| 第 52 卷第 3 期 |  | Vol. 52 No. 3 | | 2022 年 6 月 | Jun 2022 |
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所屬欄目：醫藥及中間體
西他列汀關(guān)鍵中間體的合成研究 |
| 陳云華1，2，譚建德2，周魏魏2，繆炳林2，徐 龍2，周麗萍1
（1.臺州職業(yè)技術(shù)學(xué)院 化學(xué)制藥研究所，浙江 臺州 318000；2.臺州達辰藥業(yè)有限公司，浙江 臨海 317016） |
| 摘 要：水合肼（2）經(jīng)三氟乙酸乙酯和氯乙酰氯取代反應，Vilsmeier試劑關(guān)環(huán)，得中間體3，再經(jīng)乙二胺取代，鹽酸乙醇關(guān)環(huán)制得西他列汀關(guān)鍵中間體3-三氟甲基-5，6，7，8-四氫-1，2，4-三唑-［4，3-a］并吡嗪鹽酸鹽（1），其結構經(jīng)1H NMR和MS確證，總收率達55%。此反應條件溫和，同時(shí)避免含磷廢水產(chǎn)生，更適合工業(yè)化生產(chǎn)。 |
| 關(guān)鍵詞：西他列��；關(guān)鍵中間體；脫水；合成 |
| 中圖分類(lèi)號：TQ246.3 文獻標識碼：A 文章編號：1009-9212（2022）03-0023-04 |
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| Research on the Synthesis of Key Intermediate of Sitagliptin |
| CHEN Yun-hua1,2, TAN Jian-de2, ZHOU Wei-wei2, MIAO Bing-lin2, XU Long2, ZHOU Li-ping1
(1.Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, China; 2.Taizhou Dachen Pharmaceutical Co., Ltd., Linhai 317016, China) |
| Abstract：Using hydrazine hydrate (2) as the raw material, compound 3 was obtained through the reaction with ethyl trifluoroacetate, then chloracetylation, cyclization using Vilsmeier reagent. Compound 3 was subjected to ethylendiamine, dehydration and recyclization under hydrochloric acid to obtain the key intermediate of sitagliptin (1) in an overall yield of 55%. The structures of the intermediate and product were characterized by 1H NMR and MS spectra. The advantages of this present process include mild reaction condition and avoiding phosphorus wastewater. Therefore it is promising for industrial application. |
| Key words：Sitagliptin; key intermediate; dehydration; synthesis |
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基金項目：臺州市科技計劃項目（21gyb24），浙江省教育廳高等學(xué)校訪(fǎng)問(wèn)工程師校企合作項目（FG2020223）。
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作者簡(jiǎn)介：陳云華（1966—），男，浙江溫嶺人，高級工程師，研究方向：藥物及中間體合成及工藝優(yōu)化（E-mail：1325100132@qq.com）。
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收稿日期：2022-03-15
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