A New Method for the Synthesis of Substituted 8,9,10,11-Tetrahydroindolo[1,2-a]Quinoxalin-6(5H)-Ones

Article abstract of DOI:10.1007/s10593-017-2090-0

(Figure presented.). The reaction of 1-(cyclohexen-1-yl)pyrrolidines with 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones resulted in the formation of 8,9,10,11-tetrahydroindolo[1,2-a]quinoxalin-6(5H)-ones via a tandem sequence of Stork enamine alkylation and intramolecular annulation. Oxidative dehydrogenation gave indolo[1,2-a]quinoxalin-6(5H)-one.

Full text of DOI:10.1007/s10593-017-2090-0

DOI 10.1007/s10593-017-2090-0
Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
A new method for the synthesis of substituted
8,9,10,11-tetrahydroindolo[1,2-a]quinoxalin-6(5H)-ones
Vakhid A. Mamedov1,2*, Elena A. Khafizova1,2, Anastasiya I. Zamaletdinova1,2,
Julia K. Voronina1, Saniya F. Kadyrova1, Ekaterina V. Mironova1,
Dmitry B. Krivolapov1, Ildar Kh. Rizvanov1, Oleg G. Sinyashin1,2
1 A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences,
8 Akademika Arbuzova St., Kazan 420088, Republic of Tatarstan, Russia;
e-mail: mamedov@iopc.ru
2 Kazan National Research Technological University,
68 Karla Marksa St., Kazan 420015, Republic of Tatarstan, Russia
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2017, 53(5), 560–567
Submitted December 20, 2016
Accepted after revision February 14, 2017
The reaction of 1-(cyclohexen-1-yl)pyrrolidines with 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones resulted in the formation of 8,9,10,11-
tetrahydroindolo[1,2-a]quinoxalin-6(5H)-ones via a tandem sequence of Stork enamine alkylation and intramolecular annulation.
Oxidative dehydrogenation gave indolo[1,2-a]quinoxalin-6(5H)-one.
Keywords: 3-(α-chlorobenzyl)quinoxalin-2(1H)-ones, 1-(cyclohexen-1-yl)pyrrolidines, 8,9,10,11-tetrahydroindolo[1,2-a]quinoxalin-
6(5H)-ones, Stork reaction, tetrahydroindolo[a]annulation, X-ray structural analysis.
Quinoxalines are an important class of nitrogen
heterocycles1 that have shown a broad spectrum of
biological activity and are known as antitumor2a and anti-
HIV2b drugs, as well as antagonists of glucagon2c and
angiotensin receptors.2d They are also used as matrix for
the synthesis of GABA, benzodiazepines, receptor agonists
or antagonists,3 and other therapeutic targets.4 Valuable
biological activity has been discovered among condensed
quinoxaline derivatives, such as pyrrolo[1,2-a]quinoxa-
lines,5–7 triazolo[4,3-a]quinoxalines,7,8 and imidazo[1,5-a]-
quinoxalines.7–9 In a continuation of our studies5–7,9 aimed
at the development of synthetic methods and search for
new biologically active molecules, in the current work we
aimed at the synthesis of polycyclic condensed
5,6-dihydroindolo[1,2-а]quinoxaline derivatives, since the
indole moiety represents a significant structural feature of
various alkaloids10 that exhibit a wide range of biological
effects (for example, antiviral,11 antitumor,12 anti-
microbial,13 and anti-inflammatory activity).14
vatives.15–28 The most important among these are 1-(2-amino-
phenyl)indoles, which can react with various sources of
carbon atom, such as aldehydes,15 ketones,16,17 alkenes,18
and alkynes,19–21 giving the respective indolo[1,2-а]-
quinoxaline derivatives. Of secondary importance are
methods based on the reaction of indole derivatives
containing a carboxy,22 alkoxycarbonyl,23 amide,24 or
aldehyde25 group at position 2, while the closure of
pyrazine ring in the quinoxaline system can occur either in
a single step23c,24 or in two steps (starting with the creation
