Synthesis of Pyrido-Fused Imidazo[4,5-c]quinolines by I2-DMSO Promoted Oxidative Cross Coupling and Intramolecular Cyclization

Article abstract of DOI:10.1055/s-0036-1588366

The synthesis of a series of novel quinoline fused imidazo[4,5-c]quinolines was accomplished by a simple, efficient, iodine-dimethyl- sulfoxide (I₂-DMSO) promoted sequential oxidative cross coupling- followed by intramolecular cyclization of py

Full text of DOI:10.1055/s-0036-1588366

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–J
paper
A
A. Kale et al.
Paper
Synthesis
Synthesis of Pyrido-Fused Imidazo[4,5-c]quinolines by I2-DMSO
Promoted Oxidative Cross Coupling and Intramolecular Cyclization
Ashok Kalea
Chiranjeevi Bingia
N
Nagarjuna Chary Ragib
Prabhakar Sripadib
Prabhakar Rao Tadikamallac
Krishnaiah Atmakur*a,d
I2, DMSO
80 °C, 3 h
N
O
O
N
Ar
Ar
N
N
N
O
a Division of Crop Protection Chemicals, CSIR-Indian Institute of
Chemical Technology, Tarnaka, Hyderabad 500 007, India
krishnu@iict.res.in
b National Center for Mass Spectrometry, CSIR-Indian Institute
of Chemical Technology, Tarnaka, Hyderabad 500 007, India
c Centre for NMR & Structural Chemistry, CSIR-Indian Institute
of Chemical Technology, Tarnaka, Hyderabad 500 007, India
d AcSIR-Indian Institute of Chemical Technology, Tarnaka,
Hyderabad 500 007, India
H2N
I2, DMSO
80 °C, 3 h
Ar
H
N
N
26 examples
yields up to 86%
wide substrate scope
Received: 20.09.2016
Accepted after revision: 08.11.2016
Published online: 07.12.2016
cules with a quinoline skeleton possess a variety of biologi-
cal effects including antimicrobial,5–9 anticancer10–17 and
antiviral18–20 activities. Quinoline compounds were also re-
ported to inhibit DENV2 RNA expression in Huh-7-DV-Fluc
cells.21 Additionally, annulation of IP compounds has led to
the synthesis of compounds that demonstrate a variety of
pharmacological properties.22 Therefore, the synthesis of N-
heterocycles having both an IP and a quinoline moiety in a
single molecular framework may generate significant levels
of activity.23 With this background, a literature survey was
conducted that revealed that surprisingly very few reports
are available on the construction of quinoline-fused imid-
azopyridine compounds. For example, Kundu reported24
the synthesis of quinoline-fused imidazopyridine com-
pounds starting from pyridazoimidazole, arylamine and
carbonyl compounds through Pictet–Springler cyclization.
Chauhan also reported25 on the use of similar reaction con-
ditions involving cyanuric chloride. Very recently, Zhang26
reported on a synthesis starting from 2-bromophenacyl-
bromide, 2-aminopyridine, and carbonyl compounds. How-
ever, these methods use a catalyst together with an additive
and/or ligand. Therefore, there remains a need to develop
simple methodologies to synthesize the quinoline-fused
imidazo pyridine compounds. With this background, and
also as a part of our research work on the synthesis of N-
rich heterocyclic compounds of biological interest,27 herein,
we report the synthesis of quinoline-fused imidazo pyri-
dine compounds by a simple I2-DMSO promoted reaction of
pyridoimidazole arylamines and carbonyl compounds in a
one-pot reaction without involving any metal catalyst, ad-
ditive or ligand.
DOI: 10.1055/s-0036-1588366; Art ID: ss-2016-n0655-op
Abstract The synthesis of a series of novel quinoline fused imid-
azo[4,5-c]quinolines was accomplished by a simple, efficient, iodine–
dimethyl sulfoxide (I2–DMSO) promoted sequential oxidative cross
coupling followed by intramolecular cyclization of pyridoimidazole aryl-
amines and carbonyl compounds in a one-pot reaction. Simple reaction
conditions, no metal catalyst, no additives, no ligand, selective product
formation and high yields are the advantages of this method.
Key words benzaldehydes, acetophenones, imidazopyridine, oxida-
tive coupling
Polyheterocycles are vital structural motifs with nu-
merous applications in pharmaceutical and material sci-
ence.1 Among them, a wide range of biological activities2
are associated with nitrogen-rich polycyclic frameworks.
Accordingly, the construction of this framework through
controlled organic synthesis, and in particular through cas-
cade sequences,3 is a current goal of organic chemists. To
realize these goals, approaches have often been explored
that are based on multicomponent reactions. In this con-
text, our attention was drawn to the annulation of imidazo
pyridines to synthesize pyrido-fused imidazo[4,5-c]quino-
line compounds. Imidazo pyridine (IP) compounds are priv-
ileged N-fused heterocycles that exhibit diverse biological
activities such as antiviral, antibacterial, and anti-inflam-
matory action, and can function as CXC chemokine receptor
type-4 (CXCR 4) antagonists. Furthermore, numerous drugs
with an IP core moiety such as Nicopidem and Alpidem
have also come on the market.4 On the other hand, mole-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

B
A. Kale et al.
Paper
Synthesis
Initially, 2-(imidazo[1,2-a]pyridin-2-yl)aniline (1a) was
prepared by following a reported method.25 Thus obtained
compound 1a (1.0 mmol) was reacted with acetophenone
2a (1.0 mmol) under Kornblum reaction conditions to give
quinoline-fused pyridoimidazole 3a through formation of
the C-3 dicarbonylated compound28 followed by its intra-
molecular cyclization. To our delight, the reaction proceed-
ed as per our presumption and gave the desired product 3a
exclusively in 46% yield (Scheme 1).
attempts were made to obtain crystals that were suitable
for X-ray crystallography studies. However, these attempts
were unsuccessful. Therefore, extensive NMR studies were
conducted to determine the exact structure of the product.
