Preparation method for pharmaceutical crystal form of febuxostat

A febuxostat, crystal form technology, applied in organic chemistry methods, organic chemistry and other directions, can solve the problems of unsuitable terminal solvent, cumbersome operation process, poor process stability, etc., and achieves strong operability and low process cost. Effect

Active Publication Date: 2017-04-19
YANGTZE RIVER PHARM GRP CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The preparation method of crystal form A disclosed in the patent CN1275126A is prepared by crystallization with methanol water as a solvent. The operation process is cumbersome, the process stability is poor, and the methanol solvent used is a controlled second-class organic solvent, which is not suitable for the production of raw materials. terminal solvent

Method used

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  • Preparation method for pharmaceutical crystal form of febuxostat
  • Preparation method for pharmaceutical crystal form of febuxostat
  • Preparation method for pharmaceutical crystal form of febuxostat

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 (by the method of the present invention, the volume-to-weight ratio of aqueous ethanol and febuxostat is 7L / kg)

[0034] Add 50.0g of febuxostat to a 500ml three-necked bottle, add 350ml of ethanol with a weight percentage of 90% ethanol aqueous solution, stir, heat and reflux until completely dissolved and then stir for 30min. When the temperature of the reaction system was slowly lowered to 63° C., 0.15 g of febuxostat medicinal crystal form seed (form A) was added, and solids were precipitated in the reaction system. Continue to stir and cool down to 35°C, keep stirring for 1h, filter with suction until no liquid flows out, collect the filter cake in a hot air drying oven at a controlled temperature of 55-60°C and dry for 6h to obtain 41.0g of a white solid with a yield of 82% and a chromatographic purity of 99.96%. Sampling detection, powder X-ray diffraction spectrum and infrared spectrum are consistent with the spectrum disclosed in the patent applica...

Embodiment 2

[0035] Embodiment 2 (by the method of the present invention, the volume-to-weight ratio of aqueous ethanol and febuxostat is 8L / kg)

[0036] Add 10.0g of febuxostat to a 250ml three-necked bottle, add 80ml of ethanol with a weight percentage of 90% ethanol aqueous solution, stir, heat to reflux until completely dissolved and then stir for 30min. When the temperature of the reaction system was slowly lowered to 63° C., 30 mg of febuxostat medicinal crystal form seed crystal (form A) was added, and a solid precipitated out of the reaction system. Continue stirring to cool down to 35°C, keep stirring for 1 hour, filter with suction until no liquid flows out, collect the filter cake in a hot-air drying oven at a controlled temperature of 55-60°C and dry for 6 hours to obtain 6.7 g of white solid, with a yield of 67%. Sampling and detection showed that the powder X-ray diffraction spectrum and infrared spectrum were consistent with the spectrum disclosed in the patent application C...

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Abstract

The invention discloses a preparation method for a pharmaceutical crystal form of febuxostat. The preparation method comprises the following steps: dissolving the febuxostat in an ethanol aqueous solution, and carrying out heating and dissolving under stirring; carrying out hot filtration, slowly cooling a filtrate, adding a seed crystal, carrying out stirring until a solid is separated, continuing cooling, maintaining the temperature, and carrying out crystallization; and carrying out filtering, placing a filter cake in a hot-air drying oven, and carrying out drying so as to obtain a product. The method provided by the invention has the advantages of simple and convenient operation, good repeatability, high product purity and yield, good crystal stability, and applicability to industrial production.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of febuxostat medicinal crystal form. Background technique [0002] The chemical name of febuxostat is 2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-5-thiazolecarboxylic acid, which has the following structure: [0003] [0004] Febuxostat is a drug developed by Teijin Corporation of Japan for the treatment of gout and hyperuricemia. It was approved for marketing by the European Union in April 2008, and then launched in the United States and China in 2009 and 2013, respectively. Febuxostat is a specific and selective inhibitor of non-purine xanthine oxidase / xanthine dehydrogenase (XO). Compared with allopurinol, it has higher selectivity and more Strong activity, can rapidly reduce blood uric acid level, no dose adjustment is needed for patients with mild to moderate renal insufficiency, and there is no obvious adverse reaction. [0005] Patent CN12751...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D277/56
CPCC07B2200/13C07D277/56
Inventor 施连勇陈小青张海波陈令武顾诚周华新徐助雄刘旭尹必喜
Owner YANGTZE RIVER PHARM GRP CO LTD
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