Convenient synthesis of 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines by sequential chemoselective Suzuki reaction followed by double C-N coupling

Article abstract of DOI:10.1016/j.tet.2018.01.010

A convenient and regioselective synthesis of two series of indolo[2,3-b]quinolines, namely 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines, has been developed. The synthesis, proceeds in moderate to high yields, involving chemoselective palladium catalyzed Suzuki reaction of 2,3-dihaloquinolines with 2-bromophenylboronic acid, followed by a double Buchwald-Hartwig C-N coupling.

Full text of DOI:10.1016/j.tet.2018.01.010

Accepted Manuscript
Convenient synthesis of 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines
by sequential chemoselective Suzuki reaction followed by double C-N coupling
Ghazwan Ali Salman, Sophie Janke, Ngo Nghia Pham, Peter Ehlers, Peter Langer
PII:
S0040-4020(18)30022-X
10.1016/j.tet.2018.01.010
TET 29225
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 October 2017
Revised Date: 3 January 2018
Accepted Date: 5 January 2018
Please cite this article as: Salman GA, Janke S, Pham NN, Ehlers P, Langer P, Convenient synthesis
of 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines by sequential chemoselective Suzuki
reaction followed by double C-N coupling, Tetrahedron (2018), doi: 10.1016/j.tet.2018.01.010.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

1
ACCEPTED MANUSCRIPT
Convenient
synthesis
of
10H-indolo[3,2-b]quinolines
and
6H-indolo[2,3-b]quinolines by sequential chemoselective Suzuki
reaction followed by double C-N coupling
Ghazwan Ali Salman,¶a,b Sophie Janke,¶a,c Ngo Nghia Pham,a,c,d Peter Ehlers,a,c Peter
Langer*a,c
a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany. E-mail:
peter.langer@uni-rostock.de; Fax: +49 381 498 6412; Tel: +49 381 498 6410
b Department of Chemistry, College of Science, University Al-Mustansiriyah, Palestine St, Mustansiriya,
Baghdad, Iraq
c Leibniz Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock,
Germany
d Faculty of Chemistry, VNU University of Science Hanoi (VNU-HUS), 19 Le Thanh Tong, Hoan Kiem, Hanoi,
Vietnam
¶ These authors contributed equally to this work
Abstract: A convenient and regioselective synthesis of two series of indolo[2,3-b]quinolines,
namely 10H-indolo[3,2-b]quinolines and 6H-indolo[2,3-b]quinolines, has been developed.
The synthesis, proceeds in moderate to high yields, involving chemoselective palladium
catalyzed Suzuki reaction of 2,3-dihaloquinolines with 2-bromophenylboronic acid, followed
by a double Buchwald-Hartwig C-N coupling.
Keywords: heterocycles; cyclization; palladium; regioselectivity
Graphical abstract:

2
ACCEPTED MANUSCRIPT
Introduction
Indolo[2,3-b]quinoline and indolo[3,2-b]quinoline are fused scaffolds of quinoline and indole
with biological importance. A number of derivatives have been discovered with antimalarial,
antitumor and antiplasmodial activities, to name but a few.[1] A reason for their biological
importance is their capability to form π-π stacking interactions in living systems.[2]
The synthesis of N-substituted indoloquinolines has gained increasing attention recently.[3]
Theoretically, the substitution can occur at two positions, namely at the quinoline and the
indole ring. The former is known for cryptolepine and neocryptolepine (Figure 1), which have
been found in several plants and have been known for antitumor and antimalarial activities.[4]
N
N
N
N
CH3
CH3
cryptolepine
neocryptolepine
Figure 1: Examples for N-substituted indolo[2,3-b]quinoline and indolo[3,2-b]quinoline
In comparison, N-substituted indolo[2,3-b]quinoline and indolo[3,2-b]quinoline have not been
found in nature and has been solely synthesized in the laboratory instead.[5] A number of these
compounds have been discovered with relevant biological activities (Figure 2).
N
N
antiinfective agent[6]
hemozoin inhibitor[7]

3
ACCEPTED MANUSCRIPT
cytotoxic DNA topoisomerase II inhibitor[8]
potential inducer of apoptosis[9]
Figure 2: Examples of synthesized N-substituted indoloquinolines with biological activities
In recent years, we and others studied palladium catalyzed syntheses and functionalization of
various heterocyclic systems.[10] In particular, we studied the combination of the
regioselective Suzuki reaction of polyhalogenated heterocycles with 2-bromophenylboronic
acid and subsequent double Buchwald-Hartwig reaction. Very recently, we reported the
synthesis of 11H-indolo[3,2-c]quinolines based on the employment of 3,4-dihaloquinolines as
starting material.[10a] In the present study, we report what is, to the best of our knowledge, a
new synthesis of indolo[2,3-b]quinolines and indolo[3,2-b]quinolines which is based on
chemoselective Suzuki reactions of 2,3-dihaloquinolines, followed by double C-N coupling
(Scheme 1). Our methodology is high yielding and allows for a selective synthesis of two
series of regioisomeric products based on the choice of the starting material.
Br
Br
Br
N
R
N
N
Cl
Br
N
Cl
Br
3a-h
1a
2a
R
H2N
R
N
(HO)2B
Br
I
N
N
N
1b
4a-n
2b
Scheme 1: Synthetic strategy of the present paper
Results and discussion
Our starting point was to identify suitable 2,3-dihaloquinolines as starting materials. 2-chloro-
3-bromoquinoline (1a) was prepared according to a previously reported procedure.[11] Product
1a was then transformed to 2-iodo-3-bromoquinoline (1b).[11] In case of the synthesis of 1b,
the addition of copper iodide was reported. In our hands, it was necessary to add copper
iodide. The Suzuki reaction of 1a with 2-bromophenylboronic acid afforded the desired
product 2a in 75% (Scheme 2). Changing the base (Cs2CO3, K2CO3), solvent (dioxane) or
catalyst led to no improvements of the yields. The reaction proceeded with excellent

4
ACCEPTED MANUSCRIPT
chemoselectivity in favor of position 3. The selectivity can be explained by the fact that
bromine is a better leaving group than chlorine. The leaving group ability obviously overrides
electronic factors. Usually, position 2 of the quinoline moiety is more reactive than position 3
in palladium catalyzed cross-coupling reactions, because it is electronically more deficient.
The reaction of 1b with 2-bromophenylboronic acid afforded the desired product 2b in 60%.
The reaction proceeded chemoselectively at position 2 which is electronically more deficient
than position 3 and also bears an iodine atom which is a better leaving group than bromine.
2,3-Dichloro- and 2,3-dibromoquinoline are less attractive starting materials, because of the
lack of reactivity of chlorine located at position 3 and a less pronounced difference of the
reactivity of positions 2 and 3 in these molecules.
Br
Br
(HO)2B
Pd(dppf)Cl2 10 mol%
Cs2CO3 2.0 equiv.
THF, 60 °C, 10 h
N
Cl
Br
Br
N
Cl
1a
2a (75%)
Br
Br
Br
I
(HO)2B
N
Pd(PPh3)4 5 mol%
CsF 2.0 equiv.
dioxane, 60 °C, 24 h
N
2b (60%)
1b
Scheme 2: Chemoselective Suzuki reaction of 2,3-dihaloquinolines 1a and 1b
Subsequently, we attempted to carry out the double carbon-nitrogen coupling reaction. For the
optimization study, 2a and p-toluidine were chosen as model substrates (Table 1). In the
presence of the catalyst Pd2dba3 with the base NaOtBu in toluene, different sterically
hindered, electron rich monodentate and bidentate ligands were applied which can be
successfully applied in Buchwald-Hartwig reactions. Among them, PtBu3ꢀHBF4 gave a very
high yield (95%) making further optimization of the reaction conditions (solvent, base
temperature) unnecessary. Furthermore, to rule out that the product is formed by nucleophilic
aromatic substitution we performed the reaction without employment of the palladium
catalyst under otherwise identical conditions. It was found that there is no formation of the
desired product without catalyst, even the substitution at the highly reactive position 2 of the

5
ACCEPTED MANUSCRIPT
quinoline by the amine was not observed, proofing the reaction undergoes a double
Buchwald-Hartwig C-N coupling.
Table 1: Optimization study for the double C-N coupling reaction of 2a and p-toluidine
Entry
Ligand
Xantphos
PtBu3·HBF4
SPhos
Yield
59
1
2
3
4
5
95
68
dppf
55
(S)-BINAP
68
Reaction conditions: 2a (0.10 mmol), p-toluidine (0.15 mmol), Pd2dba3 (0.005 mmol), ligand
(0.010 mmol for monodentate or 0.005 mmol for bidentate ligands), NaOtBu (0.24 mmol),
toluene (2.0 ml), 100 °C, 14 h. The yields are referred to as isolated
With the optimized conditions in hand, the scope of the reaction was examined (Table 2).
Various primary amines could be successfully applied, ranging from benzylic amines to
electronically rich and electronically poor aniline derivatives. Indoloquinolines 3a-h were
isolated in good to excellent yields. The yields of the products derived from electron-rich
anilines were generally higher than those of products derived from electron-poor amines.
Unfortunately, aliphatic amines such as n-hexyl- or allyl amine were not suitable and gave no
desired product.

