| 引用本文: | 蒋清伟,张印广,王迷娟.安立生坦合成新工艺研究[J].中国现代应用药学,2019,36(6):698-701. |
| JIANG Qingwei,ZHANG Yinguang,WANG Mijuan.New Method for Synthesis of Ambrisentan[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(6):698-701. |
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| 摘要: |
| 目的 改进安立生坦的合成工艺。方法 以2-羟基-3-甲氧基-3，3-二苯基丙酸甲酯为起始原料，先水解再经过（R）-（+）-1-苯乙胺拆分得到（S）-2-羟基-3-甲氧基-3，3-二苯基丙酸，最后在氨基锂的作用下，与4，6-二甲基-2-甲磺酰基嘧啶反应得到安立生坦。结果 所得产品经HPLC检测纯度为99.91%，ee值为99.9%，总收率为33.8%，并通过1H-NMR、13C-NMR和ESI-MS进行了结构确证。结论 该工艺操作简便，质量可靠，成本低廉，适合工业化生产。 |
| 关键词: 安立生坦 肺动脉高压 合成 新工艺 (R)-(+)-1-苯乙胺 |
| DOI：10.13748/j.cnki.issn1007-7693.2019.06.010 |
| 分类号:R914.5 |
| 基金项目: |
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| New Method for Synthesis of Ambrisentan |
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JIANG Qingwei1, ZHANG Yinguang1, WANG Mijuan2
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1.Beijing Union Second Pharmaceutical Factory, Beijing 102600, China;2.Beijing Union Pharmaceutical Factory, Beijing 102600, China
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| Abstract: |
| OBJECTIVE To improve the synthetic method of ambrisentan. METHODS As the starting material, methyl 2-hydroxy-3-methoxy-3,3-diphenylpropionate was firstly hydrolyzed and then resoluted with (R)-(+)-1-phenylethylamine to give (S)-2-hydroxyl-3-methoxy-3,3-diphenylpropionic acid, and finally reacted with 4,6-dimethyl-2-methylsulfonyl pyrimidine in the presence of LiNH2 to obtain ambrisentan. RESULTS The product was detected by HPLC with the purity of 99.91% and the enantiomeric excess of 99.9%, and the overall yield was 33.8%. The structure of the product had been confirmed by 1H-NMR, 13C-NMR and ESI-MS. CONCLUSION This synthetic method is easy to operate with reliable quality and low cost, and it is suitable for industrial production. |
| Key words: ambrisentan pulmonary arterial hypertension synthesis new method (R)-(+)-1-phenylethylamine |
