Visible-light-activated C-C and C-N bond formation in the synthesis of imidazo[1,2-: A] pyridines and imidazo[2,1- b] thiazoles under catalyst and solvent-free conditions

Article abstract of DOI:10.1039/c8nj03339k

The formation of a 3-aminoimidazo-fused heterocyclic compound and its derivatives through a multicomponent one-pot reaction, activated by visible light, is reported. The noticeable feature of this protocol is the utilization of a universally available energy source to activate the reaction. The reported methodology is the first protocol that represents the implementation of visible light for this Ugi-type synthesis from 2-aminoheterocycles, aldehydes, and isocyanides as well as offers the advantages of improved selectivity, outstanding yields, solvent and catalyst-free conditions, environmental sustainability and convenient access to starting materials.

Full text of DOI:10.1039/c8nj03339k

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Visible-light-activated C–C and C–N bond
formation in the synthesis of imidazo[1,2-
a]pyridines and imidazo[2,1-b]thiazoles under
catalyst and solvent-free conditions
Cite this:DOI: 10.1039/c8nj03339k
Km Neha Shivhare,a Manish K. Jaiswal,b Anushree Srivastava,a Saurabh K. Tiwaria
a
and I. R. Siddiqui
*
The formation of a 3-aminoimidazo-fused heterocyclic compound and its derivatives through a
multicomponent one-pot reaction, activated by visible light, is reported. The noticeable feature of this
protocol is the utilization of a universally available energy source to activate the reaction. The reported
methodology is the first protocol that represents the implementation of visible light for this Ugi-type
synthesis from 2-aminoheterocycles, aldehydes, and isocyanides as well as offers the advantages of
improved selectivity, outstanding yields, solvent and catalyst-free conditions, environmental sustainability
and convenient access to starting materials.
Received 4th July 2018,
Accepted 27th August 2018
DOI: 10.1039/c8nj03339k
rsc.li/njc
the synthesis of imidazo-fused heterocyclic scaffolds using visible
Introduction
´
light via the Groebke–Blackburn–Bienayme reaction (GBBR) using
Among nitrogen derivatives, imidazo-fused heterocycles are aldehydes, isocyanides, and 2-aminoheterocycle building blocks
becoming more crucial in medicinal chemistry, because of their under catalyst- and solvent-free conditions at ambient temperature.
broad range of pharmacological and biological activities, such as Model reactions for the synthesis of imidazo[1,2-a]pyridines and
antibacterial, antiviral, anti-inflammatory, and fungicidal prop- imidazo[2,1-b]thiazoles are shown in Scheme 1.
erties. Commercially available drugs containing imidazo-fused
A comparative account of the present work with previous
heterocycle moieties are alpidem (anxiolytic drug), zolimidine reported protocols is shown in Scheme 2. Our intensive atten-
(anti-ulcer drug), olprinone (PDE 3 inhibitor), zolpidem (hypnotic tion has been paid to green synthesis, Scheme 2 shows the tight
drug), saripidem and necopidem (sedative agents), and an optically legislation to maintain greenness in synthetic procedure direct
active drug (GSK812397), with a prospect for the treatment of to prevent the generation of waste, avoid the use of auxiliary
HIV infection, levamisole etc. shown in Fig. 1.1–7
Organic transformations activated by visible light have requirement with operational simplicity.
substances, ambient temperature, and minimize the energy
received considerable attention from the scientific community
Due to their high pharmacological and biological activities,
by virtue of their worthwhile and green perspectives.8 Recently, many strategies for the synthesis of imidazo-fused heterocycles
organic chemist are exploring visible light as an efficient and from 2-amino heterocycles, aldehydes and isocyanides have
versatile method to initiate various chemical transformations. been reported in the literature. Previous reactions dealing with
Handling during the synthesis of organic compounds under aspects of these three reactants in the presence of zirconium(IV)
exposure to visible light is safer than with ultraviolet light,9 and the chloride in polyethylene glycol-400,11 b-cyclodextrin-SO3H as
synthesized molecules are stable towards photodecomposition. a catalyst,12 Sc(OTf)3,13 heterogeneous solid acid catalysts,14
Photo-induced protocols provide a radical pathway for such nano-catalysts,15 zinc chloride,16 K-10 clay,17 and nano-
reactions to occur, which are otherwise complicated through magnetically modified sulfuric acid18 etc. have been reported.
conventional strategies.10
Other recent strategies for the synthesis of imidazo[1,2-
Hence, in continuation with our interest in the development of a]pyridines are Cu-catalysed reactions,19–26 reactions with various
MCRs in a greener way, we represent a crucial one-pot strategy for solvents,27,28 and reactions at high temperature.29 Many of these
procedures have many advantages; however, they have some
issues such as the use of expensive catalysts, volatile solvents,
high temperatures, isolation of intermediates, long reaction time
and typical workup procedures. Therefore, we turn towards a
greener methodology, which can overcome some drawbacks
a Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad,
Allahabad-211002, India. E-mail: dr.irsiddiqui@gmail.com
b Indian Institute of Technology Delhi, Department of Chemistry, Hauz Khas,
New Delhi 110016, India
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Fig. 1 Examples of biologically active compounds containing an imidazo-fused heterocycle framework.
Scheme 1 Model reactions for the synthesis of imidazo[1,2-a]pyridine and imidazo[2,1-b]thiazole derivatives.
discussed above. As a continuation of our research on the synthesis we report a catalyst-free, solvent-free visible light mediated
of heterocyclic compounds in an eco-friendly manner,30–32 methodology in the present work.
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Scheme 2 Comparison of the present work with previous reported protocols.
Results and discussion
the reactions were repeated for optimizing the visible light
intensity for the sake of reducing the intensity of visible light
used (Table 1, entry 2).
To understand the role of visible light for activation of the
reaction, the reaction was also performed in the absence of the
CFL at room temperature (Table 1, entry 4), and only a trace
amount of the product was formed, which indicated the crucial
role of visible light in the reaction.