6
ACCEPTED MANUSCRIPT
Table 2: Synthesis of indoloquinolines 3a-h
3a (95%)
3b (91%)
3c (89%)
3d (92%)
3e (83%)
3f (75%)
N
N
MeO
3g (68%)
3h (80%)
Reaction conditions: 2a (0.150 mmol), amine (0.225 mmol), Pd2dba3 (0.0075 mmol),
PtBu3ꢀHBF4 (0.015 mmol), NaOtBu (0.36 mmol), toluene (3.0 ml), 100 °C, 24 h. The yields
are referred as isolated.
The Suzuki reaction of 2b with various amines afforded 10H-indolo[3,2-b]quinolines 4a-n in
moderate to excellent yields (Table 3). These products are regioisomers of products 3a-h.

7
ACCEPTED MANUSCRIPT
Products 4a-f were prepared under identical conditions as reported above for products 3a-h.
However, application of bidentate ligand (S)-BINAP instead of PtBu3ꢀHBF4 for reactions of
electronically poor anilines and aliphatic amines led to higher yields. For example, using (S)-
BINAP instead of PtBu3ꢀHBF4, the yield of indoloquinoline 4g was improved from 51 to
95%. (S)-BINAP was previously reported as an ideal ligand for double C-N coupling reaction
for this type of amines.[12] Bidentate ligands accelerating the process of reductive elimination,
thereby minimizing ß-hydride elimination as a side reaction in case of aliphatic amines.
Table 3: Synthesis of indoloquinolines 4a-n
OMe
N
N
4a (74%)a
4b (75%) a
4c (50%) a
MeO
OMe
OMe
N
N
N
N
4d (45%) a
4e (39%) a
4f (54%) a
4g (95%) b
4h (87%) b
4i (89%) b

8
ACCEPTED MANUSCRIPT
4j (72%) b
4k (92%) b
4l (67%) b
4m (67%) b
4n (83%) b
a
Reaction conditions:
For 4a-f: 2b (0.150 mmol), amine (0.225 mmol), Pd2dba3
(0.0075 mmol), PtBu3ꢀHBF4 (0.015 mmol), NaOtBu (0.36 mmol), toluene (3 ml), 100 °C,
b
24 h. The yields are referred as isolated. For 4g-n: 2b (0.150 mmol), amine (0.225 mmol),
Pd2dba3 (0.0075 mmol), (S)-BINAP (0.0075 mmol), NaOtBu (0.36 mmol), toluene (3 ml),
100 °C, 24 h. The yields are referred as isolated.
Conclusion
In summary, two series of isomeric indoloquinolines were synthesized by regioselective
Suzuki reaction, followed by double C-N coupling. The difference in the reactivity of the
halogen atoms was crucial for the regioselectivity of the Suzuki reaction. For the double C-N
coupling, the monodentate ligand PtBu3ꢀHBF4 proved to be most efficient for both 2,3-
dihaloquinolines and electronically neutral and -rich anilines. For aliphatic and electronically
poor amines, (S)-BINAP gave better yields.
Experimental Section
General. If not otherwise indicated, chemicals used in this study were obtained from
commercial sources. No further purifications were done. Solvents, which were employed for

9
ACCEPTED MANUSCRIPT
work-up and purification processes, were distilled according to standard procedures. Silica gel
(particle sizes 0.006 - 0.043 mm) were used for column chromatography.
Micro-Hot-Stage Galen TM III Cambridge Instrument was used for melting point
determination. The results were not further corrected.
NMR samples were measured with Bruker AVANCE 250 II (built 2006), Bruker AVANCE
300 III (built 2007) and AVANCE 500 (built 2001). NMR-peaks were calibrated using
1
standard peaks of chloroform (7.260 ppm for H and at 77.160 ppm for 13C). For peak
descriptions, following abbreviations were used: s (singlet), d (doublet), t (triplet), dd (doublet
doublet), td (triplet doublet), dt (doublet triplet), ddd (double doublet doublet).
IR measurement was performed with Nicolet 380 FT-IR spectrometer using ATR sampling
technique. W (weak), m (medium) and s (strong) were used for peak description.
GC/MS-measurements were conducted with Finnigan MAT 95-XP device using HP-5
capillary column with helium carrier gas and electron ionization (EI) scan technique at 70 eV.
For HRMS, Finnigan MAT 95 XP device was employed. Only signals with deviation of less
than ±2 mDa were accounted as correct.
General experimental procedures
Synthesis of 3-(2-bromophenyl)-2-chloroquinoline (2a)
3-Bromo-2-chloroquinoline (1a) (3.0 mmol), (2-bromophenyl)boronic acid (3.6 mmol),
Pd(dppf)Cl2 (0.3 mmol) and Cs2CO3 (6.0 mmol) were subjected to a dried glass pressure tube.
After that, the tube was evacuated and backfilled three times with argon. The solids were
solved in 5.0 ml of dried THF, sealed with a Teflon cap before being heated to 60 °C for 10
hours. After 10 hours the reaction was completed (monitored by TLC). It was allowed to cool
to room temperature. The solvent was removed in vacuo. The crude oil was purified by
column chromatography (heptane).
Synthesis of 3-bromo-2-(2-bromophenyl)quinoline (2b)
3-Bromo-2-iodoquinoline (1b) (3.0 mmol), (2-bromophenyl)boronic acid (3.6 mmol),
Pd(PPh3)4 (0.3 mmol) and CsF (6.0 mmol) were subjected to a dried glass pressure tube. After
that, the tube was evacuated and backfilled three times with argon. The solids were solved in

10
ACCEPTED MANUSCRIPT
5.0 ml of dried dioxane, sealed with a Teflon cap before being heated to 60 °C for 24 hours.
After 24 hours, it was allowed to cool to room temperature. The solvent was removed in
vacuo. The crude oil was purified by column chromatography (heptane).
Synthesis of indoloquinolines 3a-h and indoloquinolines 4a-n
3-(2-Bromophenyl)-2-chloroquinoline (2a) or 3-bromo-2-(2-bromophenyl)quinoline (2b)
(0.15 mmol), amine (0.225 mmol), Pd2dba3 (0.0075 mmol), PtBu3ꢀHBF4 (0.015 mmol) or
(S)-BINAP (0.0075 mmol) and NaOtBu (0.36 mmol) were subjected to a dried glass pressure
tube. After that, the tube was evacuated and backfilled three times with argon and 3.0 ml of
dried toluene was added. The mixture was heated to 100 °C for 14 hours. After the reaction
completed (monitored by TLC), it was allowed to cool to room temperature. The solvent was
removed under reduced pressure. The crude oil was purified by column chromatography
(heptane/ethyl acetate).
3-(2-Bromophenyl)-2-chloroquinoline (2a)
Yellow solid, mp. 124 - 125 °C. 1H NMR (300 MHz, Chloroform-d) δ = 8.10 (d, 3J = 8.5 Hz,
3
4
1H, CHAr), 8.07 (s, 1H, CHAr), 7.85 (dd, J = 8.2 Hz, J = 1.6 Hz, 1H, CHAr), 7.78 (ddd,
3
4
3
4
3J = 8.5 Hz, J = 7.0 Hz, J = 1.5 Hz, 1H, CHAr), 7.72 (dd, J = 7.8 Hz, J = 1.6 Hz, 1H,
CHAr), 7.60 (ddd, 3J = 8.1 Hz, 3J = 7.0 Hz, 4J = 1.2 Hz, 1H, CHAr), 7.47 - 7.40 (m, 1H, CHAr),
7.38 - 7.29 (m, 2H, CHAr). 13C NMR (75 MHz, CDCl3) δ = 150.0 (CAr), 147.4 (CAr),
139.2 (CHAr), 138.7 (CAr), 134.3 (CAr), 132.9 (CHAr), 131.4 (CHAr), 130.9 (CHAr),
130.2 (CHAr), 128.6 (CHAr), 127.8 (CHAr), 127.5 (CHAr), 127.5 (CHAr), 127.0 (CAr),
124.1 (CAr). IR (ATR, cm-1): ṽ = 3055 (w), 2921 (w), 1560 (m), 1477 (m), 1362 (m),
1134 (m), 1095 (m), 1023 (m), 922 (m), 747 (s), 653 (m), 596 (m). MS (EI, 70 eV):
m/z (%) = 321 (17), 320 (10), 319 ([M]+, 63), 318 (12), 317 (49), 240 (34), 239 (19), 238
(100), 204 (16), 203 (96), 202 (28), 201 (27), 150 (11), 119 (13), 101 (18). HRMS (EI):
Calculated for C15H9N81BrCl [M]+ 318.95809 found 318.95836, calculated for
C15H9N81Br37Cl 320.95514 found 320.05587.
3-Bromo-2-(2-bromophenyl)quinoline (2b)
1
Yellow solid, mp. 123 - 125 °C. H NMR (300 MHz, Chloroform-d) δ = 8.51 (s, 1H, CHAr),
3
4
8.16 (dd, J = 8.6 Hz, J = 1.0 Hz, 1H, CHAr), 7.88 - 7.81 (m, 1H, CHAr), 7.78 (ddd,
3J = 8.5 Hz, 3J = 6.9 Hz, 4J = 1.5 Hz, 1H, CHAr), 7.70 (ddd, 3J = 8.0 Hz, 4J = 1.2 Hz,
5J = 0.5 Hz, 1H, CHAr), 7.62 (ddd, 3J = 8.2 Hz, 3J = 7.0 Hz, 4J = 1.2 Hz, 1H, CHAr),

