First-Generation Process Development for the Synthesis of Baloxavir Marboxil: Early-Stage Development of Synthetic Methods to Prepare Baloxavir Marboxil Intermediates

Described herein is the discovery and development of a process to prepare chiral triazinanone R -3 and diastereomeric intermediate 5, the key intermediates in the synthesis of the cap-dependent endonuclease inhibitor baloxavir marboxil (1), which can suppress the replication of influenza virus. Chir...

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Bibliographic Details
Published inOrganic process research & development Vol. 28; no. 6; pp. 2117 - 2127
Main Authors Anan, Kosuke, Miyagawa, Masayoshi, Okano, Azusa, Sugimoto, Hideki, Miyake, Naoki, Fukui, Nobuaki, Kijima, Akihito, Tanimoto, Emi, Kawai, Makoto
Format Journal Article
LanguageEnglish
Published American Chemical Society 21.06.2024
Subjects
optical resolution
baloxavir marboxil
S-033188
antiviral agent for influenza
scalable process
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Summary:Described herein is the discovery and development of a process to prepare chiral triazinanone R -3 and diastereomeric intermediate 5, the key intermediates in the synthesis of the cap-dependent endonuclease inhibitor baloxavir marboxil (1), which can suppress the replication of influenza virus. Chiral triazinanone R -3 was obtained via optical resolution of its racemic form rac -3. Diastereomeric intermediate 5 was obtained by the condensation reaction of triazinanone R -3 and thiepin alcohol 4 using a combination of T3P and MsOH. These reactions were performed successfully on kilogram scale and were critical to the establishment of the baloxavir marboxil manufacturing process.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.3c00514