Novel crystal forms of anticancer compound CX1409 dihydrate and DMSO solvate, and preparation method and applications thereof
A technology of CX1409 and dihydrate, applied in organic chemical methods, medical preparations containing active ingredients, organic chemistry, etc., can solve problems such as poor storage, easy degradation, and restrictions on popularization and application, and achieve the effect of performance improvement
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Embodiment 1
[0073] Embodiment 1: the preparation of CX1409 crude product
[0074] The preparation flow chart of CX1409 crude product is shown in the following formula:
[0075]
[0076] Specifically include the following steps:
[0077] (1) Dissolve CX1409-01 (15g) in DMF (45mL), then add imidazole (5.22g), control the temperature at about 20-25°C while stirring, slowly add TESCl (6.74g), dropwise, 20 Stir at ~25°C for 0.5h. After the reaction was complete, purified water (105 mL) and DCM (150 mL) were added to separate the layers. The organic phase was washed with water (105 mL) and saturated NaCl (75 mL). The liquid was separated, and the organic phase was evaporated to dryness to obtain the crude product. Add n-hexane (150 mL) and EA (15 mL) to the crude product, stir at room temperature for 1 h, filter with suction, wash the filter cake with a small amount of n-hexane, and vacuum-dry at 40°C for 2 h to obtain 16.7 g of the product CX1409-05.
[0078] (2) Under the protection o...
Embodiment 2
[0084] Example 2: Preparation of CX1409 dihydrate crystal form C
[0085] Weigh 1.0 g of crude CX1409 (prepared in Example 1) and add it to 5 mL of tetrahydrofuran, stir for 10 min, then add 6 mL of tetrahydrofuran, heat to 55 ° C to dissolve until clear, and keep for 45 min; slowly drop the clear solution into Stir in 9mL of 55°C water at a low speed, slowly cool down to 30°C (cooling rate is 0.5°C / min), grow crystals at constant temperature for 60 minutes, then continue to slowly cool down to 10°C (cooling rate is 0.3°C / min), grow crystals for 120 minutes The resulting crystals were collected by filtration and dried at 40° C. for 16 h under vacuum to obtain 725 mg of Form C (purity: 99.43%), whose powder X-ray diffraction pattern is shown in image 3 .
Embodiment 3
[0086] Example 3: Preparation of CX1409 dihydrate crystal form C
[0087] Weigh 1.0 g of CX1409 crude product (prepared in Example 1) and add it to 10 mL of tetrahydrofuran, heat to 50 ° C to dissolve until clear, and keep for 30 min; slowly drop the clear solution into 9 mL of 50 ° C water, stir at a low speed , slowly cool down to 25°C (cooling rate is 0.5°C / min), grow crystals at constant temperature for 40 minutes, then continue to slowly cool down to 5°C (cooling rate is 0.3°C / min), grow crystals for 90 minutes; the obtained crystals are collected by filtration, and in Drying at 40°C for 16 h under vacuum conditions yielded 786 mg of Form C (purity: 99.37%), and its powder X-ray diffraction pattern is shown in image 3 .
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