| 氘代AZD9291的合成 |
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| 引用本文： | 康芳圆,庞学海,王颖伟,陈元伟.氘代AZD9291的合成[J].合成化学,2016,24(3):263-265. |
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| 作者姓名： | 康芳圆 庞学海 王颖伟 陈元伟 |
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| 作者单位： | 1. 中国科学院 成都有机化学研究所，四川 成都 610041； 2. 中国科学院大学，北京 100049； 3. 四川大学 生物治疗国家重点实验室，四川 成都 610041 |
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| 摘 要： | 吲哚和2，4-二氯嘧啶经偶联反应制得3-(2-氯嘧啶-4-基)-1H-吲哚(1)； 1与CD3I 经取代反应制得3-(2-氯嘧啶-4-基)-1-(甲基-d3)-吲哚(2)； 2经两步亲核取代反应制得N′-(2-二甲基氨基乙基)-2-甲氧基-N′-甲基-N-{［4-(1-(甲基-d3)吲哚-3-基)］嘧啶-2-基}-5-硝基苯-1,4-二胺(4)； 4经还原反应后，与氯丙酰氯发生缩合反应合成了氘代AZD9291，总收率8.5%，其结构经1H NMR, 13C NMR和ESI-MS表征。
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| 关 键 词： | AZD9291 表皮生长因子受体 氘代药物 药物合成 |
| 收稿时间： | 2015-04-15 |
Synthesis of Deuterated AZD9291 |
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| KANG Fang-yuan,PANG Xue-hai,WANG Ying-wei,CHEN Yuan-wei.Synthesis of Deuterated AZD9291[J].Chinese Journal of Synthetic Chemistry,2016,24(3):263-265. |
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| Authors: | KANG Fang-yuan PANG Xue-hai WANG Ying-wei CHEN Yuan-wei |
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| Institution: | 1. Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China; 2. University of Chinese Academy of Science, Beijing 100049, China; 3. State Key Labboratory of Biotheraphy, Sichuan Univeristy, Chengdu 610041, China |
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| Abstract: | The synthesis of deuterated AZD9291 was reported.3-(2-Chloropyrimidin-4-yl)-1H-indole (1) was prepared by coupling reaction of indole with 2,4-dichloropyrimidine.3-(2-Chloropyrimidin-4-yl)-1-( methyl-d3 )-lindole(2) was obtained by substitution reaction of 1 with iodomethane-d3 .N′-(2-dimethylaminoethyl)-2-methoxy-N′-methyl-N-{4-(1-methyl-d3 ) indol-3-yl] pyrimidin-2-yl}benzene-1,2,4-triamine(4) was obtained by two substitution reactions from 2.Then deuterated AZD9291 in to-tal yield of 8.5% was synthesized by condensation reaction following the reduction 4.The structure was confirmed by 1 H NMR, 13 C NMR and ESI-MS. |
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| Keywords: | AZD9291 EGFR deuterated drug drug synthesis |
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