We performed the GBBR among aldehydes, isocyanides and
2-aminoheterocycles using visible light as an activator. Owing
to our initial study, considerable attention has been paid to the
reaction conditions; since two of the reactants among three
were in the liquid physical state, we thought of carrying out this
reaction under solvent free conditions. We have taken all three
reactants together with 1 mmol of (1a), 1 mmol of (2a) and
1 mmol of (3a) in a closed round bottom flask and a CFL (24 W)
was used as the source of visible light. Under this condition,
we obtained 97% yield within 3 hours (Table 1, entry 1). Product
formation (4a) was confirmed by TLC analysis by the appearance
of a dark spot of the product after 3 hours. Excellent results
were obtained when the first set of reaction conditions tried,
A control experiment indicated that only a trace amount of
product (4a) was formed when the reaction was performed in
the dark at room temperature (Scheme 3, entry 1). When the
reaction was performed at different temperatures like 35 1C
and 60 1C, the corresponding product was obtained in 18%
and 29% yield (Scheme 3, entry 2 & 3), respectively. These
observations indicated that the compact fluorescent lamp (CFL)
plays an important role in the reported reaction procedure.
Reactions were also repeated in the presence of photocatalysts
such as Rose Bengal and Eosin Y (Scheme 3, entry 4 & 5)
but did not enhance the yield of the product, hence we
observed via control experiments that a catalyst free condition
(Scheme 3, entry 6) was appreciable over others for our
adopted route. When the reaction was carried out in the
presence of radical inhibitors such as benzoquinone33 and
(2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) (Scheme 3, entry
7 & 8) a rapid decrease in the yield of product (4a) was observed
and upon further increasing the amount of the inhibitor
(TEMPO), the reaction was fully suppressed. This finding
indicated that a free radical pathway is involved in the reaction.
The structure of the synthesized N-(tert-butyl)-2-phenyl-imidazo-
Table 1 Screening of visible light intensities for the synthesis of N-(tert-
butyl)-2-phenyl-imidazo[1,2-a]pyridin-3-amine
Entry
Reaction conditiona
Time (h)
Yieldb (%)
1
2
3
4
5
24 W, CFL, rt
20 W, CFL, rt
32 W, CFL, rt
No light, rt
3.00
3.25
3.00
3.00
3.00
97
95
97
Trace
82
32 W, LED, rt
1
[1,2-a]pyridin-3-amine was confirmed by recording its H NMR,
a
13C NMR, and IR spectra.
Reaction conditions: 2-aminopyridine (1 mmol), benzaldehyde
(1 mmol) and tert-butylisocyanide (1 mmol) in a sealed RB under
b
On the basis of a literature survey of visible-light induced
protocols,34–39 the proposed mechanism for the synthesis of
different reaction conditions. Isolated yield, W = watt (unit of visible
light intensity), rt = room temparature.
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Scheme 3 Control experiments. Reaction conditions: 1a (1 mmol), 2a (1 mmol) and 3a (1 mmol) in neat condition were irradiated in a closed round
bottom flask at room temperature using a CFL (24 W). a Yield (%) of the product in the presence of Rose Bengal (2 mmol%). b Yield (%) of the product in the
presence of Eosin Y (2 mmol%). c Yield (%) of the product in the absence of the photocatalyst. d Yield (%) of the product in the presence of benzoquinone
(1 mmol). e Yield (%) of the product in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (1 equivalent); rt = room temperature, 25–30 1C.
N-tert-butyl-2-phenylimidazo[1,2-a]pyridine-3-amine is outlined mixed together in a sealed round bottom flask. The mechanism
in Scheme 4. A one-pot reaction was carried out in which involved the reaction of 2-aminoheterocycle and benzaldehyde to
2-aminoheterocycle (1), aldehyde (2) and isocyanide (3) were form an imine (intermediate-(I)) which was afterwards attacked by
Scheme 4 A plausible mechanism for C–C and C–N bond formation and synthesis of imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles.
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Table 2 The synthesis of 3-aminoimidazo[1,2-a]pyridines via the Groebke–Blackburn–Bienayme reactiona
´
Entry
1
Comp. 1
Comp. 2
Comp. 3
Productb
Time (h)
3.00
Yieldc (%)
97
2
3
1a
1a
2a
2a
3.00
3.00
98
95
4
5
6
2a
2a
2a
3b
3b
3b
5.00
2.75
2.50
83
95
96
7
8
1d
1d
2a
3c
3c
3.00
2.50
90
90
9
1d
1d
3b
3b
2.75
2.75
93
93
10
11
1a
3b
3.00
90
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Table 2 (continued)
Entry
12
Comp. 1
Comp. 2
Comp. 3
Productb
Time (h)
3.00
Yieldc (%)
88
1a
3a
13
14
15
1a
1a
1a
3b
3a
3b
2.50
2.50
2.25
97
97
97
2c
23
16
1a
3b
2.75
91
a
b
Reaction conditions: 2-aminoheterocycle (1 mmol), aldehyde (1 mmol) and isocyanide (1 mmol). All the compounds were confirmed by
1H NMR and 13C NMR spectral analyses. Isolated yield.
c
the isocyanide to provide intermediate-(II). This intermediate (II) Conclusions
influenced by visible light radiation to generate free radical
In conclusion, it is of great importance to explore an efficient and
which were further cyclized followed by a 1,3-H shift to give the
convenient synthetic method to meet the increasing scientific and
desirable product.
practical demand for visible light activated, ‘real’ green one-pot
strategy for the synthesis of imidazo-fused heterocycles via GBBR.
All three reactants were mixed together in a pot without any prior
After optimizing the reaction conditions, in order to check
the applicability of our method, we extended it to various
amines, aldehydes, and isocyanides to obtain the corres-
activation. The key features of this procedure are mild conditions,
ponding imidazopyridine and imidazothiazole derivatives with
appreciable yield, operational accessibility, atom efficiency and
good to excellent yield (Tables 2 and 3). All the results indicate
that the electronic nature of the aminoheterocycles has an
ecologically innocuous processes.
impact on the effectiveness of the reaction, and all the corres-
ponding products are obtained in good to excellent yields.
