A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one

A novel synthesis of the anticancer drug gefitinib (Iressa) through novel alternative pathway has been successfully carried out. The synthesis was performed using 6,7-dimethoxy-3H-quinazolin-4-one as the starting material through four reaction stages: Chlorination, nucleophilic aromatic substitution...

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Main Authors: Santoso, Prio, Danova, Ade, Hermawati, Elvira, Natalia, Dessy, Alni, Anita
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2025
Online Access:http://journalarticle.ukm.my/25630/
http://journalarticle.ukm.my/25630/1/SE%207.pdf
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author Santoso, Prio
Danova, Ade
Hermawati, Elvira
Natalia, Dessy
Alni, Anita
author_facet Santoso, Prio
Danova, Ade
Hermawati, Elvira
Natalia, Dessy
Alni, Anita
author_sort Santoso, Prio
building UKM Institutional Repository
collection Online Access
description A novel synthesis of the anticancer drug gefitinib (Iressa) through novel alternative pathway has been successfully carried out. The synthesis was performed using 6,7-dimethoxy-3H-quinazolin-4-one as the starting material through four reaction stages: Chlorination, nucleophilic aromatic substitution, demethylation, and Williamson etherification to produce gefitinib. The chlorination of 6,7-dimethoxy-3H-quinazolin-4-one as the first key step in this synthesis followed by aromatic substitution were effective to produce the target product with high yield (98% for two steps). In addition, synthesis of gefitinib from this precursor omits the necessity for functional group protection and deprotection. Purification was carried out using crystallization and radial chromatography. The structural analysis of the resulting compound was performed using FTIR, 1H-NMR, 13C-NMR, and mass spectrometry. The purity of the resulting compounds was measured using HPLC and melting point measurements (195-197 °C). The overall yield obtained through this pathway was 21%.
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spelling oai:generic.eprints.org:256302025-07-16T05:25:26Z http://journalarticle.ukm.my/25630/ A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one Santoso, Prio Danova, Ade Hermawati, Elvira Natalia, Dessy Alni, Anita A novel synthesis of the anticancer drug gefitinib (Iressa) through novel alternative pathway has been successfully carried out. The synthesis was performed using 6,7-dimethoxy-3H-quinazolin-4-one as the starting material through four reaction stages: Chlorination, nucleophilic aromatic substitution, demethylation, and Williamson etherification to produce gefitinib. The chlorination of 6,7-dimethoxy-3H-quinazolin-4-one as the first key step in this synthesis followed by aromatic substitution were effective to produce the target product with high yield (98% for two steps). In addition, synthesis of gefitinib from this precursor omits the necessity for functional group protection and deprotection. Purification was carried out using crystallization and radial chromatography. The structural analysis of the resulting compound was performed using FTIR, 1H-NMR, 13C-NMR, and mass spectrometry. The purity of the resulting compounds was measured using HPLC and melting point measurements (195-197 °C). The overall yield obtained through this pathway was 21%. Penerbit Universiti Kebangsaan Malaysia 2025 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/25630/1/SE%207.pdf Santoso, Prio and Danova, Ade and Hermawati, Elvira and Natalia, Dessy and Alni, Anita (2025) A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one. Sains Malaysiana, 54 (4). pp. 1053-1062. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol54num4_2025/contentsVol54num4_2025.html
spellingShingle Santoso, Prio
Danova, Ade
Hermawati, Elvira
Natalia, Dessy
Alni, Anita
A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one
title A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one
title_full A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one
title_fullStr A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one
title_full_unstemmed A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one
title_short A novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3H-quinazolin-4-one
title_sort novel synthesis of anti-cancer drug gefitinib from 6,7-dimethoxy-3h-quinazolin-4-one
url http://journalarticle.ukm.my/25630/
http://journalarticle.ukm.my/25630/
http://journalarticle.ukm.my/25630/1/SE%207.pdf