Synthesis of the (3R,6S)-3-Amino-6-(2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache

Synthesis of the (3R,6S)-3-Amino-6-(2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache

Two novel routes have been developed to the (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one 2 of the CGRP receptor antagonist clinical candidate telcagepant (MK-0974, 1). The first employs a ring-closing metathesis of the styrene 7 as the key reaction, while the second ma...

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Veröffentlicht in:Organic letters 2008-08, Vol.10 (15), p.3235-3238
Hauptverfasser: Burgey, Christopher S, Paone, Daniel V, Shaw, Anthony W, Deng, James Z, Nguyen, Diem N, Potteiger, Craig M, Graham, Samuel L, Vacca, Joseph P, Williams, Theresa M
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Azepines - chemical synthesis
Imidazoles - chemical synthesis
Receptors, Calcitonin Gene-Related Peptide - antagonists & inhibitors
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container_end_page 3238
container_issue 15
container_start_page 3235
container_title Organic letters
container_volume 10
creator Burgey, Christopher S
Paone, Daniel V
Shaw, Anthony W
Deng, James Z
Nguyen, Diem N
Potteiger, Craig M
Graham, Samuel L
Vacca, Joseph P
Williams, Theresa M
description Two novel routes have been developed to the (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one 2 of the CGRP receptor antagonist clinical candidate telcagepant (MK-0974, 1). The first employs a ring-closing metathesis of the styrene 7 as the key reaction, while the second makes use of a highly diastereoselective Hayashi−Miyaura Rh-catalyzed arylboronic acid addition to nitroalkene 16. The latter route has been implemented to produce multigram quantities of telcagepant for extensive preclinical evaluation.
doi_str_mv 10.1021/ol8011524
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subjects Azepines - chemical synthesis
Imidazoles - chemical synthesis
Receptors, Calcitonin Gene-Related Peptide - antagonists & inhibitors
title Synthesis of the (3R,6S)-3-Amino-6-(2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache
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