11
ACCEPTED MANUSCRIPT
3
3
7.53 - 7.43 (m, 1H, CHAr), 7.43 - 7.39 (m, 1H, CHAr), 7.34 (ddd, J = 8.0 Hz, J = 7.0 Hz,
4J = 2.1 Hz, 1H, CHAr). 13C NMR (75 MHz, CDCl3) δ = 158.43 (CAr), 146.31 (CAr),
141.30 (CAr), 139.38 (CHAr), 132.80 (CHAr), 130.35 (CHAr), 130.35 (CHAr), 130.35 (CHAr),
129.70 (CHAr), 128.79 (CAr), 128.01 (CHAr), 127.57 (CHAr), 126.77 (CHAr), 122.71 (CAr),
118.11 (CAr). IR (ATR, cm-1): ṽ = 3056 (w), 2917 (w), 1573 (m), 1476 (m), 1432 (m),
1396 (m), 1367 (m), 1084 (m), 1034 (m), 1023 (m), 954 (m), 909 (m), 859 (m), 754 (s),
725 (m), 710 (m), 651 (m), 592 (m), 485 (m), 462 (m). MS (EI, 70 eV): m/z (%) = 365 (17),
363 ([M]+, 35), 361 (17), 285 (16), 284 (98), 283 (17), 282 (100), 204 (15), 203 (91), 202
(25), 201 (16), 176 (15), 175 (12), 142 (15), 141 (13), 102 (14), 101 (31), 75 (36), 74 (16), 51
(14), 50 (13). HRMS (EI): Calculated for C15H9Br2N 360.90963 found 360.90927, calculated
81
for C15H9Br81BrN 362.90758 found 362.90717, calculated for C15H9 Br2N 364.90553 found
364.90548.
6-(p-Tolyl)-6H-indolo[2,3-b]quinoline (3a)
1
White solid, mp. 135 - 137 °C. H NMR (300 MHz, Chloroform-d) δ = 8.79 (s, 1H, CHAr),
3
4
3
3
8.21 (dd, J = 7.7 Hz, J = 1.0 Hz, 1H, CHAr), 8.09 (dd, J = 8.4 Hz, J = 1.2 Hz, 1H, CHAr),
3
4
8.02 (dd, J = 8.3 Hz, J = 1.5 Hz, 1H, CHAr), 7.72 - 7.61 (m, 3H, CHAr), 7.53 - 7.42 (m, 5H,
CHAr), 7.38 - 7.34 (m, 1H, CHAr), 2.51 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3)
δ = 152.9 (CAr), 147.0 (CAr), 142.9 (CAr), 137.5 (CAr), 133.8 (CAr), 130.4 (2CHAr),
128.8 (CHAr), 128.4 (CHAr), 128.3 (CHAr), 128.2 (CHAr), 127.5 (CHAr), 127.4 (2CHAr),
124.7 (CAr), 123.4 (CHAr), 121.5 (CHAr), 120.9 (CAr), 120.8 (CHAr), 118.5 (CAr),
110.3 (CHAr), 21.5 (CH3).
IR (ATR, cm-1): ṽ = 3064 (w), 3033 (w), 2958 (w), 2918 (w),
2851 (w), 1602 (m), 1516 (m), 1460 (m), 1407 (m), 1226 (m), 897 (m), 740 (s), 596 (m),
475 (m). MS (EI, 70 eV): m/z (%) = 309 (22), 308 [M]+ (100), 307 (86), 292 (13), 190 (4),
140 (5), 29 (3). HRMS (ESI): Calculated for C22H16N2 [M+H]+ 309.13862 found 309.13878.
6-(4-Methoxyphenyl)-6H-indolo[2,3-b]quinoline (3b)
1
Pale yellow solid, mp. 182 - 184 °C. H NMR (300 MHz, Chloroform-d) δ = 8.80 (s, 1H,
CHAr), 8.21 (d, 3J = 7.3 Hz, 1H, CHAr), 8.10 (d, 3J = 8.5 Hz, 1H, CHAr), 8.03 (dd, 3J = 8.0 Hz,
4J = 1.6 Hz, 1H, CHAr), 7.73 - 7.60 (m, 3H, CHAr), 7.55 - 7.49 (m, 1H, CHAr), 7.49 - 7.43 (m,
3
3
1H, CHAr), 7.40 (d, J = 8.2 Hz, 1H, CHAr), 7.36 - 7.31 (m, 1H, CHAr), 7.16 (d, J = 8.9 Hz,
2H, CHAr), 3.94 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ = 159.1 (CAr), 143.2 (CAr),
129.1 (CAr), 129.0 (2CAr), 129.0 (2CHAr), 128.5 (CHAr), 128.3 (CHAr), 128.1 (CHAr),
127.8 (CHAr), 124.7 (CAr), 124.7 (CAr), 123.5 (CHAr), 121.5 (CHAr), 120.9 (CHAr),

12
ACCEPTED MANUSCRIPT
120.8 (CHAr), 118.6 (CAr), 115.1 (2CHAr), 110.3 (CHAr), 55.7 (OCH3). IR (ATR, cm-1):
ṽ = 3050 (w), 3033 (w), 3015 (w), 2955 (w), 2918 (w), 1602 (m), 1516 (m), 1461 (m),
1408 (m), 1227 (m), 1176 (m), 1024 (m), 742 (s), 598 (m), 476 (m). MS (EI, 70 eV):
m/z (%) = 325 (24), 324 [M]+ (100), 323 (29), 309 (33), 281 (16), 280 (13), 279 (13), 218
(10), 140 (12). HRMS (ESI): Calculated for C22H16N2O [M+H]+ 325.13354 found 325.13339.
6-(4-Ethoxyphenyl)-6H-indolo[2,3-b]quinoline (3c)
1
White solid, mp. 165 - 166 °C. H NMR (300 MHz, Chloroform-d) δ = 8.78 (s, 1H, CHAr),
3
4
3
8.20 (dt, J = 7.6 Hz, J = 1.0 Hz, 1H, CHAr), 8.10 (d, J = 8.6 Hz, 1H, CHAr), 8.02 (dd,
4
3
3
4
3J = 8.1 Hz, J = 1.5 Hz, 1H, CHAr), 7.68 (ddd, J = 8.5 Hz, J = 6.8 Hz, J = 1.5 Hz, 1H,
CHAr), 7.62 (d, 3J = 8.9 Hz, 2H, CHAr), 7.55 - 7.49 (m, 1H, CHAr), 7.49 - 7.44 (m, 1H, CHAr),
3
4
3
7.46 - 7.38 (m, 1H, CHAr), 7.34 (td, J = 7.5 Hz, J = 1.1 Hz, 1H, CHAr), 7.15 (d, J = 8.9 Hz,
3
3
2H, CHAr), 4.16 (q, J = 7.0 Hz, 2H, OCH2), 1.51 (t, J = 7.0 Hz, 3H, CH3). 13C NMR
(63 MHz, CDCl3) δ = 158.4 (CAr), 153.1 (CAr), 147.0 (CAr), 143.2 (CAr), 128.9 (CAr),
128.9 (2CHAr), 128.8 (CHAr), 128.8 (CAr), 128.4 (CHAr), 128.3 (CHAr), 128.2 (CHAr),
127.5 (CHAr), 124.7 (CAr), 123.4 (CHAr), 121.5 (CHAr), 120.8 (CHAr), 118.4 (CAr),
115.5 (2CHAr), 110.2 (CHAr), 63.9 (OCH2), 15.0 (CH3). IR (ATR, cm-1): ṽ = 3044 (w),
2981 (w), 2934 (w), 2876 (w), 2738 (w), 1603 (m), 1514 (m), 1473 (m), 1407 (m), 1224 (m),
1112 (m), 1041 (m), 742 (s), 587 (m). MS (EI, 70 eV): m/z (%) = 339 (24), 338 [M]+ (100),
310 (29), 309 (94), 281 (31), 280 (24), 279 (26), 218 (19), 29 (24). HRMS (ESI): Calculated
for C23H18N2O [M+H]+ 339.14919 found 339.14919.
6-(3,5-Dimethoxyphenyl)-6H-indolo[2,3-b]quinoline (3d)
1
White solid, mp. 143 - 145 °C. H NMR (300 MHz, Chloroform-d) δ = 8.79 (s, 1H, CHAr),
3
4
4
3
8.20 (ddd, J = 7.7 Hz, J = 1.3 Hz, J = 0.8 Hz, 1H, CHAr), 8.12 (d, J = 8.5 Hz, 1H, CHAr),
8.02 (ddd, 3J = 8.7 Hz, 4J = 1.5 Hz, 5J = 0.6 Hz, 1H, CHAr), 7.69 (ddd, 3J = 8.5 Hz,
4
3
4
5
3J = 6.8 Hz, J = 1.5 Hz, 1H, CHAr), 7.57 (ddd, J = 8.2 Hz, J = 1.5 Hz, J = 0.7 Hz, 1H,
3
CHAr), 7.55 - 7.50 (m, 1H, CHAr), 7.50 - 7.45 (m, 1H, CHAr), 7.35 (ddd, J = 7.6 Hz,
4
4
4
3J = 6.8 Hz, J = 1.5 Hz, 1H, CHAr), 6.95 (d, J = 2.3 Hz, 2H, CHAr), 6.61 (dd, J = 2.3 Hz,
1H, CHAr), 3.88 (s, 6H, 2xOCH3). 13C NMR (75 MHz, CDCl3) δ = 161.5 (2CArOCH3),
152.7 (CAr), 147.0 (CAr), 142.6 (CAr), 138.0 (CAr), 128.9 (CHAr), 128.4 (2CHAr), 128.3 (CHAr),
127.6 (CHAr), 124.8 (CAr), 123.6 (CHAr), 121.5 (CHAr), 121.0 (CAr), 121.0 (CHAr),
118.5 (CAr), 110.6 (CHAr), 105.8 (2CHAr), 100.2 (CHAr), 55.7 (2OCH3). IR (ATR, cm-1):
ṽ = 3055 (w), 2998 (w), 2931 (w), 2833 (w), 1593 (m), 1460 (m), 1405 (m), 1221 (m), 1193

