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在室温离子氢化条件下通过吡啶 -2-氧基 -7-氮杂苯并三唑醚的裂解合成 3,4-二取代吡啶 -2(1)-酮的新型文库。

Novel library synthesis of 3,4-disubstituted pyridin-2(1)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature.

作者信息

Pierre Romain, Brethon Anne, Jacques Sylvain A, Blond Aurélie, Chambon Sandrine, Talano Sandrine, Raffin Catherine, Musicki Branislav, Bouix-Peter Claire, Tomas Loic, Ouvry Gilles, Morgentin Rémy, Hennequin Laurent F, Harris Craig S

机构信息

Galderma SA, Rue d'Entre-deux-Villes 10, 1814 Vevey, Switzerland.

Edelris, 60, Avenue Rockefeller, Bioparc, Bioserra 1 Building, 69008 Lyon, France.

出版信息

Beilstein J Org Chem. 2021 Jan 18;17:156-165. doi: 10.3762/bjoc.17.16. eCollection 2021.

DOI:10.3762/bjoc.17.16
PMID:33564326
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7849264/
Abstract

In our hands, efficient access to the 4-amino-3-carboxamide disubstituted pyridine-2(1)-one kinase hinge-binder motif proved to be more challenging than anticipated requiring a significant investment in route scouting and optimization. This full paper focuses on the synthesis issues that we encountered during our route exploration and the original solutions we found that helped us to identify two optimized library-style processes to prepare our large kinase inhibitor library.

摘要

在我们的研究中，事实证明，要高效获得4-氨基-3-羧酰胺二取代吡啶-2(1)-酮激酶铰链结合基序比预期更具挑战性，需要在路线探索和优化方面投入大量精力。这篇全文聚焦于我们在路线探索过程中遇到的合成问题，以及我们找到的原创解决方案，这些方案帮助我们确定了两种优化的库式方法来制备我们的大型激酶抑制剂库。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/0d654658002f/Beilstein_J_Org_Chem-17-156-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/58d4c71e159a/Beilstein_J_Org_Chem-17-156-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/41d63b126b82/Beilstein_J_Org_Chem-17-156-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/543c32de32c0/Beilstein_J_Org_Chem-17-156-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/37e7a2752013/Beilstein_J_Org_Chem-17-156-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/0b84eece50b2/Beilstein_J_Org_Chem-17-156-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/5fb091bc2f74/Beilstein_J_Org_Chem-17-156-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/0d654658002f/Beilstein_J_Org_Chem-17-156-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/58d4c71e159a/Beilstein_J_Org_Chem-17-156-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/41d63b126b82/Beilstein_J_Org_Chem-17-156-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/543c32de32c0/Beilstein_J_Org_Chem-17-156-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/37e7a2752013/Beilstein_J_Org_Chem-17-156-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/0b84eece50b2/Beilstein_J_Org_Chem-17-156-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/5fb091bc2f74/Beilstein_J_Org_Chem-17-156-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7849264/0d654658002f/Beilstein_J_Org_Chem-17-156-g008.jpg

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本文引用的文献

1
Denitrogenative Suzuki and carbonylative Suzuki coupling reactions of benzotriazoles with boronic acids.苯并三唑与硼酸的脱氮铃木反应和羰基化铃木偶联反应。
Chem Sci. 2017 May 1;8(5):3852-3857. doi: 10.1039/c7sc00367f. Epub 2017 Mar 15.
2
Transition-metal-catalyzed synthesis of phenols and aryl thiols.过渡金属催化的酚类和芳基硫醇的合成。
Beilstein J Org Chem. 2017 Mar 23;13:589-611. doi: 10.3762/bjoc.13.58. eCollection 2017.
3
Synthesis and Antiviral Evaluation of Octadecyloxyethyl Benzyl 9-[(2-Phosphonomethoxy)ethyl]guanine (ODE-Bn-PMEG), a Potent Inhibitor of Transient HPV DNA Amplification.
十八烷氧基乙基苄基9-[(2-膦酰甲氧基)乙基]鸟嘌呤（ODE-Bn-PMEG）的合成与抗病毒评估，一种有效的瞬时人乳头瘤病毒DNA扩增抑制剂
J Med Chem. 2016 Dec 8;59(23):10470-10478. doi: 10.1021/acs.jmedchem.6b00659. Epub 2016 Nov 28.
4
Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR.吡啶酮作为表皮生长因子受体（EGFR）T790M双突变体的高选择性非共价抑制剂
ACS Med Chem Lett. 2015 Dec 17;7(1):100-4. doi: 10.1021/acsmedchemlett.5b00428. eCollection 2016 Jan 14.
5
The discovery of tricyclic pyridone JAK2 inhibitors. Part 1: hit to lead.三环吡啶酮 JAK2 抑制剂的发现。第 1 部分：从苗头化合物到先导化合物。
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7421-5. doi: 10.1016/j.bmcl.2010.10.031. Epub 2010 Oct 12.
6
Phosphorus trichloride-mediated and microwave-assisted synthesis of a small collection of amides bearing strong electron-withdrawing group substituted anilines.三氯化磷介导和微波辅助合成一小系列带有强吸电子基团取代苯胺的酰胺。
J Comb Chem. 2009 May-Jun;11(3):335-7. doi: 10.1021/cc900011z.
7
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Bioorg Med Chem Lett. 2007 Aug 15;17(16):4568-74. doi: 10.1016/j.bmcl.2007.05.090. Epub 2007 Jun 6.
8
The selective reaction of aryl halides with KOH: synthesis of phenols, aromatic ethers, and benzofurans.芳基卤化物与氢氧化钾的选择性反应：酚类、芳香醚和苯并呋喃的合成。
J Am Chem Soc. 2006 Aug 23;128(33):10694-5. doi: 10.1021/ja0639719.