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Preparation method of palbociclib crystal form A

A technology of palbocoxib and its crystal form, which is applied in the field of chemical synthesis, can solve problems such as difficulty in ensuring product purity, difficulty in compound purification, skin irritation, etc., and achieves simple and easy preparation methods, easy post-processing, and harm to the human body and the environment. less harmful effect

Inactive Publication Date: 2017-01-11
PEKING UNIV FOUNDER GRP CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] 1. Although this method has fewer steps, the required reaction temperature is higher (>120°C), which makes it difficult to be widely used in industry
And anisole is rarely used in industry, has a special unpleasant smell, is flammable, is irritating to human skin, and is harmful to the environment
[0010] 2. The "one-step synthesis method" undergoes three steps: deprotection, preparation of free base, and preparation of crystal form. This method is easier to introduce unknown impurities, and it is not easy to realize the purification of the compound, and it is difficult to guarantee the purity of the product

Method used

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  • Preparation method of palbociclib crystal form A
  • Preparation method of palbociclib crystal form A
  • Preparation method of palbociclib crystal form A

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1: Preparation of Salts of Palbociclib

[0056] Weigh 10 g of compound INB, add 230 ml of methanol and 3 ml of water. When the temperature was raised to 55°C, the solution was yellow and suspended; 8.5 grams of isethionic acid was added dropwise, and the solution gradually became clear; the temperature was raised to 65°C, and stirred for 12 hours; a large amount of solids were precipitated in the system, and filtered to obtain 10.02 grams of the product INC sample, the yield 86.4%.

Embodiment 2

[0057] Example 2: Preparation of Palbociclib Free Base Crystal Form A

[0058] Weigh 10 grams of the product INC of Example 1, add 150 milliliters of water and 30 milliliters of methanol, and the solution is clarified. After filtering, add sodium hydroxide solution (5% W / W) dropwise to the mother liquor to adjust the pH of the solution to >8. Stirring was continued at room temperature for 3 hours, a large amount of solid precipitated and was filtered. To obtain a solid, add 150 ml of water, stir for 1 hour, filter, and wash with water. After drying, 5.4 g of the product was obtained with a yield of 84.5%. 99.9% pure.

Embodiment 3

[0059] Embodiment 3: determination of crystal form

[0060] Detect Example 2 product powder X-ray diffraction (PXRD):

[0061] Use the Rigaku Dmax / 2400 type X-ray polycrystalline powder diffractometer (condition: Cu Kα, 40kV) to measure;

[0062] Please refer to the attached manual for the PXRD spectrum figure 1 :

[0063] Peak table of PXRD pattern:

[0064]

[0065]

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Abstract

The invention provides a preparation method of a palbociclib crystal form A. The preparation method is simple and easy to perform. The used reagents are all common reagents. The preparation method is suitable for industrial massive production. The product purity is high and meets requirements of pharmaceutical crystal form.

Description

technical field [0001] The invention provides a method for preparing palbocoxib crystal form A, which belongs to the technical field of chemical synthesis. Background technique [0002] Palbociclib, English name: Palbociclib, molecular formula: C 24 h 29 N 7 o 2 , [0003] CAS number: 571190-30-2; chemical structure: [0004] [0005] Palbociclib is an oral cyclin-dependent kinase (CDKs) 4 and 6 inhibitor developed by Pfizer. CDKs 4 and 6 are key regulators of the cell cycle that trigger cell cycle progression. The indication for palbociclib is combined with letrozole for the treatment of estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+ / HER2-) postmenopausal patients with advanced breast cancer, as an initial endocrine therapy-based regimen for the treatment of metastases disease. [0006] WO2014128588A1 discloses a preparation method of Palbociclib crystal form A, which uses a "one-pot method" (the following formula) to directly ...

Claims

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Application Information

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IPC IPC(8): C07D471/04
CPCC07D471/04C07B2200/13
Inventor 易崇勤刘鹏李学义冀蕾黄琪
Owner PEKING UNIV FOUNDER GRP CO LTD
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