Nucleophilic aromatic substitution of heterocycles using a high-temperature and high-pressure flow reactor

被引：20

作者：

Charaschanya, Manwika ^{[1
]}

Bogdan, Andrew R. ^{[2
]}

Wang, Ying ^{[2
]}

Djuric, Stevan W. ^{[2
]}

机构：

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66047 USA

[2] AbbVie Inc, Discovery Chem & Technol, 1 North Waukegan Rd, N Chicago, IL 60064 USA

来源：

TETRAHEDRON LETTERS | 2016年 / 57卷 / 09期

关键词：

Flow chemistry; High-temperature reactions; Nucleophilic aromatic substitution; ORGANIC-SYNTHESIS; N-2,N-4-DISUBSTITUTED QUINAZOLINE-2,4-DIAMINES; MULTISTEP SYNTHESIS; CHEMISTRY; INHIBITORS; SERIES; QUINAZOLINES; DISCOVERY;

D O I：

10.1016/j.tetlet.2016.01.080

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We report herein a high-temperature and high-pressure continuous-flow protocol to carry out nucleophilic aromatic substitution (SNAr) of heterocycles with nitrogen nucleophiles. Utilizing the Phoenix Flow Reactor (TM) in parallel with Design-of-Experiment software enabled rapid optimization of the SNAr protocol. This protocol facilitated efficient synthesis of a broad range of 2-aminoquinazolines, and was extended to 2-aminoquinoxalines and 2-aminobenzimidazoles. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1035 / 1039

页数：5

共 30 条

[1] The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry [J].

Baumann, Marcus ;

Baxendale, Ian R. .

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 2015, 11 :1194-1219

[2] The flow synthesis of heterocycles for natural product and medicinal chemistry applications [J].

Baumann, Marcus ;

Baxendale, Ian R. ;

Ley, Steven V. .

MOLECULAR DIVERSITY, 2011, 15 (03) :613-630

[3] A flow process for the multi-step synthesis of the alkaloid natural product oxomaritidine: a new paradigm for molecular assembly [J].

Baxendale, Ian R. ;

Deeley, Jon ;

Griffiths-Jones, Charlotte M. ;

Ley, Steven V. ;

Saaby, Steen ;

Tranmer, Geoffrey K. .

CHEMICAL COMMUNICATIONS, 2006, (24) :2566-2568

[4] The integration of flow reactors into synthetic organic chemistry [J].

Baxendale, Ian R. .

JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, 2013, 88 (04) :519-552

[5] Continuous-Flow Synthesis of 1-Substituted Benzotriazoles from Chloronitrobenzenes and Amines in a CN Bond Formation/Hydrogenation/Diazotization/Cyclization Sequence [J].

Chen, Mao ;

Buchwald, Stephen L. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2013, 52 (15) :4247-4250

[6] Structure-Activity Relationship Study Reveals ML240 and ML241 as Potent and Selective Inhibitors of p97 ATPase [J].

Chou, Tsui-Fen ;

Li, Kelin ;

Frankowski, Kevin J. ;

Schoenen, Frank J. ;

Deshaies, Raymond J. .

CHEMMEDCHEM, 2013, 8 (02) :297-312

[7] Synthesis of quinazolinones and quinazolines [J].

Connolly, DJ ;

Cusack, D ;

O'Sullivan, TP ;

Guiry, PJ .

TETRAHEDRON, 2005, 61 (43) :10153-10202

[8] Translating High-Temperature Microwave Chemistry to Scalable Continuous Flow Processes [J].

Damm, Markus ;

Glasnov, Toma N. ;

Kappe, C. Oliver .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2010, 14 (01) :215-224

[9] Developing Continuous-Flow Microreactors as Tools for Synthetic Chemists [J].

Geyer, Karolin ;

Gustafsson, Tomas ;

Seeberger, Peter H. .

SYNLETT, 2009, (15) :2382-2391

[10] Direct uncatalyzed amination of 2-chloropyridine using a flow reactor [J].

Hamper, Bruce C. ;

Tesfu, Eden .

SYNLETT, 2007, (14) :2257-2261

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