N
N
N
N
N
N
O
O
N
N
3b
4a
N
Figure 1 Structures of 3a and 4a
O
O
N
In this instance, compound 3b was subjected to exten-
sive NMR studies. On the 2D NOESY spectrum, a weak NOE
correlation was observed between the proton at δ = 8.13,
8.86 ppm (ca. 4 Å) and δ = 8.13, 8.27 ppm (Figure 2). Fur-
thermore, a strong heteronuclear correlation by HMBC was
observed between the carbonyl carbon at δ = 193.5 ppm
and aromatic protons at δ = 8.13 ppm (Figure 2), supporting
the structure of 3b (Figure 1). This was further confirmed
by the 1D and 2D NMR experiments.
I2, DMSO
3a
N
80 °C, 3 h
H2N
2a
1a
N
N
N
O
4a
Scheme 1
Excited by the exclusive formation of 3a, experiments
were carried out to improve the yields by varying reaction
parameters. When the quantity of I2 was increased to 1.2
equivalents, an increase in the yield to 63% was observed.
Further increase in the quantity of I2 to 1.5 equivalents
raised the yield to 84%. However, no change in the yield was
observed upon further increase in iodine quantity. Reac-
tions performed in a range of temperatures revealed that
80 °C was optimal for this reaction. Subsequently, experi-
ments were also carried out by employing iodine along
with bases such as piperidine, triethylamine, KOH, DBU or
DABCO. However, no significant improvement in the yield
of 3a was observed. Furthermore, when the reaction was
carried out with KI, NaI, NIS or CuI rather than with iodine,
no product formation was observed.
The structure of 3a was determined based on the spec-
tral data. The 1H NMR spectra showed one doublet signal at
δ = 8.98–8.95 ppm (1 H), three multiplets at δ = 8.94–8.91
(1 H), 8.32–8.27 (1 H), and 8.26–8.21 ppm (2 H), a doublet
signal at δ = 8.10–8.04 ppm (1 H), followed by three multi-
plet signals at δ = 7.88–7.83 (2 H), 7.73–7.68 (2 H), and
7.58–7.52 ppm (2 H), and a triplet at δ = 7.12–7.07 ppm
(1 H) accounting for all the aromatic protons. Given that
this data is equally consistent with compound 4a (Figure 1),
Figure 2 HMBC spectroscopic analysis of 3b
The structure of 3b was unambiguously confirmed by
extensive mass spectral analysis.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

C
A. Kale et al.
Paper
Synthesis
Positive ion ESI mass spectral analysis of 3b showed an
abundant protonated molecule [M + H]+ ion at m/z 338 in
addition to [M + H – CO]+ (m/z 310) (Figure 3). The HRMS
data confirmed the elemental composition for the ion m/z
338 as C22H16N3O.
Table 1 HRMS Data of 3b and the Product Ions Formed During MS/MS
of the [M + H]+ Ion
Ion
(m/z)
Molecular
formula
Calcd
mass
Found
mass
Error
(ppm)
338
310
218
191
119
91
C22H16NO
C21H16N3
C14H8N3
C13H7N2
C8H7O
338.13
310.13
218.07
191.06
119.04
91.055
338.128
310.133
218.071
191.060
119.049
91.0548
4.7
4.3
4.9
5.2
5.5
5.7
C7H7
H+
H+
N
N
N
N
O
N
N
Figure 3 Positive ion ESI mass spectrum of compound 3b
– CO
C7H7
m/z 91
We then performed MS/MS experiments on the [M +
H]+ ion (m/z 338).
C21H16N3
m/z 310
N
The ESI-MS/MS spectrum of the [M + H]+ ion of com-
pound 3b (m/z 338) is shown in (Figure 4). The spectrum
displayed product ions at m/z 310, 218, 191, 119, 91, and
78. The elemental composition of these ions as obtained
from HRMS data is summarized in Table 1. Formation of the
product ions at m/z 310, 191, 91, and 78 can be explained
by both the possible structures 3b and 4a (Figure 1). How-
ever, the major ions at m/z 218 and 119 can only be ex-
plained by structure 3b. The fragmentation pathway of the
[M + H]+ ion is depicted in (Scheme 2). The ion m/z 119 can-
not be explained by structure 4a, whereas the ion m/z 218
could be formed from structure 4a by the loss of C8H10N.
radical from the [M + H]+ ion. However, the elemental com-
position of the ion m/z 218 (C14H8N3) reveals that it is
formed from [M + H]+ ion by the loss of C8H8O, which can
only be explained by structure 3b. Thus, the fragmentation
pattern confirms the structure of compound as 3b.
C22H16N3O
+
C
O
N
m/z 338
N
+
C8H7O
C14H8N3
N
m/z 119
m/z 218
N
+
C13H7N2
m/z 191
Scheme 2 Fragmentation pathway for the [M + H]+ ion of compound
3b
acted with phenylglyoxal 2b under similar reaction condi-
tions to those in Scheme 1. Gratifyingly, this reaction gave
3a in 84% yield (Scheme 3). Subsequently, same reaction
was carried out without I2 under similar reaction condi-
tions and no formation of either 3a or 3aa was observed.
However, when the reaction was conducted at 110 °C for
6 hours, formation of 3a was observed in 22% yield along
with 3aa in 62% yield. To verify the yield improvements of
3a if any, the same reaction was extended to 12 hours and a
perceptible improvement in the yield of 3a (38%) was ob-
served. However, no further improvement in yield was ob-
served after 24 hours heating. Critically, in the presence of
I2 in DMSO, compound 3aa was completely converted into
the desire product 3a. These studies substantiate the for-
mation of 3a through oxidative coupling product 3aa, fol-
lowed by intramolecular cyclization.
Figure 4 ESI-MS/MS spectrum of [M + H]+ ion (m/z 338) of compound
Having confirmed the structure of 3a and established
the reaction conditions, this protocol was generalized by
reacting compound 1a with a range of electron-rich, neu-
tral, and electron-deficient aryl methyl ketones and also
with 2-acetyl naphthalene and 2-acetyl furan (Table 2).
