Method for synthesizing diastereomer impurity in dolutegravir raw material

Abstract

The invention provides a method for synthesizing a diastereomer impurity in a dolutegravir raw material, which comprises the following steps: 1, carrying out condensation reaction on SM1 serving as araw material and 2,4-difluorobenzylamine to generate a compound I; 2, reacting the compound I with an alkali in a reaction solvent to generate a compound II; 3, hydrolyzing the compound II under an acidic condition to generate a compound III; 4, carrying out acid catalytic reaction on the compound III and R-aminobutanol in a reaction solvent to generate a compound IV; 5, generating a compound V from the compound IV in a reaction solvent under the catalysis of a condensing agent; and 6, demethylating the compound V under the action of an alkali metal salt to generate an impurity VI. The synthetic method of the diastereoisomer impurity in the dolutegravir raw material is simple in process and available in raw material, and the prepared new impurity can provide a reference substance for quality analysis of dolutegravir, so that the quality standard of dolutegravir is improved.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a method for synthesizing diastereomer impurities in dolutegravir raw materials. Background technique [0002] Dolutegravir (DTG) is an antiviral drug developed and marketed by GSK in August 2013 for the treatment of HIV-1. It is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor used in combination with other antiretroviral drugs to treat HIV-1 infection. DTG inhibits HIV integrase by binding to the integrase active site to block the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration; currently dolutegravir can be used alone or in combination with other drugs for the treatment of adults and HIV-1 infection in adolescents over 12 years old and children weighing more than 40 kg; therefore, it is of great significance to conduct research on dolutegravir. [0003] The research on the impurities of dolutegravir can be used fo...

AI Technical Summary

Problems solved by technology

[0003] The research on the impurities of dolutegravir can be used for the qualitative and quantitative analysis of impurities in the production of dolutegravir, so as to improve the quality standard of dolutegravir and provide important guidance for the safe drug use of the people; while the existing Research rarely mentions the impurities of dolutegravir, so it is found that it is very difficult to further improve the quality of dolutegravir

Images