Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step

1-Phenyl-1H-1,2,3-triazole 1 (ARUK3001185) was prepared on large scale from aniline 4 by application of both (1) a copper catalyzed azide–alkyne cycloaddition (CuAAC) with (trimethylsilyl)acetylene, and (2) a Clark modification of the Sakai reaction. The one-pot Sakai–Clark method with (MeO)(2)CHCH[...

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Autores principales: Atkinson, Benjamin N., Willis, Nicky J., Smith, Jennifer, Gill, Rebecca, Ali, Jody, Xu, Zhou, Lai, Ping-Shan, Fish, Paul V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478995/
https://www.ncbi.nlm.nih.gov/pubmed/36275171
http://dx.doi.org/10.1039/d2ra05132j
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author Atkinson, Benjamin N.
Willis, Nicky J.
Smith, Jennifer
Gill, Rebecca
Ali, Jody
Xu, Zhou
Lai, Ping-Shan
Fish, Paul V.
author_facet Atkinson, Benjamin N.
Willis, Nicky J.
Smith, Jennifer
Gill, Rebecca
Ali, Jody
Xu, Zhou
Lai, Ping-Shan
Fish, Paul V.
author_sort Atkinson, Benjamin N.
collection PubMed
description 1-Phenyl-1H-1,2,3-triazole 1 (ARUK3001185) was prepared on large scale from aniline 4 by application of both (1) a copper catalyzed azide–alkyne cycloaddition (CuAAC) with (trimethylsilyl)acetylene, and (2) a Clark modification of the Sakai reaction. The one-pot Sakai–Clark method with (MeO)(2)CHCH[double bond, length as m-dash]NNHTos (2b) proved to be superior as it was operationally simple, metal-free, and avoided the use of aryl azide 7. The Sakai–Clark method has been reliably performed on large scale to produce >100 g of 1 in good efficiency and high purity.
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spelling pubmed-94789952022-10-20 Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step Atkinson, Benjamin N. Willis, Nicky J. Smith, Jennifer Gill, Rebecca Ali, Jody Xu, Zhou Lai, Ping-Shan Fish, Paul V. RSC Adv Chemistry 1-Phenyl-1H-1,2,3-triazole 1 (ARUK3001185) was prepared on large scale from aniline 4 by application of both (1) a copper catalyzed azide–alkyne cycloaddition (CuAAC) with (trimethylsilyl)acetylene, and (2) a Clark modification of the Sakai reaction. The one-pot Sakai–Clark method with (MeO)(2)CHCH[double bond, length as m-dash]NNHTos (2b) proved to be superior as it was operationally simple, metal-free, and avoided the use of aryl azide 7. The Sakai–Clark method has been reliably performed on large scale to produce >100 g of 1 in good efficiency and high purity. The Royal Society of Chemistry 2022-09-16 /pmc/articles/PMC9478995/ /pubmed/36275171 http://dx.doi.org/10.1039/d2ra05132j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Atkinson, Benjamin N.
Willis, Nicky J.
Smith, Jennifer
Gill, Rebecca
Ali, Jody
Xu, Zhou
Lai, Ping-Shan
Fish, Paul V.
Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
title Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
title_full Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
title_fullStr Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
title_full_unstemmed Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
title_short Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
title_sort large-scale synthesis of notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1h-1,2,3-triazole (aruk3001185) employing a modified sakai reaction as the key step
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478995/
https://www.ncbi.nlm.nih.gov/pubmed/36275171
http://dx.doi.org/10.1039/d2ra05132j
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