For example, aminoazines bearing an electron-withdrawing
group like nitro gave (4d) in moderate yield (83%) with a
Experimental section
General information
prolonged reaction time, while electron donating groups Commercial reagents were purchased from Aldrich and Alfa
like methyl gave (4e) in excellent yield (95%) with a shorter Aesar and were used without further purification. 1H and
reaction time. On the other hand aldehydes with an electron 13C NMR spectra were recorded on a Bruker AVANCE 400
donating group decreased the yield (Table 2, 4k & 4l) whereas instrument using CDCl3 as solvent. Chemical shifts d are
electron withdrawing groups like nitro and cyanide afforded expressed in parts per million (ppm) and internally referenced
the corresponding imidazo-[1,2-a]pyridines (Table 2, 4m & 4n) to tetramethylsilane (TMS). Coupling constant, J is reported
in excellent yields (97%) with a reduction in reaction time.
in Hz. The following abbreviations were used: s = singlet,
The above results prompted us to extend this protocol to a d = doublet, t = triplet, q = quartet, m = multiplet. All the reaction
wide range of substrates and it is predicted to be extremely procedures were monitored by TLC using 40 pre-coated sheets
promising in the field of diversity-oriented synthesis (DOS).
of silica gel G/UV-254 of 0.25 mm thickness (Merck 60F254) and
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Table 3 The synthesis of 3-aminoimidazo[2,1-b]thiazole via the Groebke–Blackburn–Bienayme reactiona
´
Entry
17
Comp. 1
Comp. 2
Comp. 3
Productb
Time (h)
3.25
Yieldc (%)
2a
3b
93
18
1e
1e
2f
3b
3b
2.25
3.00
97
83
19
20
21
2c
1e
1e
1e
2a
2f
3a
3a
3a
2.50
2.00
2.25
92
97
82
22
2c
a
b
Reaction conditions: 2-aminoheterocycle (1 mmol), aldehyde (1 mmol) and isocyanide (1 mmol). All the compounds were confirmed by
1H NMR and 13C NMR spectral analyses. Isolated yield.
c
TLC plates were visualized by exposure to ultraviolet light light from a 24 W, white CFL. The 24 W CFL was placed 9 cm
and/or by exposure to iodine vapours and the product was away from the reaction mixture. The reaction progress was
obtained by column chromatography performed on silica gel monitored using TLC with a mixture of hexane – EtOAc (7/3)
(60–120 mesh). Infrared spectra were recorded on a Perkin which indicated that the reaction proceeded in a good manner and
Elmer FT-IR Spectrometer and are reported in frequency of was completed in 3 hours. Since it was a solvent and catalyst free
absorption. Mass spectra were recorded on a JEOL SX-102 (FAB) reaction, the product was directly subjected to silica gel column
mass spectrometer at 70 eV. Elemental analysis for C, H, N was chromatography (hexane/EtOAc) to afford 3-aminoimidazo-fused
performed on a Perkin Elmer model 2400 CHNS/O analyzer at heterocycles (4a–4v) as a solid.
SAIF Chandigarh.
N-(tert-Butyl)-2-phenylimidazo[1,2-a]pyridine-3-amine (4a)29.
White solid; isolated yield 97%; M.p.-162–165 1C; 1H-NMR
(400 MHz, CDCl3), d: 8.19 (d, J = 6.7 Hz, 1H), 7.89–7.87
Methods of preparation
General procedure for the synthesis of 3-aminoimidazo-fused (m, 2H), 7.56 (d, J = 9.2 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.32–7.26
heterocycles. 2-Amino heterocycles (1 mmol), aldehydes (1 mmol) (m, 1H), 7.14–7.8 (m, 1H), 6.79 (t, J = 6.7 Hz, 1H), 3.16 (s, 1H),
and isonitriles (1 mmol) were added to a sealed round bottom 1.07 (s, 9H); 13C-NMR (100 MHz, CDCl3), d: 141.9, 140.7, 136.5,
flask. The resulting mixture was stirred under exposure to visible 129.7, 128.9, 123.4, 122.9, 116.8, 110.6, 55.9, 29.6; IR nmax/cmÀ1
:
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3319, 2966, 2928, 1606, 1509, 1445, 1368, 1335, 1213, 1025, 745; 1.26–1.11 (m, 6H); 13C-NMR (100 MHz, CDCl3), d: 143.1, 138.8,
MS: m/z: 273.17 (M+, 100%), 268.1 (19%); anal. calculated for 136.9, 133.7, 128.8, 128.8, 127.2, 126.5, 56.8, 34.9, 25.5, 24.7; IR
C
17H19N3: C, 76.37; H, 7.92; N, 15.72 found: C, 76.28; H, 7.85;
n
max/cmÀ1: 3247, 2925, 2852, 1496, 1445, 1356, 1317, 1186, 767,
689; MS: m/z: 292.17 (M+, 100%), 293.17 (20%); anal. calculated
N, 15.63.
N-Cyclohexyl-2-phenylimidazo[1,2-a]pyridine-3-amine (4b)29. for C18H20N4: C, 73.94; H, 6.89; N, 19.16 found: C, 73.88;
White solid; isolated yield 98%; M.p.-177–180 1C; 1H-NMR H, 6.80; N, 19.09.
(400 MHz, CDCl3), d: 8.30 (d, J = 6.7 Hz, 1H), 8.03 (d, J = 7.2
N-Benzyl-2-phenylimidazo[1,2-a]pyrazin-3-amine (4g)40. Off
Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.47–7.43 (m, 2H), 7.34–7.26 white solid; isolated yield 90%; M.p.-150–155 1C; 1H-NMR
(m, 1H), 7.21–7.16 (m, 1H), 7.12–7.15 (m, 1H), 6.94–6.89 (m, 1H), (400 MHz, CDCl3), d: 8.95 (d, J = 1.3 Hz, 1H), 7.99–7.94 (m,
6.7 (t, J = 6.5 Hz, 1H), 3.15 (m, 1H), 2.17–2.14 (m, 2H), 1.91–1.89 2H), 7.85 (dd, J1 = 4.6 and J2 = 1.5 Hz, 1H), 7.78 (d, J = 4.6 Hz,
(m, 2H), 1.50–1.46 (m, 2H), 1.44–1.40 (m, 2H), 1.28–1.21 (m, 2H); 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.37–7.30
13C-NMR (100 MHz, CDCl3), d: 141.0, 134.1, 128.3, 127.1, 127.0, (m, 5H), 4.20 (d, J = 2.5 Hz, 2H), 3.67 (s, 1H), 2.19 (s, 1H);
125.1, 124.0, 122.7, 117.1, 111.6, 57.0, 34.1, 25.7, 24.8; IR 13C-NMR (100 MHz, CDCl3), d: 143.50, 138.80, 138.61, 136.82,
n
max/cmÀ1: 3237, 2917, 2845, 1560, 1440, 1361, 1331, 1223, 734; 133.33, 129.08, 129.04, 128.94, 128.42, 128.19, 128.03, 127.41,
MS: m/z 291.17 (M+, 100%), 292.17 (21%); anal. calculated for 127.14, 115.39, 52.40; IR nmax/cmÀ1: 3250, 2935, 2863, 1503,
C19H21N3: C, 78.32; H, 7.26; N, 14.42 found: C, 78.25; H, 7.18; 1439, 1365, 1349, 1193, 779, 697; MS: m/z: 300.15 (M+, 100%),
N, 14.38.
