A clean industrial scheme for de-ketalization of EIDD-2801 intermediate in water to give molnupiravir (MK-4482) anti-COVID-19 agent (containing its pharmaceutical analytical analysis)

2023 vol 2 issue 2
Full paper

S. A. Siadati, M. Samadi, M. Soheilizad, L. Firoozpour, M. Payab, S. Bagherpour, and B. Dindari

Pages 202-216
https://doi.org/10.58332/scirad2023v2i2a05

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Abstract
Due to the need for molnupiravir (EIDD-2801, MK-4482) anti-COVID-19 agent, in the present report, we have systematically investigated the effect of different solvents, acids (as catalyst), temperature, and other parameters which play rolls in De-ketalization process of its key intermediate. At the first glance, it might seem to be easy, but the complex nature of MK-4482 agent, and also the ultra-high purity of the crude (which is required for an active pharmaceutical ingredient (API)), make this process more complicated. As would be shown below, even a little change in the type of solvent, solvent ratio, the type or the amount of catalyst, and the temperature could directly change the reaction fate (it may lead to emergence of un-controlled impurity profile, or even it could block the reaction). However, in this work, we have been able to run this de-ketalization process only in water as the whole of the system. Here, it was observed that the high energy water molecules have been able to hydrolyze the ketal intermediate of MK-4482. 

Keywords 
Molnupiravir, EIDD-2801, MK-4482, clean chemistry, COVID-19, De-ketalization in water

First published: 26.06.2023