Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine

[Image: see text] The process selection and subsequent development of a reliable, scalable synthesis of the anticancer prodrug tirapazamine (SR259075) is described in this paper. Reaction of benzofuroxan with cyanamide in acetonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene at 20–25 °C...

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Autores principales: Lienard, Philippe, Elenbaas, Steven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364547/
https://www.ncbi.nlm.nih.gov/pubmed/32685820
http://dx.doi.org/10.1021/acsomega.0c01250
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author Lienard, Philippe
Elenbaas, Steven
author_facet Lienard, Philippe
Elenbaas, Steven
author_sort Lienard, Philippe
collection PubMed
description [Image: see text] The process selection and subsequent development of a reliable, scalable synthesis of the anticancer prodrug tirapazamine (SR259075) is described in this paper. Reaction of benzofuroxan with cyanamide in acetonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene at 20–25 °C afforded, after an acidic workup, the targeted molecule in good yield at a kilogram scale. Notable critical parameters and safety enhancements are defined and successfully implemented to produce three consecutive validation batches in a reproducible manner.
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spelling pubmed-73645472020-07-17 Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine Lienard, Philippe Elenbaas, Steven ACS Omega [Image: see text] The process selection and subsequent development of a reliable, scalable synthesis of the anticancer prodrug tirapazamine (SR259075) is described in this paper. Reaction of benzofuroxan with cyanamide in acetonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene at 20–25 °C afforded, after an acidic workup, the targeted molecule in good yield at a kilogram scale. Notable critical parameters and safety enhancements are defined and successfully implemented to produce three consecutive validation batches in a reproducible manner. American Chemical Society 2020-07-01 /pmc/articles/PMC7364547/ /pubmed/32685820 http://dx.doi.org/10.1021/acsomega.0c01250 Text en Copyright © 2020 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 Lienard, Philippe
Elenbaas, Steven
Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine
title Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine
title_full Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine
title_fullStr Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine
title_full_unstemmed Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine
title_short Development and Validation of a Kilogram-Scale Synthesis of Tirapazamine
title_sort development and validation of a kilogram-scale synthesis of tirapazamine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364547/
https://www.ncbi.nlm.nih.gov/pubmed/32685820
http://dx.doi.org/10.1021/acsomega.0c01250
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