In(OTf)3 assisted synthesis of β-carboline C-3 tethered imidazo[1,2-a]azine derivatives

Article abstract of DOI:10.1039/c6nj03210a

Synthesis of β-carboline based natural products and synthetic derivatives is one of the frontier areas of research owing to their medicinal properties. It is envisaged that 3-formyl-9H-β-carboline is a potential precursor and offers new vistas for the construction of a variety of heterocyclic architectures at the C-3 position of the β-carboline skeleton. In this context, an efficient protocol has been developed for the synthesis of β-carboline C-3 tethered imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[1,2-a]pyrazine derivatives via exploration of the Groebke-Blackburn-Bienayme (GBB) reaction. The present protocol offers several advantages like operational simplicity, high atom economy, appreciable structural diversity and easy purification procedure.

Full text of DOI:10.1039/c6nj03210a

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The role of atropisomers on the photo-reactivity and fatigue of
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DOI: 10.1039/C6NJ03210A
New Journal of Chemistry
ARTICLE
In(OTf)3 Assisted Synthesis of β-Carboline C-3
Tethered Imidazo[1,2-a]azine Derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
b
Nisha Devi, Dharmender Singh, Gurpreet Kaur, Satbir Mor, V. P. R. Kishore
c
c
d
a*
Putta, Saibabu Polina, Chandi C. Malakar and Virender Singh
DOI: 10.1039/x0xx00000x
www.rsc.org/
Synthesis of β-carboline based natural products and synthetic derivatives is one of the frontier areas
of research owing to their medicinal properties. It is envisaged that 3-formyl-9H-β-carboline is a
potential precursor and offers new vistas for construction of variety of heterocyclic architectures at
C-3 position of β-carboline skeleton. In this context, an efficient protocol has been developed to
serve the synthesis of β-carbolines C-3 tethered imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine,
and imidazo[1,2-a]pyrazine derivatives via exploration of Groebke-Blackburn-Bienayme (GBB)
reaction. The present protocol offers several advantages like operational simplicity, high atom
economy, appreciable structural diversity and easy purification procedure.
In organic synthesis, generation of complexity from simple and
readily available starting materials in minimal number of steps is
always desired and multicomponent reactions (MCR) offer an
Introduction
8
efficient tool to fulfil this purpose. In this aspect, Groebke-
β-Carboline, also known as norharmane, is a prototype compound
belonging to a class of nitrogen containing heterocycles which is
chemically pyrido[3,4-b]indole framework. β-Carboline containing
alkaloids are wide spread in animal and plant kingdom, and it is
estimated that this framework is represented by more than one
Blackburn-Bienayme (GBB) reaction, a variant of Ugi reaction
results in formation of a densely substituted N-fused imidazole
framework which is represented by several commercial drugs like
Zolpidem, Olprinone, Soraprazan, Zolmidine and many others
1
9
under pre-clinical trials. GBB reaction is one of the most newly
third of total natural products extracted from different sources
2
discovered (1998) methodology which has been applauded by the
scientific community as indicated by increasing number of
publications in this field including more than 2000 patent
(
Figure 1). Nature uses L-tryptophan as the key precursor for the
biosynthesis of β-carboline skeleton which is considered to be the
reason behind their colossal abundance. This privileged scaffold is
3
1
0
applications since 1998.
gifted with broad spectrum of pharmacological properties including
anticancer, antimalarial, anxiolytic, antibacterial, antifungal,
antiviral, anti-HIV, anti-alzheimer, antihypnotic, anticonvulsant
4
etc. It has been revealed that bulk of these alkaloids display potent
O
HO
anticancer properties by intercalating into DNA strands, inhibiting
topoisomerases, CDK, MK-2, Ikk, kinesin-like protein Eg5 and PLK1
O
O
N
N
O
N
N
N
H
NH
N
N
H
5
H
O
etc. Interestingly, some of β-carboline containing drugs have also
O
HN
O
O
N
N
been commercialized successfully such as tadalafil and abecarnil
are used clinically for the treatment of erectile dysfunction and CNS
N
MeO
OMe
OH
OH
Hyrtioerectine A
Xestomanzamine A
Azatoxin
O
6
Tadalafil (Cialis)
disorders. Due to their enormous medicinal importance, synthesis
R3
N
of β-carboline containing derivatives have been an exciting area of
research and accordingly several elegant approaches have been
N
O
N
N
N
H
N Cl
N
N
H
N
N
R4
NH
7
CH3
N
R2
H
R1
devised.
Harmine
2
H N
N
O
O
N
Fascaplycine
Annomontine
CH
3
O
N
N
H
3
C
O
N
N
HO
F
2
H N
N
N
O
NH2
NH
Zolpidem
(treatment of insomnia)
N
F
Soraprazan
N
Type 2 Diabetes Agent
N
CN
O
F
N
N
3
H C
N
N
S
O
N
S
H
O
Antiviral Agent
Olprinone (cardiotonic)
Zolmidine
Figure 1. Examples of β-carboline and imidazo[1,2-a]azine
containing bioactive natural products and commercial drugs
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
this precursor for installation of diversity at β–Carboline skeleton
but not adequate to demonstrate its significance as depicted in
1
5-16
Figure 3.
Therefore, we herein wish to report the synthesis of β-
carboline C-3 tethered imidazo[1,2-a]pyridines, imidazo[1,2-
a]pyrimidines, and imidazo[1,2-a]pyrazine derivatives via
exploration of Groebke-Blackburn-Bienayme multicomponent
reaction of 3-formyl-9H-pyrido[3,4-b]indoles, 2-aminoazines and
isonitriles.
Figure 2. Pictorial representation of versatility of 3-formyl-9H-β-
carboline
Results and Discussion
The present study commenced with the synthesis of substituted 3-
formyl-9H-β-carbolines (6a-c) which was achieved via modification
1
5,
Recently, our research group reviewed the potential of this
methodology (GBB) and updated the pharmacology of imidazo[1,2-
a]pyridine frameworks which revealed that these drug-like
in the previously reported procedure as described in Scheme 1.
1
7
L-tryptophan (1) was used as the precursor and subjected to
11
Pictet-Spengler (P-S) condensation with various aldehydes (a-c) in
dry DCM at room temperature for the chemical synthesis of
tetrahydro-β-carboline derivatives (2a-c). It was pleasing to see
that P-S condensation with L-tryptophan (1) was very fast as
compared to tryptophan ester and the reaction was completed in
molecules display wide range of biological properties like
1
2
anticancer, antimicrobial, antiviral, anticonvulsant and many
1
3
more. Fascinated by the medicinal profile of these two
pharmacophores, we developed β-carboline C-1 imidazopyridine
1
4a
1
5
hybrids via the application of this 3-component approach. The
preliminary biological screening provided us intriguing results
which inspired us to further expand the domain of library. Recently,
Kamal and co-workers discovered that β-carboline C-3 tethered
4
5 min only. Next, the oxidation of C-ring of tetrahydro-β-
carbolines (2a-c) was achieved via reaction with KMnO in
anhydrous DMF (45 min) to produce the β-carboline derivatives
4
(
4
3a-c). It was interesting to see that oxidation with KMnO was
1
5
1
7
benzimidazole derivatives act as potent anticancer agents. The
findings of Kamal et al. further guided us to introduce
imidazopyridine framework (which is isostere/mimic of
benzimidazole) at C-3 position in β–carboline and supported the
designed prototype for our current anticancer project. Accordingly,
we explored 3-formyl-9H-β-carbolines for the synthesis of designed
prototype as this precursor has a lot of potential and offer several
avenues to introduce variety of bioactive heterocyclic scaffolds at
C-3 position of β–carboline which is not possible through classical
methods like Pictet-Spengler (P-S) or Bischler Napieralski
cyclisation. It is projected that presence of two nucleophilic sites
selective and no decarboxylation was observed.
Further
treatment of 3a-c with methyl iodide in presence of K CO yielded
2 3
the corresponding methyl ester (4a-c) in high yield (83-87%) and
reduction of ester functionality with LiAlH in dry THF furnished the
alcohols (5a-c) in excellent yield (90-95%) within 15 min. The
oxidation of alcohol derivatives (5a-c) with MnO in dry DCM
4
2
yielded the desired 3-formyl-9H-β-carbolines (6a-c) in 73-88% yield.
This method has advantages including application to gram scale
synthesis and convenience of avoiding column chromatography
purification.
(N-2 and N-9) in close proximity of electrophilic site (formyl group
at C-3) with several sites for diversification at C-1, C-4, C-5, C-6, C-7
and C-8 makes this precursor a useful template in this prospect
Having synthesized starting substrates, next we intended at
achieving the synthesis of our targeted prototype i.e. β-carboline
tethered imidazoazines. Accordingly, the optimization studies were
performed by using 1-(4-bromophenyl)-9H-pyrido[3,4-b]indole-3-
carbaldehyde (6b), 2-aminopyridine (A) and ethylisocyanoacetate
(Figure 2). A detailed review of literature database revealed that
only limited approaches were documented toward exploration of
(X) as model substrates. After an extensive review of literature, it
was concluded that H O, EtOH, MeOH and toluene were the best
2
1
8
solvents for various multicomponent transformations. As water
shows unique reactivity profile, we initiated our studies in water as
o
a solvent under catalyst-free condition at 100 C but the formation
1
9
of desired product was not observed (Table 1, entry 1).
1
5-16
Figure 3. A summary of previous reports
toward exploration of
Scheme 1. Synthesis of 3-formyl-9H-pyrido[3,4-b]indole derivatives
3-formyl-9H-β-carbolines
2
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Table 1. Optimization of reaction conditions
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ARTICLE
a
reaction was completed within 35 min and product was afforded in
2% yield (Table 1, entry 4). Further, it was observed that yield of
6
the desired product dropped dramatically upon decreasing the
catalyst loading which resulted in incomplete conversion of
substrates as well (Table 1, entry 5). Interestingly, an increase in
catalyst loading to 15 mol% resulted in increased yield (73%) and
shorter duration (Table 1, entry 6). However, when catalyst loading
was further increased to 20 mol%, the reaction time was reduced
considerably (5 min), but yield was dropped slightly from 73% to
6
9% (Table 1, entry 7). On the other hand, reaction at room
b
Entry Catalyst
Solvent
Temp. Time
Yield
(%)
temperature yielded the product in poor yield and the reaction was
not completed even after 48 h (Table 1, entry 8). In comparison to
EtOH, the desired product was obtained even in lower yield when
MeOH and toluene were used as solvent (Table 1, entries 9-11).
Similarly, p-TSA and TFA catalysed reactions in toluene and
dichloromethane offered the product in 55% and 45% yields
respectively. After a careful optimization of reaction parameters
such as solvent and catalyst loading, we screened the efficiency of
other Lewis acids for similar transformation (Table 1, entries 14-
20). All the Lewis acids yielded the desired product albeit in
moderate yield (Table 1, entries 14-20). The results of
standardization studies are presented in Table-1 which led us to
conclude that the reaction of model substrates in the presence of
d
o
c
(mol%)
(
C)
e
e
1
2
-
-
H
EtOH
2
O
100
80
100
80
48 h
48 h
48 h
35
6b
29 + 6b
6b
3
4
In(OTf)
In(OTf)
3
(10)
(10) EtOH
H
2
O
3
62
min
1.5 h
15
5
6
In(OTf)
In(OTf)
3
(5)
EtOH
80
80
48 + 6b
73
3
(15) EtOH
min
5 min
48 h
25
7
8
9
In(OTf)
In(OTf)
In(OTf)
3
3
3
(20) EtOH
(10) EtOH
(15) MeOH
80
rt
80
69
20 + 6b
69
15 mol% of In(OTf) as catalyst in EtOH as solvent under refluxing
3
min
48 h
50
conditions refers to be the best reaction conditions for the
synthesis of β-carboline C-3 substituted imidazo[1,2-a]pyridine
(Table 1, entry 6) (7bAX).