13
ACCEPTED MANUSCRIPT
(m), 1148 (m), 1063 (m), 1016 (m), 782 (m), 731 (s), 685 (m), 574 (m), 473 (m).
MS (EI, 70 eV): m/z (%) = 355 (24), 354 [M]+ (100), 353 (83), 325 (14), 324 (31), 281 (14),
280 (10), 279 (12), 267 (22), 218 (23), 190 (10). HRMS (ESI): Calculated for C23H18N2O2
[M+H]+ 355.14410 found 355.14436.
6-(Naphthalen-1-yl)-6H-indolo[2,3-b]quinoline (3e)
Pale yellow solid, mp. 155 - 157 °C. 1H NMR (300 MHz, Chloroform-d) δ = 8.89 (d,
3
5
5J = 0.8 Hz, 1H, CHAr), 8.28 (dd, J = 7.3 Hz, J = 0.9 Hz, 1H, CHAr), 8.12 - 8.07 (m, 1H,
CHAr), 8.07 - 8.01 (m, 2H, CHAr), 7.99 (d, 3J = 8.7 Hz, 1H, CHAr), 7.79 - 7.69 (m, 2H, CHAr),
3
3
4
7.64 (ddd, J = 8.5 Hz, J = 6.8 Hz, J = 1.5 Hz, 1H, CHAr), 7.57 - 7.49 (m, 1H, CHAr), 7.46
3
4
3
(dt, J = 6.8 Hz, J = 1.3 Hz, 1H, CHAr), 7.46 - 7.25 (m, 4H, CHAr), 6.96 (dt, J = 8.1 Hz,
5J = 0.8 Hz, 1H, CHAr). 13C NMR (63 MHz, CDCl3) δ = 153.8 (CAr), 146.9 (CAr), 144.0 (CAr),
135.1 (CAr), 133.0 (CAr), 131.1 (CAr), 129.5 (CHAr), 129.0 (CHAr), 128.7 (CHAr),
128.5 (CHAr), 128.4 (CHAr), 128.2 (CHAr), 127.9 (CHAr), 127.6 (CHAr), 127.0 (CHAr),
126.7 (CHAr), 126.2 (CHAr), 124.7 (CAr), 123.7 (CHAr), 123.6 (CHAr), 122.2 (CAr),
121.5 (CHAr), 120.8 (CHAr), 118.6 (CAr), 110.8 (CHAr). IR (ATR, cm-1): ṽ = 3050 (w), 2957
(w), 2922 (m), 2851 (w), 1600 (m), 1468 (m), 1409 (m), 1224 (m), 1015 (m), 741 (s), 587
(m), 478 (m). MS (EI, 70 eV): m/z (%) = 345 (13), 344 [M]+ (61), 343 (100), 342 (31), 172
(11). HRMS (ESI): Calculated for C25H16N2 [M+H]+ 345.13862 found 345.13882.
6-(4-Fluorophenyl)-6H-indolo[2,3-b]quinoline (3f)
1
Pale yellow solid, mp. 166 - 167 °C. H NMR (300 MHz, Chloroform-d) δ = 8.79 (s, 1H,
CHAr), 8.21 (dt, 3J = 7.6 Hz, 4J = 0.9 Hz, 1H, CHAr), 8.08 (d, 3J = 8.5 Hz, 1H, CHAr), 8.03 (dd,
4
3J = 8.2 Hz, J = 1.5 Hz, 1H, CHAr), 7.77 - 7.65 (m, 3H, CHAr), 7.51 (m, 2H, CHAr), 7.42 (d,
13
3J = 8.1 Hz, 1H, CHAr), 7.40 - 7.30 (m, 3H, CHAr). C NMR (75 MHz, CDCl3) δ = 161.8 (d,
4
1JCF = 246.9 Hz, CFAr), 152.8 (CAr), 146.9 (CAr), 142.7 (CAr), 132.4 (d, JCF = 3.1 Hz, CAr),
3
129.4 (CHAr), 129.3 (d, JCF = 8.5 Hz, 2CHAr), 128.5 (CHAr), 128.3 (CHAr), 128.2 (CHAr),
127.7 (CHAr), 124.8 (CAr), 123.7 (CHAr), 121.6 (CHAr), 121.1 (CHAr), 121.0 (CAr),
2
118.4 (CAr), 116.7 (d, JCF = 22.8 Hz, 2CHAr), 110.1 (CHAr). IR (ATR, cm-1): ṽ = 3053 (w),
1604 (m), 1510 (m), 1461 (m), 1403 (m), 1220 (m), 1159 (m), 839 (m), 783 (m), 732 (s), 595
(m), 509 (m), 446 (m). MS (EI, 70 eV): m/z (%) = 313 (21), 312 [M]+ (99), 311 (100), 310
(19; 156 (12), 75 (16). HRMS (ESI): Calculated for C21H13FN2 [M+H]+ 313.11355 found
313.11384.
6-(4-Chlorophenyl)-6H-indolo[2,3-b]quinoline (3g)

14
ACCEPTED MANUSCRIPT
1
Pale yellow solid, mp. 193 - 195 °C. H NMR (300 MHz, Chloroform-d) δ = 8.77 (s, 1H,
3
4
3
4
CHAr), 8.20 (dd, J = 7.7 Hz, J = 0.9 Hz, 1H, CHAr), 8.08 (dd, J = 8.7 Hz, J = 1.2 Hz, 1H,
3
4
CHAr), 8.02 (dd, J = 8.2 Hz, J = 1.5 Hz, 1H, CHAr), 7.76 - 7.66 (m, 3H, CHAr), 7.65 - 7.57
(m, 2H, CHAr), 7.59 - 7.48 (m, 1H, CHAr), 7.51 - 7.43 (m, 2H, CHAr), 7.43 - 7.31 (m, 1H,
CHAr). 13C NMR (75 MHz, CDCl3) δ = 152.5 (CAr), 146.9 (CAr), 142.3 (CAr), 135.0 (CAr),
133.1 (CAr), 129.9 (2CHAr), 129.1 (CHAr), 128.7 (2CHAr), 128.5 (CHAr), 128.4 (CHAr),
128.2 (CHAr), 127.7 (CHAr), 124.9 (CAr), 123.7 (CHAr), 121.7 (CHAr), 121.3 (CHAr),
121.1 (CAr), 118.5 (CAr), 110.1 (CHAr). IR (ATR, cm-1): ṽ = 3421 (w), 3044 (w), 2959 (w),
2923 (w), 2852 (w), 1601 (m), 1496 (m), 1405 (m), 1223 (m), 1088 (m), 1014 (m), 740 (s),
586 (m). MS (EI, 70 eV): m/z (%) = 330 (33), 329 (45), 328 [M]+ (100), 327 (74), 293 (19),
292 (37), 291 (13), 146 (30), 75 (16). HRMS (ESI): Calculated for C21H13ClN2 [M+H]+
329.0840 found 329.08391, calculated for C21H13N2Cl [M]+ 328.07618 found 328.07527,
37
calculated for C21H13N2 Cl [M]+ 330.07323 found 330.07376.
6-(4-Methoxybenzyl)-6H-indolo[2,3-b]quinoline (3h)
1
Pale yellow solid, mp. 157 - 159 °C. H NMR (300 MHz, Chloroform-d) δ = 8.76 (s, 1H,
3
3
4
5
CHAr), 8.17 (d, J = 8.4 Hz, 1H, CHAr), 8.16 (ddd, J = 7.7 Hz, J = 1.2 Hz, J = 0.7 Hz, 1H,
3
4
3
3
CHAr), 8.03 (dd, J = 8.2 Hz, J = 1.3 Hz, 1H, CHAr), 7.73 (ddd, J = 8.5 Hz, J = 6.8 Hz,
4J = 1.5 Hz, 1H, CHAr), 7.53 - 7.48 (m, 1H, CHAr), 7.48 - 7.44 (m, 1H, CHAr), 7.34 (d,
3J = 8.2 Hz, 1H, CHAr), 7.35 - 7.27 (m, 2H, CHAr), 7.30 - 7.27 (m, 1H, CHAr), 6.80 (d,
13
3J = 8.6 Hz, 2H, CHAr), 5.72 (s, 2H, CH2), 3.74 (s, 3H, OCH3). C NMR (75 MHz, CDCl3)
δ = 159.1 (CAr), 142.2 (CAr), 129.5 (CAr), 129.0 (CHAr), 128.8 (2CHAr), 128.6 (CHAr), 128.2
(CHAr), 127.8 (CAr), 127.7 (CHAr), 124.5 (CAr), 123.2 (CHAr), 121.6 (CHAr), 121.1 (CHAr),
120.8 (CAr), 120.3 (CHAr), 120.2 (CAr), 118.4 (CAr), 114.2 (2CHAr), 109.9 (CHAr),
55.4 (OCH3), 44.7(CH2). IR (ATR, cm-1): ṽ = 3053 (w), 3033 (w), 3002 (w), 2957 (w), 2929
(w), 2838 (w), 2552 (w), 1605 (m), 1514 (m), 1467 (m), 1403 (m), 1244 (m), 1203 (m), 1116
(m), 1031 (m), 742 (s), 475 (m). MS (EI, 70 eV): m/z (%) = 339 (16), 338 [M]+ (67), 337 (14),
323 (10), 190 (11), 121 (100), 78 (10). HRMS (ESI): Calculated for C23H18N2O [M+H]+
339.14919 found 339.14898.
10-(p-Tolyl)-10H-indolo[3,2-b]quinoline (4a)
1
3
Yellow solid, mp. 132 - 133 °C. H NMR (250 MHz, Chloroform-d) δ = 8.63 (d, J = 7.4 Hz,
3
3
1H, CHAr), 8.37 (d, J = 8.7 Hz, 1H, CHAr), 7.97 (s, 1H, CHAr), 7.87 (dd, J = 8.2 Hz,
4J = 1.5 Hz, 1H, CHAr), 7.68 (ddd, 3J = 8.5 Hz, 3J = 6.8 Hz, 4J = 1.5 Hz, 1H, CHAr),

