NIS-promoted multicomponent reaction of 2-aminopyridines with aldehydes and nitromethane for the synthesis of 3-nitroimidazo[1.2-a]pyridines

Article abstract of DOI:10.1002/jhet.3869

An efficient synthesis of 3-nitroimidazo[1,2-a]pyridines has been developed via N-iodosuccinimide (NIS)-mediated multicomponents reaction of 2-aminopyridines, aldehydes, and nitromethane under metal-free conditions. This protocol has many advantages such as broad substituent scope, mild and eco-friendly conditions, high step economy, and good yields.

Full text of DOI:10.1002/jhet.3869

Received: 29 September 2019
DOI: 10.1002/jhet.3869
Revised: 28 November 2019
Accepted: 3 December 2019
C O M M U N I C A T I O N S
NIS-promoted multicomponent reaction of
2-aminopyridines with aldehydes and nitromethane for
the synthesis of 3-nitroimidazo[1.2-a]pyridines
Jinwei Sun1
| Xinrui Yang1 | Yun Liu2
| Yi Wang3 | Yi Pan3
1Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Jiangsu Key Laboratory of Atmospheric
Environment Monitoring and Pollution Control, School of Chemistry and Materials Science, Nanjing University of Information Science and
Technology, Nanjing, Jiangsu, China
2School of Chemistry and Material Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
3School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China
Correspondence
Jinwei Sun, Jiangsu Collaborative
Abstract
Innovation Center of Atmospheric
Environment and Equipment Technology,
Jiangsu Key Laboratory of Atmospheric
Environment Monitoring and Pollution
Control, School of Chemistry and
Materials Science, Nanjing University of
Information Science and Technology,
Nanjing, Jiangsu 210044, China.
An efficient synthesis of 3-nitroimidazo[1,2-a]pyridines has been developed via N-
iodosuccinimide (NIS)-mediated multicomponents reaction of 2-aminopyridines,
aldehydes, and nitromethane under metal-free conditions. This protocol has many
advantages such as broad substituent scope, mild and eco-friendly conditions, high
step economy, and good yields.
K E Y W O R D S
Email: gysunjinwei@126.com
2-aminopyridines, 3-nitroimidazo[1,2-a]pyridines, aldehydes, metal-free synthesis, NIS promotion,
nitromethane
Yun Liu, School of Chemistry and Material
Science, Jiangsu Normal University,
Xuzhou, Jiangsu 221116, China.
Email: liu__yun3@sina.com
Yi Wang, School of Chemistry & Chemical
Engineering, Nanjing University, Nanjing
210023, China.
Email: yiwang@nju.edu.cn
Funding information
Natural Science Foundation of Jiangsu
Province, Grant/Award Numbers:
201910300018Z, 17KJB150016,
BK20170939
1 | INTRODUCTION
As an important class of imidazopyridine derivatives,
3-nitroimidazo[1.2-a]pyridines are attractive synthetic tar-
Imidazo[1,2-a]pyridine is a privileged structure in the
area of materials[1,2] and pharmaceuticals.[3–8] This struc-
ture has also been found in several commercial drugs,
including zolpidem, saripidem, zolimidine, and
olprinone.[9–11] Hence, the syntheses of these compounds
have drawn significant attention in the past decade.[12–22]
get molecules. In 2012, Liang's group reported an example
to synthesize 3-nitroimidazo[1.2-a]pyridines via copper-
catalyzed three-components reaction of 2-aminopyridines
with aldehydes and nitromethane (Scheme 1a).[23] Mean-
while, they investigated the reaction of 2-aminopyridines
with nitroolefins and found that this pathway led to the
J Heterocycl Chem. 2020;1–7.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals, Inc.
1

2
SUN ET AL.
desired products as well (Scheme 1b).[24] More recently,
metal-free conditions are highly desired. Following our con-
tinuous interest in heterocycle synthesis,[27–31] herein, we
reported an efficient protocol to assemble 3-nitroimidazo
[1,2-a]pyridines via N-iodosuccinimide (NIS)-promoted
three-component reaction of 2-aminopyridines with alde-
hydes and nitromethane (Scheme 1d).
using
copper-based
metal-organic
frameworks[25]
(Scheme 1c) or magnetic carbon nanotube supported cop-
per[26] as catalysts for the synthesis of 3-nitroimidazo
[1,2-a] pyridines have also been developed.