301.15 (21%); anal. calculated for C19H16N4: C, 75.98; H, 5.37;
N-Benzyl-2-phenylimidazo[1,2-a]pyridin-3-amine (4c)40. White N, 18.65 found: C, 76.03; H, 5.40; N, 18.76.
solid; isolated yield 95%; 1H-NMR (400 MHz, CDCl3), d: 8.13–
N-Benzyl-2-(pyridin-4-yl)imidazo[1,2-a]pyrazin-3-amine (4h)40.
7.98 (m, 3H), 7.60–7.57 (m, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.40–7.27 Off white solid; isolated yield 90%; M.p.-144–148 1C; 1H-NMR
(m, 6H), 7.19–7.13 (m, 1H), 6.79–6.75 (m, 1H), 4.19 (d, J = 6.2 Hz, (400 MHz, CDCl3), d: 9.00 (d, J = 1.4 Hz, 1H), 8.64 (dd, J1 = 4.5 and
2H), 3.54 (t, J = 6.0 Hz, 1H), 2.49 (s, 1H); 13C-NMR (100 MHz, J2 = 1.6 Hz, 2H), 7.89 (dd, J1 = 4.5 and J2 = 1.6 Hz, 2H), 7.82–7.78
CDCl3), d: 141.49, 138.98, 136.09, 134.09, 128.79, 128.29, 127.80, (m, 2H), 7.28 (dd, J1 = 5.2 and J2 = 1.8 Hz, 3H), 7.23 (dd,
127.64, 127.20, 125.79, 124.29, 122.52, 117.42, 112.02, 52.54; J1 = 6.8 and J2 = 2.5 Hz, 2H), 4.22 (d, J = 6.3 Hz, 2H), 3.68
IR nmax/cmÀ1: 3246, 2924, 2849, 1568, 1451, 1364, 1337, 1229, (t, J = 6.2 Hz, 1H); 13C-NMR (100 MHz, CDCl3), d: 150.50, 144.31,
741; MS: m/z: 299.17 (M+, 100%), 300.17 (23%); anal. calculated 140.92, 138.19, 137.16, 135.68, 129.44, 129.12, 128.43, 128.34,
for C20H17N3: C, 80.24; H, 5.72; N, 14.04 found: C, 80.29; H, 5.78; 128.27, 121.37, 115.32, 52.60; IR nmax/cmÀ1 3267, 2949, 2874,
N, 14.35.
1523, 1449, 1378, 1354, 1201, 789, 706; MS: m/z: 301.15
N-Cyclohexyl-6-nitro-2-phenylimidazo[1,2-a]pyridine-3-amine (M+, 100%), 302.15 (20%): anal. calculated for C18H15N5: C, 71.76;
(4d)29. Golden yellow solid; isolated yield 83%; M.p.-160–164 1C; H, 5.02; N, 23.24 found: C, 71.80; H, 5.37; N, 23.29.
1H-NMR (400 MHz, CDCl3), d: 9.19 (d, J = 2.5 Hz, 1H), 8.04
N-Cyclohexyl-2-(furan-2-yl)imidazo[1,2-a]pyrazin-3-amine (4i)29.
(d, J = 7.2 Hz, 2H), 7.97 (dd, J1 = 9.7 Hz and J2 = 2.3 Hz, 1H), 7.53 Brown solid; isolated yield 93%; M.p.-115–120 1C; 1H-NMR
(d, J = 9.9 Hz, 1H), 7.47–7.52 (m, 2H), 7.35–7.40 (m, 1H), 3.26 (400 MHz, CDCl3), d: 8.92 (d, J = 1.5 Hz, 1H), 7.97–7.91 (m, 1H),
(d, J = 4.3 Hz, 1H), 3.09–2.95 (m, 1H), 1.83 (d, J = 12.3 Hz, 2H), 7.81 (d, J = 4.9 Hz, 1H), 7.52 (d, J = 2 Hz, 1H), 6.93–6.95 (m, 1H),
1.75–1.67 (m, 3H), 1.35–1.14 (m, 5H); 13C-NMR (100 MHz, 6.56–6.59 (m, 1H), 3.79 (s, 1H), 4.5 (s, 1H), 1.89–1.84 (m, 2H),
CDCl3), d: 141.5, 138.1, 135.8, 134.4, 129.0, 128.9, 122.8, 122.7, 1.71–1.74 (m, 2H), 1.34–1.15 (m, 6H); 13C-NMR (100 MHz, CDCl3),
119.1, 118.6, 117.1; IR nmax/cmÀ1: 3257, 2919, 2849, 1640, 1539, d: 149.5, 143.4, 142.1, 137.5, 129.2, 127.2, 115.8, 111.7, 107.7, 57.0,
1501, 1431, 1348, 1320; MS: m/z: 336 (M+, 100%), 337 (22%); 34.1, 25.7, 25.0; IR nmax/cmÀ1: 3282, 2969, 2851, 1632, 1505, 1446,
anal. calculated for C19H20N4O2: C, 67.84; H, 5.99; N, 16.66 1360, 1337, 1206, 1029, 750, 700; MS: m/z: 282.15 (M+, 100%),
found: C, 67.79; H, 6.18; N, 16.83.
N-Cyclohexyl-5-methyl-2-phenylimidazo[1,2-a]pyridin-3-amine N, 19.84 found: C, 68.00; H, 6.38; N, 19.77.
