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. 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.

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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.
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