Multicomponent Tether Catalysis Synthesis of Highly Functionalized 4-(Pyridin-2-ylmethyl)-2-aminopyrroles via Cascade Reaction Is Accompanied by Decarboxylation

Article abstract of DOI:10.1021/acs.joc.9b01814

A multicomponent tether catalysis protocol for the synthesis of 4-(pyridin-2-ylmethyl)-2-aminopyrroles (PMAPs) was constructed by simply refluxing a mixture of ethyl 2-(pyridin-2-yl)acetates 1 and various types of arylglyoxal monohydrates 2 and different heterocyclic ketene aminals 3 in EtOH solvent. Based on this reaction, a series of highly functionalized PMAPs were obtained through a novel cascade reaction accompanied by a decarboxylation mechanism. As a result, the pyridin-2-ylmethyl was successfully introduced in the target compounds, and a library of PMAPs were easily constructed using the cascade reaction described in this study. This protocol demonstrated that the most important feature was the decarboxylation reaction of the 2-(pyridin-2-yl)acetates 1, which can be used in the synthesis of pyridin-2-ylmethyl-substituted heterocycles, including pyrroles, pyridines, quinolones, and other heterocyclic compounds resembling those found in nature.

Full text of DOI:10.1021/acs.joc.9b01814

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Article
Multi-component Tether Catalysis Synthesis of Highly
Functionalized 4-(Pyridin-2-ylmethyl)-2-amino-pyrroles via
Cascade Reaction is Accompanied by Decarboxylation
Kun Li, Li Chen, Yun-Xiang Fan, Yao Wei, and Sheng-Jiao Yan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01814 • Publication Date (Web): 29 Aug 2019
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Multi-component Tether Catalysis Synthesis of
Highly Functionalized 4-(Pyridin-2-ylmethyl)-2-
amino-pyrroles via Cascade Reaction is
Accompanied by Decarboxylation
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Kun Li, Li Chen, Yun-Xiang Fan, Yao Wei and Sheng-Jiao Yan*
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of
Education, School of Chemical Science and Technology, Yunnan University, Kunming, 650091,
P. R. China.
KEYWORDS: 2-Aminopyrroles, Tether catalysis, Cascade reaction, Decarboxylation,
Heterocyclic ketene aminals.
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ABSTRACT: A multi-component tether catalysis protocol for the synthesis of 4-(pyridin-2-
ylmethyl)-2-aminopyrroles (PMAPs) was constructed by simply refluxing a mixture of ethyl 2-
(pyridin-2-yl)acetates 1 and various types of arylglyoxal monohydrates 2 and different
heterocyclic ketene aminals 3 in EtOH solvent. Based on this reaction, a series of highly
functionalized PMAPs was obtained through a novel cascade reaction accompanied by a
decarboxylation mechanism. As a result, the pyridin-2-ylmethyl was successfully introduced in
the target compounds, and a library of PMAPs was easily constructed using the cascade reaction
described in this study. This protocol demonstrated that the most important feature was the
decarboxylation reaction of the 2-(pyridin-2-yl)acetates 1, which can be used in the synthesis of
pyridin-2-ylmethyl-substituted heterocycles including pyrroles, pyridines, quinolones, and other
heterocyclic compounds resembling those found in nature.
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 INTRODUCTION
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Pyrrole derivatives are vital N-containing heterocycles and are a common structural motif in
numerous natural products, biologically important molecules, and pharmaceuticals.1 Examples
are the central cannabinoid (CB1) receptor antagonist (Fig. 1, URB447), the anti-tumor agent
neolamellarin A, and the antihyperlipidemic agent atorvastatin.2 Consequently, a greater number
of chemists and pharmacologists have been interested in these types of heterocycles and have
constructed many protocols for the synthesis of pyrrole derivatives.2-3 A general method involves
the use of Paal-Knorr condensations to synthesize pyrroles.4 Furthermore, N-sulfonyl-1,2,3-
triazoles also have been widely used as the substrate to synthesize pyrroles.5
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Currently, there has been an increasing number of protocols for synthesizing pyrroles.6 Among
pyrrole derivatives, there has been great interest in 2-aminopyrrole in recent years due to the 2-
aminopyrrole skeleton being incorporated in many medicinal compounds, as well as its broad-
spectrum and unique biological activities including mitogen-activated protein kinase kinase
(MEK) inhibitor,7 metallo--lactamase (MBL) inhibitor,8 (Fig. 1), tumor necrosis factor (TNF)-
production inhibitor, phosphodiesterase (PDE) inhibitor,9 protein kinase casein kinase 2 (CK2)
inhibitor;10 antagonist against corticotropin-releasing factor (CRF) receptors (Fig. 1);11 and
antimalarial, anti-bacterial, and cytotoxic activities.12 As a result, an increasing number of
procedures have been used to synthesize pyrroles13-16 including (1) a multicomponent reaction
base on nitrile or isocyanide-containing substrates and (2) cycloisomerization of alkyne and
allene-containing substrates catalyzed by transition metal complexes. For example, Ye and co-
workers reported a gold-catalyzed intermolecular ynamide amination-initiated aza-Nazarov
cyclization to synthesize 2-aminopyrroles (Scheme 1).16a Zhu and co-workers described an
oxidative Strecker reaction (mediated by 2-iodoxybenzoic acid and tetra-butylammonium
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bromide) followed by a [4+1]-cycloaddition of the resulting α,β-unsaturated imidoyl cyanides
with isocyanides to provide 2-aminopyrroles (Scheme 1).16b (3) Our group recently established a
simple protocol that uses Morita–Baylis–Hillman (MBH) acetates reacted with heterocyclic
ketene aminals (HKAs) via base-promoted tandem Michael addition, elimination, and
aromatization for the facile synthesis of 2-aminopyrroles.17
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Figure 1. Biological activity of pyrroles and compounds 4–5.
Pyridine derivatives are one of the most important classes of nitrogen heterocyclic compounds
and are ubiquitous structural motifs in biologically active molecules or drugs.18-21 Constructing
hybrid molecules that are combined with the pyridine skeleton and 2-aminopyrrole skeleton may
increase the chance for excellent biological activities. The hybrid molecules are 4-(pyridin-2-
ylmethyl)-2-aminopyrroles (PMAPs). The reported methods for their synthesis usually have
some shortcomings, such as the need for expensive transition metal additives and poor
selectivity. Additionally, methods for synthesis of biological heterocycles substituted by
pyridinylmethyl, quinolin-2-ylmethyl, and other benzyl groups are very rare. The scarcity may
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be due to the fact that when using the alkylation agents, the N-alkylation products are always
obtained rather that the C-alkylation products.
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Scheme 1. Methods for the Construction of 2-Aminopyrrole Derivatives
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Heterocyclic ketene aminals (HKAs) are fascinating and versatile building blocks22 and were
widely used to synthesize various heterocycles with important biological activities including
antitumor,23 anti-anxiety,24 anti-leishmanial,25 antibacterial,26 and pesticide.27 To further extend
the use of HKAs in synthesis, we herein report the construction of a library of functionalized 2-
aminopyrrole derivatives based on multicomponent reactions between HKAs, ethyl 2-(pyridin-2-
yl)acetates, and arylglyoxal monohydrates. The process occurs in refluxing ethanol without any
added catalyst.
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RESULTS AND DISCUSSION
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In order to achieve optimal conditions, first, ethyl 2-(pyridin-2-yl)acetates 1a (0.5 mmol),
arylglyoxal monohydrate 2b (0.5 mmol), and HKA 3a were mixed without any added catalyst at
reflux in different solvents including ethanol, acetonitrile, tetrahydrofuran (THF), 1,4-dioxane,
and toluene. The results showed that ethanol was the most optimal solvent, and gave the product
4e with a moderate yield (79%) (Table 1, entries 1–5). In an attempt to use a more
environmentally friendly solvent, water was used as a solvent in this cascade reaction, and the
results showed that we obtained a lower yield compared with ethanol (Table 1, entry 1 vs. 6).
Next, a mixture of ethanol and water at different volume ratios served as the solvent and was
screened at reflux without any other catalyst (Table 1, entries 7–9). The results showed that
ethanol is the most optimal solvent when compared to other solvents, including the mixed
solvents (Table 1, entry 1 vs. 2–9). Based on the optimal solvents, the basic catalyst including
Et3N, pyridine, and Cs2CO3 were applied in this reaction that was refluxed in ethanol for 12
hours (Table 1, entries 10–12). The results demonstrated that the basic catalyst could not
promote the reaction at all, and a low yield (35–66%) was obtained. Next, acid catalysts
including CH3COOH, p-TsOH, and NH2SO3H were screened under the same conditions. The
results revealed that these three catalysts also could not promote the yield of the cascade reaction
(Table 1, entries 12–15). Comparing all of the conditions, we found that the optimal conditions
were the use of ethanol as the solvent without any other catalyst at reflux for 12 hours (Table 1,
entry 1 vs. 2–15).
