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Photoredox Catalysis in a Complex Pharmaceutical Setting: Toward the Preparation of JAK2 Inhibitor LY2784544
[Image: see text] We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in go...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260666/ https://www.ncbi.nlm.nih.gov/pubmed/25356724 http://dx.doi.org/10.1021/jo502288q |
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author | Douglas, James J. Cole, Kevin P. Stephenson, Corey R. J. |
author_facet | Douglas, James J. Cole, Kevin P. Stephenson, Corey R. J. |
author_sort | Douglas, James J. |
collection | PubMed |
description | [Image: see text] We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N-methyl substituted tertiary amines, and therefore it represents an attractive tool for medicinal chemistry. Furthermore, a number of other interesting photoredox reactions were discovered during the course of this investigation, such as a formal methylation reaction via C–N bond cleavage, functionalization of C–H bonds alpha to amides, and a visible light-mediated iminium ion reduction. |
format | Online Article Text |
id | pubmed-4260666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-42606662015-10-30 Photoredox Catalysis in a Complex Pharmaceutical Setting: Toward the Preparation of JAK2 Inhibitor LY2784544 Douglas, James J. Cole, Kevin P. Stephenson, Corey R. J. J Org Chem [Image: see text] We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N-methyl substituted tertiary amines, and therefore it represents an attractive tool for medicinal chemistry. Furthermore, a number of other interesting photoredox reactions were discovered during the course of this investigation, such as a formal methylation reaction via C–N bond cleavage, functionalization of C–H bonds alpha to amides, and a visible light-mediated iminium ion reduction. American Chemical Society 2014-10-30 2014-12-05 /pmc/articles/PMC4260666/ /pubmed/25356724 http://dx.doi.org/10.1021/jo502288q Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Douglas, James J. Cole, Kevin P. Stephenson, Corey R. J. Photoredox Catalysis in a Complex Pharmaceutical Setting: Toward the Preparation of JAK2 Inhibitor LY2784544 |
title | Photoredox Catalysis in a
Complex Pharmaceutical Setting:
Toward the Preparation of JAK2 Inhibitor LY2784544 |
title_full | Photoredox Catalysis in a
Complex Pharmaceutical Setting:
Toward the Preparation of JAK2 Inhibitor LY2784544 |
title_fullStr | Photoredox Catalysis in a
Complex Pharmaceutical Setting:
Toward the Preparation of JAK2 Inhibitor LY2784544 |
title_full_unstemmed | Photoredox Catalysis in a
Complex Pharmaceutical Setting:
Toward the Preparation of JAK2 Inhibitor LY2784544 |
title_short | Photoredox Catalysis in a
Complex Pharmaceutical Setting:
Toward the Preparation of JAK2 Inhibitor LY2784544 |
title_sort | photoredox catalysis in a
complex pharmaceutical setting:
toward the preparation of jak2 inhibitor ly2784544 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260666/ https://www.ncbi.nlm.nih.gov/pubmed/25356724 http://dx.doi.org/10.1021/jo502288q |
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