New Synthesis Technology Of Delavirdine Mesylate

Delavirdine mesylate a non-nucleoside reverse transcriptase inhibitors is listed in 1997 by the Food and Drug Administration approval. It is used in the treatment of acquired immunodeficiency syndrome with other anti-human immunodeficiency virus HIV drugs clinically.In this paper, 5-nitro-indole-2-carboxylate as a starting material was subjected to catalytic hydrogenation, sulfonylation, and finally hydrolysis to give 5-methylsulfonyl amino-indole-2-carboxylic acid. And then 5-methanesulfonyl-amino-indole-2-carboxylic acid condense with 1- [3-(1-ethylamino)-2-pyridinyl] piperazine to get the delavirdine. A good method that is reliable and a high purity is gotten during the process in which we prepare the intermediate(5-amino-indole-2-carboxylic acid ethyl ester, 5-methyl sulfonamido indole-2-carboxylic acid ethyl ester, 5-methyl sulfonamido indole-2-carboxylic acid) according to the time, temperature of reaction, the amount of solvent and other conditions.In a process of preparing the intermediate 5-methanesulfonyl-amino-indole-2-carboxylic acid with 5-nitro-indole-2-carboxylate as a starting material, we have simplified the catalytic hydrogenation, sulfonylation reaction, after the end of the hydrolysis reaction, it is activated by activated carbon adsorption directly and recrystallization process, to get the 5-sulfonamide-indole-2-carboxylic acid whose purity is more than 99%.5-methanesulfonyl-amino-indole-2-carboxylic acid and 1-[3-(1-ethylamino)-2-pyridinyl] piperazine condensation reaction step in the industrial scale experiment, we will not only treated simplistic, but it will yield increased to over 90%.In 5-nitro-indole-2-carboxylic acid ethyl ester as a raw material, the total yield of the delavirdine mesylate kilograms amplification, obtained 67.0%, by kilograms amplification experiments, we learned that this synthetic route has a high stability, good repeatability and it is simple post-treatment, suitable for industrial mass production.