Convenient synthesis of 12-methyl[1]benzoxepino[3,4-b]quinolin-13(6H)-ones

Article abstract of DOI:10.1007/s10593-018-2322-y

[Figure not available: see fulltext.] In this work, a construction of 12-methyl[1]benzoxepino[3,4-b]quinolin-13(6H)-ones, structurally intriguing hybrid molecules consisting of fused 4-methylquinoline and 1-benzoxepin-5-one units, has been successfully achieved via a two-step procedure, involving the onepot synthesis of 2-(aryloxymethyl)-4-methylquinoline-3-carboxylic acids followed by their intramolecular Friedel–Crafts cyclization reaction. Our synthetic protocol described here could be attractive as it is simple, easy to handle and does not involve the use of expensive reagents or catalysts.

Full text of DOI:10.1007/s10593-018-2322-y

DOI 10.1007/s10593-018-2322-y
Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
Convenient synthesis of 12-methyl[1]benzoxepino-
3,4-b]quinolin-13(6H)-ones
[
1
1
1
1
Yu Wang , Mingqin Chang , Hong Zhang , Yang Li *
1
Institute of Superfine Chemicals, Bohai University,
Jinzhou 121000, China; е-mail: bhuzh@163.com
Published in Khimiya Geterotsiklicheskikh Soedinenii,
Submitted January 20, 2018
Accepted after revision April 17, 2018
2
018, 54(6), 650–657
In this work, a construction of 12-methyl[1]benzoxepino[3,4-b]quinolin-13(6H)-ones, structurally intriguing hybrid molecules consisting
of fused 4-methylquinoline and 1-benzoxepin-5-one units, has been successfully achieved via a two-step procedure, involving the one-
pot synthesis of 2-(aryloxymethyl)-4-methylquinoline-3-carboxylic acids followed by their intramolecular Friedel–Crafts cyclization
reaction. Our synthetic protocol described here could be attractive as it is simple, easy to handle and does not involve the use of expen-
sive reagents or catalysts.
Keywords: 1-benzoxepin-5-one, hybrid molecule, 4-methylquinoline, Friedel–Crafts cyclization, one-pot synthesis.
1
-Benzoxepine ring is one of the privileged medicinal
O
OH
O
O
scaffolds found in a small number of biologically active
Cl
1
2
Me
natural products, such as pterulone (1), ptaeroxylin (2),
Me
3
and bauhiniastatins (e.g., bauhiniastatin 1 (3)) (Fig. 1), and
O
Me
O
has wide application in the design and discovery of novel
1
2
4
,5
bioactive molecules. Many compounds containing the
1
-benzoxepine core are of great pharmaceutical interest due
Me
to their potent biological properties, such as antimyco-
O
6
7
Me
OMe
bacterial, anticancer, and antifungal activities, and could
O
8
be potentially applied as topoisomerase I, cyclo-
9
10
N
oxygenase, and PI3-kinase inhibitors. As a consequence,
considerable synthetic efforts have been devoted
surrounding the 1-benzoxepine template for further
modification and functionalization by both organic and
medicinal chemists with the aim of enhancing the potency
HO
O
3
4
Me
1
1–13
of this class of compounds.
Me O
On the other hand, the 4-methylquinoline (4-MeQ)
scaffold, too, is a pharmacologically significant structural
unit, and many 4-methylquinoline-based heterocyclic
compounds have been used as drug-like chemical probes in
pharmacological studies or for the development of new
N
R
N
O
5
6
1
4,15
medicinal products.
quinoline (4) was reported to show potent inhibitory effects
against β(1–3) glucan synthase with lower IC50 value
For example, 4-methyl-2-phenyl-
Figure 1. Structures of 1-benzoxepine-containing natural
products 1–3, bioactive 4-methylquinolines 4, 5, and the target
hybrid molecules 6.
0
009-3122/18/54(6)-0650©2018 Springer Science+Business Media, LLC
650

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
Scheme 1
Me
O
Me
O
Me
N
O
OH
OH
O
1
. K CO , MeCN, , 3 h
PPA
2
3
OEt
CH Cl
+
R
2. KOH, EtOH, H2O, , 2 h
N
145°C, 4–6 h
62–74%
R
N
3. 1 M HCl
80–91%
O
2
R
9
8a–l
7a–l
6a–l
(
0.23 μg/ml) than the well-known β(1–3) glucan synthase
oxymethylquinoline-3-carboxylic acid intermediates 7.
Subsequently, the intramolecular Friedel–Crafts cyclization
reaction between 2-aryloxymethyl moiety and 3-carboxylic
acid group would construct the desired 1-benzoxepine
skeleton through the generation of a new C–C bond.
1
6
inhibitor aculeacin A (IC50 50.5 μg/ml). In this regard,
Jain et al.17 have described the synthesis and anti-
tuberculosis activity of a series of ring-substituted
4
-methylquinolines, such as 2,8-dicyclopentyl-4-methyl-
quinoline (5), and established that these molecules could be
regarded as promising lead compounds for antituberculosis
drug development. Due to their biological activities,
Accordingly, with this assumption in mind, starting
27
compound 9 obtained by the described method was first
subjected to the Williamson reaction with 1.1 equiv of
interest in the synthesis of novel and interesting types of
4
phenols 8a–l in the presence of K
2
CO as the base and
3
-methylquinoline-based derivatives continues unabated.1
8,19
refluxing MeCN as the solvent. The reaction proceeded
very smoothly, and the substrates were completely
consumed within 3 h as monitored by TLC. It is worthy to
mention that the reaction proceeded also in DMF as the
solvent. We adopted herein MeCN as the solvent of choice
simply because of its low boiling point, thus bringing much
convenience to subsequent work-up procedure. Since the
resulting aryloxymethyl ethers from the Williamson
reaction did not interfere with further ethyl ester hydrolysis
reaction, purification at this stage was unnecessary. As
such, we simply evaporated MeCN to dryness, added
aqueous-ethanolic potassium hydroxide solution directly to
the residue, and continued to reflux for additional 2 h. After
an acidic work-up followed by purification of the resulting
crude products by recrystallization from ethanol, the
corresponding 2-aryloxymethylquinoline-3-carboxylic acids
7a–l were obtained in high yields as listed in Table 1.
On the basis of the literature data, and considering the
fact that combination of different pharmacophores in a
molecular framework is an important goal of synthetic
organic chemistry and plays a prominent role in modern
drug discovery,20 we felt that it would be a worthwhile
endeavor to construct 4-methylquinoline–1-benzoxepine
fused hybrids as possible drug candidates for current
pharmacological studies. Accordingly, with this context
and in continuation of our studies concerning the synthesis
of novel and potential biologically active quinoline-based
heterocycles,2
1–25
we herein would like to report the design
and synthesis of 4-methylquinoline-based 1-benzoxepine
derivatives, wherein the 1-benzoxepine ring is fused at its 3
and 4 positions to the b position of the 4-methylquinoline
ring to give a tetracyclic structure exemplified by com-
pounds 6 as shown in Figure 1.
