Improvement of synthesis process of mirabegron / 中国药科大学学报

ABSTRACT

@#Overactive bladder is a syndrome characterized by urgent urination, often accompanied by frequent urination and nocturia. The incidence of the disease is high all over the world, and it has a great impact on the lives of patients, which has been paid more and more attention by scholars at home and abroad. It is currently estimated that 50 million to 100 million people worldwide suffer from the disease. 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.