Considering the existing synthetic routes to
3-nitroimidazo[1,2-a], pyridines usually use metal catalysts,
which may result in environmental pollution; the develop-
ment of eco-friendly method to these compounds under
2 | RESULTS AND DISCUSSION
To begin our work, we employed 2-aminopyridine 1a,
benzaldehyde 2a, and nitromethane 3 as the model reac-
tants. Initially, by heating 1a (1.5 mmol), 2a (0.5 mmol),
3 (0.5 mmol), and NIS (0.5 mmol) in dimethylformamide
(DMF) at 90ꢀC for 6 hours; 4a was isolated in 45% yield
(Table 1, entry 1). Other solvents such as dioxane, ben-
zene, dichloro ethane, and ethanol were also examined,
but no improved result was given (Table 1, entries 2-5).
Pleasingly, changing the solvent to acetonitrile led to 4a
in 78% yield (Table 1, entry 6). Next, we examined other
additives but did not get better result (Table1, entry 7-9).
In addition, the loading of NIS has also been examined.
The results showed 1 equivalent of NIS was the best
choice (Table 1, entry 10-11). Finally, we tried to lower
the temperature but found that the yield of 4a decreased
as well (Table 1, entry 12). Therefore, we set the reaction
conditions to refluxing the mixture of 1a (1.5 mmol), 2a
(0.5 mmol), 3 (0.5 mmol), and NIS (0.5 mmol) in acetoni-
trile for 6 hours.
ꢀ
SCHEME 1 Synthesis of 3-nitroimidazo[1,2-a]pyridines
TABLE 1 Optimization of reaction
conditionsa
Entry
Solvent
Additive (equivalent)
NIS (1)
Temperature (ꢀC)
Yield (%)b
1
DMF
90
45
2
Dioxane
NIS (1)
90
42
3
Benzene
NIS (1)
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
60
36
4
Dichloroethane
Ethanol
NIS (1)
25
5
NIS (1)
30
6
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
NIS (1)
78
7
I2 (1)
73
8
ICl (1)
trace
trace
36
9
NBS (1)
NIS (0.5)
NIS (1.5)
NIS (1)
10
11
12
78
55
aConditions: 1a (1.5 mmol), 2a (0.5 mmol), 3 (0.5 mmol), and NIS (0.5 mmol) heating in solvent for 6 hours.
bIsolated yield.

SUN ET AL.
3
TABLE 2 Scope of 1 and 2a,b
aConditions: 1 (1.5 mmol), 2 (0.5 mmol), 3 (0.5 mmol), and NIS (0.5 mmol) refluxing in acetonitrile (5 mL) for 6 hours.
bIsolated yields.
With the optimal conditions in hand, we then
explored the scope of reactants 1 and 2 (Table 2). Firstly,
we used various benzaldehydes 2 to react with 1a and
3 under the optimal conditions. It showed that a variety
of mono-substituted benzaldehydes 2b-i attached with
electron-neutral (Ph), electron-withdrawing (Cl, NO2), or
electron-donating groups (Me, OMe) participated in the
reaction smoothly, providing the corresponding
3-nitroimidazo[1,2-a]pyridines 4b-i in 60% to 76% yields.
For disubstituted benzaldehydes 2j and 2k, the target
products 4j and 4k were afforded in 60% and 72% yields,
respectively.
Next, the scope of 2-aminopyridines was screened. It
showed that 2-aminopyridines 1b-d including ortho-,
meta-, or para-substituent formed the desired products 5a-
c in good yields as well. All products, 4 and 5, were char-
acterized by nuclear magnetic resonance (NMR) and high-
resolution mass spectrometry (HRMS), and the data of
known compound 4a were in accordance with previous
report.[24]

4
SUN ET AL.
result suggested that the reaction was probably carried
out via a radical process (Scheme 2d).