Electron-rich functional groups such as methyl, 4-methoxy,
2,4-dimethoxy, and 3,4,5-trimethoxy aryl methyl ketones
3b
The reaction pathway for the formation of compound 3a
and the requirement for I2 were then verified by conducting
a series of control experiments. Thus, compound 1a was re-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

D
A. Kale et al.
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Synthesis
Table 2 Synthesis of Phenyl(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-
6-yl)methanones 3a
N
N
O
O
N
N
O
N
N
I2, DMSO
N
R2
R2
80 °C, 3 h
N
R1
H2N
N
O
R1
H2N
1a
1a
I2, DMSO
80 °C, 3 h
2b
3a, 84%
N
O
O
H2N
N
O
DMSO
N
3a–s
N
R3
110 °C, 6 h
R3
N
O
2a
H2N
1a
2b
O
Entry
Product R1
R2
R3
Time (h)
Yield (%)b
3aa, 62%
3a, 22%
1
2
3a
3b
3c
3d
3e
3f
H
H
H
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
84
86
85
81
81
79
82
80
84
86
82
80
84
78
86
74
71
82
78
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Cl
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Cl
H
H
H
H
H
4-Me
4-OMe
4-OEt
4-F
Scheme 3
3
4
5
gave better yields than electron-deficient aryl methyl ke-
tones. When the reaction was conducted with different
substituents on the benzene ring of the imidazopyridine,
3o–p were obtained in good yields. Experiments were also
carried out with substrates bearing a range of substituents
on the imidazo pyridine ring to give the product 3q–s in
good yields. Compound 3t was also obtained in 78% yield by
reacting 1b with 2j (Scheme 4).
6
4-Br
7
3g
3h
3i
4-Cl
8
4-NO2
9
3,5-(OMe)2
10
11
12
13
14
15
16
17
18
19
3j
3,4,5-(OMe)3
3k
3l
4-CF3
4-OBn
H
S
N
3m
3n
3o
3p
3q
3r
N
O
H
O
N
H
S
N
O
O
I2, DMSO
80 °C, 3 h
H
N
O
4-Me
furyl
naphthyl
H2N
O
O
1b
2j
3t, 78%
O
3s
Scheme 4
a Reaction conditions: i. 2 (1.66 mmol), I2 (2.5 mmol), DMSO (5 mL), r.t.,
5 min; ii. 1 (1.66 mmol), 80 °C, ca. 3 h.
b Yield of isolated product.
The protocol was also extended to aldehydes and, to our
satisfaction, was found to be quite compatible, producing
the corresponding products 6 in excellent yields (Table 3).
A plausible mechanism has been proposed for the for-
mation of 3a, whereby the aryl methyl ketone forms
phenylglyoxal under Kornblum reaction conditions
(Scheme 5). Nucleophilic attack of the imidazopyridine on
the electron-deficient carbonyl carbon of phenylglyoxal,
which is activated by iodine, leads to A. Further, subsequent
intramolecular cyclization reaction gives 3a.
In conclusion, we have developed a simple and highly
efficient method for the synthesis of pyrido-fused imid-
azo[4,5-c]quinolines by means of oxidative cross coupling
followed by an intramolecular cyclization of pyridoimid-
azole arylamines and carbonyl compounds promoted by
I2/DMSO. Advantageously, this methodology provides a
straightforward, one-pot, high yielding approach that does
not require prior activation of C(sp2)–H or the use of any
metal catalyst or base. The conditions can promote mecha-
H2N
O
O
N
O
I2 / DMSO
N
I
O
O
H2N
N
N
N
N
O
N
O
N
N
H
O
– HI
– H2O
H2N
O
O
I
A
Scheme 5 Proposed mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

E
A. Kale et al.
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Synthesis
Table 3 Synthesis of 6-Phenylpyrido[2′,1′:2,3]imidazo[4,5-c]quino-
lines 6a
scans. The HRMS experiments were performed with a Exactive OR-
BITRAP mass spectrometer (Thermo Scientific, Waltham, MA, USA)
equipped with an ESI source. The data was acquired using Xcallibur
software (Thermo Scientific). The sample was introduced into the
source by flow injection (10 μL loop) using MeOH as the mobile phase
at a flow rate of 30 μL/min. The HRMS data for the fragment ions
(product ions) was obtained by in-source fragmentation (all ion frag-
mentation) using a HCD cell and the collision energies used were 10
to 25 eV. Elemental composition for the parent as well as product ions
was obtained from the measured accurate mass values by using the
software.
N
N
N
I2, DMSO
80 °C, 3 h
O
N
N
R
H2N
1a
5
6a–f
R
Entry
Product
R
Time (h)
Yield (%)b
1
2
3
4
5
6
6a
6b
6c
6d
6e
6f
H
3
3
3
3
3
3
80
83
79
78
76
74
Phenyl(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)methanone
3a; Typical Procedure
Me
F
To a two-necked round-bottomed flask equipped with a reflux con-
denser and a stopper was added acetophenone (2a; 200 mg, 1.66
mmol, 1 equiv.), molecular iodine (635 mg, 2.5 mmol, 1.5 equiv.), and
DMSO (5 mL) and the reaction mixture was stirred at r.t. for ca. 5 min.
To this, 2-(imidazo[1,2-a]pyridin-2-yl)aniline (1a; 348 mg, 1.66
mmol, 1 equiv.) was added and the reaction mixture was heated to
80 °C for 3 h. The course of the reaction was monitored by TLC. Upon
completion of the reaction, the mixture was allowed to cool to r.t.,
then the iodine was quenched with 1 N aq Na2S2O3 solution (10 mL)
by stirring the reaction mixture at r.t. for ca. 10 min. The reaction
mixture was washed with water and extracted into EtOAc, and the or-
ganic layer was dried over anhydrous sodium sulfate and evaporated
under reduced pressure. The residue was passed through a column
silica gel (EtOAc–hexane, 40:60) to give the pure 3a.
Cl
Br
CN
a Reaction conditions: i. 5 (1.8 mmol), I2 (0.9 mmol), DMSO (5 mL), r.t., 5
min; ii. 2-(imidazo[1,2-a]pyridin-2-yl)aniline (1a; 1.8 mmol), 80 °C, ca. 3 h.
b Yield of isolated product.
nistically distinct reactions and the formation of new C–C
and C–N bonds. The scope and utility of this protocol is
general and the approach is anticipated to be suitable for a
number of applications.
Yield: 450 mg (84%); pale yellow solid; mp 204–206 °C.
