Scalable Process of Methimazole,Organic Process Research & Development

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Scalable Process of Methimazole
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2022-12-15 , DOI: 10.1021/acs.oprd.2c00185
Ramesh Goura _{1,

2} , Surendra Babu Manubolu Surya ₂ , Naresh Kumar Katari ₂ , Ramprasad Achampeta Kodanda ₁ , Pradeep Rebelly ₁

Affiliation

Base hydrolysis of imidazole carboxylate was observed to be an efficient route for the scalable synthesis of the antithyroid drug methimazole. Ethyl 3-methyl-2-thioxo-2,3-dihydro-1H-imidazole-1-carboxylate (12) was produced as a key intermediate in the reaction of 1-methyl-1H-imidazole (4) with ethyl chloroformate (11) and sulfur. Compound 12 undergoes hydrolysis in two steps in the presence of a base to give methimazole (1) with an overall yield of 78%. The process was studied through the Quality by Design (QbD) concept and observed to be robust.

中文翻译：

甲巯咪唑的可扩展工艺

观察到咪唑羧酸盐的碱水解是可扩展合成抗甲状腺药物甲巯咪唑的有效途径。3-甲基-2-硫代-2,3-二氢-1H-咪唑-1-甲酸乙酯 ( 12 ) 是 1-甲基-1H-咪唑 ( 4 ) 与氯甲酸乙酯 ( 11 ) 反应中的关键中间体) 和硫磺。化合物12在碱存在下分两步水解得到甲巯咪唑( 1 )，总收率为78％。该过程通过质量源于设计 (QbD) 概念进行了研究，并观察到其稳健性。

更新日期：2022-12-15

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