Straightforward Synthesis of Novel 4-Styrylquinolines/4-Styrylquinolin-2-ones and 9-Styryldihydroacridin-1(2 H)-ones from Substituted 2′-Aminochalcones

Article abstract of DOI:10.1055/s-0039-1707985

An alternative and efficient one-step approach to develop small libraries of polysubstituted 4-styrylquinolines/4-styrylquinolin-2-ones and 9-styryldihydroacridin-1-ones is described. According to this approach, new series of these compounds were straightforwardly synthesized in high yields starting from synthetically available 2′-aminochalcones and 1,3-dicarbonyl compounds in glacial acetic acid as a catalyst via the Friedl?nder reaction. Our approach also offers an expeditious way to access novel molecular hybrids in whose structures styryl and chalcone fragments are attached at the C4 and C3 positions, respectively, of the quinoline ring. All synthesized compounds were fully characterized by means of IR, HRMS and NMR techniques, and most were screened at the National Cancer Institute, USA, for their antitumor activity.

Full text of DOI:10.1055/s-0039-1707985

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–S
paper
A
en
A. Meléndez et al.
Paper
Synthesis
Straightforward Synthesis of Novel 4-Styrylquinolines/4-Styryl-
quinolin-2-ones and 9-Styryldihydroacridin-1(2H)-ones from
Substituted 2′-Aminochalcones
Angie Meléndeza
Esteban Plataa
Diego Rodrígueza
Diana Ardilaa
Sergio A. Guerreroa
Lina M. Acostaa
Justo Cobob
Ar
O
Ph
10 examples
O
up to 81% yield
N
H
O
1,3-dicarbonyl
compounds
Ar
Ar
Ar
AcOH, 60 °C
12–18 h
NH2
O
O
PhCHO
Manuel Noguerasb
Alirio Palma*a
Ph
X
KOH, EtOH
rt, 3 h
N
N
Y
42 examples
up to 91% yield
7 examples
up to 88% yield
a Laboratorio de Síntesis Orgánica, Escuela de Química,
Universidad Industrial de Santander, Carrera 27, Calle 9,
A.A 678, 680002 Bucaramanga, Colombia
apalma@uis.edu.co
b Inorganic and Organic Department, University of Jaén,
Campus Las Lagunillas s/n, 23071 Jaén, Spain
X = Y = Me; X–Y = CH2CH2CH2; X = OEt, Y = Me;
X = Ph, Y = Me; X = NH2, Y = Me
Received: 28.12.2019
Accepted after revision: 10.02.2020
Published online: 11.03.2020
olines, have also generated continuous interest among
chemists and biochemists, mainly because of applications
in medicinal chemistry as potential anti-HIV,10 antimicro-
bial,11 antimalarial,12 anti-Alzheimer13 and anticancer
agents,14 among others.15 It is not surprising, therefore, that
the development of new synthetic approaches to access this
class of compounds has attracted the attention of organic
and medicinal chemists.16 Contrary to 2-styrylquinolines,
4-styrylquinolines have been less investigated,17 and there-
fore scarcely reported due, in part, to the lack of general
methods for their synthesis. This kind of compound is usu-
ally prepared by employing Heck coupling between 4-halo-
quinolines and different aryl vinyl compounds18 or by
achieving the direct alkenylation of 4-methylquinolines
with aromatic aldehydes either through Perkin-type con-
densation19 or via a 4-C(sp3)–H bond activation with transi-
tion-metal catalysts.16k More recently, an Arbuzov/Horner–
Wadsworth–Emmons sequence was also proposed to ac-
cess 4-styrylquinolines from substituted 4-(halomethyl)-
quinolines.17c
Although these approaches are sufficiently effective and
versatile, some limitations nevertheless remain, for exam-
ple the need to pre-synthesize the required 4-alkylquino-
line or 4-halogenoquinoline starting materials, and the use
of harsh reaction conditions or expensive catalysts. Hence,
there is still a need to develop more attractive methodolo-
gies that guarantee not only the efficient and straightfor-
ward synthesis of unknown functionalized 4-styrylquino-
lines, but also permit a high-throughput access to libraries
of these compounds from inexpensive and synthetically
available precursors. To overcome these limitations, the
DOI: 10.1055/s-0039-1707985; Art ID: ss-2019-m0713-op
Abstract An alternative and efficient one-step approach to develop
small libraries of polysubstituted 4-styrylquinolines/4-styrylquinolin-2-
ones and 9-styryldihydroacridin-1-ones is described. According to this
approach, new series of these compounds were straightforwardly syn-
thesized in high yields starting from synthetically available 2′-amino-
chalcones and 1,3-dicarbonyl compounds in glacial acetic acid as a cata-
lyst via the Friedländer reaction. Our approach also offers an
expeditious way to access novel molecular hybrids in whose structures
styryl and chalcone fragments are attached at the C4 and C3 positions,
respectively, of the quinoline ring. All synthesized compounds were ful-
ly characterized by means of IR, HRMS and NMR techniques, and most
were screened at the National Cancer Institute, USA, for their antitumor
activity.
Key words 4-styrylquinolines, Friedländer reaction, 2′-aminochal-
cones, quinoline–chalcone hybrids, Claisen–Schmidt condensation
The quinoline nucleus is present in a wide range of nat-
ural and synthetic bioactive compounds and is considered
one of the privileged scaffolds in drug discovery.1 Quinoline
derivatives are well-known substances of great therapeutic
importance, particularly in the treatment of microbial,2 ma-
larial,3 fungal,4 inflammatory,5 viral,6 protozoal,3b,6a,7 cardio-
vascular8 and neoplastic diseases.1c,9 Moreover, several
well-known natural anticancer agents, including camptoth-
ecin, topotecan and irinotecan, contain a quinoline ring.1c,3b
On the other hand, a literature search revealed that
compounds in which a styryl fragment is attached at differ-
ent positions of the quinoline ring, especially 2-styrylquin-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. Meléndez et al.
Paper
Synthesis
Friedländer reaction between synthetically available 2′-
aminochalcones and commercial 1,3-dicarbonyl com-
pounds would be a reliable alternative.
hydroacridin-1-ones by means of their reaction with 1,3-
dicarbonyl substrates under classical Friedländer reaction
conditions,22 as shown in the retrosynthetic pathway de-
picted in Scheme 1.
In such a way, we here report the chemical behavior of a
series of 2′-aminochalcones in their reaction with a variety
of 1,3-dicarbonyl compounds for the efficient synthesis
of novel 4-styrylquinolines/4-styrylquinolin-2-ones and
9-styryldihydroacridin-1-ones, as well as quinoline-based
hybrid molecules containing both styryl and chalcone
moieties.
It is well known that substituted 2′-aminochalcones,
which are easily accessible by the condensation of 2′-ami-
noacetophenone and aromatic aldehydes, give access to 2-
substituted 1-azaflavanones via intramolecular nucleophil-
ic aza-Michael addition.20 In contrast, their use as valuable
precursors in the Friedländer reaction has remained practi-
cally unexplored.21 Keeping this picture, we envisioned
such chalcones as key intermediates to afford unreported 4-
styrylquinolines/4-styrylquinolin-2-ones and 9-styryldi-
Table 1 Optimization of the Reaction Conditions between 1a and 2a
Ph
O
O
O
acid/solvent
temperature
Ph
+
MeCOCH2COMe
+
N
H
Ph
NH2
2a
N
1a
3a
3'a
Entry
Acid
AcOH
Solvent
Temp (°C)
Time (h)
Yield (%) 3a
Yield (%) 3′a
1
2
EtOH
EtOH
EtOH
MeOH
MeOH
MeOH
toluene
toluene
MeCN
MeCN
EtOH
EtOH
EtOH
EtOH
EtOH
ionic liquid
–
60
80
15
62
74
57
45
56
48
25
33
35
42
65
57
50
38
30
–
–
AcOH
15
–
3
AcOH
100
60
15
22
–
4
AcOH
20
5
AcOH
80
20
–
6
AcOH
100
20
10
–
7
AcOH
60–80
100
60–80
24–30
30
8
AcOH
–
9
AcOH
18–24
24
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
AcOH
100
60
–
p-TsOH (10 mol%)
p-TsOH (10 mol%)
p-TsOH (10 mol%)
p-TsOH (20 mol%)
Amberlyst 15 (10 mol%)
–
15
–
80
15
15
26
38
52
–
100
60
15
15
60
15
60–80
15–24
15
AcOH (1 equiv)
AcOH (1 equiv)
AcOH (8.75 equiv)
AcOH (8.75 equiv)
AcOH (17.5 equiv)
AcOH (35 equiv)
AcOH (52.4 equiv)
AcOH (52.4 equiv)
AcOH (52.4 equiv)
AcOH (70.0 equiv)
AcOH (52.4 equiv)
60
80
60
80
60
60
60
60
50
60
60
60
62
67
69
73
80
87
87
60
86
88
–
–
15
–
–
15
–
–
15
–
–
12
–
–
12
–
–
12
–
–
15
–
–
12–15
12–15
12–15
–
–
–
–
–
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

C
A. Meléndez et al.
Paper
Synthesis
reaction time at 15 hours and performed the reaction at 60
or 80 °C with 1 or 8.75 equivalents of AcOH (entries 17–20).
Applying these conditions, 3a was obtained in similar yields
to those obtained in entries 1 and 2. Nevertheless, there
was a significant improvement by increasing the amount of
AcOH (entries 21–23): the desired product 3a was obtained
in 87% yield when the reaction was performed at 60 °C for
12 hours with a fixed molar ratio of 1a/2a/AcOH at 1:1:52.4
(entry 23). Remarkably, under these conditions, the alter-
native aza-Michael product was not detected at all. Other
reaction conditions did not afford better results (entries 21,
22, 24–27). From these trials, we concluded that the opti-
mum conditions are those highlighted in entry 23.
To explore the scope of this protocol, we tried such opti-
mized conditions using differently substituted 2′-amino-
chalcones with 2a as fixed 1,3-dicarbonyl component. The
obtained results, summarized in Table 2, show that the
electronic nature and position (para or meta) of the substit-
uent on the benzene ring of the styryl fragment practically
did not affect the yield of the expected Friedländer prod-
ucts 3. However, 2′-aminochalcones bearing a Me or OMe
group at the para position of the benzene ring exhibited
relatively higher efficiencies than their meta-substituted
analogues, and provided the corresponding 4-styrylquino-
lines 3b and 3c in better yields (84% vs 80% and 89% vs 78%,
respectively). Among the tested 2′-aminochalcones, 2-thio-
phenyl derivative 1j exhibited the highest efficiency and af-
forded the corresponding 4-styrylquinoline 3j in the best
yield (91%).
Ar
Ar
O
O
Y
O
O
Ar
X
NH2
N
N
H
X = Y = Me; X–Y = CH2CH2CH2; X = OEt, Y = Me;
X = Ph, Y = Me; X = NH2, Y = Me
Scheme 1 Retrosynthetic analysis of 4-styrylquinolines via strategic
Friedländer reaction
The reaction between 2′-aminochalcone 1a, namely (E)-
1-(2-aminophenyl)-3-phenylprop-2-en-1-one, and pen-
tane-2,4-dione (2a) was chosen as the model to implement
later on other reagents. We started studying that reaction in
ethanol (5 mL) in the presence of acetic acid as a catalyst, at
60 °C for 15 hours (TLC control), isolating a single product
in 62% yield (Table 1, entry 1). NMR analysis confirmed that
this product was the desired Friedländer product, (E)-1-(2-
methyl-4-styrylquinolin-3-yl)ethan-1-one (3a), and not the
alternative aza-Michael product 2-phenyl-2,3-dihydroquin-
olin-4(1H)-one (3′a). We moved then to further optimize
the reaction conditions by evaluating several variables, such
as solvent type, acid catalyst, temperature, reaction time
and reactants/catalyst molar ratio. The results are summa-
rized in Table 1.
Initially, we fixed the molar ratio of 2′-aminochalcone
1a/pentane-2,4-dione (2a)/glacial acetic acid at 1:1:1, and
solvent and temperature (60, 80 and 100 °C) were changed
(entries 1–10). Methanol, toluene and acetonitrile did not
improve the results in comparison with ethanol, even when
extending the reaction time to 24–30 hours (entries 7–10).
Ethanol exhibited the highest efficiency, affording 3a in 74%
yield when the reaction was run at 80 °C (entry 2). Increas-
ing the reaction temperature to 100 °C (entries 3 and 6) re-
sulted in a reduction in the 3a yield in favor of formation of
the alternative aza-Michael product 3′a.
Table 2 Scope of the Protocol with Respect to the 2′-Aminochalcone
Component 1a
Ar
O
O
Ar
AcOH
+
MeCOCH2COMe
NH2
2a
N
We also tested stronger acids than acetic acid as cata-
lysts, such as p-toluenesulfonic acid and Amberlyst 15, but
none afforded better results (entries 11–15). The best result
among these two catalysts was obtained with 10 mol% p-
TsOH at 60 °C, furnishing 3a in 65% yield (entry 11). Again,
an increased reaction temperature or the use of a larger
amount of p-TsOH showed a detrimental effect on the yield
of 3a, favoring the concomitant formation of 3′a (entries
12–14). The use of Amberlyst 15 (10 mol%) gave 3′a as the
major product, with 3a as the minor product in 30% yield
(entry 15). Attempts to promote the Friedländer reaction in
the ionic liquid 1-butyl-3-methylimidazolium tetrafluoro-
borate (a green reaction medium) did not afford the desired
product 3a, and the reactants were recovered unchanged
(entry 16).
1
3
Ar
Ph
Product
Yield (%)
3a
3b
3c
3d
3e
3f
87
84
89
85
80
81
85
80
78
91
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
4-F3CC6H4
3-MeC6H4
3-MeOC6H4
2-thienyl
3g
3h
3i
3j
Next, we investigated the reaction between 1a and 2a
with acetic acid as fixed solvent and catalyst (entries 17–
25). First, we fixed the molar ratio of 1a/2a at 1:1 and the
a Reaction conditions: a solution of 1 (1.0 mmol), 2a (1.0 mmol) in AcOH
(3 mL) was stirred at 60 °C for 12 h.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

D
A. Meléndez et al.
Paper
Synthesis
Encouraged by the preliminary scope of the approach
with respect to the 2′-aminochalcone component 1, we be-
gan to explore the scope with respect to the 1,3-dicarbonyl
component 2. The obtained results are summarized in Table
3. The realized experiments clearly revealed that 1-phenyl-
butane-1,3-dione (2b) and ethyl 3-oxobutanoate (2c)
worked very well and efficiently afforded the correspond-
ing 4-styrylquinolines 4a–j and 5a–j in yields comparable
to those obtained for their analogues 3a–j. Similarly, ethyl
3-oxo-3-phenylpropionate (2d), 1,3-cyclohexanedione (2e)
and 3-oxobutanamide (2f) also participated smoothly in
this transformation (Table 3), though providing the 4-sty-
rylquinolin-2-ones 6a–j, 9-styryldihydroacridin-1-ones
7a–f and 4-styrylquinolines 8a–f with lower efficiency.
This is due to their lower reactivity compared to that shown
by 2a–c, and so a slightly longer reaction time (18 h) was
necessary for substrate consumption.
Table 3 Scope of the Protocol with Respect to the 1,3-Dicarbonyl Component 2a
PhCOCH2COMe
(2b)
4
Ar
MeCOCH2CO2Et
O
(2c)
(2d)
5
6
O
Y
Ar
PhCOCH2CO2Et
AcOH
X
NH2
N
(2e)
(2f)
1,3-cyclohexanedione
MeCOCH2CONH2
7
8
1
4–8
2
X
Y
Ar
Product
Yield (%)
2b
2c
2d
Ph
Me
Ph
4a
4b
4c
4d
4e
4f
77
78
80
81
85
87
88
77
72
97
84
82
85
85
82
86
90
75
73
90
72
71
72
78
76
79
81
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
4-F3CC6H4
3-MeC6H4
3-MeOC6H4
2-thienyl
Ph
4g
4h
4i
4j
OEt
Me
5a
5b
5c
5d
5e
5f
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
4-F3CC6H4
3-MeC6H4
3-MeOC6H4
2-thienyl
Ph
5g
5h
5i
5j
Ph
O
6a
6b
6c
6d
6e
6f
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
4-F3CC6H4
6g
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

E
A. Meléndez et al.
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Synthesis
Table 3 (continued)
2
X
Y
Ar
Product
Yield (%)
3-MeC6H4
3-MeOC6H4
2-thienyl
Ph
6h
6i
65
63
80
63
69
68
73
67
70
80
77
80
79
74
83
6j
2e
–CH2CH2CH2–
7a
7b
7c
7d
7e
7f
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
Ph
2f
NH2
Me
8a
8b
8c
8d
8e
8f
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
a Reaction conditions: 1 (1.0 mmol), 2 (1.0 mmol), AcOH (3 mL), stirring, 60 °C, 12 h (for compounds 4 and 5) or 18 h (for compounds 6–8).
It is noteworthy that all of these reactions proceeded
with total regioselectivity, affording only one of the two
possible isomeric quinolines (quinolinones), that is, giving
exclusively the products shown in Tables 2 and 3.
and a conjugated carbonyl group, are the most relevant fea-
tures in the IR spectra of 3, 4, 7 and 9, respectively. The IR
spectra of 5 and 8 showed absorption bands at 1706–1724
cm–1, and at 3175–3237 and 1667–1674 cm–1, attributed to
ester and amide functions, respectively. The IR spectra of 6
revealed the band of the lactam NH group at 3126–3141
cm–1 in addition to overlapped absorption bands at 1664–
1676 cm–1 corresponding to the lactam C=O and the benzo-
In an attempt to extend the scope of our approach, we
also evaluated the reaction of 1a with less active 1,3-dicar-
bonyl compounds or analogues such as diethyl malonate,
1,3-indandione, 1,3-diphenylpropane-1,3-dione, 2-cyano-
acetamide, ethyl 2-cyanoacetate and malononitrile, but
none of them reacted under the established reaction condi-
tions, with 1a being recovered unchanged. These observa-
tions indicate that the reactivity of the 1,3-dicarbonyl com-
ponent is one of the driving forces in performing the
Friedländer reaction efficiently.
Table 4 Synthesis of Molecular Hybrids 9a–g via the Claisen–Schmidt
Condensation of 3a–g with Benzaldehydea
Ar
Ar
O
O
O
KOH/EtOH
rt, 3 h
Motivated by the fact that quinoline-based chalcones
represent a class of compounds with a diverse and remark-
able biological interest,23 and to demonstrate the synthetic
usefulness of the 3-acetyl-substituted 4-styrylquinolines 3
as a key building block, we further examined the possibility
of developing new hybrid chalcones bearing the styrylquin-
oline fragment. Fortunately, the selected 3-acetyl-4-styryl-
quinolines 3a–g worked very well on treatment with equi-
molar amounts of benzaldehyde and KOH in ethanol (3 mL),
yielding the desired molecular hybrids 9a–g in good yields
(Table 4).
