872728-81-9Relevant articles and documents
Method for refining dabigatran etexilate and method for controlling specific degradation impurities of dabigatran etexilate
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Paragraph 0050-0052, (2021/08/28)
The invention provides a method for refining dabigatran etexilate and a method for controlling specific degradation impurities of dabigatran etexilate. The dabigatran etexilate compound is 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridine-2-yl-amino]-ethyl propionate mesylate, the invention also relates to a control method of specific degradation impurities in the refining process of the compound. The method comprises the following steps: stirring and mixing dabigatran etexilate and acetonitrile, then heating to a reflux state, carrying out heat preservation for 1-2 hours in the reflux state, then carrying out slow cooling, filter pressing, vacuum drying and other technological processes to obtain dabigatran etexilate, and salifying the dabigatran etexilate and methanesulfonic acid to obtain dabigatran etexilate mesylate. The dabigatran etexilate obtained by the refining method provided by the invention has the advantages of high purity, no solvent residue, mild reaction conditions and easiness in industrial production.
Preparation process of Pradaxa
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, (2018/03/06)
The invention discloses a preparation process of Pradaxa. After obtaining a compound 3 with the structural formula as shown in the description, an alkali liquor is added to separate out the compound 3; micro-molecule alcohol is used for refining; under the action of a reaction solvent and an organic alkali, the compound 3 and hexyl chloroformate conduct a condensation reaction to obtain a compound2 with the structural formula as shown in the description; an acid liquor is used for washing, and vacuum concentration is performed till the product is dry; an organic solvent is used for refining;and the compound 2 and methanesulfonic acid are salified to obtain Pradaxa. Through the continuous operation that solid-liquid separation is performed after the alkali liquor is added to separate outthe compound 3, the problems that lots of acid is evaporated to corrode equipment due to vacuum concentration and many degradation impurities are produced by heating are solved. The pickling process is adopted to control specific impurities in a reaction liquid of the compound 2. At last, an appropriate methanesulfonic acid charge ratio and an appropriate charging temperature are adopted to guarantee correct product crystal forms.
Novel hemi-salt of dabigatran etexilate and preparation method thereof
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Paragraph 0077-0079, (2018/05/29)
The present invention relates to a dabigatran etexilate hemic acid added salt and a method for manufacturing the same. More specifically, the present invention relates to a dabigatran hemi fumarate and hemi citrate, and a method for manufacturing the same. Since the crystalline dabigatran etexilate hemi fumarate and hemi citrate of the present invention are stable to heat and excellent in filtering and drying properties, the hemic acid added salt of the present invention can be used as an active ingredient of a pharmaceutical composition for preventing and treating stroke of patients suffering from thromboembolism and atrial fibrillation.COPYRIGHT KIPO 2018