N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide and poly(N-bromo-N-ethylbenzene-1,3-disulfonamide) as mild and efficient catalysts for solvent-free synthesis of N-cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin- 3-amine derivatives

Article abstract of DOI:10.1002/jhet.1875

N-Cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine derivatives have been synthesized in good to high yields from o-aminopyridine, aromatic and aliphatic aldehydes, and cyclohexyl isocyanide in the presence of N,N,N′,N′-tetrabromobenzene-1,3-disulfon

Full text of DOI:10.1002/jhet.1875

Month 2014
N,N,N0,N0-Tetrabromobenzene-1,3-disulfonamide and Poly(N-bromo-N-
ethylbenzene-1,3-disulfonamide) as Mild and Efficient Catalysts for
Solvent-free Synthesis of N-Cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]
pyridin-3-amine Derivatives
*
Ramin Ghorbani-Vaghei and Mostafa Amiri
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali-Sina University, 65174, Hamedan, Iran
*
E-mail: rgvaghei@yahoo.com
Received August 28, 2012
DOI 10.1002/jhet.1875
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
N-Cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine derivatives have been synthesized in good
to high yields from o-aminopyridine, aromatic and aliphatic aldehydes, and cyclohexyl isocyanide in
the presence of N,N,N0,N0-tetrabromobenzene-1,3-disulfonamide and poly(N-bromo-N-ethylbenzene-1,3-
disulfonamide) as catalysts, at room temperature under solvent-free conditions.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
imidazo[1,2-a]pyridines are a class of nitrogen bridgehead
heterocycles that have received considerable attention
because of their interesting biological activities [1].
Imidazo[1,2-a]pyridines have been shown to possess a
broad range of biological activities and have been investigated
for treatment of conditions such as gastric disease [2,3],
heart diseases [4], migraines [5], viral diseases [6–10],
HIV-1 inhibitors [11], and activity against the colon cancer
cell lines HT-29 and Caco-2 [12]. The most common route
for the preparation of imidazo[1,2-a]pyridines involves the
condensation of o-aminopyridine, aldehydes, and isocya-
nides in the presence of a catalyst [13–24]. However, some
of these condensations have some demerits such as the
requirement of expensive and excess amount of catalyst,
Synthesis of organic molecules via green, mild, and sim-
ple procedures is currently receiving considerable atten-
tion. Also, reducing or eliminating the use and generation
of hazardous substances is a goal of green chemistry. The
development of simple, versatile, and environmentally
friendly processes or methodologies for widely used
organic compounds from readily available reagents is one
of the major challenges for chemists in organic synthesis.
Organic compounds containing nitrogen are widespread
in numerous natural products and widely used as various
artificial chemicals. Heterocyclic compounds always attri-
bute remarkable attention in pharmaceutical industry
because of their wide therapeutic values. Among them,
© 2014 HeteroCorporation

R. Ghorbani-Vaghei and M. Amiri
Vol 000
longer time, difficulties in work-up procedure, and harsh
reaction conditions [25,26]. Because of the interesting
properties of imidazo[1,2-a]pyridines, the development of
synthetic methods that enable a facile access to this hetero-
cycle is desirable.
(Table 2, entry 4a) used as a model compound. In the
absence of a catalyst, no product was observed, even after
prolonged reaction time (Table 1, entry 1). Because the
synthesis of N-cyclohexyl-2-phenylimidazo[1,2-a]pyridin-
3-amines failed in the absence of a catalyst, the effect of
catalyst was also investigated in various conditions, and
the results are presented in (Table 1). With respect to the
solvent system, the best results were achieved using
ethanol (Table 1, entry 7). In recent years, the synthesis
of compounds under solvent-free conditions is an impor-
tant task in heterocyclic synthesis. Therefore, we decided
to repeat this reaction under solvent-free reaction with
various ratios of catalysts. We found that the reaction was
rapid and gave good to high yields of the products when
using TBBDA (0.05 g) and PBBS (60 min, 95%, entry 16).
To test the generality and versatility of this new procedure
in the synthesis of N-cyclohexyl-2-aryl(alkyl)-imidazo[1,2-
a]pyridin-3-amines, we examined a number of aliphatic
and aromatic aldehydes and cyclohexyl isocyanide under
optimized conditions (Table 2).