According to the previous literature[23–25] and our
experimental results, the plausible mechanism was pro-
posed in Scheme 3. Firstly, the three-components reac-
tion of 1a with 2a and 3 forms intermediate I via path A
or B. Then, NIS extracts hydrogen radical of I, generating
radical intermediate II and succimide (NHS), dispelling
an iodine atom. Subsequently, II is transformed to inter-
mediate III via the reaction with iodine radical,[32]
followed by cyclization. At last, III underwent resonance
and oxidation processes, giving the final product 4a.
3 | CONCLUSION
In conclusion,
a
convenient NIS-promoted mul-
ticomponent reaction has been developed to assemble
3-nitroimidazo[1,2-a]pyridines under metal-free condi-
tions. Various functional groups could survive in this
reaction and a range of products were obtained in good
yields.
SCHEME 2 Control experiments
4 | EXPERIMENTAL
4.1 | General
Melting points are uncorrected. 1H NMR spectra were mea-
sured at 400/500 MHz with CDCl3 as solvent. The chemical
shifts (δ) are reported in parts per million relative to the
residual deuterated solvent signal, and coupling coupling
constants (J) are given in Hertz. 13C NMR spectra were
measured at 100/125 MHz with CDCl3 as solvent.
4.2 | General procedure for the
preparation of 4
SCHEME 3 Plausible reaction mechanism
The mixture of 2-aminopyridine 1a (1.5 mmol), aldehyde
2
(0.5 mmol), nitromethane 3 (0.5 mmol), and NIS
To shed light on the plausible reaction mechanism,
several control experiments were carried out (Scheme 2).
Firstly, we prepared imine 6 by refluxing the mixture of
1a and 2a in acetonitrile for 3 hours (Scheme 2a). Then,
we exposed imine 6 with nitromethane 3 and NIS in ace-
tonitrile and obtained 4a in 85% yield (Scheme 2b). Sec-
ondly, by refluxing the mixture of 2-aminopyridine 1a
with nitroolefin 7 in the presence of NIS, we obtained 4a
in 82% yield (Scheme 2c). These results showed that
6 and 7 were the possible reaction intermediates. Thirdly,
by adding 3 equivalent of TEMPO to the standard condi-
tions, the reaction was remarkably suppressed. This
(0.5 mmol) was refluxed in acetonitrile (5 mL) for 6 hours in
a round bottle. After the reaction was completed, the solvent
was removed under reduced pressure, and the residue was
separated by flash chromatography on a silica gel column
with ethyl acetate/petroleum as eluent to give the products 4.
4.2.1 | 3-nitro-2-phenylimidazo[1,2-a]
pyridine (4a)
Yield: 78%. Yellow solid, mp 171-173ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.53 (d, J = 7.2 Hz, 1H), 7.93-7.87

SUN ET AL.
5
(m, 3H), 7.68 (t, J = 8.0 Hz, 1H), 7.53-7.51 (m, 3H), 7.30
(td, J = 7.2, 0.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
150.3, 145.2, 131.9, 130.9, 130.3, 128.3, 128.2, 118.4, 116.5.
HRMS (ESI) m/z calcd for C13H10N3O2 [M + H]+
240.0773, found, 240.0770.
143.0, 140.4, 130.9, 130.7, 130.6, 128.8, 128.2, 127.8, 127.2,
126.8, 118.3, 116.5. HRMS (ESI) m/z calcd for
C19H14N3O2 [M + H]+ 316.1086, found, 316.1090.
4.2.6 | 2-(4-Methoxyphenyl)-
3-nitroimidazo[1,2-a]pyridine (4f)
4.2.2 | 2-(4-Chlorophenyl)-3-nitroimidazo
[1,2-a]pyridine (4b)
Yield: 75%. Yellow solid, mp 169-170ꢀC. 1H NMR
(500 MHz, CDCl3) δ 9.51 (d, J = 7.0 Hz, 1H), 7.94 (d,
J = 8.9 Hz, 2H), 7.81 (d, J = 8.9 Hz, 1H), 7.68-7.54 (m,
1H), 7.24 (dd, J = 7.0, 1.2 Hz, 1H), 7.02 (d, J = 8.9 Hz,
2H), 3.89 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 161.3,
150.3, 145.2, 131.9, 130.9, 128.3, 124.0, 118.1, 116.2, 113.6,
55.4. HRMS (ESI) m/z calcd for C14H12N3O3 [M + H]+
270.0879, found, 270.0876.
