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Current Organic Chemistry

Author(s): Dhanaji M. Mohite, Arjun P. Pandey and Pandurang M. Chavhan*

DOI: 10.2174/1385272827666230111161632

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Modified Synthesis and Isolation of an Advanced Intermediate of Remdesivir

Page: [2143 - 2150] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Synthesis and isolation of an advanced intermediate (S)-2-Ethylbutyl 2-(((S)-(4- nitrophenoxy) (phenoxy) phosphoryl) amino) propanoate (1b), which is being used for the manufacture of the prodrug diastereoisomer 1d called Remdesivir have been carried out in high yield with efficient stereoselectivity. The isolated advanced intermediate 1b was a diastereoselective nucleoside phosphoramidate prodrug used as an antiviral agent having a mixture of two (SS) and (SR) diastereomers with stereocenter at phosphorus, which was purified by converting into a more stable diastereoselective isomer (SS) by simple physical fractional crystallization process, resulting in an improved yield of ~45%. The recrystallization has been afforded diastereomerically in 99% pure (SS)-isomer 1b. The 1H NMR characterization data confirm the (SS)-isomer (1b). The developed process holds significant potential for large-scale reactions relatively with commercially available low-cost solvents and co-solvents, resulting in an alternative cheaper process.

Graphical Abstract

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