15
ACCEPTED MANUSCRIPT
13
7.63 - 7.34 (m, 8H, CHAr), 2.52 (s, 3H, CH3). C NMR (63 MHz, CDCl3) δ = 146.28 (CAr),
145.06 (CAr), 144.59 (CAr), 137.99 (CAr), 134.51 (CAr), 134.28 (CAr), 130.91 (2CHAr), 129.95
(CHAr), 129.27 (CHAr), 127.43 (CHAr), 127.10 (CAr), 126.87 (CHAr), 126.79 (2CHAr), 125.49
(CHAr), 122.31 (CHAr), 122.08 (CAr), 120.74 (CHAr), 112.52 (CHAr), 109.95 (CHAr), 21.42
(CH3). IR (ATR, cm-1): ṽ = 3052 (w), 2917 (w), 2853 (w), 1603 (m), 1514 (m), 1457 (m),
1325 (m), 1213 (m), 821 (m), 742 (s), 475 (m), 444 (m). MS (EI, 70 eV): m/z (%) = 309 (26),
308 ([M]+, 100), 307 (11), 91 (10), 89 (12), 65 (10). HRMS (EI): Calculated for C22H16N2
308.13080 found 308.13063.
10-(4-(tert-Butyl)phenyl)-10H-indolo[3,2-b]quinoline (4b)
1
3
Yellow oil. H NMR (300 MHz, Chloroform-d) δ = 8.69 (d, J = 7.8 Hz, 1H, CHAr), 8.42 (d,
3J = 8.5 Hz, 1H, CHAr), 8.05 (s, 1H, CHAr), 7.94 - 7.85 (m, 1H, CHAr), 7.75 - 7.63 (m, 3H,
CHAr), 7.60 (ddd, 3J = 8.4 Hz, 3J = 7.1 Hz, 4J = 1.3 Hz, 1H, CHAr), 7.57 - 7.51 (m, 3H, CHAr),
7.47 (dt, 3J = 8.3 Hz, 4J = 0.9 Hz, 1H, CHAr), 7.40 (ddd, 3J = 8.0 Hz, 3J = 7.1 Hz, 4J = 1.0 Hz,
13
1H, CHAr), 1.46 (s, 9H, 3xCH3). C NMR (75 MHz, CDCl3) δ = 151.17 (CAr), 145.11 (CAr),
134.32 (CAr), 134.25 (CAr), 130.22 (CHAr), 128.77 (CHAr), 127.9 (CAr), 127.45 (CHAr),
127.23 (2CHAr), 127.1 (CHAr), 127.03 (CHAr), 126.47 (2xCHAr), 125.63 (CHAr),
122.66 (CHAr), 122.4 (CAr), 120.89 (CHAr), 113.10 (CAr), 110.12 (CAr), 100.12 (CHAr),
35.03 (CtBu), 31.57 (3CH3). IR (ATR, cm-1): ṽ = 3048 (w), 2958 (w), 2902 (w), 2865 (w),
1604 (m), 1512 (m), 1457 (m), 1416 (m), 1391 (m), 1324 (m), 1217 (m), 847 (m), 740 (s),
562 (m), 475 (m). MS (EI, 70 eV): m/z (%) = 351 (25), 350 ([M]+, 100), 336 (17), 335 (76),
320 (14), 293 (11), 217 (27), 190 (20), 167 (11), 153 (28), 90 (12), 89 (21), 41 (15), 39 (11).
HRMS (ESI): Calculated for C25H22N2 [M+H]+ 351.18558 found 351.18577.
10-(4-Methoxyphenyl)-10H-indolo[3,2-b]quinoline (4c)
1
3
Yellow solid, mp. 128 - 129 °C. H NMR (250 MHz, Chloroform-d) δ = 8.52 (d, J = 7.4 Hz,
3
3
1H, CHAr), 8.27 (d, J = 8.6 Hz, 1H, CHAr), 7.79 (s, 1H, CHAr), 7.74 (dd, J = 8.6 Hz,
4J = 1.3 Hz, 1H, CHAr), 7.56 (ddd, 3J = 8.5 Hz, 3J = 6.8 Hz, 4J = 1.5 Hz, 1H, CHAr), 7.5 - 7.33
3
3
(m, 4H, CHAr), 7.27 (d, J = 7.6 Hz, 2H, CHAr), 7.04 (d, J = 8.9 Hz, 2H, CHAr), 3.81 (s, 3H,
OCH3). 13C NMR (63 MHz, CDCl3) δ = 159.23 (CAr), 146.04 (CAr), 145.33 (CAr), 144.39
(CAr), 134.54 (CAr), 129.96 (CHAr), 129.62 (CAr), 129.14 (CHAr), 128.44 (2xCHAr), 127.37
(CHAr), 127.05 (CAr), 126.74 (CHAr), 125.45 (CHAr), 122.29 (CHAr), 121.81 (CAr), 120.62
(CHAr), 115.46 (2xCHAr), 112.44 (CHAr), 109.82 (CHAr), 55.74 (OCH3). IR (ATR, cm-1):
ṽ = 3050 (w), 3004 (w), 2952 (w), 2930 (w), 2903 (w), 2833 (w), 1606 (m), 1511 (m), 1457

16
ACCEPTED MANUSCRIPT
(m), 1413 (m), 1325 (m), 1246 (m), 1215 (m), 1179 (m), 1032 (m), 832 (m), 742 (s), 580 (m),
479 (m). MS (EI, 70 eV): m/z (%) = 325 (29), 324 ([M]+, 100), 309 (32), 281 (22), 280 (26),
279 (26), 140 (11), 64 (10), 63 (13). HRMS (ESI): Calculated for C22H16N2O [M+H]+
325.13354 found 325.13388.
10-(3-Methoxyphenyl)-10H-indolo[3,2-b]quinoline (4d)
1
3
Yellow oil. H NMR (300 MHz, Chloroform-d) δ = 8.61 (d, J = 8.1 Hz, 1H, CHAr), 8.34 (d,
3J = 8.5 Hz, 1H, CHAr), 7.99 (s, 1H, CHAr), 7.81 (dd, 3J = 8.3 Hz, 4J = 1.4 Hz, 1H, CHAr), 7.62
3
3
4
(ddd, J = 8.5 Hz, J = 6.7 Hz, J = 1.5 Hz, 1H, CHAr), 7.56 - 7.38 (m, 4H, CHAr), 7.33 (ddd,
3
4
3J = 8.0 Hz, J = 7.1 Hz, J = 1.0 Hz, 1H, CHAr), 7.16 - 7.11 (m, 1H, CHAr), 7.08 (t,
3
4
4
4J = 2.2 Hz, 1H, CHAr), 6.99 (ddd, J = 8.4 Hz, J = 2.5 Hz, J = 0.9 Hz, 1H, CHAr), 3.82 (s,
3H, OCH3). 13C NMR (75 MHz, CDCl3) δ = 161.20 (CAr), 144.88 (CAr), 138.20 (CAr),
134.06 (CAr), 131.07 (CHAr), 130.33 (CHAr), 128.77 (CHAr), 127.50 (CHAr), 127.24 (CHAr),
127.00 (CHAr), 125.73 (CHAr), 122.75 (CHAr), 121.9 (CAr), 121.7 (CAr), 121.09 (CHAr),
119.11 (CHAr), 113.63 (CHAr), 113.3 (CAr), 113.2 (CAr), 112.73 (CHAr), 110.14 (CHAr),
55.74 (OCH3). IR (ATR, cm-1): ṽ = 3060 (w), 2924 (w), 1594 (m), 1497 (m), 1458 (m), 1388
(m), 1319 (m), 1254 (m), 1223 (m), 1212 (m), 1127 (m), 1035 (m), 785 (m), 730 (s), 675 (m),
475 (m), 444 (m). MS (EI, 70 eV): m/z (%) = 325 (23), 324 ([M]+, 100), 281 (18), 280 (17),
279 (16), 140 (10), 92 (11), 89 (10), 64 (11), 63 (12). HRMS (ESI): Calculated for C22H16N2O
[M+H]+ 325.13354 found 325.13396.
10-(2-Methoxyphenyl)-10H-indolo[3,2-b]quinoline (4e)
1
3
Yellow solid, mp. 198 - 199 °C. H NMR (300 MHz, Chloroform-d) δ = 8.58 (d, J = 7.7 Hz,
3
3
4
1H, CHAr), 8.33 (d, J = 8.5 Hz, 1H, CHAr), 7.78 (dd, J = 8.3 Hz, J = 1.4 Hz, 1H, CHAr),
3
3
4
7.67 (s, 1H, CHAr), 7.58 (ddd, J = 8.5 Hz, J = 6.8 Hz, J = 1.5 Hz, 1H, CHAr), 7.53 - 7.38
3
3
4
(m, 4H, CHAr), 7.29 (ddd, J = 7.9 Hz, J = 7.2 Hz, J = 0.9 Hz, 1H, CHAr), 7.19 - 7.06 (m,
3H, CHAr), 3.62 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ = 156.07 (CAr), 146.0 (CAr),
145.41 (CAr), 144.0 (CAr), 134.47 (CAr), 130.12 (CHAr), 129.98 (CHAr), 129.78 (CHAr),
128.90 (CHAr), 127.43 (CHAr), 127.12 (CAr), 126.79 (CHAr), 125.41 (CHAr), 125.09 (CAr),
122.38 (CHAr), 121.7 (CAr), 121.51 (CHAr), 120.59 (CHAr), 113.4 (CHAr), 113.00 (CHAr),
110.37 (CHAr), 55.81 (OCH3). IR (ATR, cm-1): ṽ = 3054 (w), 3015 (w), 2954 (w), 2930 (w),
2835 (w), 1606 (m), 1499 (m), 1460 (m), 1390 (m), 1325 (m), 1245 (m), 1217 (m), 1178 (m),
1018 (m), 762 (m), 738 (s), 596 (m), 477 (m). MS (EI, 70 eV): m/z (%) = 325 (19), 324

