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Synlett 2018; 29(07): 922-927
DOI: 10.1055/s-0036-1591907
letter
© Georg Thieme Verlag Stuttgart · New York

Highly Efficient Synthesis of Polysubstituted 2-Aminopyrroles via a Multicomponent Domino Reaction

Jiaan Shao*
a   Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P. R. of China   eMail: shaojia_an@126.com
,
Di Ke
b   College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. of China   eMail: wentengchen@zju.edu.cn
,
Ke Shu
b   College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. of China   eMail: wentengchen@zju.edu.cn
,
En Chen
b   College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. of China   eMail: wentengchen@zju.edu.cn
,
Yongping Yu
b   College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. of China   eMail: wentengchen@zju.edu.cn
,
Wenteng Chen*
b   College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang 310058, P. R. of China   eMail: wentengchen@zju.edu.cn
› InstitutsangabenThis study was supported by the National Natural Science Foundation of China (No. 81402778) and Zhejiang Provincial Natural Science (LY18H300001) to W. Chen; National Natural Science Foundation of China (No. 81602959), the Science Foundation of Zhejiang Sci-Tech University (No.16062192-Y) to J. Shao; the National Natural Science Foundation of China (No. 81673291 and 81473074), and Alzheimer's & Aging Research Center, USA to Y. Yu; and the Fundamental Research Funds for the Central Universities (2017FZA7016).
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Publikationsverlauf

Received: 29. November 2017

Accepted after revision: 01. Januar 2018

Publikationsdatum:
15. Februar 2018 (online)

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Abstract

A highly efficient approach to polysubstituted 2-amino­pyrroles containing a coumarin derivative unit at the 5-position of the pyrrole ring was developed via a novel multicomponent domino reaction of glyoxal monohydrate derivatives, anilines, coumarin derivatives, and malononitrile. This transformation proceeded via an α-amino­ketone as the key intermediate.

Key words

2-aminopyrroles - domino reaction - multicomponent reaction - coumarin derivatives - heterocycles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591907.
  • Supporting Information
 

  • References and Notes

  • 9 Satoshi Y. Junya S. Yoshiyuki F. Ayumu S. Mitsunori K. Yoshihide T. Atsuko O. Kazuko Y. Tsuneo O. Imada Takashi I. Tomoya Y. WO 2014142255, 2014
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  • 11 CCDC 1583386 contains the supplementary crystallographic data for 2a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 12 General Procedure of 2a–y A mixture of glyoxal monohydrate derivative (0.5 mmol, 1.0 equiv), coumarin derivative (0.5 mmol, 1.0 equiv), and amine (0.5 mmol, 1.0 equiv) were stirred in DCE (3 mL) at rt for 15 min. Then, malononitrile (0.5 mmol, 1.0 equiv) and Et3N (0.5 mmol, 1.0 equiv) were added to the mixture and the reaction was stirred for another 8 h under N2. After the reaction was complete, the mixture was diluted with DCM (10 mL). The mixture was then washed with H2O (5 mL). The organic extracts were collected and concentrated. Purification of the crude product was carried out by chromatography (silica gel, MeOH/DCM = 1:30) to afford 2a–y as the desired products. 2-Amino-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1-isobutyl-4-(p-tolyl)-1H-pyrrole-3-carbonitrile (2a) Pale yellow solid, 164 mg, 79% yield; mp 231.7–233.4 °C. 1H NMR (500 MHz, CD3OD): δ = 7.87 (dd, J = 8.0, 1.3 Hz, 1 H), 7.68–7.60 (m, 1 H), 7.39–7.31 (m, 2 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.03 (d, J = 8.0 Hz, 2 H), 3.45 (qd, J = 14.8, 7.6 Hz, 2 H), 2.23 (s, 3 H), 1.91 (dt, J = 13.7, 7.0 Hz, 1 H), 0.86 (d, J = 6.7 Hz, 3 H), 0.81 (d, J = 6.7 Hz, 3 H). 13C NMR (125 MHz, CD3OD): δ = 165.68, 163.96, 153.27, 149.26, 136.23, 132.97, 130.61, 128.50, 127.47, 124.99, 124.16, 123.86, 118.11, 116.20, 115.44, 111.76, 96.18, 72.19, 50.48, 28.70, 19.77, 18.93, 18.78. HRMS (ESI): m/z calcd for C25H24N3O3[M + H]+: 414.1812; found: 414.1812.