Cangrelor (Figure 1) is a parenteral drug that reversibly inhibits the P2Y12 receptor; like ticagrelor, it does not require metabolic activation. It has a rather short half-life of 3 to 4minutes; and, with an infusion of 4mg/kg per minute, peak inhibition occurs after 15minutes. Cangrelor also has a rapid offset, with normal levels of platelet aggregation returning after 60minutes. Inhibitors of platelet activation and aggregation are substances that are useful during percutaneous coronary intervention and other catheterization techniques in order to reduce bleeding complications and in the treatment of acute coronary syndromes and clotting disorders in general. One class of antiplatelet agents includes the inhibitors of the P2Y12 receptor, a G-protein coupled purinergic receptor which is an important component of platelet activation. Cangrelor (trade name kengreal in the US and kengrexal in Europe) was approved by the United States Food and Drug Administration in 2015. In continuation of our ongoing research to improve the process and identify impurities we now report a novel, convenient, and readily scalable approach for the synthesis of the key intermediate of cangrelor. A detailed study has been undertaken to identify, synthesize and characterize the cangrelor intermediates using up-to-date spectral techniques (IR, NMR, and HRMS). The synthesis of cangrelor has been reported in the literature starting from 2mercaptoadenosine (Scheme 1). The synthesis involves seven stages and additional purifications to get cangrelor. During the synthesis, compound 5 serves as a key precursor. This material is highly expensive. The reported preparation of this compound involves four steps. However, the preparation suffers from certain drawbacks, most importantly the availability of the starting material as being difficult to access. A lot of purification procedures were involved in each stage, and these present difficulties in scale-up. Therefore, a synthetic route starting from more readily available and cheaper substrates was sought. The synthetic process reported in the literature shows that the

中文翻译：

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开发用于合成关键坎格雷洛中间体的新型可扩展工艺

Cangrelor（图 1）是一种胃肠外药物，可逆地抑制 P2Y12 受体；像替格瑞洛一样，它不需要代谢激活。它的半衰期很短，只有 3 到 4 分钟；并且，每分钟输注 4mg/kg，15 分钟后出现峰值抑制。Cangrelor 也有一个快速的抵消作用，60 分钟后血小板聚集恢复到正常水平。血小板活化和聚集的抑制剂是在经皮冠状动脉介入术和其他导管插入技术期间有用的物质，以减少出血并发症和一般用于治疗急性冠状动脉综合征和凝血障碍。一类抗血小板药物包括 P2Y12 受体抑制剂，这是一种 G 蛋白偶联的嘌呤能受体，是血小板活化的重要组成部分。Cangrelor（美国商品名 kengreal 和欧洲商品名 kengrexal）于 2015 年获得美国食品和药物管理局的批准。 为了继续我们正在进行的改进工艺和识别杂质的研究，我们现在报告了一种新颖、方便且易于扩展的坎格雷洛关键中间体的合成方法 已经进行了一项详细的研究，以使用最新的光谱技术（IR、NMR 和 HRMS）识别、合成和表征坎格雷洛中间体。文献中已经报道了从 2mercaptoadenosine 开始合成坎格雷洛（方案 1）。合成涉及七个阶段和额外的纯化以获得坎格雷洛。在合成过程中，化合物 5 作为关键前体。这种材料非常昂贵。据报道，该化合物的制备包括四个步骤。然而，该制剂存在某些缺点，最重要的是难以获得起始材料。每个阶段都涉及许多纯化程序，这些都给放大带来了困难。因此，寻求从更容易获得和更便宜的底物开始的合成路线。文献报道的合成过程表明，