Preparation method of mirabegron

Abstract

The invention discloses a preparation method of mirabegron, and the method comprises: S1, carrying out reduction reaction on p-nitrophenylacetonitrile to obtain p-nitrophenylacetaldehyde; S2, carryingout condensation reduction on the p-nitrophenylacetaldehyde and (R) 2-amino-1-phenethyl alcohol to obtain (R) 2-(4-nitrophenethyl) amino)-1-phenyl ethyl alcohol; S3, carrying out reduction on the (R)2-amino-1-phenethyl alcohol to obtain (R) 2-(4-nitrophenethyl) amino)-1-phenyl ethyl alcohol to obtain an intermediate (R) 2-((4-aminophenyl ethyl) amino)-1-phenyl ethyl alcohol; and S4, carrying outcondensation on the (R) 2-((4-aminophenyl ethyl) amino)-1-phenyl ethyl alcohol and aminothiazole acetic acid to obtain the mirabegron. According to the method, the starting raw materials are cheap and easy to obtain, the reaction conditions are controllable, the synthetic route steps are few, the yield is high, the cost is low, and the prepared mirabegron is high in purity.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a preparation method of mirabegron. Background technique [0002] Mirabegron was developed by Japan's Astellas Pharmaceutical Company (Astellas), and Yamanouchi Pharmaceutical Co., Ltd. applied for the compound patent of Mirabegron in Japan on October 17, 1997, and protected its preparation method. At present, it has applied for patent protection in many countries and regions such as the United States, Europe, and China. On September 16, 2011, Mirabegron was launched for sale in Japan. In June 2012, it was approved by the US FDA for listing in the United States. As the first orally effective β3 adrenergic receptor agonist drug for the treatment of overactive bladder, the successful marketing of Mirabegron has filled the gap in the treatment of overactive bladder with β adrenergic receptor agonists. [0003] The currently disclosed synthetic routes mainly incl...

AI Technical Summary

Problems solved by technology

[0012] This route is a new route, but it is difficult to realize industrial production because the oxidation of this route uses highly polluting potassium permanganate and the starting materials are not easy to obtain.

[0013] From the above review, it can be known that the synthesis of mirabegron is difficult to realize industrial production because the synthesis route is too long and the yield is low, or because the cost of expensive reagents is high, or the starting materials that are difficult to obtain are used. Therefore, the development of raw materials The synthesis route of mirabegron with cheap and easy to obtain, few reaction steps and low cost has broad prospects

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