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Synlett 2019; 30(10): 1246-1252
DOI: 10.1055/s-0037-1611827
DOI: 10.1055/s-0037-1611827
letter
Synthesis of 3-Halo-7-azaindoles through a 5-endo-dig Electrophilic Cyclization Reaction
We are grateful to Research Corporation for Science Advancement for a Cottrell College Science Award (ID 23248). Authors are also thankful for support provided by the University of West Florida (UWF), UWF’s Office of Research and Sponsored Programs and Office of Undergraduate Research. Our research is also supported by the National Institute of General Medical Sciences of the National Institutes of Health under grant number 1T34GM110517-01. The content is solely the responsibility of the authors and it does not necessarily represent the official views of the National Institutes of Health.Further Information
Publication History
Received: 16 April 2019
Accepted after revision: 24 April 2019
Publication Date:
20 May 2019 (online)
Abstract
Biologically useful 7-azaindoles were synthesized by electrophilic cyclization of 3-alkynyl-N,N-dimethylpyridine-2-amines with molecular iodine. By this simple atom-economical approach under ambient reaction conditions, a library of interesting 3-iodo-7-azaindoles were synthesized in high yields. To synthesize the corresponding 3-bromo- and 3-chloro-7-azaindoles, an environmentally benign copper-mediated cyclization was employed, with inexpensive, nontoxic, and noncorrosive sodium chloride and sodium bromide as the sources of chlorine and bromine, respectively.
Key words
electrophilic cyclization - iodocyclization - bromocyclization - chlorocyclization - azaindolesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611827.
- Supporting Information
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- 25 Halocyclization Reaction; General Procedures Method A. To a 6-dram vial containing the starting alkyne (0.3 mmol) was added CH2Cl2 (4.0 mL). I2 (2.0 equiv) was then added, and the mixture was stirred at r.t. for 24 h. The reaction mixture was finally purified by column chromatography (silica gel, hexanes–EtOAc). Method B. To a 6-dram vial containing the starting alkyne (0.3 mmol) was added 95% EtOH (4.0 mL). The appropriate sodium halide (5.0 equiv) and CuSO4·5 H2O (5.0 equiv) were added, and the mixture was stirred at r.t. for 48 h. The mixture was finally purified by column chromatography (silica gel, hexanes–EtOAc). 3-Iodo-1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine (20a) Yellow-brown solid; yield: 93 mg (93%); mp 86–89 °C. 1H NMR (400 MHz, CDCl3): δ = 3.80 (s, 3 H), 7.17 (dd, J = 7.6, 4.4 Hz, 1 H), 7.48–7.54 (m, 5 H), 7.76 (dd, J = 8.0, 1.2 Hz, 1 H), 8.37 (dd, J = 4.4, 1.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 30.56, 56.49, 116.93, 123.69, 128.55, 128.70, 128.97, 129.16, 129.26, 130.69, 131.16, 142.16, 143.98, 148.73. Other characterization data agreed with the previously reported values (See ref. 26).
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