of N(5)–C(6) bond and followed by ring closure forming
the N(12)–C(6а) bond,22 or starting by the formation of
N(12)–C(12а) bond and then ring closure by forming the
new N(5)–C(6) bond).23a,b,25 The third type of methods are
based on intramolecular reductive closure of 1-(2-nitro-
phenyl)-1H-indole derivatives containing an alkoxy-
carbonyl26 or acetylene27 group. Finally, the fourth type of
methods rely on intramolecular ring closure reactions of
ketals formed by reactions of dimethylketals derived from
α-bromocyclohexanone with 2-benzoyl-3-methylindole
derivatives in the presence of ammonium acetate.28
The methods for the synthesis of indolo[1,2-а]-
quinoxalines are mainly based on the use of indole deri-
0009-3122/17/53(05)-0560©2017 Springer Science+Business Media New York
560

Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
Scheme 1
Besides these methods, there is only one additional route
for the synthesis of indolo[1,2-а]quinoxalines, which
requires the irradiation of 2-benzoylquinoxaline derivatives
with high pressure mercury lamp in the presence of
trifluoroacetic acid.29
It should be noted that the methods for the synthesis of
indolo[1,2-а]quinoxalines starting from substituted indoles
first require access to such indole derivatives, which can be
obtained through laborious multistep processes. The
method based on the use of quinoxaline derivatives has
been applied only to their benzoyl derivatives and can not
be extended to other quinoxalines.
However, performing the reaction of 3-(α-chlorobenzyl)-
quinoxalin-2(1H)-one (1а) with 1-(cyclohexen-1-yl)pyrro-
lidine (2a) under various relatively mild conditions (in
dioxane at room temperature for 12 h and at 70°С for 3 h,
in DMF at room temperature for 12 h and at 70°С for 3 h,
in refluxing acetonitrile for 3 h) resulted in a mixture of
During our studies aimed at the synthesis and use of
nitrogen-containing
heterocyclic
compounds,5–7,9,30,31
including quinoxalines and their condensed analogs, it was
shown that quinoxalinone derivatives containing substi-
tuents with electrophilic reactive sites at position 3 were
capable of annulation reactions. Depending on the nature of
substituent, such reactions produced pyrrolo[1,2-a]-,5
imidazo[1,5-a]-,9 or thiazolo[3,4-a]quinoxalines.30 Follow-
ing this logic, in the current work we set out to perform the
synthesis of tetrahydroindolo[1,2-а]quinoxalines I starting
from 3-[(aryl)(2-oxocyclohexyl)methyl]quinoxalin-2(1H)-
ones II (Scheme 1), assuming that the reaction conditions
are suitable for annulation of tetrahydroindole ring as a
result of intramolecular nucleophilic attack by the N-4
nitrogen atom at the carbon atom of the carbonyl group.
In order to achieve these goals, we employed the
available 3-(α-chlorobenzyl)quinoxalin-2(1H)-one deriva-
tives 1a–h,31 which reacted depending on the reaction
conditions either as α-substituted benzyl chlorides, or as
hetero analogs of α-chloro ketones – α-chloroimines. There
are literature precedents for successful use of enamine
alkylation with such electrophiles as benzyl halides, which
is considered a convenient method for the Stork synthesis
of alkyl ketones.32 Involving α-chloro ketones in this
reaction allowed to synthesize 1,4-diketones,33 while the
use of 3-α-(chlorobenzyl)quinoxalin-2(1H)-ones 1a–h in
the role of alkylating reagents and 1-(cyclohexen-1-yl)-
pyrrolidines 2a,b as alkylation substrates can lead to new
quinoxalin-2(1H)-one derivatives, 3-[(aryl)(2-oxocyclo-
hexyl)methyl]quinoxalin-2(1H)-ones 5 via the respective
immonium derivatives 4 (Scheme 2, Table 1).
