| 第 52 卷第 5 期 |  | Vol. 52 No. 5 | | 2022 年 10 月 | Oct 2022 |
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所屬欄目：醫藥及中間體
吡咯喹啉醌關(guān)鍵中間體的合成工藝研究 |
| 毛聯(lián)崗
（連云港杰瑞藥業(yè)有限公司，江蘇 連云港 222000） |
| 摘 要：以1-甲氧基-5-甲基-2，4-二硝基苯（2）為原料，經(jīng)縮合、還原和環(huán)合制得6-氨基-5-甲氧基-1H-吲哚-2-甲酸乙酯（4），優(yōu)化條件下收率70%；4與乙醛酸酯和丙酮酸酯發(fā)生三組分一鍋反應得到吡咯喹啉醌關(guān)鍵中間體5-甲氧基-1H-吡咯［2，3-f］喹啉-2，7，9-三甲酸2-乙酯7，9二烷基酯（1），優(yōu)化條件下收率90%。對影響收率的催化劑結構、反應溫度、溶劑、乙醛酸酯和丙酮酸酯結構等因素進(jìn)行了考察。通過(guò)IR、1H NMR、13C NMR和ESI-MS確證了1及中間體的結構。該制備工藝原料價(jià)廉、環(huán)保，收率高，具有工業(yè)化應用前景。 |
| 關(guān)鍵詞：吡咯喹啉醌；5-甲氧基-1H-吡咯［2，3-f］喹啉-2，7，9-三甲酸2-乙酯7，9二烷基酯；一鍋反應 |
| 中圖分類(lèi)號：TQ28 文獻標識碼：A 文章編號：1009-9212（2022）05-0035-05 |
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| Synthesis of Key Intermediate of Pyrroloquinoline Quinone |
| MAO Lian-gang
(Lianyungang Jari Pharmaceutical Co., Ltd., Lianyungang 222000, China) |
| Abstract：Ethyl 6-amino-5-methoxy-1H-indole-2-carboxylate (4) was obtained from 1-methoxy-5-methyl-2,4-dinitrobenzene (2) through condensation, reduction and cyclization with a yield of 70%. Then 2-ethyl,7,9-dialkyl 5-methoxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid ester (1) was synthesized from 4 and glyoxylic ester, pyruvate through a simple one-pot reaction with a yield of 90%. The affecting factors including the structures of the catalysts, the reaction temperature, the solvent, and the structures of glyoxylic ester and pyruvate were investigated. The structures of the compound 1 and intermediate were characterized by IR, 1H NMR, 13C NMR and ESI-MS. The synthetic process had the advantages including low in raw material cost, environment-friendly, high yield and suitable for industrial production. |
| Key words：pyrroloquinoline quinone; 2-ethyl,7,9-dialkyl 5-methoxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid ester; one-pot reaction |
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作者簡(jiǎn)介：毛聯(lián)崗（1976—），男，山西昔陽(yáng)人，高級工程師，研究方向：藥物合成及質(zhì)量控制（E-mail：718838263@qq.com）。
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收稿日期：2022-06-10
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