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Table 1. Optimized Conditions for the Synthesis of 4ea
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entry
solvent
catalyst
time/h
yieldb (%)
1
2
EtOH
MeCN
–
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THF
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1,4-dioxane
toluene
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H2O
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EtOH/H2O=1:5
EtOH/H2O=1:2
EtOH/H2O=1:1
EtOH
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–
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–
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Et3N
EtOH
pyridine
Cs2CO3
CH3COOH
p-TsOH
NH2SO3H
EtOH
EtOH
EtOH
EtOH
0
a Reagents and conditions: 1a (0.5 mmol), 2b (0.5 mmol), 3a (0.5 mmol), catalyst (0.05 mmol),
solvent (3.0 mL). b Isolated yield based on 3a.
Once we determined the optimized conditions, we explored the scope and limitations of the
cascade reaction of ethyl 2-(pyridin-2-yl)acetates 1 and arylglyoxal monohydrates 2 and HKAs 3
(Table 2). The results showed that the substituted groups of ethyl 2-(pyridin-2-yl)acetates 1 and
arylglyoxal monohydrates 2 exerted only a slight effect on the yield of the target compounds 4,
and we almost could not arrive at obvious rules for the substituted group. In general, this cascade
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Table 2. Synthesis of 4-(Pyridin-2-ylmethyl)-2-aminopyrroles 4
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a 1–3 (0.5 mmol), EtOH (3.0 mL). b 1–3 (1.0 mmol), EtOH (5.0 mL).
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reaction can smoothly proceed with the different structures of the 2-(pyridin-2-yl)acetates 1 and
arylglyoxal monohydrates 2 to produce compounds 4 with moderate to good yield. The
substituted group of HKAs 3 has a different effect on the yield of the target compounds. The
effect of substitution on the aryl group of HKAs was also evaluated. Substitution at C-4 of the
aryl group has a slight effect on the yield. When the substituents were at C-2 of the aryl group,
yields were slightly lower (Table 2, 4i, 4n and 4r). Overall, all of the substrates can be used in
the reaction, and all will produce compounds 4 in moderate to good yield (Table 2, entries 1–28).
To illustrate this new synthetic method, a larger scale (1–3, 1.0 mmol) synthesis of compound 4e
was carried out, and we obtained 309 mg compound 4e with an increasing yield up to 78%
(Table 2). Alkylglyoxal monohydrates 2e–2f were used as substrates to test this cascade reaction,
and the results showed that alkylglyoxal monohydrates 2e–2f did not react with ethyl 2-(pyridin-
2-yl)acetates 1a and HKA 3a, and we could not obtain the target compounds 4c'–4d' (SI,
Scheme S1).
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Table 3. Synthesis of 4-(Pyridin-2-ylmethyl)-2-aminopyrroles 5a-b
a Reagents and conditions: 1–3 (0.5 mmol), EtOH (3.0 mL). b Isolated yield based on 3.
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To further explore the scope and limitations of the cascade reaction, a variety of HKAs 3 with
electron-withdrawing groups was used as the substrate in this cascade reaction (Table 3). The
results showed that all of the substituted groups of HKAs 3 had a slight influence on the yield of
the reaction. Overall, different substituted HKAs can be used in the reaction and give compounds
5 with good yield (Table 3).
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To determine the structure of PMAPs, compound 4a was selected as a representative
compound and characterized by X-ray crystallography (Supporting Information, Figure S1,
CCDC 1920258).
To determine the tether catalysis mechanism, control experiments were performed using
substrates 1d–1g as reagents that were reacted with arylglyoxal monohydrate 2b and HKA 3a.
Substrates 1d–1g did not react with arylglyoxal monohydrate 2b and HKA 3a under the same
conditions (SI, Scheme S2). Substrates 1a–1d produced the target compounds with satisfactory
yields (Table 2), but positive results were not obtained for substrates 1d–1g. Thus, it was
successfully demonstrated that intermediate 7 is necessary for the cascade reaction to proceed so
that intermediates 8 and 9 can be formed (Scheme 2).
To explain the possible mechanism of the cascade reaction, we used target compound 4e as a
representative compound. The hypothesis for the mechanism of the cascade reaction is shown in
Scheme 2. Initially, the 2-(pyridin-2-yl)acetate 1a react with the arylglyoxal monohydrate 2b via
1,2-addition to form the intermediate 6. Next, the intermediate 7 is produced from intermediate 6
by enolate formation. Then, intermediate 7 gives compound 8 via an intramolecular tether-
catalyzed cyclization reaction. Compound 9 is obtained from compound 8 through another
intramolecular cyclization reaction and loses one molecule of ethanol. Compound 9 gives
intermediate 10 via a enol-ketone tautomerization. Then, α-C of substrate 3a attacks the carbonyl
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group of intermediate 10 by a 1,2-addition reaction, and imine-enamine tautomerization follows
to obtain intermediate 12. The amino group of intermediate 12 subsequently attacks the
intramolecular benzylic carbon, which results in the loss of one molecule of CO2 to produce
intermediate 13. The intermediate 13 gets one proton from solvent to form intermediate 14.
Ultimately, intermediate 14 forms compound 4e by losing one molecule of water.
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Scheme 2. Proposed Mechanism of the Cascade Reaction
To probe the mechanism of this cascade reaction, 2,2-dihydroxy-1-phenylethanone (2b) and
HKA (3a) and the solvent EtOH (3 mL) were charged in a round-bottom flask. Next, ethyl 2-
(pyridin-2-yl)acetate (1a) was added. The reaction was refluxed only for 3 hours. Then, the
reaction mixture was injected into the high-performance liquid chromatography-high resolution
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mass spectrometry (HPLC-HRMS) system. The four molecular ion peaks that appeared in the
high-resolution mass spectrum were: HRMS (TOF ES+): m/z calcd. for C17H18NO4 [M+H]+,
300.1230; found, 300.1236; HRMS (TOF ES+): m/z calcd. for C17H18NO4 [M+H]+, 300.1230;
found, 300.1224; HRMS (TOF ES+): m/z calcd. for C17H18NO4 [M+H]+, 300.1230; found,
300.1230. There are the HRMS spectra of intermediates 6/7/8; HRMS (TOF ES+): m/z calcd. for
C15H12NO3 [M+H]+, 254.0812; found, 254.0816; HRMS (TOF ES+): m/z calcd. for C15H12NO3
[M+H]+, 254.0812; found, 254.0819, which are the HRMS spectra of intermediate 9/10; HRMS
(TOF ES+): m/z calcd. for C26H23FN3O4 [M+H]+, 460.1667; found, 460.1663, which is the
HRMS spectra of compound 11 or 12; HRMS (TOF ES+): m/z calcd. for C25H21FN3O [M+H]+,
398.1663; found, 398.1661), which is the HRMS spectrum of target compound 4e (supporting
information, Figure S83−Figure S90). Based on the molecular ion peaks of intermediate 6–12,
the proposed mechanism of the cascade reaction is reasonable (Scheme 2).
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This cascade reaction via a novel mechanism including a tether catalysis and a
decarboxylation mechanism (Scheme 2). As a result, the pyridin-2-ylmethyl was successfully
introduced in the target compounds, and a library of PMAPs was easily constructed using the
cascade reaction described in this study. The novel mechanism was been confirmed by the high
resolution mass spectrometry (HRMS) of intermediates 6–12 (Supporting information, Figure
S84−Figure S89) and the control experiments (Supporting Information, Scheme S2). This
protocol demonstrated that the most important feature was the tether catalysis and
decarboxylation reaction of the 2-(pyridin-2-yl)acetates 1. In future studies, these reactions will
be used in this efficient and concise one-step protocol for the synthesis of pyridin-2-ylmethyl-
substituted heterocycles including pyrroles, pyridines, quinolones, and other heterocyclic
compounds resembling those found in nature.
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 CONCLUSIONS
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In conclusion, we have developed a procedure consisting of an tether catalysis reaction for the
synthesis of PMAPs by simply refluxing a mixture of ethyl 2-(pyridin-2-yl)acetates 1 and
various types of arylglyoxal monohydrates 2 and different heterocyclic ketene aminals 3 in EtOH
solvent (Scheme 2). Using this procedure, a series of highly functionalized PMAPs was obtained
through a novel cascade reaction accompanying a decarboxylation mechanism. Consequently,
the functionalized pyridin-2-ylmethyl was simply and rapidly introduced in the pyrrole skeleton,
and the library of PMAPs was easily constructed using the cascade reaction described in this
study. This protocol demonstrated that the most important feature was the decarboxylation
reaction of the 2-(pyridin-2-yl)acetates 1, and it can be used in the synthesis of pyridin-2-
ylmethyl-substituted heterocycles including pyrroles, pyridines, quinolones, and other
heterocyclic compounds resembling those found in nature.
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 EXPERIMENTAL SECTION
General Methods. All compounds were fully characterised by spectroscopic data. The NMR
spectra were recorded on a Bruker DRX600. Chemical shifts (δ) are expressed in ppm, J values
are given in Hz, and deuterated DMSO-d6 were used as solvent. IR spectra were recorded on a
FT-IR Thermo Nicolet Avatar 360 using a KBr pellet. The reactions were monitored by thin
layer chromatography (TLC) using silica gel GF254. The melting points were determined on a
XT-4A melting point apparatus and are uncorrected; HRMS were performed on an Agilent
LC/Msd TOF instrument.