As shown in Table 2, a series of aromatic, aliphatic, and
heterocyclic aldehydes underwent electron-withdrawing
and electron-donating groups reaction with o-aminopyridine
and cyclohexyl isocyanide smoothly to afford a wide range
of substituted N-cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]
pyridin-3-amine derivatives in good to high yields in the
presence of TBBDA and PBBS as catalysts. The nature
and electronic properties of the aldehyde substrates affect
the conversion rate. Aromatic aldehydes react faster than
the aliphatic aldehydes.
RESULTS AND DISCUSSION
In continuation of our interest in the application of N,N,N0,
N0-tetrabromobenzene-1,3-disulfonamide (TBBDA) and poly
(N-bromo-N-ethylbenzene-1,3-disulfonamide) (PBBS) in
organic synthesis [27–39], we herein report a simple
and improved protocol for the synthesis N-cyclohexyl-2-aryl
(alkyl)-imidazo[1,2-a]pyridin-3-amines in good to high
yields, from o-aminopyridine, aromatic and aliphatic alde-
hydes, and cyclohexyl isocyanide (Scheme 1). TBBDA and
PBBS play an especially important role as Lewis acid cata-
lysts in the chemistry of these compounds. Therefore, we
describe herein an efficient process for the synthesis of
N-cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine
derivatives.
The advantages of TBBDA and PBBS are as follows:
1. The preparation of TBBDA and PBBS are easy.
2. TBBDA and PBBS are stable under atmospheric
conditions for 2 months.
3. After completion of the reaction, the catalysts are
recovered and can be reused several times without
decreasing the yield.
Initially, we decided to explore the role of our catalysts
in various solvents and various conditions for the synthesis
of N-cyclohexyl-2-phenylimidazo[1,2-a]pyridin-3-amines
It is likely that these catalysts release Br+ in situ, which
can act as an electrophilic species. Therefore, the mecha-
nism shown in Scheme 2 can be suggested for the conver-
sion of the o-aminopyridine, various aliphatic and aromatic
aldehydes, and cyclohexyl isocyanide to N-cyclohexyl-2-
aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine derivatives.
Scheme 1. Synthesis of imidazo[1,2-a]pyridine derivatives.
CONCLUSION
In summary, in this study we have introduced a new and
useful catalytic application of TBBDA and PBBS as
efficient catalysts for the synthesis of aliphatic and
aromatic imidazo[1,2-a]pyridine derivatives, from the
reaction of aldehydes, o-aminopyridine, and cyclohexyl
isocyanide under solvent-free conditions. Moreover, the
method has advantages in terms of high yields of products,
short reaction time, operational simplicity, and easy work-
up product.
EXPERIMENTAL
All commercially available chemicals were obtained from
Merck and Fluka companies and used without further purification
unless otherwise stated. Nuclear magnetic resonance, 1H, and
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Mild Synthesis of N-Cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine
Table 1
Optimization of reaction conditions for the synthesis of N-cyclohexyl-2-phenylimidazo[1,2-a]pyridin-3-amine.
Entry
Solvent/condition
TBBDA/PBBS
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
CH3CO2Et
H2O
CH2Cl2
Neat
Neat
Neat
Neat
—
24
10
10
10
10
10
10
8
5
4
3.5
24
2
0/0
15/8
0.01/0.01
0.02/0.04
0.03/0.05
0.04/0.07
0.05/0.08
0.1/0.12
0.05/0.07
0.05/0.07
0.05/0.07
0.05/0.07
—
0.01/0.01
0.02/0.04
0.03/0.05
0.05/0.07
0.06/0.08
0.1/0.12
30/20
40/25
40/30
65/35
65/60
35/20
50/50
15/10
40/30
0/0
9
10
11
12
13
14
15
16
17
18
15/5
2
2
1
2
30/15
55/30
95/90
94/65
94/85
Neat
Neat
Neat
2
aStandardization of reaction conditions: benzaldehyde (1 mmol), o-aminopyridine (1 mmol), cyclohexyl isocyanide (1 mmol).
13CNMR spectra were recorded on Bruker Avance 300 FT NMR
spectrometers. Infrared (IR) spectroscopy was conducted on a
Perkin Elmer GX FTIR spectrometer. Mass spectra were recorded
on a Shimadzu QP 1100 BX Mass Spectrometer. Elemental
analyses (C, H, and N) were performed with a Heraeus CHN-
Rapid analyzer.