1
0
In(OTf)
In(OTf)
3
(15) Toluene
(15) Toluene
rt
120
24 + 6b
65
11
3
min
6.5 h
7 h
1 h
4 h
12
13
14
15
16
p-TSA (15)
TFA (15)
Toluene
CH Cl
120
60
80
80
80
55
45
59
50
53
2
2
Having optimized conditions in hand, we investigated the scope of
reaction by reacting 3-formyl-9H-β-carbolines (6a-c), 2-
aminopyridines (A-F) and isocyanides (X-Z) as depicted in Scheme
La(OTf)
Yb(OTf)
Zn(OTf)
3
(15) EtOH
(15) EtOH
(15) EtOH
3
2
45
2. It was satisfying to note that all the substrates responded
min
3.5 h
5 h
3 h
2.5 h
positively to yield the desired β-carboline C-3 substituted
imidazo[1,2-a]pyridine derivatives in moderate to good yields (52-
17
18
19
20
AgOTf (15)
InCl (15)
LaCl (15)
EtOH
EtOH
EtOH
EtOH
80
80
80
80
47
26
42
34
3
7
6%). It was observed that reaction was relatively faster with tert-
butylisonitrile (Z) as compared to methyl or ethyl isocyanoacetate
X-Y). Similarly, it was analysed that this multicomponent
3
ZnCl
2
(15)
(
a
All the reaction were carried out with 0.25 mmol of 6b, 0.26 mmol
of 2-amino pyridine (A), 0.28 mmol of isonitrile (X) in 3 mL of
transformation was more facile with 6b (3-formyl-9H-β-carboline
derivative accommodating 4-bromophenyl substituent at C-1
position) as compared to other precursors (6a and 6c). Overall, the
reaction was found to be general and competent to afford the
desired library of compounds (7) (Figure 4).
b
c
solvent. Anhydrous solvent was used for entries 9-13. The
temperature of oil bath. Isolated yields of the purified product
d
d
(The yield for entries 2, 5, 8 and 10 are on actual basis). No catalyst
was used for entries 1-2.
However, when the reaction was executed in EtOH as the solvent,
formation of product was observed but starting materials were not
consumed completely even after 48 h (Table 1, entry 2). A short
silica gel column chromatographic purification of the reaction
mixture yielded the pure product in 29% yield and the
spectroscopic analysis confirmed the structure of product as 7bAX.
Thereafter, we next focused on improving the efficacy of the
methodology for the synthesis of β-carboline substituted
imidazo[1,2-a]pyridines. Our recent studies revealed that In(OTf)3
was a superior catalyst for GBB transformation and therefore, we
1
4
envisaged to explore In(OTf) to increase the yield of product.
3
However, reaction failed to deliver the desired product in water in
presence of In(OTf) which indicates that solubility of reactants was
3
Scheme 2. In(OTf)
imidazo[1,2-a]pyridine derivatives (7)
3
assisted synthesis of β-carboline C-3 substituted
a limiting factor (Table 1, entry 3). Interestingly, when the reactants
o
were assembled in EtOH at 80 C in presence of In(OTf) (10 mol%),
3
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Figure 5. Structure of β-carboline C-3 substituted imidazo[1,2-
a]pyrazine and imidazo[1,2-a]pyrimidine derivatives (8-9)
Scheme 4. Synthesis of β-carboline C-3 substituted imidazo[1,2-
a]pyridine (11bAX) from 3-formyl, 9-methylpyrido[3,4-b]indole
(10b)
Figure 4. Library of various β-carboline C-3 tethered imidazo[1,2-
a]pyridine derivatives (7)
To examine the effect of substituent at N-9 on the course of
reaction, the study was further extended with N-methyl derivative
of 6b. Interestingly 10b showed more affinity toward 2-
aminopyridine (A) and ethylisocyanoacetate (X) in presence of
In(OTf) (10 mol%) in EtOH to afford 11bAX (Scheme 4). It was
3
observed that GBB reaction with 10b was faster as compared to 6b
The applicability of this multicomponent approach was further
examined by varying the amine component with 2-aminopyrazine
(G) and 2-aminopyrimidine (H) as illustrated in Scheme 3.
Surprisingly, reaction of 2-aminopyrazine (G) and 2-
aminopyrimidine (H) was even faster and more facile as compared
to 2-aminopyridines (A-F). The reaction was completed within 2-5
min in presence of 10 mol% of In(OTf) (lower catalyst loading
3
relative to synthesis of 7) in EtOH and the desired β-carboline C-3
tethered imidazo[1,2-a]pyrazine (8) and imidazo[1,2-a]pyrimidine
and was completed in 10 min to produce the desired product in
69% yield. To further expand the scope of methodology, it was
decided to remove the tert-butyl substituent so that the resulting
primary amine group can be further functionalised. Treatment of
7bAZ with 40% aqueous HBF
4
in toluene (Scheme 5) successfully
afforded 2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-
yl)imidazo[1,2-a]pyridin-3-amine (12bAZ) in excellent yield.
(9) derivatives (Figure 5) were produced smoothly in 70-84% yield
(
2
Scheme 3). More importantly, the reaction was regioselective with
-aminopyrimidine to afford 3-aminoimidazopyrimidines (9).
2
0
Based on the observation of studies, a plausible mechanism for the
formation of β-carboline C-3 tethered imidazo[1,2-a]azine
N
R3 NH
N
NH2
N
G
N
HN
N
R1
N
70-79%
N
H
N
R1
8
In(OTf)3 (10 mol%),
EtOH, 80 oC,
6a-c
CHO
2-5 min
R3 NH
CN R3
N
X-Z
7
8-84%
HN
N
N
N
N
R1
9
N
NH2
H
Scheme 3. Synthesis of β-carboline C-3 substituted imidazo[1,2-
a]pyrazine and imidazo[1,2-a]pyrimidine derivatives (8-9)
Scheme 5. HBF
a]pyridine via dealkylation of 7bAZ
4
assisted synthesis of 3-aminoimidazo[1,2-
4
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E. Merck (silica gel 60 PF254, 0.25 mm). Column chromatography
was performed using Spectrochem make silica gel (60–120 mesh).
Melting points were determined in open head capillary tubes on a
Precision Digital melting point apparatus (LABCO make) containing
silicon oil and are uncorrected. IR spectra were recorded using
1
13
Agilent FTIR spectrophotometer. H NMR and C NMR spectra
were recorded either on Avance III Bruker spectrometer at
1
13
operating frequencies of 400MHz ( H) or 100 MHz ( C) as indicated
in the individual spectrum, using TMS as an internal standard. The
MS spectra were recorded on Xevo G2-SQ TOF (Water, USA) or
Thermo Finnigan LCQ Advantage, Ion Trap Mass Spectrometer.
Elemental analyses were performed on a Carlo–Erba’s 108 or an
Elementar’s Vario EL III microanalyzer. The room temperature
Figure 6. Proposed mechanism for the formation of β-carboline C-3
tethered imidazo[1,2-a]azine conjugates (7-9 and 11).
1
varied between 25 °C and 35 °C. The multiplicity in H-NMR spectra
is presented as s for singlet; d for doublet; dd for doublet of
doublet; t for triplet and m for multiplet.
derivatives (7-9 and 11) is depicted in Figure 6. It is anticipated that
reaction proceeds with the initial formation of Schiff base (13) via
the condensation of 3-fomyl β-carbolines (6a-c) and 2-aminoazine
Experimental Section
General procedure for the synthesis of compounds 7 and 11 as
exemplified for ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-
b]indol-3-yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (7bAX). To a
stirred solution of 2-aminopyridine A (0.10 g, 1.06 mmol) and (1-(4-
bromophenyl)-9H-pyrido[3,4-b]indole-3-carbaldehyde, 6b (0.35 g,
(A-H) followed by a nonconcerted [4+1] cycloaddition between the
Schiff base (13) and isonitrile (X-Z) to generate the intermediate 14.
Further, 1,3-prototropic shift may yield the β-carboline C-3 linked
imidazo[1,2-a]azines (7-9 and 11).
3
1.01 mmol) in EtOH (3 mL), In(OTf) (0.09 g, 0.16 mmol) was added.
Thereafter, ethyl isocyanoacetate, X (127 µL, 1.17 mmol) was
Conclusions
added to the reaction mixture and the content was refluxed at 80
o
In summary, we have successfully demonstrated the
applicability of 3-formyl 1-aryl-9H-pyrido[3,4-b]indole for the
synthesis of β-carboline C-3 tethered imidazo-azine derivatives
C for 15 minutes. After the completion of reaction, as monitored
by TLC, the reaction content was cooled to room temperature and
5
mL of ice cold water was added to the reaction content which
via exploration of In(OTf)
3
assisted Groebke-Blackburn-
resulted in the formation of a yellow solid. The solid product was
filtered under vacuum, air dried, triturated and washed with
hexane: ethylacetate (70:30, v/v) (4 x 5 mL) to obtain the
analytically pure product 7bAX (0.37 g from 0.10 g, 64%) as a
yellow solid.
Bienayme multicomponent approach. The reaction was found
to be more facile with 1-(4-bromophenyl)-9H-pyrido[3,4-
b]indole-3-carbaldehyde, 2-aminopyrazine/2-aminopyrimidine
and tert-butylisocyanide in comparison to other substrates.
Scope of the reaction was further extended by carrying out
Ethyl
2-((2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo[1,2-a]
4
the HBF mediated dealkylation of one of the derivatives
pyridin-3-yl)amino)acetate (7aAX). Yield: 66% (0.32 g from 0.10 g)
afforded from tert-butylisocyanide. The anticancer evaluation
studies are underway and will be reported in due course of
time. Further, it is envisaged that 3-formyl 9H-pyrido[3,4-
o
f
as a light yellow solid; m.p. 82-83 C; R = 0.79 (hexane/EtOAc,
-
1
1
3
0/70, v/v); IR (neat): νmax(cm ) = 1732 (CO
400 MHz, CDCl ) δ = 3.60 (t, J = 7.1 Hz, 3 H, CO
), 4.08 (t, J = 7.1 Hz, 3 H, CO CH CH ), 6.82 (t, J = 6.7 Hz, 1
), 7.14-7.18 (m, 1 H, ArH), 7.31 (t, J = 7.4 Hz, 1 H, ArH),
.51 (t, J = 8.4 Hz, 2 H, ArH), 7.56 (d, J = 8.0 Hz, 1 H, ArH), 7.59-7.64
m, 3 H, ArH), 8.03 (d, J = 7.6 Hz, 2 H, ArH), 8.14 (d, J = 6.6 Hz, 1 H,
ArH), 8.22 (d, J = 7.9 Hz, 1 H, ArH), 8.56 (s, 1 H, NHβ-carboline), 8.87 (s,
2
Et), 3249(NH); H NMR
(
3
2
CH CH ), 3.91 (s, 2
2
3
b]indole is
a potent precursor and offer unlimited
H, NHCH
2
2
2
3
opportunities for installation of bioactive heterocyclic
frameworks to generate molecular hybrids which may display
unique properties and deliver drugs, ligands and other
materials.
