An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement

Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearra...

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Detalles Bibliográficos
Autores principales: Brocklesby, Kayleigh L., Waby, Jennifer S., Cawthorne, Chris, Smith, Graham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381755/
https://www.ncbi.nlm.nih.gov/pubmed/28413233
http://dx.doi.org/10.1016/j.tetlet.2017.02.082
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author Brocklesby, Kayleigh L.
Waby, Jennifer S.
Cawthorne, Chris
Smith, Graham
author_facet Brocklesby, Kayleigh L.
Waby, Jennifer S.
Cawthorne, Chris
Smith, Graham
author_sort Brocklesby, Kayleigh L.
collection PubMed
description Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12–14).
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spelling pubmed-53817552017-04-12 An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement Brocklesby, Kayleigh L. Waby, Jennifer S. Cawthorne, Chris Smith, Graham Tetrahedron Lett Article Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12–14). Elsevier 2017-04-12 /pmc/articles/PMC5381755/ /pubmed/28413233 http://dx.doi.org/10.1016/j.tetlet.2017.02.082 Text en © 2017 The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brocklesby, Kayleigh L.
Waby, Jennifer S.
Cawthorne, Chris
Smith, Graham
An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement
title An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement
title_full An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement
title_fullStr An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement
title_full_unstemmed An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement
title_short An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement
title_sort alternative synthesis of vandetanib (caprelsa™) via a microwave accelerated dimroth rearrangement
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381755/
https://www.ncbi.nlm.nih.gov/pubmed/28413233
http://dx.doi.org/10.1016/j.tetlet.2017.02.082
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