Transition-metal-free insertion of benzyl bromides into 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde: One-pot switchable syntheses of benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-arylquinolin-4-ones mediated by base

Article abstract of DOI:10.1016/j.tet.2019.03.058

A transition-metal-free insertion of benzyl group between aldehyde and imidazole of 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde was achieved for the first time. Two diverse sets of quinolin-4-one derivatives: benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones (2) and 3-arylquinolin-4-ones (3) were synthesized based on identical starting materials 2-(1H-benzo[d]imidazol-1-yl)benzaldehydes (1) and benzyl bromides. In the preparations, two key intermediates I and II were involved and might be synthesized in situ through the reaction of an intra-Breslow intermediate with benzyl bromide via an enol attack in the presence of base or a NHC-based enamine attack in the absence of base, respectively, in which the intra-Breslow intermediate might function as a nucleophilic reagent by following two novel different pathways.

Full text of DOI:10.1016/j.tet.2019.03.058

Accepted Manuscript
Transition-metal-free insertion of benzyl bromides into 2-(1H-
benzo[d]imidazol-1-yl)benzaldehyde: One-pot switchable syntheses of
benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-arylquinolin-4-ones mediated by
base
Huayan Xu, Liang Xu, Xiaowei Luo, Junfeng Wang, Xuefeng Zhou, Bin Yang, Ding Li,
Zaigang Luo, Yonghong Liu, Shengrong Liao
PII:
S0040-4020(19)30387-4
https://doi.org/10.1016/j.tet.2019.03.058
TET 30244
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 February 2019
Revised Date: 23 March 2019
Accepted Date: 29 March 2019
Please cite this article as: Xu H, Xu L, Luo X, Wang J, Zhou X, Yang B, Li D, Luo Z, Liu Y, Liao S,
Transition-metal-free insertion of benzyl bromides into 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde: One-
pot switchable syntheses of benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-arylquinolin-4-ones
mediated by base, Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.03.058.
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Transition-metal-free insertion of benzyl
bromides into
2-(1H-benzo[d]imidazol-1-yl)benzaldehyde:
one-pot switchable syntheses of
benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones
and 3-arylquinolin-4-ones mediated by base
Huayan Xua, Liang Xub, Xiaowei Luob, Junfeng Wangb, Xuefeng Zhoub, Bin Yangb, Ding Lic,*, Zaigang Luoa,*,
Yonghong Liub,*, Shengrong Liaob,*
aCollege of Chemical Engineering, Anhui University of Science and Technology, Huainan 232001, P. R. China
bCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine
Materia Medica, Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese
Academy of Sciences, Guangzhou 510301, China
cSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Transition-metal-free insertion of benzyl bromides into 2-(1H-benzo[d]imidazol-1-
yl)benzaldehyde: one-pot switchable syntheses of benzo[4,5]imidazo[1,2-a]quinolin-
5(7H)-ones and 3-arylquinolin-4-ones mediated by base
Huayan Xua, Liang Xub, Xiaowei Luob, Junfeng Wangb, Xuefeng Zhoub, Bin Yangb, Ding Lic,*, Zaigang
Luoa,*, Yonghong Liub,*, Shengrong Liaob,*
aCollege of Chemical Engineering, Anhui University of Science and Technology, Huainan 232001, P. R. China
bCAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Center for Marine
Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
cSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A transition-metal-free insertion of benzyl group between aldehyde and imidazole of 2-(1H-
benzo[d]imidazol-1-yl)benzaldehyde was achieved for the first time. Two diverse sets of
quinolin-4-one derivatives: benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones (2) and 3-
arylquinolin-4-ones (3) were synthesized based on identical starting materials 2-(1H-
benzo[d]imidazol-1-yl)benzaldehydes (1) and benzyl bromides. In the preparations, two key
intermediates I and II were involved and might be synthesized in situ through the reaction of an
intra-Breslow intermediate with benzyl bromide via an enol attack in the presence of base or a
NHC-based enamine attack in the absence of base, respectively, in which the intra-Breslow
intermediate might function as a nucleophilic reagent by following two novel different
pathways.
Available online
Keywords:
Quinolin-4-one derivatives
One-pot strategy
Intra-Breslow intermediate
Enol attack
NHC-based enamine attack
2009 Elsevier Ltd. All rights reserved.
1. Introduction
synthesis of 3-arylquinolin-4-ones mainly relies on the known
classical reaction Conrad-Limpach2-3,5,9 (Scheme 1, B) or its
variant cyclizations6,10. In recent years, the transition-metal
catalyzed C-C bond couplings11 or the methods of combining the
couplings with the Conrad-Limpach cyclization3c-e (Scheme 1, B)
have been used increasingly. Besides, Meinwald rearrangement
from the epoxide substrate could also conveniently deliver 3-
arylquinolin-4-ones with acid (TfOH or BF3) catalysis12. Indeed,
these elegant methods can furnish the target compounds
smoothly; however, they generally suffer from some limitations
including: 1) tedious operations for the synthesis of complex
substrates, and 2) expensive transition-metal catalyst recruited in
the reaction. Therefore, development of novel strategies for their
rapid, efficient, and economical preparations still attracts high
interest.
The benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-
arylquinolin-4-ones are two kinds of significant quinolin-4-one
derivatives and possess a variety of fascinating biological
activities. For example, the former have been investigated as cell
proliferation inhibitors, or quadruplex nucleotide stabilizers in
DNA1. The latter have been extensively studied as anticancer2
and antimalarial3 agents, carbonic anhydrase4 and efflux pumps
inhibitors5, or human estrogen receptor activators6. Due to these
diverse and significant pharmaceutical applications, a number of
synthetic methods have been developed. The general route to the
benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones is through
a
sequential reactions of 2-fluorobenzoyl chlorides with potassium
3-ethoxy-3-oxopropanoate, CS2, and 1,2-diaminobenzenes,
respectively1,7 (Scheme 1, A1). This route is feasible but requires
The imidazolin-2-ylidene-based NHC organocatalysis can
avoid multistep operations in constructing numerous complicated
organic molecules with high efficiency13. In our ongoing research
project of exploring anticancer agents, we synthesized 7-benzyl-
9,10-dimethyl-6-phenylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2a) by heating 2-(5,6-dimethyl-1H-benzo[d]imidazol-1-
yl)benzaldehyde (1a) with benzyl bromide in the presence of
base via a one-pot operation, and 1-(2-(benzylamino)-4,5-
dimethylphenyl)-3-phenylquinolin-4(1H)-one (3a) by heating the
multistep process thus is laborious. Then
a
direct
cyclocondensation (Scheme 1, A2) between 2-halobenzoyl
chlorides and 2-(1H-benzo[d]imidazol-2-yl)acetonitriles has been
employed but requires strong base (tBuOK) and electron
withdrawing substitution (CN)8. Similarly, the strategies for the
Corresponding author. E-mail address: ljrss@126.com (S. L.);
yonghongliu@scsio.ac.cn (Y. L.); luozi139@163.com (Z. L.);
liding@mail.sysu.edu.cn (D. L.)

2
Tetrahedron
above two reaction partners firstly in toluene followed with
(Table 1, entry 10), however, other organic bases such as Et N,
ACCEPTED MANUSCRIPT
3
adjusting the reaction mixture to basic condition (Scheme 1, C).
During these processes, we found that a novel unusual insertion
of benzyl group between aldehyde and imidazole of 2-(1H-
benzo[d]imidazol-1-yl)benzaldehydes has been realized for the
first time, and a benzo[d]imidazolyl intra-Breslow intermediate
could function as nucleophilic reagent to react with benzyl
bromide via an enol attack or a NHC-based enamine attack,
respectively, with subsequent rearrangement to form new C(sp2)-
C(sp2)-C(sp2) bond. This is different from that reported in
previous studies, which had benzo[d]imidazolium or
imidazolium salt (NHC precursor) used directly as nucleophilic
reagent14. This one-pot strategy can be employed to efficiently
build bioactive N-heteroaromatic compounds, while avoiding the
usage of transition-metal catalyst and multistep protocols.
Herein, we report these two novel insertion modes for the facile
preparation of compounds 2 and 3 in detail.
DBU were avoided because of their reactions with benzyl
bromide. Other solvents (Table 1, entries 11-15), and lower
(Table 1, entry 16) or higher reaction temperature (Table 1, entry
17) showed varied low efficiencies. Changes of the molar ratio
for Na2CO3 (Table 1, entries 18-19) or benzyl bromide (Table 1,
entries 20-21) resulted in lower yields. Surprisingly, benzyl
chloride (Table 1, entry 22) as an electrophile instead of bromide
caused
a significantly decreased yield (4%). Under O2
atmosphere (Table 1, entry 23) moderate yield (48%) was
accomplished, whereas under N2 atmosphere (Table 1, entry 24)
relatively low yield (18%) was obtained. Using other oxidants
such as DDQ, Na2S2O8, or Oxone (Table 1, entry 25), no any
product was found. Thus, the optimal conditions were obtained
for molar ratio of 1a : benzyl bromide : Na2CO3 = 1 : 6 : 2, and
the reaction mixture should be heated at 90 ˚C for 18 h using
sulfolane (0.4 M) as the solvent.
Table 1. Optimization of conditions for the synthesis of
compound 2aa
Base
Temp.
(˚C)
90
Yield(%)
Entry
Solvent
(equiv.)
2ab
71(67c)
40
1
Na2CO3 (2.0)
Cs2CO3 (2.0)
CsHCO3 (2.0)
K2CO3 (2.0)
NaOtBu (2.0)
NaOH (2.0)
NaOAc (2.0)
NaHCO3 (2.0)
K3PO3 (2.0)
DIPEA (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
DMF
2d
3e
4
90
90
31
90
1
5
90
1
6
90
12
7
90
20
8
90
trace
0
9
90
10
11
12
13
90
38
90
27
Scheme 1. Routes to benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
ones (2) and 3-arylquinolin-4-ones (3).
DMSO
90
46
NMO
90
21
Diphenyl
ether
2. Results and discussion
14
Na2CO3 (2.0)
90
0
15
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (1.0)
Na2CO3 (4.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Na2CO3 (2.0)
Toluene
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
Sulfolane
90
60
120
90
90
90
90
90
90
90
90
1
16
8
17
60
30
63
62
65
4
18
19
20f
21g
22h
23i
24j
25k
48
18
0
Scheme 2. Synthesis of compound 1.
aThe reactions were performed on a 0.1 mmol scale under air
The substrates (compound 1) used in these two one-pot
strategies were synthesized readily in 17-70% yields (Scheme 2).
Based on the discovery of the reaction for synthesis of compound
2a, compound 1a and benzyl bromide were selected as the model
substrates (Table 1). A series of bases were examined in order to
improve the yield (Table 1, entries 1-10), and Na2CO3 was found
to be the best in 71% yield when using sulfolane as the solvent
(Table 1, entry 1). Of note was that a large amount of dibenzyl
carbonate was generated in the product mixture when Cs2CO3
(Table 1, entry 2) or CsHCO3 (Table 1, entry 3) was used as the
base. The organic base DIPEA could also afford 38% yield
atmosphere for 18 h.
bThe yields were determined by using NMR with 1,3,5-
trimethoxybenzene as an internal standard.
cIsolated yield on a 0.2 mmol scale.
dDibenzyl carbonate (64% yield) was found in the reaction.
eDibenzyl carbonate (16% yield) was found in the reaction.
f4.0 equiv. BnBr was used.
g8.0 equiv. BnBr was used.
h6.0 equiv. BnCl replaced the BnBr.