1
products 4а and 3а in variable ratio, according to H NMR
data. Elevated temperatures, as a rule, led to the formation
of mostly the intramolecular condensation products 3 from
Scheme 2
Table 1. The reaction conditions, yields, and melting points of 8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-6(5H)-ones 3a–i
Quinoxalinone
Enamine
Product
R1
R2
R3
R4
Yield*, %
Mp, °С
Ph
4-O2NC6H4
4-ClC6H4
4-BrC6H4
Ph
H
H
H
H
H
H
H
H
H
71 (45)
82 (42)
64 (42)
59 (19)
80 (57)
65 (35)
52 (24)
67 (26)
54 (12)*3
325–326
318–322
331–333
312–315
>350
1a
1b
1c
1d
1e
1f
1g
1a
1h
2a
2a
2a
2a
2a
2a
2a
2b
2a
3а
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
Me
Me
Me
H
H
H
H
Ph
Ph
340–342
>350
H, CO2H*2
Ph
Hex
H
H
H
H
t-Bu
H
328–332
208–210
* Overall yield (the yield of analytically pure sample precipitated during the reaction is indicated in parentheses).
*2 Mixture of isomers.
*3 For the reaction performed in MeCN.
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Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
intermediate compound 4, even though the latter also
7.81, and ~7.35 ppm, respectively (the latter signal
overlapped with the signals of phenyl group protons).
Replacing the aryl groups in the starting quinoxalin-
2(1H)-ones with a hexyl group allowed to synthesize the
respective 8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-6(5H)-
one, albeit at a relatively low yield. The reaction of 3-(1-chloro-
heptyl)quinoxalin-2(1H)-one (1h) with 1-(cyclohexen-1-yl)-
pyrrolidine (2a) in dioxane and DMF under various
temperature regimes led to a mixture of products, while the
reaction in refluxing acetonitrile proceeded with the
formation of mostly the desired product 3i (Scheme 2,
Table 1).
The formation of 8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-ones 3a–i can be explained with
nucleophilic attack by the N-4 nitrogen atom on the
electrophilic carbon atom of the immonium group in the
Stork alkylation product 4, accompanied by the closure of
pyrroline ring, leading to the intermediate product A. This
intermediate product underwent aromatization under the
reaction conditions via intermediate B by elimination of
pyrrolidinium chloride (Scheme 3).
remained in the mixture. The evidence for the formation of
intermediate compound 4 was provided by 1H NMR
spectrum of the residue obtained after evaporation of the
reaction mixture. In addition to other signals, this spectrum
contained a sharp doublet (J = 11.0 Hz), a double double
doublet (J = 11.0, 6.0, and 3.2 Hz), and a double doublet
(J = 6.1 and 6.8 Hz) at 4.66, 3.65, and 3.24 ppm,
corresponding to the α-benzyl proton and protons at
positions 1 and 5 of the cyclohexylidene ring.
The formation of 8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-ones 3a–h was first of all indicated by
the presence of 1H NMR doublet signal of the Н-1
hydrogen atom (J = 8.3 Hz) at 8.01 ppm, which was
characteristic for similar systems,5–7,30,31c,d as well as the
signals of other protons belonging to aromatic rings, two
multiplet signals at 1.69–1.72 and 1.90–1.93 ppm, and two
double doublet signals (J ≈ 6 Hz) at 2.47 and 3.24 ppm for
the cyclohexene ring protons (the data are given for
compound 3а). Another characteristic signal is the
broadened singlet of amide proton at ~11 ppm.
A comparative analysis of 1Н NMR spectra of
compounds 3a,е–h allowed us to achieve complete
assignment of all signals. The phenyl group at position 7 of
the tetrahydroindoloquinoxalinone system in all of these
compounds, regardless of the presence or absence of
substituents in the cyclohexene ring of the tetrahydroindole
system or in the benzene ring of the quinoxalinone system,
gave a distinct resonance that was dependent on the
character of substituents, and the multiplicity was easily
interpreted (see Experimental).
