Palbociclib crystalline compound and preparation method thereof

A compound and crystal form technology, which is applied in the field of palbociclib new crystal form compound and its preparation, can solve the problems of unguaranteed pharmaceutical crystal form and excessive ignition residue, so as to improve the quality of drug production, improve solubility and reaction The effect of mild conditions

Active Publication Date: 2017-06-20
SHANDONG YUXIN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its preparation process is precipitated from an aqueous solution rich in inorganic salts, which will bring the risk of excessive residue on ignition. The prepared product has not been compared with the original research prescription for the dissolution rate of the preparation, so it cannot guarantee that it can meet the requirements of the pharmaceutical crystal form.

Method used

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  • Palbociclib crystalline compound and preparation method thereof
  • Palbociclib crystalline compound and preparation method thereof
  • Palbociclib crystalline compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: Preparation of palbociclib crystal form compound

[0037]Take 50g of palbociclib in a reaction flask, add 1000ml of a mixed solution of dimethyl carbonate and ethanol (the volume ratio of dimethyl carbonate and ethanol is 3:1), heat to 70°C, stir to dissolve, and filter while hot ; While stirring, cool down to 20°C (the cooling range is 5°C per 10 minutes), add pre-cooled ethanol at a flow rate of 1.0mL / min to the solution (1000ml of ethanol is until the crystals come out, and continue to cool down to -5°C (cooling The amplitude is 1°C every 10 minutes), stirring for 3h. Vacuum suction filtration, the filter cake was vacuum-dried at 50°C for 6h to obtain 45.3g of light yellow solid with a yield of 90.5%.

Embodiment 2

[0038] Embodiment 2: Preparation of palbociclib crystal form compound

[0039] Take 50g of palbociclib in a reaction flask, add 1500ml of a mixed solution of dimethyl carbonate and ethanol (the volume ratio of dimethyl carbonate and ethanol is 2:1), heat to 75°C, stir to dissolve, and filter while hot While stirring, the temperature was lowered to 25°C (the cooling range was 5°C per 10 minutes), and 3000ml of pre-cooled ethanol was added to the solution at a flow rate of 1.5mL / min until crystallization, and the temperature was continued to drop to -10°C (the cooling range was 1°C every 10 minutes), stirring for 2h. After vacuum filtration, the filter cake was vacuum-dried at 50° C. for 4 hours to obtain 44.8 g of a light yellow solid with a yield of 89.6%. The X-ray powder diffraction spectrum of the obtained crystal measured by Cu-Kα rays is similar to that of Example 1.

Embodiment 3

[0040] Embodiment 3: Preparation of palbociclib crystal form compound

[0041] Take 50g of palbociclib in a reaction flask, add 2000ml of a mixed solution of dimethyl carbonate and ethanol (the volume ratio of dimethyl carbonate and ethanol is 2:1), heat to 65°C, stir to dissolve, and filter while hot While stirring, the temperature was lowered to 30° C. (the temperature drop was 5° C. per 10 minutes), and 2000 ml of pre-cooled ethanol was added to the solution at a flow rate of 2 mL / min to crystallization, and the temperature was continued to drop to -5° C. (the temperature drop was 5° C. per 10 minutes). 10 minutes at 1 ° C), stirred for 2h. After vacuum filtration, the filter cake was vacuum-dried at 50° C. for 5 h to obtain 45.7 g of a light yellow solid with a yield of 91.5%. The X-ray powder diffraction spectrum obtained by measuring the prepared palbociclib crystals using Cu-Kα rays is similar to that of Example 1.

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Abstract

The invention belongs to the technical field of medicines, and discloses a palbociclib crystalline compound and a preparation method thereof. An X-ray powder diffraction spectrum represented by a diffraction angle of 2theta plus/minus 0.2 degree displays characteristic diffraction peaks at the positions of 3.21 degrees, 5.62 degrees, 6.53 degrees, 9.12 degrees, 13.41 degrees, 14.43 degrees, 15.53 degrees, 21.72 degrees, 24.61 degrees and 27.71 degrees; the X-ray powder diffraction spectrum obtained by measuring with Cu-Kalpha rays is as shown in Figure 1, and is totally different from that in the prior art. The palbociclib crystalline compound has better water solubility and higher stability, the preparation method is simple and easy to operate, after the palbociclib crystalline compound is prepared into a drug composition, the drug use safety is greatly improved, and the drug composition is very suitable for clinic application.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and specifically relates to a new crystal form compound of palbociclib and a preparation method thereof. Background technique [0002] Palbociclib (Palbociclib) is a selective CDK4 / 6 inhibitor developed by Pfizer Pharmaceuticals Co., Ltd. (Pfizer). On February 3, 2015, based on the progression-free survival (PFS) proved by clinical trials, the FDA adopted accelerated review Approved by the pathway, it is used in combination with Letrozole (Letrozole) as an initial regimen based on endocrine therapy for the treatment of estrogen receptor positive (ER + ), human epidermal growth factor receptor 2 negative (HER2 - ) breast cancer in postmenopausal women. The CAS number of Palbociclib is 571190-30-2, and its chemical name is: 6-acetyl-8-cyclopentyl-5-methyl-2-[[5-(piperazin-1-yl)pyridine- 2-yl]amino]-8H-pyrido[2,3-D]pyrimidin-7-one, molecular weight: 447.54, chemical formula: C 24 h ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04
CPCC07B2200/13C07D471/04
Inventor 李华张珍珍华伟
Owner SHANDONG YUXIN PHARMA CO LTD
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