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. 2018 Dec 20;12(1):144.
doi: 10.1186/s13065-018-0504-4.

Development of a practical synthesis of etravirine via a microwave-promoted amination

Da Feng  1 , Fenju Wei  1 , Zhao Wang  1 , Dongwei Kang  2 , Peng Zhan  3 , Xinyong Liu  4
Affiliations

Development of a practical synthesis of etravirine via a microwave-promoted amination

Da Feng et al. Chem Cent J. .

Abstract

Background: Etravirine (ETV) was approved as the second generation drug for use in individuals infected with HIV-1 in 2008 by the U.S. FDA with its unique antiviral activity, high specificity, and low toxicity. However, there are some shortcomings of the existing synthetic routes, such as the long reaction time and poor yield.

Results: This article describes our efforts to develop an efficient, practical, microwave-promoted synthetic method for one key intermediate of ETV, which is capable of being operated on a scale-up synthesis level. Through this optimized synthetic procedure, the amination reaction time decreased from 12 h to 15 min and the overall yield improved from 30.4 to 38.5%.

Conclusion: Overall, we developed a practical synthesis of ETV via a microwave-promoted method, and the synthetic procedure could be amenable to scale-up, and production costs could be significantly lowered.

Keywords: Amination; Etravirine; Microwave-promoted; Synthesis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Scheme 1
Scheme 1
Synthesis of etravirine with 5-bromo-2,4,6-trichloropyrimidine (2) as starting material [6]
Scheme 2
Scheme 2
Synthesis of etravirine with 2,4,6-trichloropyrimidine (6) as starting material [7]
Scheme 3
Scheme 3
Synthesis of etravirine with 4-guanidinobenzonitrile (12) as starting material [8]
Scheme 4
Scheme 4
Synthesis of etravirine with 4-aminobenzonitrile (3) as intermediate [9]
Scheme 5
Scheme 5
Amination reaction of the intermediate 9
Scheme 6
Scheme 6
The reaction mechanism of the intermediate 6 and 7
Scheme 7
Scheme 7
Synthetic route and yield of etravirine
See this image and copyright information in PMC

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