Typical procedure for the preparation of N-cyclohexyl-2-
phenylimidazo[1,2-a]pyridine-3-amine. To a mixture of
o-amino pyridine (1 mmol, 0.108 g), benzaldehyde (1 mmol,
0.106 g), and cyclohexyl isocyanide (1 mmol, 0.109 g) was
added a catalytic amount of TBBDA (0.905 mmol, 0.05 g) or
[PBBS] (0.07 g), and the mixture was stirred for an appropriate
Table 2
Synthesis of N-cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine derivatives.
TBBDA
PBBS
Time (min)
Entry
Aldehyde
Product
Time (min)
60
Yield(%)
95
Yield(%)
90
Ref.
11
4a
70
4b
4c
55
25
90
85
80
85
80
11
11
65
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei and M. Amiri
Vol 000
Table 2
(Continued)
TBBDA
PBBS
Time (min)
Entry
4d
Aldehyde
Product
Time (min)
30
Yield(%)
Yield(%)
75
Ref.
11
90
90
4e
50
94
75
85
11
4f
100
70
40
45
—
4g
60
80
110
60
—
4h
90
55
90
85
50
65
70
—
4i
120
—
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Mild Synthesis of N-Cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine
Table 2
(Continued)
TBBDA
Time (min)
PBBS
Time (min)
Entry
Aldehyde
Product
Yield(%)
Yield(%)
Ref.
11
4j
12
30
90
35
60
4k
94
90
60
90
75
11
11
4l
40
65
55
80
4m
85
80
—
4n
65
88
60
75
—
4o
80
95
90
85
—
4p
75
80
70
80
—
(Continues)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei and M. Amiri
Vol 000
Table 2
(Continued)
TBBDA
PBBS
Time (min)
Entry
Aldehyde
Product
Time (min)
50
Yield(%)
Yield(%)
Ref.
4q
75
75
50
—
The products were characterized by comparing their spectroscopic and physical data with those of the samples synthesized by a reported procedure.
time (Table 2). The progress of the reaction was monitored by TLC
(n-hexane/ethyl acetate, 2:1). After completion of the reaction,
CH2Cl2 (10mL) was added, and the catalyst was removed by
filtration. Evaporation of the solvent under reduced pressure gave
the crude product. The crude product was purified by TLC using
n-hexane/ethyl acetate (70:60) as the eluent system to afford the
N-cyclohexyl-2-phenylimidazo[1,2-a]pyridin-3-amine (95%).
requires C, 78.96; H, 7.89; N, 13.15%]; IR (KBr) (nmax/cmꢁ1):
3125 (NH), 2905, 1623. 1H NMR (200 MHz, DMSO-d6): dH
(ppm) 1.12–2.11 (10H, m, 5CH2 of cyclohexyl), 3.03 (2H, t,
J = 8.2 Hz CH2-CH2-Ar), 3.27 (2H, t, J = 4 Hz CH2-CH2-Ar), 4.18
(1H, s, br, CH-N), 4.60 (1H, s, C-NH), 6.72 (1H, d, J = 3.4 Hz Ar-
H), 7.21–7.36 (5H, m, Ar-H), 7.43 (1H, t, J = 3.3 Hz Ar-H), 7.88
(1H, d, J = 3.4 Hz Ar-H), 8.10 (1H, s, J = 5.4 Hz Ar-H). 13C NMR
(50 MHz, DMSO-d6): dC (ppm) 24.77, 25.81, 29.73, 38.81, 38.86,
49.34 (CH-N of cyclohexyl), 124.16, 125.59, 126.19, 128.28,
128.82, 129.55, 130.05, 131.12, 133.86, 135.64, 136.82, 139.78,
4f.
