Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines

[Image: see text] This study reports two strategies for preparing O-alkyl derivatives of 6-substituted-4-(trifluoromethyl)pyrimidin-(1H)-ones: a linear protocol of alkylation, using a CCC-building block followed by [3 + 3]-type cyclocondensation with 2-methylisothiourea sulfate and a convergent prot...

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Autores principales: Mittersteiner, Mateus, Pereira, Genilson S., Wessjohann, Ludger A., Bonacorso, Helio G., Martins, Marcos A. P., Zanatta, Nilo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178747/
https://www.ncbi.nlm.nih.gov/pubmed/35694463
http://dx.doi.org/10.1021/acsomega.2c01925
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author Mittersteiner, Mateus
Pereira, Genilson S.
Wessjohann, Ludger A.
Bonacorso, Helio G.
Martins, Marcos A. P.
Zanatta, Nilo
author_facet Mittersteiner, Mateus
Pereira, Genilson S.
Wessjohann, Ludger A.
Bonacorso, Helio G.
Martins, Marcos A. P.
Zanatta, Nilo
author_sort Mittersteiner, Mateus
collection PubMed
description [Image: see text] This study reports two strategies for preparing O-alkyl derivatives of 6-substituted-4-(trifluoromethyl)pyrimidin-(1H)-ones: a linear protocol of alkylation, using a CCC-building block followed by [3 + 3]-type cyclocondensation with 2-methylisothiourea sulfate and a convergent protocol based on direct alkylation, using 4-(iodomethyl)-2-(methylthio)-6-(trihalomethyl)pyrimidines. It was found that the cyclocondensation strategy is not feasible; thus, the direct chemoselective O-alkylation was performed, and 18 derivatives of the targeted pyrimidines were obtained in 70–98% yields. The structure of the products was unambiguously determined via single crystal X-ray analyses and two-dimensional nuclear magnetic resonance experiments.
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spelling pubmed-91787472022-06-10 Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines Mittersteiner, Mateus Pereira, Genilson S. Wessjohann, Ludger A. Bonacorso, Helio G. Martins, Marcos A. P. Zanatta, Nilo ACS Omega [Image: see text] This study reports two strategies for preparing O-alkyl derivatives of 6-substituted-4-(trifluoromethyl)pyrimidin-(1H)-ones: a linear protocol of alkylation, using a CCC-building block followed by [3 + 3]-type cyclocondensation with 2-methylisothiourea sulfate and a convergent protocol based on direct alkylation, using 4-(iodomethyl)-2-(methylthio)-6-(trihalomethyl)pyrimidines. It was found that the cyclocondensation strategy is not feasible; thus, the direct chemoselective O-alkylation was performed, and 18 derivatives of the targeted pyrimidines were obtained in 70–98% yields. The structure of the products was unambiguously determined via single crystal X-ray analyses and two-dimensional nuclear magnetic resonance experiments. American Chemical Society 2022-05-24 /pmc/articles/PMC9178747/ /pubmed/35694463 http://dx.doi.org/10.1021/acsomega.2c01925 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Mittersteiner, Mateus
Pereira, Genilson S.
Wessjohann, Ludger A.
Bonacorso, Helio G.
Martins, Marcos A. P.
Zanatta, Nilo
Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines
title Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines
title_full Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines
title_fullStr Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines
title_full_unstemmed Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines
title_short Chemoselective O-Alkylation of 4-(Trifluoromethyl)pyrimidin-2(1H)-ones Using 4-(Iodomethyl)pyrimidines
title_sort chemoselective o-alkylation of 4-(trifluoromethyl)pyrimidin-2(1h)-ones using 4-(iodomethyl)pyrimidines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178747/
https://www.ncbi.nlm.nih.gov/pubmed/35694463
http://dx.doi.org/10.1021/acsomega.2c01925
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