Pyrrole–aminopyrimidine ensembles: Cycloaddition of guanidine to acylethynylpyrroles

Article abstract of DOI:10.3390/molecules26061692

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

Full text of DOI:10.3390/molecules26061692

molecules
Article
Pyrrole–Aminopyrimidine Ensembles: Cycloaddition of
Guanidine to Acylethynylpyrroles
Olga V. Petrova, Arsalan B. Budaev, Elena F. Sagitova, Igor A. Ushakov, Lyubov N. Sobenina, Andrey V. Ivanov
and Boris A. Trofimov *
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Street,
664033 Irkutsk, Russia; ol_petr@irioch.irk.ru (O.V.P.); arsalan@irioch.irk.ru (A.B.B.); sagitova@irioch.irk.ru (E.F.S.);
igor-papa71@mail.ru (I.A.U.); sobenina@irioch.irk.ru (L.N.S.); ivanov@irioch.irk.ru (A.V.I.)
* Correspondence: boris_trofimov@irioch.irk.ru; Tel.: +7-(3952)-41-93-46
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; guanidine; cyclocondensation; aminopyrimidine
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Citation: Petrova, O.V.; Budaev,
1. Introduction
A.B.; Sagitova, E.F.; Ushakov, I.A.;
One of the main trends in modern organic chemistry is the synthesis of heterocyclic en-
Sobenina, L.N.; Ivanov, A.V.;
sembles, each of the fragments of which has promising biological activity. These ensembles
include, in particular, pyrrole–pyrimidines, which combine two of the most fundamental
life-supporting molecular systems in their molecule and represent privileged objects for
drug design.
Trofimov, B.A. Pyrrole–
Aminopyrimidine Ensembles:
Cycloaddition of Guanidine to
Acylethynylpyrroles. Molecules 2021,
26, 1692. https://doi.org/
The pyrrole core is a key structural motif in a plethora of natural products such
10.3390/molecules26061692
as chlorophyll, hemoglobin, bile pigments, vitamin B12, and others [
derivatives are also important components of a number of pharmaceuticals and new
compounds with a variety of pharmacological activity [ ]. Basing on pyrroles, anti-
tumor agent sunitinib, the anti-hyperlipidemic atorvastatin [ ], neotropic aloracetam [ ],
], and nonsteroidal anti-inflammatory agent tolmetin [
1]. Pyrrole and its
Academic Editor: Jacek Nycz
2,3
2,
3
2
Received: 26 February 2021
Accepted: 12 March 2021
Published: 17 March 2021
antipsychotic elopiprazole [
2
2]
were created.
The pyrimidine ring is a main structural moiety of nucleic acids, vitamins, coenzymes,
and uric acid [ ], as well as the frequent scaffold in medicines [ ]. According to the liter-
ature data, the presence of the amino group in pyrimidine enhances its pharmacological
properties [ ]. The aminopyrimidine ring is a fragment of nucleotide bases in DNA and
RNA, which are important components of living cells [ ]. Substituted 2-aminopyrimidines
exhibit cardiotonic [ ], antitrypanosomal and antiplasmodial [ ], antimicrobial [ 11
and antiplatelet aggregation activity [12]. They are also ligands of histamine H4 and H3
receptors [13 14], inhibitors of IRAK4 (interleukin-1 receptor-associated kinase 4) [15],
4
4,5
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with regard to jurisdictional claims in
published maps and institutional affil-
iations.
5
4
6
7
8– ]
,
the vascular endothelial growth factor inhibitor [16], serine/threonine protein kinase in-
hibitors, candidates for treating drug-resistant tuberculosis [17]. There are numerous
Copyright:
© 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
2-aminopyrimidine-tailored pharmaceuticals [18
,19] including antiviral (Lamivudine [18],
Etravirine and Rilpivirine [19]), anti-cancer (Imatinib [18
,
19], Erlotinib, Lapatinib [18], Nilo-
tinib, Dabrafenib, Ceritinib, Osimertinib, and Pazopanib [19]), anxiolytic (Buspirone) [19],
hypolipidemic (Rosuvastatin) [18], etc.
2-Aminopyrimidines with pyrrole substituents represent molecular systems, which
could be particularly promising for medicinal chemistry, due to the presence of two
Molecules 2021, 26, 1692. https://doi.org/10.3390/molecules26061692
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 1692
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pharmacologically active units in their structure. This assumption is supported by the fact
that among pyrrole–aminopyrimidines there are inhibitors of JAK2 (Janus kinase 2) [20
,21],
Cdc7 kinase (Cell division cycle 7-related protein kinase) [22 23], and Polo-like kinase 1 [24],
,
as well as representatives with prominent antifungal activity against Aspergillus niger [25].
The fact that pyrrole–aminopyrimidines have a great potential for cancer treatment [20–24]
generates interest in the targeted synthesis of these derivatives.
Few known syntheses of pyrrole–aminopyrimidine ensembles are based on three
approaches. The first is to build up the pyrrole moiety on aminopyrimidines starting from
1-(2-aminopyrimidin-4-yl)-2-bromoethanones [20,23,26].
The second approach involves construction of the aminopyrimidine ring via the
addition of guanidine to pyrroles with ethylenic substituents. Among the latter are 3-
dimethylamino-2-(pyrrole-2-carbonyl)acrylonitrile [27], benzylidene acetyl pyrrole [28],
pyrrolylenaminone [20], pyrrolyl vinamidinium salts [29].
The third approach to the synthesis of pyrrole–aminopyrimidine ensembles is the
coupling of halopyrimidines with pyrroles under Buchwald–Hartwig conditions [21] or
their boronate derivative under Suzuki reaction conditions and PdCl2(dppf) catalysis [21].
(Pyrrol-2-yl)-2-aminopyrimidine was also obtained from N-Boc-pyrrole, which was depro-
tonated upon treatment with LiTMP (Lithium tetramethylpiperidide) and, after subsequent
transmetalation (using ZnCl2 TMEDA) and coupling with 2,4-dichloropyrimidine, was
·
transformed into N-Boc-2-(2-chloro-4-pyrimidyl)pyrrole [30]. The chloro group of the latter
was substituted with allylamine, and after subsequent cleavage of the allyl group under
classical conditions afforded the target product.
The most common approach to the synthesis of aminopyrimidines, i.e., cycloconden-
sation of alkynones with guanidine [31
pyrrole–aminopyrimidines.
–38], was not always applied to the preparation of
To our knowledge, there is only one work concerning the synthesis of pyrrole–
aminopyrimidines from guanidine and pyrrol-2-ylhexynones [39], obtained by glyoxylation
of N-methyl- and N-benzylpyrroles with oxalyl chloride and subsequent Pd/Cu-catalyzed
decarbonylative alkynylation of the pyrrolylglyoxylyl chlorides with hexyne (Scheme 1).
Scheme 1. Synthesis of pyrrole–aminopyrimidines from pyrrol-2-ylhexynones and guanidine. Previ-
ous work [39].
This is likely due to the fact that, until recently, alkynones with pyrrole substituents
were difficult to obtain. Such compounds have become readily available owing to the
discovery of the cross-coupling reaction of pyrroles with acylhaloacetylenes in the medium
of solid oxides and metal salts [40–42], and was widely used by us in the synthesis of
diverse pyrrole heterocyclic ensembles and fused heterocyclic systems [42].
2. Results and Discussion
In the present paper, we have developed an effective method for the assembly of
pyrrole–aminopyrimidines via the reaction of 2-acylethynylpyrroles 1a–v, obtained accord-
ing to Scheme 2, with guanidine nitrate.

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Scheme 2. Synthesis of 2-acylethynylpyrroles.
To commence the investigation, 2-benzoylethynyl-5-phenylpyrrole (1l, 1.0 equiv) was
refluxed with guanidine nitrate ( , 1.0 equiv) in the presence of Na2CO3 (2.0 equiv) in
2
MeCN for 4 h (Scheme 3). These conditions are known [36] to be effective for the synthesis
of 2-aminopyrimidines from alkynones and guanidine. However, in our case, the yield of
the target pyrrole–aminopyrimidine 3l did not exceed 11%.
Scheme 3. The reaction of 2-benzoylethynyl-5-phenylpyrrole (1l) with guanidine nitrate.
Therefore, in order to find optimal reaction conditions for the construction of pyrrole–
aminopyrimidine ensembles, we screened combinations of bases, solvents, reagent ratio,
temperature, and reaction time using the same pyrrole 1l and guanidine nitrate as reference
reagents (Scheme 3, Table 1). The reaction was carried out open to air and controlled by the
1H-NMR spectroscopy.
The results showed that the yield of the pyrrole–aminopyrimidine 3l depended on the
nature of the base, solvent and other reaction conditions. As seen from Table 1, among the
bases tested, only KOH, Cs2CO3 and K3PO4 demonstrated a good activity (entries 11, 12,
16 and 18–22). However, in the case of the latter two bases, a significant excess of both the
base and guanidine should be used to achieve a preparatively acceptable yield of aminopy-
rimidine 3l. As the solvents, MeCN, t-BuOH, THF (tetrahydrofuran) and DMSO (dimethyl
sulfoxide) were checked and it was established that yields of aminopyrimidine 3l reached a
maximum, when the reaction was carried out in DMSO in the presence of KOH (entry 22).
Using this catalytic system, the effect of the ratio of reagents and reaction conditions on
the yield of the target product was examined. Finally, the desired aminopyrimidine 3l was
obtained in 89% isolated yield, when 2-benzoylethynyl-5-phenylpyrrole (1l), guanidine
and KOH in a ratio of 1:1:1.5 were reacted in DMSO at 110–115 ◦C for 4 h (entry 22).