(4e)29. Golden red solid; isolated yield 95%; M.p.-75–80 1C;
N-Cyclohexyl-2-(4-isopropylphenyl)imidazo[1,2-a]pyrazin-3-amine
283.15 (17%); anal. calculated for C16H18N4O: C, 68.06; H, 6.43;
1
1H-NMR (400 MHz, CDCl3), d: 7.98–7.95 (m, 2H), 7.49–7.44 (m, (4j)29. Creamy solid; isolated yield 93%; M.p.-140–143 1C; H-NMR
3H), 7.35–7.30 (m, 1H), 7.03 (dd, 1H, J1 = 8.9 and J2 = 6.9 Hz), (400 MHz, CDCl3), d: 8.98 (d, J = 1.5 Hz, 1H), 8.2–8.0 (m, 1H),
6.45 (d, 1H, J = 6.4 Hz), 3.14 (s, 1H), 2.96 (s, 3H), 2.78 (s, 1H), 7.93–7.91 (m, 2H), 7.82 (d, J = 4.9 Hz, 1H), 7.33 (d, J = 8.3 Hz, 2H),
1.70 (s, 2H), 1.60 (s, 2H), 1.05–0.98 (m, 6H); 13C-NMR (100 MHz, 3.21 (s, 1H), 3.00 (s, 1H), 2.97–3.00 (m, 1H), 1.85 (d, J = 10.3 Hz,
CDCl3), d: 143.3, 138.0, 135.9, 134.9, 128.5, 128.0, 127.1, 127.1, 2H), 1.70–1.73 (m, 2H), 1.5 (d, J = 6.8 Hz, 6H), 1.26–1.13 (m, 6H);
123.9, 60.1, 33.0, 26.0, 25.0, 20.0; IR nmax/cmÀ1: 3330, 3055, 13C-NMR (100 MHz, CDCl3), d: 149.2, 143.2, 139.2, 136.6, 131.2,
2920, 2852, 1550, 1510, 1447, 1395, 1365, 1220, 1073, 765; MS: 128.8, 127.5, 127.0, 126.4, 115.6, 56.7, 34.1, 34.0, 29.9, 25.7, 24.7,
m/z: 305 (M+, 100%), 306 (22%); anal. calculated for C20H23N3: 24.0; IR nmax/cmÀ1: 3250, 2953, 2925, 2850, 1550, 1505, 1449,
C, 78.60; H, 7.60; N, 13.75 found: C, 78.53; H, 7.49; N, 13.80.
1350, 1289, 1200, 845, 730; MS: m/z 334.2 (M+, 100%), 335 (23%);
anal. calculated for C21H26N4: C, 75.41; H, 7.84; N, 16.75 found:
N-Cyclohexyl-2-phenylimidazo[1,2-a]pyrazin-3-amine (4f)29
.
Brown solid; isolated yield 96%; M.p.-160–165 1C; 1H-NMR C, 75.36; H, 7.78; N, 16.69.
(400 MHz, CDCl3), d: 8.95 (s, 1H), 7.9 (d, 6.7 Hz, 3H), 7.83
4-Bromo-2-(3-(cyclohexylamino)imidazo[1,2-a]pyridin-2-yl)phenol
(d, J = 4.3 Hz, 1H), 7.48–7.45 (m, 2H), 7.38–7.34 (m, 1H), 3.27 (4k)29. Off-white solid; isolated yield 90%; M.p.-150–155 1C; 1H-NMR
(s, 1H), 3.00 (s, 1H), 1.80 (d, J = 10.2 Hz, 2H), 1.70–1.68 (m, 2H), (400 MHz, CDCl3), d: 13.12 (s, 1H), 8.50–8.29 (m, 1H), 8.09–8.03
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(m, 1H), 7.49 (d, 1H, J = 9.3 Hz), 7.30–7.23 (m, 2H), 6.89–6.85 (400 MHz, CDCl3), d: 8.10 (d, 6.8 Hz, 1H), 7.99 (d, J = 8.3 Hz,
(m, 2H), 3.05–2.98 (m, 2H), 1.83 (d, 2H, J = 12.3 Hz), 1.77–1.75 2H), 7.51 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 8.3 Hz, 2H), 7.13–7.09
(m, 2H), 1.40–1.29 (m, 3H), 1.23–1.12 (m, 3H); 13C-NMR (m, 1H), 6.79–6.76 (m, 1H), 3.11–3.0 (s, 1H), 2.98–2.91 (m, 2H),
(100 MHz, CDCl3), d: 157.0, 140.1, 135.2, 132.0, 129.3, 125.1, 1.82 (d, J = 12.2 Hz, 2H), 1.72–1.70 (m, 2H), 1.3 (d, J = 6.8 Hz,
122.9, 122.1, 119.2, 119.0, 116.9, 112.6, 110.4, 57.4, 33.9, 26.0, 6H), 1.26–1.14 (m, 6H); 13C-NMR (100 MHz, CDCl3), d: 147.8,
25.1; IR nmax/cmÀ1: 3350, 3070, 2929, 2849, 1636, 1474, 1369, 141.7, 136.4, 132.1, 126.9, 126.7, 124.9, 123.5, 122.9, 117.4,
1339, 1279, 1241, 1079, 810, 740; MS: m/z: 385.00 (M+, 100%), 111.6, 56.8, 34.2, 34.0, 25.9, 24.6, 24.2; IR nmax/cmÀ1: 3260,
387.10 (98%); anal. calculated for C19H20BrN3O: C, 59.08; 2958, 2929, 2851, 1628, 1506, 1450, 1363, 1345, 1224, 1105, 845,
H, 5.22; N, 10.88 found: C, 57.45; H, 5.76; N, 10.93.
752; MS: m/z: 333.2 (M+, 100%), 334 (23%); anal. calculated
N-tert-Butyl-2-(4-(dimethylamino)phenyl)imidazo[1,2-a]pyridin- for C22H27N3: C, 79.24; H, 8.16; N, 12.6 found: C, 79.19; H, 8.10;
3-amine (4l)41. Creamy yellow solid; isolated yield 88%; N, 12.2.