The materials were purchased from Adamas-beta Corporation Limited. All chemicals and
solvents were used as received without further purification unless otherwise stated. Column
chromatography was performed on silica gel (200–300 mesh).
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The procedure for the synthesis of HKAs 3a–3g.28a-b
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HKAs (3a–3f) were prepared according to the literature.28a The mixture of ketene dithioacetals
(10 mmol) and 1,2-diaminoethane (12 mmol) in anhydrous toluene (40 mL) was stirred for about
8 hours at reflux. The mixture was cooled to room temperature and the product collected by
filtration as a withe or yellow solid with 85–92%.
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HKA (3g) were prepared according to the literature.28b The mixture of ketene dithioacetals (10
mmol) and 1,2-diaminoethane (12 mmol) in ethanol (40 mL) was stirred for about 8 hours at
reflux. The mixture was cooled to room temperature and the product collected by filtration as a
withe solid (3g) with 86%.
1-(4-Fluorophenyl)-2-(imidazolidin-2-ylidene)ethanone (3a):28c Withe solid (1.86 g, 90%);
Mp: 206–208 °C [Lit. 206 °C]; 1H NMR (600 MHz, DMSO-d6): δ = 9.25 (s, 1H, NH), 7.78–7.76
(m, 2H, ArH), 7.40 (s, 1H, NH), 7.17 (t, J = 8.8 Hz, 2H, ArH), 5.24 (s, 1H, CH), 3.61 (t, J = 8.3
Hz, 2H, CH2), 3.45 (t, J = 8.3 Hz, 2H, CH2); HRMS (TOF ES+): m/z calcd for C11H12FN2O
[(M+H)+], 207.0928; found, 207.0928.
1-(4-Chlorophenyl)-2-(imidazolidin-2-ylidene)ethanone (3b):28d Withe solid (2.05 g, 92%);
Mp: 236–237.5 °C [Lit. 238°C]; 1H NMR (600 MHz, DMSO-d6): δ = 9.26 (s, 1H, NH), 7.73 (d,
J = 8.5 Hz, 2H, ArH), 7.42 (s, 1H, NH), 7.41 (d, J = 8.5 Hz, 2H, ArH), 5.25 (s, 1H, CH), 3.60
(d, J = 7.7 Hz, 2H, CH2), 3.46 (d, J = 7.7 Hz, 2H, CH2); HRMS (TOF ES+): m/z calcd for
C11H12ClN2O [(M+H)+], 223.0633; found, 223.0634.
1-(4-Bromophenyl)-2-(imidazolidin-2-ylidene)ethanone (3c):28d Yellow solid (2.35 g, 88%);
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Mp: 272–274°C [Lit. 275°C]; H NMR (600 MHz, DMSO-d6): δ = 9.25 (s, 1H, NH), 7.66 (d, J
= 8.4 Hz, 2H, ArH), 7.56 (d, J = 8.4 Hz, 2H, ArH), 7.43 (s, 1H, NH), 5.24 (s, 1H, CH), 3.61 (d,
J = 7.7 Hz, 2H, CH2), 3.46 (d, J = 7.7 Hz, 2H, CH2); HRMS (TOF ES+): m/z calcd for
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C11H12BrN2O [(M+H)+], 267.0128; found, 267.0128.
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2-(Imidazolidin-2-ylidene)-1-(p-tolyl)ethanone (3d):28d Withe solid (1.82 g, 90%); Mp: 244–
245 °C [Lit. 245°C]; 1H NMR (600 MHz, DMSO-d6): δ = 9.26 (s, 1H, NH), 7.61 (d, J = 8.0 Hz,
2H, ArH), 7.33 (s, 1H, NH), 7.16 (d, J = 8.0 Hz, 2H, ArH), 5.24 (s, 1H, CH), 3.59 (d, J = 7.6
Hz, 2H, CH2), 3.43 (d, J = 7.6 Hz, 2H, CH2), 2.31 (s, 3H, CH3); HRMS (TOF ES+): m/z calcd for
C12H14N2O [(M+H)+], 203.1179; found, 203.1176.
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2-(Imidazolidin-2-ylidene)-1-(4-methoxyphenyl)ethanone (3e):28d Withe solid (1.99 g, 91%);
Mp: 217–219 °C [Lit. 218°C]; 1H NMR (600 MHz, DMSO-d6): δ = 9.24 (s, 1H, NH), 7.68 (d, J
= 8.6 Hz, 2H, ArH), 7.28 (s, 1H, NH), 6.90 (d, J = 8.6 Hz, 2H, ArH), 5.23 (s, 1H, CH), 3.77 (s,
3H, CH3), 3.59 (t, J = 8.3 Hz, 2H, CH2), 3.43 (t, J = 8.3 Hz, 2H, CH2); HRMS (TOF ES+): m/z
calcd for C12H15N2O2 [(M+H)+], 219.1128; found, 219.1128.
1-(2-Chlorophenyl)-2-(imidazolidin-2-ylidene)ethan-1-one (3f):28e Yellow solid (1.89 g,
85%); Mp: 240–241 °C [Lit. 242°C]; 1H NMR (600 MHz, DMSO-d6): δ = 9.00 (s, 1H, NH), 7.46
(s, 1H, NH), 7.38–7.28 (m, 4H, ArH), 4.72 (s, 1H, CH), 3.61 (t, J = 8.5 Hz, 2H, CH2), 3.44 (t, J
= 8.5 Hz, 2H, CH2); HRMS (TOF ES+): m/z calcd for C11H12ClN2O [(M+H)+], 223.0633; found,
223.0637.
2-(Nitromethylene)imidazolidine (3g):28b White solid (1.11 g, 86%); Mp: 168–169 °C [Lit.
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170°C]; H NMR (600 MHz, DMSO-d6): δ = 8.29 (s, 2H, NH), 6.34 (s, 1H, CH), 3.58 (s, 4H,
CH2); HRMS (TOF ES+): m/zcalcd for C4H7N3NaO2 [(M+Na)+], 152.0430; found, 152.0434.
1-(Imidazolidin-2-ylidene)propan-2-one(3h):28f White solid (87%); Mp: 145–147 °C [Lit.
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148°C]; H NMR (600 MHz, DMSO-d6): δ = 8.88 (s, 1H, NH), 7.07 (s, 1H, NH), 4.51 (s, 1H,
CH), 3.50 (t, J = 8.1 Hz, 2H, CH2), 3.35 (t, J = 8.1 Hz, 2H, CH2), 1.73 (s, 3H, CH3); HRMS
(TOF ES+): m/z calcd for C6H11N2O [(M+H)+], 127.0866; found, 127.0866.
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General procedure for the synthesis of 4-(pyridin-2-ylmethyl)-2-aminopyrroles 4–5.
Arylglyoxal monohydrates 1 (0.5 mmol), ethyl 2-pyridylacetates 2 (0.5 mmol), and ethanol (3
mL) were placed into a 5-mL round-bottom flask. Then, heterocyclic ketene amines (HKAs) 3
(0.5 mmol) were added to this mixture, and the mixture was refluxed until the completion of the
reaction, which was monitored by thin-layer chromatography (TLC, approximately 12 hours).
The reaction mixture was cooled to room temperature. The mixture was extracted three times
with ethyl acetate (25 mL). The combined organic extracts were washed with water and brine,
and finally dried over MgSO4. The solvent was removed in vacuum to afford a crude residue,
which was purified by flash column chromatography to provide 4–5 with good yield of 61−83%.
(4-Fluorophenyl)(5-(4-fluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]im-
idazol-7-yl)methanone (4a): Yellow solid (168 mg, 81%); Mp: 173.0–173.5 °C; IR (KBr) 3435,
2962, 2368, 1598, 1528, 1417, 1249, 1164, 1079, 769cm-1; 1H NMR (600 MHz, DMSO-d6): δ =
8.39–8.38 (m, 1H, NCH), 7.57 (d, J = 1.8 Hz, 1H, ArH), 7.53–7.47 (m, 4H, ArH), 7.23–7.17 (m,
4H, ArH), 7.12–7.04 (m, 2H, ArH), 5.72 (s, 1H, NH), 4.03 (t, J = 8.8 Hz, 4H, ArCH2, NCH2),
3.78 (t, J = 1.5 Hz, 2H, NHCH2); 13C{1H} NMR (150 MHz, DMSO-d6): δ = 187.2, 163.7 (d, J =
244.5 Hz), 162.0, 161.6 (d, J = 243.0 Hz), 153.9, 148.9, 138.4, 136.5, 130.4, 130.3, 128.1, 123.3,
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122.6, 121.2, 119.6, 116.0, 115.6, 100.7, 49.1, 44.7, 34.8; F NMR (470 MHz, DMSO-d6) δ =
110.7, 115.2; HRMS (TOF ES+): m/z calcd for C25H20F2N3O [(M+H)+], 416.1569; found,
416.1569.