Prior to the current investigation, there have been few
reports concerning the synthesis of ethyl 2-chloromethyl-
To the best of our knowledge, these newly synthesized
30
compounds except compound 7a have not been reported
earlier, and their structures have been confirmed based on
their spectroscopic and analytical data which are in good
agreement with the proposed structures (see Experimental).
4
-methylquinoline-3-carboxylate (9) through the Friedländer
26,27
annulation reaction.
Although the compound could be
considered as a useful building block to participate in a
wide array of chemical transformations for the design of
new and interesting quinoline derivatives, to our know-
ledge, the further modification of it has been very limited
1
As an example, the H NMR spectrum of compound 7a did
not show signals attributable to chloromethyl and ethoxy
protons of its precursor 9, but instead contained a one-
proton singlet at 13.61 ppm and a two-proton singlet at
5.36 ppm, readily recognizable as arising from carboxylic
and methylene protons, respectively. Moreover, the
presence of a total of 9 aromatic protons in the range of
6.95–8.20 ppm exactly matches its structure as well.
Further, the structure of compound 7a was confirmed by its
2
8
so far. In this regard, Degtyarenko et al. reported its
synthetic application with amines or mercaptanes for the
synthesis of 4-methylquinoline-based derivatives. Just
2
9
recently, Xu et al. reported the reaction of compound 9
with salicylonitriles or 2-mercaptobenzonitrile for the facile
synthesis of benzofuran- or benzothiophene-fused naphthy-
ridines. Due to structural diversity being an essential
component of the search for new leads, we became
interested in exploring the further synthetic application of
compound 9 as an ideal starting material for facile
synthesis of the desired 4-methylquinoline-based 1-benz-
oxepine derivatives. Our synthetic plan, as shown in
Scheme 1, was to make use of the active 2-chloromethyl
group of compound 9 to generate 2-aryloxymethyl moiety
through Williamson ether reaction with substituted phenols
13
C NMR spectrum, which revealed the presence of carboxyl
carbon at 168.7 ppm and methylene carbon at 70.5 ppm,
along with the signals due to the aromatic carbons. The other
synthesized compounds exhibited similar spectral characte-
ristics but for the substituents which were recognized by
characteristic signals with appropriate chemical shifts.
Having a series of the synthesized precursors 7a–l in
hand, our attention was turned to their intramolecular
Friedel–Crafts cyclization reaction for construction of the
tetracyclic title compounds. In our first attempts to carry
out the transformation of carboxylic acid 7a into benzoxepino-
8
followed by a further in situ ethyl ester hydrolysis
reaction at position 3 to afford the corresponding 2-aryl-
6
51

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
Table 1. Yields and physical properties of compounds 7a–l and 6a–l
Entry
Carboxylic acids
Mp, °C
Yield, %
Benzoxepinoquinolinones
Mp, °C
Yield, %
72
Me
O
2
10–212
1
30
87
217–218
(
217–219°C)
N
O
6a
Me
COOH
2
197–199
82
206–207
65
O
N
7b
Me
3
4
213–214
192–194
80
86
201–201
218–219
62
69
Me
N
COOH
O
5
6
184–186
195–197
91
83
227–228
228–229
74
63
7e
OMe
Me
N
O
O
F
6
f
7
8
9
207–208
210–211
198–199
190–192
86
88
84
82
213–215
238–239
240–242
249–251
66
71
63
69
Cl
Me
N
O
O
6h
Br
Me
N
O
1
1
1
0
1
2
O
6j
213–214
227–228
89
251–252
242–244
70
72
Me
N
O
87
O
6l
6
52

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
Scheme 2
MeO
Me
Me O
Me O
N
5'
6'
6'
'
COOH
2'
4'
5'
OMe
4
'
O
4
N
5'
6'
2'
O
O
N
2'
6
d'
7d
6d
OMe
quinolinone 6a using Eaton's reagent as the mild cycli-
3
1
zation reagent at 80°C, the reaction scarcely proceeded
and the desired product 6a was detected only in negligible
amount that did not warrant isolation. We also tried the
reaction using POCl as the cyclization reagent, which has
3
32
recently been used for this type of transformation. How-
ever, this purported approach was ineffective in our hands
and the reaction did not proceed satisfactorily, giving poor
yields of highly impure products. In addition, switching to
other cyclization reagents, such as sulfuric acid, hydrogen
fluoride, and trifluoroacetic anhydride, was also to no avail.
After these fruitless attempts, we were delight to find
1
Figure 2. The H NMR spectrum of compound 6d.
1
In the H NMR spectrum of compound 6d (Fig. 2),
2
1
that the use of polyphosphoric acid (PPA) was suitable to
promote the reaction, and the reaction temperature of 145°C
was found to be optimal to complete the transformation,
giving compound 6a in a good yield of 72%. Upon further
increasing the reaction temperature, the crude product was
always contaminated with a small amount of impurities,
which may be attributed to side reactions, such as poly-
merization. Due to the simplicity of the procedure requiring
no additional solvent, no further optimization in reaction
conditions was necessary and the above-mentioned condi-
tions were chosen for the following work. Thereafter, in a
similar fashion, we further extended the reaction to other
quinoline-3-carboxylic acids 7b–l. As expected, these
substrates were equally amenable to the reaction process
without any experimental difficulties, successfully furnish-
ing the corresponding targeted products 6b–l in satisfactory
yields. The results of this series of experiments are
compiled in Table 1.
particularly characteristic was the signal due to the C-2'
hydrogen appeared as a doublet at 6.66 ppm with a small
coupling constant J = 2.4, which is a typical value for meta-
proton coupling with C-6' hydrogen. Correspondingly, the
signal due to C-6' hydrogen appears as a doublet of
doublets at 6.83 ppm with the J values 8.8 and 2.4 Hz
which arose from coupling with both C-5' and C-2'
hydrogen atoms. If the cyclization reaction occurred at the
C-2' position leading to the corresponding product 6d', the
splitting pattern of meta-proton coupling doublet could not
1
appear in its H NMR spectrum.
Similarly, the cyclization reaction of acid 7l could also
occur theoretically at either a- or b-position of the naphtha-
lene ring, resulting in two possible structural isomers.
1
However, the analysis of H NMR spectrum revealed that
the cyclization reaction selectively took place at the
a-position of the naphthalene ring to give product 6l as the
sole product as shown in Scheme 3.
1
The newly synthesized compounds 6a–l have never been
reported, and their structures were all easily established
based on their spectral data and elemental analyses, which
were in good agreement with the proposed structures (see
Experimental). In particular, we would like to comment on
the intramolecular cyclization of compounds 7d and 7l
The H NMR spectrum of compound 6l (Fig. 3) exhi-
bited two doublet signals that can be assigned to H-b and H-c
at 7.22 and 7.95 ppm with a coupling constant J = 8.8,
(
entries 4 and 12, Table 1). In the case of compound 7d, the
intramolecular cyclization reaction in principle should give
rise to two possible structural isomers 6d and 6d' because
of the existence of two vacant ortho sites, C-2' and C-4', in
the 3-methoxyphenyl group of compound 6d. But in fact,
1
the H NMR spectrum of the product suggested that the
cyclization reaction selectively occurred with the C–C
bond forming at the C-4' position, thereby affording
structure 6d as the sole product as shown in Scheme 2.