Molecules 2021, 26, 1692
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Table 1. Effect of reaction conditions on the synthesis of pyrrole–aminopyrimidine ensemble 3l from
2-benzoylethynyl-5-phenylpyrrole (1l) and guanidine nitrate 2.
Ratio 1l/2/Base,
mol
Content of 3l in the
◦
Entry
Base
Solvent
T, C
Time, h
Reaction Mixture, % a
11 b
68 c
1
2
Na2CO3 MeCN
1/1/1.5
1/1/1.5
82
82
4
4
KOH
Et3N
MeCN
t-
BuOH
t-
BuOH
THF
THF
THF
THF
THF
THF
3
1/1/1.5
82
4
0
0 d
4
DBU
1/1/1.5
82
4
5
6
7
8
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K3PO4
K3PO4
K3PO4
K3PO4
KOH
1/2/1.5
1/2/2
1/2/4
1/6/12
1/10/20
1/10/20
1/10/20
1/10/20
1/5/6
1/5/6
1/5/6
1/5/6
1/1/2
66
66
66
66
66
66
66
66
20
65–70
85–90
85–90
20
70–75
110–
115
110–
115
110–
115
110–
115
4
14
18
4
4
7
12
18
16
4
4
6
0
0
15
62
68
74
89
91
0
traces
59 e
80 e
0
9
10
11
12
13
14
15
16
17
18
THF
THF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
1
13
KOH
1/2/4
93
19
20
21
22
KOH
KOH
KOH
KOH
DMSO
DMSO
DMSO
DMSO
1/1/2
4
4
4
4
100 (77)
1/1/1
95 (82)
1/1.5/2
1/1/1.5
100 (88)
100 (89)
a The isolated yield of the product is indicated in parentheses; b conversion of pyrrole 1l
is 89%; c content of unidentified products is ~20%; d mixture of unidentified compounds;
e strong tarring of the reaction mixture. THF: tetrahydrofuran; DMSO: dimethyl sulfoxide.
Having established near to optimal reaction conditions, we have further investigated
the substrate scope of this reaction (Figure 1). The experiments revealed that the reaction of
2-acylethynylpyrroles 1a–v with guanidine nitrate in these conditions proceeded efficiently
and selectively thus offering a short-cut to pyrrole–aminopyrimidine ensembles 3a–v in
good to high yields.
As follows from Figure 1, the reaction tolerates different (aliphatic, cycloaliphatic, aro-
matic and vinyl) substituents in the pyrrole ring, i.e., the synthesis has quite general character.
The moderate yield of aminopyrimidine 3a is due to the formation of side products: 3-
[2-(2-amino-6-phenylpyrimidin-4-yl)-1H-pyrrol-1-yl]-1-phenyl-3-(1H-pyrrol-2-yl)prop-2-en-
1-one (4a, 13%) and 3-[2-amino-4-phenyl-6-(1H-pyrrol-2-yl)pyrimidin-5-yl]-1-phenyl-3-(1H-
pyrrol-2-yl)prop-2-en-1-one (5a, 8%) (Scheme 4). Using the reagents ratio of 1a
:2:KOH
= 1:2:2.5 allowed to increase the yield of the aminopyrimidine 3a to 40%, the content of
adduct 4a in this case in the reaction mixture did not exceed 6% and adduct
5 was not
detected at all.
The formation of pyrrole–aminopyrimidine 3, probably, proceeds as nucleophilic ad-
dition of guanidine to the triple bond of 2-acylethynylpyrrole , intramolecular cyclization
of adduct with participation of the carbonyl group and elimination of water from the
intermediate 3,4-dihydropyrimidin-4-ol B (Scheme 5).
1
A

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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. The reaction of 2-benzoylethynylpyrrole 1a with guanidine nitrate.

Molecules 2021, 26, 1692
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Scheme 5. Proposed route of pyrrole–aminopyrimidine ensembles 3 formation.
The formation of compound
of adduct , existing in the reaction mixture due to the deprotonating ability of the
super-base KOH/DMSO system, to the starting 2-acylethynylpyrrole 1a (Scheme 6).
4 likely involves the nucleophilic addition of N-anion
C
A
Scheme 6. Proposed route of adduct 4a formation.
Adduct
rimidine ring to the triple bond of pyrrole 1a (Scheme 7).
A control experiment showed that adducts and
addition of aminopyrimidine 3a to the triple bond of the starting 2-acylethynylpyrrole 1a.
5, is, probably, a result of the attack of carbocentered anion D of the aminopy-
4
5 did not result from the direct
Scheme 7. Proposed route of adduct 5a formation.

Molecules 2021, 26, 1692
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3. Materials and Methods
3.1. General Procedures
1H, 13C, 15N and 19F NMR spectra (Nuclear magnetic resonance spectra) were recorded
in CDCl3 and DMSO-d6 using a Bruker Avance 400 NMR spectrometer (Germany, 400.13,
100.6, 40.5 and 376.5 MHz, respectively). The assignment of signals in the 1H NMR spectra
was made using COSY and NOESY experiments. Resonance signals of carbon atoms were
assigned based on 1H-13C HSQC and 1H-13C HMBC experiments. The values of the
δ
15N
were measured through the 2D 1H-15N HMBC experiment. The chemical shifts (
δ) are given
in ppm and referenced to residual solvent: 7.27 ppm (CDCl3) and 2.50 ppm (DMSO-d6)
for 1H, 77.1 ppm (CDCl3) and 39.5 ppm (DMSO-d6) for 13C and 15N-MeNO2 (0.0 ppm),
respectively. The 19F chemical shifts were referenced to CFCl3. Coupling constants in hertz
(Hz) were measured from one-dimensional spectra and multiplicities were abbreviated
as following: br (broad), s (singlet), d (doublet), dd (doublet of doublets), m (multiplet).
1
The chemical shifts were recorded in ppm, coupling constants (J) in Hz. H-,13C- and 19F-
NMR spectra of all new synthetized molecules available in Supplementary Materials.
Infrared (IR) spectra were obtained on a Varian 3100 IF-IR spectrometer (Germany;
400–4000 cm−1, KBr pellets or films). The (C, H, N) microanalyses were performed on a
Flash EA 1112 CHNS-O/MAS (CHN Analyzer, Thermo Fisher Scientific, Monza, Italy)
instrument. The chlorine and sulfur content was determined by using the titrimetric
method. Fluorine content was determined on a SPECOL 11 (Carl Zeiss, Jena, Germany)
spectrophotometer. Melting points (uncorrected) were determined with melting point
SMP50 (Stone, Staffordshire, UK).
3.2. Synthetic Procedures
2-Acylethynylpyrroles 1a,f
enes accordingly to methodology [40
rroles 1a,f l,n were given in [40 43
tained accordingly to the following procedure:
–
l,n
–
–
r
were obtained from pyrroles and 2-acylbromoacetyl-
42]. Physico-chemical characteristics 2-acylethynylpy-
47]. 2-Acylethynylpyrroles 1b,c e,m,s were ob-
–
–
r
,
–
–
–v
The corresponding pyrrole (1 mmol) and acyl(bromo)acetylene (1 mmol) were care-
fully ground in a porcelain mortar with alumina [10-fold amount by weight of combined
mass of pyrrole and acyl(bromo)acetylene] at 20–25 ◦C for 5 min. The reaction mixture
was left for 2 h. Then the mixture was subjected to column chromatography (alumina,
eluent–n-hexane/diethyl ether, gradient 1:0–1:1); this afforded pure 2-acylethynylpyrroles
1b,c–e,m,s–v.
3-(1-Methyl-1H-pyrrol-2-yl)-1-phenylprop-2-yn-1-one (1b): 182 mg (87%), yellow crystals, m.p.
59 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ
: 8.20–8.18 (m, 2H, H-2,6, COPh), 7.64–7.61 (m, 1H,
H-4, COPh), 7.54–7.50 (m, 2H, H-3,5, COPh), 6.86–6.85 (m, 2H, H-3,5, pyrrole), 6.21–6.20
m, 1H, H-4, pyrrole), 3.85 (s, 3H, NMe); 13C-NMR (100.6 MHz, CDCl3)
: 176.9, 136.7,
133.4, 128.8 (2C), 128.3 (2C), 127.6, 120.9, 112.5, 109.4, 94.7, 87.4, 34.6; IR (KBr) : 3114, 2936,
(
δ
ν
2362, 2168, 1630, 1448, 1326, 1255, 1173, 1035, 998, 729, 695, 649. Anal. Calcd. for C14H11NO:
C, 80.36%; H, 5.30%; N, 6.69%. Found: C, 80.12%; H, 5.03%; N, 6.37%.
3-(1-Benzyl-1H-pyrrol-2-yl)-1-phenylprop-2-yn-1-one (1c): 271 mg (95%), light yellow crystals,
m.p. 111 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.07–8.04 (m, 2H, H-2,6, COPh), 7.61–7.57
(m, 1H, H-4, COPh), 7.47–7.43 (m, 2H, H-3,5, COPh), 7.39–7.35 (m, 2H, H-3,5 Ph), 7.33–7.27
(m, 1H, H-4, Ph), 7.23–7.21 (m, 2H, H-2,6, Ph), 6.92–6.91 (m, 2H, H-3,5, pyrrole), 6.28–6.27
(m, 1H, H-4, pyrrole), 5.34 (s, 2H, CH2); 13C-NMR (100.6 MHz, CDCl3)
δ
: 177.4, 137.1, 133.7,
129.2 (2C), 129.0 (2C), 128.9, 128.6 (2C), 128.0, 127.2 (2C), 126.9, 121.4, 112.9, 110.3, 95.1, 87.3,
51.9; IR (KBr) : 3115, 3061, 3027, 2170, 1612, 1572, 1470, 1445, 1412, 1329, 1308, 1260, 1218,
ν
1165, 1072, 1000, 748, 730, 697, 651. Anal. Calcd. for C20H15NO: C, 84.19%; H, 5.30%; N,
4.91%. Found: C, 84.12%; H, 5.37%; N, 4.87%.
3-(4-Ethyl-5-propyl-1H-pyrrol-2-yl)-1-phenylprop-2-yn-1-one (1d): 125 mg (47%), yellow crys-
tals, m.p. 162 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.57 (br s, 1H, NH), 8.19–8.16 (m, 2H,
H-2,6, Ph), 7.61–7.58 (m, 1H, H-4, Ph), 7.51–7.47 (m, 2H, H-3,5, Ph), 6.74 (d, J = 2.3 Hz,