(4-Chlorophenyl)(5-(4-fluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]-
imidazol-7-yl)methanone (4b): Yellow solid (168 mg, 78%); Mp: 214.1–210.5 °C; IR (KBr)
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3434, 2896, 1592, 1506, 1416, 1299, 1227 1164, 1084, 1245, 764cm-1; H NMR (600 MHz,
DMSO-d6) δ = 8.31–8.30 (m, 1H, NCH), 7.52–7.49 (m, 1H, ArH), 7.42–7.40 (m, 6H, ArH),
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7.39–7.34 (m, 2H, ArH), 7.16–7.13 (m, 1H, ArH), 7.04–7.96 (m, 1H, ArH), 5.70 (s, 1H, NH),
3.95 (t, J = 4.4 Hz, 4H, ArCH2, NCH2), 3.71–3.68 (m, 2H, NHCH2); 13C{1H} NMR (150 MHz,
DMSO-d6) δ = 187.1, 162.0, 161.6 (d, J = 241.5Hz), 154.1, 148.9, 140.6, 136.5, 135.2, 130.3 (d,
J = 7.5 Hz), 129.7, 128.7, 128.1, 123.4, 122.6, 121.2, 119.5, 116.0 (d, J = 21.0Hz), 100.7, 49.1,
44.7, 34.8; HRMS (TOF ES+): m/z calcd for C25H20ClFN3O [(M+H)+], 432.1273; found,
432.1264.
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(5-(4-Fluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)(p-
tolyl)methanone (4c): Yellow solid (162 mg, 79%); Mp: 207.8–208.0 °C; IR (KBr) 3433, 1593,
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1531, 1504, 1414, 1298, 1225, 1163, 1079, 763cm-1; H NMR (600 MHz, DMSO-d6) δ= 8.32–
8.31 (m, 1H, NCH), 7.50–7.47 (m, 1H, ArCH), 7.42–7.40 (m, 2H, ArH), 7.32 (d, J = 8.0 Hz, 2H,
ArH), 7.15–7.11 (m, 4H, ArH), 7.03–7.01 (m, 4H, ArH), 6.95 (d, J = 7.8 Hz, 1H, ArH), 5.42 (s,
1H, NH), 3.98–3.92 (m, 4H, ArCH2, NCH2), 3.70–3.66 (m, 2H, NHCH2), 2.27 (s,3H, ArCH3);
13C{1H} NMR (150 MHz, DMSO-d6) δ = 188.4, 162.2, 161.5 (d, J = 243.0 Hz), 153.6, 148.9,
140.4, 139.2, 136.4, 130.2 (d, J = 7.5 Hz), 129.2, 128.2, 128.0, 123.1, 122.6, 121.2, 119.8, 115.9
(d, J = 21.0 Hz), 101.0, 49.1, 44.7, 34.7, 21.5; HRMS (TOF ES+): m/z calcd for C26H23FN3O
[(M+H)+], 412.1820; found, 412.1823.
(5-(4-Fluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)(4-
methoxyphenyl)methanone (4d): Yellow solid (164 mg, 77%); Mp: 180.1–180.5 °C; IR (KBr)
3419, 1595, 1529, 1503, 1417, 1305, 1251, 1162, 841, 770cm-1; 1H NMR (600 MHz, DMSO-d6)
δ = 8.32–8.31 (m, 1H, NCH), 7.50–7.47 (m, 1H, ArCH), 7.45–7.40 (m, 4H, ArCH), 7.13 (d, J =
8.9 Hz, 2H, ArH), 7.03–7.01 (m, 1H, ArCH), 6.97 (d, J = 7.9 Hz, 1H, ArH), 6.87–6.86 (m, 2H,
ArH), 5.47 (s, 1H, NH), 4.00–3.93 (m, 4H, ArCH2, NCH2), 3.73 (s, 3H, COCH3), 3.69–3.66 (m,
2H, NHCH2); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 187.7, 162.3, 161.6, 161.6 (d, J = 243.0
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Hz), 153.2, 148.9, 136.5, 134.2, 130.2, 130.2, 128.3, 123.0, 122.7, 121.2, 120.1, 116.0 (d, J =
21.0 Hz), 113.9, 100.9, 55.7, 49.1, 44.7, 34.8; 19F NMR (470 MHz, DMSO-d6) δ = 115.4; HRMS
(TOF ES+): m/z calcd for C26H23FN3O2 [(M+H)+], 428.1769; found, 428.1766.
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(4-Fluorophenyl)(5-phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4e): Yellow solid (157 mg, 79%); Mp: 191.0–191.2 °C; IR (KBr) 3429, 2930,
1603, 1553, 1294, 1219, 1151, 763cm-1; 1H NMR (600 MHz, DMSO-d6) δ = 8.39–8.38 (m, 1H,
NCH), 7.58–7.56 (m, 1H, ArH), 7.53–7.51 (m, 2H, ArH), 7.43–7.41 (m, 1H, ArH), 7.37 (t, J =
7.5 Hz, 3H, ArH), 7.27 (d, J = 7.3 Hz, 1H, ArH), 7.19 (t, J = 8.9 Hz, 2H, ArH), 7.11–7.10 (m,
1H, ArH), 7.04 (d, J = 7.8 Hz, 1H, ArH), 5.73 (s, 1H, NH), 4.07–4.04 (m, 4H, ArCH2, NCH2),
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3.79–3.76 (m, 2H, NHCH2); C{1H} NMR (150 MHz, DMSO-d6) δ = 187.2, 162.9, 162.2,
154.0, 148.9, 138.4, 136.5, 131.7, 130.4 (d, J = 9.0 Hz), 129.0, 128.2, 127.2, 124.3, 122.5, 121.2,
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119.5, 115.6, 115.5, 100.8, 49.1, 44.9, 34.9; F NMR (470 MHz, DMSO-d6) δ = 110.7; HRMS
(TOF ES+): m/z calcd for C25H21FN3O [(M+H)+], 398.1663; found, 398.1664.
(4-Chlorophenyl)(5-phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4f): Yellow solid (163 mg, 79%); Mp: 190.2–190.8°C; IR (KBr) 3433, 2893,
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1593, 1529, 1417, 1298, 1166, 1083, 643cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.38 (d, J =
4.1 Hz, 1H, NCH), 7.58 (d, J = 1.6 Hz, 1H, ArH), 7.46–7.41 (m, 3H, ArH), 7.38 (t, J = 5.1 Hz,
5H, ArH), 7.27 (d, J = 7.3Hz, 1H, ArH), 7.11 (d, J = 1.7 Hz, 1H, ArH), 7.04 (d, J = 7.9 Hz, 1H,
ArH), 5.79 (s, 1H, NH), 4.05 (t, J = 3.4 Hz, 4H, ArCH2, NCH2), 3.78 (t, J = 7.5 Hz, 2H,
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NHCH2); C{1H} NMR (150 MHz, DMSO-d6) δ =187.2, 162.1, 154.2, 148.9, 140.6, 136.5,
135.2, 131.6, 129.7, 129.0, 128.7, 128.2, 127.2, 124.5, 122.5, 121.2, 119.4, 100.8, 49.1, 44.9,
34.9; HRMS (TOF ES+): m/z calcd for C25H21ClN3O [(M+H)+], 414.1368; found, 414.1364.
(5-Phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)(p-tolyl)meth-
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anone (4g): Yellow solid (151 mg, 77%); Mp: 226.5–226.8 °C; IR (KBr) 3322, 3057, 2893,
1599, 1535, 1415, 1298, 1168, 1079, 762cm-1; 1H NMR (600 MHz, DMSO-d6) δ= 8.32–8.31 (m,
1H, NCH), 7.50–7.48 (m, 1H, ArCH), 7.34–7.27 (m, 6H, ArH), 7.19–7.17 (m, 1H, ArH), 7.12 (d,
J = 7.7 Hz, 2H, ArH), 7.03–7.01 (m, 1H, ArH), 6.95 (d, J = 7.9 Hz, 1H, ArH), 5.42 (s, 1H, NH),
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4.01–3.94 (m, 4H, ArCH2, NCH2), 3.70–3.67 (m, 2H, NHCH2), 2.27 (s, 3H, ArCH3); C{1H}
NMR (150 MHz, DMSO-d6) δ= 188.4, 162.2, 153.7, 148.9, 140.4, 139.3, 136.4, 131.8, 129.2,
129.0, 128.1, 123.1, 127.1, 124.1, 122.5, 121.1, 119.8, 101.1, 49.1, 44.9, 34.9, 21.5; HRMS
(TOF ES+): m/z calcd for C26H24N3O [(M+H)+], 394.1914; found, 394.1912.
(4-Methoxyphenyl)(5-phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4h): Yellow solid (159 mg, 78%); Mp: 165.1–165.4 °C; IR (KBr) 3435, 1598,
1527, 1417, 1303, 1249, 1164, 1079, 1034, 843, 769cm-1; H NMR (600 MHz, DMSO-d6) δ=
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8.32–8.31 (m, 1H, NCH), 7.50–7.47 (m, 1H, ArCH), 7.45–7.44 (m, 2H, ArCH), 7.35 (t, J = 1.1
Hz, 2H, ArH), 7.29 (t, J = 7.6 Hz, 2H, ArH), 7.18 (t, J = 7.3 Hz, 1H, ArH), 7.03–7.01 (m, 2H,
ArH), 6.97 (d, J = 7.9Hz, 1H, ArH), 6.87 (t, J = 1.8 Hz, 2H, ArH), 5.47 (s, 1H, NH), 4.03–3.95
(m, 4H, ArCH2, NCH2), 3.73 (s, 3H, COCH3), 3.70–3.67 (m, 2H, NHCH2); C{1H} NMR (150
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MHz, DMSO-d6) δ= 187.7, 162.4, 161.6, 153.3, 148.9, 136.4, 134.3, 131.8, 130.2, 129.0, 128.1,
127.0, 124.0, 122.5, 121.1, 120.0, 113.9, 101.1, 55.7, 49.1, 44.9, 34.9; HRMS (TOF ES+): m/z
calcd for C26H24N3O2 [(M+H)+], 410.1863; found, 410.1862.