2,20-(1,4-Phenylene)bis(N-cyclohexylimidazo[1,2-a]
pyridin-3-amine) (Table 2, entry 4f). Colorless crystal (70%): mp
260–262ꢀC (dec). [Found: C, 76.48; H, 7.22; N, 16.74. C32H36N6
requires C, 76.16; H, 7.19; N, 16.65%]; IR (KBr) (nmax/cmꢁ1):
3195 (NH), 2925, 1613. 1H NMR (200 MHz, DMSO-d6): dH
(ppm) 1.11–2.20 (20H, m, 10CH2 of cyclohexyl), 4.20 (2H, s, br,
CH-N), 5.11 (2H, d, J = 6 Hz NH-C), 6.81 (2H, t, J = 2.2Hz), 7.10
(2H, t, J = 6.2 Hz H-Ar), 7.53–7.62 (4H, m, Ar-H), 7.70 (2H,
d, J = 1.1Hz), 7.82 (2H, d, J = 2.4 Hz); 13C NMR (50 MHz,
DMSO-d6): dC (ppm) 23.66, 23.79, 31.04 (carbons of
cyclohexyl), 50.41 (CH-N of cyclohexyl), 123.27, 123.59, 125.72,
126.63, 126.87, 128.78, 129.86, 133.11, 136.82, 148.15 (C-Ar).
140.80, 141.20, 146.91, 149.26 (C-Ar).
4h. N-Cyclohexyl-2-(5-methylthiophen-2-yl)imidazo[1,2-a]
pyridin-3-amine (Table 2, entry 4h). Colorless crystal (90%): mp
220–222ꢀC (dec). [Found: 69.72; H, 6.85; N, 13.59. C18H21N3S
requires C, 69.42; H, 6.80; N, 13.49%]; IR (KBr) (nmax/cmꢁ1):
3185 (NH), 2935, 1615; 1H NMR (200 MHz, DMSO-d6): dH
(ppm) 1.10–2.12 (10H, m, 5CH2 of cyclohexyl), 2.42 (3H,
s, CH3), 4.24 (1H, m, CH-N of cyclohexyl), 5.14 (1H, s br, CH-
NH), 6.74 (1H, t, J = 2.6 Hz Ar-H), 7.19 (1H, t, J = 6.85 Hz Ar-H),
6.91, 6.92 (1H, d, J =1.9 Hz Ar-H), 7.03 (1H, d, J = 13 Hz Ar-H),
7.20 (1H, t, Ar-H), 7.65 (1H, d, J = 1 Hz Ar-H), 7.87 (1H,
d, J = 2 Hz Ar-H), 16.24 (methyl), 24.71, 25.75, 32.81 (carbons of
4g.
N-Cyclohexyl-2-phenethylimidazo[1,2-a]pyridin-3-
amine (Table 2, entry 4g). Colorless crystal (80%): mp 203–206ꢀC
(dec). [Found: C, 79.26; H, 7.92; N, 13.25. C21H25N3
Scheme 2. Proposed mechanism for preparation of N-cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine derivatives.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Mild Synthesis of N-Cyclohexyl-2-aryl(alkyl)-imidazo[1,2-a]pyridin-3-amine
cyclohexyl), 56.25 (CH-N of cyclohexyl), 120.05, 124.25, 125.79,
128.74, 129.68, 132.07, 136.61, 139.15, 141.48, 146.35, 149.10
(C-Ar).
Ar-H), 7.98 (1H, d, Ar-H); 13C NMR (50MHz, DMSO-d6): dC
(ppm) 18.12, 21.05, 23.40, 25.31, 32.18 (carbons of cyclohexyl),
58.11 (CH-N of cyclohexyl), 122.01, 126.74, 128.37, 128.74,
132.35, 136.82, 145.88 (C-Ar).
4i.
N-Cyclohexyl-2-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]
pyridin-3-amine (Table 2, entry 4h). Colorless crystal (85%):
mp 255–257ꢀC (dec). [Found: C, 69.68; H, 7.03; N, 11.12.
C22H27N3O3 requires C, 69.27; H, 7.13; N, 11.02%]; IR (KBr)
(nmax/cmꢁ1): 3225 (NH), 2945, 1643; 1H NMR (200MHz, DMSO-
d6): dH (ppm) 1.13–2.14 (10H, m, 5CH2 of cyclohexyl), 3.85 (9H, s,
OCH3), 4.20 (1H, m, CH-N of cyclohexyl), 5.19 (1H, d, J=7.4Hz
CH-NH), 6.92 (2H, s, H-Ar), 7.34 (1H, d, J= 6.2 Hz Ar-H), 7.37
(1H, t, J= 1.3 Hz Ar-H), 7.84 (1H, d, J= 1.3 Hz Ar-H) 7.89 (1H, t,
J=1.3Hz Ar-H). 13C NMR (50 MHz, DMSO-d6): dC (ppm) 24.66,
24.79, 32.82 (carbons of cyclohexyl), 49.41 (CH-N of cyclohexyl),
54.66, 55.79, 111.27, 117.58, 125.72, 126.63, 126.87, 128.78,
129.66, 133.11, 136.82, 141.05, 141.30, 146.19, 150.15 (C-Ar).
