳（1957）,男，湖北黄梅人，教授，硕士研究生导师.研究方向：化学工程与技术.
更新日期/Last Update: 2014-06-15