1
Figure 3. The H NMR spectrum of compound 6l.
Scheme 3
6
53

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
which is a typical value for ortho-protons coupling in
naphthalene ring. Especially, the one-proton doublet at
markedly high δ value (8.95 ppm) could be easily ascribed
H Ar); 7.84 (1H, t, J = 7.6, H Ar); 8.05 (1H, d, J = 8.0,
H Ar); 8.20 (1H, d, J = 8.4, H Ar); 13.61 (1H, s, COOH).
13
H
C NMR spectrum, δ, ppm: 15.1; 70.5; 114.4; 120.8;
to H-d due to the intramolecular interaction between the
carbonyl oxygen atom and this proton resulting in the
downfield shift. Further, if the cyclization reaction
occurred at the C-b position giving compound 6l' as the
product, there should have been two one-proton singlet
124.5; 126.2; 127.2; 127.5; 129.0; 129.2; 130.1; 141.8;
145.4; 152.6; 157.8; 168.7. Found, %: C 73.92; H 5.00; N 4.62.
C
18
H
15NO . Calculated, %: C 73.71; H 5.15; N 4.78.
3
4-Methyl-2-[(o-tolyloxy)methyl]quinoline-3-carboxylic
–
1
acid (7b). White solid. IR spectrum, ν, cm : 3447
1
signals due to H-a and H-c in its H NMR spectrum.
(COOH), 3059, 2919, 1724 (C=O), 1610, 1572, 1508.
1
In conclusion, we have provided an easy access to
structurally new and biologically promising polycyclic
fused 4-methylquinoline-based 1-benzoxepine derivatives
through a simple and effective two-step procedure. In view
of the synergism of both the 1-benzoxepine ring and
H NMR spectrum, δ, ppm (J, Hz): 2.16 (3H, s, CH ); 2.72
3
(3H, s, CH
3
); 5.38 (2H, s, ArCH O); 6.83 (1H, t, J = 7.2,
2
H Ar); 7.05 (1H, d, J = 8.0, H Ar); 7.10–7.14 (2H, m,
H Ar); 7.73 (1H, t, J = 7.2, H Ar); 7.86 (1H, t, J = 7.2,
H Ar); 8.08 (1H, d, J = 8.4, H Ar); 8.22 (1H, d, J = 8.4,
H Ar); 13.55 (1H, s, COOH). 13C NMR spectrum, δ, ppm:
15.2; 15.7; 70.3; 110.7; 120.2; 124.6; 125.8; 126.3; 126.5;
127.3; 127.4; 128.8; 130.2; 130.3; 142.3; 145.2; 152.7;
155.9; 168.6. Found, %: C 74.41; H 5.68; N 4.27.
4
-methylquinoline unit in a molecular framework, these
newly synthesized compounds would likely possess
significant biological activities and might be potentially
applied for the development of biologically and pharma-
ceutically important drugs. Currently, the studies
concerning their application are underway.
C
19
H
17NO . Calculated, %: C 74.25; H 5.58; N 4.56.
3
2-[(2-Methoxyphenoxy)methyl]-4-methylquinoline-
–1
3
-carboxylic acid (7c). White solid. IR spectrum, ν, cm :
Experimental
3
430 (COOH), 3077, 2963, 1718 (C=O), 1616, 1569, 1506.
1
Infrared spectra were recorded on a Shimadzu FTIR-
H NMR spectrum, δ, ppm (J, Hz): 2.76 (3H, s, CH ); 3.77
3
8
400S spectrophotometer in KBr pellets in the range of 400–
(3H, s, OCH
3
); 5.36 (2H, s, ArCH O); 6.86 (1H, td, J = 7.6,
2
–
1
1
13
4
000 cm . H and C NMR spectra were recorded on a
J = 1.2, H Ar); 6.94 (1H, td, J = 7.6, J = 1.2, H Ar); 7.00
(1H, dd, J = 7.6, J = 1.2, H Ar); 7.10 (1H, dd, J = 7.6,
J = 1.2, H Ar); 7.74 (1H, t, J = 7.6, H Ar); 7.87 (1H, t,
J = 7.6, H Ar); 8.07 (1H, d, J = 8.4, H Ar); 8.24 (1H, d,
Brucker Avance NMR spectrometer (400 and 100 MHz,
respectively) in CDCl
3
(compounds 6a,b,e,g–l) or in
DMSO-d (compounds 6c,d,f, 7a–l). The reported chemical
6
13
shift (δ) values are given in parts per million downfield
from TMS as the internal standard. Elemental analyses
were performed for C, H, and N using an Elementar vario
EL III element analyzer. Melting points were determined
using a WRS-1B melting point apparatus. The progress of
reactions was monitored by thin-layer chromatography
J = 8.4, H Ar); 13.60 (1H, s, COOH). C NMR spectrum,
δ, ppm: 15.2; 55.3; 71.3; 112.2; 114.1; 120.3; 121.5; 124.5;
126.2; 127.3; 127.6; 129.0; 130.2; 142.0; 145.4; 147.5; 149.2;
152.5; 168.6. Found, %: C 70.93; H 5.07; N 4.09.
C
19
H
17NO . Calculated, %: C 70.58; H 5.30; N 4.33.
4
2-[(3-Methoxyphenoxy)methyl]-4-methylquinoline-
–
1
(
TLC) on silica gel GF254 using EtOAc – petroleum ether
3-carboxylic acid (7d). White solid. IR spectrum, ν, cm :
as eluent. The chemicals used in this work were obtained
from Fluka and were used without further purification.
Synthesis of 2-(aryloxymethyl)-4-methylquinoline-
3405 (COOH), 3058, 2871, 1716 (C=O), 1614, 1575, 1487.
1
H NMR spectrum, δ, ppm (J, Hz): 2.84 (3H, s, CH
3
); 3.84
(3H, s, OCH
3
); 5.48 (2H, s, ArCH
2
O); 6.66 (1H, dd,
3
-carboxylic acids 7a–l (General method). Phenol or sub-
J = 8.0, J = 1.6, H Ar); 6.71 (1H, d, J = 7.6, H Ar); 6.74
(1H, d, J = 1.6, H Ar); 7.31 (1H, t, J = 8.0, H Ar); 7.84
(1H, t, J = 7.6, H Ar); 7.97 (1H, t, J = 7.6, H Ar); 8.18 (1H,
d, J = 8.4, H Ar); 8.33 (1H, d, J = 8.4, H Ar); 13.72 (1H, s,
COOH). 13C NMR spectrum, δ, ppm: 15.1; 54.7; 70.6;
100.8; 106.4; 106.7; 124.5; 126.2; 127.2; 127.5; 129.0; 129.6;
130.2; 141.8; 145.4; 152.6; 159.1; 160.1; 168.7. Found, %:
stituted phenol 8a–l (1.1 mmol) and anhydrous K
2
CO
3
(
415 mg, 3 mmol) were added to a stirred solution of ethyl
2
-(chloromethyl)-4-methylquinoline-3-carboxylate 9 (264 mg,
1
mmol) in MeCN (15 ml). The resulting mixture was
heated at refluxing temperature for 3 h. The conversion was
monitored by TLC. After completion, the reaction mixture
was evaporated to dryness; a solution of KOH (1.12 g,
C 70.35; H 5.58; N 4.17. C19
C 70.58; H 5.30; N 4.33.
