Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment... more Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment of COVID-19. Herein we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on decagram scale: the first step at 200 g, and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production ... more Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound 1 was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine 1 was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.
A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiven... more A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile and acetone. Isolation and purification procedures are improved in comparison to our earlier report, as all intermediates can be isolated via aqueous acid treatment and recrystallization. The key steps in the synthesis, namely ester formation, hydroxamination and deprotection were done on multigram scale to afford molnupiravir in 36-41% yield with average purity of 98 wt% by q-NMR and 99 area % by HPLC
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment... more Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment of COVID-19. Herein we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on decagram scale: the first step at 200 g, and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production ... more Pyrrolo[2,1-f][1,2,4]triazine (1) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound 1 was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine 1 was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.
A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiven... more A scalable four step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile and acetone. Isolation and purification procedures are improved in comparison to our earlier report, as all intermediates can be isolated via aqueous acid treatment and recrystallization. The key steps in the synthesis, namely ester formation, hydroxamination and deprotection were done on multigram scale to afford molnupiravir in 36-41% yield with average purity of 98 wt% by q-NMR and 99 area % by HPLC
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML K... more ... Contributor(s): Yasuhiro Uozumi, Yutaka Matsuura. PR Likhar*, M. Roy, S. Roy, MS Subhas, ML Kantam, B. Sreedhar. Indian Institute of Chemical Technology, Hyderbad, India. ... Georg Thieme Verlag KG Stuttgart - New York. Alle Rechte vorbehalten. Impressum / Disclaimer.
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