M.p.-185–189 1C; 1H-NMR (400 MHz, CDCl3), d: 8.26 (d, J =
N-Cyclohexyl-6-methoxy-2-phenylbenzo[d]imidazo[2,1-b]thiazol-
6.9 Hz, 1H), 7.79 (d, J = 6.8 Hz, 2H), 7.54 (d, J = 9.3 Hz, 1H), 7.09 3-amine (4q)29. Orange solid; isolated yield 93%; M.p.-60–65 1C;
(t, J = 8 Hz, 1H), 6.73–6.80 (m, 3H), 3.00 (s, 6H), 1.10 (s, 9H); 1H-NMR (400 MHz, CDCl3), d: 7.93 (d, J = 8.8 Hz, 1H), 7.84–7.87 (m,
13C-NMR (100 MHz, CDCl3), d: 150.0, 141.9, 140.9, 129.1, 123.9, 2H), 7.42–7.40 (m, 2H), 7.27–7.23 (m, 1H), 7.14 (d, J = 2.4, 1H),
123.4, 122.0, 121.8, 116.9, 111.9, 110.0, 56.7, 40.7, 29.8; IR 6.99–7.02 (m, 1H), 3.87 (s, 3H), 3.16 (s, 1H), 2.97 (s, 1H), 1.87
n
max/cmÀ1: 3429, 2370, 1633, 1413, 760; MS: m/z: 308.20 (d, J = 10.3 Hz, 2H), 1.67–1.65 (m, 2H), 1.27–1.13 (m, 6H);
(M+, 100%), 309.20 (21%); anal. calculated for C19H24N4: C, 13C-NMR (100 MHz, CDCl3), d: 156.4, 142.9, 137.5, 134.9, 131.5,
73.99; H, 7.84; N, 18.17 found: C, 74.11; H, 7.76; N, 18.20. 129.0, 128.3, 127.2, 126.8, 126.4, 114.1, 112.9, 108.7, 57.3, 56.0,
N-Cyclohexyl-2-(4-nitrophenyl)imidazo[1,2-a]pyridine-3-amine 33.5, 25.9, 25.0; IR nmax/cmÀ1: 3307, 2929, 2850, 1661, 1603, 1572,
(4m)29. Orange-red brown color solid; isolated yield 97%; 1546, 1469, 1448, 1397, 1264, 1180, 1026, 830, 702; MS: m/z: 389.1
M.p.-200–204 1C; 1H-NMR (400 MHz, CDCl3), d: 8.35–8.29 (M+, 100%), 390.1 (25%); anal. calculated for C22H23N3OS:
(m, 4H), 8.09 (d, 1H, J = 6.9 Hz), 7.4 (d, 1H, J = 9.2 Hz), 7.20–7.16 C, 70.92; H, 5.95; N, 10.79 found: C, 70.88; H, 5.90; N, 10.74.
(m, 1H), 6.9 (t, 1H, J = 6.5 Hz), 3.10 (d, 1H, J = 5.0 Hz), 3.00–2.95
N-Cyclohexyl-6-methoxy-2-(4-nitrophenyl)benzo[d]imidazo-
(m, 1H), 1.89–1.84 (m, 3H), 1.74–1.72 (m, 2H), 1.29–1.14 (m, 6H); [2,1-b]thiazol-3-amine (4r)29. Orange solid; isolated yield 97%;
13C-NMR (100 MHz, CDCl3), d: 147.0, 142.8, 140.8, 134.7, 126.9, M.p.-185–190 1C; 1H-NMR (400 MHz, CDCl3), d: 8.19–8.12
125.8, 124.8, 123.7, 122.5, 118.1, 12.9, 56.9, 34.1, 25.8, 24.9; IR (m, 2H), 8.10–8.05 (m, 2H), 7.80 (d, J = 8.8 Hz, 1H), 7.17 (d,
n
max/cmÀ1: 3239, 2920, 2850, 1601, 1510, 1449, 1368, 1330, 1112, J = 2.4 Hz, 1H), 6.99–7.02 (m, 1H), 3.83 (s, 3H), 3.10 (d, J =
857, 729; MS: m/z: 336.15 (M+, 100%), 337.15 (22%); anal. calculated 4.4 Hz, 1H), 2.93–2.91 (m, 1H), 1.85 (d, J = 12.7 Hz, 2H), 1.69–1.67
for C19H20N4O2: C, 67.84; H, 5.99; N, 16.66 found: C, 68.02; H, 6.10; (m, 2H), 1.25–1.18 (m, 4H), 1.16–1.2 (m, 2H); 13C-NMR (100 MHz,
N, 16.70.
CDCl3), d: 157.3, 145.9, 144.1, 141.0, 135.9, 131.9, 131.0, 127.0,
4-(3-(tert-Butylamino)imidazo[1,2-a]pyridin-2-yl)benzonitrile 126.2, 123.5, 114.1, 113.0, 108.9, 57.7, 56.0, 33.9, 32.5, 25.7, 24.8,
(4n)41. Light yellow solid; isolated yield 97%. M.p.-155–160 1C. 22.9, 14.0; IR nmax/cmÀ1: 3336, 2929, 2850, 1595, 1496, 1330,
1H-NMR (400 MHz, CDCl3) d: 8.20–8.16 (m, 3H), 7.70 (d, J = 1267, 1230, 1110, 1033, 853, 709; MS: m/z: 434.1 (M+, 100%),
8 Hz, 2H), 7.51 (d, J = 9.2 Hz, 1H), 7.20 (t, J = 6.8 Hz, 1H), 6.79 435.1 (25%); anal. calculated for C22H22N4O3S: C, 63.58; H, 5.10;
(t, J = 6.8 Hz, 1H), 3.07 (s, 1H), 1.10 (s, 9H). 13C-NMR (100 MHz, N, 12.89 found: C, 63.47; H, 5.07; N, 12.84.
CDCl3) d: 143.1, 140.1, 137.7, 133.0, 132.6, 131.8, 129.1, 128.4,
128.1, 127.7, 127.1, 126.9, 126.5, 125.4, 125.1, 124.7, 123.8, thiazol-3-amine (4s)29. Brown oil; isolated yield 83%; 1H-NMR
119.4, 116.4, 114.3, 112.2, 111.5, 56.9, 30.9, 29.6; IR nmax/cmÀ1
(400 MHz, CDCl3), d: 7.9–7.93 (m, 1H), 7.45 (d, J = 1.5 Hz, 1H),
N-Cyclohexyl-2-(furan-2-yl)-6-methoxybenzo[d]imidazo[2,1-b]-
:
3330, 2969, 2925, 1633, 1610, 1500, 754, 549; MS: m/z 290.10 7.13 (s, 1H), 6.98–6.94 (m, 1H), 6.64–6.63 (m, 1H), 6.51–6.50 (m,
(M+, 100%), 291.10 (20%); anal. calculated for C18H18N4: 1H), 3.87 (s, 3H), 3.61–3.64 (m, 1H), 2.95–2.90 (m, 1H), 2.06–2.0
C, 74.46; H, 6.25; N, 19.30 found: C, 74.39; H, 6.19; N, 19.70.