Molecules 2021, 26, 1692
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1H, H-3, pyrrole), 2.61–2.57 (m, 2H, CH2), 2.47–2.41 (m, 2H, CH2), 1.69–1.60 (m, 2H, CH2),
1.21–1.17 (m, 3H, CH3), 0.99–0.96 (m, 3H, CH3); 13C-NMR (100.6 MHz, CDCl3)
δ
: 177.7,
137.2, 136.2, 133.6, 129.3 (2C), 128.5 (2C), 124.8, 121.2, 107.1, 93.7, 91.5, 28.1, 22.8, 18.8, 15.3,
13.9; IR (KBr) : 3438, 2955, 2867, 2430, 2362, 2160, 1601, 1564, 1473, 1345, 1256, 1164, 1033,
ν
829, 692, 645. Anal. Calcd. for C18H19NO: C, 81.47%; H, 7.22%; N, 5.28%. Found: C, 81.23%;
H, 7.08%; N, 5.19%.
3-(5-Butyl-4-propyl-1H-pyrrol-2-yl)-1-phenylprop-2-yn-1-one (1e): 150 mg (51%), yellow crys-
◦
tals, m.p. 62–63 C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.57 (br s, 1H, NH), 8.19–8.17 (m, 2H,
H-2,6, Ph), 7.61–7.58 (m, 1H, H-4, Ph), 7.51–7.48 (m, 2H, H-3,5, Ph), 6.71 (d, J = 2.3 Hz, 1H,
H-3, pyrrole), 2.62–2.59 (m, 2H, CH2), 2.40–2.36 (m, 2H, CH2), 1.61–1.55 (m, 4H, 2CH2),
1.41–1.33 (m, 2H, CH2), 0.98–0.93 (m, 6H, 2CH3); 13C-NMR (100.6 MHz, CDCl3)
δ
: 177.7,
137.1, 137.0, 133.4, 129.2 (2C), 128.4 (2C), 122.9, 121.9, 106.9, 93.9, 92.4, 31.6, 27.6, 25.8, 24.0,
22.4, 13.9, 13.7; IR (film) : 3298, 2956, 2928, 2865, 2377, 2157, 1614, 1567, 1469, 1318, 1241,
ν
1164, 1040, 976, 823, 698, 646. Anal. Calcd. for C20H23NO: C, 81.87%; H, 7.90%; N, 4.77%.
Found: C, 81.64%; H, 7.55%; N, 4.70%.
1-(Furan-2-yl)-3-(5-phenyl-1H-pyrrol-2-yl)prop-2-yn-1-one (1m): 154 mg (59%), red crystals,
m.p. 164 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 9.15 (br s, 1H, NH), 7.69–7.68 (m, 1H, H-5,
furyl), 7.57–7.55 (m, 2H, H-2,6, Ph), 7.45–7.39 (m, 3H, H-3,4,5, Ph), 7.34–7.30 (m, 1H, H-3,
furyl), 6.91 (dd, J = 2.5, 3.8 Hz, 1H, H-3, pyrrole), 6.60–6.57 (m, 2H, H-4, furyl, H-4, pyrrole);
13C-NMR (100.6 MHz, CDCl3)
δ: 164.7, 153.2, 147.7, 137.7, 131.0, 129.2 (2C), 128.1, 124.8
(2C), 122.6, 120.1, 112.7, 110.7, 108.4, 92.5, 88.1; IR (KBr) : 3311, 2172, 1661, 1608, 1550, 1457,
ν
1388, 1258, 1160, 1043, 972, 910, 760, 695, 593. Anal. Calcd. for C17H11NO2: C, 78.15%; H,
4.24%; N, 5.36%. Found: C, 78.04%; H, 4.13%; N, 5.22%.
3-(4,5-Diphenyl-1-vinyl-1H-pyrrol-2-yl)-1-phenylprop-2-yn-1-one (1s): 291 mg (78%), yellow
crystals, m.p. 106 ◦C; 1H-NMR (400.13 MHz, CDCl3)
(
δ
: 8.21–8.20 (m, 2H, Ph), 7.65–7.62
m, 1H, Ph), 7.55–7.51 (m, 2H, Ph), 7.42–7.40 (m, 3H, Ph), 7.33–7.31 (m, 2H, Ph), 7.23–7.15
(m, 6H, Ph, H-3, pyrrole), 6.79 (dd, J = 9.0, 15.8 Hz, 1H, HX), 5.19 (d, J = 15.8 Hz, 1H, HB),
5.67 (d, J = 9.0 Hz, 1H, HA); 13C-NMR (100.6 MHz, CDCl3)
: 177.4, 137.1, 135.3, 134.2,
133.8, 131.0 (2C), 130.9, 130.6, 129.4 (2C), 128.8, 128.7 (2C), 128.6 (2C), 128.4 (2C), 128.1 (2C),
126.5, 125.2, 123.1, 111.9, 108.8, 95.4, 87.8; IR (KBr) : 3060, 2162, 1617, 1575, 1455, 1385,
δ
ν
1310, 1269, 1165, 1008, 821, 767, 697. Anal. Calcd. for C27H19NO: C, 86.84%; H, 5.13%; N,
3.75%. Found: C, 86.61%; H, 5.03%; N, 3.88%.
3-(5-(4-Chlorophenyl)-1-vinyl-1H-pyrrol-2-yl)-1-phenylprop-2-yn-1-one (1t): 289 mg (87%), yel-
low crystals, m.p. 100–102 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.19–8.17 (m, 2H, H-2,6,
COPh), 7.64–7.61 (m, 1H, H-4, COPh), 7.54–7.50 (m, 2H, H-3,5, COPh), 7.41–7.40 (m, 4H,
H-2,3,5,6, 4-Cl-C6H4), 7.02 (d, J = 3.9 Hz, 1H, H-3, pyrrole), 6.88 (dd, J = 8.8, 15.8 Hz, 1H,
HX), 6.36 (d, J = 3.9 Hz, 1H, H-4, pyrrole), 5.69 (d, J = 15.8 Hz, 1H, HB), 5.32 (d, J = 8.8 Hz,
1H, HA); 13C-NMR (100.6 MHz, CDCl3)
δ: 177.4, 137.8, 137.0, 134.4, 133.9, 130.7, 130.2 (2C),
129.9, 129.4 (2C), 128.9 (2C), 128.6 (2C), 123.4, 113.6, 111.7, 110.3, 95.4, 87.7; IR (film) : 3063,
ν
2236, 2172, 1630, 1458, 1313, 1259, 1093, 993, 780, 698. Anal. Calcd. for C21H14NOCl: C,
76.02%; H, 4.25%; Cl, 10.68%; N, 4.22%. Found: C, 75.91%; H, 4.11%; Cl, 10.57%; N, 4.37%.
3-(5-(2-Fluorophenyl)-1-vinyl-1H-pyrrol-2-yl)-1-(furan-2-yl)prop-2-yn-1-one (1u): 226 mg (74%),
yellow crystals, m.p. 55–57 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 7.68–7.67 (m, 1H, H-5,
furyl), 7.44–7.35 (m, 3H, H-4,5,6, 2-F-C6H4), 7.25–7.15 (m, 2H, H-3, 2-F-C6H4, H-3, furyl),
7.01 (d, J = 3.8 Hz, 1H, H-3, pyrrole), 6.89 (dd, J = 8.9, 15.8 Hz, 1H, HX), 6.60 (dd, J = 1.8,
3.7 Hz, 1H, H-4, furyl), 6.37 (d, J = 3.8 Hz, 1H, H-4, pyrrole), 5.57 (d, J = 15.8 Hz, 1H, HB),
5.14 (d, J = 8.9 Hz, 1H, HA); 13C-NMR (100.6 MHz, CDCl3) : 164.1, 159.3 (d, 1JCF = 249.2
δ
Hz, C-2, 2-F-C6H4), 152.8, 147.5, 132.5, 131.5, 130.5 (d, 3JCF = 8.3 Hz, C-4, 2-F-C6H4), 130.2
d, 4JCF = 2.4 Hz, C-5, 2-F-C6H4), 124.1 (d, 3JCF = 3.7 Hz, C-6, 2-F-C6H4), 123.0, 119.8, 119.1
(d, 2JCF = 14.9 Hz, C-1, 2-F-C6H4), 115.9 (d, 2JCF = 21.6 Hz, C-3, 2-F-C6H4), 112.8, 112.5 (2C),
108.0, 94.1, 86.3; 19F-NMR (376.5 MHz, CDCl3)
112.8. IR (KBr) : 2925, 2361, 2175, 1626,
(
δ
:
−
ν

