High-purity high-yield aclidinium bromide preparation method suitable for industrial production

Abstract

The invention discloses a high-purity high-yield aclidinium bromide preparation method suitable for industrial production. The preparation method comprises the following steps: 1) adding methyl 2,2-di(2-thienyl)-2-hydroxyacetate and TBDMSCl into solvent, dropwisely adding alkali, and reacting at (-10)-30 DEG C for 2-10 hours; 2) mixing 3-(R)-quinuclidinol and anhydrous methylbenzene, adding alkali in batches, stirring at room temperature, adding the product in the step 1) in batches, and performing heating reaction at 50-150 DEG C for 2-20 hours; 3) mixing the product in the step 2) with the solvent, dropwisely adding acid under a low-temperature condition, reacting for 1-15 hours, regulating the pH value after the reaction is completed, and cooling; and 4) mixing the product in the step 3) with the solvent, adding 3-phenoxypropyl bromide, performing heating reaction at 50-100 DEG C for 1-5 hours, and purifying after the reaction is completed. The preparation method is simple and convenient; the prepared product has high purity and less side reaction; and the preparation method is suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry; in particular, it relates to a preparation method of aclidinium bromide crude drug. Background technique [0002] Chronic obstructive pulmonary disease, a common respiratory disease, is a preventable and treatable disease characterized by airflow limitation. Its airflow limitation is not fully reversible and develops progressively. Aclidinium bromide (Aclidinium bromide) was developed by American Forest Laboratory Pharmaceutical Company and Almirall Company. In 2013, it was approved for marketing by the US FDA. The trade name is Tudorza Pressair. ) long-term maintenance treatment of bronchospasm. Tudorza is administered twice a day and is an inhaled long-acting anticholinergic drug. Its mechanism of action is to promote bronchodilation by inhibiting the effect of acetylcholine on muscarinic receptors in tracheal smooth muscle. This product is an inhaled long-acting anti-M choline drug, which...

AI Technical Summary

Problems solved by technology

At present, there are many methods for the synthesis of aclidinium bromide, but there are generally disadvantages of relatively low synthesis efficiency and relatively high synthesis cost.