(m, 2H), 1.73–1.71 (m, 2H), 1.35–1.16 (m, 6H); 13C-NMR
N-Cyclohexyl-2-(furan-2-yl)imidazo[1,2-a]pyridine-3-amine (4o)29. (100 MHz, CDCl3), d: 156.9, 150.7, 143.2, 140.5, 131.4, 130.0,
Creamy solid; isolated yield 97%; M.p.-125–127 1C; 1H-NMR 128.3, 127.2, 114.5, 113.0, 111.1, 108.5, 104.2, 58.0, 56.0, 33.5,
(400 MHz, CDCl3), d: 8.03 (d, 6.7 Hz, 1H), 7.52–7.55 (m, 2H), 29.9, 25.9, 25.0; IR nmax/cmÀ1: 3355, 2926, 2849, 1600, 1539,
7.13–7.08 (m, 1H), 6.84 (d, J = 3.3 Hz, 1H), 6.75 (t, J = 6.5 Hz, 1500, 1464, 1350, 1265, 1234, 1170, 1040, 807, 734; MS: m/z:
1H), 6.52–6.55 (m, 1H), 3.59 (d, J = 6.7 Hz, 1H), 2.99–2.91 379.1 (M+, 100%), 380.1 (23%); anal. calculated for C20H21N3O2S:
(m, 1H), 1.8 (d, J = 12.1 Hz, 2H), 1.74–1.72 (m, 2H), 1.32–1.12 C, 66.47; H, 5.58; N, 11.07 found: C, 66.35; H, 5.52; N, 11.01.
(m, 6H); 13C-NMR (100 MHz, CDCl3), d: 150.2, 141.5, 128.0,
125.3, 123.8, 122.7, 111.5, 111.4, 106.3, 56.9, 34.0, 25.76, 24.9; 3-amine (4t)29
N-(tert-Butyl)-6-methoxy-2-phenylbenzo[d]imidazo[2,1-b]thiazol-
Creamy white solid; isolated yield 92%;
.
IR nmax/cmÀ1: 3220, 2921, 2851, 1541, 1491, 1350, 1339, 1090, M.p.-150–154 1C; 1H-NMR (400 MHz, CDCl3), d: 8.22 (d, J =
1010, 740, 727; MS: m/z: 281.15 (M+, 100%), 282.15 (18%); anal. 8.7 Hz, 1H), 7.79–7.72 (m, 2H), 7.45–7.38 (m, 2H), 7.30–7.25
calculated for C17H19N3O: C, 72.57; H, 6.81; N, 14.94 found: (m, 1H), 7.15 (d, J = 2.4 Hz, 1H), 6.94–6.97 (m, 1H), 3.88 (s, 3H),
C, 72.45; H, 6.76; N, 14.90.
3.20 (s, 1H), 1.05 (s, 9H); 13C-NMR (100 MHz, CDCl3), d: 156.9,
N-Cyclohexyl-2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-3-amine 143.0, 140.9, 135.1, 131.5, 128.1, 127.8, 127.9, 126.8, 115.5,
1
(4p)29. White solid; isolated yield 91%; M.p.-161–166 1C; H-NMR 112.4, 108.6, 56.8, 55.9, 29.8; IR nmax/cmÀ1: 3286, 2967, 2967,
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6 S. Payra, A. Saha, C. M. Wu, B. Selvaratnam, T. Dramstad,
L. Mahoney, S. K. Verma, S. Thareja, R. Koodali and
S. Banerjee, New J. Chem., 2016, 40, 9753–9760.
7 M. J. Miller, I. Farahmandian, F. Arfaa, N. Katz, E. Winsor
and E. Bennett, South. Med. J., 1978, 71, 137–140.
8 (a) J. Davies, S. G. Booth, S. Essafi, R. A. W. Dryfe and D. Leonori,
Angew. Chem., Int. Ed., 2015, 54, 14017–14021; (b) D. P. Hari and
B. Konig, Chem. Commun., 2014, 50, 6688–6699.
9 K. Yamada, M. Okada, T. Fukuyama, D. Ravelli, M. Fagnoni
and I. Ryu, Org. Lett., 2015, 17, 1292–1295.
10 J. Jin and D. W. C. MacMillan, Nature, 2015, 525, 87–90.
11 S. K. Guchhait and C. Madaan, Synlett, 2009, 628–632.
12 J. Wu, F. Z. Xu, S. L. Feng, W. Xue and Z. Z. Wang,
Heterocycles, 2016, 92, 1629–1642.
13 S. Shaaban and B. F. Abdel-Wahab, Mol. Diversity, 2016, 20,
233–254.
14 A. Shaabani, M. Seyyedhamzeh, S. Shaabani and N. Ganji,
Res. Chem. Intermed., 2015, 41, 2377–2383.
15 A. Shaabani, H. Nosrati and M. Seyyedhamzeh, Res. Chem.
Intermed., 2015, 41, 3719–3727.
16 A. L. Rousseau, P. Matlaba and C. J. Parkinson, Tetrahedron
Lett., 2007, 48, 4079–4082.
2924, 2854, 1604, 1553, 1492, 1445, 1366, 1300, 1235, 1194,
1068, 1029, 910, 730, 700; MS: m/z: 363.1 (M+, 100%), 364.1
(23%); anal. calculated for C20H21N3OS: C, 69.39; H, 5.82; N,
11.56 found: C, 69.28; H, 5.75; N, 11.51.
N-(tert-Butyl)-6-methoxy-2-(4-nitrophenyl)benzo[d]imidazo-
[2,1-b]thiazol-3-amine (4u)29. Orange solid; isolated yield 97%;
M.p.-183–188 1C; 1H-NMR (400 MHz, CDCl3), d: 8.19–8.12
(m, 2H), 8.10–8.05 (m, 2H), 7.80 (d, J = 8.8 Hz, 1H), 7.17 (d,
J = 2.4 Hz, 1H), 6.99–7.03 (m, 1H), 3.83 (s, 3H), 3.10 (s, 1H),
1.15 (s, 9H); 13C-NMR (100 MHz, CDCl3), d: 157.3, 145.9, 144.1,
141.0, 135.9, 131.9, 131.0, 127.0, 126.2, 123.5, 114.1, 113.0,
108.9, 57.7, 56.0, 29.7; IR nmax/cmÀ1: 3336, 2929, 2850, 1595,
1496, 1267, 1230, 1110, 1033, 853, 709; MS: m/z: 408.1
(M+, 100%), 409.1 (23%); anal. calculated for C20H20N4O3S:
C, 61.75; H, 4.94; N, 13.72 found: C, 61.67; H, 4.88; N, 13.69.
