A kind of refining method of pralatrexate intermediate

A refining method, the technology of pralatrexate, which is applied in the field of medicine, can solve the problems that there is no refining method for the finished product of pralatrexate, and achieve the effects of cost saving, process simplification and yield improvement

Active Publication Date: 2021-02-12
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

And the finished product of pralatrexate does not have a better refining method at present, so improving the purity of PLQS-6 is an urgent problem to be solved

Method used

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  • A kind of refining method of pralatrexate intermediate

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Add 15g of crude pralatrexate intermediate PLQS-6 and 225ml of methanol into a 500ml three-necked flask, heat until completely dissolved, add 4.5g of activated carbon to decolorize for 0.5h while it is hot, filter while it is hot, cool the filtrate to 0-5°C and stir Crystallize, filter, rinse the filter cake with methanol, and dry to obtain 13.9 g of the refined product of pralatrexate intermediate PLQS-6. The purity is 99.89%, and the yield is 92.7%.

Embodiment 2

[0022] Add 15g of the crude product of pralatrexate intermediate PLQS-6 and 75ml of methanol into a 500ml three-neck flask, heat until completely dissolved, add 1.5g of activated carbon to decolorize for 0.5h while it is hot, filter while it is hot, cool the filtrate to 0-5°C and stir Crystallize, filter, rinse the filter cake with methanol, and dry to obtain 14.0 g of the refined product of pralatrexate intermediate PLQS-6. The purity is 99.83%, and the yield is 93.3%.

Embodiment 3

[0024] Add 15g of crude pralatrexate intermediate PLQS-6 and 300ml of methanol into a 500ml three-neck flask, heat until completely dissolved, add 6.0g of activated carbon to decolorize for 0.5h while it is hot, filter while it is hot, cool the filtrate to 0-5°C and stir Crystallize, filter, rinse the filter cake with methanol, and dry to obtain 13.4 g of the refined product of pralatrexate intermediate PLQS-6. The purity is 99.85%, and the yield is 89.3%.

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Abstract

The invention belongs to the technical field of medicine, and in particular relates to a method for refining a pralatrexate intermediate. The method comprises the steps of: adding the crude product of the intermediate 10-propargyl-10-desazaaminopterin dimethyl ester (PLQS-6) into a refined solvent, heating and dissolving, decolorizing activated carbon, hot filtering, cooling the filtrate and stirring for crystallization, The filter cake is washed with a refined solvent to obtain a high-purity pralatrexate intermediate PLQS‑6. The refined solvents used are all low-boiling solvents, which not only avoids the problem of excessive dissolved residues of DMF and DMSO, but also facilitates the recycling of refined solvents and saves costs. The application of column chromatographic separation is avoided, the yield is improved, the entire process operation is simplified, the operation method is simple, the yield and purity are high, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for refining a pralatrexate intermediate. Background technique [0002] Pralatrexate, trade name Folotyn, is the first new targeted folic acid preparation approved by the FDA for the treatment of peripheral T-cell lymphoma. The chemical name of pralatrexate is 10-propargyl-10-desazaaminopterin. First disclosed in "Synthesis and Antitumor Activity of 10-Propargyl-10-deazaaminopterin" J.Medical Chem.36:2228-2231 (1993) by Joseph I. DeGraw; J William T. Colwell et al. It was then studied by Sirotanak et al and O'Connor et al. Its molecular structure is as follows: [0003] [0004] Pralatrexate is synthesized from p-carboxyphenylacetic acid as a starting material through a series of chemical transformations. Firstly, the intermediate 4-methyl formate, methyl phenylacetate (PLQS-1), the intermediate ɑ-propargyl-(4-methyl formate)-methyl phenylacetate (PLQ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D475/08
CPCC07D475/08
Inventor 张贵民李燕陈成富
Owner LUNAN PHARMA GROUP CORPORATION
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