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

A kind of synthetic method of sofosbuvir

A synthesis method and synthesis route technology, applied in chemical instruments and methods, preparation of sugar derivatives, sugar derivatives, etc., can solve the problem of low conversion rate of raw materials, and achieve simple purification, less by-product content, and low price Effect

Active Publication Date: 2021-06-04
ZENJI RES LAB
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] Purpose of the invention: the purpose of the present invention is to provide a synthetic method of sofosbuvir, which solves the problem of low raw material conversion rate and high content of various by-products in the preparation of sofosbuvir in the prior art

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 synthetic method of sofosbuvir
  • A kind of synthetic method of sofosbuvir
  • A kind of synthetic method of sofosbuvir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Add 20.0g (0.0768mol) of compound 1 to the reaction flask, add 40.0g (0.0882mol) of compound 2 and 150g of dichloromethane, cool down to 0°C, add 3.1g (0.0232mol) of aluminum trichloride, and then dropwise add pyridine 24.3g (0.307mol); then react at 20°C, stop the reaction when HPLC detects that the content of sofosbuvir no longer increases. At this time, the HPLC data related to compound 1 in the reaction solution:

[0033] Compound 1(%) Compound 6(%) Sofosbuvir (%) Compound 4(%) 1.33 0.46 97.78 0.43

[0034] Add 120 g of 10% dilute hydrochloric acid to the reaction solution to quench the reaction, extract with 300 g of ethyl acetate, recover the solvent under reduced pressure, and purify to obtain 39.68 g of pure sofosbuvir, yield: 97.5%.

Embodiment 2

[0036] Preparation of sofosbuvir with different molar amounts of aluminum trichloride

[0037] Add 20.0g (0.0768mol) of compound 1, 40.0g (0.0882mol) of compound 2 and 150g of dichloromethane to the reaction flask respectively, and cool down to 0°C; add different molar amounts of aluminum trichloride, and then dropwise add pyridine 24.3 g (0.307mol); then react at 20°C, stop the reaction when HPLC detects that the content of sofosbuvir no longer increases, and process it according to the same post-treatment method as in Example 1. At this time, the HPLC data related to compound 1 in the reaction solution :

[0038]

[0039] It is found through experiments that good reaction results can be obtained when the molar ratio of aluminum trichloride to compound 1 is in the range of 0.1-0.8.

Embodiment 3

[0041] Preparation of sofosbuvir with different molar amounts of pyridine

[0042] Add 20.0g (0.0768mol) of compound 1, 40.0g (0.0882mol) of compound 2 and 150g of dichloromethane to the reaction flask respectively, and cool down to 0°C; add 3.1g (0.0232mol) of aluminum trichloride, and then add dropwise Different molar amounts of pyridine; then react at 20°C, stop the reaction when HPLC detects that the content of sofosbuvir no longer increases, and process it according to the same post-treatment method as in Example 1. At this time, the HPLC data related to compound 1 in the reaction solution :

[0043]

[0044]

[0045] It is found through experiments that the molar amount of the base has a great influence on the reaction conversion rate, regioselectivity and stereoselectivity, and it is optimal that pyridine is 4 times the molar amount of the compound.

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 discloses a synthesis method of sofosbuvir. Add compound 1, compound 2 and dichloromethane into a reaction bottle, cool down to 0°C, then add aluminum trichloride, and add an appropriate amount of pyridine. The reaction produces sofosbuvir at a reaction temperature of ~20°C. The invention has high reaction conversion rate, good regioselectivity and stereoselectivity, thereby reducing the synthesis cost of sofosbuvir and having remarkable social and economic benefits.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of sofosbuvir. Background technique [0002] Viral hepatitis C is caused by the hepatitis C virus (HCV), and infection with the hepatitis C virus (HCV) is a serious health problem. Sofosbuvir is an important drug developed by Gilead for the treatment of hepatitis C virus. Its structural formula is as follows: [0003] [0004] The reported synthesis methods mainly include: [0005] 1. In J.Med.Chem., 2010, 53(19), 7202–7218, the synthetic route is as follows: [0006] [0007] The specific method is as follows: compound 1 and compound 5 react in tetrahydrofuran solution in the presence of N-methylimidazole to generate sofosbuvir and an equivalent amount of by-product compound 6 (sofosbuvir isomer). The pure product sofosbuvir was then isolated by preparative HPLC with a final yield of 15.2%. Obviously, this method is not suitable for industrial...

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): C07H19/10C07H1/02
CPCC07H1/02C07H19/10
Inventor 葛敏付明伟
Owner ZENJI RES LAB