Azilsartan crystal and its preparation method and application
A technology of crystals and crystals, applied in the field of azilsartan crystals and its preparation, can solve the problems of poor stability, many impurities, poor solubility of azilsartan, etc., and achieve good solubility, high purity, and safe production and preparation process Effect
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Embodiment 1
[0036] Preparation of Crude Azilsartan
[0037] References J.Med.Chem, 1996,39,5228-5235, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl ) [1,1'-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid methyl ester compound 100.0 g, placed in a reaction flask, added 0.4 mol / L sodium hydroxide 1700ml, react at 73-75°C for 2 hours. After the reaction, cool to room temperature, add dropwise acid aqueous solution to pH=3-4, and precipitate azilsartan crude product.
Embodiment 2
[0039] Put 3 g of the crude product of azilsartan prepared in Example 1 into a reaction flask, add 100 ml of tetrahydrofuran, stir at reflux at 65° C. for 1 hour, heat filter, and naturally cool and crystallize the filtrate to obtain 2.5 g of a solid, which is azilsartan crystals. HPLC purity 99.87%.
[0040] X-ray powder diffraction spectrum, DSC spectrum, TGA spectrum, infrared spectrum are respectively as attached figure 1 , 2 , 3, 4 shown.
[0041]figure 1 The detailed data in the X-ray powder diffraction pattern are shown in Table 1.
[0042] The X-ray powder diffraction data of the azilsartan crystal of table 1 embodiment 1
[0043]
[0044]
[0045] In Table 1, the characteristic diffraction peaks of the crystal of the present invention are: 6.889±0.2°, 7.638±0.2°, 8.664±0.2°, 9.080±0.2°, 10.500±0.2°, 12.691±0.2°, 16.423±0.2°, 18.316± 0.2°, 18.61±0.2°, 19.2854±0.2°, 19.898±0.2°, 20.333±0.2°, 21.417±0.2°, 21.772±0.2°, 22.996±0.2°, 23.489±0.2°, 25.168±0.2°, 25.6...
Embodiment 3
[0051] Add 50 g of the crude product of azilsartan obtained in Example 1, add 200 ml of ethanol, beat and wash at 10-30 ° C for 1 h, and obtain 45 g of anhydrous azilsartan crystals (for the preparation method of anhydrous azilsartan crystals, please refer to literature J .Med.Chem, 1996,39,5228-5235), its X-ray powder diffraction pattern is shown in Figure 5 . Add 100ml of THF to 10g of the obtained azilsartan anhydrous crystal, stir the suspension at 10-30°C for 2h, filter to obtain a solid, and obtain 8.5g of the azilsartan crystal of the present invention, with an HPLC purity of 99.91%. Its X-ray powder diffraction pattern is as figure 1 shown.
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Abstract
Description
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