奥美沙坦酯合成新方法研究

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Abstract Objective To study the synthesis methods of angiotensin Ⅱ receptor antagonist olmesartan medoxomil. Methods Taking diaminomaleonitrile (2) and trimethyl orthobutyrate as starting materials to obtain intermediate Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate (6) through cyclization, hydrolysis, esterification and Grignard reaction. Then target compound olmesartan medoxomil was obtained through condensation between compound 6 and N-(Triphenylmethyl)-5-(4′-Methylbiphenyl-2-yl)Tetrazole (7) which followed by three steps including hydrolysis, substitution and deprotection. Results Optimized and confirmed the synthesis routes of olmesartan medoxomil, the total yield was 34.9% (calculated by diaminomaleonitrile, the reported yield in literature was 25.0%) and the purity was 99.5% (Normalization method of high performance liquid chromatography was used for detection). The chemical structure was characterized by nuclear magnetic resonance spectrometry and mass spectrometry. Conclusion The synthetic route has the advantages of low cost, simple operations, mild conditions and high yields, which make it more suitable for industrial production.

Key words： Antihypertensive Angiotensin Ⅱ receptor antagonists Olmesartan medoxomil Synthesis

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	LI Fangjuan1 MENG Xiangli2 WU Yiyan1 MENG Fanqin1 GUO Qiang1 ZHAO Yujia1

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LI Fangjuan1 MENG Xiangli2 WU Yiyan1 MENG Fanqin1 GUO Qiang1 ZHAO Yujia1. Study on the new synthetic process for Olmesartan Medoxomil[J]. 中国医药导报, 2019, 16(7): 25-27,36.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2019/V16/I7/25

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