A new crystal form of sofosbuvir and its preparation method
A technology of sofosbuvir and Wei crystal, applied in the field of new crystal forms of sofosbuvir and its preparation, can solve problems such as being unfavorable for dry granulation operation, unfavorable for industrial application, difficult to be pressed into ribbons, etc., and achieve process stability Good, stable and controllable quality, short drying time
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Embodiment 1
[0044] Embodiment 1: Preparation of sofosbuvir β crystal form
[0045] Put 100g of sofosbuvir form 1 into 200ml of acetone, heat to 35-45°C, slowly add 400ml of isopropyl ether within 5 minutes, add 200ml of isopropyl ether after stirring for 0.5 hours, and cool the mixture to 5-10°C in an ice-water bath After continuing to stir for 1 hour, filter, wash the filter cake with isopropyl ether, and vacuum-dry at 35-50°C for 4-5 hours to obtain sofosbuvir β crystal form, weight 90g, yield 90%. figure 1 , and its X-ray diffraction data are shown in Table 1:
[0046] Sofosbuvir β crystal form X-ray diffraction data of Table 1 Example 1
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Embodiment 2
[0049] Embodiment 2: Preparation of sofosbuvir β crystal form
[0050] Put 112g of sofosbuvir form 1 into 600ml of isopropanol, heat to 25-40°C, add about 0.6g of sofosbuvir β crystal form prepared in Example 1 under stirring as a seed crystal, and continue stirring for 0.5 hours Slowly add 600ml of n-heptane, stir for 1 hour, continue to add 2400ml of n-heptane, continue stirring for 1 hour, filter, wash the filter cake with isopropanol:n-heptane = 1:5, and vacuum dry at 35-50°C for 7-8 Sofosbuvir β crystal form was obtained in 1 hour, weight 102g, yield 91%, and its X-ray diffraction data are as shown in Table 2:
[0051] Sofosbuvir β crystal form X-ray diffraction data of Table 2 Example 2
[0052] 2θ(°) Relative Strength(%) 8.046 100.0 10.338 37.4 12.371 75.2 13.432 15.8 16.172 10.7 16.762 26.3 17.162 13.9 18.653 10.0 19.346 37.1 19.953 29.9 20.785 29.3
Embodiment 3
[0053] Embodiment 3: Preparation of sofosbuvir β crystal form
[0054] Put 164g of sofosbuvir form 1 into 410ml of ethanol, heat to 25-40°C, stir for 1 hour, then slowly add 410ml of n-heptane, keep stirring at the temperature until the system is viscous, continue to add 1640ml of n-heptane, and continue stirring after adding After filtering for 1 hour, the filter cake was washed with ethanol:n-heptane = 1:2, and vacuum-dried at 35-50°C for 7-8 hours to obtain sofosbuvir β-crystal form, weighing 154g, yield 94%. , and its X-ray diffraction data are shown in Table 2:
[0055] Sofosbuvir β crystal form X-ray diffraction data of Table 3 Example 3
[0056] 2θ(°) Relative Strength(%) 8.160 100.0 10.438 47.7 12.457 70.1 13.531 15.3 16.255 11.0 16.927 17.2 17.245 27.0 18.755 14.5 19.443 55.7 20.077 43.5 20.869 41.0
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