Method for preparing impurity oxalate of intermediate condensation compound of pradaxa

By reacting p-aminobenzamidine dihydrochloride with n-hexyl chloroformate, combined with oxalic acid dihydrate, the impurity oxalate of the dabigatran etexilate intermediate condensate is prepared, solving the unknown problem in the dabigatran etexilate intermediate condensate. The problem of low impurity purity has been solved, and high-purity preparation and technological progress have been achieved.

CN105348148AActive Publication Date: 2016-02-24SHANDONG XINHUA PHARMA CO LTD
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Patent Information

Application Number
CN201510862480.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2015-11-30
Publication Date
2016-02-24
Estimated Expiration
2035-11-30

AI Technical Summary

Technical Problem

In the preparation process of dabigatran etexilate intermediate condensate, there are a large number of unknown impurities, resulting in low purity and affecting product quality and technological progress.

Method used

The impurity oxalate of dabigatran etexilate intermediate condensate is prepared by reacting p-aminobenzamidine dihydrochloride with n-hexyl chloroformate, combined with oxalic acid dihydrate, using specific reaction steps and conditions, including in 18 Add p-aminobenzamidine dihydrochloride solid in batches at -22°C, control the reaction time and temperature, then add water and acetone to dissolve, cool down to crystallize, filter and dry.

Benefits of technology

The high-purity preparation of the impurity oxalate, the condensation product of dabigatran etexilate etexilate, was achieved. The HPLC content was greater than 98%, and the yield reached more than 46.5%, which promoted the impurity research and synthesis technology progress of dabigatran etexilate etexilate.

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Abstract

The invention belongs to the field of medicinal chemistry and particularly relates to a method for preparing the impurity oxalate of an intermediate condensation compound of pradaxa. Hexyl chloroformate, dichloromethane, sodium hydroxide and water are added into a reaction flask, a 4-aminobenzamidine dihydrochloride solid is added, and a reaction is carried out; water is added after the reaction is finished, stirring and standing are carried out, and a water layer is separated and removed; an organic layer is steamed for removing dichloromethane, and a thick solid is obtained; the thick solid is added with acetone, heated and dissolved, added with oxalic acid dihydrate, cooled for crystallization, filtered and dried, and the impurity oxalate of the intermediate condensation compound of pradaxa is obtained. The HPLC content of the impurity oxalate (IIa), prepared and obtained through the preparing method, of the intermediate condensation compound of pradaxa is higher than 98%; synthesis of the impurity oxalate of the intermediate condensation compound of pradaxa is beneficial to impurity research of pradaxa, and the technological progress of synthesizing pradaxa is promoted.
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