IR (KBr): 2925, 1655, 1490, 1357, 1251, 1114, 985, 852, 705 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 8.98–8.95 (d, J = 9.0 Hz, 1 H), 8.94–8.91
(m, 1 H), 8.32–8.27 (m, 1 H), 8.26–8.21 (m, 2 H), 8.10–8.04 (m, 1 H ),
7.88–7.83 (m, 2 H), 7.73–7.68 (m, 2 H), 7.58–7.52 (m, 2 H), 7.12–7.07
(t, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 192, 164.2, 149.2, 143.7, 143.9, 134.2,
132.1, 131.4, 130.1, 129.5, 129.3, 128.3, 123.1, 121.8, 120, 117.3,
114.4, 114.1, 113.1.
Melting points were measured with a CINTEX programmable melting
point apparatus and are uncorrected. 1H and 13C NMR spectra of sam-
ples in CDCl3 and DMSO-d6 were recorded with Bruker AVANCE 300,
400 and 500 MHz spectrometers. Chemical shifts (δ) are reported rel-
ative to TMS (δ = 0.0 ppm) as the internal standard. Mass spectra
were recorded with ESI and EI spectrometers. ESI high-resolution
mass spectra were recorded with a QSTAR XL hybrid MS/MS system
(Applied Bio systems/MDS sciex, foster city, USA), equipped with an
ESI source (IICT, Hyderabad), EI high-resolution mass spectra were re-
corded with a JEOL-AccuToF mass spectrometer. IR spectra were re-
corded with a Thermo Nicolet nexus-670 spectrometer with refer-
ence to KBr. TLC was performed on Merck 60 F-254 silica gel plates.
The chemicals used in this work were obtained from commercial
channels and were used without purification.
ESI-MS: m/z = 324 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H14N3O: 324.1125; found:
324.1124.
Pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl(p-tolyl)methanone
(3b)
Yield: 276 mg (86%); pale yellow solid; mp 221–223 °C.
IR (KBr): 2922, 1654, 1419, 1356, 1252, 1182, 1023, 897, 752 cm−1
.
Mass Spectrometric Analysis
1H NMR (400 MHz, CDCl3): δ = 8.90–8.80 (m, 2 H), 8.32–8.24 (m, 1 H),
8.16–8.10 (m, 2 H), 7.98–7.92 (m, 1 H), 7.87–7.76 (m, 2 H), 7.64–7.56
(m, 1 H), 7.38–7.32 (m, 2 H), 7.04–6.97 (t, J = 6.9 Hz, 1 H), 2.56 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 193.4, 150.6, 148.1, 145.3, 143.7,
143.5, 133.7, 131.7, 130.1, 130.5, 129.4, 129.2, 129.1, 128.0, 122.7,
122.6, 120.5, 117.7, 112.4, 21.8.
Positive ESI-MS and MS/MS analyses were performed with a Quattro
LC Triple quadrupole mass spectrometer (Micromass, Manchester,
UK) under the control of Mass Lynx software (version 4.1). Sample
was introduced into the source by using an infusion pump [Harvard
Apparatus (Holliston, MA, USA)] at a flow rate of 10 μL/min. Capillary
and cone voltages were kept at 3.50 kV and 30 V, respectively. Nitro-
gen was used as the desolvation gas. The source and desolvation tem-
peratures were kept at 100 °C and 250 °C, respectively. For full-scan
experiments, the MS1 was scanned from m/z 40 to 600. For the
MS/MS experiments, keeping MS1 static, the precursor ion of interest
was mass selected and the product ions spectrum was obtained by
scanning MS2. Argon was used as the collision gas, and the collision
gas cell was kept at a pressure of 4.0 × 10–4 mbar. The collision energy
used was 15–30 eV. The spectra reported were averages of 25 to 30
ESI-MS: m/z = 338 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C22H16N3O: 338.1283; found:
338.1287.
(4-Methoxyphenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3c)
Yield: 280 mg (85%); pale yellow solid; mp 216–218 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

F
A. Kale et al.
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Synthesis
IR (KBr): 2923, 1644, 1491, 1331, 1261, 1174, 1024, 898, 767 cm−1
.
(4-Chlorophenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3g)
1H NMR (400 MHz, CDCl3): δ = 8.88–8.78 (m, 2 H), 8.38–8.16 (m, 3 H),
8.05–7.92 (m, 1 H), 7.90–7.73 (m, 2 H), 7.68–7.54 (m, 1 H), 7.12–6.89
(m, 3 H), 3.92 (s, 3 H).
Yield: 280 mg (82%); pale yellow solid; mp 218–220 °C.
IR (KBr): 2924, 1654, 1491, 1249, 1087, 1025, 894, 832, 758 cm−1
.
13C NMR (125 MHz, CDCl3): δ = 191.3, 160.4, 158.1, 148.1, 133.9,
133.2, 131.3, 130.9, 129.6, 129.3, 129.0, 128.3, 128.0, 124.8, 118.6,
117.2, 115.5, 113.2, 55.1.
1H NMR (300 MHz, CDCl3+DMSO-d6): δ = 9.01–8.96 (m, 1 H), 8.86–
8.83 (m, 1 H), 8.26–8.21 (m, 3 H), 8.09–8.01 (m, 1 H), 7.86–7.80 (m,
2 H), 7.71–7.69 (m, 1 H), 7.36–7.31 (m, 2 H), 7.13–7.10 (t, J = 6.5 Hz,
1 H).
ESI-MS: m/z = 354 [M + H]+.
13C NMR (75 MHz, CDCl3+DMSO-d6): δ = 191.5, 146, 142.7, 139.9,
133.5, 132.4, 131.2, 129.4, 128.9, 128.2, 128.1, 122.3, 121.3, 121.2,
119.7, 116.5, 112.6, 127.9, 124.7.
HRMS (ESI): m/z [M + H]+ calcd for C22H16N3O2: 354.1236; found:
354.1237.
(4-Ethoxyphenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
ESI-MS: m/z 358 [M + H]+.
yl)methanone (3d)
HRMS (ESI): m/z [M + H]+ calcd for C21H13ClN3O: 358.0738; found:
Yield: 284 mg (81%); pale yellow solid; mp 227–229 °C.
358.0734.
IR (KBr): 2923, 1608, 1485, 1355, 1253, 1172, 897, 835, 753 cm−1
.
