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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。
2,3,5,6-tetramethylpyrazine (2) was oxidized by chloroperbenzoic acid 2,3,5,6-tetramethylpyrazine mono-nitroxide (3), 2 reaction was complete, The yield 93.5%; 3 and acetic anhydride after Boekelheide reaction, and then hydrolysis, chlorination 2-chloromethyl-3,5,6-trimethyl pyrazine (6); 6 and ethyl ferulate 7) Ethyl 3- [3-methoxy-4 - [(3,5,6-trimethylpyrazin-2-yl) methoxy] phenyl] acrylate 8). After the reaction, water is added to precipitate crystals, which simplifies the post-treatment and the yield is 98.6%. 8 and then by hydrolysis, into the salt of pyridarrel sodium (1), purity of 99.7%, the total yield of 34.2% (2 dollars). 1 is a new generation of thromboxane synthase inhibitors discovered by the authors and is currently in phase II clinical research.