Scheme 3
1
The comparison of Н NMR spectra for compound 3a
and 2-methyl-7-phenyl-8,9,10,11-tetrahydroindolo[1,2-a]-
quinoxalin-6(5H)-one 3f, the structure of which was
established by X-ray structural studies, as well as spectra of
compound 3f with the spectrum of the major isomer of
carboxylic acid 3g enabled complete assignment of all
proton signals of the benzene ring in the quinoxaline
system. For example, the downfield doublet signals of Н-1
proton at ~8.00 ppm in the case of compound 3f were
observed at 7.80 ppm as a singlet signal, due to the
presence of electron-donating methyl group at position 2,
which affected both the chemical shift and multiplicity of
the adjacent Н-1 proton signal. The signals of Н-3 and Н-4
protons in compound 3f were observed as doublets with
J = 8.2 and 8.1 Hz at 7.04 and 7.17 ppm. At the same time,
in the case of compound 3е, the Н-1 and Н-4 protons of
2,3-dimethylbenzene ring of quinoxaline system resonated
as singlet signals at 7.77 and 7.04 ppm.
The presence of cyclohexene moiety in the structure of
8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-6(5H)-ones 3
suggests possibilities for the synthesis of their aromatic
analogs, which was achieved in the case of 7-phenyl-
8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-6(5H)-one (3а).
Refluxing of the latter with chloranil in xylene for 50 h led
to 7-phenylindolo[1,2-а]quinoxalin-6(5H)-one (6) as an
oxidative dehydrogenation product (Scheme 4).
1
Scheme 4
The comparison of Н NMR spectra of compounds 3f
and 3g allowed to assign the proton signals of the benzene
ring in product 3g (both the major and minor isomers with
the carboxy group at positions 3 and 2, respectively). The
Н-1, Н-2, and Н-4 protons of the major product gave a
doublet signal (J = 8.9 Hz), double doublet (J = 8.9,
1.9 Hz), and another doublet (J = 1.9 Hz) at 8.08, 7.69, and
7.88 ppm, respectively. At the same time, the Н-1, Н-3, and
Н-4 protons of the minor product gave a broadened singlet
and two broadened doublet signals (J = 8.7 Hz) at 8.60,
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Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
The molecular and crystal structures of compounds
3a,d–f,h,i were established and analyzed by X-ray
crystallography. The molecular geometry of compounds
3a,d–f,h,i (Fig. 1, in the case of compound 3f) in the
studied crystals featured a condensed tetracyclic framework
including a 13-membered conjugated system of three rings
(the largest deviation from the median plane was 0.157(9) Å
in compound 3d). The cyclohexene ring assumed a half
chair conformation where the peripheral sp3-hybridized С(9)
and С(10) carbon atoms were located above and and below
the plane of conjugated ring system, respectively.
The crystal structure motifs were the same in all of the
studied samples: the molecules were linked in the crystal
lattice by a classical N–H···O hydrogen bond, forming
centrosymmetric dimers (shown in Fig. 2а for the case of
compound 3e), which were further ordered in stacks
Figure 1. The molecular structure of compound 3f with atoms
represented by thermal vibration ellipsoids of 50% probability.
through π···π
and СН···π interactions. The crystal
structure of compound 3a also generally corresponded to
this description of linked array of molecular stacks, but it
had some differences, being a crystal solvate with DMSO
in 1:1 ratio (Fig. 2b). The presence of N–H···O hydrogen
bonds in this compound resulted in the formation of a
centrosymmetric tetramer instead of centrosymmetric
dimer. The molecules of tetrahydroindolo[1,2-а]quinoxalin-
6(5H)-one 3а in the tetramer were not linked directly, but
rather through DMSO molecules.