H
17NO . Calculated, %:
4
2
0 mmol) in 80% ethanol (25 ml) was added directly to the
residue and the reflux was continued for 2 h. After cooling,
the reaction mixture was acidified to pH 4–5 with 1 M HCl
to induce precipitation. After filtration and washing with
water, the crude precipitate was recrystallized from
ethanol. The yields and melting points of products 7a–l are
listed in Table 1.
2-[(4-Methoxyphenoxy)methyl]-4-methylquinoline-
–1
3-carboxylic acid (7e). White solid. IR spectrum, ν, cm :
3441 (COOH), 3058, 2923, 1727 (C=O), 1616, 1558, 1509.
1
H NMR spectrum, δ, ppm (J, Hz): 2.70 (3H, s, CH ); 3.67
3
(3H, s, OCH
3
); 5.30 (2H, s, ArCH O); 6.85 (2H, d, J = 8.8,
2
H Ar); 6.95 (2H, d, J = 8.8, H Ar); 7.71 (1H, t, J = 7.6,
H Ar); 7.84 (1H, t, J = 7.6, H Ar); 8.04 (1H, d, J = 8.0,
H Ar); 8.20 (1H, d, J = 8.4, H Ar); 13.58 (1H, s, COOH).
4
-Methyl-2-(phenoxymethyl)quinoline-3-carboxylic acid
–1
(
7a). White solid. IR spectrum, ν, cm : 3442 (COOH),
1
13
3
075, 2961, 1721 (C=O), 1600, 1569, 1490. H NMR
spectrum, δ, ppm (J, Hz): 2.71 (3H, s, CH ); 5.36 (2H, s,
ArCH O); 6.95 (1H, t, J = 7.2, H Ar); 7.02 (2H, d, J = 8.0,
H Ar); 7.29 (2H, t, J = 8.0, H Ar); 7.71 (1H, t, J = 7.6,
C NMR spectrum, δ, ppm: 15.0; 55.0; 71.2; 114.2; 115.5;
3
124.5; 126.2; 127.2; 127.5; 129.0; 130.1; 141.7; 145.4; 151.8;
152.9; 153.4; 168.7. Found, %: C 70.37; H 5.07; N 4.49.
C
2
19
H
17NO . Calculated, %: C 70.58; H 5.30; N 4.33.
4
6
54

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
2
-[(2-Fluorophenoxy)methyl]-4-methylquinoline-
δ, ppm: 15.2; 70.6; 114.7; 125.1; 126.4; 127.7; 128.6;
–
1
3
-carboxylic acid (7f). White solid. IR spectrum, ν, cm :
128.9; 129.5; 129.8; 131.9; 139.5; 147.3; 155.4; 156.6;
3
384 (COOH), 3066, 2918, 1718 (C=O), 1646, 1592, 1503.
168.5. Found, %: C 57.85; H 3.98; N 3.61. C18
H
14BrNO .
3
1
H NMR spectrum, δ, ppm (J, Hz): 2.72 (3H, s, CH ); 5.43
3
Calculated, %: C 58.08; H 3.79; N 3.76.
(
2H, s, ArCH
2
O); 6.92–6.97 (1H, m, H Ar); 7.09 (1H, t,
4-Methyl-2-[(naphthalen-1-yloxy)methyl]quinoline-
–1
J = 8.0, H Ar); 7.19–7.27 (2H, m, H Ar); 7.72 (1H, t,
J = 7.6, H Ar); 7.85 (1H, t, J = 7.6, H Ar); 8.05 (1H, d,
J = 8.0, H Ar); 8.21 (1H, d, J = 8.4, H Ar); 13.66 (1H, s,
3-carboxylic acid (7k). White solid. IR spectrum, ν, cm :
3431 (COOH), 3065, 2931, 1718 (C=O), 1611, 1570, 1508.
1
H NMR spectrum, δ, ppm (J, Hz): 2.70 (3H, s, CH ); 5.70
3
13
COOH). C NMR spectrum, δ, ppm: 15.2; 71.3; 114.8;
(2H, s, ArCH O); 7.58 (1H, t, J = 7.6, H Ar); 7.62–7.72
2
1
1
1
15.7; 115.9; 121.2 (2С); 124.4 (2С); 124.5; 124.6; 126.2;
27.4; 129.0; 130.2; 142.1; 145.5; 145.7; 145.8; 150.3;
52.0; 152.7; 168.6. Found, %: C 69.73; H 4.34; N 4.29.
(4H, m, H Ar); 7.87 (1H, t, J = 7.2, H Ar); 7.94 (2H, t,
J = 8.4, H Ar); 8.11 (1H, d, J = 8.0, H Ar); 8.23 (1H, d,
J = 8.4, H Ar); 8.33 (1H, d, J = 8.4, H Ar); 13.64 (1H, s,
COOH). C NMR spectrum, δ, ppm: 14.8; 76.2; 120.1;
121.2; 122.8; 125.1; 125.2; 125.3; 126.5; 127.1; 127.3;
127.5; 129.1; 129.3; 130.9; 133.0; 136.2; 145.0; 146.6;
151.8; 156.9; 168.6. Found, %: C 77.20; H 4.82; N 3.93.
13
C
18
H
14FNO
3
. Calculated, %: C 69.45; H 4.53; N 4.50.
2
-[(2-Chlorophenoxy)methyl]-4-methylquinoline-
–1
3
-carboxylic acid (7g). White solid. IR spectrum, ν, cm :
3
431 (COOH), 3019, 2964, 1726 (C=O), 1614, 1578, 1486.
1
H NMR spectrum, δ, ppm (J, Hz): 2.69 (3H, s, CH
3
); 5.41
C
22
H
17NO . Calculated, %: C 76.95; H 4.99; N 4.08.
3
(
2H, s, ArCH
2
O); 6.84 (1H, t, J = 7.8, H Ar); 7.06 (1H, d,
4-Methyl-2-[(naphthalen-2-yloxy)methyl]quinoline-
–1
J = 8.4, H Ar); 7.12–7.15 (2H, m, H Ar); 7.72 (1H, t,
J = 7.8, H Ar); 7.90 (1H, t, J = 8.4, H Ar); 8.08 (1H, d,
J = 8.4, H Ar); 8.16 (1H, d, J = 7.8, H Ar); 13.61 (1H, s,
3-carboxylic acid (7l). White solid. IR spectrum, ν, cm :
3438 (COOH), 3035, 2953, 1721 (C=O), 1603, 1569, 1509.