iUnder O2 atmosphere.
As a comparative study, the synthesis of 3-arylquinolin-4-ones
ACCEPTED MANUSCRIPT
jUnder N2 atmosphere.
(3) was performed on the basis of a two-step, one-pot operation.
In the first step, compound 1 was just heated together with benzyl
bromide until the completion of the starting materials, and then
the base was added. Extensive exploration of reaction conditions
revealed that the optimal reaction conditions are (Table 2, entry
1): the reaction was heated at 130 ˚C for 15 h in toluene (0.4 M)
at step 1, and then stirred at ambient temperature in methanol (0.1
M) in the presence of DBU for 4 h at step 2, with molar ratio of
1a: benzyl bromide : DBU = 1 : 4 : 2. Of particular note was that
the concentration of 1a in toluene must not be less than 0.4 M in
order to prevent the formation of 7,8-dimethyl-11H-
kDDQ, Na2S2O8, or Oxone was used as oxidant.
With the optimized conditions in hand, the reaction scope for
the synthesis of compound
2 was investigated through
introduction of various substitutive groups to the substrates. As
shown in Scheme 3, different substitutions of R3, such as H,
electron-withdrawing groups (CF3), electron-donating groups
t
(Me, OMe, Bu), halides (F, Cl, Br), on the phenyl ring of the
benzyl bromides (2a-i) were allowed in moderate yields (42-
67%). The electron withdrawing substitutions (2b, 2f-i) seems to
be slightly superior to the electron donating ones (2c-e) for the
reaction. Surprisingly, compound 2j with steric congesting 2-Br-
5-MeO still provided a moderate yield (66%). Naphthalenyl
function (2k) could also contribute a moderate yield (63%) by
replacing the phenyl group. The thiophen-3-yl function was
suitable (2l) but the product must be carefully treated due to its
instability during the purification. Further studies showed that
substitutive groups such as F (2m and 2p), Cl (2n), Br (2o),
electron-donating OMe (2q) on the benzaldehyde ring, were all
tolerated, whereas the halo-functionalized derivatives (2m-p)
afforded slightly lower yields (41-50%) than that (70%) of the
OMe-substituted compound (2q). These results indicated that the
electron donating groups on the benzaldehyde ring might be
favorable to the reaction. Meanwhile, when 5,6-
benzo[4,5]imidazo[1,2-a]indol-11-one15,
intramolecular by-product of 1a.
which
was
an
Table 2. Optimization of conditions for the synthesis of
compound 3a
Base(equiv.,
step 2)
Yield(%)
Entry
Solvent
3ab
91
20
17
70
51
76
12
10
85
88
81
17
51
87
58
80
53
27
1a
2
step 1: Toluene; step 2: MeOH
step 1: Xylene; step 2: MeOH
step 1: Sulfolane; step 2:MeOH
step 1: Dioxane; step 2: MeOH
step 1: DMF; step 2: MeOH
step 1: CHCl3; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: DCM
step 1: Toluene; step 2: DMF
DBU (2.0)
DBU (2.0)
DBU (2.0)
DBU (2.0)
DBU (2.0)
DBU (2.0)
Et3N (2.0)
DIPEA (2.0)
NaOH (2.0)
Cs2CO3 (2.0)
K2CO3 (2.0)
K3PO3 (2.0)
DBU (1.0)
DBU (3.0)
DBU (2.0)
DBU (2.0)
DBU (2.0)
DBU (2.0)
dimethylbenzo[d]imidazole
moiety
was
replaced
by
benzo[d]imidazole (2r-t) or imidazole unit (2u), the reaction still
went on smoothly. Of note was that 2-bromo-6-
(bromomethyl)pyridine as the electrophile was also compatible to
this cyclization (e.g. synthesis of 2t).
3
4
5
6
7
8
9
10
11
12
13
14
15c
16d
17
18
step 1: Toluene;
Sulfolane
step 2:
19
DBU (2.0)
12
20e
21f
22g
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
step 1: Toluene; step 2: MeOH
DBU (2.0)
DBU (2.0)
DBU (2.0)
36
62
9
aThe reactions were performed on a 0.2 mmol scale in a sealed
tube at 130 ˚C for 15 h in step 1, and then at rt for 4 h in step 2.
bIsolated yields.
c2.0 equiv. BnBr was used.
d6.0 equiv. BnBr was used.
eThe reaction was heated at 90 ˚C in step 1.
fThe reaction was heated at 90 ˚C for 24 h in step 2.
g4.0 equiv. BnCl instead of BnBr.
Following the optimal conditions, the scope for the synthesis
of compound 3 was also examined. As shown in Scheme 4,
substitutive groups on benzyl bromide such as H (3a), electron
withdrawing CF3 (3b), NO2 (3c), halides (3e-f), were all suitable
Scheme
3.
Scope
study
for
the
synthesis
of
benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-one 2
aIsolated yields were indicated.
t
in good to high yields (75-91%), while the electron donating Bu
(3d) showed much less efficiency (37%), which indicated that the
electron withdrawing groups might be beneficial. It was further
confirmed by compound 3g with an electron withdrawing 2-

4
Tetrahedron
bromo-6-(bromomethyl)pyridine unit, giving an excellent 94%
In order to understand the mechanisms for the
ACCEPTED MANUSCRIPT
yield. Of note was that when the benzene ring was replaced by
the thiophen-3-yl group (3h), the reaction should be performed at
a lower temperature (90 ºC) in step 1. Not surprisingly, the
benzo[d]imidazole substrates (3i-m) could also provide good
yields (70-85%). Furthermore, substitutive groups such as Cl
(3n), OMe (3o), and CF3 (3p) at the benzaldehyde ring were
permitted, nevertheless, the electron donating group (3o) is
superior to the electron withdrawing ones (3n and 3p) for the
reaction. The structures of 2c and 3i were unambiguously
determined by using X-ray crystallographic analysis (see the
Supporting Information).
transformations, the two key intermediates I and II for the
synthesis of compounds 2 and 3, respectively, were isolated and
characterized by using H, 13C-NMR, and HRMS. Compound I
1
was further determined by using X-ray crystallographic analysis
(see the Supporting Information). We speculated, in terms of
their structures, that 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde
was firstly benzylated to form a NHC precursor 3-benzyl-1-(2-
formylphenyl)-1H-benzo[d]imidazol-3-ium salt, which was
rapidly transformed into an intra-Breslow intermediate (Scheme
5) no matter whether there was base or not. Then, if the base was
added simultaneously with the substrates, an additional
benzylation would take place immediately at the 1-position of the
Breslow intermediate via an enol attack fashion to form the
intermediate I, which was then converted into the final product
2a smoothly. If base was absent in the first step, the benzylation
would happen at the 2-position via a NHC-based enamine attack
to produce intermediate II. This process might be supported by
two previous articles that the C-C coupling between the
aldehydes and the benzyl bromides was successful under the
thiazol-2-ylidene-NHC
catalysts16.
Additionally,
using
deuterium-labeled (d4) methanol as the solvent in step 2, only one
hydrogen atom in product 3a was deuterated (measured by
HRMS, see Supporting Information). This deuterium should
originate from the last protonation step of the benzyl amine
moiety, which demonstrated that the proposed mechanistic
transformation for conversion of II to 3a is reasonable (Scheme
5).
3. Conclusion
In summary, we established two novel one-pot strategies for
the insertion of benzyl group between aldehyde and imidazole of
2-(1H-benzo[d]imidazol-1-yl)benzaldehyde under transition-
metal-free conditions, and realized the facile syntheses of fused
Scheme 4. Scope study for the synthesis of 3-arylquinolin-4-one
3.
benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones
and
3-
arylquinolin-4-ones with the formation of new C(sp2)-C(sp2)-
C(sp2) bond. Mechanistic study demonstrated that the bifurcation
for the synthesis of compound 2 and 3 was attributed to the
different position of intra-Breslow intermediate nucleophilic
attack to benzyl bromide. These easily-operated methods might
be employed to efficiently construct a variety of N-heterocycles
for the development of bioactive agents.
aIsolated yields were indicated.
bHeated at 90 ˚C in step 1.
4. Experimental section
4.1 General information
Solvents such as DMF, DMSO, MeOH, and DME were
obtained from commercial suppliers and kept with 4Å MS
(stored under N2 atmosphere). Toluene, xylene, and dioxane were
dried under CaH2 and distilled. CHCl3 and CH2Cl2 were dried
under CaCl2 and distilled. NMO, sulfolane, and diphenyl ether
were dried using 4Å MS and distilled. Unless otherwise noted,
other chemicals obtained from commercial suppliers were used
without further purification. Melting points (m.p.) were
determined by using a SRSO-ptiMelt automated melting point
instrument without correction. Analytical thin layer
chromatography was performed on Polygram SIL HSGF254
plates. Visualization was accomplished with short wave UV
light, or I2 staining. Flash column chromatography was
performed using silica gel (200-300 mesh). The NMR spectra
were recorded on Bruker AC 500 or 700 NMR spectrometer with
TMS as an internal standard. The residual solvent peaks were
1
used for the chemical shifts as an internal references (ppm): H
Scheme 5. Possible mechanisms for syntheses of compounds
2 and 3.
(CDCl3: δ = 7.26, DMSO-d6: δ = 2.50, CO(CD3)2: δ = 2.05,
MeOD: δ = 3.31), 13C (CDCl3: δ = 77.0, DMSO-d6: δ = 39.5,

