Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives
A robust, practical, and scalable approach for the construction of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives <b>13</b> via the addition of Grignard reagents to 4-amino-2-chloronicotinonitrile (<b>15</b>) was developed. Starting with various Grignard reagents,...
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doaj-504a1877896d4360b5ff268b66c7ff6d2020-12-02T21:43:05ZengMDPI AGMolecules1420-30492020-12-01255667566710.3390/molecules25235667Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one DerivativesMing-Shu Wang0Yi Gong1Zhi-Cheng Yu2Yan-Guang Tian3Lin-Sheng Zhuo4Wei Huang5Neng-Fang She6Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaKey Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, ChinaA robust, practical, and scalable approach for the construction of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives <b>13</b> via the addition of Grignard reagents to 4-amino-2-chloronicotinonitrile (<b>15</b>) was developed. Starting with various Grignard reagents, a wide range of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives <b>13</b> were conveniently synthesized in moderate-to-good yields through addition–acidolysis–cyclocondensation. In addition, the robustness and applicability of this synthetic route was proven on a 100 g scale, which would enable convenient sample preparation in the preclinical development of 1,6-naphthyridin-4-one-based MET-targeting antitumor drug candidates.https://www.mdpi.com/1420-3049/25/23/56671,6-naphthyridineGrignard reagentkinase inhibitorantitumor drug candidate |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ming-Shu Wang Yi Gong Zhi-Cheng Yu Yan-Guang Tian Lin-Sheng Zhuo Wei Huang Neng-Fang She |
spellingShingle |
Ming-Shu Wang Yi Gong Zhi-Cheng Yu Yan-Guang Tian Lin-Sheng Zhuo Wei Huang Neng-Fang She Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives Molecules 1,6-naphthyridine Grignard reagent kinase inhibitor antitumor drug candidate |
author_facet |
Ming-Shu Wang Yi Gong Zhi-Cheng Yu Yan-Guang Tian Lin-Sheng Zhuo Wei Huang Neng-Fang She |
author_sort |
Ming-Shu Wang |
title |
Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives |
title_short |
Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives |
title_full |
Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives |
title_fullStr |
Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives |
title_full_unstemmed |
Grignard Reagent Utilization Enables a Practical and Scalable Construction of 3-Substituted 5-Chloro-1,6-naphthyridin-4-one Derivatives |
title_sort |
grignard reagent utilization enables a practical and scalable construction of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-12-01 |
description |
A robust, practical, and scalable approach for the construction of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives <b>13</b> via the addition of Grignard reagents to 4-amino-2-chloronicotinonitrile (<b>15</b>) was developed. Starting with various Grignard reagents, a wide range of 3-substituted 5-chloro-1,6-naphthyridin-4-one derivatives <b>13</b> were conveniently synthesized in moderate-to-good yields through addition–acidolysis–cyclocondensation. In addition, the robustness and applicability of this synthetic route was proven on a 100 g scale, which would enable convenient sample preparation in the preclinical development of 1,6-naphthyridin-4-one-based MET-targeting antitumor drug candidates. |
topic |
1,6-naphthyridine Grignard reagent kinase inhibitor antitumor drug candidate |
url |
https://www.mdpi.com/1420-3049/25/23/5667 |
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