Fit-for-purpose synthesis of dual leucine zipper kinase (DLK) inhibitor GNE-834

[Display omitted] •A fit-for-purpose synthesis of DLK inhibitor.•Suzuki–Miyaura coupling at 500 g scale.•Separation of diastereomers by resolution. A practical fit-for-purpose synthesis of dual leucine zipper kinase (DLK) inhibitor GNE-834 (1) was developed. The key CC bond was constructed via a Suz...

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Bibliographic Details
Published inTetrahedron letters Vol. 61; no. 43; pp. 152430 - 152434
Main Authors Xu, Jie, Carrera, Diane E., Beaudry, Danial, Siu, Michael, Huestis, Malcolm P., Liu, Wendy, Angelaud, Rémy, Gosselin, Francis
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 22.10.2020
Elsevier
Subjects
ALS
Chemistry
Chemistry, Organic
DLK inhibitor
Physical Sciences
Reductive amination
Resolution
Science & Technology
Suzuki coupling
Suzuki coupling
Reductive amination
ALS
DLK inhibitor
Resolution
AMYOTROPHIC-LATERAL-SCLEROSIS
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Summary:[Display omitted] •A fit-for-purpose synthesis of DLK inhibitor.•Suzuki–Miyaura coupling at 500 g scale.•Separation of diastereomers by resolution. A practical fit-for-purpose synthesis of dual leucine zipper kinase (DLK) inhibitor GNE-834 (1) was developed. The key CC bond was constructed via a Suzuki–Miyaura cross-coupling of iodopyrazole 2 and pyridine boronic ester 3 to afford ketone 12. Subsequent selective reductive amination of ketone 12 with morpholine followed by a resolution via tosylate salt formation provided GNE-834 (1) in 39% overall yield from iodide 2 with 98.9 A% HPLC purity.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2020.152430