Method for preparing prucalopride intermediate 1-(3-methoxypropyl)-4-piperidylamine

Abstract

The invention belongs to the medicinal chemistry field and relates to a method for preparing a prucalopride intermediate 1-(3-methoxypropyl)-4-piperidylamine. The prucalopride is clinically used for treating female constipation of un-relievable hypocatharsis, and is the first dihydrobenzofuran carboxylic acid type novel intestinal motility accelerant. In lots of prucalopride synthetic routes, the 1-(3-methoxypropyl)-4-piperidylamine is one of essential intermediates. The invention provides a new route for synthesizing the 1-(3-methoxypropyl)-4-piperidylamine; 4-piperidone is taken as the raw material for the route and the route has the characteristics of easy-to-get raw materials, mild reaction conditions and high product yield; and besides, the method is applicable to industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to a method for preparing prucalopride intermediate 1-(3-methoxypropyl)-4-piperidinamine (structure I). [0002] [0003] I. Background technique [0004] Prucalopride is a selective 5-H- 4 Receptor agonist. In October 2009, the European Medicines Agency approved its monosuccinate for marketing. It is clinically used to treat female constipation that cannot be relieved by laxatives. Prucalopride is the first dihydrobenzofuran carboxylic acid derivative. A new kind of intestinal prokinetic agent, which can efficiently and selectively stimulate 5-HT 4a and 5-HT 4b Receptors, increase gastrointestinal motility, improve constipation symptoms. [0005] In many synthetic routes of prucalopride, 1-(3-methoxypropyl)-4-piperidinamine is one of the essential intermediates, and the usual synthetic method is to replace 4 -Piperidone is directly reduced to amine, but the reaction conditi...

AI Technical Summary

Problems solved by technology

[0005] In many synthetic routes of prucalopride, 1-(3-methoxypropyl)-4-piperidinamine is one of the essential intermediates, and the usual synthetic method is to replace 4 -Piperidone is directly reduced to amine, but the reaction conditions are relatively harsh, and the yield is low, which is not suitable for industrial production. In addition, there are also documents that first reduce piperidone to oxime, and then reduce oxime to amine, but this kind of synthetic method is usually Some expensive and dangerous catalysts will be selected, such as lithium aluminum hydride, and the purity of the resulting product is not high