Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of high-purity tenofovir

A tenofovir and high-purity technology, which is applied to the preparation of high-purity tenofovir and the field of drug preparation, can solve the problems of low quality and low yield of finished products, and achieve good product quality and high reaction yield. , the effect of large application value

Active Publication Date: 2016-09-14
AURISCO PHARMACEUTICAL CO LTD
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] But the tenofovir product that above-mentioned preparation method obtains has the problems of low yield and low quality of finished product, so it is necessary to improve the preparation and purification method of tenofovir

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of preparation method of high-purity tenofovir
  • A kind of preparation method of high-purity tenofovir
  • A kind of preparation method of high-purity tenofovir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] The preparation of embodiment 1 high-purity tenofovir (one-pot method and acid-base method refining)

[0030] Under nitrogen protection, DMF (50g), R-propylene carbonate (17.2g, 168mmol), adenine (20g, 148mmol), and NaOH (0.2g, 5mmol) were put in successively, and the temperature was raised to 125-135°C, and kept for reaction 6 -8 hours; lower the temperature to 60-70°C, add magnesium tert-butoxide (20.3g, 119mmol), then add DESMP (64g, 199mmol) dropwise, after dropping, keep the temperature at 60-70°C for 6-8 hours, esterification reaction End, lower the temperature, add acetic acid to neutralize, concentrate and dry DMF under reduced pressure (80°C, ≤5mmHg), add 48% hydrobromic acid (160g) to dissolve evenly, heat up to 90-100°C for 3-5 hours, and then cool down to 20-25°C, then add 40% NaOH solution to adjust the pH value to 3.0, cool to 5-8°C for crystallization for 3 hours, filter with suction to obtain 48g of PMPA crude product, and use 5% hydrochloric acid (140g ...

Embodiment 2

[0031] The preparation of embodiment 2 high-purity tenofovir (one-pot method and acid-base method refining)

[0032] Under nitrogen protection, DMF (50g), R-propylene carbonate (17.2g, 168mmol), adenine (20g, 148mmol), and NaOH (0.2g, 5mmol) were put in successively, and the temperature was raised to 125-135°C, and kept for reaction 6 -8 hours; lower the temperature to 60-70°C, add sodium tert-butoxide (17.1g, 178mmol), then add DESMP (64g, 199mmol) dropwise, after dropping, keep warm at 60-70°C for 6-8 hours, esterification reaction End, lower the temperature, add acetic acid to neutralize, concentrate and dry DMF under reduced pressure (80°C, ≤5mmHg), add 48% hydrobromic acid (160g) to dissolve evenly, heat up to 90-100°C for 3-5 hours, and then cool down to 20-25°C, then add 40% NaOH solution to adjust the pH value to 3.0, cool down to 5-8°C to crystallize, and filter with suction to obtain 46g of crude PMPA, which is dissolved in 5% hydrochloric acid (140g) at 20-25°C , a...

Embodiment 5

[0043] Under nitrogen protection, DMF (120g), R-propylene carbonate (17.2g, 168mmol), adenine (20g, 148mmol), and NaOH (0.2g, 5mmol) were put in successively, the temperature was raised to 125-135°C, and the reaction was kept for 35 Hours; cool down to 60-70°C, add magnesium tert-butoxide (20.3g, 119mmol), then add DESMP (76g, 193mmol) dropwise, dropwise, keep warm at 50-60°C for 6-8 hours, the esterification reaction ends, Lower the temperature, add acetic acid to neutralize, concentrate and dry DMF under reduced pressure (80°C, ≤5mmHg), add 48% hydrobromic acid (160g) to dissolve evenly, raise the temperature to 90-100°C and keep it warm for 3-5 hours, then cool down to 20- 25°C, then add 40% NaOH solution to adjust the pH value to 3.0, cool down to 5-8°C for crystallization for 3 hours, filter with suction to obtain 33g of PMPA crude product, dissolve PMPA crude product at 20-25°C with 5% hydrochloric acid, and then use Adjust the pH value to 2.5 with 10% sodium hydroxide, ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a preparation method of high-purity tenofovir. Using adenine and (R)-propylene carbonate as raw materials, a one-pot method was used to prepare crude tenofovir, and then purified by an acid-base method to obtain high-purity tenofovir. The method of the invention is a one-pot method for preparing tenofovir, the three-step reaction can be completed at one time without separation, the preparation method is simple, the raw materials are easy to obtain, the reaction yield is high, and the product quality is good. The method of the invention is beneficial to environmental protection and is suitable for industrial production , has great application value. The inventive method is shown in following reaction formula: .

Description

technical field [0001] The invention relates to medicinal chemistry, in particular to a preparation method of medicine, in particular to a preparation method of high-purity tenofovir. Background technique [0002] Tenofovir disoproxil fumarate is a highly effective antiviral drug, especially has a good therapeutic effect on retroviral infection, and its mechanism of action is by inhibiting the nucleus in retroviruses (such as HIV, HBV). Nucleotide reverse transcriptase to prevent the continuous replication of the virus in the infected host. Tenofovir (PMPA) chemical name: (R)-6-amino-9H-purinyl isopropoxymethyl phosphate, is the active ingredient of the antiviral drug tenofovir disoproxil fumarate, represented by the following structural formula : [0003] [0004] At present, the preparation of relevant tenofovir mainly contains the following several methods: [0005] Patent EP0654037B1 first discloses the synthesis method of tenofovir, as shown in the following formu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07F9/6561
Inventor 褚定军范永剑聂丰彬
Owner AURISCO PHARMACEUTICAL CO LTD