(2-Chlorophenyl)(5-phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4i): Yellow solid (156 mg, 76%); Mp: 169.4–169.9 °C; IR (KBr) 3383, 1611,
1534, 1478, 1414, 1361, 1254, 1219, 973, 743cm-1; 1H NMR (600 MHz, DMSO-d6) δ= 8.25 (d, J
= 2.4 Hz, 1H, NCH), 7.49 (t, J = 7.4 Hz, 1H, ArCH), 7.28–7.17 (m, 8H, ArCH), 7.04–6.96 (m,
4H, ArCH), 3.97 (t, 2H, NCH2), 3.77 (d, J = 7.1 Hz, 4H, ArCH2, NCH2); C{1H} NMR (150
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MHz, DMSO-d6) δ= 185.4, 161.5, 155.5, 148.9, 141.7, 136.4, 131.5, 130.3, 130.0, 129.6, 129.0,
128.1, 128.0, 127.4, 127.3, 124.4, 122.3, 121.2, 101.4, 49.1, 44.7, 34.5; HRMS (TOF ES+): m/z
calcd for C25H21ClN3O [(M+H)+], 414.1368; found, 414.1364.
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(4-Fluorophenyl)(6-(pyridin-2-ylmethyl)-5-(p-tolyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4j): Yellow solid (166 mg, 81%); Mp: 179.0–179.2 °C; IR (KBr) 3433, 3262,
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1604, 1539, 1502, 1418, 1223, 1156, 766 cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.38–8.37
(m, 1H, NCH), 7.59–7.56 (m, 1H, ArH), 7.53–7.50 (m, 2H, ArH), 7.29 (d, J = 8.0 Hz, 2H, ArH),
7.20–7.17 (m, 4H, ArH), 7.11–7.09 (m, 1H, ArH), 7.03 (d, J = 7.9 Hz,1H, ArH), 5.70 (s, 1H,
NH), 4.05–4.01 (m, 4H, ArCH2, NCH2), 3.78–3.75 (m, 2H, NHCH2); 13C{1H} NMR (150 MHz,
DMSO-d6) δ =187.1, 163.7 (d, J = 244.5 Hz), 162.3, 153.9, 148.9, 138.5, 136.4 (d, J = 9.0 Hz),
130.4 (d, J = 7.0 Hz), 129.6, 128.8, 128.2, 124.3, 122.4, 121.1, 119.0, 115.6, 115.4, 100.8, 49.1,
44.8, 34.9, 21.2; HRMS (TOF ES+): m/z calcd for C26H23FN3O [(M+H)+], 412.1820; found,
412.1818.
(4-Chlorophenyl)(6-(pyridin-2-ylmethyl)-5-(p-tolyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4k): Yellow solid (172 mg, 81%); Mp: 227.3–227.9 °C; IR (KBr) 3433, 2962,
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1595, 1531, 1414, 1298, 1228, 1166, 1083, 632cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.30–
8.29 (m, 1H, NCH), 7.49 (d, J = 1.8 Hz, 1H, ArH), 7.38–7.37 (m, 4H, ArH), 7.34–7.33 (m, 2H,
ArH), 7.21 (d, J = 8.1 Hz, 2H, ArH), 7.10 (d, J = 8.0 Hz, 1H, ArH), 6.95 (d, J = 7.8 Hz, 1H,
ArH), 5.70 (s, 1H, NH), 3.96–3.93 (m, 4H, ArCH2, NCH2), 3.70 (t, J = 4.6 Hz, 2H, NHCH2),
2.22 (s, 3H, ArCH3); 13C{1H} NMR (150 MHz, DMSO-d6) δ =187.1, 162.2, 154.0, 148.9, 140.7,
136.6, 136.5, 135.2, 129.7, 129.6, 128.7, 128.7, 128.2, 124.5, 122.4, 121.1, 118.9, 100.7, 49.1,
44.8, 34.9, 21.2; HRMS (TOF ES+): m/z calcd for C26H23ClN3O [(M+H)+], 428.1524; found,
428.1518.
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(6-(Pyridin-2-ylmethyl)-5-(p-tolyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)(p-tolyl)meth-
anone (4l): Yellow solid (169 mg, 83%); Mp: 166.1–166.9 °C; IR (KBr) 3385, 2927, 1595,
1532, 1415, 1298, 1167, 760cm-1; 1H NMR (600 MHz, DMSO-d6) δ= 8.31–8.30 (m, 1H, NCH),
7.50–7.47 (m, 1H, ArCH), 7.31 (d, J = 8.0 Hz, 2H, ArH), 7.21 (d, J = 8.1 Hz, 2H, ArH), 7.12–
7.08 (m, 4H, ArH), 7.02–7.00 (m, 1H, ArH), 6.94 (d, J = 7.9 Hz, 1H, ArH), 5.38 (s, 1H, NH),
3.99–3.91 (m, 4H, ArCH2, NCH2), 3.69–3.66 (m, 2H, NHCH2), 2.26 (s, 3H, ArCH3), 2.21 (s, 3H,
ArCH3); 13C{1H} NMR (150 MHz, DMSO-d6) δ= 188.4, 162.4, 153.5, 148.9, 140.3, 139.3,
136.4, 129.6, 129.2, 128.9, 128.9, 128.1, 124.1, 122.5, 121.1, 119.2, 101.1, 49.1, 44.8, 34.9, 21.5,
21.2; HRMS (TOF ES+): m/z calcd for C27H26N3O [(M+H)+], 408.2070; found, 408.2075.
(4-Methoxyphenyl)(6-(pyridin-2-ylmethyl)-5-(p-tolyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-
7-yl)methanone (4m): Yellow solid (165 mg, 78%); Mp: 171.0–171.2 °C; IR (KBr) 3315, 2925,
1600, 1530, 1418, 1305, 1251, 1163, 1077, 1037, 841, 771cm-1; 1H NMR (600 MHz, DMSO-d6)
δ= 8.31–8.30 (m, 1H, NCH), 7.48–7.43 (m, 3H, ArCH), 7.21 (d, J = 8.1 Hz, 2H, ArH), 7.09 (d, J
= 7.9 Hz, 2H, ArH), 7.01 (s, 2H, ArH), 6.95 (d, J = 7.9 Hz, 1H, ArH), 6.87–6.85 (m, 2H, ArH),
5.44 (s, 1H, NH), 4.01–3.92 (m, 4H, ArCH2, NCH2), 3.73 (s, 3H, COCH3), 3.69 (t, J = 1.7 Hz,
2H, NHCH2), 2.21 (s,3H, ArCH3); 13C{1H} NMR (150 MHz, DMSO-d6) δ= 187.7, 162.5, 161.5,
153.1, 148.9, 136.4, 136.3, 134.3, 130.1, 129.6, 129.0, 128.1, 124.0, 122.5, 121.1, 119.5, 113.9,
101.0, 55.7, 49.1, 44.8, 34.9, 21.2; HRMS (TOF ES+): m/z calcd for C27H26N3O2 [(M+H)+],
424.2020; found, 424.2017.
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(2-Chlorophenyl)(6-(pyridin-2-ylmethyl)-5-(p-tolyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)methanone (4n): Yellow solid (132 mg, 62%); Mp: 205.1–205.2 °C; IR (KBr) 3343, 1546,
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1527, 1470, 1414, 1282, 1229, 975, 749cm-1; H NMR (600 MHz, DMSO-d6) δ= 8.24 (s, 1H,
NCH), 7.49 (t, J = 7.6 Hz, 1H, ArCH), 7.24 (t, J = 6.7 Hz, 2H, ArCH), 7.16 (d, J = 7.4 Hz, 3H,
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ArCH), 7.08 (d, J = 7.4 Hz, 3H, ArCH), 7.02 (t, J = 5.8 Hz, 3H, ArCH), 3.95 (t, J = 8.1 Hz, 2H,
NCH2), 3.76 (s, 4H, ArCH2, NCH2), 2.20 (s, 3H, ArCH3); 13C{1H} NMR (150 MHz, DMSO-d6)
δ= 185.3, 161.6, 155.4, 148.8, 141.7, 136.7, 136.4, 130.3, 129.9, 129.6, 128.6, 128.1, 128.0,
127.4, 124.4, 122.3, 121.2, 101.4, 49.1, 44.6, 34.5, 21.2; HRMS (TOF ES+): m/z calcd for
C26H23ClN3O [(M+H)+], 428.1524; found, 428.1522.