17
ACCEPTED MANUSCRIPT
([M]+, 100), 309 (45), 308 (10), 280 (15), 279 (25), 140 (11), 63 (11), 51 (13). HRMS (ESI):
Calculated for C22H16N2O [M+H]+ 325.13354 found 325.13387.
10-(3,5-Dimethoxyphenyl)-10H-indolo[3,2-b]quinoline (4f)
1
3
Yellow solid, mp. 182 - 183 °C. H NMR (300 MHz, Chloroform-d) δ = 8.65 (d, J = 7.8 Hz,
3
3
1H, CHAr), 8.39 (d, J = 8.6 Hz, 1H, CHAr), 8.09 (s, 1H, CHAr), 7.90 (dd, J = 8.3 Hz,
3
3
4J = 1.4 Hz, 1H, CHAr), 7.74 - 7.49 (m, 4H, CHAr), 7.40 (ddd, J = 7.9 Hz, J = 7.0 Hz,
4
4
4J = 1.2 Hz, 1H, CHAr), 6.78 (d, J = 2.2 Hz, 2H, CHAr), 6.62 (dd, J = 2.3 Hz, 1H, CHAr),
3.87 (s, 6H, 2xOCH3). 13C NMR (75 MHz, CDCl3) δ = 146.0 (CAr), 162.1 (2xCAr),
144.7 (CAr), 146.1 (CAr), 144.3 (CAr), 138.8 (CAr), 134.0 (CAr), 130.1 (CHAr), 129.0 (CAr),
128.9 (CHAr), 127.5 (CHAr), 127.1 (CHAr), 125.6 (CAr), 122.5 (CHAr), 122.1 (CHAr),
121.0 (CHAr), 113.1 (CHAr), 110.3 (CHAr), 106.8, 105.2 (CHAr), 100.0 (CHAr), 55.8
(2xOCH3). IR (ATR, cm-1): ṽ = 3053 (w), 2999 (w), 2928 (w), 2834 (w), 1594 (m), 1459 (m),
1408 (m), 1203 (m), 1152 (m), 1056 (m), 822 (m), 750 (m), 733 (s), 694 (m), 474 (m), 441
(m). MS (EI, 70 eV): m/z (%) = 355 (23), 354 ([M]+, 100), 295 (11), 279 (4), 267 (7), 177 (4),
140 (5), 89 (4), 79 (5), 63 (4). HRMS (ESI): Calculated for C23H18N2O2 [M+H]+ 355.14410
found 355.14440.
10-(4-Fluorophenyl)-10H-indolo[3,2-b]quinoline (4g)
Yellow solid, mp. 160 - 161 °C. 1H NMR (250 MHz, Chloroform-d) δ = 8.46 (dt, 3J = 7.8 Hz,
3
4
4
4J = 1.0 Hz, 1H, CHAr), 8.22 (dd, J = 8.6 Hz, J = 1.1 Hz, 1H, CHAr), 7.73 (d, J = 0.8 Hz,
3
4
3
3
1H, CHAr), 7.69 (dd, J = 8.3 Hz, J = 1.5 Hz, 1H, CHAr), 7.53 (ddd, J = 8.5 Hz, J = 6.8 Hz,
4J = 1.5 Hz, 1H, CHAr), 7.47 - 7.32 (m, 4H, CHAr), 7.27 - 7.15 (m, 4H, CHAr). 13C NMR
(63 MHz, CDCl3) δ = 161.82 (d, 1J = 248.1 Hz, CFAr), 146.07 (CAr), 144.83 (CAr),
4
144.59 (CAr), 134.08 (CAr), 133.05 (d, J = 3.1 Hz, CAr), 129.97 (CHAr), 129.20 (CHAr),
3
128.86 (d, J = 8.6 Hz, 2CHAr), 127.35 (CHAr), 126.94 (CAr), 126.86 (CHAr), 125.54 (CHAr),
2
122.26 (CHAr), 122.06 (CAr), 120.92 (CHAr), 117.25 (d, J = 22.8 Hz, 2CHAr), 112.21 (CHAr),
109.60 (CHAr). 19F NMR (282 MHz, CDCl3) δ = -112.80 (FCAr). IR (ATR, cm-1):
ṽ = 3043 (w), 1608 (m), 1510 (m), 1412 (m), 1325 (m), 1217 (m), 1135 (m), 840 (m), 808
(m), 734 (s), 575 (m), 509 (m), 477 (m). MS (EI, 70 eV): m/z (%) = 313 (25), 312 ([M]+,
100), 311 (19), 310 (12), 156 (10), 95 (11), 75 (16). HRMS (EI): Calculated for C21H13FN2
312.10573 found 312.10549.
10-(4-Chlorophenyl)-10H-indolo[3,2-b]quinoline (4h)

