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A kind of purification process of methotrexate or its salt

A kind of methotrexate, the technology of technology, is applied in the purification technology field of methotrexate or its salt, can solve the problems such as excessive ammonia water, environmental pollution and the like

Active Publication Date: 2021-04-27
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method still uses hydrochloric acid and ammonia water for acid-base adjustment, which requires more ammonia water and causes greater environmental pollution.

Method used

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  • A kind of purification process of methotrexate or its salt
  • A kind of purification process of methotrexate or its salt
  • A kind of purification process of methotrexate or its salt

Examples

Experimental program
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Effect test

preparation example Construction

[0029] Preparation of pH 6.0 buffer: prepare a mixture of 0.2M disodium hydrogen phosphate and 0.1M citric acid (volume ratio 630:370), and use 0.1M citric acid or 0.2M dihydrogen phosphate if necessary Sodium adjusts pH to 6.0;

[0030] Preparation of mobile phase: the mixture (volume ratio of 90:10) of the pH 6.0 buffer and acetonitrile prepared above was filtered and degassed;

[0031] The detection wavelength is 302nm; the flow rate is 1.2ml / min; the injection volume is 20μl; the column temperature is room temperature.

Embodiment 1

[0033] Add 450ml of water, 24.2g of tetraaminopyrimidine sulfate and 15.9g of zinc p-thraniloyl L-glutamate into a 1.0L flask, stir, heat to 50±5°C, continue to stir for 1.0h, then add 1 26.6g tribromoacetone of / 3, temperature is controlled at 50 ± 5 ℃, controls pH=2.35 ± 0.15 with 20% (mass percentage) NaOH aqueous solution, adds 1 / 3 tribromoacetone every 30min, continues to use 20% ( mass percent) NaOH aqueous solution to maintain the pH, and reacted for 3.5h.

[0034] After the reaction is complete, control the temperature of the reaction solution to 45°C, adjust the pH to 1.8 with dilute hydrochloric acid, filter, wash with water, add 35ml of water and 35ml of acetone to the filter cake, add 10% (mass percentage) NaOH aqueous solution dropwise, adjust the pH to 8.5, and filter , wash the filter cake with a small amount of acetone / water (volume ratio 1:1), add 210ml of acetone dropwise to the filtrate to crystallize, continue to stir for 1h, filter, wash the filter cake wi...

Embodiment 2

[0036] Add 450ml of water, 24.2g of tetraaminopyrimidine sulfate and 15.9g of zinc p-thraniloyl L-glutamate into a 1.0L flask, stir, heat to 50±5°C, continue to stir for 1.0h, then add 1 26.6g tribromoacetone of / 3, temperature is controlled at 50 ± 5 ℃, controls pH=2.35 ± 0.15 with 20% (mass percentage) NaOH aqueous solution, adds 1 / 3 tribromoacetone every 30min, continues to use 20% ( mass percent) NaOH aqueous solution to maintain the pH, and reacted for 3.5h.

[0037] After the reaction is complete, control the temperature of the reaction solution to 30°C, adjust the pH to 1.5 with dilute hydrochloric acid, filter, wash with water, add 35ml of water and 35ml of acetone to the filter cake, add 10% (mass percentage) NaOH aqueous solution dropwise, adjust the pH to 8.5, and filter , wash the filter cake with a small amount of acetone / water (volume ratio 1:1), add 210ml of acetone dropwise to the filtrate to crystallize, continue to stir for 1h, filter, wash the filter cake wi...

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Abstract

The invention relates to a purification process of methotrexate or its salt with simple process, convenient operation, high yield and good quality reproducibility. The process includes four steps of providing an aqueous solution of methotrexate, pretreatment and filtration, base adjustment and crystallization.

Description

[0001] This application claims the priority of the Chinese patent application with the application number 201610649766.1 submitted to the China Patent Office on August 9, 2016, and the title of the invention is "a purification process for methotrexate salt", the entire content of which is incorporated herein by reference Applying. technical field [0002] The invention relates to a purification process of a compound, in particular to a purification process of methotrexate or a salt thereof. Background technique [0003] Methotrexate is an immunosuppressant that acts by competitive inhibition of dihydrofolate reductase. It has been used to treat childhood leukemia since its discovery in the 1940s, and it has been used in the treatment of psoriasis since the 1950s. It is now a commonly used anti-malignant tumor drug in clinical practice, mainly for acute leukemia, breast cancer, chorionic epithelial Carcinoma and malignant mole, head and neck tumors, bone tumors, leukemic men...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D475/08
CPCC07D475/08
Inventor 毛文纲严伟顾贤德唐波赵栩强
Owner ZHEJIANG HISUN PHARMA CO LTD