MeOD: δ = 49.0, CO(CD3)2: δ = 206). 19F (CF3CO2H: -76, PhF: -
1H), 7.37 (d, J = 8.4 Hz, 1H), 6.96 (s, 1H), 2.38 (s, 3H), 2.32 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 187.06, 142.16, 141.83,
138.20, 137.09, 134.16, 134.08, 132.70, 132.58, 132.14, 129.38,
123.54, 120.69, 109.70, 20.49, 20.18. FTIR (neat): 2962, 2891,
1691, 1585, 1450, 1230, 1180, 999, 920, 839, 785 cm-1. ESI-MS
(m/z): 329.0, 331.0 [M + H]+
ACCEPTED MANUSCRIPT
113). The data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, and
m = multiplet), integration, and coupling constant in Hz. Mass
spectrometry data were collected with a Bruker maXis/Q-TOF
instrument for high-resolution or a Bruker amaZon SL instrument
for low-resolution with both by using ESI ionization. No effort
was taken to optimize substrate yields.
4.2.5. 2-(5,6-dimethyl-1H-benzo[d] imidazol-1-yl)-
4-fluorobenzaldehyde (1e)
4.2 Synthesis of compound 1
Following the general procedure A, compound 1e was
obtained as a white solid in 47% yield (0.86 g), mp: 114-116 ˚C.
1H NMR (500 MHz, CDCl3) δ 9.67 (s, 1H), 8.19 (dd, J = 8.8, 6.2
Hz, 1H), 7.95 (s, 1H), 7.66 (s, 1H), 7.36 (td, J = 8.3, 2.3 Hz, 1H),
7.22 (dd, J = 8.5, 2.4 Hz, 1H), 7.02 (s, 1H), 2.40 (s, 3H), 2.34 (s,
General procedure A: To a 25 mL flask, 2-flurobenzaldehydes
(2.0 equiv., 13.6 mmol), benzo[d]imidazoles (1.0 equiv., 6.8
mmol), and K2CO3 (2.0 equiv., 13.6 mmol, 1.88 g) in DMF (5.0
mL) were added, and the reaction was stirred at 80 ˚C for 10 h.
Upon the completion of the starting materials, the solvent was
removed under the reduced pressure, and the residue was
dissolved in AcOEt (150 mL). The organic layer was washed
with H2O (40 mL × 3), dried over anhydrous Na2SO4, and
removed under the reduced pressure. The crude was purified with
silica gel column chromatography (PE/EA=5:1-1:2 as the
eluents) to afford the target compound 1.
3H). 13C NMR (125 MHz, CDCl3) δ 187.01, 166.36 (d, JFC
=
258.75 Hz), 142.16, 141.97, 140.41 (d, JFC = 10.0 Hz), 134.19,
133.98, 132.71, 131.97 (d, JFC = 11.25 Hz), 128.23 (d, JFC = 2.5
Hz), 120.83, 116.92 (d, JFC = 21.25 Hz), 115.02 (d, JFC = 23.75
Hz), 109.82, 20.55, 20.22. FTIR (neat): 2922, 2880, 1695, 1602,
1489, 1469, 1201, 1105, 883, 840, 734 cm-1. ESI-MS (m/z):
269.1 [M + H]+.
4.2.6. 2-(5,6-dimethyl-1H-benzo[d] imidazol-1-yl)-
4-methoxybenzaldehyde (1f)
4.2.1. 2-(5,6-dimethyl-1H-benzo[d] imidazol-1-
yl)benzaldehyde (1a)
Following the general procedure A, compound 1f was
obtained as a white solid in 70% yield (1.3 g), mp: 125-128 ˚C.
1H NMR (500 MHz, CDCl3) δ 9.57 (s, 1H), 8.08 (d, J = 8.8 Hz,
1H), 7.94 (s, 1H), 7.62 (s, 1H), 7.12 (dd, J = 8.8, 2.1 Hz, 1H),
7.02 (s, 1H), 6.92 (d, J = 2.4 Hz, 1H), 3.92 (s, 3H), 2.38 (s, 3H),
2.32 (s, 3H).13C NMR (125 MHz, CDCl3) δ 187.21, 165.03,
142.35, 141.84, 140.25, 134.18, 133.68, 132.19, 131.23, 124.92,
120.53, 115.06, 112.67, 110.02, 55.98, 20.45, 20.14. FTIR (neat):
2964, 2924, 2877, 1682, 1599, 1491, 1458, 1246, 1209, 1182,
1024, 871, 837 cm-1. ESI-MS (m/z): 281.1 [M + H]+.
Following the general procedure A, compound 1a was
obtained as a white solid in 45% yield (0.77 g), mp: 128-130 ˚C.
1H NMR (500 MHz, CDCl3) δ 9.72 (s, 1H), 8.14 (d, J = 7.8 Hz,
1H), 7.96 (s, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.72 – 7.61 (m, 2H),
7.48 (d, J = 7.8 Hz, 1H), 6.99 (s, 1H), 2.39 (s, 3H), 2.32 (s, 3H).
13C NMR (125 MHz, CDCl3) δ 188.52, 142.48, 141.90, 138.32,
135.39, 134.40, 133.80, 132.31, 131.60, 129.35, 129.26, 127.81,
120.61, 109.94, 20.51, 20.21. FTIR (neat): 2941, 2860, 1693,
1599, 1490, 1468, 1274, 1192, 843, 770 cm-1. ESI-MS (m/z):
251.1 [M + H]+.
4.2.7. 2-(1H-benzo[d] imidazol-1-yl)-4-
(trifluoromethyl)benzaldehyde (1g)
Following the general procedure A, compound 1g was
obtained as a slight yellow oil in 43% yield (0.85 g). H NMR
(500 MHz, CDCl3) δ 9.76 (s, 1H), 8.27 (d, J = 8.1 Hz, 1H), 8.09
(s, 1H), 7.92 (dd, J = 13.5, 7.8 Hz, 2H), 7.80 (s, 1H), 7.43 – 7.32
(m, 2H), 7.22 (d, J = 7.5 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ
187.19, 143.38, 142.86, 138.25, 136.87 (q, JFC = 32.5 Hz),
135.44, 133.87, 130.41, 126.31 (q, JFC = 3.75 Hz), 125.06 (q, JFC
= 3.75 Hz), 124.85, 123.73, 122.64 (q, JFC = 272.5 Hz), 121.01,
109.54. 19F NMR (470 MHz, CDCl3) δ -63.13. FTIR (neat):
2862, 1703, 1612, 1490, 1461, 1313, 1174, 1131, 1070, 842, 744
cm-1. ESI-MS (m/z): 291.1 [M + H]+.
4.2.2. 2-(5,6-dimethyl-1H-benzo[d] imidazol-1-yl)-
6-fluorobenzaldehyde (1b)
Following the general procedure A, compound 1b was
obtained as a white solid in 55% yield (1.0 g), mp: 149-151 ˚C.
1H NMR (500 MHz, CDCl3) δ 9.94 (s, 1H), 7.90 (s, 1H), 7.75 (td,
J = 8.2, 5.8 Hz, 1H), 7.63 (s, 1H), 7.36 (t, J = 9.2 Hz, 1H), 7.30
(d, J = 7.9 Hz, 1H), 6.96 (s, 1H), 2.38 (s, 3H), 2.32 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 185.51, 163.55 (d, JFC = 263.75 Hz),
142.33, 141.89, 137.92, 135.91 (d, JFC = 13.75 Hz), 133.60,
133.52, 132.23, 123.96, 120.65, 117.35 (d, JFC = 21.25 Hz),
109.95, 20.50, 20.19. FTIR (neat): 2962, 2918, 1690, 1608, 1571,
1492, 1462, 1244, 1186, 897, 841, 810 cm-1. ESI-MS (m/z):
269.1 [M + H]+.
1
4.2.8. 2-(1H-benzo[d] imidazol-1-yl)benzaldehyde
(1h)1 7
4.2.3. 2-chloro-6-(5,6-dimethyl-1H-
benzo[d]imidazol-1-yl)benzaldehyde (1c)
Following the general procedure A, compound 1h was
Following the general procedure A, compound 1c was
obtained as a white solid in 57% yield (1.1 g), mp: 129-131 ˚C.
1H NMR (500 MHz, CDCl3) δ 10.11 (s, 1H), 7.88 (s, 1H), 7.70 –
7.64 (m, 2H), 7.63 (s, 1H), 7.41 (dd, J = 6.7, 2.3 Hz, 1H), 6.91 (s,
1H), 2.39 (s, 3H), 2.32 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
187.72, 142.51, 141.93, 137.91, 137.45, 134.30, 133.50, 133.47,
132.12, 131.61, 129.47, 127.24, 120.68, 109.95, 20.51, 20.22.
FTIR (neat): 2920, 1697, 1585, 1489, 1456, 1229, 1188, 849, 797
cm-1. ESI-MS (m/z): 285.1 [M + H]+
1
obtained as a colorless oil in 62% yield (0.94 g). H NMR (500
MHz, CDCl3) δ 9.71 (s, 1H), 8.14 (d, J = 7.7 Hz, 1H), 8.07 (s,
1H), 7.90 (d, J = 7.9 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.68 (t, J =
7.6 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.34 (dt, J = 14.9, 7.2 Hz,
2H), 7.22 (d, J = 7.9 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ
188.29, 143.29, 143.22, 137.77, 135.69, 135.40, 131.59, 129.56,
129.53, 127.87, 124.34, 123.22, 120.67, 109.88. FTIR (neat):
2858, 2760, 1693, 1597, 1489, 1460, 1286, 1228, 1193, 823, 740
cm-1. ESI-MS (m/z): 223.1 [M + H]+.
4.2.4. 5-bromo-2-(5,6-dimethyl-1H-
benzo[d]imidazol-1-yl)benzaldehyde (1d)
4.2.9. 2-(1H-imidazol-1-yl)benzaldehyde (1i)1 8
Following the general procedure A, compound 1i was
Following the general procedure A, compound 1d was
1
obtained as a colorless oil in 17% yield (0.2 g). H NMR (500
obtained as a slight yellow solid in 24% yield (0.54 g), mp: 188-
MHz, CDCl3) δ 9.76 (s, 1H), 8.05 – 7.96 (m, 1H), 7.77 – 7.65 (m,
2H), 7.60 – 7.55 (m, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.22 (d, J =
0.8 Hz, 1H), 7.19 (d, J = 1.2 Hz, 1H). 13C NMR (125 MHz,
1
190 ˚C. H NMR (500 MHz, CDCl3) δ 9.63 (s, 1H), 8.23 (d, J =
2.3 Hz, 1H), 7.92 (s, 1H), 7.90 (dd, J = 8.4, 2.4 Hz, 1H), 7.63 (s,

6
Tetrahedron
ACCEPTED MANUSCRIPT
CDCl ) δ 188.36, 139.26, 138.24, 134.96, 130.76, 130.24,
131.01, 130.75, 130.72, 129.07, 128.99, 128.09, 127.35, 125.73,
3
129.15, 128.88, 126.83, 121.85. FTIR (neat): 2924, 2852, 1687,
1599, 1494, 1400, 1303, 1242, 1193, 1056, 822, 766, 660 cm-1.
ESI-MS (m/z): 173.1 [M + H]+.
125.64, 124.26, 115.19, 114.23, 110.69, 102.47, 47.56, 21.31,
21.03, 20.49, 20.18. FTIR (neat): 2918, 2850, 1625, 1587, 1541,
1479, 1415, 1303, 1182, 813, 750 cm-1. HRMS (ESI): m/z calcd
for C32H29N2O [M+H]+ 457.2274, found 457.2290.
4.3.4. 7-(3-methoxybenzyl)-6-(3-methoxyphenyl)-
9,10-dimethylbenzo[4,5] imidazo[1,2-a]quinolin-
5(7H)-one (2d)
4.3 Synthesis of compound 2
General procedure B: To a 5 mL vial back-filled with dried
air, compound 1 (1.0 equiv., 0.2 mmol), benzyl bromides (6.0
equiv., 1.2 mmol), and Na2CO3 (2.0 equiv. 0.4 mmol, 42 mg) in
sulfolane (0.5 mL) were added, and the reaction was heated at 90
˚C for 18 h. Upon the completion of the starting materials, the
reaction mixture was dissolved in 100 mL H2O, and extracted
with dichloromethane (40 mL × 3). The organic layers were
combined, dried over anhydrous Na2SO4, and removed. The
crude was purified by using silica gel column chromatography
(PE/EA = 10:1 – 1:2 as eluents) to afford the target compound 2.
Following the general procedure B, compound 2d was
obtained as a white solid in 56% yield (54.7 mg), mp: 106-108
˚C. 1H NMR (500 MHz, CDCl3) δ 8.66 (dd, J = 8.0, 1.4 Hz, 1H),
8.46 (d, J = 8.5 Hz, 1H), 8.03 (s, 1H), 7.84 – 7.75 (m, 1H), 7.52
(t, J = 7.5 Hz, 1H), 7.22 – 7.14 (m, 1H), 7.09 (t, J = 7.9 Hz, 1H),
6.93 – 6.78 (m, 3H), 6.73 (dd, J = 8.2, 2.2 Hz, 1H), 6.65 (d, J =
1.4 Hz, 1H), 6.30 (d, J = 7.7 Hz, 1H), 6.24 (s, 1H), 4.84 (d, J =
4.2 Hz, 2H), 3.70 (s, 3H), 3.51 (s, 3H), 2.47 (s, 3H), 2.31 (s, 3H).
13C NMR (125 MHz, CDCl3) δ 173.80, 159.76, 159.35, 146.07,
137.26, 135.49, 135.14, 133.41, 133.25, 131.25, 130.89, 129.57,
129.14, 128.08, 127.20, 125.61, 124.49, 124.39, 117.69, 116.40,
115.25, 114.33, 112.45, 111.50, 110.50, 102.57, 55.14, 54.77,
47.69, 20.50, 20.18. FTIR (neat): 2922, 2878, 1595, 1533, 1489,
1415, 1263, 1037, 754, 686 cm-1. HRMS (ESI): m/z calcd for
C32H29N2O3 [M+H]+ 489.2173, found 489.2184.
4.3.1 7-benzyl-9,10-dimethyl-6-
phenylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-one
(2a)
Following the general procedure B, compound 2a was
obtained as a white solid in 67% yield (57.3 mg), mp: 233-235
˚C. 1H NMR (500 MHz, CDCl3) δ 8.67 (dd, J = 7.9, 1.1 Hz, 1H),
8.47 (d, J = 8.5 Hz, 1H), 8.04 (s, 1H), 7.84 – 7.77 (m, 1H), 7.53
(t, J = 7.5 Hz, 1H), 7.25 – 7.21 (m, 1H), 7.21 – 7.14 (m, 7H),
6.87 (s, 1H), 6.70 (d, J = 6.7 Hz, 2H), 4.85 (s, 2H), 2.47 (s, 3H),
2.31 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 173.85, 146.19,
135.49, 135.31, 133.74, 133.43, 133.19, 132.00, 131.29, 130.92,
128.84, 128.47, 128.18, 128.06, 127.36, 127.33, 127.25, 125.55,
124.41, 115.26, 114.33, 110.59, 102.67, 47.83, 20.54, 20.20.
FTIR (neat): 2957, 2922, 2853, 1726, 1597, 1533, 1494, 1418,
1256, 1074, 746, 700 cm-1. HRMS (ESI): m/z calcd for
C30H25N2O [M+H]+ 429.1961, found 429.1979.
4.3.5. 7-(4-(tert-butyl)benzyl)-6-(4-(tert-
butyl)phenyl)-9,10-dimethylbenzo[4,5] imidazo[1,2-
a]quinolin-5(7H)-one (2e)
Following the general procedure B, compound 2e was
obtained as a white solid in 60% yield (64.8 mg), mp: 290-292
˚C. 1H NMR (500 MHz, CDCl3) δ 8.65 (dd, J = 8.0, 1.5 Hz, 1H),
8.45 (d, J = 8.5 Hz, 1H), 8.02 (s, 1H), 7.78 (ddd, J = 8.6, 7.2, 1.7
Hz, 1H), 7.54 – 7.48 (m, 1H), 7.16 (d, J = 8.4 Hz, 2H), 7.14 –
7.11 (m, 2H), 7.08 – 7.04 (m, 2H), 6.92 (s, 1H), 6.57 (d, J = 8.4
Hz, 2H), 4.83 (s, 2H), 2.47 (s, 3H), 2.32 (s, 3H), 1.30 (s, 9H),
1.28 (s, 9H).13C NMR (125 MHz, CDCl3) δ 173.92, 150.25,
149.55, 146.39, 135.48, 133.63, 133.26, 132.42, 131.55, 131.01,
130.73, 130.45, 128.09, 127.30, 125.68, 125.18, 124.85, 124.25,
115.18, 114.22, 110.48, 102.55, 47.85, 34.43, 34.41, 31.36,
31.32, 20.50, 20.15. FTIR (neat): 2920, 2870, 1625, 1601, 1545,
1523, 1487, 1344, 1136, 1095, 804, 731, 671 cm-1. HRMS (ESI):
m/z calcd for C38H41N2O [M+H]+ 541.3213, found 541.3229.
4.3.2. 9,10-dimethyl-7-(4-(trifluoromethyl)benzyl)-
6-(4-(trifluoromethyl)phenyl)benzo[4,5]imidazo
[1,2-a]quinolin-5(7H)-one (2b)
Following the general procedure B, compound 2b was
obtained as a white solid in 66% yield (77.4 mg), mp: 285-287
1
˚C. H NMR (500 MHz, CDCl3) δ 8.61 (d, J = 7.9 Hz, 1H), 8.48
(d, J = 8.5 Hz, 1H), 8.07 (s, 1H), 7.82 (t, J = 7.8 Hz, 1H), 7.52 (t,
J = 7.5 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 7.9 Hz,
2H), 7.26 (d, J = 7.4 Hz, 2H), 6.90 (s, 1H), 6.77 (d, J = 7.9 Hz,
2H), 4.90 (s, 2H), 2.50 (s, 3H), 2.34 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 173.69, 146.09, 139.11, 137.79, 135.55, 134.05,
133.10, 132.50, 132.12, 131.42, 130.09 (q, JFC = 67.33 Hz),
129.33 (q, JFC = 64.32 Hz), 129.03, 127.98, 127.23, 125.62,
125.42, 124.81, 124.78, 124.26 (d, JFC = 271 Hz), 123.86 (d, JFC
= 270 Hz), 115.47, 114.59, 110.29, 110.17, 48.34, 20.57, 20.23.
FTIR (neat): 2958, 2920, 2852, 1726, 1600, 1539, 1516, 1321,
1153, 1107, 1066, 1018, 821, 766 cm-1. HRMS (ESI): m/z calcd
for C32H23F6N2O [M+H]+ 565.1709, found 565.1721.
4.3.6. 7-(4-fluorobenzyl)-6-(4-fluorophenyl)-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2f)
Following the general procedure B, compound 2f was
obtained as a white solid in 60% yield (55.7 mg), mp: 263-266
˚C. 1H NMR (500 MHz, CDCl3) δ 8.70 (d, J = 7.5 Hz, 1H), 8.48
(d, J = 8.5 Hz, 1H), 8.06 (s, 1H), 7.82 (ddd, J = 8.6, 7.2, 1.6 Hz,
1H), 7.55 (t, J = 7.4 Hz, 1H), 7.18 – 7.11 (m, 2H), 6.95 – 6.84
(m, 5H), 6.67 (dd, J = 8.6, 5.2 Hz, 2H), 4.87 (s, 2H), 2.48 (s, 3H),
2.33 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 174.03, 162.16 (d,
JFC = 245 Hz), 162.10 (d, JFC = 245 Hz), 146.11, 135.50, 133.62
(d, JFC = 7.5 Hz), 133.56, 133.02, 131.52, 131.07, 130.83 (d, JFC
= 1.25 Hz), 129.63 (d, JFC = 3.75 Hz), 128.02, 127.27, 127.05 (d,
JFC = 7.0 Hz), 125.48, 124.52, 115.55 (d, JFC = 21.25 Hz),
115.28, 115.05 (d, JFC = 21.25 Hz), 114.40, 110.36, 101.33,
47.34, 20.51, 20.20. 19F NMR (470 MHz, CDCl3) δ -108.50, -
112.87. FTIR (neat): 2954, 2922, 2852, 1721, 1595, 1537, 1504,
1415, 1220, 1153, 815, 759, 737 cm-1. HRMS (ESI): m/z calcd
for C30H23F2N2O [M+H]+ 465.1773, found 465.1793.
4.3.3. 9,10-dimethyl-7-(4-methylbenzyl)-6-(p-
tolyl)benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-one
(2c)
Following the general procedure B, compound 2c was
obtained as a white solid in 42% yield (38.3 mg), mp: 253-156
˚C. 1H NMR (500 MHz, CDCl3) δ 8.66 (dd, J = 8.0, 1.5 Hz, 1H),
8.44 (d, J = 8.5 Hz, 1H), 8.00 (s, 1H), 7.78 (ddd, J = 8.6, 7.2, 1.6
Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.11 (d, J = 7.9 Hz, 2H), 7.03
(d, J = 7.8 Hz, 2H), 6.97 (d, J = 7.9 Hz, 2H), 6.86 (s, 1H), 6.63
(d, J = 8.0 Hz, 2H), 4.82 (s, 2H), 2.45 (s, 3H), 2.33 (s, 3H), 2.29
(s, 3H), 2.28 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 174.01,
146.36, 137.01, 136.81, 135.49, 133.23, 133.18, 132.50, 131.74,
4.3.7. 7-(3-chlorobenzyl)-6-(3-chlorophenyl)-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2g)
Following the general procedure B, compound 2g was
obtained as a white solid in 63% yield (62.5 mg), mp: 244-246