Yield: 70%. Yellow solid, mp 184-185ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.52 (d, J = 7.0 Hz, 1H), 7.92-7.81
(m, 3H), 7.73-7.61 (m, 1H), 7.49 (d, J = 8.6 Hz, 2H), 7.30
(td, J = 7.0, 1.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
149.0, 145.1, 136.5, 131.5, 131.1, 130.3, 128.5, 128.2, 118.4,
116.7. HRMS (ESI) m/z calcd for C13H9ClN3O2 [M + H]+
274.0383, found, 274.0378.
4.2.7 | 2-(2-Chlorophenyl)-3-nitroimidazo
[1,2-a]pyridine (4g)
4.2.3 | 3-Nitro-2-(4-nitrophenyl)imidazo
[1,2-a]pyridine (4c)
Yield: 66%. Yellow oil. 1H NMR (500 MHz, CDCl3) δ 9.52
(d, J = 7.0 Hz, 1H), 7.87 (d, J = 8.9 Hz, 1H), 7.72-7.64 (m,
1H), 7.53 (ddd, J = 7.8, 4.1, 1.5 Hz, 2H), 7.42 (dtd,
J = 20.2, 7.5, 1.6 Hz, 2H), 7.33 (td, J = 7.0, 1.2 Hz, 1H).
13C NMR (125 MHz, CDCl3) δ 147.3, 145.0, 133.9, 131.9,
130.9, 130.8, 130.7, 129.5, 127.8, 126.7, 118.5, 116.8.
HRMS (ESI) m/z calcd for C13H9ClN3O2 [M + H]+
274.0383, found, 274.0385.
Yield: 66%. Yellow solid, mp 216-218ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.53 (d, J = 7.0 Hz, 1H), 8.36 (d,
J = 8.9 Hz, 2H), 8.09 (d, J = 8.9 Hz, 2H), 7.89 (d,
J = 8.9 Hz, 1H), 7.75-7.69 (m, 1H), 7.36 (td, J = 7.0,
1.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 148.7, 147.4,
145.2, 138.2, 131.4, 131.3, 128.1, 123.3, 118.7, 117.2.
HRMS (ESI) m/z calcd for C13H9N4O4 [M + H]+
285.0624, found, 285.0621.
4.2.8 | 2-(3-Bromophenyl)-3-nitroimidazo
[1,2-a]pyridine (4h)
4.2.4 | 3-Nitro-2-(p-tolyl)imidazo[1,2-a]
pyridine (4d)
Yield: 68%. Yellow solid, mp 139-140ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.51 (d, J = 7.0 Hz, 1H), 8.06 (t,
J = 1.8 Hz, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.73-7.55 (m,
2H), 7.38 (t, J = 7.9 Hz, 1H), 7.31 (td, J = 7.0, 1.2 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 148.5, 145.1, 133.8, 133.1,
132.9, 131.1, 129.6, 128.7, 128.1, 122.1, 118.4, 116.8.
HRMS (ESI) m/z calcd for C13H9BrN3O2 [M + H]+
317.9878, found, 317.9870.
Yield: 70%. Yellow solid, mp 203-205ꢀC. 1H NMR
(500 MHz, CDCl3) δ 9.52 (d, J = 7.0 Hz, 1H), 7.85-7.80
(m, 3H), 7.70-7.61 (m, 1H), 7.32 (d, J = 7.9 Hz, 2H), 7.28
(dd, J = 7.0, 1.2 Hz, 1H), 2.44 (s, 3H). 13C NMR
(125 MHz, CDCl3) δ 150.5, 145.2, 140.6, 130.8, 130.0,
128.9, 128.2, 118.2, 116.3, 21.6. HRMS (ESI) m/z calcd for
C14H12N3O2 [M + H]+ 254.0930, found, 254.0925.
