Gram-scale stereoselective synthesis of next generation of Trk Inhibitor LOXO-195

[Display omitted] A gram-scale stereoselective synthesis of next generation of Trk Inhibitor LOXO-195 is reported. Starting from two commercially available and cheap building blocks, LOXO-195 is prepared via 9 steps in 26% overall yield with excellent enantioselectivity (ee > 99%). The new synthe...

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Bibliographic Details
Published inTetrahedron letters Vol. 104; pp. 154019 - 154023
Main Authors Wang, Lingli, Zhang, Dengyou, Luo, Zhibo, Feng, Jingchao, Liao, Wei, Li, Jin, Wang, Jiansong
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 17.08.2022
Elsevier
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
Stereoselective synthesis
Suzuki coupling
Trk inhibitors
Suzuki coupling
Trk inhibitors
Stereoselective synthesis
SUZUKI
DIRECT ARYLATION REACTIONS
RESISTANCE
RECEPTOR
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Summary:[Display omitted] A gram-scale stereoselective synthesis of next generation of Trk Inhibitor LOXO-195 is reported. Starting from two commercially available and cheap building blocks, LOXO-195 is prepared via 9 steps in 26% overall yield with excellent enantioselectivity (ee > 99%). The new synthesis reported herein features a development of an efficient Csp2-Csp3 suzuki coupling from key intermediates 19 and 16, which allows to make LOXO-195 in a more convergent fashion compared to the reported synthetic route.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2022.154019