˚C. 1H NMR (500 MHz, CDCl3) δ 8.63 (dd, J = 8.0, 1.5 Hz, 1H),
124.53, 118.25, 118.00, 116.63, 115.30, 114.52, 113.90, 112.81,
111.92, 110.11, 102.32, 55.41, 54.91, 48.37, 20.53, 20.14. FTIR
(neat): 2922, 2850, 1730, 1591, 1539, 1485, 1294, 1234, 1055,
1012, 810, 758 cm-1. HRMS (ESI): m/z calcd for C32H27Br2N2O3
[M+H]+ 645.0383, found 645.0392, 647.0384, 649.0361.
ACCEPTED MANUSCRIPT
8.46 (d, J = 8.5 Hz, 1H), 8.04 (s, 1H), 7.81 (ddd, J = 8.7, 7.2, 1.7
Hz, 1H), 7.57 – 7.50 (m, 1H), 7.24 (ddd, J = 8.0, 2.0, 1.2 Hz,
1H), 7.20 (d, J = 8.7 Hz, 1H), 7.17 – 7.09 (m, 4H), 6.87 (s, 1H),
6.68 (s, 1H), 6.58 (d, J = 7.7 Hz, 1H), 4.86 (s, 2H), 2.48 (s, 3H),
2.34 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 173.74, 145.95,
137.10, 135.58, 135.53, 134.75, 134.14, 133.75, 133.05, 132.15,
131.75, 131.21, 130.44, 129.99, 129.18, 128.05, 127.92, 127.55,
127.22, 125.52, 125.48, 124.65, 123.38, 115.35, 114.48, 110.27,
101.28, 47.76, 20.53, 20.22. FTIR (neat): 2924, 2852, 1721,
1599, 1539, 1485, 1417, 1039, 771, 748, 677 cm-1. HRMS (ESI):
m/z calcd for C30H23Cl2N2O [M+H]+ 497.1182, found 497.1188.
4.3.11. 9,10-dimethyl-6-(naphthalen-2-yl)-7-
(naphthalen-2-ylmethyl)benzo[4,5]imidazo[1,2-
a]quinolin-5(7H)-one (2k)
Following the general procedure B, compound 2k was
obtained as a white solid in 63% yield (66.5 mg), mp: 164-166
1
˚C. H NMR (500 MHz, Acetone) δ 8.78 (d, J = 8.5 Hz, 1H),
8.50 (dd, J = 7.9, 1.6 Hz, 1H), 8.37 (s, 1H), 7.87 (ddd, J = 8.7,
7.2, 1.7 Hz, 1H), 7.82 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 7.9 Hz,
1H), 7.70 (d, J = 8.4 Hz, 1H), 7.67 (s, 1H), 7.61 (d, J = 7.9 Hz,
1H), 7.57 (d, J = 8.6 Hz, 1H), 7.56 – 7.52 (m, 1H), 7.48 – 7.42
(m, 2H), 7.40 (ddd, J = 8.3, 3.4, 1.7 Hz, 2H), 7.30 (d, J = 11.1
Hz, 2H), 7.26 – 7.22 (m, 1H), 7.19 (s, 1H), 6.80 (dd, J = 8.5, 1.7
Hz, 1H), 5.10 (q, J = 17.4 Hz, 2H), 2.47 (s, 3H), 2.28 (s, 3H).13C
NMR (125 MHz, CO(CD3)2) δ 173.73, 147.64, 136.62, 134.32,
134.00, 133.99, 133.56, 133.30, 133.11, 132.06, 131.87, 131.61,
128.86, 128.40, 128.31, 128.28, 128.27, 128.09, 128.03, 127.46,
126.88, 126.64, 126.55, 126.33, 126.12, 125.36, 124.77, 124.58,
121.47, 116.88, 115.10, 111.65, 102.41, 48.83, 20.09, 19.90.
FTIR (neat): 2920, 2850, 1595, 1531, 1485, 1416, 1271, 1186,
841, 808, 756, 738 cm-1. HRMS (ESI): m/z calcd for C38H29N2O
[M+H]+ 529.2274, found 529.2288.
4.3.8. 7-(3-bromobenzyl)-6-(3-bromophenyl)-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2h)
Following the general procedure B, compound 2h was
obtained as a white solid in 64% yield (74.8 mg), mp: 245-248
˚C. 1H NMR (500 MHz, CDCl3) δ 8.64 (dd, J = 8.0, 1.4 Hz, 1H),
8.47 (d, J = 8.5 Hz, 1H), 8.05 (s, 1H), 7.82 (ddd, J = 8.6, 7.2, 1.6
Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.39 (ddd, J = 18.1, 9.9, 5.1 Hz,
2H), 7.29 (t, J = 1.7 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 7.09 (dd, J
= 15.1, 7.7 Hz, 2H), 6.88 (s, 1H), 6.84 (s, 1H), 6.63 (d, J = 7.8
Hz, 1H), 4.87 (s, 2H), 2.49 (s, 3H), 2.34 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 173.78, 145.96, 137.34, 135.89, 135.54, 134.94,
133.74, 133.06, 131.74, 131.20, 130.93, 130.44, 130.28, 129.42,
128.45, 128.06, 127.23, 125.51, 124.64, 123.82, 122.96, 122.39,
115.35, 114.47, 110.26, 101.23, 47.74, 20.53, 20.21. FTIR (neat):
2922, 2852, 1718, 1601, 1581, 1539, 1483, 1415, 1261, 1071,
769, 748, 675 cm-1. HRMS (ESI): m/z calcd for C30H23Br2N2O
[M+H]+ 585.0172, found 585.0178, 587.0165, 589.0143.
4.3.12. 9,10-dimethyl-6-(thiophen-3-yl)-7-
(thiophen-3-ylmethyl)benzo[4,5] imidazo[1,2-
a]quinolin-5(7H)-one (2l)
Following the general procedure B, compound 2l was
4.3.9. 7-(3,4-dichlorobenzyl)-6-(3,4-
dichlorophenyl)-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2i)
obtained as a white solid in 31% yield (27.3 mg), mp: 249-250
˚C. H NMR (500 MHz, CDCl3) δ 8.71 (d, J = 7.9 Hz, 1H), 8.47
1
(d, J = 8.5 Hz, 1H), 8.05 (s, 1H), 7.81 (t, J = 7.4 Hz, 1H), 7.54 (t,
J = 7.5 Hz, 1H), 7.31 (dd, J = 4.6, 3.0 Hz, 1H), 7.19 (dd, J = 4.9,
3.0 Hz, 1H), 7.13 (d, J = 2.1 Hz, 1H), 7.04 (d, J = 5.3 Hz, 2H),
6.66 (s, 1H), 6.58 (d, J = 4.9 Hz, 1H), 4.92 (s, 2H), 2.45 (s, 3H),
2.36 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 172.90, 145.88,
136.10, 135.23, 133.93, 132.89, 132.49, 131.86, 131.22, 130.88,
128.07, 127.19, 126.50, 125.77, 125.72, 124.91, 124.75, 124.69,
121.28, 115.33, 114.49, 110.82, 97.37, 44.36, 20.55, 20.26. FTIR
(neat): 3057, 2918, 2854, 1593, 1539, 1514, 1427, 1298, 1182,
1072, 1031, 831, 750 cm-1. HRMS (ESI): m/z calcd for
C26H21N2OS2 [M+H]+ 441.1090, found 441.1088.
Following the general procedure B, compound 2i was
obtained as a white solid in 58% yield (65.4 mg), mp: 275-278
˚C. 1H NMR (500 MHz, CDCl3) δ 8.61 (dd, J = 8.0, 1.5 Hz, 1H),
8.46 (d, J = 8.5 Hz, 1H), 8.05 (s, 1H), 7.82 (ddd, J = 8.6, 7.2, 1.6
Hz, 1H), 7.54 (t, J = 7.3 Hz, 1H), 7.32 (dd, J = 13.7, 8.2 Hz, 2H),
7.18 (d, J = 2.0 Hz, 1H), 7.11 (dd, J = 8.1, 2.0 Hz, 1H), 6.88 (s,
1H), 6.82 (d, J = 2.0 Hz, 1H), 6.56 (dd, J = 8.3, 2.1 Hz, 1H), 4.86
(d, J = 2.7 Hz, 2H), 2.49 (s, 3H), 2.35 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 173.75, 145.89, 135.51, 135.10, 133.97, 133.90,
133.82, 133.24, 132.88, 132.27, 132.08, 132.06, 131.68, 131.59,
131.42, 130.76, 129.88, 128.02, 127.26, 127.22, 125.37, 124.81,
124.51, 115.40, 114.58, 110.14, 100.11, 47.61, 20.56, 20.25.
FTIR (neat): 2918, 2849, 1721, 1599, 1529, 1487, 1418, 1130,
1030, 756, 732 cm-1. HRMS (ESI): m/z calcd for C30H21Cl4N2O
[M+H]+ 565.0403, found 565.0403.
4.3.13. 7-(4-(tert-butyl)benzyl)-6-(4-(tert-
butyl)phenyl)-4-fluoro-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2m)
Following the general procedure B, compound 2m was
obtained as a white solid in 50% yield (55.8 mg), mp: 299-300
1
4.3.10. 7-(2-bromo-5-methoxybenzyl)-6-(2-bromo-5-
methoxyphenyl)-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2j)
˚C. H NMR (500 MHz, CDCl3) δ 8.23 (d, J = 8.7 Hz, 1H), 7.95
(s, 1H), 7.68 (td, J = 8.4, 5.2 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2H),
7.12 (dd, J = 10.7, 8.5 Hz, 3H), 7.04 (d, J = 8.3 Hz, 2H), 6.89 (s,
1H), 6.57 (d, J = 8.3 Hz, 2H), 4.78 (s, 2H), 2.45 (s, 3H), 2.31 (s,
3H), 1.29 (s, 9H), 1.28 (s, 9H). 13C NMR (125 MHz, CDCl3) δ
173.28 (d, JFC = 2.5 Hz), 162.61 (d, JFC = 262.5 Hz), 150.28,
149.64, 145.98, 137.40 (d, JFC = 3.75 Hz), 133.81, 133.59,
132.30, 131.64, 130.95 (d, JFC = 10.0 Hz), 130.93, 129.84,
127.15, 125.19, 125.17, 124.77, 115.63 (d, JFC = 6.25 Hz),
114.27, 111.70 (d, JFC = 22.5 Hz), 111.16 (d, JFC = 3.75 Hz),
110.49, 103.54, 47.80, 34.43, 34.40, 31.34, 31.31, 20.48, 20.13.
FTIR (neat): 2955, 2880, 2840, 1599, 1583, 1539, 1514, 1259,
1027, 970, 813 cm-1. HRMS (ESI): m/z calcd for C38H40FN2O
[M+H]+ 559.3119, found 559.3133.
Following the general procedure B, compound 2j was
obtained as a white solid in 66% yield (85.0 mg), mp: 254-255
˚C. 1H NMR (500 MHz, CDCl3) δ 8.67 (dd, J = 7.9, 1.3 Hz, 1H),
8.48 (d, J = 8.5 Hz, 1H), 8.06 (s, 1H), 7.82 (ddd, J = 8.6, 7.2, 1.6
Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.45 (d, J = 8.9 Hz, 1H), 7.35
(d, J = 8.7 Hz, 1H), 6.86 (s, 1H), 6.69 (dd, J = 8.9, 3.1 Hz, 1H),
6.63 (dd, J = 8.7, 3.0 Hz, 1H), 6.47 (d, J = 3.0 Hz, 1H), 6.19 (d, J
= 2.9 Hz, 1H), 4.87 (q, J = 18.5 Hz, 2H), 3.60 (s, 3H), 3.42 (s,
3H), 2.48 (s, 3H), 2.33 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
173.12, 159.03, 158.45, 145.72, 135.67, 135.38, 135.21, 133.68,
133.33, 132.92, 132.81, 131.64, 131.14, 128.22, 127.21, 125.47,

