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A kind of production technology of vidarabine monophosphate

A technology of vidarabine monophosphate and vidarabine monophosphate crude product, which is applied in the direction of preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., and can solve the problems of high toxicity of pyridine and expensive price of solvent acetonitrile, etc. Achieve the effects of easy control, reduced quantity, high yield and high purity

Active Publication Date: 2019-07-05
海南卓科制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The solvent acetonitrile used in this method is more expensive, and pyridine is highly toxic.

Method used

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  • A kind of production technology of vidarabine monophosphate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] A kind of production technique of vidarabine monophosphate, it comprises the steps:

[0038] S1 Mix 30 g of vidarabine in 3 mL of tetrahydrofuran, stir and cool down to 0°C;

[0039] S2 Add 30.83 g of di-n-butylphosphoryl chloride in batches to the cooled system in step S1, and continue the reaction at 10°C after the addition is completed until the remaining amount of adenosine vidarabine does not exceed 3% of the added amount;

[0040] S3 Add 1.5 g of palladium catalyst to the reaction system after the stop of step S2, heat up to 50° C., stir for 8 h, filter, wash the filter cake with ethanol, collect the filtrate, remove the solvent under reduced pressure, and obtain the crude product of adenosine monophosphate ;

[0041] The preparation method of described palladium catalyst comprises the steps:

[0042] Add 17.7g of palladium chloride and 203.3g of magnesium chloride hexahydrate into 20mL of saturated ammonia solution, and stir until completely dissolved; then add...

Embodiment 2

[0047] A kind of production technique of vidarabine monophosphate, it comprises the steps:

[0048] S1 Mix 30 g of vidarabine in 3 mL of acetone, stir and cool down to -5°C;

[0049] S2 Add 52.12 g of bis(4-nitrophenyl)phosphoryl chloride in batches to the cooled system in step S1, and continue the reaction at 5°C until the remaining amount of adenosine vidarabine does not exceed 3% of the added amount stop;

[0050] S3 Add 1.5 g of palladium catalyst to the reaction system after the stop of step S2, heat up to 50° C., stir for 8 h, filter, wash the filter cake with ethanol, collect the filtrate, remove the solvent under reduced pressure, and obtain the crude product of adenosine monophosphate ; The preparation method of the palladium catalyst is the same as in Example 1;

[0051]S4, after dissolving the vidarabine monophosphate crude product obtained in step S3 in water at 40°C, gradually add a mixed solution of ether, methanol, and triethylamine (ether:methanol:triethylami...

Embodiment 3

[0053] A kind of production technique of vidarabine monophosphate, it comprises the steps:

[0054] S1 Mix 30 g of vidarabine with 3 mL of dioxane, stir and cool down to 8°C;

[0055] S2 Add 32.54 g of bis(2-chloroethyl)phosphoryl chloride in batches to the cooled system in step S1, and continue the reaction at 15°C until the remaining amount of adenosine vidarabine does not exceed 1% of the added amount stop;

[0056] S3 Add 1.5 g of palladium catalyst to the reaction system after the stop of step S2, heat up to 50° C., stir for 8 h, filter, wash the filter cake with ethanol, collect the filtrate, remove the solvent under reduced pressure, and obtain the crude product of adenosine monophosphate ;

[0057] The preparation method of described palladium catalyst is with embodiment 1;

[0058] S4, after dissolving the vidarabine monophosphate crude product obtained in step S3 in water at 40°C, gradually add a mixed solution of ether, methanol, and ethyl acetate (the volume rat...

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Abstract

The invention belongs to the technical field of preparation of vidarabine monophosphate and particularly relates to a production process of vidarabine monophosphate. The production process of vidarabine monophosphate comprises the following steps of S1 dissolving vidarabine into organic solvent and cooling down the mixture; S2, adding in phosphoryl chloride to perform thermal reaction until that the residual content of the vidarabine is not higher than 3% of the added amount; S3, adding in palladium catalysts for catalytic reduction, then filtering reaction products, removing the solvent fromthe obtained filter liquor to obtain crude vidarabine monophosphate; S4, recrystallizing the crude vidarabine monophosphate obtained in S3 for purification. The production process of vidarabine monophosphate introduces the phosphoryl chloride relatively low in reactivity to react with the raw vidarabine, the reaction process is mild and easy to control, so that the produced quantity of side products can be reduced from the source; meanwhile, the novel palladium catalysts can selectively reduce introduced ether groups, thereby simplifying purification processes and achieving high product yieldand purity.

Description

technical field [0001] The invention belongs to the technical field of preparation of adenosine vidarabine monophosphate, and in particular relates to a production process of adenosine vidarabine monophosphate. Background technique [0002] Vidarabine monophosphate (AraAMP) is the monophosphate compound of vidarabine monophosphate (Ara-A), which is a synthetic adenosine antiviral drug. At present, it is mainly used for chronic viral hepatitis, herpes simplex virus, herpes zoster virus, vaccinia virus, various animal herpes viruses and a few carcinogenic RNA viruses in China. Its pharmacological effect is because it can combine with deoxyribonucleic acid polymerase to reduce its activity, thereby inhibiting DNA synthesis. After adenosine monophosphate enters cells, it is phosphorylated to generate adenosine vidarabine diphosphate and adenosine vidarabine Triphosphate, and the antiviral effect is mainly caused by the monophosphate vidarabine triphosphate, which competes with ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/20C07H1/00C07H1/06
CPCC07H1/00C07H1/06C07H19/20
Inventor 李强
Owner 海南卓科制药有限公司
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