米拉贝隆的合成工艺改进
Improvement of synthesis process of mirabegron
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摘要: 米拉贝隆是一种β-3肾上腺素受体的激动剂，用于治疗膀胱过度活动症。本研究在文献方法的基础上，对米拉贝隆的合成工艺进行了改进。以盐酸对硝基苯乙胺、(R)-扁桃酸和2-氨基噻唑-4-乙酸为起始原料，经过酰胺缩合、羰基还原、硝基还原及酰胺缩合4步反应以及一步精制，得到高纯度的目标产物，总收率39%。将第3步硝基还原的氢源，由氢气改为了甲酸铵，增加了工业化可行性；并且对米拉贝隆的精制进行了研究，提高了米拉贝隆的纯度。改进后的工艺操作简化，反应条件温和，为米拉贝隆的制备和精制提供了一种新的方法。Abstract: Mirabegron is an agonist of human β-3 adrenergic receptor used to treat symptoms of overactive bladder. In this study, the synthesis process of mirabegron was improved based on literatures. Using p-nitrophenethylamine hydrochloride, (R)-mandelicacid and 2-aminothiazole-4-acetic acid as starting materials, the target product with high purity was obtained through four steps of amide condensation, carbonyl reduction, nitro reduction and amide condensation, and one-step purification, with a total yield of 39%. In this study, the hydrogen source of nitro reduction in step 3 was changed from hydrogen to ammonium formate, which increased the feasibility of industrialization, and mirabegron was refined to improve the purity of the product. The improved process has the advantages of simplified operation and mild reaction conditions, which provides a new method for the preparation and purification of mirabegron.
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Keywords:
- mirabegron /
- overactive bladder /
- nitro reduction /
- process improvement /
- synthesis
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