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Method for purifying clofarabine by using chromatographic column

A clofarabine and chromatographic column technology, applied in the field of clofarabine purification, can solve problems such as being difficult to remove, and achieve the effect of simple operation

Inactive Publication Date: 2009-07-08
深圳万乐药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the physical and chemical properties of clofarabine and its α-configuration isomer are very close, conventional purification methods such as recrystallization are difficult to remove the α-configuration isomer from clofarabine

Method used

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  • Method for purifying clofarabine by using chromatographic column
  • Method for purifying clofarabine by using chromatographic column

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 600ml of MCI-gel CHP20P filler to a 2L beaker and soak in 1L of absolute ethanol for 10h. After stirring evenly, put it into a glass chromatographic column by wet method, the diameter of the chromatographic column is 5cm, and the length of the column is 100cm. Elute with 10L of purified water until the effluent has no ethanol, and the flow rate is controlled at 6ml / min. The time required is about 4h. Add 10 g of crude clofarabine to be purified into 4 L of purified water, and heat until completely dissolved. Cool naturally to room temperature and load the sample. The time required is about 2h. Use 5L purified water, 5L purified water and 250ml ethanol mixture, 5L purified water and 500ml ethanol mixture, 5L purified water and 750mL ethanol mixture, 5L purified water and 1L ethanol mixture to elute sequentially, and the flow rate is controlled at 6ml / min . The effluent was collected and tested for purity by HPLC. Collect clofarabine purity greater than 99.8%, t...

Embodiment 2

[0024] Add 600ml of MCI-gel CHP20P reverse packing to a 2L beaker, soak in 1L of absolute ethanol for 15h. After stirring evenly, put it into a glass chromatographic column by wet method, the diameter of the chromatographic column is 5cm, and the column length is 50cm. Elute with 10L of purified water until the effluent has no ethanol, and the flow rate is controlled at 6ml / min. Add 5 g of crude clofarabine to be purified into 4 L of purified water, and heat until completely dissolved. Cool naturally to room temperature and load the sample. The time required is about 2h. Use 5L purified water, 5L purified water mixed with 250ml methanol, 5L purified water mixed with 500ml methanol, 5L purified water mixed with 750mM methanol, 5L purified water mixed with 1L methanol, and the flow rate is controlled at 2ml / min . The effluent was collected and tested for purity by HPLC. The fractions of clofarabine with a purity greater than 99.8% and a single impurity less than 0.1% were c...

Embodiment 3

[0026] Add 600ml of MCI-gel CHP20SS reverse packing to a 2L beaker and soak in 1L of absolute ethanol for 15h. After stirring evenly, put it into a glass chromatographic column by wet method, the diameter of the chromatographic column is 5cm, and the column length is 50cm. Elute with 10L of purified water until the effluent has no ethanol, and the flow rate is controlled at 6ml / min. Add 2.5 g of crude clofarabine to be purified into 4 L of purified water, and heat until completely dissolved. Cool naturally to room temperature and load the sample. The time required is about 2h. Use 5L of purified water, 5L of purified water and 250ml of acetone mixture, 5L of purified water and 500ml of acetone mixture, 5L of purified water and 750mL of acetone mixture, 5L of purified water and 1L of acetone mixture, and the flow rate is controlled at 4ml / min . The effluent was collected and tested for purity by HPLC. The fractions of clofarabine with a purity greater than 99.8% and a sing...

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Abstract

The invention discloses a method for purifying clofarabine by a chromatographic column. The method adopts an inverse macroporous adsorption resin as a chromatographic column packing material to prepare the chromatographic column, adds a crude product water solution of the clofarabine with a concentration of between 0.001 and 0.025 weight percent into the chromatographic column, then performs the elution by pure water first, then orderly uses pure water / organic solution mixed liquids with the gradually reduced volume ratios as eluents for gradient elution, and collects and concentrates the eluents with qualified purity. The purification method ensures that the purity of a clofarabine product reaches more than 99.8 percent and the yield reaches more than 90 percent, has simple operation, and is suitable for industrial mass production.

Description

technical field [0001] The present invention relates to a method for purifying clofarabine, in particular to a method for purifying clofarabine with a chromatographic column. Background technique [0002] Clofarabine is a nucleoside purine anticancer drug, which has effects on a variety of solid tumors, and is particularly effective in the treatment of acute leukemia. It is the first FDA-approved drug specifically for childhood leukemia. Its structural formula is as follows: [0003] [0004] U.S. patent application WO03011877 discloses the synthesis method of clofarabine, starting from 1,3,5-tri-O-benzoyl-α-D-ribofuranose, and obtaining 1 after rearrangement, fluorination and bromination. -Bromo-2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-ribofuranose, which is synthesized by deprotection after condensation with 2-chloroadenine. Wherein the condensation and deprotection reaction formulas are shown below. [0005] [0006] The product of the above condensation reaction is...

Claims

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Application Information

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IPC IPC(8): C07H19/173A61P35/00
Inventor 苏军张广明王庆秋
Owner 深圳万乐药业有限公司
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