Molecules 2021, 26, 1692
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1458, 1394, 1280, 1037, 759. Anal. Calcd. for C19H12FNO2: C, 74.75%; H, 3.96%; F, 6.22%; N,
4.59%. Found: C, 74.68%; H, 3.77%; F, 6.18%; N, 4.63%.
3-(5-(2-Fluorophenyl)-1-vinyl-1H-pyrrol-2-yl)-1-(thiophen-2-yl)prop-2-yn-1-one (1v): 260 mg
(81%), yellow crystals, m.p. 67–69 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 7.94 (dd, J = 1.0,
3.8 Hz, 1H, H-3, thienyl), 7.72 (dd, J = 1.0, 4.9 Hz, 1H, H-5, thienyl), 7.44–7.38 (m, 2H, H-4,6,
2-F-C6H4), 7.25–7.15 (m, 3H, H-3,5, 2-F-C6H4, H-4, thienyl), 7.02 (d, J = 3.8 Hz, 1H, H-3,
pyrrole), 6.90 (dd, J = 8.8, 15.8 Hz, 1H, HX), 6.39 (d, J = 3.8 Hz, 1H, H-4, pyrrole), 5.53
(
d, J = 15.8 Hz, 1H, HB), 5.16 (d, J = 8.8 Hz, 1H, HA); 13C-NMR (100.6 MHz, CDCl3)
δ: 168.9,
159.4 (d, 1JCF = 249.2 Hz, C-2, 2-F-C6H4), 144.7, 134.6, 134.2, 132.4, 131.5 (d, 4JCF = 2.9 Hz,
C-5, 2-F-C6H4), 130.5 (d, 3JCF= 7.9 Hz, C-4, 2-F-C6H4), 130.3, 128.2, 124.2 (d, 3JCF = 3.7 Hz,
C-6, 2-F-C6H4), 123.0, 119.2 (d, 2JCF = 14.5 Hz, C-1, 2-F-C6H4), 115.9 (d, 2JCF = 22.0 Hz, C-3,
2-F-C6H4), 112.9, 112.7, 108.5, 94.2, 85.9; 19F-NMR (376.5 MHz, CDCl3)
ν
δ:
−
112.6. IR (KBr)
: 2925, 2859, 2361, 2170, 1603, 1462, 1409, 1267, 1226, 1045, 966, 760, 716. Anal. Calcd.
for C19H12FNOS: C, 71.01%; H, 3.76%; F, 5.91%; N, 4.36%; S, 9.98%. Found: C, 70.88%; H,
3.66%; F, 5.70%; N, 4.45%; S, 9.61%.
General Procedure for the pyrrole–aminopyrimidine ensembles 3a–v synthesis: A mixture of
guanidine nitrate (49 mg, 0.40 mmol) and KOH 0.5H2O (39 mg, 0.60 mmol) was stirred
·
in DMSO (8 mL) at 110–115 ◦C for 30 min. Then the 2-acylethynylpyrrole
1 (0.40 mmol)
was added, and the mixture was stirred for 4 h. After cooling to 20–25 ◦C, the reaction
mixture was diluted with saturated solution of NaCl (40 mL). The precipitate was filtered
off, washed with water (3
were purified by column chromatography (SiO2, eluent–n-hexane/diethyl ether, gradient
×
20 mL) and dried. The obtained pyrrole–aminopyrimidines
1:0–0:1).
4-Phenyl-6-(1H-pyrrol-2-yl)pyrimidin-2-amine (3a): 24 mg (25%), beige crystals, m.p. 96 ◦C;
1H-NMR (400.13 MHz, CDCl3)
δ
: 9.75 (br s, 1H, NH), 8.04–8.02 (m, 2H, H-2,6, Ph), 7.50–
7.49 (m, 3H, H-3,4,5, Ph), 7.28 (s, 1H, H-5, pyrimidine), 6.95–6.92 (m, 2H, H-3,5, pyrrole),
6.35–6.34 (m, 1H, H-4, pyrrole), 5.13 (br s, 2H, NH2); 13C-NMR (100.6 MHz, CDCl3)
: 165.5
δ
(C-6, pyrimidine), 163.3 (C-2, pyrimidine), 158.3 (C-4, pyrimidine), 137.8 (C-1, Ph), 130.4
(C-4, Ph), 129.9 (C-2, pyrrole), 128.8 (C-3,5, Ph), 127.1 (C-2,6, Ph), 121.5 (C-5, pyrrole), 110.8
(C-4, pyrrole), 110.5 (C-3, pyrrole), 101.9 (C-5, pyrimidine); 15N-NMR (40.5 MHz, CDCl3)
δ
:
−
304.9 (NH2),
−
233.8 (NH),
−
157.3 (N-1),
−
148.9 (N-3); IR (KBr) ν: 3464, 3418, 3350,
3175, 1634, 1582, 1555, 1534, 1468, 1454, 1423, 1359, 1257, 1227, 1112, 1035, 997, 911, 880, 773,
732, 701. Anal. Calcd. for C14H12N4: C, 71.17%; H, 5.12%; N, 23.71%. Found: C, 70.83%; H,
4.74%; N, 23.45%.
4-(1-Methyl-1H-pyrrol-2-yl)-6-phenylpyrimidin-2-amine (3b): 81 mg (81%), beige crystals, m.p.
129 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.03–8.01 (m, 2H, H-2,6, Ph), 7.49–7.48 (m, 3H,
H-3,4,5, Ph), 7.29 (s, 1H, H-5, pyrimidine), 6.85–6.84 (m, 1H, H-5, pyrrole), 6.79–6.78 (m,
1H, H-3, pyrrole), 6.21–6.20 (m, 1H, H-4, pyrrole), 5.07 (br s, 2H, NH2), 4.08 (s, 3H, NMe);
13C-NMR (100.6 MHz, CDCl3)
δ: 165.1, 163.0, 160.6, 138.8, 130.4, 130.2, 128.7 (2C), 128.3,
127.0 (2C), 113.4, 108.2, 104.4, 37.7; IR (KBr) : 3478, 3319, 3199, 3059, 2956, 1628, 1570, 1528,
ν
1487, 1455, 1433, 1381, 1345, 1216, 1117, 1090, 1057, 838, 802, 766, 736, 694, 644. Anal. Calcd.
for C15H14N4: C, 71.98%; H, 5.64%; N, 22.38%. Found: C, 71.80%; H, 5.48%; N, 22.31%.
4-(1-Benzyl-1H-pyrrol-2-yl)-6-phenylpyrimidin-2-amine (3c): 107 mg (82%), light yellow crys-
◦
1
tals, m.p. 112–114 C; H-NMR (400.13 MHz, CDCl3) δ: 7.99–7.97 (m, 2H, H-2,6, Ph),
7.47–7.46 (m, 3H, H-3,4,5, Ph), 7.31–7.26 (m, 3H, H-3,5, CH2Ph, H-5, pyrimidine), 7.24–7.20
(m, 1H, H-4, CH2Ph), 7.11–7.09 (m, 2H, H-2,6, CH2Ph), 6.92–6.91 (m, 1H, H-5, pyrrole),
6.89–6.88 (m, 1H, H-3, pyrrole), 6.29–6.28 (m, 1H, H-4, pyrrole), 5.82 (s, 2H, CH2), 4.97 (br s,
2H, NH2); 13C-NMR (100.6 MHz, CDCl3)
δ
: 165.1, 162.9, 160.4, 139.5, 138.0, 130.2, 130.1,
128.7 (2C), 128.6 (2C), 128.0, 127.2, 127.0 (2C), 126.7 (2C), 113.9, 108.9, 104.5, 52.6; IR (KBr)
: 3493, 3319, 3197, 3113, 3023, 2926, 1625, 1569, 1537, 1479, 1453, 1430, 1407, 1359, 1229,
ν
1114, 1087, 1025, 834, 802, 769, 739, 720, 694, 643. Anal. Calcd. for C21H18N4: C, 77.28%; H,
5.56%; N, 17.17%. Found: C, 77.20%; H, 5.49%; N, 17.23%.