(4-Nitrophenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3h)
1H NMR (400 MHz, CDCl3): δ = 8.85–8.80 (m, 2 H), 8.23–8.21 (m, 1 H),
8.19–8.12 (m, 2 H), 8.01–7.96 (m, 1 H), 7.78–7.73 (m, 2 H), 7.73–7.58
(m, 1 H), 6.98–6.96 (m, 1 H), 6.91–6.86 (m, 2 H), 4.12–4.05 (q, J = 11.0,
14.7 Hz, 2 H), 4.42–4.36 (t, J = 7.0 Hz, 3 H).
Yield: 281 mg (80%); pale yellow solid; mp 225–227 °C.
IR (KBr): 2924, 1617, 1524, 1487, 1361, 1246, 929, 864, 721 cm−1
.
13C NMR (100 MHz, CDCl3): δ = 191.7, 164.1, 149.1, 143.8, 143.6,
134.1, 132.1, 131.4, 130.0, 129.4, 129.2, 128.3, 123.1, 121.7, 120.1,
117.2, 114.4, 114.0, 113.1, 63.9, 14.6.
ESI-MS: m/z 368 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C23H18N3O2: 368.1012; found:
1H NMR (500 MHz, CDCl3): δ = 9.59–9.53 (m, 1 H), 7.86–7.82 (d, J =
8.9 Hz, 1 H), 7.57–7.49 (m, 2 H), 7.39–7.29 (m, 2 H), 7.16–7.02 (m,
6 H).
13C NMR (125 MHz, CDCl3): δ = 193.2, 149.8, 147.9, 145.1, 143.3,
143.5, 133.1, 131.5, 130.3, 129.9, 129.1, 128.9, 128.8, 127.8, 122.5,
122.4, 120.3, 117.5, 112.1.
368.1014.
ESI-MS: m/z = 369 [M + H]+.
(4-Fluorophenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3e)
HRMS (ESI): m/z [M + H]+ calcd for C21H13N4O3: 369.1652; found:
369.1654.
Yield: 256 mg (80%); pale yellow solid; mp 203–205 °C.
IR (KBr): 2924, 1661, 1409, 1327, 1110, 1066, 896, 853, 754 cm−1
.
(3,5-Dimethoxyphenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3i)
1H NMR (400 MHz, CDCl3): δ = 9.04–9.00 (d, J = 7.0 Hz, 1 H), 8.98–8.93
(m, 1 H), 8.39–8.22 (m, 4 H), 8.16–8.09 (d, J = 9.0 Hz, 1 H), 7.91–7.85
(m, 2 H), 7.78–7.71 (m, 1 H), 7.26–7.20 (m, 1 H), 7.18–7.11 (t, J =
6.8 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 192.0, 170.32, 163.27 (d, 2J =
251.6 Hz), 143.8, 143.6, 136.1, 134.1, 132.2, 131.2, 130.0, 128.7, 128.6
(d, 1J = 8.0 Hz), 127.4, 123.0, 120.2, 117.4, 114.8, 114.5, 113.0.
Yield: 304 mg (84%); pale yellow solid; mp 208–210 °C.
IR (KBr): 2927, 1648, 1437, 1333, 1186, 1028, 999, 759, 721 cm−1
.
1H NMR (300 MHz, CDCl3): δ = 9.91–9.86 (m, 2 H), 8.46–8.41 (m, 1 H),
8.10–8.06 (m, 1 H), 8.05–8.00 (m, 1 H), 7.93–7.91 (m, 3 H), 7.67–7.61
(m, 1 H), 7.09–7.01 (m, 1 H), 6.96–6.93 (m, 1 H), 3.98 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 192.2, 154.5, 149.9, 149.1, 147.9, 143.8,
130.6, 130.0, 129.1, 129, 128.7, 128.0, 124.1, 122.8, 120.4, 117.7,
112.4, 112.5, 110, 56.2, 56.1.
ESI-MS: m/z = 342 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H13FN3O: 342.1035; found:
ESI-MS: m/z = 384 [M + H]+.
342.1037.
HRMS (ESI): m/z [M + H]+ calcd for C23H18N3O3: 384.1345; found:
384.1346.
(4-Bromophenyl)(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3f)
Yield: 300 mg (79%); pale yellow solid; mp 214–216 °C.
IR (KBr): 2923, 1653, 1490, 1322, 1171, 1066, 897, 834, 739 cm−1
Pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl(3,4,5-trimethoxyphe-
nyl)methanone (3j)
.
1H NMR (500 MHz, CDCl3): δ = 9.10–9.06 (d, J = 9.0 Hz, 1 H), 8.96–8.91
(m, 1 H), 8.39–8.35 (m, 1 H), 8.23–8.21 (m, 2 H), 8.09–7.99 (m, 1 H),
7.91–7.88 (m, 2 H), 7.84–7.81 (m, 3 H), 7.16–7.10 (t, J = 6.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 191.9, 154.4, 148.2, 147.8, 134.6,
133.4, 132.5, 132.2, 131.2, 130.3, 129.9, 129.4, 129.3, 128.6, 128.1,
124.4, 119.1, 117.7, 116.3.
Yield: 330 mg (86%); pale yellow solid; mp 197–199 °C.
IR (KBr): 2930, 1649, 1491, 1334, 1187, 1029, 961, 833, 721 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 8.89–8.83 (m, 1 H), 8.32–8.27 (m, 2 H),
8.02–7.98 (d, J = 9.0 Hz, 1 H), 7.86–7.80 (m, 2 H), 7.72–7.63 (m, 2 H),
7.59–7.52 (m, 1 H), 7.51–7.44 (m, 1 H), 7.05–6.99 (t, J = 6.8 Hz, 1 H),
3.99 (s, 3 H), 3.88 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 192.3, 152.9, 150.1, 148.2, 143.7,
132.9, 132.1, 131.9, 131.8, 130.65, 130.6, 130.0, 129.1, 128.5, 128.4,
122.8, 117.8, 112.4, 109.2, 61.1, 56.2.
ESI-MS: m/z = 402 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H13BrN3O: 402.0235; found:
402.0235.
ESI-MS: m/z = 414 [M + H]+.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

G
A. Kale et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C24H20N3O4: 414.1442; found
414.1448.
13C NMR (100 MHz, CDCl3): δ = 189.4, 157.4, 147.6, 133.0, 132.6,
132.2, 131.7, 130.0, 129.7, 129.1, 127.9, 125.9, 118.6, 117.2, 116.3,
116.0, 115.8, 115.6, 115.4.