The structures of 3–9 were established mainly by a
combined study of IR, HRMS, 1H NMR and 13C NMR spectra
(see the Experimental Section). The presence of stretching
vibration bands in the ranges 1690–1694, 1659–1666,
1667–1681 and 1638–1650 cm–1, attributed to a carbonyl
H
+
N
N
3a–g
9a–g
Substrate Ar
Product
Yield (%)
3a
3b
3c
3d
3e
3f
Ph
4-MeC6H4
9a
9b
9c
9d
9e
9f
74
73
76
80
82
85
88
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
4-F3CC6H4
3g
9g
a Reaction conditions: 3 (1.0 mmol), benzaldehyde (1.0 mmol), KOH (1.0
mmol), EtOH (3 mL). Yield of isolated product after recrystallization.
Thieme. All rights reserved. Synthesis 2020, 52, A–S

F
A. Meléndez et al.
Paper
Synthesis
yl C=O groups. Additionally, the IR spectra of 3–9 showed
the characteristic absorption band at 947–986 cm–1 at-
tributed to a trans-disubstituted alkene.
Additionally, the molecular structures of representative
compounds 4h and 9b were unambiguously established by
single crystal X-ray diffraction analysis. The X-ray crystal
structures of these compounds (shown in Figure 1 with the
atomic numbering schemes) agree with the E and E,E con-
figurations of the styryl and chalcone fragments deduced
from NMR analysis.
Unequivocal assignment of NMR signals was performed
using 2D NMR experiments (COSY, HMBC and HSQC). First,
the trans-configuration of the styryl fragment in com-
pounds 3–8 was deduced from coupling constant values in
1
the H NMR spectra (JHA,HB ~16.5 Hz), where HA and HB are
the - and -protons with respect to the C4/C9 position of
the quinoline/dihydroacridinone ring, and appear at  7.04–
7.96 and 6.60–7.15, respectively.
The formation of the quinoline/dihydroacridin-1-one
ring was confirmed by the appearance, among other carbon
atoms, of three quaternary carbon atoms [C2, C3 and C4 (for
compounds 3–5 and 8), and C4a, C9a and C9 (for com-
pounds 7)] in analyzed 13C NMR spectra, whose signals ap-
pear at  153.7–153.8, 133.6–133.9 and 139.0–140.2 (for 3),
at  155.0–155.1, 131.2–131.4 and 140.9–141.9 (for 4), at 
154.7–154.8, 126.1–126.3 and 141.5–142.4 (for 5), at 
155.0–155.1, 130.5–130.7 and 139.5–140.1 (for 8), and at 
162.1, 122.9–123.1 and 148.9–149.7 (for 7), respectively.
Likewise, the presence of a low field singlet at  12.08–
12.30 and signals at  160.3–162.0 (C2), 129.2–130.4 (C3)
Figure 1 Single crystal X-ray structures of 4h and 9b (ORTEP view with
atom-labeling scheme)
1
and 144.3–146.5 (C4) in the H/13C NMR spectra of 6 con-
Most of the synthesized compounds of series 3–8 were
selected by the National Cancer Institute, USA, for investiga-
tion of antitumor activity under their drug discovery pro-
gram. The screening is a two-stage process, beginning with
the evaluation of all selected compounds against approxi-
mately 60 cell lines, at a single dose of 10 M, representing
leukemia, melanoma and lung, colon, CNS, ovary, renal,
prostate and breast cancers. Details of this test system and
the information, which is encoded by the activity pattern
over all cell lines, have been published.24 Results for each
compound are reported as a mean graph of the percent
growth of treated cells when compared to untreated control
cells, and are available for analysis by the COMPARE pro-
gram.24a Unfortunately, the results of the primary assay
showed that all tested compounds 3–8 proved to have limit-
ed activity (see Tables 1S–5S in the Supporting Informa-
tion).
In conclusion, we have developed a reliable one-step
synthetic approach with advantages such as readily avail-
able starting materials, mild reaction conditions and high
yields for the assembly of new polysubstituted 4-sty-
rylquinolines and 4-styrylquinolin-2(1H)-ones, as well as
9-styryldihydroacridin-1(2H)-ones, from substituted 2′-
aminochalcones and 1,3-dicarbonyl compounds. The syn-
thetic usefulness of our approach was successfully extend-
ed to the synthesis of novel quinoline-based hybrid mole-
cules containing both styryl and chalcone moieties. Anti-
tumor activity studies of molecular hybrids 9 and other
related compounds are in progress and will be the subject
of another report.
firmed the formation of the quinolin-2-one ring. Correla-
tions from HA to C3 (C9a)/C4a (C8a) and from HB to C4 (C9)
in HMBC spectra corroborate the formation of the quino-
line/dihydroacridinone ring.
As expected, the other groups attached at the C2 and C3
positions of the quinoline ring, namely 2-methyl and 3-ace-
tyl (3), 2-methyl and 3-benzoyl (4), 2-methyl and 3-ethoxy-
carbonyl (5), 3-benzoyl (6), cyclohexanone-fused ring (7),
and 2-methyl and 3-amido (8) groups, showed the appro-
priate signals in the corresponding 1H/13C NMR spectra (see
the Experimental Section).
In turn, the formation of molecular hybrids 9 was estab-
lished by disappearance of the methyl signals ( 2.46–2.49
and 32.3–32.4) of the 3-acetyl group in both the 1H and 13
C
NMR spectra and by the appearance of signals for the newly
formed 3-arylpropen-1-one (chalcone) fragment. As far as
the Claisen–Schmidt condensation is concerned, it proceed-
ed in a highly stereoselective manner giving exclusively the
E stereoisomer, as was corroborated upon 1H NMR analysis
of the crude reaction mixture. As in the case of the precur-
sors 3, the trans configuration of the arylpropen-1-one
fragment was deduced on the basis of the coupling constant
values (JHA′,HB′ ~16.3 Hz) between HA′ and HB′ (- and -pro-
tons with respect to the carbonyl group), whose signals in
1
the H NMR spectra appear at  6.90–6.95 and 7.19–7.20,
respectively. 3J correlations from HA′ to C3 ( 131.5–131.8),
3
and from HB′ to C=O ( 198.2–198.6), as well as J correla-
tions from the ortho-aromatic protons H2′′/H6′′ to =CHB′ (
146.5–147.1), and from HA′ to quaternary aromatic carbon
atom C1′′ ( 134.0–134.2) in HMBC spectra also corroborate
the formation of such a propenone fragment.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

G
A. Meléndez et al.
Paper
Synthesis
(E)-1-(2-Methyl-4-(4-methylstyryl)quinolin-3-yl)ethan-1-one (3b)
All reagents and solvents were purchased from Sigma-Aldrich or Mer-
ck, and used without further purification. Monitoring of the reactions
was performed using silica gel TLC plates (Merck silica gel 60 F254).
Spots were visualized by UV light at 254 and 365 nm. Column chro-
matography was performed on Merck Kieselgel 230–400 mesh
(ASTM). Melting points were determined with a MEL-TEMP 1201D
capillary apparatus and are uncorrected. IR spectra were recorded on
a Bruker Tensor 27 spectrometer (equipped with a platinum ATR cell).
1H and 13C NMR spectra were measured at 25 °C on a Bruker Avance
III 400 spectrometer, using CDCl3 (for compounds 3–5, 7 and 9) and
DMSO-d6 (for compounds 6 and 8) as solvents. Chemical shifts () and
coupling constant (J) values are reported in ppm and Hz, respectively.
Chemical shifts are relative to the solvent peaks used as reference
(CDCl3:  7.26 for 1H and  77.23 for 13C, or DMSO-d6:  2.50 for 1H and
39.51 for 13C). NMR multiplicity assignments: q = quartet, t = triplet, d
= doublet, s = singlet, br = broad, m = multiplet. High-resolution mass
spectra were recorded on a Waters Micromass AutoSpect NT system
(equipped with a direct inlet probe) operating at 70 eV. UHPLC-HRMS
data were obtained on a Dionex Ultimate 3000 chromatograph cou-
pled to an Orbitrap Exactive Plus spectrometer, via electrospray ion-
ization. Elemental analyses were performed with a Vario Micro cube
CHN/S analyzer.
Yellow solid; yield: 0.25 g (84%); mp 168–170 °C; Rf = 0.45 (25% ethyl
acetate–heptane).
IR (ATR): 1692 (C=O), 1633 (C=N), 1610 (C=C vinyl), 1562 (C=C arom.),
1492 (C=C arom.), 979 cm–1 (=C–H trans).
1H NMR:  = 8.08 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.2 Hz,
1 H, H8), 7.73 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H7), 7.55–7.51 (m, 1 H,
H6), 7.50 (d, J = 16.4 Hz, 1 H, HAC=), 7.47–7.45 (m, 2 H, H2′, H6′), 7.23
(br d, J = 7.8 Hz, 2 H, H3′, H5′), 6.89 (d, J = 16.4 Hz, 1 H, =CHB), 2.67 (s,
3 H, 2-CH3), 2.47 (s, 3 H, 3-(CO)CH3), 2.40 (s, 3 H, 4′-CH3).
13C NMR:  = 206.4 (C=O), 153.7 (C2), 147.3 (C8a), 140.1 (C4), 139.5
(=CHB), 139.3 (C4′), 133.6 (C3), 133.4 (C1′), 130.2 (C7), 129.7 (C3′, C5′),
129.2 (C8), 127.0 (C2′, C6′), 126.5 (C6), 124.8 (C4a), 124.6 (C5), 120.5
(HAC=), 32.3 (3-(CO)CH3), 23.8 (2-CH3), 21.4 (4′-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H19NO: 302.1539; found:
302.1540.
Anal. Calcd for C21H19NO: C, 83.69; H, 6.35; N, 4.65; O, 5.31. Found: C,
83.73; H, 6.33; N, 4.67; O, 5.29.
(E)-1-(4-(4-Methoxystyryl)-2-methylquinolin-3-yl)ethan-1-one
(3c)
Yellow solid; yield: 0.28 g (89%); mp 158–159 °C; Rf = 0.38 (25% ethyl
acetate–heptane).
Substituted (E)-4-Styrylquinolines 3a–j, 4a–j, 5a–j, 6a–j, 7a–f and
8a–f; General Procedure
IR (ATR): 1692 (C=O), 1633 (C=N), 1601 (C=C vinyl), 1562 (C=C arom.),
A solution of 1 (1.0 mmol) and 2 (1.0 mmol) in AcOH (3 mL) was
stirred for indicated time as required to complete the reaction at 60 °C
(Tables 2 and 3). Upon completion of the reaction, monitored by TLC,
the mixture was neutralized with saturated sodium carbonate solu-
tion to pH 8.0–9.0, and extracted with ethyl acetate (3 × 50 mL). The
combined organic layers were dried over anhydrous sodium sulfate,
and the solvent was removed under reduced pressure. In each case,
the resulting crude product was purified by flash chromatography on
silica gel using heptane–ethyl acetate mixtures as eluent (10:1 to 7:1
for 3–5 and 7, and 2:1 to 1:1 for 6 and 8) to give compounds 3–8 as
solids. Compounds 3–8 were synthesized for the first time, except for
3a, 5a, 5c, 5f and 5j whose synthesis was reported by the Ilangovan
group.21
1508 (C=C arom.), 979 cm–1 (=C–H trans).
1H NMR:  = 8.09 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.2 Hz,
1 H, H8), 7.72 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.55–7.50 (m, 1 H,
H6), 7.52–7.48 (m, 2 H, H2′, H6′), 7.41 (d, J = 16.3 Hz, 1 H, HAC=), 6.96–
6.93 (m, 2 H, H3′, H5′), 6.86 (d, J = 16.3 Hz, 1 H, =CHB), 3.86 (s, 3 H, 4′-
OCH3), 2.67 (s, 3 H, 2-CH3), 2.47 (s, 3 H, 3-(CO)CH3).
13C NMR:  = 206.5 (C=O), 160.5 (C4′), 153.8 (C2), 147.3 (C8a), 140.2
(C4), 139.2 (=CHB), 133.6 (C3), 130.1 (C7), 129.2 (C8), 129.0 (C1′),
128.4 (C2′, C6′), 126.5 (C6), 124.9 (C4a), 124.6 (C5), 119.2 (HAC=),
114.4 (C3′, C5′), 55.4 (4′-OCH3), 32.3 (3-(CO)CH3), 23.8 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H19NO2: 318.1489; found:
318.1487.
Anal. Calcd for C21H19NO2: C, 79.47; H, 6.03; N, 4.41; O, 10.08. Found:
C, 79.54; H, 6.05; N, 4.43; O, 10.04.
(E)-1-(2-Methyl-4-styrylquinolin-3-yl)ethan-1-one (3a)
Yellow solid; yield: 0.25 g (87%); mp 94–96 °C; Rf = 0.42 (25% ethyl
acetate–heptane).
(E)-1-(4-(4-Bromostyryl)-2-methylquinolin-3-yl)ethan-1-one (3d)
IR (ATR): 1692 (C=O), 1630 (C=N), 1612 (C=C vinyl), 1560 (C=C arom.),
Yellow solid; yield: 0.31 g (85%); mp 174–176 °C; Rf = 0.40 (25% ethyl
acetate–heptane).
1493 (C=C arom.), 972 cm–1 (=C–H trans).
1H NMR:  = 8.08 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.05 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.73 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H7), 7.57–7.55 (m, 2 H, H2′,
H6′), 7.55 (d, J = 16.5 Hz, 1 H, HAC=), 7.55–7.52 (m, 1 H, H6), 7.45–7.40
(m, 2 H, H3′, H5′), 7.39–7.35 (m, 1 H, H4′), 6.92 (d, J = 16.5 Hz, 1 H,
=CHB), 2.68 (s, 3 H, 2-CH3), 2.48 (s, 3 H, 3-(CO)CH3).
13C NMR:  = 206.3 (C=O), 153.7 (C2), 147.3 (C8a), 139.9 (C4), 139.6
(=CHB), 136.1 (C1′), 133.8 (C3), 130.2 (C7), 129.2 (C4′), 129.1 (C8),
129.0 (C3′, C5′), 127.0 (C2′, C6′), 126.6 (C6), 124.8 (C4a), 124.6 (C5),
121.6 (HAC=), 32.4 (3-(CO)CH3), 23.8 (2-CH3).
IR (ATR): 1691 (C=O), 1634 (C=N), 1612 (C=C vinyl), 1562 (C=C arom.),
1486 (C=C arom.), 978 cm–1 (=C–H trans).
1H NMR:  = 8.07–8.03 (m, 2 H, H5, H8), 7.74 (ddd, J = 8.5, 6.8, 1.4 Hz,
1 H, H7), 7.54 (d, J = 16.4 Hz, 1 H, HAC=), 7.57–7.53 (m, 3 H, H6, H2′,
H6′), 7.43–7.40 (m, 2 H, H3′, H5′), 6.85 (d, J = 16.4 Hz, 1 H, =CHB), 2.68
(s, 3 H, 2-CH3), 2.46 (s, 3 H, 3-(CO)CH3).
13C NMR:  = 206.3 (C=O), 153.7 (C2), 147.3 (C8a), 139.4 (C4), 138.3
(=CHB), 135.0 (C1′), 133.8 (C3), 132.1 (C3′, C5′), 130.3 (C7), 129.3 (C8),
128.5 (C2′, C6′), 126.7 (C6), 124.6 (C4a), 124.5 (C5), 123.2 (C4′), 122.3
(HAC=), 32.4 (3-(CO)CH3), 23.8 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C20H17NO: 288.1383; found:
288.1383.
HRMS (Q-TOF-ESI): m/z [M + H]+ calcd for C20H16BrNO: 366.0488;
found: 366.0490.
Anal. Calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87; O, 5.58. Found: C,
83.56; H, 5.98; N, 4.86; O, 5.60.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

H
A. Meléndez et al.
Paper
Synthesis
(E)-1-(4-(4-Fluorostyryl)-2-methylquinolin-3-yl)ethan-1-one (3e)
1H NMR:  = 8.09 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.74 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.57–7.51 (m, 2 H,
HAC=, H6), 7.38–7.36 (m, 2 H, H2′, H6′), 7.32 (t, J = 7.6 Hz, 1 H, H5′),
7.19 (br d, J = 7.6 Hz, 1 H, H4′), 6.89 (d, J = 16.4 Hz, 1 H, =CHB), 2.68 (s,
3 H, 2-CH3), 2.48 (s, 3 H, 3-(CO)CH3), 2.41 (s, 3 H, 3′-CH3).
13C NMR:  = 206.4 (C=O), 153.8 (C2), 147.3 (C8a), 140.0 (C4), 139.8
(=CHB), 138.7 (C3′), 136.1 (C1′), 133.7 (C3), 130.2 (C7), 130.0 (C4′),
129.2 (C8), 128.9 (C5′), 127.7 (C2′), 126.6 (C6), 124.8 (C4a), 124.6 (C5),
124.2 (C6′), 121.4 (HAC=), 32.4 (3-(CO)CH3), 23.8 (2-CH3), 21.4 (3′-
CH3).
Yellow solid; yield: 0.24 g (80%); mp 113–115 °C; Rf = 0.40 (25% ethyl
acetate–heptane).
IR (ATR): 1692 (C=O), 1634 (C=N), 1612 (C=C vinyl), 1565 (C=C arom.),
1507 (C=C arom.), 982 cm–1 (=C–H trans).
1H NMR:  = 8.06 (dd, J = 8.1, 1.4 Hz, 1 H, H5), 8.05 (dd, J = 8.4, 1.2 Hz,
1 H, H8), 7.74 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.56–7.53 (m, 1 H,
H6), 7.55–7.51 (m, 2 H, H2′, H6′), 7.46 (d, J = 16.4 Hz, 1 H, HAC=), 7.14–
7.08 (m, 2 H, H3′, H5′), 6.88 (d, J = 16.4 Hz, 1 H, =CHB), 2.68 (s, 3 H, 2-
CH3), 2.47 (s, 3 H, 3-(CO)CH3).
13C NMR:  = 206.3 (C=O), 163.2 (d, J = 249.3 Hz, C4′), 153.7 (C2), 147.3
(C8a), 139.6 (C4), 138.3 (=CHB), 133.8 (C3), 132.3 (d, J = 3.3 Hz, C1′),
130.2 (C7), 129.3 (C8), 128.7 (d, J = 8.3 Hz, C2′, C6′), 126.6 (C6), 124.7
(C4a), 124.5 (C5), 121.3 (HAC=), 116.1 (d, J = 21.6 Hz, C3′, C5′), 32.4 (3-
(CO)CH3), 23.8 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H19NO: 302.1539; found:
302.1540.
Anal. Calcd for C21H19NO: C, 83.69; H, 6.35; N, 4.65; O, 5.31. Found: C,
83.74; H, 6.36; N, 4.64; O, 5.33.
(E)-1-(4-(3-Methoxystyryl)-2-methylquinolin-3-yl)ethan-1-one
(3i)
HRMS (ESI+): m/z [M + H]+ calcd for C20H16FNO: 306.1289; found:
306.1289.
Yellow solid; yield: 0.25 g (78%); mp 133–135 °C; Rf = 0.35 (25% ethyl
acetate–heptane).
(E)-1-(4-(4-Chlorostyryl)-2-methylquinolin-3-yl)ethan-1-one (3f)
IR (ATR): 1692 (C=O), 1637 (C=N), 1595 (C=C vinyl), 1563 (C=C arom.),
Yellow solid; yield: 0.26 g (81%); mp 159–161 °C; Rf = 0.40 (25% ethyl
acetate–heptane).
1493 (C=C arom.), 978 cm–1 (=C–H trans).
1H NMR:  = 8.07 (dd, J = 8.6, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.2 Hz,
1 H, H8), 7.74 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.54 (d, J = 16.3 Hz, 1
H, HAC=), 7.56–7.52 (m, 1 H, H6), 7.34 (t, J = 7.9 Hz, 1 H, H5′), 7.16 (dt,
J = 7.9, 2.0 Hz, 1 H, H4′), 7.07 (t, J = 2.0 Hz, 1 H, H2′), 6.92 (dt, J = 7.9,
2.0 Hz, 1 H, H6′), 6.88 (d, J = 16.3 Hz, 1 H, =CHB), 3.87 (s, 3 H, 3′-OCH3),
2.68 (s, 3 H, 2-CH3), 2.48 (s, 3 H, 3-(CO)CH3).
13C NMR:  = 206.3 (C=O), 160.0 (C3′), 153.7 (C2), 147.3 (C8a), 139.7
(C4), 139.5 (=CHB), 137.5 (C1′), 133.7 (C3), 130.2 (C7), 130.0 (C5′),
129.2 (C8), 126.6 (C6), 124.8 (C4a), 124.6 (C5), 121.9 (HAC=), 119.6
(C4′), 114.7 (C6′), 112.4 (C2′), 55.4 (3′-OCH3), 32.4 (3-(CO)CH3), 23.9
(2-CH3).
IR (ATR): 1690 (C=O), 1636 (C=N), 1612 (C=C vinyl), 1562 (C=C arom.),
1491 (C=C arom.), 979 cm–1 (=C–H trans).
1H NMR:  = 8.07–8.03 (m, 2 H, H5, H8), 7.74 (ddd, J = 8.3, 6.8, 1.4 Hz,
1 H, H7), 7.54 (ddd, J = 8.3, 6.8, 1.4 Hz, 1 H, H6), 7.51 (d, J = 16.4 Hz, 1
H, HAC=), 7.49–7.47 (m, 2 H, H2′, H6′), 7.40–7.37 (m, 2 H, H3′, H5′),
6.87 (d, J = 16.4 Hz, 1 H, =CHB), 2.68 (s, 3 H, 2-CH3), 2.47 (s, 3 H, 3-
(CO)CH3).
13C NMR:  = 206.2 (C=O), 153.7 (C2), 147.3 (C8a), 139.4 (C4), 138.2
(=CHB), 135.0 (C4′), 134.5 (C1′), 133.8 (C3), 130.3 (C7), 129.3 (C8),
129.2 (C3′, C5′), 128.2 (C2′, C6′), 126.7 (C6), 124.6 (C4a), 124.5 (C5),
122.2 (HAC=), 32.4 (3-(CO)CH3), 23.8 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H19NO2: 318.1489; found:
318.1487.
HRMS (ESI+): m/z [M + H]+ calcd for C20H16ClNO: 322.0993; found:
322.0994.
Anal. Calcd for C21H19NO2: C, 79.47; H, 6.03; N, 4.41; O, 10.08. Found:
C, 79.45; H, 6.04; N, 4.40; O, 10.12.
(E)-1-(2-Methyl-4-(4-(trifluoromethyl)styryl)quinolin-3-
yl)ethan-1-one (3g)
(E)-1-(2-Methyl-4-(2-(thiophen-2-yl)vinyl)quinolin-3-yl)ethan-1-
one (3j)
Colorless solid; yield: 0.30 g (85%); mp 144–145 °C; Rf = 0.38 (25%
ethyl acetate–heptane).
Beige solid; yield: 0.27 g (91%); mp 94–96 °C; Rf = 0.38 (25% ethyl
acetate–heptane).
IR (ATR): 1693 (C=O), 1639 (C=N), 1613 (C=C vinyl), 1563 (C=C arom.),
1494 (C=C arom.), 980 cm–1 (=C–H trans).
IR (ATR): 1691 (C=O), 1624 (C=N/C=C vinyl), 1561 (C=C arom.), 1494
1H NMR:  = 8.07–8.03 (m, 2 H, H5, H8), 7.75 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H7), 7.69–7.64 (m, 4 H, H2′, H3′, H5′, H6′), 7.63 (d, J = 16.5 Hz, 1 H,
HAC=), 7.56 (ddd, J = 8.2, 6.8, 1.3 Hz, 1 H, H6), 6.95 (d, J = 16.5 Hz, 1 H,
=CHB), 2.69 (s, 3 H, 2-CH3), 2.48 (s, 3 H, 3-(CO)CH3).
13C NMR:  = 206.1 (C=O), 153.7 (C2), 147.4 (C8a), 139.4 (C1′), 139.0
(C4), 137.9 (=CHB), 133.9 (C3), 130.7 (C4′), 130.3 (C7), 129.4 (C8),
127.2 (C2′, C3′, C5′, C6′), 126.8 (C6), 126.0 (q, J = 3.7 Hz, 4′-CF3), 124.5
(C4a), 124.4 (C5), 124.3 (HAC=), 32.4 (3-(CO)CH3), 23.8 (2-CH3).
(C=C arom.), 953 cm–1 (=C–H trans).
1H NMR:  = 8.07 (dd, J = 8.3, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.73 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.55 (ddd, J = 8.4, 6.9,
1.3 Hz, 1 H, H6), 7.36 (d, J = 16.1 Hz, 1 H, HAC=), 7.33 (dd, J = 5.1, 1.0
Hz, 1 H, H5′), 7.15 (dd, J = 3.5, 1.0 Hz, 1 H, H3′), 7.06 (dd, J = 5.1, 3.5 Hz,
1 H, H4′), 7.03 (d, J = 16.1 Hz, 1 H, =CHB), 2.67 (s, 3 H, 2-CH3), 2.49 (s, 3
H, 3-(CO)CH3).
13C NMR:  = 206.4 (C=O), 153.7 (C2), 147.3 (C8a), 141.3 (C2′), 139.2
(C4), 133.6 (C3), 132.4 (=CHB), 130.3 (C7), 129.2 (C8), 128.6 (C5′),
128.0 (C3′), 126.6 (C6), 126.4 (C4′), 124.6 (C4a), 124.5 (C5), 120.6
(HAC=), 32.3 (3-(CO)CH3), 23.8 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H16F3NO: 356.1257; found:
356.1256.
(E)-1-(2-Methyl-4-(3-methylstyryl)quinolin-3-yl)ethan-1-one (3h)
HRMS (ESI+): m/z [M + H]+ calcd for C18H15NOS: 294.0947; found:
294.0947.
Yellow solid; yield: 0.24 g (80%); mp 71–72 °C; Rf = 0.40 (25% ethyl
acetate–heptane).
Anal. Calcd for C18H15NOS: C, 73.69; H, 5.15; N, 4.77; O, 5.45; S, 10.93.
Found: C, 73.65; H, 5.17; N, 4.78; O, 5.46; S, 10.94.
IR (ATR): 1694 (C=O), 1634 (C=N), 1601 (C=C vinyl), 1562 (C=C arom.),
1492 (C=C arom.), 979 cm–1 (=C–H trans).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

I
A. Meléndez et al.
Paper
Synthesis
(E)-(2-Methyl-4-styrylquinolin-3-yl)(phenyl)methanone (4a)
126.5 (C6), 125.0 (C5), 124.8 (C4a), 119.7 (HAC=), 114.1 (C3′′, C5′′),
55.3 (4′′-OCH3), 24.0 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C26H21NO2: 380.1645; found:
Yellow solid; yield: 0.27 g (77%); mp 149–150 °C; Rf = 0.29 (20% ethyl
acetate–heptane).
380.1644.
IR (ATR): 1659 (C=O), 1634 (C=N), 1593 (C=C vinyl), 1562 (C=C arom.),
1497 (C=C arom.), 978 cm–1 (=C–H trans).
Anal. Calcd for C26H21NO2: C, 82.30; H, 5.58; N, 3.69; O, 8.43. Found: C,
82.25; H, 5.60; N, 3.71; O, 8.44.
1H NMR:  = 8.12 (dd, J = 8.4, 1.5 Hz, 1 H, H5), 8.11 (dd, J = 8.3, 1.2 Hz,
1 H, H8), 7.77 (ddd, J = 8.3, 7.9, 1.5 Hz, 1 H, H7), 7.76–7.73 (m, 2 H, H2′,
H6′), 7.59–7.55 (m, 1 H, H6), 7.57–7.52 (m, 1 H, H4′), 7.39 (t, J = 7.8 Hz,
2 H, H3′, H5′), 7.30–7.25 (m, 5 H, H2′′, H3′′, H4′′, H5′′, H6′′), 7.24 (d, J =
16.5 Hz, 1 H, HAC=), 6.87 (d, J = 16.5 Hz, 1 H, =CHB), 2.61 (s, 3 H, 2-
CH3).
(E)-(4-(4-Bromostyryl)-2-methylquinolin-3-yl)(phenyl)metha-
none (4d)
Yellow solid; yield: 0.35 g (81%); mp 114–115 °C; Rf = 0.25 (20% ethyl
acetate–heptane).
13C NMR:  = 198.4 (C=O), 155.1 (C2), 147.7 (C8a), 141.6 (C4), 139.4
(=CHB), 137.2 (C1′), 136.3 (C1′′), 133.9 (C4′), 131.4 (C3), 130.2 (C7),
129.4 (C2′, C6′), 129.3 (C8), 128.9 (C3′, C5′), 128.7 (C3′′, C4′′, C5′′),
126.8 (C2′′, C6′′), 126.6 (C6), 124.9 (C5), 124.8 (C4a), 122.0 (HAC=),
24.0 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C25H19NO: 350.1539; found:
350.1541.
IR (ATR): 1665 (C=O), 1638 (C=N), 1593 (C=C vinyl), 1570 (C=C arom.),
1487 (C=C arom.), 976 cm–1 (=C–H trans).
1H NMR:  = 8.12 (dd, J = 8.5, 1.3 Hz, 1 H, H5), 8.08 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.78 (ddd, J = 8.4, 6.9, 1.3 Hz, 1 H, H7), 7.74–7.72 (m, 2 H, H2′,
H6′), 7.57 (ddd, J = 8.5, 6.9, 1.3 Hz, 1 H, H6), 7.56–7.52 (m, 1 H, H4′),
7.39 (t, J = 8.3 Hz, 2 H, H3′, H5′), 7.42–7.37 (m, 2 H, H3′′, H5′′), 7.22 (d,
J = 16.5 Hz, 1 H, HAC=), 7.14–7.11 (m, 2 H, H2′′, H6′′), 6.79 (d, J = 16.5
Hz, 1 H, =CHB), 2.61 (s, 3 H, 2-CH3).
13C NMR:  = 198.3 (C=O), 155.1 (C2), 147.7 (C8a), 141.2 (C4), 138.0
(=CHB), 137.2 (C1′), 135.1 (C1′′), 134.0 (C4′), 131.9 (C3′′, C5′′), 131.4
(C3), 130.3 (C7), 129.4 (C8), 129.3 (C2′, C6′), 129.0 (C3′, C5′), 128.3
(C2′′, C6′′), 126.7 (C6), 124.8 (C5), 124.6 (C4a), 122.8 (HAC=), 122.7
(C4′′), 24.0 (2-CH3).
Anal. Calcd for C25H19NO: C, 85.93; H, 5.48; N, 4.01; O, 4.58. Found: C,
85.86; H, 5.51; N, 4.02; O, 4.60.
(E)-(2-Methyl-4-(4-methylstyryl)quinolin-3-yl)(phenyl)metha-
none (4b)
Yellow solid; yield: 0.28 g (78%); mp 169–170 °C; Rf = 0.28 (20% ethyl
acetate–heptane).
HRMS (ESI+): m/z [M + H]+ calcd for C25H18BrNO: 428.0645; found:
428.0646.
IR (ATR): 1666 (C=O), 1637 (C=N), 1593 (C=C vinyl), 1571 (C=C arom.),
1491 (C=C arom.), 980 cm–1 (=C–H trans).
(E)-(4-(4-Fluorostyryl)-2-methylquinolin-3-yl)(phenyl)metha-
none (4e)
1H NMR:  = 8.13–8.10 (m, 2 H, H5, H8), 7.77 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H7), 7.75–7.73 (m, 2 H, H2′, H6′), 7.58–7.51 (m, 2 H, H6, H4′), 7.38
(t, J = 7.7 Hz, 2 H, H3′, H5′), 7.20 (d, J = 16.4 Hz, 1 H, HAC=), 7.18 (d, J =
7.9 Hz, 2 H, H2′′, H6′′), 7.09 (d, J = 7.9 Hz, 2 H, H3′′, H5′′), 6.84 (d, J =
16.4 Hz, 1 H, =CHB), 2.61 (s, 3 H, 2-CH3), 2.32 (s, 3 H, 4′′-CH3).
13C NMR:  = 198.5 (C=O), 155.0 (C2), 147.7 (C8a), 141.7 (C4), 139.3
(=CHB), 138.8 (C4′′), 137.3 (C1′), 133.8 (C4′), 133.5 (C1′′), 131.3 (C3),
130.2 (C7), 129.4 (C3′′, C5′′), 129.3 (C8, C2′, C6′), 128.9 (C3′, C5′), 126.8
(C2′′, C6′′), 126.5 (C6), 124.9 (C5), 124.8 (C4a), 120.9 (HAC=), 24.0 (2-
CH3), 21.3 (4′′-CH3).
Yellow solid; yield: 0.31 g (85%); mp 163–164 °C; Rf = 0.23 (20% ethyl
acetate–heptane).
IR (ATR): 1665 (C=O), 1639 (C=N), 1596 (C=C vinyl), 1564 (C=C arom.),
1504 (C=C arom.), 975 cm–1 (=C–H trans).
1H NMR:  = 8.12 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.09 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.78 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.74 (dd, J = 8.4, 1.4
Hz, 2 H, H2′, H6′), 7.59–7.54 (m, 1 H, H6), 7.57–7.53 (m, 1 H, H4′), 7.39
(dd, J = 8.4, 7.3 Hz, 2 H, H3′, H5′), 7.26–7.21 (m, 2 H, H2′′, H6′′), 7.15 (d,
J = 16.5 Hz, 1 H, HAC=), 7.00–6.94 (m, 2 H, H3′′, H5′′), 6.81 (d, J = 16.5
Hz, 1 H, =CHB), 2.61 (s, 3 H, 2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C26H21NO: 364.1696; found:
364.1696.
13C NMR:  = 198.4 (C=O), 163.0 (d, J = 247.2 Hz, C4′′), 155.1 (C2),
147.7 (C8a), 141.4 (C4), 138.1 (=CHB), 137.3 (C1′), 133.9 (C4′), 132.4
(d, J = 3.0 Hz, C1′′), 131.4 (C3), 130.3 (C7), 129.4 (C8), 129.3 (C2′, C6′),
128.9 (C3′, C5′), 128.5 (d, J = 8.1 Hz, C2′′, C6′′), 126.6 (C6), 124.8 (C5),
124.7 (C4a), 121.8 (d, J = 0.8 Hz, HAC=), 115.7 (d, J = 21.8 Hz, C3′′, C5′′),
24.0 (2-CH3).
Anal. Calcd for C26H21NO: C, 85.92; H, 5.82; N, 3.85; O, 4.40. Found: C,
85.96; H, 5.80; N, 3.84; O, 4.40.
(E)-(4-(4-Methoxystyryl)-2-methylquinolin-3-yl)(phenyl)metha-
none (4c)
Yellow solid; yield: 0.30 g (80%); mp 155–156 °C; Rf = 0.21 (20% ethyl
acetate–heptane).
HRMS (ESI+): m/z [M + H]+ calcd for C25H18FNO: 368.1445; found:
368.1443.
IR (ATR): 1666 (C=O), 1636 (C=N), 1603 (C=C vinyl), 1570 (C=C arom.),
1508 (C=C arom.), 980 cm–1 (=C–H trans).
(E)-(4-(4-Chlorostyryl)-2-methylquinolin-3-yl)(phenyl)metha-
none (4f)
1H NMR:  = 8.13 (dd, J = 8.4, 1.6 Hz, 1 H, H5), 8.10 (dd, J = 8.4, 1.5 Hz,
1 H, H8), 7.77 (ddd, J = 8.4, 7.0, 1.6 Hz, 1 H, H7), 7.75–7.72 (m, 2 H, H2′,
H6′), 7.56 (ddd, J = 8.4, 7.0, 1.5 Hz, 1 H, H6), 7.56–7.51 (m, 1 H, H4′),
7.38 (t, J = 7.8 Hz, 2 H, H3′, H5′), 7.23 (d, J = 8.7 Hz, 2 H, H2′′, H6′′), 7.11
(d, J = 16.4 Hz, 1 H, HAC=), 6.82 (d, J = 8.7 Hz, 2 H, H3′′, H5′′), 6.81 (d, J =
16.4 Hz, 1 H, =CHB), 3.79 (s, 3 H, 4′′-OCH3), 2.61 (s, 3 H, 2-CH3).
Yellow solid; yield: 0.33 g (87%); mp 154–155 °C; Rf = 0.28 (20% ethyl
acetate–heptane).
IR (ATR): 1665 (C=O), 1638 (C=N), 1593 (C=C vinyl), 1570 (C=C arom.),
1491 (C=C arom.), 976 cm–1 (=C–H trans).
1H NMR:  = 8.12 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.08 (dd, J = 8.5, 1.4 Hz,
1 H, H8), 7.78 (ddd, J = 8.5, 6.9, 1.4 Hz, 1 H, H7), 7.74–7.72 (m, 2 H, H2′,
H6′), 7.59–7.53 (m, 2 H, H6, H4′), 7.40 (t, J = 7.8 Hz, 2 H, H3′, H5′),
13C NMR:  = 198.6 (C=O), 160.1 (C4′′), 155.1 (C2), 147.7 (C8a), 141.9
(C4), 139.0 (=CHB), 137.3 (C1′), 133.8 (C4′), 131.2 (C3), 130.2 (C7),
129.3 (C8, C2′, C6′), 129.1 (C1′′), 128.9 (C3′, C5′), 128.2 (C2′′, C6′′),
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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A. Meléndez et al.
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Synthesis
7.27–7.24 (m, 2 H, H2′′, H6′′), 7.21 (d, J = 16.4 Hz, 1 H, HAC=), 7.20–
7.18 (m, 2 H, H3′′, H5′′), 6.80 (d, J = 16.4 Hz, 1 H, =CHB), 2.62 (s, 3 H, 2-
CH3).
13C NMR:  = 198.3 (C=O), 155.1 (C2), 147.7 (C8a), 141.2 (C4), 138.0
(=CHB), 137.2 (C1′), 134.7 (C4′′), 134.5 (C1′′), 134.0 (C4′), 131.4 (C3),
130.3 (C7), 129.4 (C8), 129.3 (C2′, C6′), 129.0 (C3′′, C5′′), 128.9 (C3′,
C5′), 128.0 (C2′′, C6′′), 126.7 (C6), 124.8 (C5), 124.6 (C4a), 122.6
(HAC=), 24.0 (2-CH3).
IR (ATR): 1663 (C=O), 1629 (C=N), 1604 (C=C vinyl), 1566 (C=C arom.),
1493 (C=C arom.), 982 cm–1 (=C–H trans).
1H NMR:  = 8.13–8.10 (m, 2 H, H5, H8), 7.80–7.75 (m, 1 H, H7), 7.76–
7.73 (m, 2 H, H2′, H6′), 7.58–7.55 (m, 1 H, H6), 7.57–7.52 (m, 1 H, H4′),
7.39 (t, J = 7.8 Hz, 2 H, H3′, H5′), 7.23 (d, J = 16.4 Hz, 1 H, HAC=), 7.20 (t,
J = 7.6 Hz, 1 H, H5′′), 6.88 (d, J = 7.6 Hz, 1 H, H6′′), 6.83 (d, J = 16.4 Hz, 1
H, =CHB), 6.82–6.80 (m, 1 H, H4′′), 6.78 (t, J = 1.9 Hz, 1 H, H2′′), 3.77 (s,
3 H, 3′′-OCH3), 2.61 (s, 3 H, 2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C25H18ClNO: 384.1150; found:
384.1149.
13C NMR:  = 198.4 (C=O), 159.8 (C3′′), 155.0 (C2), 147.7 (C8a), 141.5
(C4), 139.2 (=CHB), 137.7 (C1′′), 137.3 (C1′), 133.9 (C4′), 131.4 (C3),
130.2 (C7), 129.7 (C5′′), 129.4 (C2′, C6′), 129.3 (C8), 128.9 (C3′, C5′),
126.6 (C6), 124.9 (C5), 124.7 (C4a), 122.4 (HAC=), 119.5 (C6′′), 114.3
(C4′′), 112.1 (C2′′), 55.3 (3′′-OCH3), 24.0 (2-CH3).
(E)-(2-Methyl-4-(4-(trifluoromethyl)styryl)quinolin-3-yl)(phe-
nyl)methanone (4g)
HRMS (ESI+): m/z [M + H]+ calcd for C26H21NO2: 380.1645; found:
Yellow solid; yield: 0.37 g (88%); mp 121–122 °C; Rf = 0.22 (20% ethyl
380.1647.
acetate–heptane).
Anal. Calcd for C26H21NO2: C, 82.30; H, 5.58; N, 3.69; O, 8.43. Found: C,
82.25; H, 5.60; N, 3.70; O, 8.45.
IR (ATR): 1662 (C=O), 1614 (C=N), 1594 (C=C vinyl), 1564 (C=C arom.),
1492 (C=C arom.), 975 cm–1 (=C–H trans).
1H NMR:  = 8.13 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.07 (dd, J = 8.4, 1.4 Hz,
1 H, H8), 7.79 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H7), 7.76–7.72 (m, 2 H, H2′,
H6′), 7.58 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H6), 7.57–7.53 (m, 3 H, H4′,
H3′′, H5′′), 7.43–7.38 (m, 2 H, H3′, H5′), 7.36 (d, J = 8.1 Hz, 2 H, H2′′,
H6′′), 7.32 (d, J = 16.5 Hz, 1 H, HAC=), 6.88 (d, J = 16.5 Hz, 1 H, =CHB),
2.62 (s, 3 H, 2-CH3).
13C NMR:  = 198.2 (C=O), 155.1 (C2), 147.7 (C8a), 140.9 (C4), 139.5
(C1′′), 137.6 (=CHB), 137.2 (C1′), 134.1 (C4′), 131.5 (C3, C4′′), 130.4
(C7), 129.4 (C8), 129.3 (C2′, C6′), 129.0 (C3′, C5′), 127.0 (C2′′, C3′′, C5′′,
C6′′), 126.8 (C6), 125.7 (q, J = 3.6 Hz, 4′′-CF3), 124.7 (C5), 124.6 (HAC=),
124.5 (C4a), 24.0 (2-CH3).
(E)-(2-Methyl-4-(2-(thiophen-2-yl)vinyl)quinolin-3-yl)(phe-
nyl)methanone (4j)
Yellow solid; yield: 0.34 g (97%); mp 114–115 °C; Rf = 0.27 (20% ethyl
acetate–heptane).
IR (ATR): 1662 (C=O), 1620 (C=N), 1594 (C=C vinyl), 1563 (C=C arom.),
1489 (C=C arom.), 955 cm–1 (=C–H trans).
1H NMR:  = 8.12–8.09 (m, 2 H, H5, H8), 7.77 (ddd, J = 8.5, 6.8, 1.4 Hz,
1 H, H7), 7.74 (dd, J = 8.4, 1.3 Hz, 2 H, H2′, H6′), 7.57 (ddd, J = 8.3, 6.8,
1.3 Hz, 1 H, H6), 7.56–7.52 (m, 1 H, H4′), 7.39 (t, J = 7.7 Hz, 2 H, H3′,
H5′), 7.19 (dd, J = 4.8, 1.4 Hz, 1 H, H3′′), 7.09 (d, J = 16.2 Hz, 1 H, HAC=),
6.98 (d, J = 16.2 Hz, 1 H, =CHB), 6.97–6.93 (m, 2 H, H4′′, H5′′), 2.60 (s, 3
H, 2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C26H18F3NO: 418.1413; found:
418.1416.
13C NMR:  = 198.5 (C=O), 155.1 (C2), 147.8 (C8a), 141.4 (C2′′), 140.9
(C4), 137.2 (C1′), 133.9 (C4′), 132.2 (=CHB), 131.2 (C3), 130.2 (C7),
129.3 (C8, C2′, C6′), 128.9 (C3′, C5′), 127.9 (C5′′), 127.7 (C4′′), 126.6
(C6), 126.0 (C3′′), 124.8 (C5), 124.6 (C4a), 121.0 (HAC=), 24.0 (2-CH3).
(E)-(2-Methyl-4-(3-methylstyryl)quinolin-3-yl)(phenyl)metha-
none (4h)
Yellow solid; yield: 0.28 g (77%); mp 142–143 °C; Rf = 0.32 (20% ethyl
HRMS (ESI+): m/z [M + H]+ calcd for C23H17NOS: 356.1104; found:
acetate–heptane).
356.1101.
IR (ATR): 1659 (C=O), 1629 (C=N), 1593 (C=C vinyl), 1564 (C=C arom.),
1493 (C=C arom.), 983 cm–1 (=C–H trans).
Anal. Calcd for C23H17NOS: C, 77.72; H, 4.82; N, 3.94; O, 4.50; S, 9.02.
Found: C, 77.76; H, 4.84; N, 3.92; O, 4.49; S, 8.99.
1H NMR:  = 8.12 (dd, J = 8.4, 1.5 Hz, 1 H, H5), 8.11 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.80–7.76 (m, 1 H, H7), 7.76–7.74 (m, 2 H, H2′, H6′), 7.58–
7.54 (m, 1 H, H6), 7.56–7.52 (m, 1 H, H4′), 7.39 (t, J = 7.8 Hz, 2 H, H3′,
H5′), 7.23 (d, J = 16.4 Hz, 1 H, HAC=), 7.18 (t, J = 7.6 Hz, 1 H, H5′′), 7.09
(s, 1 H, H2′′), 7.08 (d, J = 7.6 Hz, 2 H, H4′′, H6′′), 6.84 (d, J = 16.4 Hz, 1 H,
=CHB), 2.61 (s, 3 H, 2-CH3), 2.31 (s, 3 H, 3′′-CH3).
13C NMR:  = 198.4 (C=O), 155.0 (C2), 147.7 (C8a), 141.7 (C4), 139.5
(=CHB), 138.3 (C3′′), 137.2 (C1′), 136.2 (C1′′), 133.9 (C4′), 131.3 (C3),
130.2 (C7), 129.5 (C4′′), 129.4 (C2′, C6′), 129.3 (C8), 128.9 (C3′, C5′),
128.6 (C5′′), 127.6 (C2′′), 126.6 (C6), 125.0 (C5), 124.8 (C4a), 124.0
(C6′′), 121.8 (HAC=), 24.0 (2-CH3), 21.4 (3′′-CH3).
Ethyl (E)-2-Methyl-4-styrylquinoline-3-carboxylate (5a)
Pale yellow solid; yield: 0.27 g (84%); mp 68–69 °C; Rf = 0.37 (25%
ethyl acetate–heptane).
IR (ATR): 1714 (C=O ester), 1640 (C=N), 1613 (C=C vinyl), 1562 (C=C
arom.), 1495 (C=C arom.), 954 cm–1 (=C–H trans).
1H NMR:  = 8.09 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.05 (dd, J = 8.4, 1.6 Hz,
1 H, H8), 7.73 (ddd, J = 8.3, 6.8, 1.4 Hz, 1 H, H7), 7.56–7.54 (m, 2 H, H2′,
H6′), 7.54–7.50 (m, 1 H, H6), 7.51 (d, J = 16.5 Hz, 1 H, HAC=), 7.43–7.39
(m, 2 H, H3′, H5′), 7.37–7.33 (m, 1 H, H4′), 6.97 (d, J = 16.5 Hz, 1 H,
=CHB), 4.37 (q, J = 7.1 Hz, 2 H, OCH2), 2.76 (s, 3 H, 2-CH3), 1.30 (t, J =
7.1 Hz, 3 H, CH2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C26H21NO: 364.1696; found:
364.1697.
Anal. Calcd for C26H21NO: C, 85.92; H, 5.82; N, 3.85; O, 4.40. Found: C,
85.95; H, 5.80; N, 3.83; O, 4.42.
13C NMR:  = 169.0 (C=O), 154.8 (C2), 147.6 (C8a), 142.1 (C4), 137.7
(=CHB), 136.3 (C1′), 130.3 (C7), 129.2 (C4′), 128.9 (C3′, C5′), 128.8 (C8),
126.9 (C2′, C6′), 126.5 (C6), 126.3 (C3), 125.2 (C5), 124.7 (C4a), 122.3
(HAC=), 61.7 (OCH2), 23.8 (2-CH3), 14.3 (CH2CH3).
(E)-(4-(3-Methoxystyryl)-2-methylquinolin-3-yl)(phenyl)metha-
none (4i)
HRMS (ESI+): m/z [M + H]+ calcd for C21H19NO2: 318.1489; found:
318.1488.
Yellow solid; yield: 0.27 g (72%); mp 96–97 °C; Rf = 0.25 (20% ethyl
acetate–heptane).
Anal. Calcd for C21H19NO2: C, 79.47; H, 6.03; N, 4.41; O, 10.08. Found:
C, 79.51; H, 6.02; N, 4.40; O, 10.07.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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A. Meléndez et al.
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Synthesis
Ethyl (E)-2-Methyl-4-(4-methylstyryl)quinoline-3-carboxylate
HRMS (ESI+): m/z [M + H]+ calcd for C21H18BrNO2: 396.0594; found:
(5b)
396.0596.
Beige solid; yield: 0.27 g (82%); mp 48–49 °C; Rf = 0.40 (25% ethyl
acetate–heptane).
Ethyl (E)-4-(4-Fluorostyryl)-2-methylquinoline-3-carboxylate (5e)
Pale yellow solid; yield: 0.27 g (82%); mp 55–56 °C; Rf = 0.34 (25%
ethyl acetate–heptane).
IR (ATR): 1718 (C=O ester), 1638 (C=N), 1611 (C=C vinyl), 1572 (C=C
arom.), 1492 (C=C arom.), 953 cm–1 (=C–H trans).
1H NMR:  = 8.09 (dd, J = 8.2, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.2 Hz,
1 H, H8), 7.73 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H7), 7.52 (ddd, J = 8.2, 6.8,
1.2 Hz, 1 H, H6), 7.47 (d, J = 16.5 Hz, 1 H, HAC=), 7.45–7.43 (m, 2 H,
H2′, H6′), 7.22 (d, J = 8.0 Hz, 2 H, H3′, H5′), 6.94 (d, J = 16.5 Hz, 1 H,
=CHB), 4.37 (q, J = 7.1 Hz, 2 H, OCH2), 2.75 (s, 3 H, 2-CH3), 2.39 (s, 3 H,
4′-CH3), 1.30 (t, J = 7.1 Hz, 3 H, CH2CH3).
13C NMR:  = 169.3 (C=O), 154.7 (C2), 147.5 (C8a), 142.3 (C4), 138.9
(C4′), 137.7 (=CHB), 133.5 (C1′), 130.3 (C7), 129.6 (C3′, C5′), 129.1 (C8),
126.8 (C2′, C6′), 126.4 (C6), 126.2 (C3), 125.2 (C5), 124.7 (C4a), 121.1
(HAC=), 61.7 (OCH2), 23.8 (2-CH3), 21.4 (4′-CH3), 14.3 (CH2CH3).
IR (ATR): 1712 (C=O ester), 1638 (C=N), 1602 (C=C vinyl), 1573 (C=C
arom.), 1492 (C=C arom.), 951 cm–1 (=C–H trans).
1H NMR:  = 8.07 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.05 (dd, J = 8.6, 1.3 Hz,
1 H, H8), 7.73 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.55–7.50 (m, 3 H, H6,
H2′, H6′), 7.43 (d, J = 16.5 Hz, 1 H, HAC=), 7.13–7.08 (m, 2 H, H3′, H5′),
6.93 (d, J = 16.5 Hz, 1 H, =CHB), 4.37 (q, J = 7.1 Hz, 2 H, OCH2), 2.75 (s, 3
H, 2-CH3), 1.30 (t, J = 7.1 Hz, 3 H, CH2CH3).
13C NMR:  = 169.0 (C=O), 163.0 (d, J = 248.2 Hz, C4′), 154.8 (C2), 147.6
(C8a), 141.9 (C4), 136.5 (=CHB), 132.5 (d, J = 3.5 Hz, C1′), 130.3 (C7),
129.2 (C8), 128.5 (d, J = 8.1 Hz, C2′, C6′), 126.5 (C6), 126.3 (C3), 125.1
(C5), 124.6 (C4a), 122.0 (HAC=), 115.9 (d, J = 21.9 Hz, C3′, C5′), 61.7
(OCH2), 23.8 (2-CH3), 14.3 (CH2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C22H21NO2: 332.1645; found:
332.1644.
HRMS (ESI+): m/z [M + H]+ calcd for C21H18FNO2: 336.1394; found:
336.1394.
Anal. Calcd for C22H21NO2: C, 79.73; H, 6.39; N, 4.23; O, 9.65. Found: C,
79.77; H, 6.37; N, 4.23; O, 9.67.
Ethyl (E)-4-(4-Chlorostyryl)-2-methylquinoline-3-carboxylate (5f)
Ethyl (E)-4-(4-Methoxystyryl)-2-methylquinoline-3-carboxylate
(5c)
Pale yellow solid; yield: 0.30 g (86%); mp 68–69 °C; Rf = 0.34 (25%
ethyl acetate–heptane).
Yellow solid; yield: 0.29 g (85%); mp 77–78 °C; Rf = 0.28 (25% ethyl
acetate–heptane).
IR (ATR): 1706 (C=O ester), 1641 (C=N), 1613 (C=C vinyl), 1592 (C=C
arom.), 1490 (C=C arom.), 950 cm–1 (=C–H trans).
IR (ATR): 1708 (C=O ester), 1637 (C=N), 1603 (C=C vinyl), 1565 (C=C
arom.), 1494 (C=C arom.), 952 cm–1 (=C–H trans).
1H NMR:  = 8.08–8.02 (m, 2 H, H5, H8), 7.74 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H7), 7.55–7.51 (m, 1 H, H6), 7.49 (d, J = 16.5 Hz, 1 H, HAC=), 7.49–
7.46 (m, 2 H, H2′, H6′), 7.40–7.36 (m, 2 H, H3′, H5′), 6.91 (d, J = 16.5
Hz, 1 H, =CHB), 4.36 (q, J = 7.1 Hz, 2 H, OCH2), 2.75 (s, 3 H, 2-CH3), 1.29
(t, J = 7.1 Hz, 3 H, CH2CH3).
13C NMR:  = 168.9 (C=O), 154.8 (C2), 147.6 (C8a), 141.8 (C4), 136.4
(=CHB), 134.7 (C1′), 134.6 (C4′), 130.4 (C7), 129.2 (C8), 129.1 (C3′, C5′),
128.0 (C2′, C6′), 126.6 (C6), 126.3 (C3), 125.1 (C5), 124.5 (C4a), 122.9
(HAC=), 61.8 (OCH2), 23.8 (2-CH3), 14.3 (CH2CH3).
1H NMR:  = 8.10 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.03 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.72 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H7), 7.53–7.49 (m, 1 H,
H6), 7.50–7.47 (m, 2 H, H2′, H6′), 7.37 (d, J = 16.5 Hz, 1 H, HAC=), 6.95–
6.92 (m, 2 H, H3′, H5′), 6.93 (d, J = 16.5 Hz, 1 H, =CHB), 4.37 (q, J = 7.1
Hz, 2 H, OCH2), 3.85 (s, 3 H, 4′-OCH3), 2.75 (s, 3 H, 2-CH3), 1.30 (t, J =
7.1 Hz, 3 H, CH2CH3).
13C NMR:  = 169.2 (C=O), 160.2 (C4′), 154.7 (C2), 147.6 (C8a), 142.4
(C4), 137.3 (=CHB), 130.2 (C7), 129.2 (C8, C1′), 128.3 (C2′, C6′), 126.4
(C6), 126.3 (C3), 125.2 (C5), 124.8 (C4a), 119.9 (HAC=), 114.3 (C3′, C5′),
61.7 (OCH2), 55.4 (4′-OCH3), 23.8 (2-CH3), 14.4 (CH2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H18ClNO2: 352.1099; found:
352.1098.
HRMS (ESI+): m/z [M + H]+ calcd for C22H21NO3: 348.1594; found:
348.1594.
Ethyl (E)-2-Methyl-4-(4-(trifluoromethyl)styryl)quinoline-3-
carboxylate (5g)
Anal. Calcd for C22H21NO3: C, 76.06; H, 6.09; N, 4.03; O, 13.82. Found:
C, 76.03; H, 6.07; N, 4.04; O, 13.86.
Beige solid; yield: 0.35 g (90%); mp 78–79 °C; Rf = 0.34 (25% ethyl
acetate–heptane).
Ethyl (E)-4-(4-Bromostyryl)-2-methylquinoline-3-carboxylate
(5d)
IR (ATR): 1709 (C=O ester), 1634 (C=N), 1614 (C=C vinyl), 1572 (C=C
arom.), 1493 (C=C arom.), 955 cm–1 (=C–H trans).
1H NMR:  = 8.06 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.05 (dd, J = 8.3, 1.3 Hz,
1 H, H8), 7.75 (ddd, J = 8.3, 6.9, 1.4 Hz, 1 H, H7), 7.66–7.63 (m, 4 H, H2′,
H3′, H5′, H6′), 7.61 (d, J = 16.5 Hz, 1 H, HAC=), 7.54 (ddd, J = 8.4, 6.9, 1.3
Hz, 1 H, H6), 6.98 (d, J = 16.5 Hz, 1 H, =CHB), 4.37 (q, J = 7.1 Hz, 2 H,
OCH2), 2.76 (s, 3 H, 2-CH3), 1.30 (t, J = 7.1 Hz, 3 H, CH2CH3).
13C NMR:  = 168.8 (C=O), 154.8 (C2), 147.6 (C8a), 141.5 (C4), 139.6
(C1′), 136.1 (=CHB), 130.5 (C7), 130.4 (C4′), 129.3 (C8), 127.0 (C2′, C3′,
C5′, C6′), 126.7 (C6), 126.3 (C3), 125.9 (q, J = 3.8 Hz, 4′-CF3), 125.0
(HAC=, C5), 124.4 (C4a), 61.8 (OCH2), 23.9 (2-CH3), 14.3 (CH2CH3).
Pale yellow solid; yield: 0.34 g (85%); mp 96–97 °C; Rf = 0.34 (25%
ethyl acetate–heptane).
IR (ATR): 1724 (C=O ester), 1640 (C=N), 1612 (C=C vinyl), 1589 (C=C
arom.), 1486 (C=C arom.), 947 cm–1 (=C–H trans).
1H NMR:  = 8.09–8.05 (m, 2 H, H5, H8), 7.74 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H7), 7.55–7.51 (m, 1 H, H6), 7.54 (d, J = 8.4 Hz, 2 H, H3′, H5′), 7.50
(d, J = 16.5 Hz, 1 H, HAC=), 7.41 (d, J = 8.4 Hz, 2 H, H2′, H6′), 6.89 (d, J =
16.5 Hz, 1 H, =CHB), 4.36 (q, J = 7.1 Hz, 2 H, OCH2), 2.75 (s, 3 H, 2-CH3),
1.29 (t, J = 7.1 Hz, 3 H, CH2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C22H18F3NO2: 386.1362; found:
386.1362.
13C NMR:  = 168.9 (C=O), 154.8 (C2), 147.6 (C8a), 141.8 (C4), 136.4
(=CHB), 135.2 (C1′), 132.1 (C3′, C5′), 130.4 (C7), 129.2 (C8), 128.3 (C2′,
C6′), 126.6 (C6), 126.3 (C3), 125.1 (C5), 124.5 (C4a), 123.1 (HAC=),
122.8 (C4′), 61.8 (OCH2), 23.8 (2-CH3), 14.3 (CH2CH3).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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A. Meléndez et al.
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Synthesis
Ethyl (E)-2-Methyl-4-(3-methylstyryl)quinoline-3-carboxylate
(5h)
13C NMR:  = 169.0 (C=O), 154.8 (C2), 147.6 (C8a), 141.5 (C4), 141.4
(C2′), 136.7 (=CHB), 130.3 (C7), 129.2 (C8), 127.8 (C4′), 127.7 (C5′),
126.5 (C6), 126.1 (C3), 126.0 (C3′), 125.1 (C5), 124.5 (C4a), 121.3
(HAC=), 61.8 (OCH2), 23.8 (2-CH3), 14.3 (CH2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C19H17NO2S: 324.1053; found:
324.1052.
Orange solid; yield: 0.25 g (75%); mp 89–90 °C; Rf = 0.40 (25% ethyl
acetate–heptane).
IR (ATR): 1714 (C=O ester), 1640 (C=N), 1600 (C=C vinyl), 1573 (C=C
arom.), 1491 (C=C arom.), 952 cm–1 (=C–H trans).
1H NMR:  = 8.09 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.05 (dd, J = 8.3, 1.3 Hz,
1 H, H8), 7.73 (ddd, J = 8.3, 6.8, 1.3 Hz, 1 H, H7), 7.54–7.50 (m, 1 H,
H6), 7.50 (d, J = 16.5 Hz, 1 H, HAC=), 7.37–7.34 (m, 2 H, H2′, H6′), 7.30
(dd, J = 8.1, 7.4 Hz, 1 H, H5′), 7.17 (br d, J = 7.4 Hz, 1 H, H4′), 6.94 (d, J =
16.5 Hz, 1 H, =CHB), 4.38 (q, J = 7.1 Hz, 2 H, OCH2), 2.76 (s, 3 H, 2-CH3),
2.40 (s, 3 H, 3′-CH3), 1.31 (t, J = 7.1 Hz, 3 H, CH2CH3).
Anal. Calcd for C19H17NO2S: C, 70.56; H, 5.30; N, 4.33; O, 9.89; S, 9.91.
Found: C, 70.62; H, 5.31; N, 4.33; O, 9.87; S, 9.87.
(E)-3-Benzoyl-4-styrylquinolin-2(1H)-one (6a)
Colorless solid; yield: 0.25 g (72%); mp >272 °C (decomp); Rf = 0.36
(50% ethyl acetate–heptane).
13C NMR:  = 169.0 (C=O), 154.7 (C2), 147.6 (C8a), 142.2 (C4), 138.5
(C3′), 137.9 (=CHB), 136.3 (C1′), 130.3 (C7), 129.6 (C4′), 129.2 (C8),
128.8 (C5′), 127.6 (C2′), 126.4 (C6), 126.3 (C3), 125.2 (C5), 124.7 (C4a),
124.1 (C6′), 122.0 (HAC=), 61.7 (OCH2), 23.8 (2-CH3), 21.4 (3′-CH3),
14.3 (CH2CH3).
HRMS (ESI+): m/z [M + Na]+ calcd for C22H21NO2: 354.1465; found:
354.1459.
IR (ATR): 3132 (N–H lactam), 1676 (C=O lactam/ketone), 1640 (C=C
vinyl), 1596 (C=C arom.), 1309 (C–N), 969 cm–1 (=C–H trans).
1H NMR:  = 12.15 (s, 1 H, 1-NH), 7.91 (dd, J = 8.1, 1.4 Hz, 1 H, H5),
7.84–7.82 (m, 2 H, H2′, H6′), 7.64–7.60 (m, 2 H, H7, H4′), 7.51–7.47
(m, 2 H, H3′, H5′), 7.43 (dd, J = 8.5, 1.1 Hz, 1 H, H8), 7.42–7.39 (m, 2 H,
H2′′, H6′′), 7.38 (d, J = 16.4 Hz, 1 H, HAC=), 7.34–7.25 (m, 4 H, H3′′, H4′′,
H5′′, H6), 6.76 (d, J = 16.4 Hz, 1 H, =CHB).
13C NMR:  = 195.4 (3-C–C=O), 160.4 (2-C=O), 145.2 (C4), 139.0 (C8a),
138.5 (=CHB), 137.2 (C1′), 136.0 (C1′′), 134.2 (C4′), 131.8 (C7), 130.1
(C3), 129.5 (C4′′), 129.4 (C2′, C6′), 129.3 (C3′, C5′), 129.2 (C3′′, C5′′),
127.4 (C2′′, C6′′), 126.7 (C5), 122.8 (C6), 122.1 (HAC=), 118.7 (C4a),
116.3 (C8).
Anal. Calcd for C22H21NO2: C, 79.73; H, 6.39; N, 4.23; O, 9.65. Found: C,
79.70; H, 6.41; N, 4.23; O, 9.66.
Ethyl (E)-4-(3-Methoxystyryl)-2-methylquinoline-3-carboxylate
(5i)
HRMS (ESI+): m/z [M + H]+ calcd for C24H17NO2: 352.1332; found:
Colorless solid; yield: 0.25 g (73%); mp 91–92 °C; Rf = 0.28 (25% ethyl
acetate–heptane).
352.1329.
IR (ATR): 1720 (C=O ester), 1640 (C=N), 1598 (C=C vinyl), 1575 (C=C
Anal. Calcd for C24H17NO2: C, 82.03; H, 4.88; N, 3.99; O, 9.11. Found: C,
82.07; H, 4.87; N, 3.98; O, 9.08.
arom.), 1493 (C=C arom.), 964 cm–1 (=C–H trans).
1H NMR:  = 8.09 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.4, 1.2 Hz,
1 H, H8), 7.73 (ddd, J = 8.4, 6.9, 1.2 Hz, 1 H, H7), 7.54–7.50 (m, 1 H,
H6), 7.50 (d, J = 16.5 Hz, 1 H, HAC=), 7.33 (t, J = 7.9 Hz, 1 H, H5′), 7.14
(br d, J = 7.8 Hz, 1 H, H6′), 7.07 (t, J = 2.0 Hz, 1 H, H2′), 6.93 (d, J = 16.5
Hz, 1 H, =CHB), 6.92–6.88 (m, 1 H, H4′), 4.37 (q, J = 7.1 Hz, 2 H, OCH2),
3.86 (s, 3 H, 3′-OCH3), 2.75 (s, 3 H, 2-CH3), 1.31 (t, J = 7.1 Hz, 3 H,
CH2CH3).
13C NMR:  = 169.0 (C=O), 160.0 (C3′), 154.8 (C2), 147.6 (C8a), 142.0
(C4), 137.7 (C1′), 137.6 (=CHB), 130.3 (C7), 129.9 (C5′), 129.2 (C8),
126.5 (C6), 126.3 (C3), 125.2 (C5), 124.6 (C4a), 122.6 (HAC=), 119.5
(C6′), 114.3 (C4′), 112.3 (C2′), 61.7 (OCH2), 55.3 (3′-OCH3), 23.8 (2-
CH3), 14.3 (CH2CH3).
(E)-3-Benzoyl-4-(4-methylstyryl)quinolin-2(1H)-one (6b)
Yellow solid; yield: 0.26 g (71%); mp >295 °C (decomp); Rf = 0.38 (50%
ethyl acetate–heptane).
IR (ATR): 3133 (N–H lactam), 1664 (C=O lactam/ketone), 1641 (C=C
vinyl), 1590 (C=C arom.), 1315 (C–N), 964 cm–1 (=C–H trans).
1H NMR:  = 12.12 (s, 1 H, 1-NH), 7.90 (dd, J = 8.2, 1.4 Hz, 1 H, H5),
7.83–7.81 (m, 2 H, H2′, H6′), 7.64–7.60 (m, 2 H, H7, H4′), 7.50–7.46
(m, 2 H, H3′, H5′), 7.43 (dd, J = 8.3, 1.2 Hz, 1 H, H8), 7.31 (d, J = 16.4 Hz,
1 H, HAC=), 7.29–7.25 (m, 3 H, H6, H2′′, H6′′), 7.12 (d, J = 7.9 Hz, 2 H,
H3′′, H5′′), 6.72 (d, J = 16.4 Hz, 1 H, =CHB), 2.26 (s, 3 H, 4′′-CH3).
13C NMR:  = 195.5 (3-C–C=O), 160.4 (2-C=O), 145.2 (C4), 139.1 (C8a),
139.0 (C4′′), 138.5 (=CHB), 137.2 (C1′), 134.2 (C4′), 133.3 (C1′′), 131.7
(C7), 129.9 (C3), 129.8 (C3′′, C5′′), 129.4 (C2′, C6′), 129.3 (C3′, C5′),
127.4 (C2′′, C6′′), 126.6 (C5), 122.8 (C6), 121.0 (HAC=), 118.7 (C4a),
116.3 (C8), 21.3 (4′′-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C22H21NO3: 348.1594; found:
348.1593.
Anal. Calcd for C22H21NO3: C, 76.06; H, 6.09; N, 4.03; O, 13.82. Found:
C, 76.00; H, 6.11; N, 4.04; O, 13.85.
HRMS (ESI+): m/z [M + H]+ calcd for C25H19NO2: 366.14885; found:
366.14902.
Ethyl (E)-2-Methyl-4-(2-(thiophen-2-yl)vinyl)quinoline-3-carbox-
ylate (5j)
Anal. Calcd for C25H19NO2: C, 82.17; H, 5.24; N, 3.83; O, 8.76. Found: C,
82.19; H, 5.23; N, 3.84; O, 8.74.
Beige solid; yield: 0.29 g (90%); mp 55–56 °C; Rf = 0.37 (25% ethyl
acetate–heptane).
IR (ATR): 1712 (C=O ester), 1624 (C=N), 1601 (C=C vinyl), 1567 (C=C
(E)-3-Benzoyl-4-(4-methoxystyryl)quinolin-2(1H)-one (6c)
arom.), 1493 (C=C arom.), 959 cm–1 (=C–H trans).
Yellow solid; yield: 0.27 g (72%); mp >257 °C (decomp); Rf = 0.26 (50%
ethyl acetate–heptane).
1H NMR:  = 8.09 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.04 (dd, J = 8.3, 1.2 Hz,
1 H, H8), 7.73 (ddd, J = 8.3, 6.8, 1.4 Hz, 1 H, H7), 7.54 (ddd, J = 8.5, 6.8,
1.2 Hz, 1 H, H6), 7.33 (d, J = 16.5 Hz, 1 H, HAC=), 7.32–7.30 (m, 1 H,
H3′), 7.13 (dd, J = 3.5, 1.1 Hz, 1 H, H5′), 7.10 (d, J = 16.5 Hz, 1 H, =CHB),
7.05 (dd, J = 5.1, 3.5 Hz, 1 H, H4′), 4.40 (q, J = 7.1 Hz, 2 H, OCH2), 2.74
(s, 3 H, 2-CH3), 1.34 (t, J = 7.1 Hz, 3 H, CH2CH3).
IR (ATR): 3126 (N–H lactam), 1665 (C=O lactam/ketone), 1637 (C=C
vinyl), 1584 (C=C arom.), 1307 (C–N), 960 cm–1 (=C–H trans).
1H NMR:  = 12.08 (s, 1 H, 1-NH), 7.92 (dd, J = 8.2, 1.4 Hz, 1 H, H5),
7.84–7.81 (m, 2 H, H2′, H6′), 7.64–7.59 (m, 2 H, H7, H4′), 7.50–7.47
(m, 2 H, H3′, H5′), 7.43 (dd, J = 8.3, 1.2 Hz, 1 H, H8), 7.37–7.34 (m, 2 H,
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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A. Meléndez et al.
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Synthesis
H2′′, H6′′), 7.27 (ddd, J = 8.2, 7.1, 1.2 Hz, 1 H, H6), 7.21 (d, J = 16.4 Hz, 1
H, HAC=), 6.85 (m, 2 H, H3′′, H5′′), 6.72 (d, J = 16.4 Hz, 1 H, =CHB), 3.74
(s, 3 H, 4′′-OCH3).
13C NMR:  = 195.5 (3-C–C=O), 160.5 (C4′′), 160.4 (2-C=O), 145.3 (C4),
139.0 (C8a), 138.3 (=CHB), 137.2 (C1′), 134.1 (C4′), 131.7 (C7), 129.7
(C2′, C6′), 129.4 (C3′, C5′), 129.2 (C3), 128.9 (C2′′, C6′′), 128.8 (C1′′),
126.6 (C5), 122.7 (C6), 119.5 (HAC=), 118.8 (C4a), 116.2 (C8), 114.7
(C3′′, C5′′), 55.7 (4′′-OCH3).
13C NMR:  = 195.3 (3-C–C=O), 160.4 (2-C=O), 145.0 (C4), 139.0 (C8a),
137.2 (C1′), 137.1 (=CHB), 135.0 (C4′′), 134.2 (C4′), 133.8 (C1′′), 131.8
(C7), 130.2 (C3), 129.4 (C2′, C6′), 129.3 (C3′, C5′), 129.2 (C3′′, C5′′),
129.1 (C2′′, C6′′), 126.7 (C5), 123.1 (HAC=), 122.8 (C6), 118.6 (C4a),
116.3 (C8).
HRMS (ESI+): m/z [M + H]+ calcd for C24H16ClNO2: 386.0942; found:
386.0941.
HRMS (ESI+): m/z [M + H]+ calcd for C25H19NO3: 382.1438; found:
(E)-3-Benzoyl-4-(4-(trifluoromethyl)styryl)quinolin-2(1H)-one
(6g)
382.1440.
Pale yellow solid; yield: 0.34 g (81%); mp >195 °C (decomp); Rf = 0.33
(50% ethyl acetate–heptane).
Anal. Calcd for C25H19NO3: C, 78.72; H, 5.02; N, 3.67; O, 12.58. Found:
C, 78.70; H, 5.00; N, 3.68; O, 12.61.
IR (ATR): 3141 (N–H lactam), 1667 (C=O lactam/ketone), 1645 (C=C
vinyl), 1594 (C=C arom.), 1323 (C–N), 964 cm–1 (=C–H trans).
(E)-3-Benzoyl-4-(4-bromostyryl)quinolin-2(1H)-one (6d)
Beige solid; yield: 0.33 g (78%); mp >262 °C (decomp); Rf = 0.31 (50%
ethyl acetate–heptane).
1H NMR:  = 12.10 (s, 1 H, 1-NH), 7.90 (d, J = 8.1 Hz, 1 H, H5), 7.83 (br
d, J = 7.6 Hz, 2 H, H2′, H6′), 7.68–7.61 (m, 6 H, H7, H4′, H2′′, H3′′, H5′′,
H6′′), 7.52 (d, J = 16.5 Hz, 1 H, HAC=), 7.50–7.47 (m, 2 H, H3′, H5′), 7.45
(d, J = 8.2 Hz, 1 H, H8), 7.28 (t, J = 7.7 Hz, 1 H, H6), 6.84 (d, J = 16.5 Hz,
1 H, =CHB).
13C NMR:  = 195.3 (3-C–C=O), 160.3 (2-C=O), 144.9 (C4), 140.0 (C1′′),
139.0 (C8a), 137.1 (C1′), 136.8 (=CHB), 134.3 (C4′), 131.9 (C7), 130.4
(C3), 129.5 (C2′, C6′), 129.3 (C3′, C5′), 128.1 (C2′′, C3′′, C5′′, C6′′), 126.7
(C5), 126.1 (q, J = 3.4 Hz, 4′′-CF3), 125.9 (C4′′), 125.3 (HAC=), 122.9
(C6), 118.5 (C4a), 116.4 (C8).
IR (ATR): 3136 (N–H lactam), 1665 (C=O lactam/ketone), 1644 (C=C
vinyl), 1591 (C=C arom.), 1312 (C–N), 964 cm–1 (=C–H trans).
1H NMR:  = 12.16 (s, 1 H, 1-NH), 7.89 (dd, J = 8.1, 1.3 Hz, 1 H, H5),
7.83–7.81 (m, 2 H, H2′, H6′), 7.64–7.60 (m, 2 H, H7, H4′), 7.52–7.50
(m, 2 H, H3′′, H5′′), 7.50–7.47 (m, 2 H, H3′, H5′), 7.43 (dd, J = 8.0, 1.2
Hz, 1 H, H8), 7.42 (d, J = 16.4 Hz, 1 H, HAC=), 7.38–7.36 (m, 2 H, H2′′,
H6′′), 7.29–7.25 (m, 1 H, H6), 6.73 (d, J = 16.4 Hz, 1 H, =CHB).
13C NMR:  = 195.4 (3-C–C=O), 160.3 (2-C=O), 145.0 (C4), 139.0 (C8a),
137.2 (=CHB), 137.1 (C1′), 135.3 (C1′′), 134.2 (C4′), 132.2 (C3′′, C5′′),
131.8 (C7), 130.2 (C3), 129.4 (C2′, C6′, C2′′, C6′′), 129.3 (C3′, C5′), 126.7
(C5), 123.1 (HAC=), 122.8 (C6), 122.5 (C4′′), 118.6 (C4a), 116.3 (C8).
HRMS (ESI+): m/z [M + H]+ calcd for C25H16F3NO2: 420.12058; found:
420.12079.
(E)-3-Benzoyl-4-(3-methylstyryl)quinolin-2(1H)-one (6h)
HRMS (ESI+): m/z [M + H]+ calcd for C24H16BrNO2: 430.04372; found:
430.04419.
Yellow solid; yield: 0.24 g (65%); mp >246 °C (decomp); Rf = 0.33 (50%
ethyl acetate–heptane).
IR (ATR): 3134 (N–H lactam), 1674 (C=O lactam/ketone), 1645 (C=C
(E)-3-Benzoyl-4-(4-fluorostyryl)quinolin-2(1H)-one (6e)
vinyl), 1596 (C=C arom.), 1311 (C–N), 974 cm–1 (=C–H trans).
Colorless solid; yield: 0.28 g (76%); mp >275 °C (decomp); Rf = 0.36
(50% ethyl acetate–heptane).
1H NMR:  = 12.30 (s, 1 H, 1-NH), 7.95–7.93 (m, 2 H, H2′, H6′), 7.84
(dd, J = 8.4, 1.3 Hz, 1 H, H5), 7.58–7.52 (m, 1 H, H4′), 7.48 (ddd, J = 8.4,
7.1, 1.3 Hz, 1 H, H7), 7.44–7.41 (m, 2 H, H3′, H5′), 7.28 (dd, J = 8.4, 1.2
Hz, 1 H, H8), 7.23 (ddd, J = 8.1, 7.1, 1.2 Hz, 1 H, H6), 7.19 (t, J = 7.5 Hz,
1 H, H5′′), 7.09 (d, J = 16.4 Hz, 1 H, HAC=), 7.08 (m, 3 H, H2′′, H4′′, H6′′),
6.88 (d, J = 16.4 Hz, 1 H, =CHB), 2.32 (s, 3 H, 3′′-CH3).
13C NMR:  = 195.2 (3-C–C=O), 162.0 (2-C=O), 146.5 (C4), 139.6
(=CHB), 138.3 (C8a), 138.0 (C5′′), 137.2 (C1′), 135.8 (C1′′), 133.6 (C4′),
131.4 (C7), 129.8 (C4′′), 129.3 (C2′, C6′), 129.2 (C3), 128.8 (C3′, C5′),
128.6 (C3′′), 127.7 (C6′′), 126.0 (C5), 124.2 (C2′′), 123.0 (C6), 120.7
(HAC=), 119.1 (C4a), 117.0 (C8), 21.3 (3′′-CH3).
IR (ATR): 3128 (N–H lactam), 1670 (C=O lactam/ketone), 1643 (C=C
vinyl), 1591 (C=C arom.), 1361 (C–N), 970 cm–1 (=C–H trans).
1H NMR:  = 12.12 (s, 1 H, 1-NH), 7.90 (br d, J = 8.1 Hz, 1 H, H5), 7.82
(br d, J = 7.6 Hz, 2 H, H2′, H6′), 7.64–7.60 (m, 2 H, H7, H4′), 7.51–7.42
(m, 5 H, H8, H2′′, H6′′, H3′, H5′), 7.32 (d, J = 16.4 Hz, 1 H, HAC=), 7.29–
7.25 (m, 1 H, H6), 7.15 (t, J = 8.8 Hz, 2 H, H3′′, H5′′), 6.75 (d, J = 16.4 Hz,
1 H, =CHB).
13C NMR:  = 195.4 (3-C–C=O), 162.8 (d, J = 245.5 Hz, C4′′), 160.4 (2-
C=O), 145.1 (C4), 139.0 (C8a), 137.2 (C1′), 137.1 (=CHB), 134.2 (C4′),
132.7 (d, J = 2.9 Hz, C1′′), 131.8 (C7), 130.1 (C3), 129.5 (d, J = 8.3 Hz,
C2′′, C6′′), 129.4 (C2′, C6′), 129.3 (C3′, C5′), 126.7 (C5), 122.8 (C6),
122.0 (HAC=), 118.6 (C4a), 116.3 (C8), 116.1 (d, J = 22.1 Hz, C3′′, C5′′).
HRMS (ESI+): m/z [M + H]+ calcd for C25H19NO2: 366.1489; found:
366.1487.
Anal. Calcd for C25H19NO2: C, 82.17; H, 5.24; N, 3.83; O, 8.76. Found: C,
82.20; H, 5.23; N, 3.82; O, 8.75.
HRMS (ESI+): m/z [M + H]+ calcd for C24H16FNO2: 370.1238; found:
370.1237.
(E)-3-Benzoyl-4-(3-methoxystyryl)quinolin-2(1H)-one (6i)
(E)-3-Benzoyl-4-(4-chlorostyryl)quinolin-2(1H)-one (6f)
Yellow solid; yield: 0.24 g (63%); mp >242 °C (decomp); Rf = 0.26 (50%
ethyl acetate–heptane).
Yellow solid; yield: 0.30 g (79%); mp >306 °C (decomp); Rf = 0.31 (50%
ethyl acetate–heptane).
IR (ATR): 3136 (N–H lactam), 1672 (C=O lactam/ketone), 1644 (C=C
IR (ATR): 3133 (N–H lactam), 1664 (C=O lactam/ketone), 1641 (C=C
vinyl), 1593 (C=C arom.), 1313 (C–N), 967 cm–1 (=C–H trans).
vinyl), 1590 (C=C arom.), 1315 (C–N), 964 cm–1 (=C–H trans).
1H NMR:  = 12.15 (s, 1 H, 1-NH), 7.91 (dd, J = 8.1, 1.4 Hz, 1 H, H5),
7.84–7.82 (m, 2 H, H2′, H6′), 7.65–7.60 (m, 2 H, H7, H4′), 7.51–7.48
(m, 2 H, H3′, H5′), 7.43 (dd, J = 8.3, 1.2 Hz, 1 H, H8), 7.39 (d, J = 16.4 Hz,
1 H, HAC=), 7.28 (ddd, J = 8.1, 7.1, 1.2 Hz, 1 H, H6), 7.22 (t, J = 7.9 Hz, 1
1H NMR:  = 12.16 (s, 1 H, 1-NH), 7.90 (dd, J = 8.2, 1.4 Hz, 1 H, H5),
7.84–7.81 (m, 2 H, H2′, H6′), 7.64–7.60 (m, 2 H, H7, H4′), 7.51–7.47
(m, 2 H, H3′, H5′), 7.45–7.42 (m, 4 H, HAC=, H8, H3′′, H5′′), 7.38–7.36
(m, 2 H, H2′′, H6′′), 7.27 (ddd, J = 8.2, 7.1, 1.1 Hz, 1 H, H6), 6.74 (d, J =
16.4 Hz, 1 H, =CHB).
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H, H5′′), 6.99 (t, J = 2.2 Hz, 1 H, H2′′), 6.92 (br d, J = 7.9 Hz, 1 H, H6′′),
6.86 (dd, J = 7.9, 2.2 Hz, 1 H, H4′′), 6.72 (d, J = 16.4 Hz, 1 H, =CHB), 3.74
(s, 3 H, 3′′-OCH3).
13C NMR:  = 195.4 (3-C–C=O), 160.4 (2-C=O), 160.0 (C3′′), 145.1 (C4),
139.0 (C8a), 138.4 (=CHB), 137.5 (C1′′), 137.2 (C1′), 134.2 (C4′), 131.8
(C7), 130.1 (C3), 130.0 (C5′′), 129.4 (C2′, C6′), 129.3 (C3′, C5′), 126.7
(C5), 122.8 (C6), 122.5 (HAC=), 120.1 (C6′′), 118.7 (C4a), 116.3 (C8),
115.2 (C4′′), 112.6 (C2′′), 55.6 (3′′-OCH3).
IR (ATR): 1678 (C=O), 1627 (C=N), 1607 (C=C vinyl), 1548 (C=C arom.),
1490 (C=C arom.), 958 cm–1 (=C–H trans).
1H NMR:  = 8.37 (dd, J = 8.6, 1.4 Hz, 1 H, H8), 8.04 (dd, J = 8.5, 1.3 Hz,
1 H, H5), 7.93 (d, J = 16.5 Hz, 1 H, HAC=), 7.79 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H6), 7.55 (d, J = 8.0 Hz, 2 H, H2′, H6′), 7.51 (ddd, J = 8.4, 6.8, 1.3 Hz,
1 H, H7), 7.23 (d, J = 8.0 Hz, 2 H, H3′, H5′), 6.67 (d, J = 16.5 Hz, 1 H,
=CHB), 3.32 (dd, J = 6.9, 5.6 Hz, 2 H, HAHB4), 2.80 (dd, J = 7.2, 5.9 Hz, 2
H, HAHB2), 2.40 (s, 3 H, 4′-CH3), 2.27–2.20 (m, 2 H, HAHB3).
HRMS (ESI+): m/z [M + H]+ calcd for C25H19NO3: 382.1438; found:
382.1439.
13C NMR:  = 199.6 (1-C=O), 162.1 (C4a), 149.6 (C9), 149.4 (C10a),
138.5 (C4′), 136.6 (=CHB), 134.1 (C1′), 131.8 (C6), 129.5 (C3′, C5′),
128.9 (C5), 128.3 (C8), 127.0 (C2′, C6′), 126.3 (C7), 126.2 (C8a), 124.8
(HAC=), 123.0 (C9a), 40.9 (C2), 34.7 (C4), 21.4 (C3, 4′-CH3).
Anal. Calcd for C25H19NO3: C, 78.72; H, 5.02; N, 3.67; O, 12.58. Found:
C, 78.65; H, 5.04; N, 3.68; O, 12.63.
HRMS (ESI+): m/z [M + H]+ calcd for C22H19NO: 314.15394; found:
314.15399.
(E)-3-Benzoyl-4-(2-(thiophen-2-yl)vinyl)quinolin-2(1H)-one (6j)
Anal. Calcd for C22H19NO: C, 84.31; H, 6.11; N, 4.47; O, 5.10. Found: C,
84.29; H, 6.13; N, 4.46; O, 5.12.
Colorless solid; yield: 0.29 g (80%); mp >261 °C (decomp); Rf = 0.36
(50% ethyl acetate–heptane).
IR (ATR): 3130 (N–H lactam), 1676 (C=O lactam/ketone), 1645 (C=C
vinyl), 1596 (C=C arom.), 1309 (C–N), 962 cm–1 (=C–H trans).
(E)-9-(4-Methoxystyryl)-3,4-dihydroacridin-1(2H)-one (7c)
Yellow solid; yield: 0.22 g (68%); mp 160–162 °C; Rf = 0.15 (50% ethyl
acetate–heptane).
1H NMR:  = 12.14 (s, 1 H, 1-NH), 7.87 (dd, J = 8.2, 1.3 Hz, 1 H, H5),
7.84–7.81 (m, 2 H, H2′, H6′), 7.66–7.60 (m, 2 H, H7, H4′), 7.52 (dd, J =
3.6, 1.2 Hz, 1 H, H5′′), 7.51–7.48 (m, 2 H, H3′, H5′), 7.43 (dd, J = 8.3, 1.2
Hz, 1 H, H8), 7.28 (ddd, J = 8.2, 7.1, 1.2 Hz, 1 H, H6), 7.18 (dd, J = 3.7,
1.2 Hz, 1 H, H3′′), 7.04 (d, J = 16.2 Hz, 1 H, HAC=), 7.02 (dd, J = 3.7, 3.6
Hz, 1 H, H4′′), 6.96 (d, J = 16.2 Hz, 1 H, =CHB).
13C NMR:  = 195.5 (3-C–C=O), 160.3 (2-C=O), 144.3 (C4), 140.8 (C2′′),
139.1 (C8a), 137.0 (C1′), 134.3 (C4′), 131.8 (=CHB), 131.7 (C7), 130.0
(C3), 129.5 (C2′, C6′), 129.3 (C3′, C5′), 129.1 (C3′′), 128.6 (C4′′), 127.8
(C5′′), 126.5 (C5), 122.9 (C6), 120.5 (HAC=), 118.4 (C4a), 116.3 (C8).
IR (ATR): 1670 (C=O), 1625 (C=N), 1602 (C=C vinyl), 1561 (C=C arom.),
1509 (C=C arom.), 979 cm–1 (=C–H trans).
1H NMR:  = 8.37 (d, J = 8.4 Hz, 1 H, H8), 8.03 (d, J = 8.4 Hz, 1 H, H5),
7.88 (d, J = 16.5 Hz, 1 H, HAC=), 7.79 (ddd, J = 8.3, 7.2, 1.4 Hz, 1 H, H6),
7.59 (d, J = 8.6 Hz, 2 H, H2′, H6′), 7.51 (ddd, J = 8.2, 7.2, 1.4 Hz, 1 H, H7),
6.95 (d, J = 8.6 Hz, 2 H, H3′, H5′), 6.66 (d, J = 16.5 Hz, 1 H, =CHB), 3.86
(s, 3 H, 4′-OCH3), 3.32 (t, J = 6.3 Hz, 2 H, HAHB4), 2.79 (t, J = 6.5 Hz, 2 H,
HAHB2), 2.23 (p, J = 6.5 Hz, 2 H, HAHB3).
HRMS (ESI+): m/z [M + H]+ calcd for C22H15NO2S: 358.0896; found:
358.0896.
13C NMR:  = 199.6 (1-C=O), 162.1 (C4a), 160.0 (C4′), 149.7 (C9), 149.4
(C10a), 136.5 (=CHB), 131.8 (C6), 129.7 (C1′), 128.9 (C5), 128.4 (C2′,
C6′), 128.3 (C8), 126.2 (C7, C8a), 123.6 (HAC=), 122.9 (C9a), 114.3 (C3′,
C5′), 55.4 (4′-OCH3), 41.0 (C2), 34.7 (C4), 21.4 (C3).
Anal. Calcd for C22H15NO2S: C, 73.93; H, 4.23; N, 3.92; O, 8.95; S, 8.97.
Found: C, 73.96; H, 4.22; N, 3.91; O, 8.97; S, 8.94.
HRMS (ESI+): m/z [M + H]+ calcd for C22H19NO2: 330.14885; found:
330.14868.
(E)-9-Styryl-3,4-dihydroacridin-1(2H)-one (7a)
Anal. Calcd for C22H19NO2: C, 80.22; H, 5.81; N, 4.25; O, 9.71. Found: C,
80.17; H, 5.82; N, 4.26; O, 9.74.
Yellow solid; yield: 0.19 g (63%); mp 161–163 °C; Rf = 0.20 (50% ethyl
acetate–heptane).
IR (ATR): 1676 (C=O), 1625 (C=N), 1606 (C=C vinyl), 1540 (C=C arom.),
1486 (C=C arom.), 956 cm–1 (=C–H trans).
(E)-9-(4-Bromostyryl)-3,4-dihydroacridin-1(2H)-one (7d)
Yellow solid; yield: 0.28 g (73%); mp 164–166 °C; Rf = 0.20 (50% ethyl
acetate–heptane).
1H NMR:  = 8.37 (dd, J = 8.6, 1.4 Hz, 1 H, H8), 8.05 (dd, J = 8.4, 1.3 Hz,
1 H, H5), 7.96 (d, J = 16.6 Hz, 1 H, HAC=), 7.80 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H6), 7.70–7.61 (m, 2 H, H2′, H6′), 7.52 (ddd, J = 8.3, 6.8, 1.3 Hz, 1
H, H7), 7.46–7.38 (m, 2 H, H3′, H5′), 7.36–7.30 (m, 1 H, H4′), 6.68 (d,
J = 16.6 Hz, 1 H, =CHB), 3.33 (dd, J = 6.9, 5.7 Hz, 2 H, HAHB4), 2.80 (dd,
J = 7.2, 5.9 Hz, 2 H, HAHB2), 2.27–2.21 (m, 2 H, HAHB3).
13C NMR:  = 199.6 (1-C=O), 162.1 (C4a), 149.4 (C9), 149.3 (C10a),
136.8 (C1′), 136.4 (=CHB), 131.9 (C6), 128.9 (C5, C4′), 128.4 (C3′, C5′),
128.2 (C8), 127.0 (C2′, C6′), 126.4 (C7), 126.1 (C8a), 125.8 (HAC=),
123.1 (C9a), 40.9 (C2), 34.7 (C4), 21.4 (C3).
IR (ATR): 1667 (C=O), 1633 (C=N), 1610 (C=C vinyl), 1541 (C=C arom.),
1485 (C=C arom.), 953 cm–1 (=C–H trans).
1H NMR:  = 8.31 (dd, J = 8.6, 1.4 Hz, 1 H, H8), 8.05 (dd, J = 8.5, 1.3 Hz,
1 H, H5), 7.92 (d, J = 16.6 Hz, 1 H, HAC=), 7.80 (ddd, J = 8.4, 6.8, 1.4 Hz,
1 H, H6), 7.55–7.50 (m, 5 H, H7, H2′, H3′, H5′, H6′), 6.60 (d, J = 16.6 Hz,
1 H, =CHB), 3.33 (dd, J = 6.9, 5.6 Hz, 2 H, HAHB4), 2.80 (dd, J = 7.3, 5.9
Hz, 2 H, HAHB2), 2.27–2.20 (m, 2 H, HAHB3).
13C NMR:  = 199.6 (1-C=O), 162.1 (C4a), 149.4 (C10a), 148.9 (C9),
135.8 (C1′), 134.8 (=CHB), 132.0 (C6), 131.9 (C3′, C5′), 129.0 (C5), 128.5
(C2′, C6′), 128.0 (C8), 126.7 (HAC=), 126.5 (C7), 125.9 (C8a), 123.0
(C9a), 122.3 (C4′), 40.9 (C2), 34.6 (C4), 21.4 (C3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H17NO: 300.13829; found:
300.13785.
Anal. Calcd for C21H17NO: C, 84.25; H, 5.72; N, 4.68; O, 5.34. Found: C,
84.29; H, 5.72; N, 4.66; O, 5.32.
HRMS (ESI+): m/z [M + H]+ calcd for C21H16BrNO: 378.04880; found:
378.04840.
(E)-9-(4-Methylstyryl)-3,4-dihydroacridin-1(2H)-one (7b)
(E)-9-(4-Fluorostyryl)-3,4-dihydroacridin-1(2H)-one (7e)
Yellow solid; yield: 0.22 g (69%); mp 129–131 °C; Rf = 0.15 (50% ethyl
acetate–heptane).
Pale orange solid; yield: 0.21 g (67%); mp 155–157 °C; Rf = 0.17 (50%
ethyl acetate–heptane).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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IR (ATR): 1681 (C=O), 1627 (C=N), 1597 (C=C vinyl), 1543 (C=C arom.),
IR (ATR): 3237 (N–H amide), 1667 (C=O amide), 1614 (C=N, C=C
1505 (C=C arom.), 982 cm–1 (=C–H trans).
vinyl), 1567 (C=C arom.), 1494 (C=C arom.), 970 cm–1 (=C–H trans).
1H NMR:  = 8.34 (dd, J = 8.4, 1.4 Hz, 1 H, H8), 8.05 (dd, J = 8.6, 1.4 Hz,
1 H, H5), 7.87 (d, J = 16.4 Hz, 1 H, HAC=), 7.80 (ddd, J = 8.4, 6.9, 1.4 Hz,
1 H, H6), 7.64–7.60 (m, 2 H, H2′, H6′), 7.53 (ddd, J = 8.3, 6.9, 1.4 Hz, 1
H, H7), 7.14–7.09 (m, 2 H, H3′, H5′), 6.64 (d, J = 16.4 Hz, 1 H, =CHB),
3.33 (t, J = 6.3 Hz, 2 H, HAHB4), 2.80 (t, J = 6.6 Hz, 2 H, HAHB2), 2.27–
2.21 (m, 2 H, HAHB3).
1H NMR:  = 8.21 (dd, J = 8.4, 1.3 Hz, 1 H, H5), 7.99 (d, J = 2.4 Hz, 1 H,
CONHAHB), 7.96 (dd, J = 8.4, 1.3 Hz, 1 H, H8), 7.75 (ddd, J = 8.4, 6.8, 1.4
Hz, 1 H, H7), 7.73 (d, J = 2.4 Hz, 1 H, CONHAHB), 7.63–7.51 (m, 1 H, H6),
7.58 (d, J = 16.5 Hz, 1 H, HAC=), 7.55 (d, J = 8.0 Hz, 2 H, H2′, H6′), 7.25
(d, J = 8.0 Hz, 2 H, H3′, H5′), 7.12 (d, J = 16.5 Hz, 1 H, =CHB), 2.66 (s, 3 H,
2-CH3), 2.35 (s, 3 H, 4′-CH3).
13C NMR:  = 199.6 (1-C=O), 162.9 (d, J = 248.2 Hz, C4′), 162.1 (C4a),
149.4 (C10a), 149.1 (C9), 135.0 (=CHB), 133.1 (d, J = 3.6 Hz, C1′), 131.9
(C6), 129.0 (C5), 128.6 (d, J = 8.1 Hz, C2′, C6′), 128.1 (C8), 126.4 (C7),
126.0 (C8a), 125.7 (d, J = 2.1 Hz, HAC=), 123.1 (C9a), 115.8 (d, J = 22.0
Hz, C3′, C5′), 40.9 (C2), 34.6 (C4), 21.4 (C3).
13C NMR:  = 170.5 (C=O), 155.1 (C2), 147.1 (C8a), 139.7 (C4), 138.6
(C4′), 137.3 (=CHB), 134.4 (C1′), 130.6 (C3), 130.1 (C7), 129.9 (C3′, C5′),
129.2 (C8), 127.4 (C2′, C6′), 126.8 (C6), 125.7 (C5), 124.8 (C4a), 121.7
(HAC=), 23.5 (2-CH3), 21.4 (4′-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C20H18N2O: 303.14918; found:
303.14902.
HRMS (ESI+): m/z [M + H]+ calcd for C21H16FNO: 318.12886; found:
318.12891.
Anal. Calcd for C20H18N2O: C, 79.44; H, 6.00; N, 9.26; O, 5.29. Found: C,
79.48; H, 5.99; N, 9.25; O, 5.28.
(E)-9-(4-Chlorostyryl)-3,4-dihydroacridin-1(2H)-one (7f)
Red solid; yield: 0.23 g (70%); mp 156–157 °C; Rf = 0.25 (50% ethyl
(E)-4-(4-Methoxystyryl)-2-methylquinoline-3-carboxamide (8c)
acetate–heptane).
Beige solid; yield: 0.25 g (80%); mp >237 °C (decomp); Rf = 0.34 (80%
IR (ATR): 1667 (C=O, C=N), 1541 (C=C vinyl, C=C arom.), 1486 (C=C
ethyl acetate–heptane).
arom.), 953 cm–1 (=C–H trans).
IR (ATR): 3195 (N–H amide), 1674 (C=O amide), 1626 (C=N, C=C
1H NMR:  = 8.32 (ddd, J = 8.5, 1.4, 0.6 Hz, 1 H, H8), 8.05 (ddd, J = 8.4,
1.3, 0.6 Hz, 1 H, H5), 7.91 (d, J = 16.6 Hz, 1 H, HAC=), 7.81 (ddd, J = 8.4,
6.8, 1.4 Hz, 1 H, H6), 7.59–7.56 (m, 2 H, H2′, H6′), 7.53 (ddd, J = 8.4,
6.8, 1.3 Hz, 1 H, H7), 7.40–7.37 (m, 2 H, H3′, H5′), 6.62 (d, J = 16.6 Hz, 1
H, =CHB), 3.33 (t, J = 6.3 Hz, 2 H, HAHB4), 2.80 (dd, J = 7.2, 5.9 Hz, 2 H,
HAHB2), 2.25 (dt, J = 8.0, 6.0 Hz, 2 H, HAHB3).
vinyl), 1567 (C=C arom.), 1506 (C=C arom.), 970 cm–1 (=C–H trans).
1H NMR:  = 8.26 (d, J = 8.4 Hz, 1 H, H5), 8.01 (s, 1 H, CONHAHB), 8.00
(d, J = 8.4 Hz, 1 H, H8), 7.81–7.77 (m, 1 H, H7), 7.77 (s, 1 H, CONHAHB),
7.64–7.60 (m, 1 H, H6), 7.61 (d, J = 8.0 Hz, 2 H, H2′, H6′), 7.52 (d, J =
16.5 Hz, 1 H, HAC=), 7.15 (d, J = 16.5 Hz, 1 H, =CHB), 7.01 (d, J = 8.0 Hz,
2 H, H3′, H5′), 3.81 (s, 3 H, 4′-OCH3), 2.68 (s, 3 H, 2-CH3).
13C NMR:  = 199.6 (1-C=O), 162.1 (C4a), 149.4 (C10a), 148.9 (C9),
135.4 (C1′), 134.8 (=CHB), 134.1 (C4′), 132.0 (C6), 129.0 (C5, C3′, C5′),
128.2 (C2′, C6′), 128.0 (C8), 126.6 (C7), 126.5 (HAC=), 126.0 (C8a),
123.1 (C9a), 40.9 (C2), 34.6 (C4), 21.4 (C3).
HRMS (ESI+): m/z [M + H]+ calcd for C21H16ClNO: 334.09932; found:
334.09991.
13C NMR:  = 170.2 (C=O), 160.3 (C4′), 155.0 (C2), 146.2 (C8a), 140.1
(C4), 137.6 (=CHB), 130.5 (C3, C7), 129.5 (C1′), 129.0 (C8, C2′, C6′),
127.0 (C6), 125.9 (C5), 124.9 (C4a), 120.1 (HAC=), 114.8 (C3′, C5′), 55.8
(4′-OCH3), 23.1 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C20H18N2O2: 319.14410; found:
319.14413.
Anal. Calcd for C20H18N2O2: C, 75.45; H, 5.70; N, 8.80; O, 10.05. Found:
C, 75.47; H, 5.72; N, 8.78; O, 10.03.
(E)-2-Methyl-4-styrylquinoline-3-carboxamide (8a)
Yellow solid; yield: 0.23 g (80%); mp >248 °C (decomp); Rf = 0.42 (80%
ethyl acetate–heptane).
(E)-4-(4-Bromostyryl)-2-methylquinoline-3-carboxamide (8d)
IR (ATR): 3195 (N–H amide), 1671 (C=O amide), 1611 (C=N, C=C
Colorless solid; yield: 0.29 g (79%); mp >214 °C (decomp); Rf = 0.42
(80% ethyl acetate–heptane).
vinyl), 1566 (C=C arom.), 1494 (C=C arom.), 968 cm–1 (=C–H trans).
1H NMR:  = 8.21 (dd, J = 8.4, 1.4 Hz, 1 H, H5), 8.00 (d, J = 2.4 Hz, 1 H,
CONHAHB), 7.97 (dd, J = 8.3, 1.4 Hz, 1 H, H8), 7.76 (ddd, J = 8.3, 6.8, 1.4
Hz, 1 H, H7), 7.74 (d, J = 2.4 Hz, 1 H, CONHAHB), 7.67–7.65 (m, 2 H, H2′,
H6′), 7.65 (d, J = 16.6 Hz, 1 H, HAC=), 7.59 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H,
H6), 7.44 (t, J = 7.5 Hz, 2 H, H3′, H5′), 7.39–7.35 (m, 1 H, H4′), 7.15 (d,
J = 16.6 Hz, 1 H, =CHB), 2.66 (s, 3 H, 2-CH3).
13C NMR:  = 170.4 (C=O), 155.1 (C2), 147.1 (C8a), 139.7 (C4), 137.3
(=CHB), 136.9 (C1′), 130.7 (C3), 130.1 (C7), 129.3 (C3′, C5′), 129.2 (C4′),
129.1 (C8), 127.5 (C2′, C6′), 126.8 (C6), 125.7 (C5), 124.8 (C4a), 122.8
(HAC=), 23.6 (2-CH3).
IR (ATR): 3227 (N–H amide), 1667 (C=O amide), 1624 (C=N), 1613
(C=C vinyl), 1562 (C=C arom.), 1494 (C=C arom.), 970 cm–1 (=C–H
trans).
1H NMR:  = 8.20 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.00 (d, J = 2.3 Hz, 1 H,
CONHAHB), 7.97 (dd, J = 8.5, 1.3 Hz, 1 H, H8), 7.76 (ddd, J = 8.4, 6.8, 1.4
Hz, 1 H, H7), 7.75 (d, J = 2.1 Hz, 1 H, CONHAHB), 7.69 (d, J = 16.6 Hz, 1
H, HAC=), 7.63 (br s, 4 H, H2′, H3′, H5′, H6′), 7.59 (ddd, J = 8.3, 6.9, 1.4
Hz, 1 H, H6), 7.12 (d, J = 16.6 Hz, 1 H, =CHB), 2.66 (s, 3 H, 2-CH3).
13C NMR:  = 170.3 (C=O), 155.1 (C2), 147.1 (C8a), 139.5 (C4), 136.1
(C1′), 136.0 (=CHB), 132.2 (C3′, C5′), 130.6 (C3), 130.1 (C7), 129.5 (C2′,
C6′), 129.2 (C8), 126.9 (C6), 125.7 (C5), 124.7 (C4a), 123.9 (HAC=),
122.1 (C4′), 23.5 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C19H16N2O: 289.13353; found:
289.13373.
Anal. Calcd for C19H16N2O: C, 79.14; H, 5.59; N, 9.72; O, 5.55. Found: C,
79.15; H, 5.58; N, 9.74; O, 5.53.
HRMS (ESI+): m/z [M + H]+ calcd for C19H15BrN2O: 367.04405; found:
367.04489.
(E)-2-Methyl-4-(4-methylstyryl)quinoline-3-carboxamide (8b)
(E)-4-(4-Fluorostyryl)-2-methylquinoline-3-carboxamide (8e)
Colorless solid; yield: 0.23 g (77%); mp 210–212 °C; Rf = 0.45 (80%
ethyl acetate–heptane).
Beige solid; yield: 0.23 g (74%); mp >245 °C (decomp); Rf = 0.40 (80%
ethyl acetate–heptane).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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A. Meléndez et al.
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Synthesis
IR (ATR): 3175 (N–H amide), 1672 (C=O amide), 1613 (C=N), 1597
(C=C vinyl), 1566 (C=C arom.), 1505 (C=C arom.), 974 cm–1 (=C–H
trans).
1H NMR:  = 8.21 (d, J = 8.3 Hz, 1 H, H5), 8.00 (br s, 1 H, CONHAHB),
7.97 (d, J = 8.5 Hz, 1 H, H8), 7.78–7.74 (m, 1 H, H7), 7.74 (br s, 1 H,
CONHAHB), 7.74–7.70 (m, 2 H, H2′, H6′), 7.61 (d, J = 16.5 Hz, 1 H,
HAC=), 7.61–7.57 (m, 1 H, H6), 7.30–7.25 (m, 2 H, H3′, H5′), 7.14 (d, J =
16.5 Hz, 1 H, =CHB), 2.66 (s, 3 H, 2-CH3).
13C NMR:  = 170.4 (C=O), 162.7 (d, J = 246.1 Hz, C4′), 155.1 (C2), 147.1
(C8a), 139.6 (C4), 136.1 (=CHB), 133.5 (d, J = 3.0 Hz, C1′), 130.6 (C3),
130.1 (C7), 129.5 (d, J = 8.2 Hz, C2′, C6′), 129.1 (C8), 126.8 (C6), 125.7
(C5), 124.8 (C4a), 122.8 (d, J = 2.2 Hz, HAC=), 116.2 (d, J = 21.4 Hz, C3′,
C5′), 23.5 (2-CH3).
13C NMR:  = 198.5 (C=O), 155.0 (C2), 147.7 (C8a), 146.8 (=CHB′), 141.4
(C4), 139.5 (=CHB), 136.3 (C1′), 134.1 (C1′′), 131.6 (C3), 131.2 (C4′′),
130.2 (C7), 129.3 (C8), 129.0 (C3′′, C5′′), 128.9 (C3′, C5′), 128.8 (C4′),
128.6 (C2′′, C6′′), 128.3 (HA′C=), 127.0 (C2′, C6′), 126.6 (C6), 125.0 (C5),
124.8 (C4a), 121.8 (HAC=), 23.9 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C27H21NO: 376.1696; found:
376.1696.
Anal. Calcd for C27H21NO: C, 86.37; H, 5.64; N, 3.73; O, 4.26. Found: C,
86.35; H, 5.65; N, 3.74; O, 4.26.
(E)-1-(2-Methyl-4-((E)-4-methylstyryl)quinolin-3-yl)-3-phenyl-
prop-2-en-1-one (9b)
Colorless solid; yield: 0.28 g (73%); mp 149–151 °C; Rf = 0.51 (38%
ethyl acetate–heptane).
HRMS (ESI+): m/z [M + H]+ calcd for C19H15FN2O: 307.12411; found:
307.12479.
IR (ATR): 1638 (C=O), 1624 (C=N), 1597 (C=C vinyl), 1560 (C=C arom.),
1489 (C=C arom.), 972 cm–1 (=C–H trans).
(E)-4-(4-Chlorostyryl)-2-methylquinoline-3-carboxamide (8f)
1H NMR:  = 8.16 (d, J = 8.4 Hz, 1 H, H5), 8.10 (d, J = 8.4 Hz, 1 H, H8),
7.77 (ddd, J = 8.4, 6.8, 1.4 Hz, 1 H, H7), 7.59–7.55 (m, 1 H, H6), 7.44
(dd, J = 7.5, 1.8 Hz, 2 H, H2′′, H6′′), 7.37 (d, J = 16.4 Hz, 1 H, HAC=),
7.38–7.32 (m, 5 H, H2′, H6′, H3′′, H4′′, H5′′), 7.20 (d, J = 16.3 Hz, 1 H,
=CHB′), 7.15 (d, J = 7.8 Hz, 2 H, H3′, H5′), 6.94 (d, J = 16.3 Hz, 1 H,
HA′C=), 6.93 (d, J = 16.4 Hz, 1 H, =CHB), 2.68 (s, 3 H, 2-CH3), 2.35 (s, 3 H,
4′-CH3).
13C NMR:  = 198.6 (C=O), 155.0 (C2), 147.7 (C8a), 146.7 (=CHB′), 141.5
(C4), 139.5 (=CHB), 139.0 (C4′), 134.1 (C1′′), 133.6 (C1′), 131.5 (C3),
131.1 (C4′′), 130.2 (C7), 129.5 (C3′, C5′), 129.3 (C8), 129.0 (C3′′, C5′′),
128.6 (C2′′, C6′′), 128.3 (HA′C=), 127.0 (C2′, C6′), 126.5 (C6), 125.0 (C5),
124.9 (C4a), 120.7 (HAC=), 23.9 (2-CH3), 21.4 (4′-CH3).
Beige solid; yield: 0.27 g (83%); mp >230 °C (decomp); Rf = 0.42 (80%
ethyl acetate–heptane).
IR (ATR): 3226 (N–H amide), 1669 (C=O amide), 1621 (C=N, C=C
vinyl), 1563 (C=C arom.), 1495 (C=C arom.), 986 cm–1 (=C–H trans).
1H NMR:  = 8.20 (dd, J = 8.5, 1.4 Hz, 1 H, H5), 8.00 (d, J = 2.3 Hz, 1 H,
CONHAHB), 7.97 (dd, J = 8.4, 1.3 Hz, 1 H, H8), 7.76 (ddd, J = 8.3, 6.9, 1.4
Hz, 1 H, H7), 7.75 (d, J = 2.3 Hz, 1 H, CONHAHB), 7.71–7.68 (m, 2 H, H2′,
H6′), 7.68 (d, J = 16.6 Hz, 1 H, HAC=), 7.59 (ddd, J = 8.3, 6.9, 1.3 Hz, 1 H,
H6), 7.52–7.49 (m, 2 H, H3′, H5′), 7.13 (d, J = 16.6 Hz, 1 H, =CHB), 2.66
(s, 3 H, 2-CH3).
13C NMR:  = 170.3 (C=O), 155.1 (C2), 147.1 (C8a), 139.5 (C4), 135.9
(=CHB), 135.8 (C1′), 133.5 (C4′), 130.7 (C3), 130.1 (C7), 129.3 (C3′, C5′),
129.2 (C2′, C6′), 129.1 (C8), 126.9 (C6), 125.7 (C5), 124.7 (C4a), 123.8
(HAC=), 23.5 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C28H23NO: 390.1852; found:
390.1852.
Anal. Calcd for C28H23NO: C, 86.34; H, 5.95; N, 3.60; O, 4.11. Found: C,
86.37; H, 5.93; N, 3.60; O, 4.10.
HRMS (ESI+): m/z [M + H]+ calcd for C19H15ClN2O: 323.09456; found:
323.09500.
(E)-1-(4-((E)-4-Methoxystyryl)-2-methylquinolin-3-yl)-3-phenyl-
(E)-1-(2-Methyl-4-((E)-styryl)quinolin-3-yl)-3-phenylprop-2-en-
prop-2-en-1-one (9c)
1-ones 9a–g; General Procedure
Colorless solid; yield: 0.31 g (76%); mp 130–131 °C; Rf = 0.44 (38%
A solution of selected 3-acetyl-4-styrylquinolines 3a–g (1.0 mmol),
benzaldehyde (1.0 mmol) and KOH (1.0 mmol) in ethanol (3 mL) was
stirred at ambient temperature for 3 h. Upon completion of the reac-
tion, monitored by TLC, the solution was filtered to isolate the formed
solid product, which was then rinsed with an ice-cold water/ethanol
solution (4:1, 10 mL). The isolated solid products were further recrys-
tallized from ethyl acetate–heptane (1:1) to afford crystals of the tar-
geted molecular hybrids 9a–g.
ethyl acetate–heptane).
IR (ATR): 1647 (C=O), 1621 (C=N), 1603 (C=C vinyl), 1572 (C=C arom.),
1509 (C=C arom.), 977 cm–1 (=C–H trans).
1H NMR:  = 8.16 (dd, J = 8.6, 1.4 Hz, 1 H, H5), 8.09 (dd, J = 8.4, 1.4 Hz,
1 H, H8), 7.77 (ddd, J = 8.4, 6.9, 1.4 Hz, 1 H, H7), 7.56 (ddd, J = 8.4, 6.9,
1.4 Hz, 1 H, H6), 7.45–7.39 (m, 4 H, H2′, H6′, H2′′, H6′′), 7.37–7.30 (m,
3 H, H3′′, H4′′, H5′′), 7.28 (d, J = 16.4 Hz, 1 H, HAC=), 7.20 (d, J = 16.4 Hz,
1 H, =CHB′), 6.94 (d, J = 16.4 Hz, 1 H, =CHB), 6.90 (d, J = 16.4 Hz, 1 H,
HA′C=), 6.88–6.85 (m, 2 H, H3′, H5′), 3.81 (s, 3 H, 4′-OCH3), 2.68 (s, 3 H,
2-CH3).
13C NMR:  = 198.6 (C=O), 160.2 (C4′), 155.0 (C2), 147.7 (C8a), 146.5
(=CHB′), 141.6 (C4), 139.1 (=CHB), 134.2 (C1′′), 131.5 (C3), 131.0 (C4′′),
130.1 (C7), 129.3 (C8), 129.1 (C1′), 129.0 (C3′′, C5′′), 128.6 (C2′′, C6′′),
128.4 (C2′, C6′), 128.3 (HA′C=), 126.4 (C6), 125.0 (C5), 124.9 (C4a),
119.4 (HAC=), 114.2 (C3′, C5′), 55.4 (4′-OCH3), 23.9 (2-CH3).
(E)-1-(2-Methyl-4-((E)-styryl)quinolin-3-yl)-3-phenylprop-2-en-
1-one (9a)
Colorless solid; yield: 0.28 g (74%); mp 134–136 °C; Rf = 0.51 (38%
ethyl acetate–heptane).
IR (ATR): 1650 (C=O), 1620 (C=N, C=C vinyl), 1572 (C=C arom.), 1494
(C=C arom.), 968 cm–1 (=C–H trans).
1H NMR:  = 8.16 (dd, J = 8.4, 1.5 Hz, 1 H, H5), 8.11 (dd, J = 8.4, 1.3 Hz,
1 H, H8), 7.78 (ddd, J = 8.4, 6.9, 1.5 Hz, 1 H, H7), 7.57 (ddd, J = 8.4, 6.9,
1.3 Hz, 1 H, H6), 7.48–7.45 (m, 4 H, H2′, H6′, H2′′, H6′′), 7.41 (d, J =
16.3 Hz, 1 H, HAC=), 7.38–7.28 (m, 6 H, H3′, H4′, H5′, H3′′, H4′′, H5′′),
7.20 (d, J = 16.3 Hz, 1 H, =CHB′), 6.95 (d, J = 16.3 Hz, 2 H, =CHB, HA′C=),
2.69 (s, 3 H, 2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C28H23NO2: 406.1802; found:
406.1802.
Anal. Calcd for C28H23NO2: C, 82.94; H, 5.72; N, 3.45; O, 7.89. Found: C,
82.99; H, 5.71; N, 3.44; O, 7.86.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

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A. Meléndez et al.
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Synthesis
(E)-1-(4-((E)-4-Bromostyryl)-2-methylquinolin-3-yl)-3-phenyl-
HRMS (ESI+): m/z [M + H]+ calcd for C27H20ClNO: 410.1306; found:
prop-2-en-1-one (9d)
410.1304.
Orange solid; yield: 0.36 g (80%); mp 131–132 °C; Rf = 0.49 (38% ethyl
acetate–heptane).
(E)-1-(2-Methyl-4-((E)-4-(trifluoromethyl)styryl)quinolin-3-yl)-3-
phenylprop-2-en-1-one (9g)
IR (ATR): 1648 (C=O), 1620 (C=N), 1590 (C=C vinyl), 1557 (C=C arom.),
1490 (C=C arom.), 977 cm–1 (=C–H trans).
Yellow solid; yield: 0.39 g (88%); mp 152–154 °C; Rf = 0.51 (38% ethyl
acetate–heptane).
1H NMR:  = 8.12–8.10 (m, 2 H, H5, H8), 7.78 (ddd, J = 8.4, 6.9, 1.4 Hz,
1 H, H7), 7.57 (ddd, J = 8.2, 6.9, 1.3 Hz, 1 H, H6), 7.48–7.44 (m, 4 H, H3′,
H5′, H2′′, H6′′), 7.39 (d, J = 16.4 Hz, 1 H, HAC=), 7.38–7.34 (m, 3 H, H3′′,
H4′′, H5′′), 7.33–7.30 (m, 2 H, H2′, H6′), 7.20 (d, J = 16.4 Hz, 1 H, =CHB′),
6.94 (d, J = 16.4 Hz, 1 H, HA′C=), 6.88 (d, J = 16.4 Hz, 1 H, =CHB), 2.68 (s,
3 H, 2-CH3).
13C NMR:  = 198.3 (C=O), 155.0 (C2), 147.7 (C8a), 146.9 (=CHB′), 140.9
(C4), 138.2 (=CHB), 135.2 (C1′), 134.0 (C1′′), 132.0 (C3′, C5′), 131.6
(C3), 131.2 (C4′′), 130.3 (C7), 129.3 (C8), 129.1 (C3′′, C5′′), 128.6 (C2′′,
C6′′), 128.4 (C2′, C6′), 128.2 (HA′C=), 126.7 (C6), 124.8 (C5), 124.7
(C4a), 122.9 (C4′), 122.5 (HAC=), 23.9 (2-CH3).
IR (ATR): 1644 (C=O), 1612 (C=N, C=C vinyl), 1568 (C=C arom.), 1492
(C=C arom.), 965 cm–1 (=C–H trans).
1H NMR:  = 8.13–8.10 (m, 2 H, H5, H8), 7.79 (ddd, J = 8.4, 6.9, 1.4 Hz,
1 H, H7), 7.61–7.54 (m, 5 H, H6, H2′, H3′, H5′, H6′), 7.49 (d, J = 16.5 Hz,
1 H, HAC=), 7.46–7.43 (m, 2 H, H2′′, H6′′), 7.42–7.33 (m, 3 H, H3′′, H4′′,
H5′′), 7.20 (d, J = 16.3 Hz, 1 H, =CHB′), 6.97 (d, J = 16.5 Hz, 1 H, =CHB),
6.95 (d, J = 16.3 Hz, 1 H, HA′C=), 2.69 (s, 3 H, 2-CH3).
13C NMR:  = 198.2 (C=O), 155.0 (C2), 147.7 (C8a), 147.1 (=CHB′), 140.6
(C4), 139.6 (C1′), 137.8 (=CHB), 134.0 (C1′′), 131.8 (C3), 131.3 (C4′′),
130.7 (C4′), 130.3 (C7), 129.4 (C8), 129.1 (C3′′, C5′′), 128.6 (C2′′, C6′′),
128.2 (HA′C=), 127.1 (C2′, C3′, C5′, C6′), 126.7 (C6), 125.8 (q, J = 3.6 Hz,
4′-CF3), 124.8 (C5), 124.6 (C4a), 124.4 (HAC=), 23.9 (2-CH3).
HRMS (ESI+): m/z [M + H]+ calcd for C27H20BrNO: 454.0801; found:
454.0801.
HRMS (ESI+): m/z [M + H]+ calcd for C28H20F3NO: 444.1570; found:
(E)-1-(4-((E)-4-Fluorostyryl)-2-methylquinolin-3-yl)-3-phenyl-
444.1566.
prop-2-en-1-one (9e)
Yellow solid; yield: 0.32 g (82%); mp 165–167 °C; Rf = 0.46 (38% ethyl
X-ray Crystallography
acetate–heptane).
Compound 4h: Chemical formula C26H21NO, Mw 363.44, orthorhom-
bic, space group Pbca, 100 K, cell dimensions a, b, c (Å) = 13.2730(16),
14.8012(16), 20.137(2); , ,  (°) = 90, 90, 90. V = 3956.1(8) Å3, Z = 8,
F(000) = 1536.0, Dx = 1.22 Mg·m–3, Mo K,  = 0.074 mm–1, crystal size
(mm) = 0.11 × 0.09 × 0.04. Data collection: Diffractometer Bruker D8
Venture (APEX 3), monochromator multilayer mirror, CCD rotation
images, thick slices ϕ and θ scans, Mo INCOATEC high-brilliance mi-
crofocus sealed tube ( = 0.71073 Å), multiscan absorption correction
(SADABS-2016/2), Tmin 0.604, Tmax 0.746. No. of measured, indepen-
IR (ATR): 1649 (C=O), 1620 (C=N), 1598 (C=C vinyl), 1561 (C=C arom.),
1506 (C=C arom.), 986 cm–1 (=C–H trans).
1H NMR:  = 8.14–8.10 (m, 2 H, H5, H8), 7.78 (ddd, J = 8.4, 6.7, 1.4 Hz,
1 H, H7), 7.57 (ddd, J = 8.1, 6.7, 1.3 Hz, 1 H, H6), 7.46–7.41 (m, 4 H, H2′,
H6′, H2′′, H6′′), 7.39–7.33 (m, 3 H, H3′′, H4′′, H5′′), 7.32 (d, J = 16.4 Hz,
1 H, HAC=), 7.20 (d, J = 16.2 Hz, 1 H, =CHB′), 7.03 (t, J = 8.6 Hz, 2 H, H3′,
H5′), 6.95 (d, J = 16.2 Hz, 1 H, HA′C=), 6.91 (d, J = 16.4 Hz, 1 H, =CHB),
2.68 (s, 3 H, 2-CH3).
13C NMR:  = 198.4 (C=O), 163.1 (d, J = 249.3 Hz, C4′), 155.0 (C2), 147.7
(C8a), 146.8 (=CHB′), 141.2 (C4), 138.3 (=CHB), 134.1 (C1′′), 132.5 (d, J =
3.3 Hz, C1′), 131.6 (C3), 131.2 (C4′′), 130.3 (C7), 129.3 (C8), 129.1 (C3′′,
C5′′), 128.7 (d, J = 8.1 Hz, C2′, C6′), 128.6 (C2′′, C6′′), 128.2 (HA′C=),
126.6 (C6), 124.9 (C5), 124.8 (C4a), 121.5 (HAC=), 115.8 (d, J = 21.9 Hz,
C3′, C5′), 23.9 (2-CH3).
dent and observed [I > 2(I)] reflections: 55850, 4538, 3611; Rint
=
0.135; θ values (°): θmax = 27.5, θmin = 2.3; range h = –17 → 17, k =
–19 → 19, l = –26 → 23; refinement on F2: R[F2 > 2(F2)] = 0.107,
wR(F2) = 0.189, S = 1.26. No. of reflections: 4538, no. of parameters:
255, no. of restraints: 0. Weighting scheme: w = 1/2(Fo2) + (0.0269P)2
+ 9.6841P, where P = (Fo2 + 2Fc2)/3. (Δ/) < 0.001; Δmax, Δmin (e·Å–3
0.41, –0.34. Computer programs: APEX3 v2018.1-0,25 SAINT
V8.38A,26 SHELXT 2014/5,27 SHELXL2018/328 and Olex2.29
)
=
HRMS (ESI+): m/z [M + H]+ calcd for C27H20FNO: 394.1602; found:
394.1601.
Compound 9b: Chemical formula C28H23NO, Mw 389.47, monoclinic,
space group P21/n, 100 K, cell dimensions a, b, c (Å) = 10.8168(6),
17.3361(10), 12.8892(6); , ,  (°) = 90, 114.132(2), 90. V = 2205.8(2)
(E)-1-(4-((E)-4-Chlorostyryl)-2-methylquinolin-3-yl)-3-phenyl-
prop-2-en-1-one (9f)
Å3, Z = 4, F(000) = 824.0, Dx = 1.17 Mg·m–3, Mo K,  = 0.070 mm–1
,
crystal size (mm) = 0.24 × 0.18 × 0.17. Data collection: Diffractometer
Bruker D8 Venture (APEX 3), monochromator multilayer mirror, CCD
rotation images, thick slices ϕ and θ scans, Mo INCOATEC high-bril-
liance microfocus sealed tube ( = 0.71073 Å), multiscan absorption
correction (SADABS-2016/2), Tmin 0.686, Tmax 0.746. No. of measured,
independent and observed [I > 2(I)] reflections: 27253, 5041, 4181,
Rint = 0.039; θ values (°): θmax = 27.5, θmin = 2.3; range h = –13 → 14, k =
–22 → 21, l = –16 → 16; refinement on F2: R[F2 > 2(F2)] = 0.044,
wR(F2) = 0.111, S = 1.016. No. of reflections: 5041, no. of parameters:
273, no. of restraints: 0. Weighting scheme: w = 1/2(Fo2) + (0.432P)2
Beige solid; yield: 0.35 g (85%); mp 154–155 °C; Rf = 0.49 (38% ethyl
acetate–heptane).
IR (ATR): 1646 (C=O), 1626 (C=N), 1596 (C=C vinyl), 1558 (C=C arom.),
1489 (C=C arom.), 971 cm–1 (=C–H trans).
1H NMR:  = 8.14–8.08 (m, 2 H, H5, H8), 7.78 (br t, J = 7.8 Hz, 1 H, H7),
7.58 (br t, J = 7.8 Hz, 1 H, H6), 7.44 (br d, J = 6.9 Hz, 2 H, H2′′, H6′′),
7.41–7.33 (m, 5 H, H2′, H6′, H3′′, H4′′, H5′′), 7.38 (d, J = 16.3 Hz, 1 H,
HAC=), 7.30 (br d, J = 8.4 Hz, 2 H, H3′, H5′), 7.19 (d, J = 16.3 Hz, 1 H,
=CHB′), 6.94 (d, J = 16.3 Hz, 1 H, HA′C=), 6.90 (d, J = 16.3 Hz, 1 H, =CHB),
2.68 (s, 3 H, 2-CH3).
13C NMR:  = 198.4 (C=O), 155.0 (C2), 147.7 (C8a), 146.9 (=CHB′), 141.0
(C4), 138.1 (=CHB), 134.7 (C1′), 134.6 (C4′), 134.0 (C1′′), 131.6 (C3),
131.2 (C4′′), 130.3 (C7), 129.3 (C8), 129.1 (C3′′, C5′′), 129.0 (C3′, C5′),
128.6 (C2′′, C6′′), 128.2 (C2′, C6′, HA′C=), 126.7 (C6), 124.9 (C5), 124.7
(C4a), 122.4 (HAC=), 23.9 (2-CH3).
+ 1.1376P, where P = (Fo2 + 2Fc2)/3. (Δ/) < 0.001; Δmax, Δmin (e·Å–3
0.26, –0.2. Computer programs: APEX3 v2018.1-0,25 SAINT
V8.38A,26 SHELXT 2014/5,27 SHELXL2018/328 and Olex2.29
)
=
CCDC 1971686 (4h) and CCDC 1971687 (9b) contain the supplemen-
tary crystallographic data for this paper. The data can be obtained
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–S

R
A. Meléndez et al.
Paper
Synthesis
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
(c) Gilbert, A. M.; Bursavich, M. G.; Lombardi, S.; Georgiadis, K.
E.; Reifenberg, E.; Flannery, C.; Morris, E. A. Bioorg. Med. Chem.
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Hazra, A.; Paira, P.; Banerjee, S.; Mondal, N. B.; Basu, A. Int. J.
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Funding Information
A.P. would like to thank Vicerrectoría de Investigación y Extensión of
the Industrial University of Santander (Grant No. 2497) for financial
(7) (a) Fournet, A.; Barrios, A. A.; Muñoz, V.; Hocquemiller, R.; Cavé,
A.; Bruneton, J. Antimicrob. Agents Chemother. 1993, 37, 859.
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R.; Figadère, B. Bioorg. Med. Chem. Lett. 2004, 14, 3635.
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Unwalla, R.; Quinet, E.; Savio, D.; Halpern, A.; Basso, M.; Keith, J.;
Clerin, V.; Chen, L.; Liu, Q. Y.; Feingold, I.; Huselton, C.; Azam, F.;
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support.
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Acknowledgment
A.P. thanks Dr. Elena Stashenko (Chromatography Laboratory, Indus-
trial University of Santander) for providing HRMS spectra. J.C. and
M.N. thank ‘Centro de Instrumentación Científico Técnica’ of Univer-
sidad de Jaén and the staff for data collection and support. Finally, the
authors thank the National Cancer Institute, USA, for performing in
vitro anticancer screening of the synthesized compounds.
Supporting Information
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Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1707985.
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