H, NHCH
2
7
(
1
3
1
1
1
1
3
H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 14.1, 49.1, 61.1,
11.1, 111.6, 112.0, 117.5, 120.5, 122.4, 122.5, 122.7, 123.8, 128.2,
Experimental
28.6, 128.7, 128.8, 129.2, 131.2, 132.4, 132.8, 138.9, 140.9, 141.1,
General Section
+
45.0, 171.0 ppm; MS (ES):m/z (%) = 462.2 [M+1] ; C28
H
23
N
5
O
2
The chemicals and reagents were purchased from Sigma Aldrich,
Acros, Avera Synthesis, Spectrochem Pvt. Ltd. and used without
(461.1852): calcd. for C, 72.87; H, 5.02; N, 15.17; found C, 73.05; H,
5.08; N, 15.26.
further purification. Anhydrous solvents (CH
2
Cl
2
) utilised in the
Ethyl 2-((6-chloro-2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo
reactions were dried and freshly distilled before use. However,
commercial anhydrous DMF, MeOH and Toluene (Spectrochem
make) were used as such without further distillation. Absolute
EtOH was used during this study. Thin layer chromatography (TLC)
was performed using pre-coated aluminium plates purchased from
[1,2-a]pyridin-3-yl)amino)acetate (7aEX). Yield: 65% (0.18 g from
o
0.07 g) as a light yellow solid; m.p. 160-161 C; R
f
= 0.64
Et),
) δ = 1.13 (t, J = 7.1 Hz, 3 H,
-1
(hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1724 (CO
2
1
3314(NH); H NMR (400 MHz, CDCl
3
CO CH CH ), 3.92 (s, 2 H, NHCH
2
2
3
2
), 4.10 (q, J = 7.1 Hz, 2 H,
J. Name., 2013, 00, 1-3 | 5
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New Journal of Chemistry
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DOI: 10.1039/C6NJ03210A
ARTICLE
CH CH
Journal Name
-
1
1
CO
t, J = 7.1 Hz, 1 H, ArH), 7.50-7.59 (m, 4 H, ArH), 7.63 (t, J = 7.5 Hz, 2
H, ArH), 8.03 (d, J = 7.5 Hz, 2 H, ArH), 8.20 (s, 1 H, ArH), 8.23 (s, 1 H,
2
2
3
), 6.33 (s, 1 H, NHCH
2
), 7.12 (d, J = 9.5 Hz 1 H, ArH), 7.33
50/50, v/v); IR (neat): νmax(cm ) =1739 (CO
(400 MHz, CDCl
H, NHCH ), 4.07 (q, J = 7.2 Hz, 2 H, CO
NHCH ), 7.05 (t, J = 6.6 Hz, 1 H, ArH), 7.13 (t, J = 7.2 Hz, 1 H, ArH),
2
Et), 3304 (NH); H NMR
(
3
) δ = 1.12 (t, J = 7.2 Hz, 3 H, CO
2
CH
2 3
CH ), 3.86 (s, 2
2
2
CH CH
2
3
), 5.94 (s, 1 H,
13
ArH), 8.51 (s, 1 H, NHβ-carboline), 8.86 (s, 1 H, ArH) ppm; C NMR (100
MHz, CDCl ) δ = 49.1, 61.4, 111.3, 111.8, 118.0, 118.8, 120.6, 120.7,
20.8, 122.5, 122.6, 125.3, 128.3, 128.9, 129.1, 129.4, 131.3, 132.7,
34.3, 138.7, 139.5, 141.0, 141.8, 144.5, 171.0 ppm; MS (ES):m/z
2
3
7.42 (t, J = 7.4 Hz, 2 H, ArH), 7.51 (d, J = 8.1 Hz, 1 H, ArH), 7.58 (d, J
= 8.1 Hz, 2 H, ArH), 7.82 (d, J = 8.2 Hz, 3 H, ArH), 8.05 (d, J = 7.7 Hz,
1
1
1 H, ArH), 8.30 (d, J = 6.4 Hz, 1 H, ArH), 8.63 (s, 1 H, ArH), 8.92 (s, 1
+
+
13
(%) = 496.1 [M+1] , 498.1 [M+3] ; C28
H
22ClN
5
O
2
(495.1462): calcd.
3
H, NHβ-carboline) ppm; C NMR (100 MHz, CDCl ) δ = 14.2, 48.8, 61.3,
for C, 67.81; H, 4.47; N, 14.12; found C, 67.96; H, 4.49; N, 14.19.
111.5, 111.8, 113.2, 116.4, 120.6, 122.0, 122.1, 123.1, 123.2, 126.0,
128.1, 128.8, 129.7, 130.9, 131.2, 132.2, 137.0, 139.9, 140.3, 141.0,
Ethyl 2-((6-methyl-2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo
+
+
[
1,2-a]pyridin-3-yl)amino)acetate (7aFX). Yield: 74% (0.16 g from
142.2, 171.0 ppm; MS (ES):m/z(%) = 540.1 [M+1] , 542.1 [M+3] ;
(539.0957): calcd. for C, 62.23; H, 4.10; N, 12.96;
o
0
.05 g) as a dark brown solid; m.p. 110-111 C; R
f
= 0.63
hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1732 (CO Et),
) δ= 1.10 (t, J = 7.1 Hz, 3 H,
), 3.91 (s, 2 H, NHCH ) 4,08 (q, J =
), 6.23 (s, 1 H, NHCH ), 6.58 (d, J = 8.4 Hz, 1
H, ArH), 7.13 (d, J = 9.2 Hz, 1 H, ArH), 7.38 (d, J = 8.9 Hz, 1 H, ArH),
.47-7.65 (m, 5 H, ArH), 8.00 (t, J = 7.4 Hz, 3 H, ArH), 8.21 (d, J = 8.0
28 5 2
C H22BrN O
-1
(
2
found C, 62.41; H, 4.13; N, 12.99.
1
3
320(NH); H NMR (400 MHz, CDCl
CO CH CH ), 2.40 (s, 3 H, ArCH
.1 Hz, 2 H, CO CH CH
3
Ethyl 2-((8-bromo-2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-
2
2
3
3
2
yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (7bBX). Yield: 73%
o
7
2
2
3
2
(0.19 g from 0.08 g) as a light yellow solid; m.p. 138-139 C; R
f
=
-1
0.50 (hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1744
1
7
(CO
2
Et), 3261 (NH); H NMR (400 MHz, CDCl
3
) δ = 1.06 (t, J = 7.1 Hz,
13
Hz, 1 H, ArH), 8.65 (s, 1 H, ArH), 8.81 (s, 1 H, ArH) ppm; C NMR
100 MHz, DMSO-d ) δ = 16.7, 21.1, 29.0, 60.4, 110.6, 112.5, 113.0,
15.3, 119.7, 120.7, 121.4, 121.9, 122.3, 128.6, 128.7, 128.9, 135.1,
37.3, 139.8, 140.7, 141.6, 142.2, 155.0, 172.0 ppm; MS (ES):m/z
3 H, CO
2
CH CH ), 3.92-3.98 (m, 4 H, NHCH and CO
2
3
2
2
CH CH ), 6.79 (t,
2
3
(
6
J = 6.8 Hz, 1 H, ArH), 7.29 (t, J = 7.7 Hz, 3 H, ArH), 7.39 (s, 1 H, ArH),
7.51 (t, J = 7.1 Hz, 2 H, ArH), 7.67 (d, J = 8.2 Hz, 2 H, ArH), 7.79 (d, J
1
1
= 7.0 Hz, 2 H, ArH), 8.14 (d, J = 6.6 Hz, 2 H, ArH), 8.71 (s, 1 H, NHβ-
+
+
13
(
%) = 476.2 [M+1] , 478.2 [M+3] ; C29
C, 73.25; H, 5.30; N, 14.73; found C, 73.41; H, 5.31; N, 14.77.
Methyl 2-((2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo[1,2-
a]pyridin-3-yl)amino)acetate (7aAY). Yield: 66% (0.16 g from 0.05
H
25
N
5
O
2
(475.2008): calcd. for
3
carboline) ppm; C NMR (100 MHz, CDCl ) δ = 14.0, 48.3, 61.5, 111.9,
112.1, 112.2, 112.7, 121.2, 121.3, 122.3, 122.5, 127.2, 128.8, 129.7,
129.9, 131.5, 132.6, 139.3, 142.2, 171.5 ppm; MS (ES):m/z(%) =
+
+
618.0 [M+1] , 620.0 [M+3] ; C28
54.30; H, 3.42; N, 11.31; found C, 54.42; H, 3.44; N, 11.36.
Ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)-7-
methylimidazo[1,2-a]pyridin-3-yl)amino)acetate (7bCX). Yield:
2 5 2
H21Br N O (617.0062): calcd. for C,
o
g) as a dark yellow solid; m.p. 149-150 C; R
f
= 0.56 (hexane/EtOAc,
-1
1
5
0/50, v/v); IR (neat): νmax(cm ) = 1740 (CO
400 MHz, CDCl ) δ = 3.60 (s, 3 H, COOCH
.37 (s, 1 H, NHCH ), 6.85 (t, J = 6.7 Hz, 1 H, ArH), 7.18 (t, J = 7.8 Hz,
2
Et), 3294(NH); H NMR
(
3
3 2
), 3.92 (s, 2 H, NHCH ),
o
6
1
7
2
f
74% (0.38 g from 0.10 g) as a yellow solid; m.p. 178-179 C; R =
-1
H, ArH), 7.28 (t, J = 7.2 Hz, 2 H, ArH), 7.48-7.56 (m, 2 H, ArH),
.58-7.65 (m, 3 H, ArH), 8.01 (d, J = 7.2 Hz, 2 H, ArH), 8.15 (d, J = 6.8
0.67 (hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1739
1
(CO
3 H, CO
= 7.1 Hz, 2 H, CO
2
Et), 3256 (NH); H NMR (400 MHz, CDCl
CH CH ), 2.42 (s, 3 H, ArCH ), 3.87 (s, 2 H, NHCH
CH CH ), 6.67 (d, J = 6.9 Hz, 1 H, NHCH
2
3
) δ = 1.13 (t, J = 7.2 Hz,
), 4.10 (q, J
), 7.29 (t, J
Hz, 1 H, ArH), 8.20 (d, J = 7.8 Hz, 1 H, ArH), 8.63 (s, 1 H, NHβ-carboline),
2
2
3
3
2
1
3
8
4
1
.86 (s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl
3
) δ = 27.4, 29.8,
2
2
3
9.0, 52.1, 111.2, 111.7, 112.3, 112.4, 117.2, 120.6, 122.4, 122.8,
28.2, 128.4, 128.8, 128.9, 129.3, 129.5, 138.6, 141.0, 171.3, 175.6
= 7.4 Hz, 1 H, ArH), 7.36 (s, 1 H, ArH), 7.50-7.55 (m, 3 H, ArH), 7.71
(d, J = 7.6 Hz, 2 H, ArH), 7.91 (d, J = 8.0 Hz, 2 H, ArH), 8.02 (d, J = 6.9
Hz, 1 H, ArH), 8.15 (d, J = 7.1 Hz, 1 H, ArH), 8.55 (s, 1 H, NHβ-carboline),
+
+
ppm; MS (ES):m/z (%) = 448.1 [M+1] , 450.1 [M+3] ; C27
447.1695): calcd. for C, 72.47; H, 4.73; N, 15.65; found C, 72.64; H,
.79; N, 15.77.
21 5 2
H N O
1
3
(
3
8.81 (s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 14.2, 21.6,
4
49.2, 61.2, 111.2, 111.7, 114.9, 115.7, 120.6, 121.7, 122.0, 122.3,
122.4, 123.0, 128.2, 128.7, 19.8, 131.4, 132.2, 132.3, 136.0, 137.7,
N-(tert-butyl)-2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo[1,2-
+
a]pyridin-3-amine (7aAZ) Yield: 76% (0.35 g from 0.10 g) as a
137.8, 140.3, 141.0, 171.0 ppm; MS (ES):m/z(%) = 554.1 [M+1] ,
o
+
yellow solid; m.p. 134-135 C; R
f
= 0.64 (hexane/EtOAc, 30/70, v/v);
556.1 [M+3] ; C29
H24BrN
5
O
2
(553.1113): calcd. for C, 62.82; H, 4.36;
-
1
1
IR (neat): νmax(cm ) = 3294 (NH); H NMR (400 MHz, CDCl
s, 9 H, C(CH ), 6.84 (t, J = 6.7 Hz, 1 H, NH), 7.21 (t, J = 7.8 Hz, 1 H,
ArH), 7.29 (d, J = 7.8 Hz, 1 H, ArH), 7.46 (d, J = 7.4 Hz, 1 H, ArH), 7.52
t, J = 5.7 Hz, 2 H, ArH), 7.58 (t, J = 7.5 Hz, 2 H, ArH), 7.67 (d, J = 9.1
3
) δ = 1.07
N, 12.63; found C, 63.03; H, 4.40; N, 12.70.
(
3
)
3
Ethyl 2-((6-bromo-2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-
yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (7bDX). Yield: 52%
o
(
(0.14 g from 0.08 g) as a light yellow solid; m.p. 128-129 C; R
f
=
-1
Hz, 1 H, ArH), 8.02 (t, J = 8.9 Hz, 3 H, ArH), 8.18 (d, J = 7.8 Hz, 1 H,
ArH), 8.35 (d, J = 6.8 Hz, 1 H, ArH), 8.64 (s, 1 H, NHβ-carboline), 8.86 (s,
0.72 (hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1739
1
(CO
3 H, CO
CO CH CH
2
Et), 3326 (NH); H NMR (400 MHz, CDCl
CH CH ), 3.88 (s, 2 H, NHCH ), 4.09 (q, J = 7.1 Hz, 2 H,
), 6.05 (s, 1 H, NHCH ), 7.23 (t, J = 7.3 Hz, 2 H, ArH), 7.32
3
) δ = 1.14 (t, J = 7.1 Hz,
1
3
1
1
1
1
H, ArH) ppm; C NMR (100 MHz, CDCl
3
) δ = 30.1, 57.3, 111.1,
2
2
3
2
11.6, 111.7, 117.3, 120.5, 122.3, 122.6, 123.7, 124.2, 127.9, 128.1,
2
2
3
2
28.6, 128.9, 129.2, 131.2, 132.4, 136.1, 138.9, 140.9, 141.1, 141.8,
(d, J = 9.4 Hz, 1 H, ArH), 7.48-7.53 (m, 2 H, ArH), 7.59 (d, J = 9.4 Hz,
1 H, ArH), 7.66 (d, J = 8.2 Hz, 2 H, ArH), 7.84 (d, J = 8.2 Hz, 2 H, ArH),
8.12 (d, J = 7.8 Hz, 1 H, ArH), 8.33 (s, 1 H, ArH), 8.72 (s, 1 H, NHβ-
+
45.6 ppm; MS (ES):m/z (%) = 432.2 [M+1] ; C28
H
25
N
5
(431.2110):
calcd. for C, 77.93; H, 5.84; N, 16.23; found C, 78.12; H, 5.89; N,
6.31.
Ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)imidazo
1,2-a]pyridin-3-yl)amino)acetate (7bAX). Yield: 64% (0.37 g from
1
3
1
3
carboline) ppm; C NMR (100 MHz, CDCl ) δ = 14.2, 48.9, 61.4, 107.2,
111.5, 111.8, 118.0, 120.8, 122.3, 122.9, 123.2, 127.5, 128.7, 129.0,
129.8, 131.4, 132.4, 133.5, 137.4, 139.3, 140.5, 141.0, 144.2, 170.8
[
o
+
+
0
.10 g) as a yellow solid; m.p. 106-107 C, R
f
= 0.53 (hexane/EtOAc,
2 5 2
ppm; MS (ES):m/z(%) = 618.0 [M+1] , 620.0 [M+3] ; C28H21Br N O
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 12
Journal Name
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View Article Online
DOI: 10.1039/C6NJ03210A
ARTICLE
(
617.0062): calcd. for C, 54.30; H, 3.42; N, 11.31; found C, 54.48; H,
.45; N, 11.39.
Ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)-6-
chloroimidazo[1,2-a]pyridin-3-yl)amino)acetate (7bEX). Yield: 68
H, ArH), 7.51-7.53 (m, 2 H, ArH), 7.56 (d, J = 9.5 Hz, 1 H, ArH), 7.60
(d, J = 7.7 Hz, 1 H, ArH), 7.72 (d, J = 8.2 Hz, 1 H, ArH), 7.92 (d, J = 8.3
Hz, 1 H, ArH), 8.04 (d, J = 7.5 Hz, 1 H, ArH), 8.20-8.23 (m, 1 H, ArH),
3
8.31 (d, J = 6.9 Hz, 1 H, ArH), 8.51 (d, J = 11.0 Hz, 1 H, ArH), 8.86 (s,
o
13
%
(0.23 g from 0.08 g) as a yellow solid; m.p. 159-160 C; R
f
= 0.70
hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1742 (CO Et),
) δ = 1.14 (t, J = 7.1 Hz, 3 H,
), 4.08 (q, J = 7.1 Hz, 2 H,
), 7.2 (t, J = 7.3 Hz, 1 H, ArH), 7.27
3
1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 30.9, 57.3, 111.1,
-1
(
2
111.2, 111.6, 111.7, 112.0, 117.3, 120.5, 122.4, 123.7, 124.2, 128.1,
128.6, 128.8, 128.9, 129.2, 129.6, 132.3, 132.4, 135.9, 136.1, 137.8,
1
3
308 (NH); H NMR (400 MHz, CDCl
3
+
CO
CO
2
2
CH
2
2
CH
3
), 3.88 (s, 2 H, NHCH
), 6.00 (s, 1 H, NHCH
2
138.9, 140.9, 141.1, 141.8 ppm; MS (ES):m/z (%) = 510.1 [M+1] ,
+
CH
CH
3
2
512.1 [M+3] ; C28
H
24BrN
5
(509.1215): calcd. for C, 65.89; H, 4.74; N,
(d, J = 11.0 Hz, 1 H, ArH), 7.46-7.52 (m, 2 H, ArH), 7.64-7.69 (m, 3 H,
13.72; found C, 66.12; H, 4.78; N, 13.79.
ArH), 7.84 (d, J = 8.0 Hz, 2 H, ArH), 8.10 (d, J = 7.6 Hz, 1 H, ArH), 8.27
Ethyl 2-((2-(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-yl)imidazo
1
3
(s, 1 H, ArH), 8.69 (s, 1 H, ArH), 8.83 (s, 1 H, NHβ-carboline) ppm;
C
[1,2-a]pyridin-3-yl)amino)acetate (7cAX). Yield: 53% (0.07 g from
o
NMR (100 MHz, CDCl
3
) δ = 14.2, 48.8, 61.4, 111.5, 111.8, 117.5,
0.03 g) as a light yellow solid; m.p. 126-127 C; R
f
= 0.53
Et),
) δ = 1.01 (t, J = 6.9 Hz, 3 H,
), 3.97 (q, J = 6.8 Hz, 2 H,
), 6.96 (t, J = 6.8 Hz, 1 H, ArH), 7.18
-1
1
1
5
20.8, 120.8, 121.0, 122.2, 122.3, 123.3, 126.0, 129.0, 129.8, 131.4,
(hexane/EtOAc, 50/50, v/v; IR (neat): νmax(cm ) = 1732 (CO
2
1
32.4, 137.2, 139.0, 140.4, 141.0, 141.0 ppm; MS (ES):m/z(%) =
3314 (NH); H NMR (400 MHz, CDCl
3
+
+
74.0 [M+1] , 576.0 [M+3] ; C28
H
21BrClN
5
O
2
(573.0567): calcd. for
CO
CO
2
2
CH
2
2
CH
3
), 3.79 (s, 2 H, NHCH
), 6.19 (s, 1 H, NHCH
2
C, 58.50; H, 3.68; N, 12.18; found C, 58.69; H, 3.71; N, 12.26.
Ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)-6-
methylimidazo[1,2-a]pyridin-3-yl)amino)acetate (7bFX). Yield:
CH
CH
3
2
(t, J = 6.5 Hz, 1 H, ArH), 7.28 (d, J = 7.3 Hz, 2 H, ArH), 7.41 (t, J = 7.4
Hz, 1 H, ArH), 7.56 (t, J = 11.6 Hz, 2 H, ArH), 7.71 (d, J = 6.1 Hz, 2 H,
o
5
2% (0.13 g from 0.05 g) as a light yellow solid; m.p. 218-219 C; R
f
ArH), 7.98 (d, J = 7.1 Hz, 3 H, ArH), 8.35 (s, 1 H, NHβ-carboline), 8.57 (s,
-1
13
=
0.70 (hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1740
3
1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 14.1, 49.0, 61.2,
1
(CO
2
Et), 3274 (NH); H NMR (400 MHz, CDCl
H, CO CH CH ), 2.37 (s, 3 H, ArCH ), 3.90 (d, J = 6.4 Hz, 2 H,
), 4.12 (q, J = 7.2 Hz, 2 H, CO CH CH ), 6.30 (t, J = 7.5 Hz, 1 H,
), 7.01 (dd, J = 1.6 Hz, J = 9.5 Hz, 1 H, ArH), 7.33 (d, J = 7.4
3
) δ = 1.14 (t, J = 7.1 Hz,
109.6, 111.2, 111.7, 112.1, 113.6, 117.4, 120.5, 122.2, 122.3, 122.7,
123.9, 128.6, 128.7, 128.9, 129.3, 129.5, 131.3, 134.7, 137.2, 138.7,
3
2
2
3
3
+
NHCH
NHCH
2
2
2
3
141.1, 144.9, 146.0, 171.0 ppm; MS (ES):m/z(%) = 496.1 [M+1] ,
+
2
1
2
498.1 [M+3] ; C28
H22ClN
5
O
2
(495.1462): calcd. for C, 67.81; H, 4.47;
Hz, 1 H, ArH), 7.49-7.58 (m, 3 H, ArH), 7.74 (d, J = 8.4 Hz, 2 H, ArH),
.89 (s, 1 H, ArH), 7.93 (d, J = 8.4 Hz, 2 H, ArH), 8.22 (d, J = 7.9 Hz, 1
N, 14.12; found C, 68.00; H, 4.50; N, 14.19.
7
Ethyl 2-((8-bromo-2-(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-
13
H, ArH), 8.40 (s, 1 H, NHβ-carboline), 8.87 (s, 1 H, ArH) ppm; C NMR
100 MHz, CDCl ) δ = 14.2, 18.6, 49.0, 61.2, 111.2, 111.6, 117.0,
20.2, 120.7, 121.7, 122.4, 122.5, 123.1, 127.1, 128.4, 128.8, 129.8,
30.0, 131.5, 132.2, 132.5, 132.6, 137.8, 140.4, 141.0, 145.5, 171.0
yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (7cBX). Yield: 61%
o
(
3
(0.10 g from 0.05 g) as a yellow solid; m.p. 123-124 C; R
f
= 0.74
Et),
) δ = 1.11 (t, J = 7.1 Hz, 3 H,
), 4.09 (q, J = 7.2 Hz, 2 H,
), 6.71 (t, J = 7.0 Hz, 1 H, NHCH ), 7.31 (t, J = 6.9 Hz, 1 H,
-1
1
1
(hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1739 (CO
2
1
3297 (NH); H NMR (400 MHz, CDCl
3
+
+
ppm; MS (ES):m/z(%) = 554.1 [M+1] , 556.1 [M+3] ; C29
553.1113): calcd. for C, 62.82; H, 4.36; N, 12.63; found C, 62.98; H,
.38; N, 12.69.
Methyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)
imidazo[1,2-a]pyridin-3-yl)amino)acetate (7bAY). Yield: 71% (0.20
H
5
24BrN O
2
CO
CO
2
2
CH
2
2
CH
3
), 3.87 (s, 2 H, NHCH
2
(
CH
CH
3
2
4
ArH), 7.42 (d, J = 7.1 Hz, 1 H, ArH), 7.52-7.58 (m, 5 H, ArH), 7.95 (d, J
= 8.4 Hz, 2 H, ArH), 8.13 (t, J = 8.1 Hz, 2 H, ArH), 8.62 (s, 1 H, NHβ-
1
3
3
carboline), 8.90 (s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 14.1,
o
g from 0.05 g) as a yellow solid; m.p. 132-133 C; R
f
= 0.85
hexane/EtOAc, 30/70, v/v); IR (neat): νmax(cm ) = 1749 (CO Et),
) δ = 3.64 (s, 3 H, COOCH ),
), 6.32 (s, 1 H, NHCH ), 6.83 (t, J = 6.7 Hz, 1 H,
49.0, 61.3, 111.7, 112.0, 112.0, 120.6, 122.1, 122.4, 122.6, 126.1,
128.8, 129.3, 129.4, 130.0, 131.3, 132.5, 133.7, 134.7, 137.2, 138.7,
-1
(
2
1
+
3
264 (NH); H NMR (400 MHz, CDCl
.91 (s, 2 H, NHCH
3
3
140.3, 141.0, 144.4, 170.8 ppm; MS (ES):m/z(%) = 574.1 [M+1] ,
+
3
2
2
576.1 [M+3] ; C28
H
21BrClN
5
O
2
(573.0567): calcd. for C, 58.50; H,
ArH), 7.17 (t, J = 7.8 Hz, 1 H, ArH), 7.32 (t, J = 7.4 Hz, 1 H, ArH), 7.51
d, J = 8.1 Hz, 1 H, ArH), 7.56 (t, J = 7.5 Hz, 1 H, ArH), 7.62 (d, J = 9.1
3.68; N, 12.18; found C, 58.62; H, 3.71; N, 12.26.