4q.
N-Cyclohexyl-2-(2-(methylthio)ethyl)imidazo[1,2-a]
pyridin-3-amine (Table 2, entry 4q). Colorless crystal (75%): mp
203–206ꢀC (dec). [Found: C, 66.59; H, 8.11; N, 14.54. C16H23N3S
requires C, 66.39; H, 8.01; N, 14.52%]; IR (KBr) (nmax/cmꢁ1): 3195
(NH), 2925, 1613; 1H NMR (200 MHz, DMSO-d6): dH (ppm) 1.15–
1.74 (10H, m, 5CH2 of cyclohexyl), 2.09 (3H, s, SCH3), 2.24 (4H,
m, CH2-CH2-S), 4.10 (1H, m, CH-NH), 5.16 (1H, bs, NH-CH),
7.36–7.64 (3H, m, Ar-H), 8.10 (1H, d, Ar-H). 13C NMR (50MHz,
DMSO-d6): dC (ppm) 17.71, 18.26, 18.54 (carbons of thiomethyl
propan), 24.40, 25.21, 33.18 (carbons of cyclohexyl), 56.11 (CH-N
of cyclohexyl), 112.95, 115.64, 122.11, 122.01, 126.13, 126.74,
128.37, 128.74, 132.35, 136.82, 145.88 (C-Ar).
4m.
N-Cyclohexyl-2-(naphthalen-1-yl)imidazo[1,2-a]
pyridin-3-amine (Table 2, entry 4m). Yellow powder (85%): mp
243–245ꢀC (dec). [Found: C, 81.25; H, 6.90; N, 12.34.
C23H23N3 requires C, 80.90; H, 6.79; N, 12.31%]; IR (KBr)
(nmax/cmꢁ1): 3205 (NH), 2915, 1623: 1H NMR (200 MHz,
DMSO-d6): dH (ppm) 1.02–2.15 (10H, m, 5CH2 of cyclohexyl),
4.21 (1H, m, CH-N of cyclohexyl), 4.41 (1H, s, J = 6.7 Hz CH-
NH), 6.99 (1H, t, J = 8.5 Ar-H), 7.25–7.60 (8H, m, Ar-H), 7.87,
7.88 (1H, d, J = 3.1 Hz Ar-H); 13C NMR (50 MHz, DMSO-d6):
dC (ppm) 24.83, 24.88, 32.68 (carbons of cyclohexyl), 49.48
(CH-N of cyclohexyl), 120.01, 120.04, 124.51, 125.94,
128.42, 128.94, 130.24, 130.38, 132.19, 133.87, 134.04,
136.32, 136.36, 141.11, 149.04 (C-Ar).
REFERENCES AND NOTES
[1] Enguehard-Gueiffier, C.; Gueiffier, A. Mini-Rev Med Chem.
2007, 7, 888.
[2] Starrett, J. E., Jr.; Montzka, T. A.; Croswell, A. R.; Cavanagh,
R. L. J Med Chem 1989, 32, 2204.
[3] Palmer, A. M.; Chrismann, S.; Münch, G.; Brehm, C.;
Zimmermann, P. J.; Buhr, W.; Senn-Bilfinger, J.; Feth, M. P.; Simon,
W. A. Bioorg Med Chem 2009, 17, 368.
[4] Michiaki, T.; Yung-Hsiung, Y.; Kazuyuki, N.; Hidenori, O.
Patent EP 52016, 1981.
[5] Maul, C.; Sundermann, B.; Hennies, H.-H.; Schneider, J.;
Gerlach, M. Patent WO 01027109, 2001.
4n.