1
H NMR spectrum, δ, ppm (J, Hz): 2.70 (3H, s, CH ); 5.48
3
13
COOH). C NMR spectrum, δ, ppm: 15.2; 70.8; 111.6;
(2H, s, ArCH O); 7.20 (1H, d, J = 8.8, H Ar); 7.35 (1H, t,
2
1
1
20.5; 125.4; 126.0; 126.5; 126.9; 127.8; 128.7; 128.9;
30.4; 131.9; 139.3; 147.2; 155.4; 156.7; 168.6. Found, %:
J = 7.6, H Ar); 7.43 (1H, d, J = 7.6, H Ar); 7.47 (1H, s,
H Ar); 7.70 (1H, t, J = 7.6, H Ar); 7.77 (1H, d, J = 8.4,
H Ar); 7.82–7.85 (3H, m, H Ar); 8.06 (1H, d, J = 8.4,
H Ar); 8.19 (1H, d, J = 8.0, H Ar); 13.74 (1H, s, COOH).
C 65.75; H 4.50; N 4.05. C18
C 65.96; H 4.31; N 4.27.
H
14ClNO . Calculated, %:
3
13
2
-[(4-Chlorophenoxy)methyl]-4-methylquinoline-
C NMR spectrum, δ, ppm: 15.1; 70.5; 107.1; 118.4;
–1
3
-carboxylic acid (7h). White solid. IR spectrum, ν, cm :
123.5; 124.5; 126.1; 126.3; 126.4; 127.2; 128.2; 128.4;
129.0 (2С); 130.0; 130.3; 133.8; 141.5; 145.4; 152.3;
155.8; 168.9. Found, %: C 76.82; H 4.68; N 4.29.
3
431 (COOH), 3050, 2964, 1720 (C=O), 1602, 1573, 1486.
1
H NMR spectrum, δ, ppm (J, Hz): 2.70 (3H, s, CH ); 5.37
3
(
2H, s, ArCH
2
O); 7.03 (2H, d, J = 8.8, H Ar); 7.34 (2H, d,
C
22
H
17NO
3
. Calculated, %: C 76.95; H 4.99; N 4.08.
J = 8.8, H Ar); 7.71 (1H, t, J = 7.6, H Ar); 7.84 (1H, t,
J = 7.6, H Ar); 8.04 (1H, d, J = 8.4, H Ar); 8.20 (1H, d,
Synthesis of 12-methyl[1]benzoxepino[3,4-b]quinolin-
13(6H)-one derivatives 6a–j and 8-methylnaphthoxepino-
[3,4-b]quinolin-7(14H)-ones 6k,l (General method). The
respective carboxylic acid 7a–l (0.5 mmol) together with
13
J = 8.4, H Ar); 13.65 (1H, s, COOH). C NMR spectrum,
δ, ppm: 15.1; 70.9; 116.2; 124.5 (2C); 126.2; 127.3; 127.4;
1
28.9; 129.0; 130.2; 141.9; 145.4; 152.2; 156.7; 168.7.
PPA (83% P
2
O , 7.5 g) was added to a round-bottom flask
5
Found, %: C 66.32; H 4.52; N 4.05. C18
Calculated, %: C 65.96; H 4.31; N 4.27.
H
14ClNO
3
.
(25 ml) and stirred at 145 °C for 4–6 h. The conversion was
monitored by TLC. After the reaction was complete, the
mixture was poured slowly with stirring into cold water
2
-[(2-Bromophenoxy)methyl]-4-methylquinoline-3-car-
–1
boxylic acid (7i). Pale-yellow solid. IR spectrum, ν, cm :
followed by neutralization with saturated NaHCO solu-
3
3
372 (COOH), 3067, 2855, 1724 (C=O), 1627, 1584, 1508.
tion. The resulting precipitate was purified by flash
chromatography (petroleum ether – EtOAc, 1:1). The
yields and melting points are listed in Table 1.
1
H NMR spectrum, δ, ppm (J, Hz): 2.67 (3H, s, CH
3
); 5.39
(
2H, s, ArCH O); 6.84 (1H, t, J = 7.2, H Ar); 7.18 (1H, d,
2
J = 7.6, H Ar); 7.26 (1H, t, J = 7.2, H Ar); 7.52 (1H, d,
J = 7.6, H Ar); 7.67 (1H, t, J = 7.6, H Ar); 7.79 (1H, t,
J = 7.6, H Ar); 8.00 (1H, d, J = 8.0, H Ar); 8.16 (1H, d,
J = 7.6, H Ar); 13.57 (1H, s, COOH). C NMR spectrum,
δ, ppm: 15.2; 71.3; 110.8; 113.6; 122.1; 124.6; 126.3;
1
1
C
12-Methyl[1]benzoxepino[3,4-b]quinolin-13(6H)-one (6a).
–1
White needle crystals. IR spectrum, ν, cm : 3059, 1706
(C=O), 1562, 1491, 1400, 1259, 1211, 1084, 1022, 871.
1
3
1
H NMR spectrum, δ, ppm (J, Hz): 2.67 (3H, s, CH ); 5.35
3
(2H, s, H oxepine); 6.98 (1H, d, J = 8.0, H Ar); 7.04 (1H, t,
J = 7.6, H Ar); 7.41 (1H, td, J = 8.4, J = 1.2, H Ar); 7.54
(1H, t, J = 8.0, H Ar); 7.70 (1H, t, J = 7.6, H Ar); 7.94 (1H,
27.4; 127.5; 128.6; 129.1; 130.3; 132.8; 142.3; 145.5;
51.8; 154.2; 168.5. Found, %: C 57.95; H 3.54; N 3.94.
13
18
2
H
14BrNO
3
. Calculated, %: C 58.08; H 3.79; N 3.76.
dd, J = 8.0, J = 1.2, H Ar); 8.01–8.06 (2H, m, H Ar). C NMR
spectrum, δ, ppm: 15.2; 75.7; 120.2; 122.0; 125.0; 127.3;
127.7; 130.0; 130.7; 130.8; 131.0; 134.9; 135.4; 145.6; 147.4;
152.2; 160.0; 193.9. Found, %: C 78.82; H 4.56; N 4.98.
-[(4-Bromophenoxy)methyl]-4-methylquinoline-3-car-
–1
boxylic acid (7j). Pale-yellow solid. IR spectrum, ν, cm :
445 (COOH), 3055, 2974, 1717 (C=O), 1601, 1571, 1488.
3
1
H NMR spectrum, δ, ppm (J, Hz): 2.72 (3H, s, CH
3
); 5.39
C
18
H
13NO . Calculated, %: C 78.53; H 4.76; N 5.09.
