Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar 17;26(6):1692.
doi: 10.3390/molecules26061692.

Pyrrole-Aminopyrimidine Ensembles: Cycloaddition of Guanidine to Acylethynylpyrroles

Olga V Petrova  1 , Arsalan B Budaev  1 , Elena F Sagitova  1 , Igor A Ushakov  1 , Lyubov N Sobenina  1 , Andrey V Ivanov  1 , Boris A Trofimov  1
Affiliations

Pyrrole-Aminopyrimidine Ensembles: Cycloaddition of Guanidine to Acylethynylpyrroles

Olga V Petrova et al. Molecules. .

Abstract

An efficient method for the synthesis of pharmaceutically prospective pyrrole-aminopyrimidine ensembles (in up to 91% yield) by the cyclocondensation of easily available acylethynylpyrroles with guanidine nitrate has been developed. The reaction proceeds under heating (110-115 °C, 4 h) in the KOH/DMSO system. In the case of 2-benzoylethynylpyrrole, the unexpected addition of the formed pyrrole-aminopyrimidine as N- (NH moiety of the pyrrole ring) and C- (CH of aminopyrimidine) nucleophiles to the triple bond is observed.

Keywords: acylethynylpyrroles; aminopyrimidine; cyclocondensation; guanidine.

PubMed Disclaimer

Conflict of interest statement

Authors reports no conflict interests.

Figures

Scheme 1
Scheme 1
Synthesis of pyrrole–aminopyrimidines from pyrrol-2-ylhexynones and guanidine. Previous work [39].
Scheme 2
Scheme 2
Synthesis of 2-acylethynylpyrroles.
Scheme 3
Scheme 3
The reaction of 2-benzoylethynyl-5-phenylpyrrole (1l) with guanidine nitrate.
Figure 1
Figure 1
Synthesis of pyrrole–aminopyrimidine ensembles 3a–v from 2-acylethynylpyrroles 1a–v and guanidine nitrate. Reagents and conditions: (i) guanidine nitrate (0.40 mmol), KOH·0.5H2O (0.60 mmol), DMSO (8 mL), 110–115 °C, 0.5 h; (ii) 2-acylethynylpyrrole (0.40 mmol), 110–115 °C, 4 h.
Scheme 4
Scheme 4
The reaction of 2-benzoylethynylpyrrole 1a with guanidine nitrate.
Scheme 5
Scheme 5
Proposed route of pyrrole–aminopyrimidine ensembles 3 formation.
Scheme 6
Scheme 6
Proposed route of adduct 4a formation.
Scheme 7
Scheme 7
Proposed route of adduct 5a formation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Jones R.A., Bean G.P. The Chemistry of Pyrroles. Academic Press; London, UK: 1977. p. 525.
    1. Bhardwaj V., Gumber D., Abbot V., Dhiman S., Sharma P. Pyrrole: A resourceful small molecule in key medicinal hetero-aromatics. RSC Adv. 2015;5:15233–15266. doi: 10.1039/C4RA15710A. - DOI
    1. Baumann M., Baxendale I.R., Ley S.V., Nikbin N. An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals. Beilstein J. Org. Chem. 2011;7:442–495. doi: 10.3762/bjoc.7.57. - DOI - PMC - PubMed
    1. Koroleva E.V., Gusak K.N., Ignatovich Z.V. Synthesis and applications of 2-aminopyrimidine derivatives as key intermediates in chemical synthesis of biomolecules. Russ. Chem. Rev. 2010;79:655–681. doi: 10.1070/RC2010v079n08ABEH004116. - DOI
    1. Vitaku E., Smith D.T., Njardarson J.T. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J. Med. Chem. 2014;57:10257–10274. doi: 10.1021/jm501100b. - DOI - PubMed

LinkOut - more resources