4.2.5 | 2-([1,1'-Biphenyl]-4-yl)-
3-nitroimidazo[1,2-a]pyridine (4e)
4.2.9 | 3-Nitro-2-(m-tolyl)imidazo[1,2-a]
pyridine (4i)
Yield: 65%. Yellow solid, mp 223-225ꢀC. 1H NMR
(500 MHz, CDCl3) δ 9.53 (d, J = 7.0 Hz, 1H), 8.11-7.95
(m, 2H), 7.86 (dt, J = 8.9, 1.1 Hz, 1H), 7.74 (d, J = 8.5 Hz,
2H), 7.67 (ddd, J = 9.0, 7.7, 1.3 Hz, 3H), 7.48 (t,
J = 7.6 Hz, 2H), 7.43-7.36 (m, 1H), 7.29 (td, J = 7.0,
1.2 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 150.0, 145.2,
Yield: 76%. Yellow solid, mp 143-144ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.51 (d, J = 7.0 Hz, 1H), 7.84 (dd,
J = 8.9, 1.0 Hz, 1H), 7.70 (d, J = 6.3 Hz, 2H), 7.68-7.62
(m, 1H), 7.39 (t, J = 7.9 Hz, 1H), 7.32 (d, J = 7.8 Hz,
1H), 7.30-7.23 (m, 1H), 2.44 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 150.5, 145.1, 137.9, 131.7, 131.0,

6
SUN ET AL.
130.8, 130.4, 128.2, 128.0, 127.2, 118.3, 116.4, 21.4.
HRMS (ESI) m/z calcd for C14H12N3O2 [M + H]+
254.0930, found, 254.0926.
5.2 | 6-Methyl-3-nitro-2-phenylimidazo
[1,2-a]pyridine (5b)
Yield: 64%. Yellow solid, mp 168-169ꢀC. 1H NMR
(500 MHz, CDCl3) δ 9.32 (s, 1H), 7.90-7.87 (m, 2H), 7.73
(d, J = 9.0 Hz, 1H), 7.51-7.48 (m, 4H), 2.51 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 150.1, 144.1, 133.7, 132.0,
130.0, 129.9, 128.1, 126.9, 126.1, 117.5, 18.7. HRMS (ESI)
m/z calcd for C14H12N3O2 [M + H]+ 254.0930, found,
254.0936.
4.2.10 | 2-(3,5-Dichlorophenyl)-
3-nitroimidazo[1,2-a]pyridine (4j)
Yield: 60%. Yellow solid, mp 160-162ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.51 (d, J = 7.0 Hz, 1H), 7.86 (d,
J = 8.9 Hz, 1H), 7.81 (d, J = 1.9 Hz, 1H), 7.73-7.67 (m, 1H),
7.50 (t, J = 1.9 Hz, 1H), 7.34 (td, J = 7.0, 1.2 Hz, 1H). 13C
NMR (100 MHz, CDCl3) δ 147.1, 145.0, 134.8, 134.7, 131.2,
130.1, 128.5, 128.1, 118.5, 117.0. HRMS (ESI) m/z calcd for
C13H18Cl2N3O2 [M + H]+ 307.9994, found, 307.9997.
5.3 | 5-Methyl-3-nitro-2-phenylimidazo
[1,2-a]pyridine (5c)
Yield: 68%. Yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.00
(dd, J = 8.3, 1.2 Hz, 2H), 7.76 (s, 1H), 7.56 (d, J = 9.0 Hz,
1H), 7.44 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.15
(dd, J = 9.1, 6.9 Hz, 1H), 6.63 (d, J = 6.8 Hz, 1H), 2.62 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 146.2, 145.8, 134.3,
133.9, 128.7, 127.9, 126.1, 124.9, 114.9, 111.6, 105.3, 18.8.
HRMS (ESI) m/z calcd for C14H12N3O2 [M + H]+
254.0930, found, 254.0928.