EI-MS: m/z = 357 [M]+.
Pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl[4-(trifluorometh-
yl)phenyl]methanone (3k)
HRMS (EI): m/z [M]+ calcd for C21H12ClN3O: 357.0667; found:
357.0668.
Yield: 304 mg (82%); pale yellow solid; mp 221–223 °C.
IR (KBr): 2923, 1667, 1409, 1523, 1175, 1064, 954, 860, 748 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 9.08–9.03 (d, J = 7.0 Hz, 1 H), 8.88–8.84
(m, 1 H), 8.37–8.34 (m, 2 H), 8.28–8.23 (m, 2 H), 8.10–8.06 (d, J =
9.1 Hz, 1 H), 7.84–7.81 (m, 2 H), 7.76–7.74 (m, 1 H), 7.68–7.63 (m,
1 H), 7.19–7.18 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 192.7, 168.5, 150.1, 147.9, 143.4,
142.4, 139.0, 134.8 (d, 2J = 32.2 Hz), 133.4, 131.9, 131.1, 130.4, 130.2,
129.5, 129.4, 128.8, 125.3, 122.7 (q, 1J = 260.4 Hz), 117.8, 112.8.
(9-Methylpyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)(phe-
nyl)methanone (3o)
Yield: 259 mg (86%); pale yellow solid; mp 210–212 °C.
IR (KBr): 2926, 1654, 1463, 1345, 1234, 1065, 914, 822, 763 cm−1
1H NMR (500 MHz, CDCl3): δ = 8.86–8.83 (d, J = 9.0 Hz, 1 H), 8.67–8.61
(m, 1 H), 8.39–8.36 (m, 1 H), 8.35–8.31 (m, 2 H), 7.96–7.94 (m, 1 H),
7.82–7.76 (m, 2 H), 7.71–7.69 (m, 1 H), 7.51–7.47 (m, 3 H), 2.49 (s,
3 H).
.
ESI-MS: m/z = 392 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C22H13F3N3O: 392.1003; found:
392.1005.
13C NMR (75 MHz, CDCl3): δ = 193.7, 148.5, 143.4, 143.3, 135.9, 134.3,
134.1, 131.6, 130.1, 129.9, 129.2, 128.5, 128.3, 126.8, 122.9, 122.8,
122.1, 120.2, 116.7, 18.4.
ESI-MS: m/z = 338 [M + H]+.
[4-(Benzyloxy)phenyl](pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3l)
HRMS (ESI): m/z [M + H]+ calcd for C22H16N3O: 338.1283; found:
338.1287.
Yield: 80% (330 mg); pale yellow solid; mp 231–233 °C.
IR (KBr): 2933, 1656, 1354, 1247, 1175, 1016, 935, 896, 744 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 9.23–9.21 (d, J = 9.0 Hz, 1 H), 8.86–8.81
(m, 1 H), 8.23–8.21 (m, 2 H), 8.13–8.09 (m, 1 H), 8.01–7.99 (m, 2 H),
7.63–7.61 (m, 1 H), 7.34–7.29 (m, 5 H), 7.28–7.27 (m, 1 H), 7.18–7.16
(m, 2 H), 7.09–7.06 (t, J = 6.5 Hz, 1 H), 5.21 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 192.0, 163.7, 162.9, 143.6, 136.1, 135.9,
134.1, 132.2, 131.2, 130.1, 129.4, 129.2, 128.7, 128.3, 127.4, 123,
122.1, 121.9, 120.2, 117.4, 114.8, 114.5, 113.0, 70.2.
(9-Chloropyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)(phe-
nyl)methanone (3p)
Yield: 215 mg (74%); pale yellow solid; mp 239–240 °C.
IR (KBr): 2921, 1655, 1568, 1487, 1327, 1254, 1176, 948, 808,
761 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 9.07 (m, 1 H), 8.87–8.84 (m, 1 H), 8.30–
8.24 (m, 2 H), 8.14–8.11 (m, 1 H), 8.03–7.99 (m, 1 H), 7.89–7.82 (m,
2 H), 7.74–7.69 (m, 1 H), 7.66–7.61 (m, 1 H), 7.59–7.55 (m, 1 H), 7.50–
7.45 (t, J = 7.7 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 193.4, 147.6, 143.4, 143.1, 135.7,
134.2, 133.3, 132.5, 131.7, 130.3, 129.7, 128.9, 128.4, 127.5, 123.0,
122.0, 121.0, 120.5, 117.7.
ESI-MS: m/z = 430 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C28H20N3O2: 430.1544; found:
430.1545.
(3-Methylpyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)(phe-
nyl)methanone (3m)
ESI-MS: m/z = 358 [M + H]+.
Yield: 252 mg (84%); pale yellow solid; mp 215–217 °C.
HRMS (ESI): m/z calcd for C21H13ClN3O: 358.0726; found: 358.0741.
IR (KBr): 2922, 1671, 1536, 1446, 1357, 1261, 1039, 926, 809,
724 cm−1
.
(9-Bromopyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)(p-tol-
1H NMR (500 MHz, CDCl3): δ = 8.15–8.09 (d, J = 7.4 Hz, 1 H), 8.02–7.97
(m, 2 H), 7.93–7.87 (m, 2 H), 7.65–7.39 (m, 6 H), 7.04 (m, 1 H), 2.45 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 193.1, 161.7, 153.9, 144.4, 143.1,
134.4, 133.7, 131.4, 129.4, 129.2, 129.1, 128.4, 127.5, 126.4, 124.6,
123.9, 116.8, 114.3, 21.6.
yl)methanone (3q)
Yield: 200 mg (71%); pale yellow solid; mp 223–225 °C.
IR (KBr): 2923, 1689, 1519, 1457, 1315, 1231, 1069, 934, 745 cm−1
.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.83 (d, J = 8.8 Hz, 1 H), 7.68–7.66
(m, 1 H), 7.64–7.62 (m, 2 H), 7.32–7.29 (m, 2 H), 7.27–7.23 (m, 1 H),
7.21–7.18 (m, 2 H), 7.13–7.09 (m, 2 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 190.9, 158.4, 148.2, 145.2, 132.8,
130.9, 130.7, 130.2, 129.9, 129.6, 129.4, 129.3, 129.2, 127.8, 118.8,
117.5, 117.2, 115.6, 21.8.
