Process for preparing tenofovir

Abstract

The invention discloses a process for preparing tenofovir. The method is characterized by comprising the steps: with adenine, (R)-propylene carbonate and p-toluenesulfonyloxy methyl phosphonic diester as raw materials, adopts a one-pot process to prepare an intermediate 2, and followed by hydrolyzing the intermediate 2 by an inorganic acid to obtain tenofovir, wherein the following reaction formula is shown in the description. With utilization of the process, the purpose that high-purity tenofovir is synthesized with utilization of cheap and easily available raw materials and with simple operation, mild reaction conditions, low cost and high yield is achieved; and the process has the advantages of energy saving and environmental protection, is suitable for large scale production, and has practical value in realization of industrial production of tenofovir.

Description

technical field [0001] The invention relates to a preparation process of tenofovir, which belongs to the technical field of drug synthesis. Background technique [0002] In 2009, the United Nations reported that the number of HIV-infected people in China had reached 740,000, and sexual transmission is becoming the main transmission route of AIDS in my country. This is a dangerous signal for the spread of AIDS from high-risk groups to the general population, and the prevention and control work is in a critical period. [0003] Tenofovir, as the first nucleotide analogue approved by the FDA for the treatment of HIV-1 infection, has also been recognized by the World Health Organization and recommended as a first-line antiviral drug. Due to the important impact of the drug, India accepted the request of Cipla, an Indian generic drug manufacturer, in September 2009 to refuse patent protection for Tenofovir to ensure that the drug can be more easily accepted by low-income countrie...

AI Technical Summary

Problems solved by technology

[0009] ①In the reaction to generate intermediate 2, when the magnesium salt mixture is converted to tenofovir, the magnesium salt mixture must be separated from the system after forced analysis with ethyl acetate, because the magnesium salt mixture is easy to absorb moisture and absorb The product has high operational requirements and is very cumbersome in actual processing;

[0010] ②Intermediate 2 must use harsh dissociation conditions due to dissociation of two ethyl groups;

[0011] ③ In terms of cost, due to the use of a large excess of trimethylsilane and sodium bromide, there are serious defects in both production cost and environmental protection

[0014] Although this process overcomes some defects of the above-mentioned paper route, because it uses a strong base such as sodium hydroxide to reflux at 120°C for 22 hours in the preparation of intermediate 1, the reaction conditions are severe and time-consuming, which is difficult in large-scale production. control

[0015] In summary, it can be seen that the preparation technology of tenofovir in the prior art has defects and deficiencies that are not suitable for industrialized production, and this area needs to study a simple method for preparing high-purity tenofovir suitable for industrialization. craft

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