An Alternative Indazole Synthesis for Merestinib

An Alternative Indazole Synthesis for Merestinib

A new synthesis of a key indazole-containing building block for the MET kinase inhibitor merestinib was designed and demonstrated. Crucial to the successful construction of the challenging indazole is an SNAr reaction, which forges the heterocyclic ring. Continuous processing was applied to two of t...

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Bibliographic Details
Published in:Organic process research & development Vol. 22; no. 3; pp. 409 - 419
Main Authors: Lu, Yu, Cole, Kevin P, Fennell, Jared W, Maloney, Todd D, Mitchell, David, Subbiah, Ramesh, Ramadas, Balakumar
Format: Journal Article
Language:English
Published: American Chemical Society 16-03-2018
Online Access:Get full text
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Summary:A new synthesis of a key indazole-containing building block for the MET kinase inhibitor merestinib was designed and demonstrated. Crucial to the successful construction of the challenging indazole is an SNAr reaction, which forges the heterocyclic ring. Continuous processing was applied to two of the five steps: nitration of a benzaldehyde and high-temperature hydrolysis of an aniline to phenol. Compared to a highly developed historical route, the new route shows clear benefits in terms of product quality and potentially manufacturability and robustness.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.8b00016