A kind of synthetic technique of (2'r)-2'-deoxy-2'-fluoro-2'-methyluridine

Abstract

The invention discloses a synthesis process of (2R')-2'-deoxyl-2'-fluoro-2'-methyluridine, relates to the technical field of synthesis of medicines, and solves the technical problems of high cost andlow product yield of the existing process. According to the synthesis process, sodium borohydride or potassium borohydride is used for reducing ribose lactone, so that an expensive reductive reagent which is sodium dihydro-bis-(2-methoxyethoxy)aluminate or lithium tri-tert-butoxyaluminum hydride is not used, and the cost is greatly reduced; N,O-bis(trimethylsilyl)acetamide is used as a silicon etherification reagent, so that the yield of glycosylation reaction is increased; the product yield can reach 85-90% and is far higher than that in route III by 58%; the product yield is obviously increased; hydroxyl at the 5' site is protected, so that side reaction in ring-closing reaction can be avoided; meanwhile, a common polar solvent which is dimethylformamide is used; the product yield undercatalysis of sodium hydrogen carbonate can reach 87-92%. The synthesis process is easy to operate; the process condition is more easily controlled; the cost is reduced; the synthesis process is applicable to large-batch production.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical synthesis, more specifically, it relates to a synthesis process of (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine. Background technique [0002] Hepatitis C virus is a kind of viral hepatitis caused by hepatitis C virus (HCV) infection. According to the statistics of the World Health Organization, there are about 180 million people infected with HCV in the world, the infection rate is 3%, and 35,000 new cases of hepatitis C occur every year. Hepatitis C is an important factor leading to liver cirrhosis and even hepatocellular carcinoma. It is extremely harmful to the life and health of patients and has become a serious social and public health problem. [0003] In December 2013, the US Food and Drug Administration (FDA) approved Gilead's Sovaldi (Sofosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection, becoming the first drug for the treatment of certain types of HCV infectio...

AI Technical Summary

Problems solved by technology

[0004] (2'R)-2'-deoxy-2'-fluoro-2'-methyluridine is an important intermediate for the synthesis of Sofosbuvir, and the synthetic methods reported in the literature mainly contain the following: Invented in China with the publication number CN101600725A The patent discloses a synthesis process of this compound. The preparation method is shown in Route 1. The synthesis route is long, expensive reducing reagents are used, and the production cost is relatively high.

[0012] To sum up, route one synthetic route is long, reducing reagent is expensive, cost is high, route two raw materials are expensive, difficult to obtain, the glycosylation reaction yield of route three is low, the product yield of route four is low, therefore, need to propose a kind of New technical solutions to increase yield and reduce costs

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