(
Ethyl 2-((6-bromo-2-(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-
Hz, 1 H, ArH), 7.73 (d, J = 8.2 Hz, 2 H, ArH), 7.92 (d, J = 8.2 Hz, 2 H,
ArH), 8.13 (d, J = 6.9 Hz, 1 H, ArH), 8.21 (d, J = 7.8 Hz, 1 H, ArH), 8.50
yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (7cDX). Yield: 57%
o
(0.09 g from 0.05 g) as a yellow solid; m.p. 156-157 C; R
f
= 0.72
Et),
) δ = 1.15 (t, J = 7.0 Hz, 3 H,
), 4.12 (q, J = 7.1 Hz, 2 H, OCH CH ),
1
3
-1
(s, 1 H, NHβ-carboline), 8.88 (s, 1 H, ArH) ppm; C NMR (100 MHz,
(hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1745 (CO
2
1
CDCl ) δ = 49.0, 52.1, 111.4, 111.7, 112.1, 117.6, 120.8, 122.4,
3
3073 (NH); H NMR (400 MHz, CDCl
3
1
22.5, 122.7, 123.1, 124.0, 128.6, 128.9, 129.8, 131.6, 132.3, 132.4,
32.8, 137.8, 140.5, 141.0, 141.2, 141.7, 145.2, 171.3 ppm; MS
OCH CH ), 3.98 (s, 2 H, NHCH
2
3
2
2
3
1
6.23 (s, 1 H, ArH), 7.22 (d, J = 9.4 Hz, 1 H, ArH), 7.32 (t, J = 7.3 Hz, 1
H, ArH), 7.52 (t, J = 10.1 Hz, 3 H, ArH), 7.58 (d, J = 8.2 Hz, 2 H, ArH),
7.97 (d, J = 8.0 Hz, 2 H, ArH), 8.21 (d, J = 7.6 Hz, 1 H, ArH), 8.27 (s, 1
+
+
(ES):m/z(%) = 526.1 [M+1] , 528.1 [M+3] ; C27
5 2
H20BrN O (525.0800):
calcd. for C, 61.61; H, 3.83; N, 13.30; found C, 61.82; H, 3.89; N,
13
13.41.
H, ArH), 8.48 (s, 1 H, NHβ-carboline), 8.85 (s, 1 H, ArH) ppm; C NMR
(100 MHz, CDCl ) δ = 14.2, 48.9, 61.3, 107.0, 111.3, 111.7, 118.0,
2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)-N-(tert-butyl)
3
imidazo[1,2-a]pyridin-3-amine (7bAZ). Yield: 73% (0.19 g from 0.05
120.6, 122.3, 122.8, 127.2, 128.7, 128.8, 129.3, 129.5, 131.3, 132.4,
133.8, 134.8, 137.0, 139.4, 140.4, 141.0, 144.4, 170.8 ppm; MS
o
f
g) as a yellow solid; m.p. 214-215 C; R = 0.80 (hexane/EtOAc,
-
1
1
+
+
3
0/70, v/v); IR (neat): νmax(cm ) = 1731 (CO
2
Et), 3328 (NH); H NMR
), 5.85 (s, 1 H, NH), 6.73-
28 5 2
(ES):m/z(%) = 574.0 [M+1] , 576.0 [M+3] ; C H21BrClN O
(
400 MHz, CDCl ) δ = 1.08 (s, 9 H, C((CH
3
3
)
3
(573.0567): calcd. for C, 58.50; H, 3.68; N, 12.18; found C, 58.67; H,
3.72; N, 12.23.
6.78 (m, 1 H, ArH), 7.12 (t, J = 7.7 Hz, 1 H, ArH), 7.31 (t, J = 7.3 Hz, 1
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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New Journal of Chemistry
Page 8 of 12
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DOI: 10.1039/C6NJ03210A
ARTICLE
Journal Name
Ethyl 2-((6-chloro-2-(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-
calcd. for C, 70.12; H, 4.79; N, 18.17; found C, 70.31; H, 4.82; N,
18.23.
yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (7cEX). Yield: 54%
o
(
0.11 g from 0.05 g) as a dark brown solid; m.p. 102-103 C; R
f
=
N-(tert-butyl)-2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo[1,2-
-1
0
.72 (hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1743
a]pyrazin-3-amine (8aGZ). Yield: 79% (0.18 from 0.05 g) as an
1
o
(CO
2
Et), 3308 (NH); H NMR (400 MHz, CDCl
H, CO CH CH ), 3.88 (s, 2 H, NHCH ), 4.13 (q, J = 7.1 Hz, 2 H,
CH CH ), 6.21 (s, 1 H, NHCH ), 7.10 (dd, J = 1.8 Hz, J = 9.6 Hz, 1
H, ArH), 7.30 (t, J = 7.3 Hz, 1 H, ArH), 7.49-7.58 (m, 5 H, ArH), 7.93
d, J = 8.4 Hz, 2 H, ArH), 8.15 (d, J = 7.7 Hz, 2 H, ArH), 8.62 (s, 1 H,
3
) δ = 1.15 (t, J = 7.2 Hz,
orange solid; m.p. 163-164 C; R
f
= 0.70 (hexane/EtOAc, 30/70, v/v);
-1
1
3
2
2
3
2
IR (neat): νmax(cm ) = 1732 (CO
CDCl ) δ = 1.11 (s, 9 H, C(CH
2
Et), 3204 (NH); H NMR (400 MHz,
CO
2
2
3
2
1
2
3
3
)
3
), 6.01 (s, 1 H, NH), 7.34 (t, J = 7.4 Hz,
1 H, ArH), 7.51-7.59 (m, 2 H, ArH), 7.63 (t, J = 7.6 Hz, 2 H, ArH), 7.81
(d, J = 4.6 Hz, 1 H, ArH), 7.99 (s, 1 H, ArH), 8.03 (d, J = 7.5 Hz, 2 H,
ArH), 8.20 (d, J = 4.5 Hz, 1 H, ArH), 8.25 (d, J = 7.9 Hz, 1 H, ArH), 8.60
(
1
3
NHβ-carboline), 8.81 (s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl
3
) δ =
1
3
C
1
1
1
4.2, 48.8, 61.3, 111.5, 111.7, 117.6, 120.6, 120.8, 122.3, 125.5,
(s, 1 H, NHβ-carboline), 8.91 (s, 1 H, ArH), 9.03 (s, 1 H, ArH) ppm;
NMR (100 MHz, CDCl ) δ = 30.2, 57.9, 111.8, 112.1, 117.1, 120.9,
122.4, 128.0, 128.6, 129.1, 129.3, 129.4, 132.7, 137.1, 141.2, 143.3
28.9, 129.4, 129.5, 131.4, 132.4, 133.6, 134.9, 137.0, 139.2, 140.4,
3
+
50.0, 144.0, 170.8 ppm; MS (ES):m/z(%) = 530.1 [M+1] , 532.1
+
+
[M+3] ; C28
H21Cl
2
N
5
O
2
(529.1072): calcd. for C, 63.40; H, 3.99; N,
24 6
ppm; MS (ES):m/z (%) = 433.2 [M+1] ; C27H N (432.2062): calcd.
13.20; found C, 63.56; H, 4.01; N,13.26.
for C, 74.98; H, 5.59; N, 19.43; found C, 75.16; H, 5.65; N, 19.54.
N-(tert-butyl)-2-(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-yl)
Ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)imidazo
imidazo[1,2-a]pyridin-3-amine (7cAZ). Yield: 66% (0.16 g from 0.05
[1,2-a]pyrazin-3-yl)amino)acetate (8bGX). Yield: 71% (0.30 g from
o
o
g) as a light orange solid; m.p. 224-225 C; R
f
= 0.53 (hexane/EtOAc,
0.08) as a dark yellow solid; m.p. 209-210 C; R
f
= 0.82
Et),
) δ = 1.13 (t, J = 7.1 Hz, 3 H,
-1
1
-1
50/50, v/v); IR (neat): νmax(cm ) = 3303 (NH); H NMR (400 MHz,
(hexane/EtOAc, 30/70, v/v); IR (neat): νmax(cm ) = 1747 (CO
2
1
CDCl ) δ = 1.08 (s, 9 H,(C(CH ) , 5.74 (s, 1 H, NH), 6.76 (t, J = 6.7 Hz,
3
3
)
3
3346(NH); H NMR (400 MHz, CDCl
3
1
7
2
8
H, ArH), 7.14 (t, J = 7.5 Hz, 1 H, ArH), 7.32 (t, J = 7.3 Hz, 1 H, ArH),
.52 (t, J = 8.1, 1 H, ArH), 7.56-7.60 (m, 4 H, ArH), 7.99 (d, J = 8.4 Hz,
H, ArH), 8.21 (d, J = 7.8 Hz, 1 H, ArH), 8.31 (d, J = 7.0 Hz, 1 H, ArH),
CO
CO
2
2
CH
2
2
CH
3
), 3.97 (d, J = 6.4 Hz, 2 H, NHCH ), 4.11 (q, J = 7.1 Hz, 2 H,
2
), 6.89 (t, J = 6.6 Hz, 1 H, NHCH ), 7.35 (t, J = 7.3 Hz, 1 H,
2
CH
CH
3
ArH), 7.52 (d, J = 8.1 Hz, 1 H, ArH), 7.58 (t, J = 7.6 Hz, 1 H, ArH), 7.76
(d, J = 8.4 Hz, 2 H, ArH), 7.84 (d, J = 4.6 Hz, 1 H, ArH), 7.93 (d, J = 8.4
1
3
.47 (s, 1 H, NHβ-carboline), 8.86 (s, 1 H, ArH) ppm; C NMR (100 MHz,
) δ = 30.1, 57.3, 111.3, 111.7, 112.0, 117.1, 120.7, 122.3,
CDCl
3
Hz, 2 H, ArH), 7.99-8.01 (dd, J
1 2
= 1.3 Hz, J = 4.8 Hz, 1 H, ArH), 8.24
1
1
4
7
22.5, 124.0, 124.2, 127.8, 128.8, 129.3, 129.4, 131.5, 132.3, 134.8,
(d, J = 7.8 Hz, 1 H, ArH), 8.49 (s, 1 H, NHβ-carboline), 8.92 (s, 1 H, ArH),
1
3
35.8, 137.3, 139.8, 141.0, 141.8, 145.5 ppm; MS (ES):m/z (%) =
3
9.03 (s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 14.1, 48.2,
+
+
66.17 [M+1] , 468.17 [M+3] ; C28
H
24ClN
5
(465.1720): calcd. for C,
61.5, 111.8, 111.8, 115.5, 121.0 122.4, 122.4, 123.4, 129.1, 129.8,
130.4, 131.5, 132.6, 134.4, 136.1, 137.4, 140.5, 140.5, 143.5, 144.4,
2.17; H, 5.19; N, 15.03; found C, 72.36; H, 5.22; N, 15.09.
+
+
General procedure for the synthesis of compounds 8 and 9 as
exemplified for ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-
b]indol-3-yl)imidazo[1,2-a]pyrazin-3-yl)amino)acetate (8bGX). To
a stirred solution of 2-aminopyrazine G (0.08 g, 0.79 mmol) and (1-
170.5 ppm; MS (ES):m/z(%) = 541.0 [M+1] , 543.0 [M+3] ;
(540.0909): calcd. for C, 59.90; H, 3.91; N, 15.52;
found C, 60.06; H, 3.94; N, 15.59.
27 6 2
C H21BrN O
Methyl
2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)
(
4-bromophenyl)-9H-pyrido[3,4-b]indole-3-carbaldehyde 6b (0.26
g, 0.75 mmol) in EtOH (3 mL), was added In(OTf) (0.04 g, 0.08
mmol) followed by the addition of ethyl isocyanoacetate X (95 µl,
imidazo[1,2-a]pyrazin-3-yl)amino)acetate (8bGY). Yield: 75% (0.21
o
3
g from 0.05) as an orange solid; m.p. 149-150 C; R
f
= 0.70
Et),
) δ = 3.65 (s, 3 H, COOCH ),
), 6.86 (s, 1 H, NHCH ), 7.36 (t, J = 7.5 Hz, 1 H,
-1
(hexane/EtOAc, 30/70, v/v); IR (neat): νmax(cm ) = 1744 (CO
2
o
1
8
7 mmol). The reaction mixture was refluxed at 80 C for 5
3240 (NH); H NMR (400 MHz, CDCl
3
3
minutes. After the completion of reaction which was monitored by
TLC, the reaction content was cooled to room temperature
followed by addition of 5 mL of ice cold water to it which resulted
in the formation of a yellow solid. Solid compound was filtered
under vacuum and was further washed with hexane:ethylacetate
3.99 (s, 2 H, NHCH
2
2
ArH), 7.53 (d, J = 8.2 Hz, 1 H, ArH), 7.59 (t, J = 7.6 Hz, 1 H, ArH), 7.77
(d, J = 8.1 Hz, 2 H, ArH), 7.85 (d, J = 4.7 Hz, 1 H, ArH), 7.94 (d, J = 8.3
Hz, 2 H, ArH), 7.98-8.01 (m, 1 H, ArH), 8.25 (d, J = 7.8 Hz, 1 H, ArH),
8.50 (s, 1 H, NHβ-carboline), 8.93 (s, 1 H, ArH), 9.04 (s, 1 H, ArH), ppm;
1
3
(
70:30, v/v) (10 mL X 4) solution to obtain the analytically pure
product 8bGX (0.30 g from 0.08 g, 71%) as a yellow solid.