2
(
2H, s, ArCH
2
O); 6.90 (2H, d, J = 8.4, H Ar); 7.08 (2H, d,
4,12-Dimethyl[1]benzoxepino[3,4-b]quinolin-13(6H)-
–1
J = 8.4, H Ar); 7.71 (1H, t, J = 7.8, H Ar); 7.90 (1H, t,
J = 8.4, H Ar); 8.07 (1H, d, J = 8.4, H Ar); 8.17 (1H, d,
one (6b). White needle crystals. IR spectrum, ν, cm :
3065, 2961, 2864, 1710 (C=O), 1592, 1510, 1447, 1395,
1
3
1
J = 7.8, H Ar); 13.43 (1H, s, COOH). C NMR spectrum,
1262, 1208, 1176, 1068, 865. H NMR spectrum, δ, ppm
6
55

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
(
J, Hz): 2.19 (3H, s, CH
3
); 2.66 (3H, s, CH
3
); 5.38 (2H, s,
(2С); 127.6; 127.8; 128.5; 128.7; 129.9; 131.7; 133.2; 133.3;
H oxepine); 6.94 (1H, t, J = 7.6, H Ar); 7.28 (1H, d,
J = 7.2, H Ar); 7.54 (1H, t, J = 8.0, H Ar); 7.70 (1H, t,
J = 7.6, H Ar); 7.79 (1H, d, J = 8.0, H Ar); 8.02–8.06 (2H,
146.1; 147.3; 151.4; 152.1; 153.8; 192.3. Found, %:
C 73.92; H 4.19; N 4.62. C18
C 73.71; H 4.12; N 4.78.
H
12FNO . Calculated, %:
2
13
m, H Ar). C NMR spectrum, δ, ppm: 15.5; 16.6; 75.6;
21.4; 124.9; 126.4; 127.2; 128.8; 130.0; 130.6; 130.9; 133.7;
4-Chloro-12-methyl[1]benzoxepino[3,4-b]quinolin-
13(6H)-one (6g). Pale-yellow needle crystals. IR spectrum,
1
1
–1
35.9; 136.4; 145.4; 147.4; 152.3; 158.2; 194.3. Found, %:
ν, cm : 3062, 2991, 2875, 1697, 1611, 1588, 1507, 1488,
1
C 78.65; H 5.16; N 5.16. C19
C 78.87; H 5.23; N 4.84.
H
15NO
2
. Calculated, %:
1414, 1377, 1297, 1164, 1042, 869. H NMR spectrum,
δ, ppm (J, Hz): 2.74 (3H, s, CH ); 5.47 (2H, s, H oxepine);
3
4
-Methoxy-12-methyl[1]benzoxepino[3,4-b]quinolin-
6.99 (1H, t, J = 7.6, H Ar); 7.53 (1H, d, J = 7.2, H Ar); 7.58
(1H, t, J = 7.2, H Ar); 7.73 (1H, t, J = 7.2, H Ar); 7.87 (1H,
–1
1
2
1
3(6H)-one (6c). White solid. IR spectrum, ν, cm : 3047,
13
966, 2818, 1699, 1613, 1592, 1517, 1457, 1410, 1387,
d, J = 7.6, H Ar); 8.04–8.08 (2H, m, H Ar). C NMR
spectrum, δ, ppm: 14.3; 75.2; 120.8; 123.7; 124.0; 126.7;
126.8; 126.9; 128.6; 129.1; 130.1; 132.2; 134.4; 144.8; 146.5;
150.5; 154.4; 191.9. Found, %: C 69.45; H 4.15; N 4.20.
1
298, 1235, 1147, 1081, 851. H NMR spectrum, δ, ppm
(
J, Hz): 2.70 (3H, s, CH
3
); 3.83 (3H, s, OCH ); 5.48 (2H, s,
3
H oxepine); 7.14 (1H, d, J = 8.0, H Ar); 7.30 (1H, d,
J = 7.6, H Ar); 7.51 (1H, t, J = 7.6, H Ar); 7.75 (1H, t,
J = 7.6, H Ar); 7.90 (1H, t, J = 7.6, H Ar); 8.13 (1H, d,
C
18
H
12ClNO . Calculated, %: C 69.80; H 3.90; N 4.52.
2
2-Chloro-12-methyl[1]benzoxepino[3,4-b]quinolin-
1
3
–1
J = 8.4, H Ar); 8.26 (1H, d, J = 8.4, H Ar). C NMR
spectrum, δ, ppm: 15.4; 56.5; 75.9; 117.2; 121.7; 121.9;
13(6H)-one (6h). Yellow solid. IR spectrum, ν, cm : 3050,
2978, 1707, 1617, 1595, 1489, 1402, 1368, 1256, 1126,
1
1
26.0; 127.2; 127.7; 128.2; 129.9; 131.7; 133.5; 145.3; 147.3;
1027, 981. H NMR spectrum, δ, ppm (J, Hz): 3.32 (3H, s,
1
49.9; 150.3; 152.5; 193.2. Found, %: C 74.40; H 5.25; N 4.22.
. Calculated, %: C 74.74; H 4.95; N 4.59.
-Methoxy-12-methyl[1]benzoxepino[3,4-b]quinolin-
3(6H)-one (6d). White needle crystals. IR spectrum,
CH ); 5.93 (2H, s, H oxepine); 7.35 (1H, d, J = 8.0, H Ar);
3
C
19
3
H
15NO
3
7.79 (1H, d, J = 7.6, H Ar); 8.27–8.33 (2H, m, H Ar); 8.49–
13
8.53 (2H, m, H Ar); 8.78 (1H, d, J = 8.0, H Ar). C NMR
spectrum, δ, ppm: 15.6; 75.8; 120.1; 121.9; 127.4; 128.3;
128.4; 128.5; 128.6; 129.2; 132.3; 136.8; 140.0; 148.3;
148.9; 151.6; 157.5; 192.8. Found, %: C 69.52; H 4.01;
1
–1
ν, cm : 3039, 2972, 2867, 1710, 1608, 1593, 1523, 1474,
1
1
411, 1359, 1226, 1168, 1035, 852. H NMR spectrum,
δ, ppm (J, Hz): 2.74 (3H, s, CH ); 3.86 (3H, s, OCH ); 5.46
2H, s, H oxepine); 6.66 (1H, d, J = 2.4, H Ar); 6.83 (1H,
3
3
N 4.23. C18
H
12ClNO . Calculated, %: C 69.80; H 3.90;
2
(
N 4.52.
dd, J = 8.4, J = 2.4, H Ar); 7.77 (1H, t, J = 8.4, H Ar); 7.92
4-Bromo-12-methyl[1]benzoxepino[3,4-b]quinolin-
–1
(
1H, t, J = 8.4, H Ar); 7.95 (1H, d, J = 8.4, H Ar); 8.13
1H, d, J = 8.0, H Ar); 8.30 (1H, d, J = 8.4, H Ar).