EI-MS: m/z = 337 [M]+.
HRMS (EI): m/z [M]+ calcd for C22H15N3O: 337.1215; found: 337.1212.
ESI-MS: m/z = 416 [M + H]+.
(3-Chloropyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)(phe-
nyl)methanone (3n)
HRMS (ESI): m/z [M + H]+ calcd for C22H15BrN3O: 416.0391; found:
416.0393.
Yield: 227 mg (78%); pale yellow solid; mp 235–237 °C.
IR (KBr): 2924, 1674, 1606, 1571, 1416, 1283, 1177, 1042, 958, 834,
752 cm−1
.
Furan-2-yl(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)meth-
1H NMR (500 MHz, CDCl3): δ = 8.58 (s, 1 H), 8.39 (m, 1 H), 8.99 (m,
1 H), 8.42 (m, 1 H), 8.04 (d, J = 7.3 Hz, 1 H), 7.64–7.58 (m, 1 H), 7.57–
7.51 (m, 1 H), 7.49–7.44 (t, J = 7.7 Hz, 1 H), 7.42–7.37 (m, 1 H), 7.32–
7.25 (m, 2 H), 7.09–7.01 (m, 1 H).
anone (3r)
Yield: 240 mg (82%); pale yellow solid; mp 198–200 °C.
IR (KBr): 2923, 1643, 1490, 1357, 1259, 1172, 896, 834, 739 cm−1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

H
A. Kale et al.
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 9.41–9.40 (m, 1 H), 9.16–9.11 (m, 1 H),
8.36–8.32 (m, 1 H), 8.01–7.96 (m, 1 H), 7.92–7.86 (m, 4 H), 7.64–7.61
(m, 1 H), 7.21–7.19 (m, 1 H), 6.98–6.96 (m, 1 H).
13C NMR (75 MHz, CDCl3 + DMSO-d6): δ = 179.3, 150.9, 148.2, 142.8,
142.1, 131.1, 129.8, 129.4, 128.9, 128.1, 125.4, 122.3, 121.6, 116.5,
112.5, 112.4, 119.7, 110.0, 97.5.
6-Phenylpyrido[2′,1′:2,3]imidazo[4,5-c]quinolines 6a–f; General
Procedure
To a two-necked round-bottomed flask equipped with a reflux con-
denser and a stopper was added benzaldehyde (5; 200 mg, 1.8 mmol,
1 equiv), molecular iodine (239 mg, 0.9 mmol, 0.5 equiv), and DMSO
(5 mL) and the reaction mixture was stirred at r.t. for ca. 5 min. To
this, 2-(imidazo[1,2-a]pyridin-2-yl)aniline (1a; 394 mg, 1.8 mmol, 1
equiv) was added and the reaction mixture was heated to 80 °C for
3 h. The course of the reaction was monitored by TLC. The reaction
mixture was allowed to cool to r.t., then the iodine was quenched
with 1 N aq Na2S2O3 solution (10 mL) by stirring the reaction mixture
at r.t. for ca. 10 min. The reaction mixture was then washed with wa-
ter and extracted into EtOAc. The organic layer was dried over anhy-
drous sodium sulfate and evaporated under reduced pressure. The
residue was passed through a column of silica gel (EtOAc–hexane,
40:60) to give pure 6.
ESI-MS: m/z = 314 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C19H12N3O2: 314.1142; found:
314.1145.
Naphthalen-2-yl(pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-
yl)methanone (3s)
Yield: 274 mg (78%); pale yellow solid; mp 231–233 °C.
IR (KBr): 2924, 1644, 1489, 1354, 1274, 1097, 952, 828, 745 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 8.98–8.95 (m, 2 H), 8.70 (s, 1 H), 8.38–
8.23 (m, 2 H), 8.21–8.10 (m, 2 H), 8.01–7.88 (m, 4 H), 7.83–7.74 (m,
1 H), 7.71–7.63 (m, 1 H), 7.61–7.53 (m, 1 H), 7.12–7.08 (t, J = 7.1 Hz,
1 H).
6-Phenylpyrido[2′,1′:2,3]imidazo[4,5-c]quinoline (6a)
Yield: 440 mg (80%); colorless solid; mp 210–212 °C.
IR (KBr): 2923, 1565, 1481, 1361, 1241, 1233, 1026, 950, 837,
13C NMR (125 MHz, CDCl3): δ = 191.1, 158.2, 148.0, 135.8, 132.5,
132.3, 132.0, 130.9, 130.6, 129.8, 129.6, 129.3, 129.2, 129.0, 128.4,
127.79, 127.0, 126.7, 123.7, 118.7, 117.4, 115.7.
ESI-MS: m/z = 374 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C25H16N3O: 374.1290; found:
758 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 8.98–8.92 (d, J = 9.0 Hz, 1 H), 8.53–8.47
(m, 1 H), 8.21–8.08 (d, J = 6.5 Hz, 1 H), 7.93–7.91 (d, J = 9.1 Hz, 1 H),
7.82–7.79 (m, 1 H), 7.74–7.71 (m, 3 H), 7.68–7.63 (m, 3 H), 7.56–7.51
(m, 1 H), 6.94–6.84 (t, J = 6.8 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 149.9, 147.5, 144.1, 147.8, 137.1, 132,
130.4, 129.9, 129.3, 129.2, 128.7, 126.8, 127.1, 121.2, 118, 120, 112.3,
112.6.
374.1287.
Benzo[4′,5′]thiazolo[2′,3′:2,3]imidazo[4,5-c]quinolin-6-yl(3,4,5-
trimethoxyphenyl)methanone (3t)
ESI-MS: m/z = 296 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C20H14N3: 296.1162; found:
Yield: 275 mg (78%); pale yellow solid; mp 257–258 °C.
IR (KBr): 2924, 1654, 1577, 1467, 1335, 1233, 1120, 993, 818,
296.1182.
737 cm−1
.
1H NMR (300 MHz, DMSO-d6 + CDCl3): δ = 9.02 (m, 1 H), 8.07–7.93
(m, 2 H), 7.91–7.80 (m, 1 H), 7.66–7.54 (m, 3 H), 7.52–7.38 (m, 3 H),
3.99 (s, 3 H), 3.90 (s, 6 H).