Ethyl 2-((2-(1-phenyl-9H-pyrido[3,4-b]indol-3-yl)imidazo[1,2-a]
pyrazin-3-yl)amino)acetate (8aGX). Yield: 74% (0.18 g from 0.05 g)
6
C NMR (100 MHz, DMSO-d ) δ = 47.1, 51.7, 111.4, 112.5, 116.7,
119.9, 121.1, 122.1, 122.2, 128.3, 128.7, 130.2, 130.6, 131.6, 131.8,
132.1, 132.4, 132.6, 135.1, 137.2, 139.9, 141.8, 142.6, 143.4, 171.4
+
+
6 2
ppm; MS (ES):m/z(%) = 527.1 [M+1] , 529.1 [M+3] ; C26H19BrN O
o
as an orange solid; m.p. 227-228 C; R
f
= 0.62 (hexane/EtOAc,
(526.0753): calcd. for C, 59.21; H, 3.63; N, 15.94; found C, 59.39; H,
3.67; N, 16.01.
-1
1
3
0/70, v/v); IR (neat): νmax(cm ) = 1738 (CO
400 MHz, CDCl ) δ = 1.10 (t, J = 7.1 Hz, 3 H, CO
.3 Hz, 2 H, NHCH ), 4.06-4.13 (m, 2 H, CO CH
), 7.35 (t, J = 7.5 Hz, 1 H, ArH), 7.52-7.67 (m, 5 H, ArH), 7.85
d, J = 4.1 Hz, 1 H, ArH), 7.99-8.05 (m, 3 H, ArH), 8.27 (d, J = 8.4 Hz,
2
Et), 3302 (NH); H NMR
CH CH ), 3.99 (d, J =
CH ), 6.99 (s, 1 H,
(
3
2
2
3
2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)-N-(tert-butyl)
5
2
2
2
3
imidazo[1,2-a]pyrimidin-3-amine (8bGZ). Yield: 70% (0.21 g from
o
NHCH
2
0.05 g) as a yellow solid; m.p. 192-193 C; R
f
= 0.72 (hexane/EtOAc,
-1
1
(
50/50, v/v); IR (neat): νmax(cm ) =1725 (CO
2
Et), 3301 (NH); H NMR
1
H, ArH), 8.54 (s, 1 H, NHβ-carboline), 8.94 (s, 1 H, ArH), 9.04 (s, 1 H,
(400 MHz, CDCl ) δ = 1.03 (s, 9 H, C(CH ), 7.36 (t, J = 7.6 Hz, 1 H,
3
3 3
)
13
ArH) ppm; C NMR (100 MHz, DMSO-d
6
) δ = 13.8, 47.3, 60.4, 111.0,
12.5, 116.6, 119.8, 121.1, 122.0, 128.3, 128.4, 128.6, 128.8, 129.0,
30.2, 130.4, 132.1, 132.7, 135.0, 138.0, 141.1, 141.7, 142.5, 143.3,
ArH), 7.43-7.53 (m, 5 H, ArH), 7.92 (t, J = 7.9 Hz, 3 H, ArH), 8.17 (t, J
= 4.9 Hz, 1 H, ArH), 8.22 (d, J = 4.6 Hz, 1 H, ArH), 8.64 (s, 1 H, NHβ-
1
1
1
1
3
3
carboline), 9.04 (s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 30.2,
+
70.8 ppm; MS (ES):m/z (%) = 463.1 [M+1] ; C27
H
22
N
6
O
2
(462.1804):
60.0, 111.8, 111.9, 112.0, 112.1, 112.2, 117.2, 121.2, 122.4, 128.0,
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 9 of 12
Journal Name
28.8, 128.9, 129.0, 129.7, 130.0, 134.5, 137.3, 143.4 ppm; MS
NP lee wa s eJ od uo r nn oa tl aod fj uC s ht em ma ri sg it nr ys
View Article Online
DOI: 10.1039/C6NJ03210A
ARTICLE
1
7.33 (t, J = 7.4 Hz, 1 H, ArH), 7.60-7.63 (m, 4 H, ArH), 7.69 (d, J = 8.3
Hz, 2 H, ArH), 8.12 (d, J = 6.7 Hz, 1 H, ArH), 8.27 (d, J = 7.8 Hz, 1 H,
+
+
(
ES):m/z(%) = 511.1 [M+1] , 513.1 [M+3] ; C27
calcd. for C, 63.41; H, 4.53; N, 16.43; found C, 63.58; H, 4.55; N,
6.49.
Ethyl 2-((2-(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-yl)imidazo
1,2-a]pyrazin-3-yl)amino)acetate (8cGX). Yield: 71% (0.08 g from
6
H23BrN (510.1168):
13
3
ArH), 8.88 (d, J = 4.8 Hz, 1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ
1
= 14.2, 33.5, 49.1, 61.2, 109.9, 110.9, 112.0, 117.6, 120.4, 121.9,
122.2, 122.7, 123.8, 128.7, 128.8, 131.4, 131.5, 131.8, 132.9, 134.1,
139.2, 141.2, 141.5, 143.6, 144.2, 170.9 ppm; MS (ES):m/z (%) =
[
o
+
+
0
.03 g) as a yellow solid; m.p. 180-181 C; R
f
= 0.67 (hexane/EtOAc,
5 2
554.1 [M+1] , 556.1 [M+3] ; C29H24BrN O (553.1113): calcd. for C,
-1
1
3
0/70, v/v); IR (neat): νmax(cm ) = 1745 (CO
2
Et), 3085 (NH); H NMR
) δ = 1.13 (t, J = 7.2 Hz, 3 H, CO CH CH ), 3.98 (d, J =
CH CH ), 6.91 (t, J =
), 7.36 (t, J = 7.5 Hz, 1 H, ArH), 7.52-7.62 (m, 4 H,
62.82; H, 4.36; N, 12.63; found C, 63.05; H, 4.41; N, 12.71.
(
400 MHz, CDCl
3
2
2
3
General procedure for the synthesis of 2-(1-(4-bromophenyl)-9H-
pyrido[3,4-b]indol-3-yl)imidazo[1,2-a]pyridin-3-amine (12bAZ). To
a stirred solution of 7bAZ (0.15 g, 0.29 mmol) in toluene (2 mL),
6.5 Hz, 2 H, NHCH
2
), 4.11 (q, J = 7.2 Hz, 2 H, CO
2
2
3
6.7 Hz, 1 H, NHCH
2
ArH), 7.85 (d, J = 4.6 Hz, 1 H, ArH), 8.00-8.02 (m, 3 H, ArH), 8.25 (d, J
7.8 Hz, 1 H, ArH), 8.48 (s, 1 H, NHβ-carboline), 8.93 (s, 1 H, ArH), 9.04
4
HBF (19 µL, 0.30 mmol) was added and refluxed the reaction
o
=
mixture at 120 C for 15 minutes. After the completion of reaction
which was monitored by TLC, the reaction content was cooled to
room temperature and toluene was decanted. Crude compound
was washed with ethyl acetate (4 x 5 mL) to obtain the analytically
pure product, 12bAZ (0.14 g from 0.15 g, 93%) as a yellow solid.
2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)imidazo[1,2-a]
1
3
(
s, 1 H, ArH) ppm; C NMR (100 MHz, CDCl
3
) δ = 14.1, 48.2, 61.5,
11.8, 115.5, 120.9, 122.3, 122.4, 129.1, 129.5, 129.6, 130.4, 131.5,
32.7, 134.4, 135.1, 136.1, 137.0, 140.5, 141.0, 143.5, 144.3, 170.1
1
1
+
+
ppm; MS (ES):m/z (%) = 497.1 [M+1] , 499.1 [M+3] ; C27
496.1415): calcd. for C, 65.26; H, 4.26; N, 16.91; found C, 65.44; H,
.28; N, 16.96.
Ethyl 2-((2-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)imidazo
1,2-a]pyrimidin-3-yl)amino)acetate (9bHX). Yield: 78% (0.23 g
6 2
H21ClN O
(
4
pyridin-3-amine (12bAZ). Yield: 93% (0.13 g from 0.15 g) as a bright
o
yellow solid; m.p. 168-169 C; R
f
= 0.44 (hexane/EtOAc, 10/90, v/v);
-1
1
[
IR (neat): νmax(cm ) = 3383 and 3390 (NH
2
); H NMR (400 MHz,
o
from 0.05 g) as a yellow solid; m.p. 171-172 C; R
f
= 0.61
hexane/EtOAc, 30/70, v/v); IR (neat): νmax(cm ) = 1732 (CO Et),
) δ = 1.01 (t, J = 7.1 Hz, 3 H,
), 3.98 (q, J = 7.1 Hz, 2 H,
), 6.46 (t, J = 6.4 Hz, 1 H, NHCH ), 7.02-7.09 (m, 1 H,
DMSO-d ) δ = 4.82 (s, 2 H, NH ), 7.36 (t, J = 7.5 Hz, 1 H, ArH), 7.52 (t,
6
2
-1
(
2
J = 6.8 Hz, 1 H, ArH), 7.61-7.65 (m, 2 H, ArH), 7.68-7.73 (m, 2 H,
ArH), 7.84 (t, J = 7.9 Hz, 1 H, ArH), 7.88-7.91 (m, 2 H, ArH), 8.08 (d, J
= 8.4 Hz, 1 H, ArH), 8.13 (d, J = 7.4 Hz, 1 H, ArH), 8.28 (d, J = 7.9 Hz,
1 H, ArH), 8.70 (t, J = 6.3 Hz, 1 H, ArH), 8.74 (d, J = 4.7 Hz, 1 H, ArH)
1
3
264 (NH); H NMR (400 MHz, CDCl
3
CO
CO
2
2
CH
2
2
CH
3
), 2.89 (s, 2 H, NHCH
2
CH
CH
3
2
13
ArH), 7.26-7.35 (m, 1 H, ArH), 7.57-7.68 (m, 2 H, ArH), 7.84 (t, J =
6
ppm; C NMR (100 MHz, DMSO-d ) δ = 110.3, 111.8, 112.9, 113.7,
7
.5 Hz, 2 H, ArH), 7.95 (s, 1 H, ArH), 8.09 (d, J = 8.2 Hz, 2 H, ArH),
.41 (t, J = 6.7 Hz, 1 H, ArH), 8.46-8.49 (m, 1 H, ArH), 8.84 (d, J = 5.2
116.2, 120.2, 120.7, 121.6, 124.3, 129.0, 129.1, 129.3, 129.6, 130.2,
130.6, 131.2, 131.9, 132.0, 134.8, 137.0, 137.6, 141.9, 142.3 ppm;
8
1
3
+
+
Hz, 1 H, ArH), 8.92 (m, 1 H, ArH) ppm; C NMR (100 MHz, CDCl
3
) δ
MS (ES):m/z (%) = 454.1 [M+1] , 456.1 [M+3] ; C24H16BrN
5
=
1
1
5
13.8, 48.0, 60.4, 108.0, 110.1, 111.5, 112.4, 119.9, 121.2, 122.1,
(453.0589): calcd. for C, 63.45; H, 3.55; N, 15.41; found C, 63.68; H,
3.60; N, 15.49.
30.5, 130.6, 131.8, 131.9, 137.4, 141.6, 141.7, 141.8, 142.9, 143.7,
+
45.8, 148.6, 152.1, 171.1 ppm; MS (ES):m/z (%) = 541.1 [M+1] ,
+
43.1 [M+3] ; C27
H21BrN
6
O
2
(540.0909): calcd. for C, 59.90; H, 3.91;
Acknowledgements
N, 15.52; found C, 60.10; H, 3.95; N, 15.59.