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4-(4-Ethyl-5-propyl-1H-pyrrol-2-yl)-6-phenylpyrimidin-2-amine (3d): 103 mg (84%), yellow
◦
1
crystals, m.p. 162 C; H-NMR (400.13 MHz, CDCl3)
(
(
δ
: 9.19 (br s, 1H, NH), 8.02–8.01
m, 2H, H-2,6, Ph), 7.48–7.47 (m, 3H, H-3,4,5, Ph), 7.20 (s, 1H, H-5, pyrimidine), 6.75
d, J = 2.2 Hz, 1H, H-3, pyrrole), 4.95 (br s, 2H, NH2), 2.61–2.57 (m, 2H, CH2), 2.49–2.44
(m, 2H, CH2), 1.69–1.64 (m, 2H, CH2), 1.24–1.20 (m, 3H, CH3), 1.00–0.96 (m, 3H, CH3);
13C-NMR (100.6 MHz, CDCl3)
: 165.0, 163.2, 158.1, 138.1, 133.2, 130.1, 128.7 (2C), 127.1,
127.0 (2C), 124.6, 110.7, 101.3, 28.0, 23.1, 19.0, 15.6, 13.9; IR (KBr) : 3483, 3307, 3184, 2959,
δ
ν
2927, 2867, 1631, 1589, 1566, 1536, 1501, 1458, 1420, 1370, 1324, 1237, 1188, 1072, 1006, 920,
824, 768, 696, 642. Anal. Calcd. for C19H22N4: C, 74.48%; H, 7.24%; N, 18.29%. Found: C,
74.31%; H, 7.11%; N, 17.98%.
4-(5-Butyl-4-propyl-1H-pyrrol-2-yl)-6-phenylpyrimidin-2-amine (3e): 122 mg (91%), yellow
crystals, m.p. 98–99 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 9.19 (br s, 1H, NH), 8.03–8.00
(
m, 2H, H-2,6, Ph), 7.48–7.46 (m, 3H, H-3,4,5, Ph), 7.19 (s, 1H, H-5, pyrimidine), 6.72 (d, J =
2.2 Hz, 1H, H-3, pyrrole), 4.98 (br s, 2H, NH2), 2.62–2.58 (m, 2H, CH2), 2.43–2.39 (m, 2H,
CH2), 1.67–1.57 (m, 4H, 2CH2), 1.44–1.35 (m, 2H, CH2), 1.00–0.93 (m, 6H, 2CH3); 13C-NMR
(100.6 MHz, CDCl3)
122.8, 111.4, 101.3, 32.0, 28.0, 25.7, 24.3, 22.6, 14.1, 13.9; IR (KBr)
δ
: 164.9, 163.2, 158.1, 138.1, 133.9, 130.1, 128.7 (2C), 127.0, 126.9 (2C),
: 3484, 3450, 3311, 3191,
ν
2954, 2926, 2863, 1635, 1588, 1565, 1535, 1500, 1459, 1421, 1370, 1333, 1231, 1188, 1073, 1008,
919, 812, 766, 696, 644. Anal. Calcd. for C21H26N4: C, 75.41%; H, 7.84%; N, 16.75%. Found:
C, 75.34%; H, 7.63%; N, 16.51%.
4-Phenyl-6-(4,5,6,7-tetrahydro-1H-indol-2-yl)pyrimidin-2-amine (3f): 95 mg (82%), dark orange
◦
1
crystals, m.p. 100–102 C; H-NMR (400.13 MHz, CDCl3)
8.01 (m, 2H, H-2,6, Ph), 7.48–7.47 (m, 3H, H-3,4,5, Ph), 7.20 (s, 1H, H-5, pyrimidine), 6.68
d, J = 2.0 Hz, 1H, H-3, pyrrole), 5.03 (br s, 2H, NH2), 2.62–2.55 (m, 4H, CH2-4,7), 1.84–1.79
(m, 4H, CH2-5,6); 13C-NMR (100.6 MHz, CDCl3)
: 165.0, 163.1, 158.3, 138.0, 132.2, 130.2,
128.7 (2C), 127.8, 127.0 (2C), 120.2, 110.0, 101.4, 23.7, 23.1, 22.9, 22.8; IR (KBr) : 3404, 3311,
δ: 9.32 (br s, 1H, NH), 8.03–
(
δ
ν
3195, 3060, 2925, 2848, 1593, 1568, 1535, 1503, 1423, 1346, 1224, 1143, 1005, 830, 808, 770, 695.
Anal. Calcd. for C18H18N4: C, 74.46%; H, 6.25%; N, 19.30%. Found: C, 74.14%; H, 6.05%;
N, 19.18%.
4-(1-Methyl-4,5,6,7-tetrahydro-◦1H-indol-2-yl)-6-phenylpyrimidin-2-amine (3g): 99 mg (81%),
dark yellow crystals, m.p. 182 C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.01–7.99 (m, 2H, H-2,6,
Ph), 7.48–7.47 (m, 3H, H-3,4,5, Ph), 7.23 (s, 1H, H-5, pyrimidine), 6.64 (s, 1H, H-3, pyrrole),
5.04 (br s, 2H, NH2), 3.91 (s, 3H, NMe), 2.63–2.60 (m, 2H, CH2-7), 2.57–2.54 (m, 2H, CH2-4),
1.91–1.86 (m, 2H, CH2-6), 1.79–1.75 (m, 2H, CH2-5); 13C-NMR (100.6 MHz, DMSO-d6)
δ:
163.1, 162.9, 160.3, 137.7, 134.3, 129.9, 128.4 (2C), 128.1, 126.6 (2C), 117.2, 112.0, 101.5, 32.6,
23.1, 22.7, 22.6, 21.7; IR (KBr) : 3489, 3376, 2941, 2915, 2363, 1604, 1585, 1561, 1530, 1495,
ν
1449, 1401, 1369, 1223, 1183, 1147, 826, 803, 772, 695. Anal. Calcd. for C19H20N4: C, 74.97%;
H, 6.62%; N, 18.41%. Found: C, 74.58%; H, 6.41%; N, 18.32%.
4-(2-Furyl)-6-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)pyrimidin-2-amine (3h): 64 mg (54%),
light brown crystals, m.p. 218 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 7.56–7.55 (m, 1H, H-5,
furyl), 7.17 (s, 1H, H-5, pyrimidine), 7.10–7.09 (m, 1H, H-3, furyl), 6.65 (s, 1H, H-3, pyrrole),
6.54 (dd, J = 1.3, 2.0 Hz, 1H, H-4, furyl), 4.99 (br s, 2H, NH2), 3.90 (s, 3H, NMe), 2.61–2.58 (m,
2H, CH2-7), 2.56–2.53 (m, 2H, CH2-4), 1.90–1.84 (m, 2H, CH2-6), 1.78–1.74 (m, 2H, CH2-5);
13C-NMR (100.6 MHz, CDCl3)
δ: 162.7, 160.7, 155.4, 152.6, 144.1, 135.4, 128.7, 118.6, 112.3,
112.1, 110.7, 102.0, 33.0, 23.5, 23.2, 23.0, 22.5; IR (KBr) : 3474, 3298, 3182, 2931, 2839, 1606,
ν
1544, 1533, 1489, 1449, 1398, 1369, 1223, 1183, 1146, 1010, 953, 800, 753, 743. Anal. Calcd. for
C17H18N4O: C, 69.37%; H, 6.16%; N, 19.03%. Found: C, 69.14%; H, 6.05%; N, 19.04%.
4-(1-Benzyl-4,5,6,7-tetrahydro-◦1H-indol-2-yl)-6-phenylpyrimidin-2-amine (3i): 73 mg (48%),
yellow crystals, m.p. 128–129 C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.00–7.98 (m, 2H, H-2,6,
Ph), 7.49–7.48 (m, 3H, H-3,4,5, Ph), 7.33–7.22 (m, 4H, H-5, pyrimidine, H-3,4,5, CH2Ph),
7.06–7.04 (m, 2H, H-2,6, CH2Ph), 6.79 (s, 1H, H-3, pyrrole), 5.82 (s, 2H, CH2Ph), 4.90 (br s,
2H, NH2), 2.63–2.61 (m, 2H, CH2-7), 2.53–2.51 (m, 2H, CH2-4), 1.85–1.78 (m, 4H, CH2-5,6);