4.2.11 | 2-(3,5-Dimethylphenyl)-
3-nitroimidazo[1,2-a]pyridine (4k)
Yield: 72%. Yellow solid, mp 152-154ꢀC. 1H NMR
(500 MHz, CDCl3) δ 9.51 (d, J = 7.0 Hz, 1H), 7.83 (d,
J = 8.9 Hz, 1H), 7.67-7.62 (m, 1H), 7.50 (s, 2H), 7.28 (dd,
J = 7.0, 1.2 Hz, 1H), 7.14 (s, 1H), 2.40 (s, 6H). 13C NMR
(125 MHz, CDCl3) δ 150.7, 145.1, 137.7, 132.0, 131.6, 130.8,
128.1, 127.6, 118.2, 116.4, 21.3. HRMS (ESI) m/z calcd for
C15H14N3O2 [M + H]+ 268.1086, found, 268.1090.
ACKNOWLEDGMENTS
This work was supported by the Natural Science Founda-
tion of Jiangsu Province (BK20170939), the Natural Sci-
ence Research Project of Jiangsu Higher Education
Institutions (17KJB150016), and Training Program of
Innovation and Entrepreneurship for Undergraduates
(201910300018Z).
5 | GENERAL PROCEDURE FOR
THE PREPARATION OF 5
The mixture of substituted 2-aminopyridine 1 (1.5 mmol),
aldehyde 2a (0.5 mmol), nitromethane 3 (0.5 mmol), and
NIS (0.5 mmol) was refluxed in acetonitrile (5 mL) for
6 hours in a round bottle. After the reaction was com-
pleted, the solvent was removed under reduced pressure,
and the residue was separated by flash chromatography
on a silica gel column with ethyl acetate/petroleum as
eluent to give the products 5.
ORCID
Jinwei Sun https://orcid.org/0000-0002-0882-2872
Yun Liu https://orcid.org/0000-0001-5783-4848
REFERENCES
[1] A. Douhal, F. Amat-Guerri, A. U. Acuna, J Phys Chem 1995,
99, 76–80.
[2] A. J. Stasyuk, M. Banasiewicz, M. K. Cyranski, D. T. Gryko,
ꢀ
J Org. Chem 2012, 77, 5552–8.
[3] K. S. Gudmundsson, J. D. Williams, J. C. Drach,
L. B. Townsend, J Med Chem 2003, 46, 1449–55.
5.1 | 8-Methyl-3-nitro-2-phenylimidazo
[1,2-a]pyridine (5a)
[4] M. Lhassani, O. Chavignon, J. M. Chezal, J. C. Teulade,
J. P. Chapat, R. Snoeck, G. Andrei, J. Balzarini, E. D. Clercq,
A. Gueiffier, Eur J Med Chem 1999, 34, 271–4.
[5] M. Anderson, J. F. Beattie, G. A. Breault, J. Breed,
K. F. Byth, J. D. Culshaw, R. P. A. Ellston, S. Green,
C. A. Minshull, R. A. Norman, R. A. Pauptit, J. Stanway,
A. P. Thomas, P. Jewsbury, J. Bioorg Med Chem Lett 2003, 13,
3021–6.
Yield: 70%. Yellow solid, mp 170-171ꢀC. 1H NMR
(400 MHz, CDCl3) δ 9.38 (d, J = 6.9 Hz, 1H), 7.92-7.89
(m, 2H), 7.52-7.48 (m, 3H), 7.45 (d, J = 7.1 Hz, 1H), 7.18
(t, J = 7.1 Hz, 1H), 2.73 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 149.8, 145.2, 132.2, 130.1, 130.0, 129.9, 128.6,
128.1, 125.9, 116.5, 16.6. HRMS (ESI) m/z calcd for
C14H12N3O2 [M + H]+ 254.0930, found, 254.0922.
[6] Hamdouchi, C.; de Blas, J.; del Prado, M.; Gruber, J.;
Heinz, B. A.; Vance, L. J Med Chem 1999, 42, 50, 59.

SUN ET AL.
7
[7] G. C. Moraski, L. D. Markley, P. A. Hipskind, H. Boshoff,
S. Cho, S. G. Franzblau, M. Miller, J. ACS Med Chem Lett
2011, 2, 466–70.
[8] R. B. Lacerda, C. K. F. de Lima, L. L. da Silva, N. C. Romeiro,
A. L. P. Miranda, E. J. Barreiro, C. A. M. Fraga, Bioorg Med
Chem Lett 2009, 17, 74–84.
