Dacomitinib solvate, novel crystalline form of dacomitinib and preparation method and use of dacomitinib in novel crystalline form
A solvate, the technology of dacomitinib, applied in the field of dacomitinib solvates, can solve the problems such as undisclosed solvates and their crystal forms
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Embodiment 1
[0116] Weigh 2.15g of Dacomitinib, add 10.5mL of tetrahydrofuran (THF), heat to reflux, dissolve, add dropwise about 14mL of methyl tert-butyl ether (MTBE), and drop it within 10min. The system appears turbid, keep After refluxing for 30 minutes, the temperature was naturally lowered to room temperature, stirred at room temperature for 1 hr, filtered, and vacuum-dried at 65°C overnight to obtain 1.3 g of 1 / 2 tetrahydrofuran solvate crystal form I of dacomitinib.
[0117] The X-ray powder diffraction data of the crystal form I are shown in the following table:
[0118]
[0119]
[0120] The 1H-NMR and X-ray powder diffraction patterns of the crystal form I are detailed in figure 1 , figure 2 , the DSC spectrum of the crystal form I is as follows image 3 As shown, there are sharp endothermic peaks at 115.7°C (±0.5°C) and 197.2°C (±0.5°C).
[0121] Such as figure 1 As shown, we found that the samples obtained in this embodiment after drying were in 1 H-NMR showed th...
experiment example 2
[0123] Weigh 2.15g of Dacomitinib, add 20mL of ethanol and water 1:1 solution, heat to reflux, dissolve, and maintain reflux for 15mins, start to cool down to room temperature naturally, and stir at room temperature for 1hr, filter, and vacuum dry at 65°C Overnight, 1.7 g of the monohydrate crystal form II of dacomitinib was obtained.
[0124] The X-ray powder diffraction data of the crystal form II are shown in the following table:
[0125]
[0126]
[0127] The crystal form II 1 For H-NMR and X-ray powder diffraction patterns, see Figure 4 , Figure 5 , the DSC spectrum of the crystal form II is as follows Figure 6 As shown, there are sharp endothermic peaks at 151.7°C (±0.5°C) and 168.3°C (±0.5°C).
[0128] Such as Figure 4 As shown, we found that the sample of this example after drying 1 H-NMR data showed that there was water in it, and the molar ratio of water to dacomitinib was about 1:1. We further vacuum-dried the sample at 65°C and found that the water...
experiment example 3
[0130] Weigh 2.15g of Dacomitinib, disperse it in 15mL of ethanol, heat to reflux, and maintain reflux for 15mins, start to cool down to room temperature naturally, and stir at room temperature for 1hr, filter, and vacuum dry overnight at 65°C to obtain 1.4g of Dacomitinib The 1 / 2 ethanol solvate crystal form III of Nisin.
[0131] The X-ray powder diffraction data of the crystal form III are shown in the following table:
[0132]
[0133]
[0134] The crystal form III 1 For H-NMR and X-ray powder diffraction patterns, see Figure 7 , Figure 8 , the DSC spectrum of the crystal form is as follows Figure 9 As shown, there are sharper endothermic peaks at 110.6°C (±0.5°C) and 198.3°C (±0.5°C).
[0135] Such as Figure 7 As shown, we found that the samples of this example after drying were in 1 H-NMR showed the presence of ethanol, and the molar ratio of ethanol to dacomitinib was 1:2. We further vacuum-dried the sample at 65°C, and found that the ethanol in the sam...
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