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(5-(3,4-Difluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)-
(4-fluorophenyl)methanone (4o): Yellow solid (173 mg, 80%); Mp: 165.1–165.5 °C; IR (KBr)
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3435, 1605, 1556, 1510, 1224, 1150, 768cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.41–8.40
(m, 1H, NCH), 7.61–7.58 (m, 2H, ArH), 7.54–7.52 (m, 2H, ArH), 7.44 (t, J = 8.8 Hz, 1H,
ArH),7.31 (d, J = 1.2 Hz, 1H, ArH), 7.21–7.19 (m, 2H, ArH), 7.13–7.11 (m, 1H, ArH), 7.07 (d, J
= 7.9 Hz, 1H, ArH), 5.75 (s, 1H, NH), 4.06 (t, J = 7.9 Hz, 4H, ArCH2, NCH2), 3.78–3.75 (m,
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2H, NHCH2); C{1H} NMR (150 MHz, DMSO-d6) δ =187.2, 163.3 (d, J = 246.0 Hz), 161.8,
154.0, 150.0 (d, J = 244.0 Hz), 149.0, 148.0 (d, J = 244.0 Hz), 138.3, 136.6, 130.4 (d, J = 9.0
Hz), 129.3, 125.1, 122.9, 122.3, 121.3, 120.8, 118.1 (d, J = 18.0 Hz), 117.0 (d, J = 18.0 Hz),
115.6 (d, J = 22.5 Hz), 100.8, 49.1, 44.8, 34.6; 19F NMR (470 MHz, DMSO-d6) δ = 138.0 (d, J =
-18.8 Hz), 140.7 (d, J = -18.8 Hz), 140.7; HRMS (TOF ES+): m/z calcd for C25H19F3N3O
[(M+H)+], 434.1475; found, 434.1473.
(4-Chlorophenyl)(5-(3,4-difluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-
a]imidazol-7-yl)methanone (4p): Yellow solid (184 mg, 82%); Mp: 209.3–209.8 °C; IR (KBr)
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3433, 1592, 1525, 1469, 1416, 1278, 1223, 1091, 768cm-1; H NMR (600 MHz, DMSO-d6) δ =
8.33 (d, J = 4.0 Hz, 1H, NCH), 7.58–7.50 (m, 2H, ArH), 7.40–7.35 (m, 5H, ArH), 7.23 (d, J =
6.0 Hz, 1H, ArH), 7.06–7.04 (m, 1H, ArH), 7.00 (d, J = 7.8 Hz, 1H, ArH), 5.72 (s, 1H, NH),
3.98 (t, J = 10.8 Hz, 4H, ArCH2, NCH2), 3.69 (t, J = 7.4 Hz, 2H, NHCH2); 13C{1H} NMR (150
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MHz, DMSO-d6) 187.2, 161.7, 154.2, 149.8 (d, J = 243.0 Hz), 149.0, 149.5 (d, J = 243.0 Hz),
140.5, 136.6, 135.4, 129.8, 129.2, 128.8, 125.1, 122.9, 122.4, 121.3, 120.7, 118.1 (d, J = 18.0
Hz), 117.1 (d, J = 18.0 Hz), 100.7, 49.1, 44.8, 34.6; HRMS (TOF ES+): m/z calcd for
C25H19ClF2N3O [(M+H)+], 450.1179; found, 450.1167.
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(5-(3,4-Difluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)-
(4-methoxyphenyl)methanone (4q): Yellow solid (178 mg, 80%); Mp: 205.9–206.3 °C; IR (KBr)
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3324, 1594, 1525, 1469, 1417, 1376, 1304, 1252, 1161, 770cm-1; H NMR (600 MHz, DMSO-
d6) δ= 8.41 (t, J = 4.0 Hz, 1H, NCH), 7.65–7.62 (m, 1H, ArCH), 7.60–7.57 (m, 1H, ArCH), 7.52
(t, J = 6.8 Hz, 2H, ArH), 7.31 (d, J = 10.6 Hz, 1H, ArH), 7.13–7.07 (m, 2H, ArCH), 6.95 (d, J =
8.7 Hz, 1H, ArH), 5.60 (s, 1H, NH), 4.09–4.04 (m, 4H, ArCH2, NCH2), 3.81 (s, 3H, COCH3),
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3.76–3.73 (m, 2H, NHCH2); C{1H} NMR (150 MHz, DMSO-d6) δ = 187.8, 162.0, 161.7,
153.3, 149.8 (d, J = 243.0 Hz), 149.5 (d, J = 243.0 Hz), 149.0, 136.6, 134.1, 130.2, 129.5, 125.0,
123.0, 121.9, 121.3, 121.3, 118.1 (d, J = 18.0 Hz), 117.0 (d, J = 18.0 Hz), 113.9, 101.0, 55.7,
49.1, 44.8, 34.6; 19F NMR (470 MHz, DMSO-d6) δ = 138.1 (d, J = -18.8 Hz), 141.2 (d, J = -18.8
Hz); HRMS (TOF ES+): m/z calcd for C26H22F2N3O2 [(M+H)+], 446.1675; found, 446.1682.
(2-Chlorophenyl)(5-(3,4-difluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-
a] -imidazol-7-yl)methanone (4r): Yellow solid (141 mg, 63%); Mp: 175.1–175.7 °C; IR (KBr)
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3383, 1606, 1530, 1475, 1416, 1271, 1220, 974, 750cm-1; H NMR (600 MHz, DMSO-d6) δ=
8.36 (s, J = 3.5 Hz, 1H, NCH), 7.58 (t, J = 6.6 Hz, 2H, ArCH), 7.44–7.33 (m, 4H, ArCH), 7.23
(d, J = 6.0 Hz, 2H, ArCH), 7.19 (s, 1H, ArCH), 7.14–7.12 (m, 1H, ArCH), 7.06 (s, 1H, ArCH),
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4.06 (t, J = 8.1 Hz, 2H, NCH2), 3.83 (d, J = 8.0 Hz, 4H, ArCH2, NCH2); C{1H} NMR (150
MHz, DMSO-d6) δ = 185.5, 161.1, 155.5, 150.6, 150.6, 149.8 (d, J = 243.0 Hz), 149.5 (d, J =
243.0 Hz), 141.6, 136.5, 130.4, 130.0, 129.6, 129.1, 128.0, 127.5, 125.0, 122.6, 122.4, 121.4,
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118.1 (d, J = 18.0 Hz), 117.1 (d, J = 18.0 Hz), 101.4, 49.1, 44.6, 34.3; HRMS (TOF ES+): m/z
calcd for C25H19ClF2N3O [(M+H)+], 450.1179; found, 450.1174.
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(6-((5-Ethylpyridin-2-yl)methyl)-5-(4-fluorophenyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-
yl)(4-fluorophenyl)methanone (4s): Yellow solid (172 mg, 78%); Mp: 186.3–186.5 °C; IR (KBr)
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3440, 1572, 1457, 1418, 1267, 1239, 1033, 753cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.25
(d, J = 1.7 Hz, 1H, NCH), 7.53–7.49 (m, 4H, ArH), 7.44–7.42 (m, 1H, ArH), 7.24–7.18 (m, 4H,
ArH), 6.96 (d, J = 8.0 Hz, 1H, ArH), 5.73 (s, 1H, NH), 4.03 (t, J = 7.9 Hz, 4H, ArCH2, NCH2),
3.76 (t, J = 7.4 Hz, 2H, NHCH2), 2.56–2.51 (m, 2H, CH2CH3), 1.16 (t, J = 7.6 Hz, 3H,
CH2CH3); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 187.2, 163.7 (d, J = 246.0 Hz), 161.6 (d, J =
243.0 Hz), 159.4, 153.9, 148.4, 138.4, 136.0, 135.8, 130.4 (d, J = 9.0 Hz), 130.2 (d, J = 7.5 Hz),
128.2, 123.2, 122.2, 119.9, 116.0 (d, J = 21.0 Hz), 115.5 (d, J = 21.0 Hz), 100.7, 49.1, 44.7, 34.3,
25.4, 15.8; HRMS (TOF ES+): m/z calcd for C27H24F2N3O [(M+H)+], 444.1882; found,
444.1883.
(4-Chlorophenyl)(6-((5-ethylpyridin-2-yl)methyl)-5-(4-fluorophenyl)-2,3-dihydro-1H-pyrrolo-
[1,2-a]imidazol-7-yl)methanone (4t): Yellow solid (181 mg, 79%); Mp: 189.1–189.6 °C; IR
(KBr) 3443, 1593, 1564, 1439, 1418, 1277, 1203, 1081, 760cm-1; H NMR (600 MHz, DMSO-
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d6) δ = 8.25 (d, J = 1.8 Hz, 1H, NCH), 7.51–7.49 (m, 2H, ArH), 7.46–7.41 (m, 5H, ArH), 7.22
(d, J = 8.8 Hz, 2H, ArH), 6.96 (d, J = 8.0 Hz, 1H, ArH), 5.78 (s, 1H, NH), 4.04–4.00 (m, 4H,
ArCH2, NCH2), 3.77 (t, J = 7.5 Hz, 2H, NHCH2), 2.56–2.53 (m, 2H, CH2CH3), 1.16 (t, J = 7.6
Hz, 3H, CH2CH3); C{1H} NMR (150 MHz, DMSO-d6) δ = 187.1, 161.0 (d, J = 243.0 Hz),
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159.3, 154.1, 148.4, 140.6, 136.1, 135.8, 135.2, 130.2 (d, J = 9.0 Hz), 129.7, 128.7, 128.1, 123.4,
122.2, 119.7, 116.0 (d, J = 21.0 Hz), 100.7, 49.1, 44.7, 34.3, 25.4, 15.9; HRMS (TOF ES+): m/z
calcd for C27H24ClFN3O [(M+H)+], 460.1586; found, 460.1586.
