吡拉格雷钠的合成工艺

发布时间：2018-07-10 16:53

  本文选题：吡拉格雷钠 + 血栓素合成酶抑制剂　； 参考：《中国医药工业杂志》2017年05期

【摘要】：2,3,5,6-四甲基吡嗪(2)经间氯过氧苯甲酸氧化得2,3,5,6-四甲基吡嗪单氮氧化物(3),2反应完全,收率93.5%;3与乙酐经Boekelheide反应后,再经水解、氯化得2-氯甲基-3,5,6-三甲基吡嗪(6);6与阿魏酸乙酯(7)经缩合反应得(E)-3-[3-甲氧基-4-[(3,5,6-三甲基吡嗪-2-基)甲氧基]苯基]丙烯酸乙酯(8),反应结束后加水即可析出晶体,简化了后处理,收率98.6%。8再经水解、成盐得吡拉格雷钠(1),纯度99.7%,总收率34.2%(以2计)。1是作者发现的新一代血栓素合成酶抑制剂,目前处于Ⅱ期临床研究阶段。
[Abstract]:After oxidation with m-chloro-peroxy benzoic acid, the reaction was complete. The yield of 93. 5N ~ 3 and acetic anhydride was 93. 5% with acetic anhydride, and then hydrolyzed, and then hydrolyzed after oxidation with m-chloro-peroxy benzoic acid to give a complete reaction with trimethyl pyrazine mono _ 2 in the yield of 93. 5% with acetic anhydride. (E) -3- [3-methoxy-4- [(3-) 5-trimethylpyrazine-2-methoxy] phenyl] ethyl acrylate (8) was synthesized by the condensation reaction of 2-chloromethyl -3-methylpyrazine (6) -trimethylpyrazine (6) -trimethylpyrazine (6) with ethyl ferulate (7). The yield of 98.6.8 was then hydrolyzed to form salt to obtain piologrel sodium (1) with a purity of 99.7. The total yield of 34.2% (in 2) was a new generation of thromboxane synthase inhibitor discovered by the authors. It is in the stage of stage 鈪，

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