[23] H. Yan, R. L. Yan, S. Z. Yang, X. A. Gao, Y. L. Wang,
G. S. Huang, Y. M. Liang, Chem Asian
2028–31.
J 2012, 7,
[24] L. R. Yan, H. Yan, C. Mao, Z. Y. Ren, X. A. Gao, G. S. Huang,
Y. M. Liang, J Org Chem 2024, 2012, 77.
[25] P. Puthiaraj, A. Ramu, K. Pitchumani, Asian J Org Chem 2014,
3, 784–91.
[9] S. Z. Langer, S. Arbilla, J. Benavides, B. Scatton, Adv Biochem
Psychopharmacol 1990, 46, 61.
[26] M. Zhang, J. Lu, J. N. Zhang, Z. H. Zhang, Catalysis Commun
[10] K. Mizushige, T. Ueda, K. Yukiiri, H. Suzuki, Cardiovasc Drug
Rev 2002, 20, 163.
[11] L. Almirante, L. Polo, A. Mugnaini, E. Provinciali, P. Rugarli,
A. Biancotti, A. Gamba, W. Murmann, J Med Chem 1965, 8,
305–12.
2016, 78, 26–32.
[27] J. W. Sun, F. Y. Wang, Y. M. Shen, H. Z. Zhi, H. Wu, Y. Liu,
Org Biomol Chem 2015, 13, 10236–43.
[28] W. L. Zhang, S. N. Yue, Y. M. Shen, H. Y. Hu, Q. H. Meng,
H. Wu, Y. Liu, Org Biomol Chem 2015, 13, 3602–9.
[29] Y. Liu, W. H. Wang, J. W. Han, J. W. Sun, Org Biomol Chem
2017, 15, 9311–8.
[12] A. K. Bagdi, S. Santra, K. Monir, A. Hajra, Chem Commun
2015, 51, 1555–75.
[13] K. Pericherla, P. Kaswan, K. Pandey, A. Kumar, Synthesis
2015, 47, 887.
[30] W. H. Wang, J. W. Sun, H. Y. Hu, Y. Liu, Org Biomol Chem
2018, 16, 1651–8.
[14] R. Goel, V. Luxami, K. Paul, Org Biomol Chem 2015, 13,
[31] W. H. Wang, J. W. Han, J. W. Sun, Y. Liu, J Org Chem 2017,
82, 2835–42.
3525–55.
[15] J. Koubachi, S. E. Kazzouli, M. Bousmina, G. Guillaumet, Eur
J Org Chem 2014, 13, 5119.
[32] Y. N. Ma, M. X. Cheng, S. D. Yang, Org Lett 2017, 19, 600–3.
[16] Y. Volkova, V. Gevorgyan, Chem Heterocycl Com 2017, 53,
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
409–12.
[17] H. Sun, H. Zhou, O. Khorev, R. Jiang, T. Yu, X. Wang, Y. Du,
Y. Ma, T. Meng, J. Shen, J Org Chem 2012, 77, 10745–51.
[18] A. L. Rousseau, P. Matlaba, C. J. Parkinson, Tetrahedron Lett
2007, 48, 4079–82.
[19] A. K. Bagdi, M. Rahman, S. Santra, A. Majee, A. Hajraa, Adv
Synth Cat 2013, 355, 1665.
[20] M. A. Tzani, M. G. Kallitsakis, T. S. Symeonidis, I. N. Lykakis,
ACS Omega 2018, 3, 17947–17956.
How to cite this article: Sun J, Yang X, Liu Y,
Wang Y, Pan Y. NIS-promoted multicomponent
reaction of 2-aminopyridines with aldehydes and
nitromethane for the synthesis of 3-nitroimidazo
[1.2-a]pyridines. J Heterocycl Chem. 2020;1–7.
https://doi.org/10.1002/jhet.3869
[21] K. Monir, A. K. Bagdi, M. Ghosh, A. Hajra, Org Lett 2014, 16,
4630–3.
[22] P. T. M. Ha, T. N. Lieu, S. H. Doan, T. T. B. Phan,
T. T. Nguyen, T. Truong, N. T. S. Phan, RSC Adv 2017, 7,
23073–82.