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

ABSTRACT: 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).

SUBMITTER: Brocklesby KL

PROVIDER: S-EPMC5381755 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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An alternative synthesis of Vandetanib (Caprelsa™) <i>via</i> a microwave accelerated Dimroth rearrangement.

Brocklesby Kayleigh L KL Waby Jennifer S JS Cawthorne Chris C Smith Graham G

Tetrahedron letters 20170401 15

Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds <i>via</i> 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). ...[more]

PMID: 28413233

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