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Molecules
Article . 2025 . Peer-reviewed
License: CC BY
Data sources: Crossref
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PubMed Central
Other literature type . 2025
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A Convenient, Pd-Free Approach to the Synthesis of Risdiplam

Authors: Georgiy Korenev; Alexey A. Gutenev; Fyodor V. Antipin; Vladimir V. Chernyshov; Julia A. Shulgina; Maria P. Korobkina; Maxim B. Nawrozkij; +1 Authors

A Convenient, Pd-Free Approach to the Synthesis of Risdiplam

Abstract

Several approaches to the synthesis of risdiplam, a pharmacologically relevant pyridopyrimidinone derivative, have been recently reported. However, most of these routes rely exclusively on palladium-catalyzed, cross-coupling reactions and involve low-yielding intermediates, which limit their scalability and complicate impurity control. In this work, we present a five-step, straightforward route to risdiplam, utilizing ethyl 2,8-dimethylimidazo[1,2-b]pyridazine-3-carboxylate—an accessible and cost-effective building block previously developed by our research group—as a starting material. The key step involves construction of the 4H-pyrido[1,2-a]pyrimidin-4-one scaffold via a copper(I)-catalyzed heterocyclization reaction. This represents a novel and convenient protocol for the synthesis of 2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-7-fluoro-4H-pyrido[1,2-a]pyrimidin-4-one, which serves as a crucial intermediate in the final stages of risdiplam synthesis. The overall process allows us to obtain the target compound with a 20% total yield (from abovementioned starting material) and high purity (99.86%, by HPLC-UV), with a maximum level of unidentified impurities not exceeding 0.046%. The developed approach eliminates the use of palladium catalysis and chromatographic purification, offering a practical and scalable alternative for risdiplam production.

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
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gold