13C NMR (125 MHz, CDCl3): δ = 192.6, 158.8, 153.2, 150.1, 144.2,
143.3, 141.7, 137.7, 133.0, 131.4, 130.2, 129.1, 126.9, 125.3, 124.2,
123.4, 122.8, 116.3, 109.0, 94.1, 61.0, 56.3.
6-(p-Tolyl)Pyrido[2′,1′:2,3]imidazo[4,5-c]quinoline (6b)
Yield: 242 mg (83%); colorless solid; mp 220–222 °C.
IR (KBr): 2922, 1595, 1489, 1362, 1129, 1062, 952, 826, 754 cm−1
.
1H NMR (400 MHz, CDCl3): δ = 8.89–8.97 (m, 2 H), 8.26–8.21 (d, J =
6.8 Hz, 1 H), 8.18–8.10 (d, J = 9.0 Hz, 1 H), 7.95–7.58 (m, 2 H), 7.76–
7.31 (m, 3 H), 7.54–7.43 (m, 2 H), 7.09–6.99 (d, J = 7.7 Hz, 1 H), 2.48 (s,
3 H).
13C NMR (75 MHz, CDCl3): δ = 152.2, 149.4, 146.4, 142.2, 133.1, 132.1,
131.9, 131.1, 130.4, 129.1, 128.1, 127.6, 125.1, 123.1, 120.4, 119.6,
118.4, 113.8, 21.6.
ESI-MS: m/z = 470 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C26H20N3O4S: 470.1150; found:
470.1169.
1-{2-(2-Aminophenyl)imidazo[1,2-a]pyridin-3-yl}-2-phenyl-
ethane-1,2-dione (3aa)
ESI-MS: m/z = 310 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3: 310.1319; found:
Yield: 200 mg (62%); pale yellow solid; mp 240–242 °C.
310.1338.
IR (KBr): 3445, 2922, 1663, 1591, 1496, 1341, 1270, 1109, 803,
730 cm−1
.
6-(4-Fluorophenyl)pyrido[2′,1′:2,3]imidazo[4,5-c]quinoline (6c)
1H NMR (500 MHz, CDCl3): δ = 13.81 (s, 2 H), 8.91–8.80 (d, J = 7.5 Hz,
1 H), 8.35–8.33 (m, 2 H), 8.20–8.14 (m, 1 H), 7.92–7.90 (m, 1 H), 7.75–
7.69 (m, 2 H), 7.66–7.61 (m, 1 H), 7.50–7.48 (m, 2 H), 7.44–7.38 (m,
1 H), 7.23–7.17 (m, 1 H), 6.89–6.81 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 188.6, 183.4, 160.6, 144.7, 144.4,
136.2, 133.9, 131.0, 128.8, 128.3, 127.3, 125.3, 125.1, 124.2, 121.4,
121.2, 117.6, 113.1, 109.1.
Yield: 237 mg (79%); colorless solid; mp 214–216 °C.
IR (KBr): 2924, 1501, 1428, 1362, 1222, 1160, 952, 844, 732 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 9.01–8.98 (d, J = 7.7 Hz, 1 H), 8.97–8.93
(d, J = 8.3 Hz, 1 H), 8.38–8.28 (m, 4 H), 8.14–8.11 (m, 1 H), 7.91–7.86
(m, 2 H), 7.74–7.71 (m, 1 H), 7.33–7.30 (m, 1 H), 7.26–7.19 (t, J = 7.3
Hz, 1 H).
ESI-MS: m/z = 342 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3O2: 342.1237; found:
13C NMR (125 MHz, CDCl3): δ = 163.4 (d, 2J = 249.4 Hz), 149.6, 147.4,
147.0, 144.9, 134.3, 130.7 (d, 1J = 8.8 Hz), 130.0, 129.4, 129.0, 126.9,
126.6, 122.6, 121.3, 120.3, 118.1, 116.2, 112.1.
342.1243.
ESI-MS: m/z = 314 [M + H]+.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J

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HRMS (ESI): m/z [M + H]+ calcd for C20H13FN3: 314.1074; found:
314.1088.
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6-(4-Chlorophenyl)pyrido[2′,1′:2,3]imidazo[4,5-c]quinoline (6d)
Yield: 241 mg (78%); colorless solid; mp 287–289 °C.
IR (KBr): 2923, 1581, 1401, 1394, 1221, 1034, 957, 821, 764 cm−1
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1H NMR (400 MHz, CDCl3): δ = 9.23 (s, 1 H), 8.11–8.06 (m, 4 H), 8.07–
8.02 (m, 1 H), 7.98–7.93 (m, 2 H), 7.85–7.81 (m, 3 H), 7.12–7.10 (t, J =
7.2 Hz, 1 H).
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6-(4-Bromophenyl)pyrido[2′,1′:2,3]imidazo[4,5-c]quinoline (6e)
Yield: 265 mg (76%); colorless solid; mp 231–233 °C.
IR (KBr): 2921, 15.3, 1422, 1322, 1025, 956, 854, 745 cm−1
.
1H NMR (500 MHz, CDCl3): δ = 8.86–8.81 (d, J = 9.0 Hz, 1 H), 8.23 (s,
1 H), 8.19–8.08 (d, J = 6.9 Hz, 1 H), 8.04–7.81 (d, J = 9.1 Hz, 1 H), 7.90–
7.75 (m, 4 H), 7.73–7.60 (m, 3 H), 6.98–6.81 (t, J = 6.8 Hz, 1 H).
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374.0287.
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4-(Pyrido[2′,1′:2,3]imidazo[4,5-c]quinolin-6-yl)benzonitrile (6f)
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cm−1
.
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8.89 (m, 4 H), 7.64–7.57 (m, 1 H), 6.94–6.91 (t, J = 6.8 Hz, 1 H).
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142.8, 141.4, 136.9, 132.5, 130.8, 130.3, 130.2, 129.0, 126.1, 122.3,
117.45, 117.4, 112.8, 112.3, 91.8.
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ESI-MS: m/z = 321 [M + H]+.
HRMS (ESI): m/z calcd for C21H13N4: 321.1127; found: 321.1134.
Acknowledgment
We are grateful to SERB-DST, New Delhi, for financial support (grant
no. SB/EMEQ-075/2013). Ashok is thankful to UGC for the award of a
JRF.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588366.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–J