13(6H)-one (6i). Yellow solid. IR spectrum, ν, cm : 3048,
(
1710, 1613, 1597, 1559, 1478, 1398, 1306, 1279, 1177,
1
3
1
C NMR spectrum, δ, ppm: 15.6; 56.3; 76.1; 103.2; 110.7;
1047, 910. H NMR spectrum, δ, ppm (J, Hz): 2.67 (3H, s,
1
1
20.3; 126.0; 127.8; 128.2; 129.8; 131.6; 132.9; 133.4;
45.9; 147.1; 152.8; 161.9; 165.4; 191.2. Found, %:
CH ); 5.46 (2H, s, H oxepine); 6.93 (1H, t, J = 8.0, H Ar);
3
7.57 (1H, t, J = 7.6, H Ar); 7.70 (1H, d, J = 8.0, H Ar); 7.74
(1H, d, J = 7.6, H Ar); 7.91 (1H, d, J = 8.4, H Ar); 8.03–
8.08 (2H, m, H Ar). 13C NMR spectrum, δ, ppm: 15.6;
76.1; 114.0; 122.3; 122.6; 124.9; 125.0; 127.5; 127.9;
130.0; 130.6; 131.3; 138.6; 145.9; 147.4; 151.5; 156.2;
C 75.54; H 4.89; N 4.72. C19
H
15NO . Calculated, %:
3
C 74.74; H 4.95; N 4.59.
2
-Methoxy-12-methyl[1]benzoxepino[3,4-b]quinolin-
–1
1
3(6H)-one (6e). White needle crystals. IR spectrum, ν, cm :
3
1
046, 2978, 2890, 1707, 1613, 1588, 1527, 1496, 1406,
192.8. Found, %: C 60.75; H 3.19; N 3.74. C18
H
12BrNO .
2
1
363, 1247, 1190, 1024, 846. H NMR spectrum, δ, ppm
Calculated, %: C 61.04; H 3.41; N 3.95.
(
J, Hz): 2.82 (3H, s, CH
3
); 3.92 (3H, s, OCH
3
); 5.44 (2H, s,
2-Bromo-12-methyl[1]benzoxepino[3,4-b]quinolin-
–1
H oxepine); 7.05 (1H, d, J = 8.8, H Ar); 7.16 (1H, dd,
J = 8.8, J = 3.2, H Ar); 7.54 (1H, t, J = 3.2, H Ar); 7.69
13(6H)-one (6j). Yellow solid. IR spectrum, ν, cm : 3046,
2989, 2876, 1705, 1578, 1519, 1488, 1397, 1310, 1230,
1
(
1H, t, J = 8.0, H Ar); 7.84 (1H, t, J = 8.0, H Ar); 8.17 (1H,
1177, 1047, 939. H NMR spectrum, δ, ppm (J, Hz): 2.75
1
3
d, J = 8.4, H Ar); 8.19 (1H, d, J = 8.4, H Ar). C NMR
spectrum, δ, ppm: 15.5; 55.9; 76.0; 111.8; 121.4; 123.9;
(3H, s, CH ); 5.41 (2H, s, H oxepine); 6.95 (1H, d, J = 8.8,
3
H Ar); 7.55 (1H, dd, J = 8.4, J = 2.4, H Ar); 7.65 (1H, t,
J = 7.6, H Ar); 7.80 (1H, t, J = 8.0, H Ar); 8.11–8.14 (3H,
m, H Ar). 13C NMR spectrum, δ, ppm: 15.5; 75.8; 110.0;
114.4; 122.1; 125.1; 127.7; 127.8; 128.0; 129.9; 131.2;
133.1; 137.8; 146.4; 147.4; 151.7; 159.0; 192.3. Found, %:
1
1
25.0; 126.2; 127.5; 128.0; 129.9; 130.9; 133.2; 146.0;
47.3; 152.5; 154.3; 154.8; 193.4. Found, %: C 74.96;
H 5.07; N 4.51. C19
H 4.95; N 4.59.
H
15NO . Calculated, %: C 74.74;
3
4
-Fluoro-12-methyl[1]benzoxepino[3,4-b]quinolin-
C 61.21; H 3.27; N 4.18. C18
C 61.04; H 3.41; N 3.95.
H
12BrNO . Calculated, %:
2
–1
1
2
1
2
3(6H)-one (6f). White solid. IR spectrum, ν, cm : 3059,
967, 2885, 1707, 1622, 1594, 1534, 1498, 1401, 1378,
8-Methylnaphtho[2',1':6,7]oxepino[3,4-b]quinolin-
1
–1
256, 1185, 1036, 872. H NMR spectrum, δ, ppm (J, Hz):
7(14H)-one (6k). White solid. IR spectrum, ν, cm : 3043,
.71 (3H, s, CH
3
); 5.57 (2H, s, H oxepine); 7.17–7.22 (1H,
2986, 1691, 1604, 1580, 1527, 1480, 1397, 1308, 1238,
1
m, H Ar); 7.60 (1H, t, J = 8.4, H Ar); 7.74–7.78 (2H, m,
H Ar); 7.91 (1H, t, J = 7.6, H Ar); 8.12 (1H, d, J = 8.4,
1191, 1051, 906. H NMR spectrum, δ, ppm (J, Hz): 2.70
(3H, s, CH ); 5.59 (2H, s, H oxepine); 7.41–7.45 (2H, m,
3
1
3
H Ar); 8.27 (1H, d, J = 8.4, H Ar). C NMR spectrum,
δ, ppm: 15.6; 76.3; 121.3; 121.5; 121.9; 122.2; 122.3; 126.1
H Ar); 7.51 (1H, d, J = 7.6, H Ar); 7.55 (1H, t, J = 7.6,
H Ar); 7.71 (2H, t, J = 8.0, H Ar); 7.97 (1H, d, J = 8.8,
6
56

Chemistry of Heterocyclic Compounds 2018, 54(6), 650–657
9. Liu, J. H.; Steigel, A.; Reininger, E.; Bauer, R. J. Nat. Prod.
H Ar); 8.04 (1H, d, J = 8.4, H Ar); 8.08 (1H, d, J = 8.4,
1
3
2
000, 63, 403.
H Ar); 8.33 (1H, d, J = 8.4, H Ar). C NMR spectrum,
1
0. Staben, S. T.; Siu, M.; Goldsmith, R.; Olivero, A. G.; Do, S.;
Burdick, D. J.; Heffron, T. P.; Dotson, J.; Sutherlin, D. P.;
Zhu, B. Y.; Tsui, V.; Le, H.; Lee, L.; Lesnick, J.; Lewis, C.;
Murray, J. M.; Nonomiya, J.; Pang, J.; Prior, W. W.; Salphati, L.;
Rouge, L.; Sampath, D.; Sideris, S.; Wiesmann, C.; Wu, P.
Bioorg. Med. Chem. Lett. 2011, 21, 4054.
δ, ppm: 15.9; 76.0; 120.7; 121.0; 122.2; 122.6; 123.7;
1
1
24.9; 125.1; 125.8; 126.1; 127.0; 127.8; 128.1; 128.8;
30.0; 130.5; 131.3; 136.9; 152.0; 158.1; 193.6. Found, %:
C 80.90; H 4.71; N 4.01. C22
C 81.21; H 4.65; N 4.30.