18
ACCEPTED MANUSCRIPT
Yellow solid, mp. 159 - 160 °C. 1H NMR (250 MHz, Chloroform-d) δ = 8.45 (dd,
3J = 8.4 Hz, 4J = 1.1 Hz, 1H, CHAr), 8.21 (d, 3J = 8.6 Hz, 1H, CHAr), 7.75 (s, 1H, CHAr), 7.68
3
4
(dd, J = 8.3 Hz, J = 1.4 Hz, 1H, CHAr), 7.58 - 7.32 (m, 7H, CHAr), 7.28 - 7.18 (m, 2H,
CHAr). 13C NMR (63 MHz, CDCl3) δ = 146.10 (CAr), 144.64 (CAr), 144.43 (CAr),
135.68 (CAr), 133.69 (CAr), 133.42 (CAr), 130.47 (2CHAr), 129.99 (CHAr), 129.19 (CHAr),
128.14 (2xCHAr), 127.37 (CHAr), 126.95 (CAr), 126.89 (CHAr), 125.59 (CHAr), 122.29 (CAr),
122.21 (CHAr), 121.09 (CHAr), 112.30 (CHAr), 109.63 (CHAr). IR (ATR, cm-1): ṽ = 3084 (w),
3054 (w), 2955 (w), 2928 (w), 2856 (w), 1606 (m), 1493 (m), 1472 (m), 1388 (m), 1325 (m),
1217 (m), 1086 (m), 831 (m), 742 (s), 477 (m). MS (EI, 70 eV): m/z (%) = 330 (32), 329 (24),
328 ([M]+, 100), 292 (19), 190 (18), 164 (13), 146 (24), 113 (13), 111 (25), 89 (28), 76 (12),
75 (46), 74 (11), 63 (19). HRMS (ESI): Calculated for C21H13ClN2 [M+H]+ 329.08401 found
329.08437, calculated for C21H1337ClN2 [M+H]+ 331.08177 found 331.08235.
10-Benzyl-10H-indolo[3,2-b]quinoline (4i)
1
3
Yellow solid, mp. 142 - 143 °C. H NMR (250 MHz, Chloroform-d) δ = 8.48 (d, J = 7.7 Hz,
3
4
3
4
1H, CHAr), 8.23 (dd, J = 8.6 Hz, J = 1.2 Hz, 1H, CHAr), 7.67 (dd, J = 8.3 Hz, J = 1.5 Hz,
3
3
4
1H, CHAr), 7.62 (s, 1H, CHAr), 7.51 (ddd, J = 8.5 Hz, J = 6.8 Hz, J = 1.5 Hz, 1H, CHAr),
7.42 (ddd, 3J = 8.3 Hz, 3J = 7.3 Hz, 4J = 1.3 Hz, 1H, CHAr), 7.34 (ddd, 3J = 8.1 Hz,
4
3J = 6.8 Hz, J = 1.2 Hz, 1H, CHAr), 7.24 - 7.06 (m, 5H, CHAr), 7.03 - 6.93 (m, 2H, CHAr),
13
5.24 (s, 2H, CH2). C NMR (63 MHz, CDCl3) δ = 145.92 (CAr), 144.61 (CAr), 144.09 (CAr),
136.41 (CAr), 133.67 (CAr), 129.95 (CHAr), 129.10 (CHAr), 128.95 (2xCHAr), 127.76 (CHAr),
127.31 (CHAr), 126.85 (CAr), 126.53 (CHAr), 126.41 (2xCHAr), 125.36 (CHAr), 122.27 (CHAr),
121.72 (CAr), 120.12 (CHAr), 111.46 (CHAr), 109.00 (CHAr), 46.61 (CH2). IR (ATR, cm-1):
ṽ = 3083 (w), 3057 (w), 3030 (w), 3004 (w), 2922 (w), 1604 (m), 1490 (m), 1474 (m), 1398
(m), 1343 (m), 1326 (m), 1200 (m), 1118 (m), 850 (m), 767 (m), 746 (s), 732 (m), 693 (m),
571 (m), 479 (m), 443 (m). MS (EI, 70 eV): m/z (%) = 309 (11), 308 ([M]+, 44), 217 (22),
190 (12), 91 (100), 89 (13), 65 (15). HRMS (EI): Calculated for C22H16N2 308.13080 found
308.13072.
10-(3-Methoxybenzyl)-10H-indolo[3,2-b]quinoline (4j)
Yellow solid, mp. 120 - 121 °C. 1H NMR (250 MHz, Chloroform-d) δ = 8.49 (dt, 3J = 7.8 Hz,
3
3
4
4J = 1.2 Hz, 1H, CHAr), 8.25 (d, J = 8.6 Hz, 1H, CHAr), 7.72 (dd, J = 8.3 Hz, J = 1.6 Hz,
3
3
4
1H, CHAr), 7.70 (s, 1H, CHAr), 7.54 (ddd, J = 8.5 Hz, J = 6.8 Hz, J = 1.5 Hz, 1H, CHAr),
3
3
4
7.50 - 7.42 (m, 1H, CHAr), 7.38 (ddd, J = 8.1 Hz, J = 6.8 Hz, J = 1.3 Hz, 1H, CHAr),

19
ACCEPTED MANUSCRIPT
3
7. - 7.18 (m, 2H, CHAr), 7.06 (t, J = 7.7 Hz, 1H, CHAr), 6.71 - 6.55 (m, 3H, CHAr), 5.29 (s,
13
2H, CH2), 3.55 (s, 3H, OCH3). C NMR (63 MHz, CDCl3) δ = 160.15 (CAr), 145.94 (CAr),
144.70 (CAr), 144.11 (CAr), 138.13 (CAr), 133.77 (CAr), 130.11 (CHAr), 130.02 (CHAr), 129.11
(CHAr), 127.35 (CHAr), 126.90 (CAr), 126.59 (CHAr), 125.41 (CHAr), 122.34 (CHAr), 121.73
(CAr), 120.19 (CHAr), 118.67 (CHAr), 112.75 (CHAr), 112.47 (CHAr), 111.56 (CHAr), 109.03
(CHAr), 55.24 (OCH3), 46.67 (CH2). IR (ATR, cm-1): ṽ = 3089 (w), 3040 (w), 2959 (w), 2930
(w), 2834 (w), 1606 (m), 1583 (m), 1474 (m), 1397 (m), 1333 (m), 1322 (m), 1270 (m), 1195
(m), 1148 (m), 1040 (m), 740 (s), 704 (m), 473 (m). MS (EI, 70 eV): m/z (%) = 339 (25), 338
([M]+, 100), 217 (11), 121 (67), 91 (12). HRMS (ESI): Calculated for C23H18N2O [M+H]+
339.14919 found 339.14947.
10-Allyl-10H-indolo[3,2-b]quinoline (4k)
1
3
4
Yellow oil. H NMR (250 MHz, Chloroform-d) δ = 8.46 (dt, J = 7.7 Hz, J = 1.0 Hz, 1H,
3
4
3
4
CHAr), 8.23 (dd, J = 8.6 Hz, J = 1.1 Hz, 1H, CHAr), 7.75 (dd, J = 8.2 Hz, J = 1.5 Hz, 1H,
CHAr), 7.67 (s, 1H, CHAr), 7.61 - 7.33 (m, 3H, CHAr), 7.26 - 7.11 (m, 2H, CHAr), 5.84 (ddt,
3
3
3
2
3J = 17.0 Hz, J = 10.0 Hz, J = 4.8 Hz, 1H, CH-allyl), 5.04 (dd, J = 10.3 Hz, J = 1.3 Hz, 1H,
3
2
3
CH-allyl (cis)), 4.92 (dd, J = 17.2 Hz, J = 1.5 Hz, 1H, CH-allyl (trans)), 4.67 (dt, J = 4.9 Hz,
2J = 1.8 Hz, 2H, CH2-allyl). 13C NMR (63 MHz, CDCl3) δ = 145.94 (CAr), 144.39 (CAr), 144.03
(CAr), 133.43 (CAr), 131.66 (CHAr), 129.81 (CHAr), 129.12 (CHAr), 127.29 (CHAr), 126.85
(CAr), 126.44 (CHAr), 125.33 (CHAr), 122.22 (CHAr), 121.65 (CAr), 119.94 (CHAr), 117.24
(CH=CH2), 111.32 (CHAr), 108.90 (CHAr), 45.31 (CH2-allyl). IR (ATR, cm-1): ṽ = 3375 (w),
3054 (w), 2980 (w), 2918 (w), 2745 (w), 2602 (w), 2495 (w), 1605 (m), 1474 (m), 1397 (m),
1326 (m), 1201 (m), 1120 (m), 744 (s), 599 (m), 479 (m). MS (EI, 70 eV): m/z (%) = 259
(19), 258 ([M]+, 100), 257 (18), 231 (22), 218 (13), 217 (77), 216 (11), 190 (51), 89 (18).
HRMS (EI): Calculated for C18H14N2 258.11515 found 258.11507.
10-Cyclopentyl-10H-indolo[3,2-b]quinoline (4l)
1
3
Yellow solid, mp. 132 - 133 °C. H NMR (250 MHz, Chloroform-d) δ = 8.50 (d, J = 7.8 Hz,
3
4
1H, CHAr), 8.24 (dd, J = 8.5 Hz, J = 1.2 Hz, 1H, CHAr), 7.91 (s, 1H, CHAr), 7.84 (dd,
4
3
3J = 8.2 Hz, J = 1.5 Hz, 1H, CHAr), 7.61 - 7.34 (m, 4H, CHAr), 7.21 (ddd, J = 7.9 Hz,
4
3
3J = 7.1 Hz, J = 1.0 Hz, 1H, CHAr), 5.03 (p, J = 8.8 Hz, 1H, CH-cyclopentyl), 2.37 - 2.17 (m,
2H, CH2), 2.15 - 1.89 (m, 4H, 2xCH2), 1.87 - 1.62 (m, 2H, CH2). 13C NMR (63 MHz, CDCl3)
δ = 146.28 (CAr), 143.94 (CAr), 143.67 (CAr), 132.65 (CAr), 129.55 (CHAr), 129.05 (CHAr),
127.35 (CHAr), 126.63 (CAr), 126.39 (CHAr), 125.32 (CHAr), 122.43 (CHAr), 122.08 (CAr),