N-Cyclohexyl-2-hexylimidazo[1,2-a]pyridin-3-amine
(Table 2, entry 4n). Colorless crystal (88%): mp 145–147ꢀC
(dec). [Found: C, 76.31; H, 9.86; N, 14.16. C19H29N3 requires
C, 76.21; H, 9.76; N, 14.03%]; IR (KBr) (nmax/cmꢁ1): 3195
(NH), 2925, 1613: 1H NMR (200MHz, DMSO-d6): dH (ppm)
0.92 (3H, t, CH3 hexyl), 1.24–2.16 (18H, m, 5CH2 of
cyclohexyl and 4CH2 hexyl), 2.75 (2H, t, J = 3.5 Hz CH2-Ar),
4.25 (1H, m, CH-N of cyclohexyl), 4.76 (1H, bs, C-NH), 6.82
(1H, t, J = 4.8 Hz Ar-H), 7.10 (1H, t, J = 2.8 Hz Ar-H), 7.77
(1H, d, J = 2.85 Hz Ar-H), 7.90 (1H, t, J = 2.1 Hz Ar-H); 13C
NMR (50 MHz, DMSO-d6): dC (ppm) 22.54, 24.40, 24.72,
25.80, 26.54, 31.75, 32.63, 33.88, 38.04, 49.39, 124.07,
[6] Gueiffier, A.; Mavel, S.; Lhassani, M.; Elhakmaoui, A.;
Snoeck, R.; Andrei, G.; Chavignon, O.; Teulade, J.-C.; Witvrouw, M.;
Balzarini, J.; De Clercq, E.; Chapat, J.-P. J Med Chem 1998, 41, 5108.
[7] Defosse, G.; Le Ber, P.; Saarmets, A.; Wick A. Patent FR
2699919 1994.
[8] Elleder, D.; Young, J. A. T.; Baiga, T. J.; Noel, J. P. Patent
WO 2009061856 2009.
[9] Véron, J.-B.; Allouchi, H.; Enguehard-Gueiffier, C.; Snoeck,
R.; Andrei, G.; De Clercq, E.; Gueiffier, A. Bioorg Med Chem 2008,
16, 9536.
[10] Gudmundsson, K. S.; Johns, B. A. Bioorg Med Chem Lett
2007, 17, 2735.
[11] Bode, M. L.; Gravestock, D.; Moleele, S. S.; Westhuyzen, C.
W.; Pelly, S. C.; Steenkamp, P. A.; Hoppe, H. C.; Khan, T.; Nkabinde,
L. A. Bioorg Med Chem Lett 2011, 19, 4227.
[12] Farkas, N. D.; Langley, C.; Rousseau, A. L.; Yadav, D. B.;
Davids, H.; de Koning, C. B. Eur J Med Chem 2011, 46, 4573.
[13] Khan, A. T.; Basha, K. S.; Lal, M. Tetrahedron Lett 2012,
53, 2211.
[14] Krasavin, M.; Tsirulnikov, S.; Nikulnikov, M.; Sandulenko,
Y.; Bukhryakov, K. Tetrahedron Lett 2008, 49, 7318.
[15] Al-Tel, T. H.; Al-Qawasmeh, R. A.; Zaarour, R. J Eur Med
Chem 2011, 46, 1874.
125.36, 128.11, 128.89, 136.30, 148.17, 149.10 (C-Ar).
4o. N-Cyclohexyl-2-isobutylimidazo[1,2-a]pyridin-3-amine
(Table 2, entry 4o). Colorless crystal (95%): mp 110–112ꢀC
(dec). [Found: C, 75.55; H, 9.51; N, 15.38. C17H25N3 requires
C, 75.23; H, 9.28; N, 15.48%]; IR (KBr) (nmax/cmꢁ1): 3305
(NH), 2895, 1643; 1H NMR (200 MHz, DMSO-d6): dH (ppm)
1.01 (6H, d, J = 4.6 Hz C(CH3)2), 1.22–2.15 (10H, m, 5CH2 of
cyclohexyl), 2.34 (1H, m, CH(CH3)2), 2.66 (1H, d, J = 3.1 Hz),
4.21 (1H, s br, CH-NH), 4.73 (1H, s, C-NH), 6.65 (1H, t,
J = 2.4 Hz Ar-H), 6.91 (1H, t, J = 4 Hz Ar-H), 7.81 (1H, d,
J = 1.4 Hz Ar-H), 7.84 (1H, d, J = 1.42 Hz Ar-H); 13C NMR
(50 MHz, DMSO-d6): dC (ppm) 17.71, 18.12, 20.05 (-CH2CH
(CH3)2), 24.40, 25.21, 33.18 (carbons of cyclohexyl), 56.11
(CH-N of cyclohexyl), 112.95, 115.64, 122.11, 122.01, 126.13,
126.74, 128.37, 128.74, 132.35, 136.82, 145.88 (C-Ar).