-(1-(4-bromophenyl)-9H-pyrido[3,4-b]indol-3-yl)-N-(tert-butyl)
imidazo[1,2-a]pyrimidin-3-amine (9bHZ). Yield: 84% (0.23 g from
2
N. D. and D. S. acknowledge Department of Science and
Technology (DST) and Council of Scientific and Industrial
Research (CSIR) New Delhi, India for Senior Research
Fellowships. V. S. gratefully acknowledges the financial
support in the form of research grant from DST (CS-361/2011),
DST-FIST (CSI-228/2011), CSIR (02(0202)/14/EMR-II), New
Delhi and TEQIP-II, NIT Jalandhar. Indian Institute of
Technology Ropar, SAIF Division, CDRI, Lucknow and Central
Instrumental Facility, GJ University of Science and Technology,
Hisar is gratefully acknowledged for recording spectroscopic
data reported in this paper.
o
0
f
.05 g) as a yellow solid; m.p. 89-90 C; R = 0.46 (hexane/EtOAc,
-1
1
3
0/70, v/v); IR (neat): νmax(cm ) = 3286 (NH); H NMR (400 MHz,
) δ = 1.10 (s, 9 H, C(CH ), 5.29 (s, 1 H, NH), 6.80-6.84 (m, 1 H,
ArH), 7.29-7.33 (m, 1 H, ArH), 7.49-7.56 (m, 2 H, ArH), 7.61 (t, J =
.5 Hz, 2 H, ArH), 7.71 (d, J = 8.3 Hz, 1 H, ArH), 7.90 (d, J = 8.2 Hz, 1
H, ArH), 8.02 (d, J = 7.5 Hz, 1 H, ArH), 8.20 (d, J = 8.0 Hz, 1 H, ArH),
CDCl
3
3 3
)
7
8
1
1
1
.47-8.48 (m, 1 H, ArH), 8.60 (d, J = 5.6 Hz, 1 H, ArH), 8.98 (d, J =
1
3
3
1.1 Hz, 1 H, ArH) ppm; C NMR (100 MHz, CDCl ) δ = 30.1, 57.5,
07.7, 107.8, 111.7, 112.7, 120.7, 122.3, 128.1, 128.8, 128.9, 129.2,
29.6, 131.5, 132.6, 141.0, 144.7, 148.9, 158.3 ppm; MS (ES):m/z
+
+
6
(%) = 511.1 [M+1] , 513.1 [M+3] ; C27H23BrN (510.1168): calcd. for
C, 63.41; H, 4.53; N, 16.43; found C, 63.59; H, 4.57; N, 16.52.
Notes and references
Ethyl 2-((2-(1-(4-bromophenyl)-9-methyl-9H-pyrido[3,4-b]indol-3-
1
R. Cao, W. Peng, Z. Wang and A. Xung, Curr. Med. Chem.,
007, 14, 479–500.
yl)imidazo[1,2-a]pyridin-3-yl)amino)acetate (11bAX). Yield: 69%
2
o
(
0.41 g from 0.10 g) as a yellow solid; m.p. 148-149 C; R
f
= 0.68
Et),
) δ = 1.15 (t, J = 7.1 Hz, 3 H,
), 3.84 (s, 2 H, NHCH ), 4.07 (q, J =
), 6.15 (s, 1 H, NHCH ), 6.80 (t, J = 6.4 Hz, 1
2
(a) K.-B. Wang, Y.-T. Di, Y. Bao, C.-M. Yuan, G. Chen, D.-H. Li,
J. Bai, H.-P. He, X.-J. Hao, Y.-H. Pei, Y.-K. Jing, Z.-L. Li and H.-
M. Hua, Org. Lett., 2014, 16, 4028–4031; (b) K.-B. Wang, C.-
M. Yuan, C.-M. Xue, D.-H. Li, Y.-K. Jing, H.-P. He, X.-J. Hao, Y.-
-1
(
hexane/EtOAc, 50/50, v/v); IR (neat): νmax(cm ) = 1731 (CO
2
1
3
328 (NH); H NMR (400 MHz, CDCl
CO CH CH ), 3.53 (s, 3 H, NCH
.1 Hz, 2 H, CO CH CH
3
2
2
3
3
2
T. Di, Z.-L. Li and H.-M. Hua, RSC Adv., 2014, 4, 53725–
3729; (c) T. D. Tran, N. B. Pham, M. Ekins, J. N. A. Hooper
7
2
2
3
2
5
and R. J. Quinn, Mar. Drugs, 2015, 13, 4556–4575; (d) R. J. R.
H, ArH), 7.15 (t, J = 7.7 Hz, 1 H, ArH), 7.25 (d, J = 4.9 Hz, 1 H, ArH),
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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ARTICLE
Jaeger, M. Lamshoft, S. Gottfried, M. Spiteller and P.
Spiteller, J. Nat. Prod., 2013, 76, 127−134; (e) S. L. Wong, H.
Journal Name
and W. A. Million, Bioorg. Med. Chem. Lett., 2003, 13, 1425–
1428.
(a) E. D. Cox and J. Cook, Chem. Rev., 1995, 95, 1797–1842;
S. Chang, G. J. Wang, M. Y. Chiang, H. Y. Huang, C. H. Chen,
7
S. C. Tsai, C. H. Lin and I. S. Chen, J. Nat. Prod., 2011, 74
2
Kaiser and B. R. Copp, J. Nat. Prod., 2011, 74, 1972−1979; (g)
W. H. Jiao, H. Gao, C. Y. Li, F. Zhao, R. W. Jiang, Y. Wang, G.
X. Zhou and X. S. Yao, J. Nat. Prod., 2010, 73, 167−171; (h) Y.
F. Chen, P. C. Kuo, H. H. Chan, I. J. Kuo, F. W. Lin, C. R. Su, M.
,
489−2496; (f) S. T. S. Chan, A. N. Pearce, M. J. Page, M.
(b) J. Royer, M. Bonin and L. Micouin, Chem. Rev., 2004, 104,
2311–2352; (c) D. Chandrasekhar, S. Borra, J. B. Nanubolu
and R. A. Maurya, Org. Lett., 2016, 18, 2974–297; (d) Y.-P.
Zhu, M.-C. Liu, Q. Cai, F.-C. Jia and A.-X. Wu, Chem. Eur. J.,
2013, 19, 10132–10137; (e) A. L. Pumphrey, H. Dong and T.
G. Driver, Angew. Chem. Int. Ed., 2012, 51, 5920–5923; (f) S.
T. Ding, Z. Z. Shi and N. Jiao, Org. Lett., 2010, 12, 1540–1543;
(g) D. B. England and A. Padwa, Org. Lett., 2008, 10, 3631-
3634.
L. Yang, D. T. Li and T. S. Wu, J. Nat. Prod., 2010, 73
993−1998; (i) L. He, S. Y. Liao, C. P. Tan, Y. Y. Lu, C. X. Xu, L.
N. Ji and Z. W. Mao, Chem. Commun., 2014, 50, 5611−5614;
j) N. S. Rajapaksa, M. A. McGowan, M. Rienzo and E. N.
Jacobsen, Org. Lett., 2013, 15, 706−709; (k) C. Rannoux, F.
Roussi, P. Retailleau and F. Gueritte, Org. Lett., 2010, 12
,
1
(
8
(a) C. de Graaff, E. Ruijter and R. V. A. Orru, Chem. Soc. Rev.,
2012, 41, 3969–4009; (b) D. M. D'Souza and T. J. J. Muller,
Chem. Soc. Rev., 2007, 36, 1095–1108; (c) A. K. Bagdi, S.
,
1
2
240−1243; (l) Q. Yin, S. G. Wang and S. L. You, Org. Lett.,
013, 15, 2688−2691; (m) K.-B. Wang, Y.-T. Di, Y. Bao, C.-M.
Santra, K. Monir and A. Hajra, Chem. Commun., 2015, 51
1555–1575; (d) R. P. Gore and A. P. Rajput, Drug Invent.
Today, 2013, , 148–152; (e) J. E. Biggs-Houck, A. Younai and
J. T Shaw, Curr. Opin. Chem. Biom., 2010, 14, 371–382; (f) H.
Bienayme and K. Bouzid, Angew. Chem., Int. Ed., 1998, 37
,
Yuan, G. Chen, D.-H. Li, J. Bai, H.-P. He, X.-J. Hao, Y.-H. Pei,
Y.-K. Jing, Z.-L. Li and H.-M. Hua, Org. Lett., 2014, 16
028−4031; (n) J. Lee, T. W. M. J. Cho, J. K. Kim, S. Joo, J. H.
5
,
4
,
Yang, G. S. Chae, K. Choi, J. H. Kwon and D. H. Choi, Chem.
Commun., 2013, 49, 6788−6790; (o) C. W. Lee, Y. Im, J. A.
Seo and J. Y. Lee, Chem. Commun., 2013, 49, 9860−9862; (p)
Q. Cai, X. W. Liang, S. G. Wang, J. W. Zhang, X. Zhang and S.
L. You, Org. Lett., 2012, 14, 5022−5025; (q) L. Wang, X. Xie
and Y. H. Liu, Org. Lett., 2012, 14, 5848−5851; (r) E. Ascic, C.
L. Hansen, S. T. L. Quement and T. E. Nielsen, Chem.
Commun., 2012, 48, 3345−3347; (s) K. C. Nicolaou, J. L.
Kiappes, W. W. Tian, V. B. Gondi and J. Becker, Org. Lett.,
2234–2237; (g) S. Vidyacharan, A. H. Shinde, B. Satpathi and
D. S. Sharada, Green Chem., 2014, 16, 1168–1175; (h) S.
Swami, N. Devi, A. Agarwala, V. Singh and R. Shrivastava,
Tetrahedron Lett., 2016, 57, 1346–1350; (i) N. Devi, D. Singh,
R. K. Sunkaria, C. C. Malakar, S. Mehra, R. K. Rawal and V.
Singh, ChemistrySelect, 2016, 1, 4696–4703; (j) F. Hu and M.
Szostak, Adv. Synth. Catal., 2015, 357, 2583–2614; (k) A. B.
Atar, J. S. Kim, K. T. Lima and Y. T. Jeong, New J. Chem.,
2015, 39, 396–402; (l) B.-L. Li, M. Zhang, H.-C. Hu, X. Dub and
Z.-H. Zhang, New J. Chem., 2014, 38, 2435-2442; (m) H. P.
Kalmode, K. S. Vadagaonkar, K. Murugan and A. C. Chaskar,
New J. Chem., 2015, 39, 4631–4639; (n) S. Banerjee and A.
Sahaa, New J. Chem., 2013, 37, 4170–4175; (o) A. Ghorbani-
2
011, 13, 3924−3927.
H. Rommelspacher, C. Wernicke, J. Lehmann, β-Carbolines:
Occurrence, Biosynthesis, and Biodegradation, 2011, , 105-
13. DOI:10.1007/978-1-4614-1542-8_6.
(a) N. Goel, N. Singh and R. Saini, Nat. Sci., 2009,
3
4
1
1
7
, 129−134;
Choghamarani and B. Tahmasbia, New J. Chem., 2016, 40,
1205–1212.
(
b) T. P. Hamsa and G. Kuttan, Eur. J. Pharmacol., 2010, 649
,
6
4−73; (c) F. Lamchouri, H. Toufik, S. M. Bouzzine, M. Hamidi
, 343−352;
d) L. Farouk, A. Laroubi, R. Aboufatima, A. Benharref and A.
Chait, J. Ethnopharmacology, 2008, 115, 449−454; (e) F. A.
Khan, A. Maalik, Z. Iqbal and I. Malik, Eur. J. Pharmacol.,
9
(a) K. Gudmundsson and S. D. Boggs, (EN) Chemical
Compounds. PCT Int. Appl., WO 2006026703, 2006; (b) C.
Hamdouchi, J. d. Blas, M. d. Prado, J. Gruber, B. A. Heinz,
and L. Vance, J. Med. Chem., 1999, 42, 50–59; (c) J. J.
Kaminsky and A. M. Doweyko, J. Med. Chem., 1999, 40, 427–
436; (d) M. Lhassani, O. Chavignon, J. M. Chezal, J. C.
Teulade, J. P. Chapat, R. Snoeck, G. Andrei, J. Balzarini, E. D.
Clerc and A. Gueiffier, Eur. J. Med. Chem., 1999, 34, 271–
274; (e) C. Maul, B. Sundermann, H.-H. Hennies, J. Schneider
and M. Gerlach, Patent WO01027109, 2001; (f) D. Elleder, J.
A. T. Young, T. J. Baiga and J. P. Noel, Patent
WO2009061856, 2009.
and M. Bouachrine, J. Mater. Environ. Sci., 2010,
(
1
2
013, 721, 391−394; (f) A. Daugan, P. Grondin, C. Ruault, A.-
C. L. M. de Gouville, H. Coste, J. Kirilovsky, F. Hyafil and R.
Labaudiniere, J. Med. Chem., 2003, 46, 4525–4532; (g) H.