8
Tetrahedron
ACCEPTED MANUSCRIPT
4.3.14. 7-(2-bromo-5-fluorobenzyl)-6-(2-bromo-5-
(s, 1H), 7.87 (d, J = 2.1 Hz, 1H), 7.12 (dd, J = 8.9, 2.1 Hz, 1H),
fluorophenyl)-4-chloro-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2n)
7.08 – 6.95 (m, 3H), 6.94 – 6.88 (m, 1H), 6.84 (s, 1H), 6.60 –
6.53 (m, 1H), 6.46 (d, J = 8.5 Hz, 1H), 4.83 (d, J = 3.5 Hz, 2H),
4.04 (s, 3H), 2.47 (s, 3H), 2.33 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 173.83, 162.26, 150.56 (d, JFC = 248.75 Hz), 150.46 (d,
JFC = 248.75 Hz), 149.85 (dt, JFC = 247.5, 12.5 Hz), 149.72 (dt,
JFC = 247.5, 7.5 Hz), 146.15, 136.74, 133.79, 132.90, 132.02 (t,
JFC = 5.0 Hz), 131.72, 130.71 (q, JFC = 2.5 Hz), 129.87, 128.35
(q, JFC = 3.75 Hz), 127.19, 121.35 (q, JFC = 2.5 Hz), 121.20 (d,
JFC = 15.0 Hz), 119.37, 117.71 (d, JFC = 17.5 Hz), 116.75 (d, JFC
= 17.5 Hz), 114.52 (d, JFC = 18.75 Hz), 114.38, 111.06, 110.14,
100.71, 99.69, 55.83, 47.24, 20.58, 20.22. FTIR (neat): 3008,
2927, 1601, 1537, 1504, 1462, 1415, 1278, 1211, 1112, 1040,
931, 817, 773, 734 cm-1. HRMS (ESI): m/z calcd for
C31H23F4N2O2 [M+H]+ 531.1690, found 531.1707.
Following the general procedure B, compound 2n was
obtained as a white solid in 41% yield (53.6 mg), mp: 305-306
˚C. H NMR (500 MHz, CDCl3) δ 8.43 (d, J = 8.5 Hz, 1H), 8.01
1
(s, 1H), 7.66 (t, J = 8.2 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.49
(dd, J = 8.8, 5.4 Hz, 1H), 7.42 (dd, J = 8.7, 5.1 Hz, 1H), 6.90 –
6.81 (m, 3H), 6.66 (dd, J = 8.9, 2.9 Hz, 1H), 6.35 (dd, J = 9.1, 2.8
Hz, 1H), 4.87 (dd, J = 56.1, 18.6 Hz, 2H), 2.48 (s, 3H), 2.35 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 172.68, 162.15 (d, JFC
=
247.5 Hz), 161.46 (d, JFC = 246.25 Hz), 144.72, 138.08, 136.10
(d, JFC = 16.25 Hz), 136.09 (d, JFC = 2.5 Hz), 134.21 (d, JFC
16.25 Hz) , 134.20, 133.45 (d, JFC = 8.75 Hz), 132.65, 131.94,
130.49, 128.50, 127.12, 122.23 (d, JFC = 2.5 Hz), 121.98, 120.93
=
4.3.18. 7-benzyl-6-phenylbenzo[4,5]imidazo[1,2-
a]quinolin-5(7H)-one (2r)
(d, JFC = 21.25 Hz), 116.83 (d, JFC = 22.5 Hz), 116.25 (d, JFC
=
21.25 Hz), 115.48 (d, JFC = 2.5 Hz), 115.47, 114.79, 114.61,
114.10 (d, JFC = 25.0 Hz), 109.95, 102.24, 48.22, 20.54, 20.16.
FTIR (neat): 2924, 2871, 1609, 1578, 1547, 1464, 1265, 1024,
808, 738, 727 cm-1. HRMS (ESI): m/z calcd for
C30H20Br2ClF2N2O [M+H]+ 654.9593, found 654.9588, 656.9573,
658.9551.
Following the general procedure B, compound 2r was
obtained as a slight yellow oil in 65% yield (52.0 mg), mp: 188-
190 ˚C. H NMR (500 MHz, CDCl3) δ 8.67 (dd, J = 8.0, 1.5 Hz,
1
1H), 8.48 (d, J = 8.5 Hz, 1H), 8.26 (d, J = 8.1 Hz, 1H), 7.80 (ddd,
J = 8.6, 7.2, 1.6 Hz, 1H), 7.58 – 7.51 (m, 1H), 7.37 – 7.32 (m,
1H), 7.29 (dd, J = 11.6, 4.4 Hz, 1H), 7.25 – 7.15 (m, 8H), 7.09
(d, J = 7.4 Hz, 1H), 6.76 – 6.72 (m, 2H), 4.88 (s, 2H). 13C NMR
(125 MHz, CDCl3) δ 174.20, 146.39, 135.52, 135.06, 134.91,
133.58, 131.93, 131.09, 129.09, 128.51, 128.26, 128.14, 127.46,
127.43, 125.65, 125.60, 124.61, 124.49, 122.62, 115.24, 113.29,
109.87, 102.63, 47.93. FTIR (neat): 2980, 2900, 1601, 1533,
1495, 1417, 1311, 1265, 1207, 1095, 1024, 727, 694 cm-1. HRMS
(ESI): m/z calcd for C28H21N2O [M+H]+ 401.1648, found
401.1665.
4.3.15. 7-benzyl-3-bromo-9,10-dimethyl-6-
phenylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-one
(2o)
Following the general procedure B, compound 2o was
obtained as a white solid in 45% yield (45.5 mg), mp: 267-268
˚C. H NMR (500 MHz, CDCl3) δ 8.75 (d, J = 2.4 Hz, 1H), 8.33
1
(d, J = 9.0 Hz, 1H), 7.94 (s, 1H), 7.85 (dd, J = 9.0, 2.4 Hz, 1H),
7.26 – 7.23 (m, 1H), 7.22 – 7.15 (m, 7H), 6.87 (s, 1H), 6.69 (d, J
= 6.9 Hz, 2H), 4.83 (s, 2H), 2.46 (s, 3H), 2.30 (s, 3H). 13C NMR
(125 MHz, CDCl3) δ 172.54, 146.21, 135.14, 134.19, 133.75,
133.63, 133.40, 133.18, 131.87, 131.52, 130.67, 128.50, 128.25,
127.47, 127.43, 127.30, 126.98, 125.51, 118.00, 117.05, 114.13,
110.77, 103.00, 47.88, 20.53, 20.20. FTIR (neat): 2968, 2929,
2860, 1603, 1575, 1531, 1492, 1300, 1253, 1074, 790, 738, 715,
696 cm-1. HRMS (ESI): m/z calcd for C30H24BrN2O [M+H]+
507.1067, found 507.1080, 509.1062.
4.3.19. 7-benzyl-6-phenyl-2-
(trifluoromethyl)benzo[4,5]imidazo[1,2-a]quinolin-
5(7H)-one (2s)
Following the general procedure B, compound 2s was
obtained as a white solid in 50% yield (46.8 mg), mp: 288-289
1
˚C. H NMR (500 MHz, CDCl3) δ 8.78 (d, J = 8.3 Hz, 1H), 8.74
(s, 1H), 8.21 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.46 –
7.38 (m, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.30 – 7.24 (m, 2H), 7.24
– 7.16 (m, 6H), 7.13 (d, J = 7.6 Hz, 1H), 6.76 – 6.70 (m, 2H),
4.90 (s, 2H).13C NMR (125 MHz, CDCl3) δ 173.22, 146.79,
135.04, 134.88, 134.75, 132.98, 132.65 (q, JFC = 32.5 Hz),
131.77, 129.32, 128.68, 128.60, 128.40, 127.89, 127.73, 127.61,
125.54, 125.11, 123.88 (q, JFC = 271.25 Hz), 123.17, 120.86 (q,
JFC = 2.5 Hz), 113.14, 112.78 (q, JFC = 3.75 Hz), 110.27, 103.61,
48.02. FTIR (neat): 3005, 2922, 1601, 1531, 1487, 1417, 1311,
1269, 1205, 1116, 754, 734 cm-1. HRMS (ESI): m/z calcd for
C29H20F3N2O [M+H]+ 469.1522, found 469.1527.
4.3.16. 7-(3-chlorobenzyl)-6-(3-chlorophenyl)-2-
fluoro-9,10-dimethylbenzo[4,5] imidazo[1,2-
a]quinolin-5(7H)-one (2p)
Following the general procedure B, compound 2p was
obtained as a white solid in 42% yield (43.2 mg), mp: 220-223
˚C. 1H NMR (500 MHz, Acetone) δ 8.49 (t, J = 6.4 Hz, 1H), 8.42
(d, J = 11.0 Hz, 1H), 8.35 (s, 1H), 7.32 (t, J = 8.2 Hz, 1H), 7.21
(dd, J = 24.8, 13.5 Hz, 7H), 6.87 (s, 1H), 6.79 (s, 1H), 5.05 (q, J
= 17.6 Hz, 2H), 2.49 (s, 3H), 2.33 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 173.28, 164.43 (d, JFC = 248.75 Hz), 146.30, 136.94,
136.29, 135.24, 134.79, 134.17 (d, JFC = 6.25 Hz), 133.06,
132.11, 131.95, 130.75 (d, JFC = 10.0 Hz), 130.38, 130.02,
129.23, 127.99, 127.68, 126.88, 125.50, 123.35, 122.11, 114.13,
112.90 (d, JFC = 22.5 Hz), 110.37, 102.26 (d, JFC = 27.5 Hz),
101.16, 47.76, 20.53, 20.25. FTIR (neat): 2949, 2924, 2854,
1620, 1583, 1541, 1479, 1402, 1307, 1223, 1184, 962, 825, 767,
688 cm-1. HRMS (ESI): m/z calcd for C30H22Cl2FN2O [M+H]+
515.1088, found 515.1087.
4.3.20. 6-(6-bromopyridin-2-yl)-7-((6-
bromopyridin-2-yl)methyl)benzo[4,5] imidazo[1,2-
a]quinolin-5(7H)-one (2t)
Following the general procedure B, compound 2t was
obtained as a white solid in 55% yield (61.4 mg), mp: 214-217
˚C. 1H NMR (500 MHz, CDCl3) δ 8.61 (dd, J = 8.0, 1.5 Hz, 1H),
8.45 (d, J = 8.5 Hz, 1H), 8.27 (d, J = 8.1 Hz, 1H), 7.84 – 7.79 (m,
1H), 7.58 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.51 (t, J =
7.7 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 7.42 – 7.39 (m, 1H), 7.38 –
7.32 (m, 3H), 7.13 (d, J = 7.7 Hz, 1H), 6.96 (d, J = 7.6 Hz, 1H),
5.06 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 173.59, 155.74,
154.04, 146.90, 141.79, 141.03, 139.40, 137.96, 135.52, 134.54,
131.66, 129.03, 128.01, 127.50, 127.15, 126.19, 125.89, 125.15,
124.95, 123.39, 119.67, 115.51, 113.49, 109.94, 100.95, 50.43.
FTIR (neat): 3054, 3034, 2972, 1737, 1626, 1600, 1537, 1495,
1467, 1404, 1352, 1298, 1213, 1116, 1078, 960, 846, 732, 694
4.3.17. 7-(3,4-difluorobenzyl)-6-(3,4-
difluorophenyl)-2-methoxy-9,10-
dimethylbenzo[4,5]imidazo[1,2-a]quinolin-5(7H)-
one (2q)
Following the general procedure B, compound 2q was
obtained as a white solid in 70% yield (74.2 mg), mp: 252-254
1
˚C. H NMR (500 MHz, CDCl3) δ 8.54 (d, J = 8.9 Hz, 1H), 7.97