[16] Marhadour, S.; Bazin, M. A.; Marchand, P. Tetrahedron Lett
2012, 53, 297.
[17] Chen, J. J.; Golebiowski, A.; McClenaghan, J.; Klopfenstein,
S. R.; West, L. Tetrahedron Lett 2001, 42, 2269.
[18] Lyon, A.; Kercher, T. S. Org Lett 2004, 6, 4989.
[19] Blackburn, C.; Guan, B. Tetrahedron Lett 2000, 41, 1495.
[20] Rousseau, A. L.; Matlaba, P.; Parkinson, C. J. Tetrahedron
Lett 2007, 48, 4079.
[21] Shaabani, A.; Soleimani, E.; Maleki, A. Tetrahedron Lett
2006, 47, 3031.
[22] Sadjadi, S.; Heravi, M. M. Tetrahedron 2011, 67, 2707.
[23] Ivachtchenko, A. V.; Ivanenkov, Y. A.; Kysil, V. M.;
Krasavin, M. Y.; Ilyin, A. P. Russ. Rev. 2011, 79, 787.
[24] Zhu, J. Eur. J. Org. Chem 2003, 2003, 1133.
4p.
N-Cyclohexyl-2-ethylimidazo[1,2-a]pyridin-3-amine
(Table 2, entry 4p). Colorless crystal (80%): mp 140–142ꢀC (dec).
[Found: C, 74.33; H, 8.72; N, 17.37. C15H21N3 requires C, 74.03;
H, 8.70; N, 17.27%]; IR (KBr) (nmax/cmꢁ1): 3315 (NH), 2885,
1633; 1H NMR (200MHz, DMSO-d6): dH (ppm) 0.90 (3H,
t, CH2-CH3), 1.06–1.74 (10H, m, 5CH2 of cyclohexyl), 2.15 (2H,
q, CH2CH3), 4.35 (1H, m, CH-N of cyclohexyl), 5.16 (1H, s
br, CH-NH), 6.77 (1H, t, Ar-H), 7.01 (1H, t, Ar-H), 7.86 (1H, d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei and M. Amiri
Vol 000
[25] Groebke, K.; Weber, L.; Mehlin, F. Synlett 1998, 11, 661.
[26] Blackburn, C. Tetrahedron Lett 1998, 39, 5469.
[27] Ghorbani-Vaghei, R.; Jalili, H.; Synthesis 2005, 4, 1099.
[28] Ghorbani-Vaghei, R.; Shahbazee, E.; Veisi, H.; Mendeleev
Commun 2005, 15, 204.
[33] Ghorbani-Vaghei, R. Tetrahedron Lett 2003, 44, 7529.
[34] Ghorbani-Vaghei, R.; Veisi, H.; Keypour, H.; Dehghani-
Firouzabadi, A. Mol Div 2010, 14, 84.
[35] Ghorbani-Vaghei, R.; Amiri, M.; Moshfeghifar, N.; Veisi, H.;
Akbari-Dadamahaleh, S. J Iran Chem Soc 2009, 6, 454.
[36] Ghorbani-Vaghei, R.; Karimi-Nami, R.; Toghraei-Semiromi,
Z.; Amiri, M.; Ghavidel, M.; Tetrahedron 2011, 67, 1930.
[37] Ghorbani-Vaghei, R.; Shahbazi, H.; Veisi, H. Tetrahedron Lett
2012, 53, 2325.
[38] Ghorbani-Vaghei, R.; Veisi, H. Mol Div 2009, 14, 249.
[39] Veisi, H.; Ghorbani-Vaghei, R. Tetrahedron 2010, 66,
7445.
[29] Ghorbani-Vaghei, R.; Zolfigol, M. A.; Chegeny, M.; Veisi, H.
Tetrahedron Lett 2006, 47, 4505.
[30] Ghorbani-Vaghei, R.; Shahbazee, E. J Braz Chem Soc 2005, 16, 644.
[31] Zolfigol, M A.; Ghorbani-Vaghei, R.; Mallakpour, S.; Chehardoli,
G.; Ghorbani- Choghamani, A.; Yazdi Hosain, A. Synthesis 2006, 10, 1631.
[32] Ghorbani-Vaghei, R.; Akbari-Dadamahaleh, S. Tetrahedron
Lett 2009, 50, 1055.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet