| 第 49 卷第 4 期 |  | Vol. 49 No. 4 | | 2019 年 8 月 | Aug 2019 |
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所屬欄目：醫藥及中間體
孤兒藥吡非尼酮的合成與晶型研究 |
| 陳艷嬌1，張 珩1*，王正雄2，楊藝虹1
（1. 武漢工程大學(xué) 化工與制藥學(xué)院，湖北 武漢 430073；2. 湖北宏源藥業(yè)科技有限公司 武漢研發(fā)中心，湖北 武漢 430206） |
| 摘 要：以2-氨基-5-甲基吡啶為起始原料，經(jīng)重氮化反應，水解后得到中間體2-羥基-5-甲基吡啶，在無(wú)水碳酸鉀和碘化銅存在下與碘苯進(jìn)行親核取代反應，生成目標產(chǎn)物吡非尼酮，經(jīng)工藝優(yōu)化后反應總收率為66.6%，較文獻報道收率提高了16.6%。終產(chǎn)物與中間體的結構經(jīng)核磁共振氫譜、質(zhì)譜確證。通過(guò)不同方法制備了吡非尼酮的三種不同晶型樣品，改善了晶型的制備工藝，提出了新的晶型制備方法。采用粉末X射線(xiàn)衍射法、差示掃描量熱法、紅外光譜法對不同晶型進(jìn)行了表征分析。 |
| 關(guān)鍵詞：吡非尼酮；多晶型；穩定性；表征方法 |
| 中圖分類(lèi)號：TQ25 文獻標識碼：A 文章編號：1009-9212（2020）04-0045-05 |
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| Synthesis and Polymorphism of Pirfenidone |
| CHEN Yan-jiao1, ZHANG Heng1, WANG Zhen-xiong2, YANG Yi-hong1
(1. School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430073, China; 2. HuBei Hongyuan Pharmacetical Technology Co., Ltd., Wuhan R&D Center , Wuhan 430206, China) |
| Abstract：Using 2-amino-5-methyl-pyridine as the starting material, 2-hydroxy-5-methyl-pyridine was obtained by diazotization and hydrolysis. Then, in the presence of anhydrous potassium carbonate and copper iodide, the reaction was carried out with iodobenzene to produce the target product named pirfenidone. The total yield of the reaction was 66.6%, this is an increase of 16.6% over that reported in the literature, and the structures of the final products and intermediates were confirmed by 1H NMR and EI-MS. Three forms of pirfenidone were prepared. The structure of the crystals was analyzed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and the infrared spectrometry (IR). |
| Key words：pirfenidone; polymorphism; stability; identification method |
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作者簡(jiǎn)介：陳艷嬌（1995—），女，湖北十堰人，碩士研究生，研究方向：藥物合成與過(guò)程開(kāi)放（E-mail：985918189@qq.com）。
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聯(lián) 系 人：張 珩，教授，研究方向：藥物合成與過(guò)程開(kāi)放（E-mail：zhzpthm@163.com）。
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收稿日期：2020-07-28
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