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[1,2-a]imidazol-7-yl)methanone (4u): Yellow solid (206 mg, 82%); Mp: 201.1–201.6 °C; IR
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(KBr) 3433, 1597, 1542, 1433, 1416, 1289, 1204, 1086, 753cm-1; H NMR (600 MHz, DMSO-
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d6) δ = 8.24 (d, J = 1.8 Hz, 1H, NCH), 7.55 (d, J = 8.3 Hz, 2H, ArH), 7.51–7.49 (m, 2H, ArH),
7.43–7.37 (m, 3H, ArH), 7.22 (d, J = 8.8 Hz, 2H, ArH), 6.96 (d, J = 8.0 Hz, 1H, ArH), 5.79 (s,
1H, NH), 4.03–3.99 (m, 4H, ArCH2, NCH2), 3.77 (t, J = 7.5 Hz, 2H, NHCH2), 2.56–2.53 (m,
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2H, CH2CH3), 1.16 (t, J = 7.6 Hz, 3H, CH2CH3); C{1H} NMR (150 MHz, DMSO-d6) δ =
187.2, 161.6 (d, J = 243.0 Hz), 159.3, 154.1, 148.4, 141.0, 136.1, 135.8, 131.6, 130.2 (d, J = 7.5
Hz), 129.9, 128.1, 124.1, 123.4, 122.2, 119.7, 116.0 (d, J = 21.0 Hz), 100.6, 49.1, 44.7, 34.3,
25.4, 15.9; HRMS (TOF ES+): m/z calcd for C27H24BrFN3O [(M+H)+], 504.1081; found,
504.1083.
(6-((5-Ethylpyridin-2-yl)methyl)-5-phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)(4-flu-
orophenyl)methanone (4v): Yellow solid (165 mg, 78%); Mp: 161.9–162.5 °C; IR (KBr) 3443,
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1560, 1453, 1419, 1247, 1227, 1037, 750cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.25 (s, 1H,
NCH), 7.54–7.52 (m, 2H, ArH), 7.44–7.36 (m, 5H, ArH), 7.28–7.25 (m, 1H, ArH), 7.19 (t, J =
8.8 Hz, 2H, ArH), 6.96 (d, J = 8.0 Hz, 1H, ArH), 5.74 (s, 1H, NH), 4.03–4.07 (m, 4H, ArCH2,
NCH2), 3.77(t, J = 7.7 Hz, 2H, NHCH2), 2.56–2.51 (m, 2H, CH2CH3), 1.16 (t, J = 7.6 Hz, 3H,
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CH2CH3); C{1H} NMR (150 MHz, DMSO-d6) δ = 187.2, 163.7 (d, J = 246.0 Hz), 159.5,
154.0, 148.4, 138.4, 135.8 (d, J = 36.0 Hz), 131.7, 130.4 (d, J = 9.0 Hz), 129.0, 128.2, 127.8,
127.1, 124.2, 122.0, 119.8, 115.5 (d, J = 21.0 Hz), 100.9, 49.1, 44.9, 34.4, 25.4, 15.8; HRMS
(TOF ES+): m/z calcd for C27H25FN3O [(M+H)+], 426.1976; found, 426.1974.
(4-Chlorophenyl)(6-((5-ethylpyridin-2-yl)methyl)-5-phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]imi-
dazol-7-yl)methanone (4w): Yellow solid (167 mg, 76%); Mp:210.2–210.5 °C; IR (KBr) 3433,
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1597, 1542, 1433, 1416, 1289, 1204, 1086, 760cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.24
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(d, J = 1.6 Hz, 1H, NCH), 7.46–7.41 (m, 4H, ArH), 7.37 (t, J = 7.6 Hz, 5H, ArH), 7.27 (t, J =
7.4 Hz, 1H, ArH), 6.96 (d, J = 7.0 Hz, 1H, ArH), 5.79 (s, 1H, NH), 4.06–4.02 (m, 4H, ArCH2,
NCH2), 3.79–3.76 (m, 2H, NHCH2), 2.57–2.53 (m, 2H, CH2CH3), 1.17(t, J = 7.6 Hz, 3H,
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CH2CH3); C{1H} NMR (150 MHz, DMSO-d6) δ =187.1, 159.5, 154.2, 148.4, 140.7, 136.0,
135.7, 135.2, 131.7, 129.7, 129.0, 128.7, 128.2, 127.1, 124.4, 122.0, 119.7, 100.8, 49.1, 44.9,
34.4, 25.4, 15.9; HRMS (TOF ES+): m/z calcd for C27H25ClN3O [(M+H)+], 442.1681; found,
442.1681.
(4-Bromophenyl)(6-((5-ethylpyridin-2-yl)methyl)-5-phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]imi-
dazol-7-yl)methanone (4x): Yellow solid (182 mg, 75%); Mp: 200.5–200.9 °C; IR (KBr) 3446,
1587, 1532, 1434, 1417, 1289, 1204, 1086, 760cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.17
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(d, J = 1.8 Hz, 1H, NCH), 7.48 (d, J = 1.7 Hz, 4H, ArH), 7.35 (d, J = 7.4 Hz, 3H, ArH), 7.31–
7.28 (m, 4H, ArH), 7.19 (d, J = 7.4 Hz, 1H, ArH), 6.88 (d, J = 8.0 Hz, 1H, ArH), 5.72 (s, 1H,
NH), 3.98–3.94 (m, 4H, ArCH2, NCH2), 3.71–3.68 (m, 2H, NHCH2), 2.49–2.45 (m, 2H,
CH2CH3), 1.09 (t, J = 7.6 Hz, 3H, CH2CH3); C{1H} NMR (150 MHz, DMSO-d6) δ =187.2,
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159.4, 154.2, 148.4, 141.0, 136.0, 135.7, 135.7, 131.6, 129.9, 129.0, 128.1, 127.2, 124.4, 124.1,
122.0, 119.6, 100.8, 49.1, 44.9, 34.4, 25.4, 15.9; HRMS (TOF ES+): m/z calcd for C27H25BrN3O
[(M+H)+], 486.1176; found, 486.1172.
(4-Fluorophenyl)(5-(4-fluorophenyl)-6-((6-methylpyridin-2-yl)methyl)-2,3-dihydro-1H-pyrr-
olo[1,2-a]imidazol-7-yl)methanone (4y): Yellow solid (178 mg, 83%); Mp: 184.9–185.5 °C; IR
(KBr) 3443, 1594, 1443, 1418, 1253, 1217, 1079, 763cm-1; 1H NMR (600 MHz, DMSO-d6) δ =
7.44–7.37 (m, 5H, ArH), 7.16–7.09 (m, 4H, ArH), 6.87 (d, J = 7.6 Hz, 1H, ArH), 6.75 (d, J =
7.7 Hz,1H, ArH),5.69 (s, 1H, NH), 3.96–3.90 (m, 4H, ArCH2, NCH2), 3.69 (t, J = 7.9 Hz, 2H,
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NHCH2), 2.30 (s, 3H, CH2CH3); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 187.3, 163.7 (d, J =
244.5 Hz), 161.6 (d, J = 243.0 Hz), 161.3, 157.0, 153.9, 138.4, 136.8, 130.3 (d, J = 9.0 Hz),
130.3, 128.1, 123.3, 120.4, 119.6, 119.3, 115.9 (d, J = 21.0 Hz), 115.5 (d, J = 21.0 Hz), 100.7,
49.1, 44.7, 34.7, 24.5; HRMS (TOF ES+): m/z calcd for C26H22F2N3O [(M+H)+], 430.1725;
found, 430.1717.
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(4-Bromophenyl)(5-(4-fluorophenyl)-6-((6-methylpyridin-2-yl)methyl)-2,3-dihydro-1H-pyrrolo
-[1,2-a]imidazol-7-yl)methanone (4z): Yellow solid (186 mg, 76%); Mp: 210.2–210.5 °C; IR
(KBr) 3434, 1587, 1506, 1457, 1415, 1228, 1163, 1074, 1015cm-1; 1H NMR (600 MHz, DMSO-
d6) δ = 7.48–7.37 (m, 5H, ArH), 7.27 (d, J = 8.3 Hz, 2H, ArH), 7.15 (t, J = 8.9 Hz, 2H, ArH),
6.88 (d, J = 7.6 Hz, 1H, ArH), 6.74 (d, J = 7.7 Hz, 1H, ArH), 5.79 (s, 1H, NH), 3.96–3.87 (m,
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4H, ArCH2, NCH2), 3.70 (t, J = 8.3 Hz, 2H, NHCH2), 2.30 (s, 3H, CH2CH3); C{1H} NMR
(150 MHz, DMSO-d6) δ = 187.3, 161.6 (d, J = 243.0 Hz), 161.2, 157.0, 154.2, 141.0, 136.8,
131.6, 130.3 (d, J = 9.0 Hz), 129.9, 128.1, 124.0, 123.4, 120.4, 119.3, 119.2, 115.9 (d, J = 22.5
Hz), 100.6, 49.1, 44.7, 34.7, 24.5; HRMS (TOF ES+): m/z calcd for C26H22BrFN3O [(M+H)+],
490.0925; found, 490.0919.