cm-1. HRMS (ESI): m/z calcd for C26H17Br2N4O [M+H]+
558.9764, found 558.9762, 560.9748, 562.9726.
(q, JFC = 32.5 Hz), 129.30, 128.86 (q, JFC = 32.5 Hz), 128.45,
ACCEPTED MANUSCRIPT
127.05, 126.98, 126.37, 125.57 (q, JFC = 2.5 Hz), 125.01 (q, JFC
3.75 Hz), 124.51, 124.26 (q, JFC = 270.0 Hz), 124.08 (q, JFC
=
=
4.3.21. 3-(4-fluorobenzyl)-4-(4-
fluorophenyl)imidazo[1,2-a]quinolin-5(3H)-one
(2u)
271.25 Hz), 123.81, 120.95, 117.18, 113.92, 46.87, 20.20, 18.55.
19F NMR (470 MHz, CDCl3) δ -62.37, -62.40. FTIR (neat): 3331,
2924, 1680, 1608, 1576, 1518, 1464, 1323, 1109, 1064, 843, 762
cm-1. HRMS (ESI): m/z calcd for C32H25F6N2O [M+H]+ 567.1866,
found 567.1864.
Following the general procedure B, compound 2u was
obtained as a slight yellow oil in 50% yield (38.6 mg), mp: 238-
1
241 ˚C. H NMR (500 MHz, CO(CD3)2) δ 8.41 (dd, J = 8.0, 1.2
4.4.3. 1-(4,5-dimethyl-2-((3-
nitrobenzyl)amino)phenyl)-3-(3-
nitrophenyl)quinolin-4(1H)-one (3c)
Hz, 1H), 8.17 (d, J = 2.6 Hz, 1H), 8.08 (d, J = 8.3 Hz, 1H), 7.72
(ddd, J = 8.5, 7.1, 1.5 Hz, 1H), 7.50 – 7.44 (m, 1H), 7.33 (d, J =
2.6 Hz, 1H), 7.25 – 7.19 (m, 2H), 7.03 – 6.96 (m, 4H), 6.83 (dd, J
= 8.8, 5.3 Hz, 2H), 4.83 (s, 2H). 13C NMR (175 MHz, CO(CD3)2)
δ 171.48, 162.72 (d, JFC = 243.25 Hz), 162.27 (d, JFC = 243.25
Hz), 143.99, 134.88 (d, JFC = 8.75 Hz), 133.61, 133.28, 131.69,
130.94, 128.79 (d, JFC = 8.75 Hz), 127.72, 126.16, 124.92,
122.58, 115.73 (d, JFC = 22.75 Hz) , 115.44, 114.68 (d, JFC = 21
Hz), 109.62, 100.53, 50.98. FTIR (neat): 2957, 2922, 2851, 1722,
1599, 1510, 1463, 1418, 1219, 1116, 817, 758, 700 cm-1. HRMS
(ESI): m/z calcd for C24H17F2N2O [M+H]+ 387.1303, found
387.1311.
Following the general procedure C, compound 3c was
obtained as a white solid in 73% yield (75.9 mg), mp: 222-223
1
˚C. H NMR (500 MHz, CDCl3) δ 8.49 (s, 1H), 8.35 (d, J = 7.9
Hz, 1H), 8.13 (s, 1H), 8.09 (dd, J = 15.6, 7.5 Hz, 3H), 7.95 (s,
1H), 7.66 – 7.61 (m, 2H), 7.50 (t, J = 7.8 Hz, 2H), 7.33 (t, J = 7.4
Hz, 1H), 7.11 (d, J = 8.5 Hz, 1H), 7.01 (s, 1H), 6.50 (s, 1H), 4.61
– 4.47 (m, 2H), 2.24 (s, 3H), 2.20 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 175.66, 148.65, 147.85, 143.09, 141.96, 140.98,
140.18, 140.00, 136.68, 134.05, 132.99, 132.57, 129.61, 129.40,
128.85, 126.84, 126.60, 126.30, 124.87, 123.69, 122.93, 122.25,
121.58, 121.50, 119.49, 117.33, 113.67, 46.27, 20.22, 18.54.
FTIR (neat): 3311, 2922, 1710, 1607, 1521, 1342, 1281, 732 cm-
1. HRMS (ESI): m/z calcd for C30H25N4O5 [M+H]+ 521.1819,
found 521.1815.
4.4 Synthesis of compound 3
General procedure C: To a 10 mL sealed tube, compound 1
(1.0 equiv., 0.2 mmol) and benzyl bromides (4.0 equiv., 0.8
mmol) in toluene (0.5 mL) were added, and the reaction was
heated at 130 ˚C for 15 h. Upon the completion of the starting
materials, toluene was removed under the reduced pressure. After
the remaining solid was totally dissolved in methanol (2.0 mL),
DBU (2.0 equiv., 0.4 mmol, 60.0 μL) was added and the reaction
was stirred at room temperature for 4 h. Then methanol was
removed, and the residue was dissolved in DCM (50 mL),
washed with H2O (20 mL × 3), and dried over anhydrous
Na2SO4. The solvent was removed and the crude was purified by
using silica gel column chromatography (PE/EA = 20:1-5:1 as
the eluents) to afford the target compound 3.
4.4.4. 1-(2-((4-(tert-butyl)benzyl)amino)-4,5-
dimethylphenyl)-3-(4-(tert-butyl)phenyl)quinolin-
4(1H)-one (3d)
Following the general procedure C, compound 3d was
obtained as a white solid in 37% yield (40.1 mg), mp: 153-154
˚C. 1H NMR (500 MHz, CDCl3) δ 8.58 (dd, J = 8.0, 1.0 Hz, 1H),
7.79 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.56 – 7.51 (m, 1H), 7.44
(d, J = 8.4 Hz, 2H), 7.40 (t, J = 7.5 Hz, 1H), 7.28 (d, J = 8.2 Hz,
2H), 7.10 (d, J = 8.1 Hz, 2H), 7.04 (d, J = 8.5 Hz, 1H), 6.98 (s,
1H), 6.70 (s, 1H), 4.36 – 4.22 (m, 2H), 3.77 (s, 1H), 2.30 (s, 3H),
2.21 (s, 3H), 1.36 (s, 9H), 1.29 (s, 9H). 13C NMR (125 MHz,
CDCl3) δ 176.17, 150.23, 149.97, 142.19, 141.73, 140.19,
139.48, 135.55, 132.20, 131.86, 129.23, 128.23, 127.20, 127.00,
126.73, 125.94, 125.54, 125.20, 124.00, 123.94, 122.69, 117.08,
113.94, 47.26, 34.49, 34.41, 31.32, 31.27, 20.16, 18.55. FTIR
(neat): 3358, 2960, 1712, 1622, 1514, 1477, 1328, 835, 758 cm-1.
HRMS (ESI): m/z calcd for C38H43N2O [M+H]+ 543.3370, found
543.3375.
4.4.1. 1-(2-(benzylamino)-4,5-dimethylphenyl)-3-
phenylquinolin-4(1H)-one (3a)
Following the general procedure C, compound 3a was
obtained as a white solid in 91% yield (78.3 mg), mp: 168-171
1
˚C. H NMR (500 MHz, CDCl3) δ 8.57 (d, J = 7.9 Hz, 1H), 7.84
(s, 1H), 7.74 (d, J = 7.5 Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.47 –
7.38 (m, 3H), 7.37 – 7.32 (m, 1H), 7.30 (d, J = 7.3 Hz, 2H), 7.26
(dd, J = 11.5, 7.2 Hz, 3H), 7.10 (d, J = 8.5 Hz, 1H), 7.02 (s, 1H),
6.71 (s, 1H), 4.47 – 4.32 (m, 2H), 4.23 – 4.06 (m, 1H), 2.32 (s,
3H), 2.25 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 175.90, 142.34,
141.54, 140.13, 139.42, 138.79, 135.08, 131.80, 129.13, 128.48,
128.07, 127.08, 127.03, 126.94, 126.81, 125.84, 123.95, 123.87,
122.54, 117.04, 113.96, 47.34, 20.08, 18.47. FTIR (neat): 3369,
2922, 1680, 1620, 1587, 1516, 1465, 1334, 762, 696 cm-1. HRMS
(ESI): m/z calcd for C30H27N2O [M+H]+ 431.2118, found
431.2114.
4.4.5. 1-(2-((3-bromobenzyl)amino)-4,5-
dimethylphenyl)-3-(3-bromophenyl)quinolin-4(1H)-
one (3e)
Following the general procedure C, compound 3e was
obtained as a white solid in 77% yield (90.2 mg), mp: 164-166
˚C. 1H NMR (500 MHz, CDCl3) δ 8.50 (dd, J = 8.1, 1.2 Hz, 1H),
7.83 (s, 1H), 7.78 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.61 – 7.56
(m, 1H), 7.45 – 7.37 (m, 2H), 7.37 – 7.32 (m, 2H), 7.25 (t, J =
7.8 Hz, 2H), 7.19 – 7.11 (m, 2H), 7.03 (d, J = 8.5 Hz, 1H), 6.99
(s, 1H), 6.57 (s, 1H), 4.38 – 4.26 (m, 2H), 2.26 (s, 3H), 2.20 (s,
3H). 13C NMR (175 MHz, CDCl3) δ 175.72, 142.58, 141.62,
141.19, 140.11, 139.73, 137.16, 132.25, 131.08, 130.25, 130.17,
129.94, 129.79, 129.63, 129.26, 127.07, 127.02, 126.93, 126.17,
125.45, 124.41, 123.82, 122.82, 122.18, 120.96, 117.15, 113.84,
46.58, 20.20, 18.55. FTIR (neat): 3319, 2922, 1681, 1608, 1516,
1323, 1255, 1068, 837, 738, 665 cm-1. HRMS (ESI): m/z calcd
for C30H25Br2N2O [M+H]+ 587.0328, found 587.0310, 589.0303,
591.0292.
4.4.2. 1-(4,5-dimethyl-2-((4-
(trifluoromethyl)benzyl)amino)phenyl)-3-(4-
(trifluoromethyl)phenyl)quinolin-4(1H)-one (3b)
Following the general procedure C, compound 3b was
obtained as a white solid in 80% yield (90.6 mg), mp: 195-197
1
˚C. H NMR (500 MHz, CDCl3) δ 8.49 (d, J = 8.0 Hz, 1H), 7.81
(s, 1H), 7.80 (d, J = 8.2 Hz, 2H), 7.62 (d, J = 8.1 Hz, 2H), 7.58 –
7.50 (m, 3H), 7.39 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H),
7.03 (d, J = 8.5 Hz, 1H), 7.00 (s, 1H), 6.56 (s, 1H), 4.41 (s, 2H),
2.26 (s, 3H), 2.20 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 175.76,
143.36, 142.84, 141.27, 140.21, 139.88, 138.75, 132.16, 129.50
4.4.6. 1-(2-((3,4-difluorobenzyl)amino)-4,5-
dimethylphenyl)-3-(3,4-difluorophenyl)quinolin-
4(1H)-one (3f)