Molecules 2021, 26, 1692
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13C-NMR (100.6 MHz, CDCl3)
δ
: 164.6, 162.8, 160.5, 139.7, 138.2, 135.5, 130.0, 128.8, 128.7
(2C), 128.5 (2C), 127.0 (2C), 126.7, 126.2 (2C), 119.1, 112.7, 104.1, 48.6, 23.5, 23.2, 23.1, 22.4;
IR (KBr) : 3426, 3299, 3188, 3031, 2926, 2847, 2361, 1965, 1622, 1560, 1497, 1442, 1409, 1340,
ν
1232, 1177, 1104, 830, 768, 699. Anal. Calcd. for C25H24N4: C, 78.92%; H, 6.36%; N, 14.73%.
Found: C, 78.83%; H, 6.30%; N, 14.80%.
4-(1-Benzyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-6-(2-furyl)pyrimidin-2-amine (3j): 87 mg (59%),
dark yellow crystals, m.p. 182 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 7.54–7.53 (m, 1H, H-5,
furyl), 7.28–7.25 (m, 2H, H-2,6, Ph), 7.21–7.18 (m, 2H, H-5, pyrimidine, H-4, Ph), 7.06–7.05
(m, 1H, H-3, furyl), 7.01–6.99 (m, 2H, H-3,5, Ph), 6.75 (s, 1H, H-3, pyrrole), 6.52 (dd, J = 1.8,
3.2 Hz, 1H, H-4, furyl), 5.78 (s, 2H, CH2Ph), 4.80 (br s, 2H, NH2), 2.59–2.56 (m, 2H, CH2-7),
2.50–2.47 (m, 2H, CH2-4), 1.82–1.72 (m, 4H, CH2-5,6); 13C-NMR (100.6 MHz, CDCl3)
δ:
162.6, 160.5, 155.4, 152.6, 144.1, 139.6, 135.7, 128.5 (2C), 128.4, 126.7, 126.2 (2C), 119.1, 113.0,
112.1, 110.6, 101.8, 48.5, 23.5, 23.1, 23.0, 22.4; IR (KBr) : 3315, 3178, 2997, 2935, 2843, 1643,
ν
1603, 1549, 1495, 1458, 1406, 1377, 1242, 1180, 1146, 1103, 1019, 951, 810, 764, 734, 694. Anal.
Calcd. for C23H22N4O: C, 74.57%; H, 5.99%; N, 15.12%. Found: C, 74.28%; H, 5.78%; N,
15.04%.
4-Phenyl-6-(1-vinyl-4,5,6,7-tetrahydro-1H-indol-2-yl)pyrimidin-2-amine (3k): 82 mg (65%), yel-
low crystals, m.p. 118 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.01–7.99 (m, 2H, H-2,6 Ph),
7.51–7.44 (m, 4H, H-3,4,5, Ph, HX), 7.23 (s, 1H, H-5, pyrimidine), 6.68 (s, 1H, H-3, pyrrole),
5.10 (br s, 2H, NH2), 5.04 (d, J = 16.0 Hz, 1H, HB), 5.01 (d, J = 8.9Hz, 1H, HA), 2.75–2.72
(m, 2H, CH2-7), 2.59–2.56 (m, 2H, CH2-4), 1.86–1.76 (m, 4H, CH2-6, CH2-5); 13C-NMR
(
100.6 MHz, CDCl3)
δ
: 165.0, 163.0, 160.2, 138.1, 134.1, 133.1, 130.2, 129.8, 128.8 (2C), 127.0
: 3485, 3312, 3199, 2927, 2847,
(2C), 120.4, 113.7, 105.4, 105.0, 24.8, 23.6, 23.2, 23.1; IR (KBr)
ν
1636, 1564, 1537, 1501, 1459, 1397, 1368, 1227, 1184, 1145, 980, 861, 827, 766, 698, 642. Anal.
Calcd. for C20H20N4: C, 75.92%; H, 6.37%; N, 17.71%. Found: C, 75.87%; H, 6.33%; N,
17.81%.
4-Phenyl-6-(5-phenyl-1H-pyrrol-2-yl)pyrimidin-2-amine (3l): 111 mg (89%), brown crystals,
◦
1
m.p. 194–196 C; H-NMR (400.13 MHz, DMSO-d6) δ: 11.55 (br s, 1H, NH), 8.17–8.15
(m, 2H, Ph), 7.88–7.85 (m, 2H, Ph), 7.68 (s, 1H, H-5, pyrimidine), 7.53–7.52 (m, 4H, Ph),
7.28–7.24 (m, 2H, Ph), 7.06–7.05 (m, 1H, H-3, pyrrole), 6.66–6.65 (m, 1H, H-4, pyrrole), 6.47
(br s, 2H, NH2); 13C-NMR (100.6 MHz, DMSO-d6)
δ: 163.9, 163.7, 158.1, 137.5, 134.4, 131.8,
130.2, 128.6 (2C), 128.5 (2C), 126.7 (2C), 126.6 (2C), 115.6, 115.4, 112.5, 108.2, 99.9; IR (KBr)
ν
:
3442, 3369, 3274, 3161, 3058, 1602, 1570, 1537, 1457, 1432, 1366, 1301, 1235, 1071, 1046, 1002,
912, 836, 755, 691, 614. Anal. Calcd. for C20H16N4: C, 76.90%; H, 5.16%; N, 17.94%. Found:
C, 76.75%; H, 5.04%; N, 17.88%.
4-(2-Furyl)-6-(5◦-phenyl-1H-pyrrol-2-yl)pyrimidin-2-amine (3m): 93 mg (77%), brown crystals,
1
m.p. 208–210 C; H-NMR (400.13 MHz, DMSO-d6)
δ: 11.59 (br s, 1H, NH), 7.92–7.91
(
(
(
(
m, 1H, H-5, furyl), 7.85–7.83 (m, 2H, H-2,6, Ph), 7.50 (s, 1H, H-5, pyrimidine), 7.43–7.39
m, 2H, H-3,5, Ph), 7.27–7.23 (m, 1H, H-4, Ph), 7.16–7.15 (m, 1H, H-3, furyl), 7.01–7.00
m, 1H, H-4, furyl), 6.71–6.69 (m, 2H, H-3,4, pyrrole), 6.50 (br s, 2H, NH2); 13C-NMR
100.6 MHz, DMSO-d6)
δ: 163.5, 158.1, 155.7, 152.5, 145.0, 135.5, 131.9, 131.7 128.7 (2C),
126.7, 124.7 (2C), 112.6, 112.5, 110.9, 108.3, 98.1; IR (KBr)
ν
: 3482, 3454, 3298, 3181, 2924,
1631, 1588, 1566, 1541, 1445, 1386, 1351, 1299, 1237, 1214, 1160, 1044, 1011, 879, 812, 750,
681, 595, 554, 424. Anal. Calcd. for C18H14N4O: C, 71.51%; H, 4.67%; N, 18.53%. Found: C,
71.39%; H, 4.59%; N, 18.65%.
4-[5-(4-Fluorophenyl)-1H-pyrrol-2-yl]-6-phenylpyrimidin-2-amine (3n): 116 mg (88%), light
yellow crystals, m.p. 221–222 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 9.75 (br s, 1H, NH),
8.05–8.03 (m, 2H, H-2,6, Ph), 7.59–7.56 (m, 2H, H-2,6, 4-F-C6H4), 7.51–7.49 (m, 3H, H-3,4,5,
Ph), 7.29 (s, 1H, H-5, pyrimidine), 7.14–7.09 (m, 2H, H-3,5, 4-F-C6H4), 6.96 (dd, J = 0.8,
2.6 Hz, 1H, H-3, pyrrole), 6.57 (dd, J = 0.8, 2.9 Hz, 1H, H-4, pyrrole), 5.07 (br s, 2H, NH2);
13C NMR (100.6 MHz, DMSO-d6)
(d, JCF = 243.9 Hz, C-4, 4-F-C6H4), 157.7 (C-4, pyrimidine), 137.1 (C-1, Ph), 134.0 (C-5,
δ
: 163.5 (C-2, pyrimidine), 163.3 (C-6, pyrimidine), 160.7
1