(4-Fluorophenyl)(6-((6-methylpyridin-2-yl)methyl)-5-phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]im
-idazol-7-yl)methanone (4a'): Yellow solid (158 mg, 77%); Mp: 171.9–172.5 °C; IR (KBr)
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3469, 1572, 1593, 1449, 1416, 1257, 1207, 1070, 755cm-1; H NMR (600 MHz, DMSO-d6) δ =
7.52–7.42 (m, 5H, ArH), 7.38 (t, J = 7.6 Hz, 2H, ArH), 7.27 (t, J = 7.3 Hz,1H, ArH), 7.18 (t, J =
7.8 Hz, 2H, ArH), 6.95 (d, J = 7.6 Hz, 1H, ArH), 6.82 (d, J = 7.7 Hz, 1H, ArH), 5.77 (d, J = 9.5
Hz, 1H, NH), 4.06–4.01 (m, 4H, ArCH2, NCH2), 3.79–3.77 (m, 2H, NHCH2), 2.38 (s, 3H,
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CH2CH3); C{1H} NMR (150 MHz, DMSO-d6) δ = 187.3, 163.7 (d, J = 246.0 Hz), 161.5,
156.9, 154.1, 136.8, 131.7, 130.3 (d, J = 9.0 Hz), 129.0, 128.2, 127.1, 124.3, 120.4, 119.5, 119.2,
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115.5 (d, J = 21.0 Hz), 100.8, 49.1, 44.9, 34.8, 24.5; HRMS (TOF ES+): m/z calcd for
C26H23FN3O [(M+H)+], 412.1820; found, 412.1819.
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(4-Bromophenyl)(6-((6-methylpyridin-2-yl)methyl)-5-phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]im
-idazol-7-yl)methanone (4b'): Yellow solid (186 mg, 79%); Mp: 192.6–192.8 °C; IR (KBr)
3433, 1592, 1504, 1457, 1415, 1248, 1167, 1078, 1013 cm-1; 1H NMR (600 MHz, DMSO-d6) δ =
7.54 (d, J = 8.4 Hz, 2H, ArH), 7.47–7.41 (m, 3H, ArH), 7.39–7.34 (m, 4H, ArH), 7.27 (t, J = 7.3
Hz, 1H, ArH), 6.95 (d, J = 7.6 Hz, 1H, ArH), 6.81 (d, J = 1.2 Hz, 1H, ArH), 5.89 (s, 1H, NH),
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4.06–3.98 (m, 4H, ArCH2, NCH2), 3.81–3.78 (m, 2H, NHCH2), 2.38 (s, 3H, CH2CH3); C{1H}
NMR (150 MHz, DMSO-d6) δ =187.3, 161.3, 157.0, 154.3, 141.0, 136.8, 131.6, 131.6, 129.8,
129.0, 128.2, 127.2, 124.4, 124.0, 120.4, 119.2, 119.2, 100.8, 49.1, 44.9, 34.8, 24.5; HRMS
(TOF ES+): m/z calcd for C26H23BrN3O [(M+H)+], 472.1019; found, 472.1018.
1-(5-Phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)ethan-1-one
(5a): White solid (111 mg, 70%); Mp: 203.9–204.5 °C; IR (KBr) 1617, 1363, 701, 644, 611, 570
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cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.46 (d, J = 4.5 Hz, 1H, NCH), 7.64–7.61 (m, 1H,
ArH), 7.39–7.34 (m, 4H, ArH), 7.25(t, J = 7.1 Hz, 1H, ArH), 7.14 (t, J = 4.8 Hz, 2H, ArH), 6.48
(s, 1H, NH), 4.14 (s, 2H, ArCH2), 4.06 (t, J = 7.7 Hz, 2H, NCH2), 3.90 (d, J = 7.0 Hz, 2H,
NHCH2), 2.14 (s, 3H, CH3); 13C{1H} NMR (150 MHz, DMSO-d6) δ =189.4, 162.5, 153.9, 149.0,
136.6, 131.8, 129.0, 128.1, 127.0, 123.5, 122.7, 121.2, 119.0, 102.3, 48.9, 45.0, 35.0, 29.6;
HRMS (TOF ES+): m/z calcd for C20H20N3O [(M+H)+], 318.1601; found, 318.1599.
1-(5-(4-Fluorophenyl)-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)-
ethan-1-one (5b): White solid (119 mg, 71%); Mp: 181.2–181.5 °C; IR (KBr) 1617, 1361, 700,
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634, 570 cm-1; H NMR (600 MHz, DMSO-d6) δ = 8.45 (d, J = 4.6 Hz, 1H, NCH), 7.64–7.61
(m, 1H, ArH), 7.46–7.44 (m, 2H, ArH), 7.22–7.13 (m, 4H, ArH), 6.47 (s, 1H, NH), 4.09 (s, 2H,
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ArCH2), 4.04 (t, J = 7.7 Hz, 2H, NCH2), 3.89 (t, 2H, NHCH2), 2.13 (s, 3H, CH3); 13C{1H} NMR
(150 MHz, DMSO-d6) δ = 189.3, 162.3, 161.5 (d, J = 246.0 Hz), 153.8, 149.0, 136.6, 130.1 (d, J
= 9.0 Hz), 128.3, 122.8, 122.5, 121.2, 119.1, 115.8 (d, J = 21.0 Hz), 102.1, 48.9, 44.8, 34.8, 29.6;
HRMS (TOF ES+): m/z calcd for C20H19FN3O [(M+H)+], 336.1507; found, 336.1507.
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1-(6-((5-Ethylpyridin-2-yl)methyl)-5-phenyl-2,3-dihydro-1H-pyrrolo[1,2-a]imidazol-7-yl)eth-
an-1-one (5c): White solid (125 mg, 75%); Mp: 183.9–184.5 °C; IR (KBr) 1617, 1460, 1375,
1361, 701, 644 cm-1; 1H NMR (600 MHz, DMSO-d6) δ = 8.31 (d, J = 1.9 Hz, 1H, NCH), 7.48–
7.47 (m, 1H, ArH), 7.40–7.34 (m, 4H, ArH), 7.25 (t, J = 7.3 Hz, 1H, ArH), 7.05 (d, J = 8.0 Hz,
1H, ArH), 6.47 (s, 1H, NH), 4.09–4.05 (m, 4H, ArCH2, NCH2), 3.91–3.88 (m, 2H, NHCH2),
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2.59–2.55 (m, 2H, CH2CH3), 2.13 (s, 3H, CH3), 1.18 (t, J = 7.6 Hz, 3H, CH2CH3); C{1H}
NMR (150 MHz, DMSO-d6) δ =189.3, 159.8, 153.9, 148.5, 136.0, 135.9, 131.9, 129.0, 128.1,
127.0, 123.4, 122.2, 119.3, 102.3, 48.9, 45.0, 34.5, 29.6, 25.4, 15.8; HRMS (TOF ES+): m/z calcd
for C22H24N3O [(M+H)+], 346.1914; found, 346.1907.
7-Nitro-5-phenyl-6-(pyridin-2-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]imidazole(5d): Yellow
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solid (72 mg, 45%); Mp: 163.9–164.5 °C; IR (KBr) 1616, 1560, 1361, 699, 643, 610 cm-1; H
NMR (600 MHz, DMSO-d6) δ = 8.47 (d, J = 4.3 Hz, 1H, NCH), 7.92 (s, 1H, NH), 7.68 (t, J =
7.4 Hz, 1H, ArH), 7.48 (d, J = 7.8 Hz, 2H, ArH), 7.41 (t, J = 7.5 Hz, 2H, ArH), 7.33 (t, J = 7.4
Hz, 1H, ArH), 7.21–7.17 (m, 2H, ArH), 4.16 (s, 2H, ArCH2), 4.13 (d, J = 5.4 Hz, 2H, NCH2),
4.02 (t, J = 8.8 Hz, 2H, NHCH2); 13C{1H} NMR (150 MHz, DMSO-d6) δ =161.1, 151.6, 149.3,
136.8, 130.5, 129.2, 128.3, 128.1, 124.2, 122.6, 121.6, 114.5, 113.0, 49.0, 45.4, 33.9; HRMS
(TOF ES+): m/z calcd for C18H17N4O2 [(M+H)+], 321.1346; found, 321.1339.
6-((5-Ethylpyridin-2-yl)methyl)-5-(4-fluorophenyl)-7-nitro-2,3-dihydro-1H-pyrrolo[1,2-a]imid
-azole (5e): Yellow solid (82 mg, 45%); Mp: 179.9–180.3 °C; IR (KBr) 1561, 1617, 1464, 1372,
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