10
Tetrahedron
Following the general procedure C, compound 3f was
1244, 756, 696 cm-1. HRMS (ESI): m/z calcd for C H N O
28 23 2
ACCEPTED MANUSCRIPT
obtained as a white solid in 85% yield (85.3 mg), mp: 171-173
˚C. H NMR (500 MHz, CDCl3) δ 8.39 (d, J = 7.9 Hz, 1H), 7.75
(s, 1H), 7.61 – 7.50 (m, 2H), 7.37 – 7.29 (m, 2H), 7.16 – 6.92 (m,
6H), 6.55 (s, 1H), 4.41 – 4.26 (m, 2H), 2.26 (s, 3H), 2.19 (s, 3H).
13C NMR (175 MHz, CDCl3) δ 175.69, 150.48 (dd, JFC = 246.25,
[M+H]+ 403.1805, found 403.1816.
1
4.4.10. 1-(2-((3-chlorobenzyl)amino)phenyl)-3-(3-
chlorophenyl)quinolin-4(1H)-one (3j)
Following the general procedure C, compound 3j was
obtained as a white solid in 83% yield (78.0 mg), mp: 151-152
˚C. H NMR (500 MHz, CO(CD3)2) δ 8.42 (d, J = 8.0 Hz, 1H),
12.25 Hz), 149.87 (dd, JFC = 246.25, 12.25 Hz), 149.42 (dd, JFC
246.25, 12.25 Hz), 149.40 (dd, JFC = 245.88, 17.5 Hz), 142.41,
=
1
8.12 (s, 1H), 7.97 (t, J = 1.7 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H),
7.65 (ddd, J = 8.5, 7.1, 1.5 Hz, 1H), 7.46 – 7.41 (m, 1H), 7.39 (d,
J = 7.9 Hz, 1H), 7.37 – 7.34 (m, 3H), 7.34 – 7.29 (m, 3H), 7.26 –
7.20 (m, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.87 – 6.80 (m, 2H), 5.95
(t, J = 5.8 Hz, 1H), 4.44 (d, J = 6.3 Hz, 2H). 13C NMR (125
MHz, CO(CD3)2) δ 175.88, 144.87, 143.68, 143.30, 141.31,
138.71, 134.59, 133.91, 132.73, 131.50, 130.71, 130.16, 129.80,
129.14, 128.16, 127.51, 127.42, 127.27, 127.16, 127.01, 126.20,
124.57, 120.96, 118.00, 117.75, 113.04, 46.21. FTIR (neat):
3325, 2922, 1681, 1620, 1575, 1516, 1477, 1323, 748, 680 cm-1.
HRMS (ESI): m/z calcd for C28H21Cl2N2O [M+H]+ 471.1025,
found 471.1019.
141.18, 140.12, 139.81, 136.35, 132.15, 131.97, 129.28, 126.86,
126.29, 124.42, 124.02 (d, JFC = 3.5 Hz), 123.80, 122.61 (d, JFC
=
3.5 Hz), 120.25, 117.51, 117.40, 117.32 (d, JFC = 17.5 Hz),
117.15, 116.70 (d, JFC = 15.75 Hz), 115.66 (d, JFC = 17.5 Hz),
113.90, 46.27, 20.19, 18.53. FTIR (neat): 3321, 2922, 1680,
1610, 1574, 1512, 1338, 1271, 1109, 812, 758 cm-1. HRMS
(ESI): m/z calcd for C30H23F4N2O [M+H]+ 503.1741, found
503.1736.
4.4.7. 3-(6-bromopyridin-2-yl)-1-(2-(((6-
bromopyridin-2-yl)methyl)amino)-4,5-
dimethylphenyl)quinolin-4(1H)-one (3g)
Following the general procedure C, compound 3g was
obtained as a white solid in 94% yield (110.5 mg), mp: 217-218
˚C. 1H NMR (500 MHz, DMSO) δ 8.90 (d, J = 7.8 Hz, 1H), 8.67
(s, 1H), 8.41 (dd, J = 8.0, 1.2 Hz, 1H), 7.80 (t, J = 7.8 Hz, 1H),
7.74 – 7.61 (m, 2H), 7.51 – 7.44 (m, 3H), 7.22 (d, J = 7.6 Hz,
1H), 7.13 (s, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.57 (s, 1H), 6.05 (t, J
= 6.3 Hz, 1H), 4.32 (d, J = 6.2 Hz, 2H), 2.17 (s, 3H), 2.12 (s,
3H). 13C NMR (125 MHz, DMSO) δ 175.10, 161.74, 154.38,
145.66, 141.36, 140.63, 140.34, 140.04, 139.98, 139.92, 139.19,
132.36, 129.27, 127.60, 126.15, 126.07, 125.53, 124.69, 124.43,
123.34, 121.47, 119.96, 117.77, 116.11, 113.36, 47.04, 19.73,
17.99. FTIR (neat): 3344, 2920, 1618, 1578, 1521, 1421, 1317,
1121, 779 cm-1. HRMS (ESI): m/z calcd for C28H23Br2N4O
[M+H]+ 589.0233, found 589.0235, 591.0221, 593.0199.
4.4.11. 1-(2-((3-bromobenzyl)amino)phenyl)-3-(3-
bromophenyl)quinolin-4(1H)-one (3k)
Following the general procedure C, compound 3k was
obtained as a white solid in 74% yield (82.6 mg), mp: 140-141
1
˚C. H NMR (500 MHz, CO(CD3)2) δ 8.43 (dd, J = 8.1, 1.3 Hz,
1H), 8.15 – 8.09 (m, 2H), 7.83 – 7.79 (m, 1H), 7.67 (ddd, J = 8.6,
7.0, 1.6 Hz, 1H), 7.50 (s, 1H), 7.49 – 7.41 (m, 2H), 7.41 – 7.31
(m, 5H), 7.24 (t, J = 7.8 Hz, 1H), 6.99 (d, J = 8.5 Hz, 1H), 6.83
(dd, J = 11.1, 4.5 Hz, 2H), 5.95 (t, J = 6.2 Hz, 1H), 4.44 (d, J =
6.3 Hz, 2H). 13C NMR (125 MHz, CO(CD3)2) δ 175.85, 144.82,
143.66, 143.53, 141.31, 139.00, 132.77, 132.02, 131.50, 130.99,
130.46, 130.43, 130.11, 129.79, 128.15, 127.86, 127.26, 127.00,
126.62, 124.55, 122.85, 122.16, 120.90, 117.98, 117.75, 113.02,
110.69, 46.12. FTIR (neat): 3346, 2922, 1712, 1608, 1577, 1521,
1479, 1317, 759, 740, 682 cm-1. HRMS (ESI): m/z calcd for
C28H21Br2N2O [M+H]+ 559.0015, found 558.9992, 560.9987,
562.9977.
4.4.8. 1-(4,5-dimethyl-2-((thiophen-3-
ylmethyl)amino)phenyl)-3-(thiophen-3-yl)quinolin-
4(1H)-one (3h)
Following the general procedure C, compound 3h was
obtained as a white solid in 94% yield (37 mg), mp: 216-217 ˚C.
1H NMR (500 MHz, CDCl3) δ 8.49 (d, J = 7.2 Hz, 1H), 8.49 (d, J
= 7.2 Hz, 1H), 8.19 (d, J = 2.0 Hz, 1H), 7.95 (s, 1H), 7.52 – 7.46
(m, 1H), 7.40 (d, J = 4.4 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.30
(dd, J = 5.0, 3.1 Hz, 1H), 7.22 (dd, J = 4.9, 3.0 Hz, 1H), 7.03 –
6.95 (m, 3H), 6.86 (d, J = 4.8 Hz, 1H), 6.72 (s, 1H), 4.33 (s, 2H),
2.31 (s, 3H), 2.21 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 175.76,
141.54, 141.40, 139.90, 139.75, 139.64, 134.76, 131.80, 129.29,
127.06, 126.82, 126.55, 126.32, 126.17, 125.91, 124.61, 124.13,
124.06, 122.93, 121.36, 117.80, 117.04, 114.08, 43.13, 20.20,
18.58. FTIR (neat): 3342, 2914, 2856, 1620, 1608, 1573, 1520,
1479, 1381, 1289, 754, 678 cm-1. HRMS (ESI): m/z calcd for
C26H23N2OS2 [M+H]+ 443.1246, found 443.1256.
4.4.12. 1-(2-((3,4-dichlorobenzyl)amino)phenyl)-3-
(3,4-dichlorophenyl)quinolin-4(1H)-one (3l)
Following the general procedure C, compound 3l was
obtained as a white solid in 75% yield (80.7 mg), mp: 148-150
1
˚C. H NMR (500 MHz, CDCl3) δ 8.30 (d, J = 7.8 Hz, 1H), 7.79
(s, 1H), 7.75 (s, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.47 (d, J = 8.0 Hz,
1H), 7.42 – 7.34 (m, 4H), 7.31 (t, J = 7.5 Hz, 1H), 7.23 – 7.17
(m, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.97 (d, J = 8.5 Hz, 1H), 6.87
(t, J = 7.3 Hz, 1H), 6.72 (d, J = 8.2 Hz, 1H), 4.90 (s, 1H), 4.49 –
4.33 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 175.64, 143.54,
142.42, 139.88, 139.74, 139.69, 134.82, 132.74, 132.24, 131.89,
131.19, 130.98, 130.68, 130.57, 129.80, 129.64, 128.71, 127.08,
126.73, 126.57, 126.32, 125.88, 124.59, 119.54, 117.50, 117.03,
112.36, 45.78. FTIR (neat): 3323, 2922, 1681, 1607, 1575, 1519,
1471, 1319, 1028, 821, 740 cm-1. HRMS (ESI): m/z calcd for
C28H19Cl4N2O [M+H]+ 539.0246, found 539.0190.
4.4.9. 1-(2-(benzylamino)phenyl)-3-phenylquinolin-
4(1H)-one (3i)
Following the general procedure C, compound 3i was
4.4.13. 1-(2-((4-
(trifluoromethyl)benzyl)amino)phenyl)-3-(4-
(trifluoromethyl)phenyl)quinolin-4(1H)-one (3m)
obtained as a white solid in 85% yield (68.3 mg), mp: 189-191
1
˚C. H NMR (500 MHz, CDCl3) δ 8.54 (d, J = 8.1 Hz, 1H), 7.80
(s, 1H), 7.68 (d, J = 7.9 Hz, 2H), 7.54 (t, J = 7.7 Hz, 1H), 7.40 (t,
J = 7.1 Hz, 3H), 7.36 (d, J = 8.8 Hz, 1H), 7.34 – 7.31 (m, 1H),
7.30 – 7.25 (m, 2H), 7.24 (d, J = 7.5 Hz, 1H), 7.22 – 7.18 (m,
3H), 7.01 (d, J = 8.5 Hz, 1H), 6.84 (dd, J = 16.8, 8.1 Hz, 2H),
4.41 – 4.31 (m, 2H), 4.26 (s, 1H). 13C NMR (125 MHz, CDCl3) δ
176.06, 143.81, 142.03, 140.04, 138.39, 135.00, 132.04, 130.95,
128.66, 128.63, 128.61, 128.21, 127.31, 127.22, 127.15, 127.03,
126.81, 126.14, 124.19, 122.93, 117.64, 116.88, 112.59, 47.19.
FTIR (neat): 3337, 2922, 1736, 1620, 1607, 1577, 1520, 1323,
Following the general procedure C, compound 3m was
obtained as a white solid in 70% yield (75.3 mg), mp: 197-200
1
˚C. H NMR (500 MHz, CDCl3) δ 8.26 (d, J = 7.8 Hz, 1H), 7.82
(s, 1H), 7.69 (d, J = 8.2 Hz, 2H), 7.53 (dt, J = 14.5, 7.4 Hz, 5H),
7.39 (d, J = 7.9 Hz, 2H), 7.35 (t, J = 7.8 Hz, 1H), 7.26 (t, J = 7.5
Hz, 1H), 7.21 (d, J = 7.7 Hz, 1H), 7.00 (d, J = 8.5 Hz, 1H), 6.86
(t, J = 7.5 Hz, 1H), 6.74 (d, J = 8.3 Hz, 1H), 5.08 (t, J = 5.9 Hz,
1H), 4.59 – 4.45 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 175.81,