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pyrrole), 131.5 (C-2, pyrrole), 129.8 (C-4, Ph), 128.2 (d, 4JCF = 2.9 Hz, C-1, 4-F-C6H4), 128.1
3
2
(C-3,5, Ph), 126.3 (C-2,6, Ph), 126.2 (d, JCF = 8.7 Hz, C-2,6, 4-F-C6H4), 115.1 (d, JCF
21.5 Hz, C-3,5, 4-F-C6H4), 112.0 (C-3, pyrrole), 107.8 (C-4, pyrrole), 99.5 (C-5, pyrimidine);
15N-NMR (40.5 MHz, DMSO-d6)
298.9 (NH2), 233.8 (NH, pyrrole), 151.2 (N-3),
147.4 (N-1); IR (KBr) : 3445, 3388, 3270, 3159, 1602, 1575, 1524, 1478, 1451, 1433, 1366,
=
δ:
−
−
−
−
ν
1301, 1233, 1157, 1047, 832, 765, 697. Anal. Calcd. for C20H15FN4: C, 72.71%; H, 4.58%; F,
5.75%; N, 16.96%. Found: C, 72.62%; H, 4.48%; F, 5.60%; N, 17.07%.
4-[5-(4-Chlorophenyl)-1H-pyrrol-2-yl]-6-phenylpyrimidin-2-amine (3o): 117 mg (84%), brown
crystals, m.p. 226 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 9.80 (br s, 1H, NH), 8.05–8.03 (m,
2H, H-2,6, Ph), 7.54–7.49 (m, 5H, H-3,4,5, Ph, H-2,6, 4-Cl-C6H4), 7.39–7.37 (m, 2H, H-3,5,
4-Cl-C6H4), 7.29 (s, 1H, H-5, pyrimidine), 6.96–6.95 (m, 1H, H-3, pyrrole), 6.62–6.61 (m, 1H,
H-4, pyrrole), 5.11 (br s, 2H, NH2); 13C-NMR (100.6 MHz, DMSO-d6)
δ
: 164.0, 163.7, 158.1,
137.5, 134.1, 132.3, 131.0, 130.9, 130.3, 128.7 (2C), 128.6 (2C), 126.8 (2C), 126.3 (2C), 112.6,
108.9, 100.1; IR (KBr) : 3434, 2925, 2858, 1622, 1583, 1531, 1470, 1432, 1360, 1290, 1231, 1113,
ν
1095, 1048, 829, 770, 692; Anal. Calcd. for C20H15ClN4: C, 69.26%; H, 4.36%; Cl, 10.22%; N,
16.15%. Found: C, 69.13%; H, 4.28%; Cl, 10.14%; N, 16.09%.
4-[5-(4-Methoxyphenyl)-1H-pyrrol-2-yl]-6-phenylpyrimidin-2-amine (3p): 108 mg (79%), yellow
crystals, m.p. 217 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 9.72 (br s, 1H, NH), 8.05–8.02 (m,
2H, H-2,6, Ph), 7.56–7.54 (m, 2H, H-2,6, 4-MeO-C6H4), 7.50–7.49 (m, 3H, H-3,4,5, Ph), 7.28
(s, 1H, H-5, pyrimidine), 6.97–6.95 (m, 3H, H-3,5, 4-MeO-C6H4, H-3, pyrrole), 6.54 (dd,
J = 0.6, 2.9 Hz, 1H, H-4, pyrrole), 5.06 (br s, 2H, NH2), 3.85 (s, 3H, MeO); 13C-NMR (100.6
MHz, DMSO-d6)
δ: 163.9, 163.8, 158.4, 158.3, 137.7, 135.7, 131.1, 130.4, 128.7 (2C), 126.8 (2C),
126.2 (2C), 124.9, 114.3 (2C), 112.8, 107.4, 99.9, 55.3; IR (KBr)
ν
: 3484, 3430, 3298, 3144, 2953,
2928, 1634, 1569, 1530, 1479, 1455, 1433, 1359, 1251, 1178, 1048, 1030, 1005, 833, 774, 706, 645.
Anal. Calcd. for C21H18N4O: C, 73.67%; H, 5.30%; N, 16.36%. Found: C, 73.59%; H, 5.24%;
N, 16.27%.
4-Phenyl-6-(1-methyl-5-phenyl-1H-pyrrol-2-yl)pyrimidin-2-amine (3q): 91 mg (70%), yellow
crystals, m.p. 60–62 oC; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.05–8.03 (m, 2H, H-2,6, Ph),
7.49–7.44 (m, 7H, Ph), 7.40–7.36 (m, 1H, H-4, Ph), 7.33 (s, 1H, H-5, pyrimidine), 6.90 (d, J =
3.8 Hz, 1H, H-3, pyrrole), 6.32 (d, J = 3.8 Hz, 1H, H-4, pyrrole), 5.11 (br s, 2H, NH2), 3.98 (s,
3H, NMe); 13C-NMR (100.6 MHz, CDCl3)
δ: 165.2, 163.0, 160.7, 140.8, 138.1, 132.9, 132.6,
130.3, 129.3 (2C), 128.8 (2C), 128.6 (2C), 127.6, 127.1 (2C), 113.5, 109.6, 105.1, 35.7; IR (KBr)
ν
:
3476, 3397, 3303, 3182, 3059, 1565, 1528, 1455, 1293, 1347, 1312, 1221, 1113, 1087, 1027, 989,
919, 836, 757, 695, 642. Anal. Calcd. for C21H18N4: C, 77.28%; H, 5.56%; N, 17.17%. Found:
C, 77.03%; H, 5.32%; N, 17.09%.
4-Phenyl-6-(5-phenyl-1-vinyl-1H-pyrrol-2-yl)pyrimidin-2-amine (3r): 123 mg (91%), light yellow
◦
crystals, m.p. 124–125 C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.03–8.01 (m, 2H, Ph), 7.62 (dd,
J = 8.5, 15.8 Hz, 1H, HX), 7.50–7.46 (m, 5H, Ph), 7.42–7.38 (m, 2H, Ph), 7.34–7.31 (m, 1H, Ph),
7.30 (s, 1H, H-5, pyrimidine), 6.89 (d, J = 3.7 Hz, 1H, H-3, pyrrole), 6.38 (d, J = 3.7 Hz, 1H,
H-4, pyrrole), 5.10 (br s, 2H, NH2), 4.96 (d, J = 8.5 Hz, 1H, HA), 4.68 (d, J = 15.8 Hz, 1H,
HB); 13C-NMR (100.6 MHz, CDCl3)
δ
: 165.3, 163.1, 160.2, 138.9, 137.8, 133.0, 132.8, 132.7,
130.3, 129.3 (2C), 128.8 (2C), 128.2 (2C), 127.3, 127.0 (2C), 114.6, 111.8, 111.2, 105.8; IR (KBr)
: 3463, 3407, 3312, 3187, 3060, 2953, 2922, 2854, 1622, 1566, 1531, 1451, 1429, 1389, 1376,
ν
1343, 1291, 1220, 1076, 1026, 963, 900, 837, 761, 695, 640. Anal. Calcd. for C22H18N4: C,
78.08%; H, 5.36%; N, 16.56%. Found: C, 78.14%; H, 5.31%; N, 16.32%.
4-(4,5-diphenyl-1-vinyl-1H-pyrrol-2-yl)-6-phenylpyrimidin-2-amine (3s): 146 mg (88%), yellow
crystals, m.p. 202 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.06–8.03 (m, 2H, H, Ph), 7.51–7.49
(m, 3H, Ph, HX), 7.40–7.32 (m, 7H, Ph), 7.21–7.13 (m, 5H, Ph, H-5, pyrimidine), 7.06 (s, 1H,
H-3, pyrrole), 5.10 (br s, 2H, NH2), 4.89 (d, J = 8.2 Hz, 1H, HA), 4.60 (d, J = 16.4 Hz, 1H,
HB); 13C-NMR (100.6 MHz, CDCl3)
δ
: 165.4, 163.1, 160.2, 137.8, 135.3, 137.8, 132.4, 132.3,
131.8, 131.4 (2C), 130.4, 128.8 (2C), 128.5 (2C), 128.2 (2C), 128.1 (2C), 128.0, 127.1 (2C), 125.9,
125.0, 114.9, 110.8, 106.1. IR (KBr) : 3418, 3059, 2363, 1637, 1588, 1567, 1535, 1498, 1449,
ν