H
15NO . Calculated, %:
2
1
4-Methylnaphtho[1',2':6,7]oxepino[3,4-b]quinolin-
11. Kamboj, R. C.; Jindal, P.; Kumar, D.; Khullar, S.; Mandal, S. K. J.
Photochem. Photobiol. A: Chem. 2014, 278, 31.
–
1
1
1
1
2
5(8H)-one (6l). White solid. IR spectrum, ν, cm : 3056,
688, 1593, 1507, 1486, 1434, 1397, 1322, 1274, 1218,
12. Rao Mangina, N. S. V. M.; Suresh, S.; Sridhar, B.;
Karunakar, G. V. Org. Biomol. Chem. 2016, 14, 3526.
1
191, 1123, 1051, 906. H NMR spectrum, δ, ppm (J, Hz):
1
3. Rao Mangina, N. S. V. M.; Kadiyala, V.; Guduru, R.;
.83 (3H, s, CH ); 5.63 (2H, s, H oxepine); 7.22 (1H, d,
3
Goutham, K.; Sridhar, B.; Karunakar, G. V. Org. Lett. 2017,
J = 8.8, H Ar); 7.53 (1H, t, J = 8.0, H Ar); 7.68 (1H, t,
J = 7.6, H Ar); 7.72 (1H, t, J = 8.0, H Ar); 7.83 (1H, t,
J = 8.0, H Ar); 7.86 (1H, d, J = 7.6, H Ar); 7.95 (1H, d,
J = 8.8, H Ar); 8.13 (1H, d, J = 8.0, H Ar); 8.21 (1H, d,
1
9, 282.
1
4. Johnson, O. H.; Hamilton, C. S. J. Am. Chem. Soc. 1941, 63,
2864.
1
5. LaMontagne, M. P.; Dagli, D.; Khan, M. S.; Blumbergs, P.
1
3
J = 8.4, H Ar); 8.95 (1H, d, J = 8.8, H Ar). C NMR
spectrum, δ, ppm: 15.0; 74.2; 118.8; 120.7; 124.3; 124.6;
J. Med. Chem. 1980, 23, 981.
16. Urbina, J. M.; Cortés, J. C. G.; Palma, A.; López, S. N.;
Zacchino, S. A.; Enriz, R. D.; Ribas, J. C.; Kouznetzov, V. V.
Bioorg. Med. Chem. 2000, 8, 691.
1
1
24.8; 127.5; 128.0; 128.6; 128.9; 129.5; 129.8; 130.6;
30.9; 135.4; 136.4; 142.9; 147.0; 150.5; 159.1; 197.6.
1
7. Jain, R.; Vaitilingam, B.; Nayyar, A.; Palde, P. B. Bioorg.
Med. Chem. Lett. 2003, 13, 1051.
Found, %: C 81.44; H 4.90; N 4.15. C22
H
15NO
2
. Calcu-
lated, %: C 81.21; H 4.65; N 4.30.
1
8. Ulven, T.; Little, P. B.; Receveur, J. M.; Frimurer, T. M.;
Rist, Ø.; Nørregaard, P. K.; Högberg, T. Bioorg. Med. Chem.
Lett. 2006, 16, 1070.
1
13
Supplementary information file containing the H and C
NMR spectra of compounds 7a–l and 6a–l is available at the
journal website at http://link.springer.com/journal/10593.
1
9. Li, A.; Huang, C.; Luo, C. W.; Li, L. J.; Yi, W. J.; Liu, T. W.;
Chao, Z. S. Catal. Commun. 2017, 98, 13.
2
2
0. Dolle, R. E.; Nelson, K. H. J. Comb. Chem. 1999, 1, 235.
1. Gao, W. T.; Lin, G. H.; Li, Y.; Tao, X. Y.; Liu, R.; Sun, L. J.
Beilstein J. Org. Chem. 2012, 8, 1849.
The project was financially supported by the National
Natural Science Foundation of China (Nos. 21476028 and
2
1402011) and the Natural Science Foundation of
2
2. Gao, W. T.; Xing, X. D.; Li, Y.; Lan, S. Tetrahedron 2014,
Liaoning Province (No. 201602006).
7
0, 2180.
2
3. Gao, W. T.; Fu, X. B.; Zhang, X. F.; Zhao, Y. N.; Wang, D. F.;
References
Li, Y. Tetrahedron Lett. 2016, 57, 4145.
1
2
3
4
5
6
. Huang, S. T.; Kuo, H. S.; Chen, C. T. Tetrahedron Lett. 2001,
24. Li, Y.; Li, K.; Gao, W. T. Chem. Heterocycl. Compd. 2016,
52, 200. [Khim. Geterotsikl. Soedin. 2016, 52, 200.]
25. Li, Y.; Wang, Y.; Zou, H. T. Mol. Diversity 2017, 21, 463.
26. Jida, M.; Deprez, B. New J. Chem. 2012, 36, 869.
27. Ryabukhin, S. V.; Volochnyuk, D. M.; Plaskon, A. S.;
Naumchik, V. S.; Tolmachev, A. A. Synthesis 2007, 1214.
28. Degtyarenko, A. S.; Tolmachev, A. A.; Volovenko, Y. M.;
Tverdokhlebov, A. V. Synthesis 2007, 3891.
4
2, 7473.
. Bruder, M.; Haseler, P. L.; Muscarella, M.; Lewis, W.;
Moody, C. J. J. Org. Chem. 2010, 75, 353.
. Pettit, G. R.; Numata, A.; Iwamoto, C.; Usami, Y.; Yamada, T.;
Ohishi, H.; Cragg, G. M. J. Nat. Prod. 2006, 69, 323.
. Boonphong, S.; Puangsombat, P.; Baramee, A.; Mahidol, C.;
Ruchirawat, S.; Kittakoop, P. J. Nat. Prod. 2007, 70, 795.
. Sarkhel, S.; Sharon, A.; Trivedi, V.; Maulik, P. R.; Singh, M. M.;
Venugopalan, P.; Ray, S. Bioorg. Med. Chem. 2003, 11, 5025.
. Saidachary, G.; Prasad, K. V.; Divya, D.; Singh, A.; Ramesh, U.;
Sridhar, B.; Raju, B. C. Eur. J. Med. Chem. 2014, 76, 460.
. Kahnberg, P.; Sterner, O. Tetrahedron 2001, 57, 7181.
. Lee, S. H.; Van, H. T. M.; Yang, S. H.; Lee, K. T.; Kwon, Y.;
Cho, W. J. Bioorg. Med. Chem. Lett. 2009, 19, 2444.
29. Xu, J.; Wang, D. L.; Liu, Z. P.; Zhang, K. X.; Ma, W.; Liu, B.
Heterocycles 2017, 94, 1055.
30. Nammalwar, B.; Murie, M.; Fortenberry, C.; Bunce, R. A.
Tetrahedron Lett. 2014, 55, 3181.
7
8
31. Eaton, P. E.; Carlson, G. R.; Lee, J. T. J. Org. Chem. 1973,
38, 4071.
32. Meesala, R.; Nagarajan, R. Tetrahedron Lett. 2010, 51, 422.
6
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