143.63, 143.08, 142.58, 140.03, 138.59, 132.22, 131.21, 129.60
C29H18Br2F5N2O [M+H]+ 662.9701, found 662.9696, 664.9682,
666.9664.
ACCEPTED MANUSCRIPT
(q, JFC = 32.5 Hz), 128.88 (q, JFC = 32.5 Hz), 128.75, 128.39,
127.04, 127.01, 126.92, 126.00, 125.60 (q, JFC = 3.75 Hz),
125.00 (q, JFC = 3.75 Hz), 124.62, 124.23 (q, JFC = 270.13 Hz),
124.05 (q, JFC = 270.38 Hz), 121.03, 117.83, 116.97, 112.50,
46.64. FTIR (neat): 3365, 2924, 1712, 1682, 1608, 1579, 1521,
1321, 1107, 1064, 756, 740 cm-1. HRMS (ESI): m/z calcd for
C30H21F6N2O [M+H]+ 539.1553, found 539.1564.
4.5. Synthesis of intermediates I and II.
4.5.1. 10,10a-dibenzyl-7,8-dimethyl-10,10a-
dihydro-11H-benzo[4,5]imidazo[1,2-a]indol-11-one
(I)
4.4.14. 1-(2-(benzylamino)-4,5-dimethylphenyl)-5-
According to the general procedure B, after the reaction was
running for two hours (we found a new weak red spot (compound
I), together with product 2 and starting material 1, on the TLC
plate), it was terminated mandatorily by adding water, and the
mixture was then extracted with AcOEt. The AcOEt layer was
dried and removed, and the crude mixture was purified using
silica gel column chromatography (PE/EA = 100:1 - 50:1) to
afford compound I as a red solid, mp: 168-169 ˚C. 1H NMR (500
MHz, DMSO) δ 7.64 – 7.60 (m, 1H), 7.51 (d, J = 9.1 Hz, 2H),
7.34 (s, 1H), 7.26 (t, J = 7.3 Hz, 2H), 7.20 (d, J = 7.2 Hz, 1H),
7.18 – 7.15 (m, 4H), 7.13 (t, J = 7.4 Hz, 2H), 7.07 (ddd, J = 10.9,
5.2, 2.7 Hz, 2H), 5.92 (s, 1H), 4.90 (d, J = 16.4 Hz, 1H), 4.46 (d,
J = 16.4 Hz, 1H), 3.37 (d, J = 13.4 Hz, 1H), 3.14 (d, J = 13.3 Hz,
1H), 2.14 (s, 3H), 1.96 (s, 3H).13C NMR (125 MHz, DMSO) δ
198.94, 161.83, 142.85, 138.30, 138.03, 133.70, 133.09, 132.01,
130.49, 128.40, 127.70, 126.87, 126.63, 126.53, 125.11, 124.25,
123.09, 117.92, 115.05, 107.69, 89.99, 45.81, 36.61, 19.52,
18.94. FTIR (neat): 2918, 1849, 1708, 1600, 1494, 1454, 1360,
1296, 1134, 841, 746, 696 cm-1. HRMS (ESI): m/z calcd for
C30H27N2O [M+H]+ 431.2118, found 431.2118.
chloro-3-phenylquinolin-4(1H)-one (3n)
Following the general procedure C, compound 3n was
obtained as a white solid in 63% yield (58.5 mg), mp: 224-226
1
˚C. H NMR (500 MHz, CDCl3) δ 7.66 (s, 1H), 7.66 – 7.63 (m,
2H), 7.37 (t, J = 7.5 Hz, 2H), 7.35 – 7.29 (m, 3H), 7.29 – 7.20
(m, 4H), 7.17 (d, J = 7.1 Hz, 2H), 6.95 (s, 1H), 6.92 (dd, J = 7.7,
2.0 Hz, 1H), 6.64 (s, 1H), 4.39 – 4.22 (m, 2H), 3.89 (s, 1H), 2.26
(s, 3H), 2.18 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 175.59,
142.80, 141.47, 141.23, 139.73, 138.69, 135.20, 134.75, 131.11,
129.13, 128.86, 128.67, 128.12, 127.35, 127.28, 126.94, 126.31,
124.59, 124.30, 123.45, 116.29, 114.19, 47.56, 20.17, 18.57.
FTIR (neat): 3354, 2920, 1712, 1614, 1573, 1519, 1462, 1304,
808, 731, 692 cm-1. HRMS (ESI): m/z calcd for C30H26ClN2O
[M+H]+ 465.1728, found 465.1736.
4.4.15. 1-(2-((3,4-dichlorobenzyl)amino)-4,5-
dimethylphenyl)-3-(3,4-dichlorophenyl)-7-
methoxyquinolin-4(1H)-one (3o)
Following the general procedure C, compound 3o was
obtained as a white solid in 90% yield (107.3 mg), mp: 259-260
1
˚C. H NMR (500 MHz, CDCl3) δ 8.26 (d, J = 9.0 Hz, 1H), 7.75
4.5.2. 10,11-dibenzyl-11-hydroxy-7,8-dimethyl-11H-
(d, J = 2.0 Hz, 1H), 7.68 (s, 1H), 7.48 (dd, J = 8.4, 2.0 Hz, 1H),
7.36 (t, J = 5.6 Hz, 3H), 7.10 (dd, J = 8.2, 1.6 Hz, 1H), 6.94 (s,
1H), 6.90 (dd, J = 9.0, 2.3 Hz, 1H), 6.51 (s, 1H), 6.33 (d, J = 2.3
Hz, 1H), 4.57 (d, J = 5.5 Hz, 1H), 4.43 – 4.30 (m, 2H), 3.76 (s,
3H), 2.25 (s, 3H), 2.18 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
175.17, 162.99, 142.20, 141.94, 140.94, 139.90, 139.68, 135.13,
132.78, 132.06, 131.11, 130.72, 130.62, 129.92, 129.23, 129.00,
128.65, 127.59, 126.51, 126.13, 123.82, 121.14, 119.87, 113.86,
113.15, 99.48, 55.59, 46.22, 20.27, 18.60. FTIR (neat): 3325,
2921, 1614, 1572, 1519, 1460, 1278, 1208, 833 cm-1. HRMS
(ESI): m/z calcd for C31H25Cl4N2O2 [M+H]+ 597.0665, found
597.0658.
benzo[4,5]imidazo[1,2-a]indol-10-ium bromide (II)
The intermediate II was obtained from the first step according
to the general procedure C. The crude product was dissolved in
MeOH and purified using semi-preparative HPLC (column:
ODS-AQ C18, 250×10 mml.D.S-5 μm, 12 nm) with MeOH:H2O
1
= 63:37 as eluent, mp: 34-37 ˚C. H NMR (500 MHz, MeOD) δ
8.03 (s, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.66 (dt, J = 7.1, 3.5 Hz,
2H), 7.60 – 7.53 (m, 2H), 7.50 (d, J = 7.0 Hz, 2H), 7.47 – 7.36
(m, 3H), 7.11 (t, J = 7.4 Hz, 1H), 7.03 (t, J = 7.5 Hz, 2H), 6.84
(d, J = 7.3 Hz, 2H), 5.93 (d, J = 15.5 Hz, 1H), 5.78 (d, J = 15.5
Hz, 1H), 3.79 (d, J = 13.5 Hz, 1H), 3.71 (d, J = 13.6 Hz, 1H),
2.48 (s, 3H), 2.40 (s, 3H). 13C NMR (125 MHz, MeOD) δ 158.15,
140.16, 139.69, 139.28, 137.04, 135.14, 134.55, 134.37, 132.19,
131.02, 130.35, 130.22, 129.37, 129.23, 129.09, 128.82, 126.81,
126.24, 115.65, 114.76, 114.67, 81.10, 50.90, 45.37, 20.60,
20.43. FTIR (neat): 3047, 2929, 1681, 1558, 1483, 1456, 1202,
1138, 979, 800, 725, 704 cm-1. HRMS (ESI): m/z calcd for
C30H27N2O [M]+ 431.2118, found 431.2113.
4.4.16. 1-(2-((2-bromo-5-
fluorobenzyl)amino)phenyl)-3-(2-bromo-5-
fluorophenyl)-7-(trifluoromethyl)quinolin-4(1H)-
one (3p)
Following the general procedure C, compound 3p was
obtained as a white solid in 34% yield (45.0 mg), mp: 247-248
˚C. 1H NMR (500 MHz, DMSO) δ 8.53 (d, J = 8.3 Hz, 1H), 8.21
(s, 1H), 7.81 – 7.73 (m, 2H), 7.65 (dd, J = 8.7, 5.3 Hz, 1H), 7.38
(t, J = 7.6 Hz, 2H), 7.31 (dd, J = 9.4, 3.1 Hz, 1H), 7.22 (td, J =
8.5, 3.1 Hz, 1H), 7.16 (s, 1H), 7.08 (td, J = 8.4, 3.1 Hz, 1H), 6.91
(dd, J = 9.6, 3.0 Hz, 1H), 6.84 (dd, J = 10.9, 4.1 Hz, 1H), 6.61 (d,
J = 8.1 Hz, 1H), 6.33 (t, J = 5.8 Hz, 1H), 4.28 (qd, J = 17.2, 5.9
Acknowledgments
We thank Prof. Liming Zhang (UC Santa Barbara) and Dr.
Zhixun Wang (Yale University) for valuable discussions and
suggestions. We also thank Dr. Zhihui Xiao, Dr. Chuanrong Li,
and Dr. Xiaohong Zheng for the help on NMR analysis, and Ms.
Aijun Sun, Ms. Yun Zhang, and Ms. Xuan Ma for the help on
HRMS and X-ray analysis. This work was supported by the
National Natural Science Foundation of China (21772210,
41476135) and Natural Science Foundation of Anhui Province
(1608085MB38).
Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 174.53, 162.18 (d, JFC
=
246.25 Hz), 161.66 (d, JFC = 246.25 Hz), 144.79, 143.06, 140.16,
139.08 (d, JFC = 6.25 Hz), 136.55 (d, JFC = 7.5 Hz), 134.41,
134.18 (q, JFC = 8.75 Hz), 131.82, 128.86, 128.73, 128.70,
125.19, 123.31 (q, JFC = 270.0 Hz), 122.95, 120.67, 119.56 (d,
JFC = 22.5 Hz), 118.71, 118.47 (d, JFC = 2.5 Hz), 116.78 (d, JFC
=
225 Hz) 116.73 (d, JFC = 2.5 Hz), 116.19 (d, JFC = 22.5 Hz),
115.72 (d, JFC = 22.5 Hz), 114.63 (d, JFC = 3.75 Hz), 112.85,
47.56. FTIR (neat): 3396, 2924, 1605, 1516, 1462, 1317, 1170,
1128, 1026, 808 cm-1. HRMS (ESI): m/z calcd for
Appendix A. Supplementary data

12
Tetrahedron
Supplementary data to this article can be found online at
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ACCEPTED MANUSCRIPT
Sci. 2011, 13, 19; (b) Janni, M.; Arora, S.; Peruncheralathan, S.,
https://doi.org
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