N-(tert-Butyl)-2-(furan-2-yl)-6-methoxybenzo[d]imidazo[2,1-b]-
thiazol-3-amine (4v)29. Brown oil; isolated yield 82%; 1H-NMR
(400 MHz, CDCl3), d: 7.9–7.03 (m, 1H), 7.45 (d, J = 1.5 Hz, 1H),
7.13 (s, 1H), 6.98–6.94 (m, 1H), 6.64–6.63 (m, 1H), 6.51–6.50 (m,
1H), 3.87 (s, 3H), 3.12 (s, 1H), 1.12 (s, 9H); 13C-NMR (100 MHz,
CDCl3), d: 156.9, 150.7, 143.2, 140.5, 131.4, 130.0, 128.3, 127.2,
114.5, 113.0, 111.1, 108.5, 104.2, 58.0, 56.0, 29.9; IR nmax/cmÀ1
:
17 R. S. Varma and D. Kumar, Tetrahedron Lett., 1999, 40,
7665–7669.
18 S. Rostamnia, K. Lamei, M. Mohammadquli, M. Sheykhan
and A. Heydari, Tetrahedron Lett., 2012, 53, 5257–5260.
19 H. Cao, X. Liu, L. Zhao, J. Cen, J. Lin, Q. Zhu and M. Fu, Org.
Lett., 2014, 16, 146–149.
3355, 2926, 2849, 1600, 1539, 1500, 1464, 1265, 1234, 1170,
1040, 807, 734; MS: m/z: 353.1 (M+, 100%), 354.1 (20%); anal.
calculated for C18H19N3O2S: C, 64.57; H, 5.42; N, 11.89 found:
C, 64.49; H, 5.35; N, 11.80.
20 H. Cao, H. Zhan, Y. Lin, X. Lin, Z. Du and H. Jiang, Org. Lett.,
2012, 14, 1688–1691.
Conflicts of interest
21 C. Wang, S. Lei, H. Cao, S. Qiu, J. Liu, H. Deng and C. Yan,
J. Org. Chem., 2015, 80, 12725–12732.
There are no conflicts to declare.
22 S. Lei, H. Cao, L. Chen, J. Liu, H. Cai and J. Tan, Adv. Synth.
Catal., 2015, 357, 3109–3114.
23 H. Cao, S. Lei, N. Li, L. Chen, J. Liu, H. Cai, S. Qiu and J. Tan,
Chem. Commun., 2015, 51, 1823–1825.
24 H. Huang, X. Ji, X. Tang, M. Zhang, X. Li and H. Jiang, Org.
Lett., 2013, 15, 6254–6257.
25 Y. Zhang, Z. Chen, W. Wu, Y. Zhang and W. Su, J. Org.
Chem., 2013, 78, 12494–12504.
Acknowledgements
We gratefully acknowledge the financial support from the
University Grant Commission and CSIR. The authors are also
grateful to SAIF, Punjab University Chandigarh, for providing
all the spectroscopic and analytical data.
26 J. Liu, W. Wei, T. Zhao, X. Liu, J. Wu, W. Yu and J. Chang,
J. Org. Chem., 2016, 81, 9326–9336.
27 H. Cao, X. Liu, L. Zhao, J. Cen, J. Lin, Q. Zhu and M. Fu, Org.
Lett., 2014, 16, 146–149.
28 P. R. Adiyala, G. S. Mani, J. B. Nanubolu, K. C. Shekar and
R. A. Maurya, Org. Lett., 2015, 17, 4308–4311.
29 S. Vidyacharan, A. H. Shinde, B. Satpathi and D. S. Sharada,
Green Chem., 2014, 16, 1168–1175.
References
1 (a) S. Bassi, M. G. Albizzati, C. Ferrarese, L. Frattola,
B. Cesana, R. Piolti and A. Farolfi, Clin. Neuropharmacol.,
1989, 12, 67–74; (b) A. Munir, S. Azam, S. Ali, A. Mehmood,
A. H. Shah, M. S. Khan, R. Manzoor, M. Sana, S. A. Mufti and
S. Fazal, Drug Des., 2017, 6, 1–7.
30 P. Rai, Rahila, H. Sagir and I. R. Siddiqui, ChemistrySelect,
2016, 1, 4550–4553.
2 Y. Katsura, S. Nishino and H. Takasugi, Chem. Pharm. Bull.,
1991, 39, 2937–2943.
31 A. Ibad, M. A. Waseem, F. Ibad, K. Ansari, A. M. Lone, G. Watal
and I. R. Siddiqui, ChemistrySelect, 2017, 2, 4587–4592.
32 Rahila, P. Rai, A. Ibad, H. Sagir and I. R. Siddiqui,
ChemistrySelect, 2016, 1, 1300–1304.
3 K. Mizushige, T. Ueda, K. Yukiiri and H. Suzuki, Cardiovasc.
Drug Rev., 2002, 20, 163–174.
4 S. Z. Langer, S. Arbilla, J. Benavides and B. Scatton, Adv.
Biochem. Psychopharmacol., 1990, 46, 61–72.
33 M. Pelaez, et al., Appl. Catal., B, 2012, 125, 331–349.
34 T. Xiong and Q. Zhang, Chem. Soc. Rev., 2016, 45, 3069–3087.
5 L. Almirante, L. Polo, A. Mugnaini, E. Provinciali, P. Rugarli,
A. Biancotti and A. Gamba, J. Med. Chem., 1965, 8, 305–312.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018

View Article Online
NJC
Paper
35 Y. Wang, P. Ren, X. Gu, X. Wen, Y. Wang, X. Guo, E. R. Waclawik, 39 T. Kaur, P. Wadhwa, S. Bagchi and A. Sharma, Chem. Commun.,
H. Zhuc and Z. Zheng, Green Chem., 2016, 18, 1482–1487. 2016, 52, 6958–6976.
36 A. Mishra, M. Srivastava, P. Rai, S. Yadav, B. P. Tripathi, 40 D. B. Salunke, E. Yoo, N. M. Shukla, R. Balakrishna,
J. Singh and J. Singh, RSC Adv., 2016, 6, 49164–49172.
S. S. Malladi, K. J. Serafin, V. W. Day, X. Wang and
37 M. Zhang, Q.-Y. Fu, G. Gao, H.-Y. He, Y. Zhang, Y.-S. Wu and
S. A. David, J. Med. Chem., 2012, 55, 8137–8151.
Z.-H. Zhang, ACS Sustainable Chem. Eng., 2017, 5, 6175–6182. 41 A. T. Baviskar, C. Madaan, R. Preet, P. Mohapatra, V. Jain,
38 N. Yadav, H. Sagir, M. D. Ansari and I. R. Siddiqui, Catal.
Lett., 2018, 148, 1676–1685.
A. Agarwal, S. K. Guchhait, C. N. Kundu, U. C. Banerjee and
P. V. Bharatam, J. Med. Chem., 2011, 54, 5013–5030.
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