Chen, P. Gao, M. Zhang, W. Liao and J. Zhang, New J. Chem.,
2
014, 38, 4155–4166; (h) S. Wang, K. Fang, G. Dong, S. Chen,
N. Liu, Z. Miao, J. Yao, J. Li, W. Zhang and C. Sheng, J. Med.
Chem., 2015, 58, 6678–6696; (i) H. Du, H. Gu, N. Li and J.
Wang, Med. Chem. Commun., 2016,
7
, 636–645; (J) A. S.
10 (a) C. Enguehard-Gueiffier and A. Gueiffier, Mini-Rev. Med.
Chem., 2007, , 888–899; (b) G. C. Moraski, P. A. Miller, M.
A. Bailey, J. Ollinger, T. Parish, H. I. Boshoff, S. Cho, J. R.
Gothelf, K. V. Gothelf, R. G. Hazell and K. A. Jorgensen,
Angew. Chem. Int. Ed., 2002, 41, 4236–4238.
(a) H. Guan, H. Chen, W. Peng, Y. Ma, R. Cao, X. Liu and A.
7
5
Anderson, S. Mulugeta, S. G. Franzblau and M. J. Miller, ACS
Xu, Eur. J. Med. Chem., 2006, 41
Funayama, K. Nishio, K. Wakabayashi, M. Nagao, K. Shimoi,
T. Ohira, S. Hasegawa and N. Saijo, Mutat. Res., 1996, 349
83−191; (c) A. C. Castro, L. C. Dang, F. Soucy, L. Grenier, H.
Mazdiyasni, M. Hottelet, L. Parent, C. Pien, V. Palombella
and J. Adams, Bioorg. Med. Chem. Lett., 2003, 13
419−2422; (d) Y. Song, D. Kesuma, J. Wang, Y. Deng, J.
,
1167−1179; (b) Y.
Infect. Dis., 2015,
Suda, H. Ohhara and T. Ogawa, Chem. Pharm. Bull., 1991,
39 1556–1567; (d) M. L. Bode, A. L. Rousseau, D.
Gravestock, S. S. Moleele and D. W. C. W. Van, WO
2010032195, 2010; (e) G. Naresh, R. Kant, and T. Narender,
Org. Lett., 2014, 16, 4528–4531; (f) K. V. Sashidhara, L. R.
Singh, D. Choudhary, A. Arun, S. Gupta, S. Adhikary, G. R.
1, 85–90; (c) M. Yamanaka, K. Miyake, S.
,
,
1
,
2
Duan, J. H. Wang and R. Z. Qi, Biochem. Biophys. Res.
Commun., 2004, 317, 128−132;
(a) L. A. Sorbera, L. Martin, P. A. Leeson and J. Castaner,
Drugs Future, 2001, 26, 15–19; (b) A. Daugan, P. Grondin, C.
Ruault, A.-C. L. M. de Gouville, H. Coste, J. Kirilovsky, F.
Hyafil and R. Labaudiniere, J. Med. Chem., 2003, 46, 4525–
Palnati, R. Konwar and R. Trivedi, RSC Adv., 2016,
80048; (g) P. Wadhwa, T. Kaur and A. Sharma, RSC Adv.,
2015, , 44353–44360; (h) D. Dheer, K. R. Reddy, S. K. Rath,
P. L. Sangwan, P. Das and R. Shankar, RSC Adv., 2016,
38033–38036; (i) S. K. Guchhait and C. Madaan, Org. Biomol.
Chem., 2010, , 3631–3634; (i) S. K. Guchhait, V. Chaudhary
6, 80037–
6
5
6
,
8
4
Peterson, B. S. Meldrum, S. Patel, J. B. Hansen, W. Loscher,
532; (c) L. Turski, D. N. Stephens, L. H. Jensen, E. N.
and C. Madaan, Org. Biomol. Chem., 2012, 10, 9271–9277;
(j) A. Modi, W. Ali and B. K. Patel, Adv. Synth. Catal., 2016,
358, 2100–2107; (k) J. Ren, M. Yang, H. Liu, D. Cao, D. Chen,
J. Li, L. Tang, J. He, Y.-L. Chen, M. Geng, B. Xiong and J. Shen,
H. H. Schneider and R. Schmiechen, J. Pharmacol. Exp. Ther.,
1
990, 253, 344–352; (d) G. N. Maw, C. M. Allerton, E. Gbekor
1
0 | J. Name., 2012, 00, 1-3
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Org. Biomol. Chem., 2015, 13, 1531–1535; (l) P. R. Adiyala,
G. S. Mani, J. B. Nanubolu, K. C. Shekar and R. A. Maurya,
Org. Lett., 2015, 17, 4308–4311.
and J. T. Shaw, Curr. Opin. Chem. Biol., 2010, 14, 371–382;
(d) A. Domling, Chem., Rev., 2006, 106, 17–89; (e) R. C. Cioc,
E. Ruijter and R. V. A. Orru, Green Chem., 2014, 16, 2958–
2975; (f) P. Slobbe, E. Ruijter and R. V. A. Orru, Med. Chem.
1
1
1 (a) N. Devi, R. K. Rawal and V. Singh, Tetrahedron, 2015, 71
83–232; (b) N. Devi, D. Singh, R. K. Rawal, J. Bariwal and V.
Singh, Curr. Top. Med. Chem., 2016, 16, 2963–2994.
,
1
Commun., 2012,
Paul, RSC Adv., 2015,
Heravi and N. Nazari, RSC Adv., 2016,
3
, 1189–1218; (g) R. Goel, V. Luxami and K.
, 81608–81637; (h) S. Sadjadi, M. M.
, 53203–53272; (i) T.
5
2 (a) A. T. Baviskar, C. Madaan, R. Preet, P. Mohapatra, V. Jain,
A. Agarwal, S. K. Guchhait, C. N. Kundu and U. C. Banerjee, J.
Med. Chem., 2011, 54, 5013–5030; (b) A. T. Baviskar, S. M.
Amrutkar, N. Trivedi, V. Chaudhary, A. Nayak, S. K. Guchhait,
U. C. Banerjee, P.V. Bharatam and C. N. Kundu, ACS Med.
6
Kaur, P. Wadhwa, S. Bagchi and A. Sharma, Chem. Commun.,
2016, 52, 6958–6976.
19 M. Adib, M. Mahdavi, M. A. Noghania and P. Mirzaei,
Tetrahedron Lett., 2007, 48, 7263–7265.
Chem. Lett., 2015,
6
, 481−485; (c) M. Hayakawa, H. Kaizawa,
20 G. S. Mandair, M. Light, A. Russell, M. Hursthouse and M.
Bradley, Tetrahedron Lett., 2002, 43, 4267–4268.
H. K.-I. Kawaguchi, N. Ishikawa, T. Koizumi, T. Ohishi, M.
Yamano, M. Okada, M. Ohta, S. Tsukamoto, F. I. Raynaud, M.
D. Waterfield, P. Parkerd and P. Workma, Bioorg. Med.
Chem., 2007, 15, 403–412.
1
1
3 (a) A. Deep, R. K. Bhatia, R. Kaur, S. Kumar, U. K. Jain, H.
Singh, S. Batra, D. Kaushik and P. K. Deb, Curr. Top. Med.
Chem.,
568026616666160530153233; (b) R. Goel, V. Luxami and K.
Paul, Curr. Top. Med. Chem., 2016, 16, DOI: 10.2174/
568026616666160414122644; (c) T. L. S. Kishbaugh, Curr.
2016,
16,
DOI:
10.2174/
1
1
Top. Med. Chem., 2016, 16, 3274–3302.
4 (a) N. Devi, D. Singh, Honey, S. Mor, S. Chaudhary, R. K
Rawal, V. Kumar, A. K Chowdhury and V. Singh, RSC Adv.,
2
016, 6, 43881–43891; (b) D. Singh, N. Devi, V. kumar, C. C.
Malakar, S. Mehra, S. Rattan, R. K. Rawal and V. Singh, Org.
Biomol. Chem., 2016, 14, 8154–8166; (c) D. Singh, N. Devi, V.
Kumar, C. C. Malakar, S. Mehra, R. K Rawal, B. S. Kaith and V.
Singh, RSC Adv., 2016,
and S. Batra, Eur. J. Org. Chem., 2010, 3684–3691; (e) V.
Singh and S. Batra, Curr. Org. Synth., 2012, , 513–528; (f) S.
Hutait, V. Singh and S. Batra, Eur. J. Org. Chem., 2010, 6269–
276; (g) V. Singh, S. Hutait, S. Biswas and S. Batra, Eur. J.
6, 88066-88076; (d) V. Singh, S. Hutait
9
6
Org. Chem., 2010, 531–539; (h) V. Singh, S. Hutait and S.
Batra, Eur. J. Org. Chem., 2009, 6211–6216.
1
1
5 A. Kamal, M. P. N. Rao, P. Swapna, V. Srinivasulu, C. Bagul, A.
B. Shaik, K. Mullagiri, J. Kovvuri, V. S. Reddy, K. Vidyasagar
and N. Nagesh, Org. Biomol. Chem., 2014, 12, 2370–2387.
6 (a) A. Kamal, V. Srinivasulu, V. L. Nayak, M. Sathish, N.
Shankaraiah, C. Bagul, N. V. S. Reddy, N. Rangaraj and N.
Nagesh, ChemMedChem, 2014, 9, 2084–2098 (b) P. Abranyi-
Balogh, A. Dancso, D. Frigyes, B. Volk, G. Keglevich and M.
Milen, Tetrahedron, 2014, 70, 5711–5719; (c) L. Liu, Q. Yang,
H. Yua, J.-L. Li, Y.-N. Pei, H.-J. Zhu, Z.-Q. Li and X.-K. Wang,
Tetrahedron, 2015, 71, 3296–3302; (d) Y. Ling, C. Xu, L. Luo,
J. Cao, J. Feng, Y. Xue, Q. Zhu, C. Ju, F. Li, Y. Zhang, Y. Zhang
and X. Ling, J. Med. Chem., 2015, 58, 9214–9227; (e) N.
Shankaraiah, P. Sharma, S. Pedapati, S. Nekkanti, V.
Srinivasulu, N. P. Kumar and A. Kamal, Lett. Drug Des.
Discov., 2016, 13, 335–342; (f) M. Zhang and D. Sun,
Anticancer Agents Med. Chem., 2015, 15, 537–547.
1
7 (a) S. Hati and S. Sen, Tetrahedron Lett., 2016, 57, 1040–
1
043; (b) A. Kamal, M. Sathish, A. V. G. Prasanthi, J. Chetna,
Y. Tangella, V. Srinivasulu, N. Shankaraiahb and A. Alarific,
RSC Adv., 2015, , 90121–90126; (c) A. Kamal, Y. Tangella, K.
5
L. Manasa, M. Sathish, V. Srinivasulu, J. Chetna and A. Alarifi,
Org Biomol Chem., 2015, 13, 8652–8662; (d) Q. Wu, R. Cao,
M. Feng, X. Guan, C. Ma, J. Liu, H. Song and W. Peng, Eur. J.
Med. Chem., 2009, 44, 533–540; (e) N. Shankaraiah, K. P.
Siraj, S. Nekkanti, V. Srinivasulu, P. Sharma, K. R. Senwar, M.
Sathish, M. V. P. S. Vishnuvardhan, S. Ramakrishna, C. Jadala,
N. Nagesh and A. Kamal, Bioorg. Chem., 2015, 59, 130–139;
(f) Z. Li, S. Chen, S. Zhu, J. Luo, Y. Zhang and Q, Weng,
Molecules 2015, 20, 13941-13957.
8 (a) R. Goel, V. Luxami and K. Paul, Org. Biomol. Chem., 2015,
1
13, 3525–3555; (b) S. Shaaban and B. F. Abdel-Wahab, Mol.
Divers., 2016, 20, 233–254; (c) J. E. Biggs-Houck, A. Younai
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DOI: 10.1039/C6NJ03210A
In(OTf) Assisted Synthesis of β-Carboline C-3 Tethered Imidazo[1,2-a]azine Derivatives
3
Nisha Devi, Dharmender Singh, Gurpreet Kaur, Satbir Mor, V. P. R. Kishore Putta, Saibabu Polina, Chandi C.
Malakar and Virender Singh
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