Preparation method of ridecevir compound

A technology of remdesivir and compounds, which is applied in the field of new synthesis and preparation of remdesivir compounds, can solve problems such as unsuitable for industrial scale-up, high cost, and low yield, and achieve high cost, low environmental pollution, and low yield. high rate effect

Pending Publication Date: 2021-08-06
HENAN TAIFENG BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The problem of the above synthetic method is that the yield is low, the cost is high, multiple column chromatography and chiral separation by preparative HPLC are required, and it is not suitable for industrial scale-up

Method used

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  • Preparation method of ridecevir compound
  • Preparation method of ridecevir compound
  • Preparation method of ridecevir compound

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Experimental program
Comparison scheme
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preparation example Construction

[0025] A preparation method of remdesivir compound, the method uses compound 1 as starting material,

[0026]

[0027] Include the following steps:

[0028] a) compound 1 generates compound 2 through cyclization reaction,

[0029]

[0030] The reaction is carried out in the solvent cyclopentanone. Compound 1 is mixed with p-toluenesulfonic acid and cyclopentanone and then reacted. The reaction is carried out at room temperature for 12 hours, and then the temperature is raised to 45°C for 3 hours; the reaction After completion, the temperature was lowered to room temperature, and then n-hexane was added dropwise to the reaction system, and compound 2 was obtained by filtering after the solid was precipitated; the molar ratio of compound 1 and p-toluenesulfonic acid added in this step was 1:0.1-0.3;

[0031] b) Compound 2 undergoes a BoC protection reaction to generate compound 3,

[0032]

[0033] This reaction is carried out in the solvent methylene chloride, compou...

Embodiment 1

[0050] The synthesis of embodiment 1 compound 2

[0051] Add 59g of compound 1 (0.205mol) and 3.5g of p-toluenesulfonic acid into the reaction flask, then add 300ml of cyclopentanone, and stir at room temperature for 12 hours. The reaction was then warmed to 45°C and the reaction was stirred for 3 hours. After TLC detects that the reaction is complete, stop the reaction. 600ml of n-hexane was added dropwise to the system under stirring at room temperature, and a solid precipitated out of the system. After stirring at room temperature for 2 hours, filter, wash the filter cake with 60ml of n-hexane, and vacuum-dry the product at 40°C for 5 hours to obtain 65 grams of compound 2 with a yield of 90 %.

Embodiment 2

[0052] The synthesis of embodiment 2 compound 3

[0053]Add 16.9g of compound 2, 0.5g of DMAP, 35g of triethylamine and 85ml of dichloromethane into the reaction flask, then add 30g of (Boc)20, heat up to 30°C for reaction, and detect the reaction by TLC. Wash, dry over anhydrous sodium sulfate, concentrate the organic phase, and recrystallize with 50ml of ethyl acetate to obtain 22.4g of intermediate 3, yield: 92%.

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PUM

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Abstract

The invention belongs to the field of medicinal chemistry, and particularly relates to a novel synthesis and preparation method of a ridecevir compound. (2R, 3R, 4R, 5R)-2-(4-aminopyrrole[2, 1-f][1, 2, 4]triazin-7-yl)-3, 4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-nitrile is taken as an initial raw material, and is subjected to ketal protection, BC protection, resolution, phosphorylation reaction, substitution reaction and deprotection reaction to prepare ridecevir. The method has the advantages of mild and easily-controlled reaction conditions, simple operation, high product yield and high purity, and is suitable for industrial mass production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to a new synthesis and preparation method of a remdesivir compound. Background technique [0002] The invention is aimed at a new type of coronavirus 2019-nCOV, which is highly contagious and widely spread. There is currently no specific drug for this virus. During clinical trials, an anti-Ebola virus drug Remdesi, which has not yet been marketed, was discovered. Wei is very effective in killing the virus. [0003] At present, there are roughly two routes for the relatively mature synthesis of remdesivir at home and abroad, as follows: [0004] (1) US2016122374A1 publicly reported the synthesis method of remdesivir, the specific route is as follows: [0005] [0006] (2) "Nature" reported the second generation synthesis method in 2016 [0007] [0008] The problems of the above synthesis method are low yield, high cost, multiple column chromatography and chiral...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/6561
CPCC07F9/6561
Inventor 沙薇张豪龙刘洋李建永宋佳
Owner HENAN TAIFENG BIOTECH CO LTD
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