20
ACCEPTED MANUSCRIPT
119.56 (CHAr), 112.39 (CHAr), 109.86 (CHAr), 56.07 (CHcyclopentyl), 28.88 (2xCH2), 25.37
(2xCH2). IR (ATR, cm-1): ṽ = 3053 (w), 2951 (w), 2869 (w), 1600 (m), 1473 (m), 1455 (m),
1407 (m), 1321 (m), 1209 (m), 1139 (m), 1119 (m), 742 (s), 595 (m), 478 (m), 448 (m). MS
(EI, 70 eV): m/z (%) = 287 (11), 286 ([M]+, 67), 257 (14), 256 (11), 219 (17), 218 (100), 117
(39), 216 (28), 190 (30), 89 (17), 69 (44), 67 (10), 41 (56), 39 (22). HRMS (ESI): Calculated
for C20H18N2 [M+H]+ 287.15428 found 287.15404.
10-Hexyl-10H-indolo[3,2-b]quinoline (4m)
Yellow oil. 1H NMR (250 MHz, Chloroform-d) δ = 8.59 (d, 3J = 7.8 Hz, 1H, CHAr), 8.36 (dd,
4
3
4
3J = 8.5 Hz, J = 1.2 Hz, 1H, CHAr), 7.93 (dd, J = 8.2 Hz, J = 1.5 Hz, 1H, CHAr), 7.87 (s,
1H, CHAr), 7.64 (tdd, 3J = 8.5 Hz, 3J = 6.9 Hz, 4J = 1.4 Hz, 2H, CHAr), 7.53 (ddd, 3J = 8.1 Hz,
3J = 6.8 Hz, 4J = 1.3 Hz, 1H, CHAr), 7.42 - 7.29 (m, 2H, CHAr), 4.24 (t, 3J = 7.2 Hz, 2H, CH2),
1.98 - 1.78 (m, 2H, CH2), 1.51 - 1.13 (m, 6H, CH2), 0.97 - 0.76 (m, 3H, CH3). 13C NMR
(63 MHz, CDCl3) δ = 145.94 (CAr), 144.53 (CAr), 143.85 (CAr), 133.60 (CAr), 129.79 (CHAr),
129.14 (CHAr), 127.26 (CHAr), 126.88 (CAr), 126.34 (CHAr), 125.32 (CHAr), 122.34 (CHAr),
121.55 (CAr), 119.67 (CHAr), 111.08 (CHAr), 108.80 (CHAr), 43.28 (CH2), 31.65 (CH2), 28.63
(CH2), 27.06 (CH2), 22.62 (CH2), 14.09 (CH3). IR (ATR, cm-1): ṽ = 3055 (w), 2953 (w), 2925
(w), 2854 (w), 1604 (m), 1474 (m), 1399 (m), 1342 (m), 1325 (m), 1193 (m), 1118 (m), 743
(s), 478 (m). MS (EI, 70 eV): m/z (%) = 302 ([M]+, 46), 232 (17), 231 (100). HRMS (ESI):
Calculated for C21H22N2 [M+H]+ 303.18558 found 303.18578.
10-Heptyl-10H-indolo[3,2-b]quinoline (4n)
1
3
4
Yellow oil. H NMR (250 MHz, Chloroform-d) δ = 8.45 (dt, J = 7.7 Hz, J = 1.0 Hz, 1H,
3
4
3
4
CHAr), 8.23 (dd, J = 8.5 Hz, J = 1.2 Hz, 1H, CHAr), 7.77 (dd, J = 8.3 Hz, J = 1.5 Hz, 1H,
CHAr), 7.69 (s, 1H, CHAr), 7.56 - 7.50 (m, 1H, CHAr), 7.50 - 7.44 (m, 1H, CHAr), 7.38 (ddd,
3
4
3J = 8.1 Hz, J = 6.8 Hz, J = 1.3 Hz, 1H, CHAr), 7.25 - 7.11 (m, 2H, CHAr), 4.05 (t,
3J = 7.2 Hz, 2H, CH2), 1.79 - 1.62 (m, 2H, CH2), 1.29 - 1.04 (m, 8H, CH2), 0.84 - 0.66 (m,
13
3H, CH3). C NMR (63 MHz, CDCl3) δ = 145.98 (CAr), 144.46 (CAr), 143.92 (CAr), 133.53
(CAr), 129.69 (CHAr), 129.20 (CHAr), 127.23 (CHAr), 126.86 (CAr), 126.24 (CHAr), 125.24
(CHAr), 122.22 (CHAr), 121.60 (CAr), 119.59 (CHAr), 110.91 (CHAr), 108.75 (CHAr), 43.18
(CH2), 31.76 (CH2), 29.11 (CH2), 28.62 (CH2), 27.32 (CH2), 22.64 (CH2), 14.11 (CH3).
IR (ATR, cm-1): ṽ = 3054 (w), 2952 (w), 2924 (w), 2853 (w), 1605 (m), 1474 (m), 1399 (m),
1342 (m), 1325 (m), 1118 (m), 742 (s), 477 (m). MS (EI, 70 eV): m/z (%) = 316 ([M]+, 36),

21
ACCEPTED MANUSCRIPT
232 (19), 231 (100), 43 (14), 41 (17), 29 (14). HRMS (ESI): Calculated for C22H24N2 [M+H]+
317.20123 found 317.20139.
References
[1]
(a) Ou T.-M., Lu Y.-J., Zhang C., Huang Z.-S., Wang X.-D., Tan J.-H., Chen Y., Ma
D.-L., Wong K.-Y., Tang J. C.-O., Chan A. S.-C., Gu L.-Q. J. Med. Chem. 2007;50:
1465-1474; (b) Dai J., Carver M., Hurley L. H., Yang D. J. Am. Chem. Soc. 2011;
133:17673-17680; (c) Caprio V., Guyen B., Opoku-Boahen Y., Mann J., Gowan S.
M., Kelland L. M., Read M. A., Neidle S. Bioorg. Med. Chem. Lett. 2000;10:2063-
2066; (d) Parvatkar P. T., Ajay A. K., Bhat M. K., Parameswaran P. S., Tilve S. G.
Med. Chem. Res. 2013;22:88-93.
[2]
(a) Lavrado J., Ohnmacht S. A., Correia I., Leitao C., Pisco S., Gunaratnam M.,
Moreira R., Neidle S., dos Santos D. J. V. A., Paulo A. Chem. Med. Chem.
2015;10:836-849; (b) Kumar S., Bawa S., Gupta H. Mini Rev. Med. Chem.
2009;9:1648-1654.
[3]
[4]
Fan L., Liu M., Ye Y., Yin G. Org. Lett. 2017;19:186-189.
(a) Kirby G. C., Paine A., Warhurst D. C., Noamese B. K., Phillipson J. D. Phytother.
Res. 1995;9:359-363; (b) Arzel E., Rocca P., Grellier P., Labaeied M., Frappier F.,
Gueritte F., Gaspard C., Marsais F., Godard A., Queguiner G. J. Med. Chem.
2001;44:949-960; (c) Aroonkit P., Thongsornkleeb C., Tummatorn J., Krajangsri S.,
Mungthin M., Ruchirawat S. Eur. J. Med. Chem. 2015;94:56-62; (d) Van Miert S.,
Hostyn S., Maes B. U. W., Cimanga K., Brun R., Kaiser M., Matyus P., Dommisse R.,
Lemiere G., Vlietinck A., Pieters L. J. Nat. Prod. 2005;68:674-677.
[5]
(a) Shi L., Wang B. Org. Lett. 2016;18:2820-2823; (b) Letessier J., Detert H. Synthesis
2012;44:290-296; (c) Mazu T. K., Etukala J. R., Zhu X. Y., Jacob M. R., Khan S. I.,
Walker L. A., Ablordeppey S. Y. Bioorg. Med. Chem. 2011;19:524-533; (d) Liu B.,
Gao H., Yu Y., Wu W., Jiang H. J. Org. Chem. 2013;78:10319–10328.
Mardenborough L. G., Zhu X. Y., Fan P., Jacob M. R., Khan S. I., Walker L. A.,
Ablordeppey S. Y. Bioorg. Med. Chem. 2005;13:3955-3963.
[6]
[7]
Figueiras M., Coelho L., Wicht K. J., Santos S. A., Lavrado J., Gut J., Rosenthal P. J.,
Nogueira F., Egan T. J., Moreira R., Paulo A. Bioorg. Med. Chem. 2015;23:1530-
1539.

22
ACCEPTED MANUSCRIPT
[8]
[9]
Luniewski W., Wietrzyk J., Godlewska J., Switalska M., Piskozub M., Peczynska-
Czoch W., Kaczmarek L. Bioorg. Med. Chem. Lett. 2012;22:6103-6107.
Sunke R., Kumar V., Ashfaq M. A., Yellanki S., Medisetti R., Kulkarni P., Shivaji
Ramarao E. V. V., Ehtesham N. Z., Pal M. RSC Adv. 2015;5:44722-44727.
[10] (a) Fairlamb I. J. S. Chem. Soc. Rev. 2007;36:1036-1045. (b) Schröter S., Stock C.,
Bach T. Tetrahedron 2005;61:2245-2267. (c) Rossi R., Bellina F., Lessi M. Adv.
Synth. Catal. 2012;354:1181-1255. (d) Pham N. N., Janke S., Salman G. A., Dang T.
T., Le T. S., Spannenberg A., Ehlers P., Langer P. Eur. J. Org. Chem. 2017:5554–
5565. (e) Ohlendorf L., Velandia J. E. D., Kónya K., Ehlers P., Villinger A., Langer P.
Adv. Synth. Catal. 2017;359:1758–1769. (f) Salman G. A., Pham N. N., Ngo T. N.,
Ehlers P., Villinger A., Langer P. Adv. Synth. Catal. 2017;359:1402-1406. (d) Pham
N. N., Salman G. A., Ponce M. B., Dang T. T., Spannenberg A., Ehlers P., Langer P.
Eur. J. Org. Chem. 2017:3865–3873.(e) Hung T. Q., Hancker S., Villinger A.,
Lochbrunner S., Dang T. T., Friedrich A., Breitsprecher W., Langer P. Org. Biomol.
Chem. 2015;13:583-591.
[11] Bogányi v, Kámán J. Tetrahedron 2013;69:9512-9519.
[12] Nozaki K., Takahashi K., Nakano K., Hiyama T., Tang H.-Z., Fujiki M., Yamaguchi
S., Tamao K. Angew. Chem., Int. Ed. Engl. 2003;42:2051-2053.