Molecules 2021, 26, 1692
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1408, 1291, 1206, 1075, 955, 910, 832, 770, 696, 638. Anal. Calcd. for C28H22N4: C, 81.13%; H,
5.35%; N, 13.52%. Found: C, 78.99%; H, 5.16%; N, 13.37%.
4-[5-(4-Chlorophenyl)-1-vinyl-1H-pyrrol-2-yl]-6-phenylpyrimidin-2-amine (3t): 78 mg (52%),
◦
light brown crystals, m.p. 156 C; 1H-NMR (400.13 MHz, CDCl3)
δ: 8.04–8.01 (m, 2H, H-2,6,
Ph), 7.63 (dd, J = 8.5, 15.8 Hz, 1H, HX), 7.51–7.49 (m, 3H, H-3,4,5, Ph), 7.41–7.35 (m, 4H,
4-Cl-C6H4), 7.29 (s, 1H, H-5, pyrimidine), 6.88 (d, J = 3.8 Hz, 1H, H-3, pyrrole), 6.36 (d, J =
3.8 Hz, 1H, H-4, pyrrole), 5.16 (br s, 2H, NH2), 5.99 (d, J = 8.5 Hz, 1H, HA), 4.67 (d, J = 15.8
Hz, 1H, HB); 13C-NMR (100.6 MHz, CDCl3)
δ
: 165.5, 163.0, 160.1, 137.8, 137.5, 133.3, 133.2,
132.7, 131.5, 130.6 (2C), 130.5, 128.8 (2C), 128.5 (2C), 127.1 (2C), 114.5, 112.2, 111.7, 105.8; IR
(KBr) : 3499, 3441, 3313, 3189, 2362, 1617, 1565, 1532, 1458, 1434, 1384, 1224, 1083, 1010,
ν
957, 896, 831, 766, 700, 642, 580, 521. Anal. Calcd. for C22H17ClN4: C, 70.87%; H, 4.60%; Cl,
9.51%; N, 15.03%. Found: C, 70.77%; H, 4.38%; Cl, 9.51%; N, 15.02%.
4-[5-(2-Fluorophenyl)-1-vinyl-1H-pyrrol-2-yl]-6-(2-furyl)pyrimidin-2-amine (3u): 104 mg (75%),
orange crystals, m.p. 169 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 7.63–7.56 (m, 2H, HX, H-5,
furyl), 7.44–7.40 (m, 1H, H-6, 2-F-C6H4), 7.37–7.32 (m, 1H, H-4, 2-F-C6H4), 7.25 (s, 1H, H-5,
pyrimidine), 7.21–7.09 (m, 3H, H-3,5, 2-F-C6H4, H-3, furyl), 6.94 (d, J = 3.8 Hz, 1H, H-3,
pyrrole), 6.56 (dd, J = 1.8, 3.4 Hz, 1H, H-4, furyl), 6.39 (d, J = 3.8 Hz, 1H, H-4, pyrrole),
5.19 (br s, 2H, NH2), 4.87 (d, J = 8.5 Hz, 1H, HA), 4.62 (d, J = 15.8 Hz, 1H, HB); 13C-NMR
(100.6 MHz, CDCl3) δ
: 162.9, 160.0, 159.4 (d, 1JCF = 248.3 Hz, C-2, 2-F-C6H4), 156.2, 152.3,
144,4, 133.2, 132.5 (d, 3JCF = 5.9 Hz, C-4, 2-F-C6H4), 131.9, 131.8, 129.7 (d, 3JCF = 8.1 Hz, C-6,
2-F-C6H4), 124.1 (d, 4JCF = 3.4 Hz, C-5, 2-F-C6H4), 121.4 (d, 2JCF = 14.9 Hz, C-1, 2-F-C6H4),
115.9 (d, 2JCF = 22.0 Hz, C-3, 2-F-C6H4), 114.3, 112.7, 112.2, 111.3, 109.7, 103.3; IR (KBr)
ν:
3433, 3363, 3195, 1631, 1600, 1550, 1459, 1408, 1222, 1160, 1108, 1079, 1017, 945, 817, 771, 750.
Anal. Calcd. for C20H15FN4O: C, 69.35%; H, 4.37%; F, 5.49%; N, 16.18%. Found: C, 69.27%;
H, 4.15%; F, 5.36%; N, 16.11%.
4-[5-(2-Fluorophenyl)-1-vinyl-1H-pyrrol-2-yl]-6-(2-thienyl)pyrimidin-2-amine (3v): 99 mg (68%),
brown crystals, m.p. 144 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 7.73–7.72 (m, 1H, H-6, 2-F-
C6H4), 7.57 (dd, J = 8.5, 15.7 Hz, 1H, Hx), 7.48–7.47 (m, 1H, H-3, thienyl), 7.43–7.40 (m, 1H,
H-5, thienyl), 7.38–7.33 (m, 1H, H-4, 2-F-C6H4),7.22 (s, 1H, H-5, pyrimidine), 7.19–7.09 (m,
3H, H-3,5, 2-F-C6H4, H-4, thienyl), 6.91 (d, J = 3.7 Hz, 1H, H-3, pyrrole), 6.39 (d, J = 3.7 Hz
,
1H, H-4, pyrrole), 5.08 (br s, 2H, NH2), 4.89 (d, J = 8.5 Hz, 1H, HA), 4.65 (d, J = 15.7 Hz,
1H, HB); 13C-NMR (100.6 MHz, CDCl3) : 162.9, 159.9, 159.8, 159.5 (d, 1JCF = 248.4 Hz, C-2,
δ
2-F-C6H4), 143.2, 133.2, 132.5 (d, 2JCF = 21.5 Hz, C-1, 2-F-C6H4), 132.0, 131.9, 129.8 (d, 3JCF
= 8.0 Hz, C-4, 2-F-C6H4), 129.0, 128.1, 126.7, 124.1 (d, 4JCF = 2.8 Hz, C-5, 2-F-C6H4), 121.4 (d,
3JCF = 15.0 Hz, C-6, 2-F-C6H4), 115.9 (d, 2JCF = 22.0 Hz, C-3, 2-F-C6H4), 114.1, 112.7, 109.7,
103.8; IR (KBr) ν: 3404, 3340, 3223, 1638, 1567, 1531, 1448, 1431, 1376, 1347, 1223, 1105, 1073,
1045, 947, 898, 816, 766, 710. Anal. Calcd. for C20H15FN4S: C, 66.28%; H, 4.17%; F, 5.24%; N,
15.46%; S, 8.85%. Found: C, 65.93%; H, 4.02%; F, 5.48%; N, 15.11%; S, 8.79%.
3-[2-(2-Amino-6-phenylpyrimidin-4-yl)-1H-pyrrol-1-yl]-1-phenyl-3-(1H-pyrrol-2-yl)prop-2-en-1-
one (4a): 11 mg (13%), yellow crystals, m.p. 137–139 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ: 13.64 (br s, 1H, NH), 7.90–7.85 (m, 4H, H-2,6, COPh, H-2,6, Ph), 7.55–7.51 (m, 1H, H-4,
COPh), 7.45–7.42 (m, 5H, H-3,5, COPh, H-3,4,5, Ph), 7.19 (s, 1H, H-5, pyrimidine), 7.16–7.15
0
(m, 2H, H-5, H-5 , pyrrole), 7.06 (dd, J = 1.7, 3.6 Hz, 1H, H-3, pyrrole), 6.76 (s, 1H, HC=), 6.42
(dd, J = 2.8, 3.6 Hz, 1H, H-4, pyrrole), 6.28 (dd, J = 2.2, 3.8 Hz, 1H, H-40, pyrrole), 6.24–6.23
(m, 1H, H-30, pyrrole), 4.88 (br s, 2H, NH2); 13C-NMR (100.6 MHz, CDCl3)
δ: 189.9, 165.2,
162.9, 158.8, 146.3, 139.4, 137.7, 133.1, 132.8, 130.3, 129.9, 129.3, 128.7 (2C), 128.6 (2C), 128.3
(2C), 127.0 (2C), 124.5, 118.6, 114.3, 112.7, 111.9, 109.7, 104.3; 15N-NMR (40.5 MHz, CDCl3)
δ
:
−
304.9 (NH2),
−
220.9 (NH),
−
208.8 (N-pyrrole),
−
148.2 (N-1),
−
145.2 (N-3); IR (KBr)
ν
: 3480, 3401, 3356, 3120, 3106, 1623, 1577, 1526, 1438, 1353, 1320, 1297, 1220, 1184, 1128,
1088, 1036, 998, 931, 909, 881, 833, 768, 696, 641. Anal. Calcd. for C27H21N5O: C, 75.16%; H,
4.91%; N, 16.23%. Found: C, 75.04%; H, 4.77%; N, 16.14%.

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3-[2-Amino-4-phenyl-6-(1H-pyrrol-2-yl)pyrimidin-5-yl]-1-phenyl-3-(1H-pyrrol-2-yl)prop-2-en-1-
one (5a): 7 mg (8%), dark yellow crystals, m.p. 182 ◦C; 1H-NMR (400.13 MHz, CDCl3)
δ:
9.96 (br s, 1H, NH’), 8.95 (br s, 1H, NH), 7.59–7.56 (m, 2H, H-2,6, COPh), 7.45–7.42 (m, 1H,
H-4, COPh), 7.31–7.30 (m, 1H, H-4, Ph), 7.29 (s, 1H, HC=), 7.25–7.23 (m, 2H, H-3,5,COPh),
7.21–7.19 (m, 2H, H-2,6, Ph), 7.14–7.10 (m, 2H, H-3,5, Ph), 6.83–6.82 (m, 1H, H-50, pyrrole),
6.78–6.77 (m, 1H, H-5, pyrrole), 6.72–6.71 (m, 1H, H-3, pyrrole), 6.66–6.65 (m, 1H, H-30,
pyrrole), 6.31–6.30 (m, 1H, H-40, pyrrole), 6.09–6.06 (m, 1H, H-4, pyrrole), 5.12 (br s, 2H,
NH2); 13C-NMR (100.6 MHz, DMSO-d6)
δ: 187.7 (C=O), 164.9 (C-4, pyrimidine), 161.4 (C-2,
pyrimidine), 154.6 (C-6, pyrimidine), 144.4 (C=), 139.6 (C-1, Ph), 139.1 (C-1, COPh), 132.3
(C-20, pyrrole), 132.0 (C-4, COPh), 128.4 (C-2, pyrrole), 128.3 (C-3,5, COPh), 127.8 (C-2,4,6,
Ph), 127.5 (C-2,6, COPh), 127.0 (C-3,5, Ph), 123.8 (C-50, pyrrole), 120.7 (C-5, pyrrole), 114.9
(C-30, pyrrole), 114.8 (C-5, pyrimidine, HC=), 112.5 (C-3, pyrrole), 110.3 (C-40, pyrrole),
109.4 (C-4, pyrrole); 15N-NMR (40.5 MHz, CDCl3)
δ:
−
225.5 (NH’),
−
223.7 (NH); IR (KBr)
ν
: 3471, 3426, 3173, 2967, 2863, 1635, 1597, 1536, 1444, 1418, 1227, 1120, 1034, 1020, 910, 738,
697. Anal. Calcd. for C27H21N5O: C, 75.16%; H, 4.91%; N, 16.23%. Found: C, 74.98%; H,
4.64%; N, 16.14%.
4. Conclusions
In summary, we developed an effective access to novel families of pyrrole–pyrimidine
ensembles, decorated with alkyl, cycloalkyl, aryl and vinyl groups, attractive objects for
drug design, by using acylethynylpyrroles as the synthetic platform. This method has
several synthetic advantages, such as the one-pot procedure, the use of readily available
starting materials and good to high yields of the target ensembles and therefore can activate
the interest of both synthetic and pharmaceutical communities.
Supplementary Materials: The following are available online, Figures S1–S68: 1H, 13C and 19F
NMR spectra.
Author Contributions: Conceptualization, B.A.T. and L.N.S.; methodology, O.V.P., A.B.B.; chem-
istry of all compounds, O.V.P., A.B.B. and E.F.S.; formal analysis, I.A.U.; writing—original draft
preparation, B.A.T., L.N.S. and O.V.P.; writing—review and editing, A.B.B., E.F.S., O.V.P. and A.V.I.
All authors have read and agreed to the published version of the manuscript.
Funding: This work was supported by the Russian Science Foundation (Project 19-73-10063).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data set presented in this study is available in this article.
Acknowledgments: Authors acknowledge Baikal Analytical Center SB RAS for collective use of
the equipment.
Conflicts of Interest: Authors reports no conflict interests.
Sample Availability: Samples of the compounds are available on request from the corresponding
authors.
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