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

Abstract

The invention belongs to the field of pharmaceutical chemistry, and relates to a method used for preparing prucalopride intermediate 1-(3-methoxypropyl)-4-piperidinamine. The method comprises following step: 1) 1-(3-methoxylpropyl)-4-piperidone is dissolved in an organic solvent, appropriate amounts of hydroxylamine hydrochloride and vinegar are added for heating reflux dehydration so as to obtain 1-(3-methoxypropyl)-4-piperidine oxime; and 2) 1-(3-methoxypropyl)-4-piperidine oxime is dissolved in an organic solvent, an appropriate amount of a catalyst is added, and H2 is added so as to obtain 1-(3-methoxypropyl)-4-piperidinamine after complete reaction. Operation of the method is simple and convenient, reaction conditions are mild, yield is high, and the method is suitable for large scale industrialized production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to a method for preparing 1-(3-methoxypropyl)-4-piperidinamine, an important intermediate of prucalopride (see I for the structure). [0002] [0003] I Background technique [0004] Prucalopride is a selective 5-HT developed by Movetis NV in Belgium--------------------------------- ------------- 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. In many synthetic routes of prucalopride, generally speaking, 1-(3-methoxypropyl)-4-piperidinamine is an essential intermediate, an...

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Problems solved by technology

In many synthetic routes of prucalopride, generally speaking, 1-(3-methoxypropyl)-4-piperidinamine is an essential intermediate, and the synthesis of this intermediate has attracted great attention. The patent US6479487 discloses the method of obtaining 1-(3-methoxypropyl)-4-piperidinamine by oximation reduction using 1-(3-methoxypropyl)-4-piperidinone as raw material, This method adopts lithium aluminum hydride as reducing agent, and post-treatment is loaded down with trivial details, and reaction yield is low

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