A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer

A novel and scalable synthesis of 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone, idelalisib 1, has been developed. This strategy controls the desfluoro impurity of 13 during reduction of nitro intermediate 4, and also arrests the formation of the enantiomer during cycli...

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Autores principales: Mekala, Nagaraju, Buddepu, Srinivasa Rao, Dehury, Sanjay K., Moturu, Krishna Murthy V. R., Indukuri, Sunil Kumar V., Vasireddi, Umamaheswara Rao, Parimi, Atchuta R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2018
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080089/
https://www.ncbi.nlm.nih.gov/pubmed/35539498
http://dx.doi.org/10.1039/c8ra00407b
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author Mekala, Nagaraju
Buddepu, Srinivasa Rao
Dehury, Sanjay K.
Moturu, Krishna Murthy V. R.
Indukuri, Sunil Kumar V.
Vasireddi, Umamaheswara Rao
Parimi, Atchuta R.
author_facet Mekala, Nagaraju
Buddepu, Srinivasa Rao
Dehury, Sanjay K.
Moturu, Krishna Murthy V. R.
Indukuri, Sunil Kumar V.
Vasireddi, Umamaheswara Rao
Parimi, Atchuta R.
author_sort Mekala, Nagaraju
collection PubMed
description A novel and scalable synthesis of 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone, idelalisib 1, has been developed. This strategy controls the desfluoro impurity of 13 during reduction of nitro intermediate 4, and also arrests the formation of the enantiomer during cyclisation of diamide 17, without affecting the neighbouring chiral centre. This process is demonstrated on a larger scale in the laboratory and achieved good chemical and chiral purities coupled with good yields.
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spelling pubmed-90800892022-05-09 A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer Mekala, Nagaraju Buddepu, Srinivasa Rao Dehury, Sanjay K. Moturu, Krishna Murthy V. R. Indukuri, Sunil Kumar V. Vasireddi, Umamaheswara Rao Parimi, Atchuta R. RSC Adv Chemistry A novel and scalable synthesis of 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone, idelalisib 1, has been developed. This strategy controls the desfluoro impurity of 13 during reduction of nitro intermediate 4, and also arrests the formation of the enantiomer during cyclisation of diamide 17, without affecting the neighbouring chiral centre. This process is demonstrated on a larger scale in the laboratory and achieved good chemical and chiral purities coupled with good yields. The Royal Society of Chemistry 2018-04-27 /pmc/articles/PMC9080089/ /pubmed/35539498 http://dx.doi.org/10.1039/c8ra00407b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Mekala, Nagaraju
Buddepu, Srinivasa Rao
Dehury, Sanjay K.
Moturu, Krishna Murthy V. R.
Indukuri, Sunil Kumar V.
Vasireddi, Umamaheswara Rao
Parimi, Atchuta R.
A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
title A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
title_full A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
title_fullStr A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
title_full_unstemmed A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
title_short A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
title_sort novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080089/
https://www.ncbi.nlm.nih.gov/pubmed/35539498
http://dx.doi.org/10.1039/c8ra00407b
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