Another difference was observed for compounds 3d and
3h (Fig. 3), which crystallized with two independent
molecules in the unit cell. At the same time, the geometry
of molecules A and B in both compounds was practically
identical, except for a very minor deviation of the
bromophenyl substituent in the molecule of compound 3d
and a rotation of tert-butyl and phenyl substituents in the
molecules A and B of compound 3h.
A detailed analysis of short intermolecular contacts
provided an explanation for the crystallization of these
compounds with two independent molecules. Thus, in
compound 3d containing a bromine atom, a weak non-
covalent Br···π interaction was observed (the distance from
the Br atom to the centroid of the ring was 4.156(9) Å, to
the ring plane – 3.640 Å, while the С–Br–centroid angle
was 105.79°), which involved the bromine atom of
molecule В, while the surroundings of the bromine atom in
molecule А prevented any bonding, even the formation of
very weak interactions. Thus, the crystallization of this
compound with two independent molecules in the unit cell
was associated with the differences in the environment
around the bromine atoms.
The different geometry of molecules А and В in the
crystals of compound 3h can be also explained by the
presence of weak noncovalent interactions, which were
different for the molecules А and В. For example, the
different orientation of the tert-butyl group can be
explained by the presence of a short СН···π contact
between the molecules А and В, involving the Н(92F) atom
of tert-butyl group in the molecule А and the five-membered
heterocycle of molecule В (the Н(92F)···centroid distance was
equal to 3.009 Å, С(92А)···centroid – 3.668(7) Å), Н(92F)···ring
plane – 2.89 Å, the С(92А)–Н(92F)···centroid angle was
126.96°, where centroid represents the centroid of ring
moiety). The different orientation of the phenyl substituents
was analogously caused by the presence of СН···π
interaction between these substituents in the molecules А
and В, involving the aromatic ring of molecule А and the
Figure 2. Hydrogen-bonded associates in the crystals of compounds (a) 3е, (b) 3a.
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Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
Figure 3. Geometry differences in two independent molecules in the crystals of compounds (а) 3d and (b) 3h.
СН group of molecule В (the Н(3А)···centroid distance
was 2.818 Å, С(3А)···centroid – 3.400(8) Å), Н(92F)···ring
plane – 2.74 Å, the С(92А)–Н(92F)···centroid angle was
121.74°). The parameters of hydrogen bonds, stacking, and
С–Н···π-interactions in the crystals of the studied
compounds are presented in Tables S2–S4 of the
Supplementary information file.
positively charged ions. The data were processed with the
FlexAnalysis 3.0 software (Bruker Daltonik GmbH, Bremen,
Germany). The matrix was 2,5-dihydroxybenzoic acid or
p-nitroaniline. Mass spectra with accurate mass values
were obtained by using a mixture consisting of the sample
in DMF (5 mg/ml) and the reference compound PEG-400
(1 mg/ml) in МеCN in the ratio of 1:5 with sequential
addition and evaporation of 10 mg/ml matrix solution in
MeCN (0.5 μl) and the sample mixture (0.5 μl). In a range
of cases, CsCl was added for increasing the yield of
positively charged cationized molecules. The indicated
composition provided that the absolute error of mass
determination did not exceed 0.0030 atomic mass units.
Melting points were determined on a Boetius hot stage
apparatus. All solvents were purified according to standard
procedures prior to use.
Thus, we have developed a simple one-pot method for
the synthesis of tetrahydroindolo[1,2-a]quinoxalin-6(5H)-
ones and found suitable conditions for the aromatization of
these compounds. The method is based on a two-stage
process comprising
a Stork alkylation reaction of
1-(cyclohexen-1-yl)pyrrolidines with 3-α-(chlorobenzyl)-
quinoxalin-2(1H)-ones, followed by annulation of tetra-
hydroindole ring in the intermediate products, 1-{2-[aryl-
(3-oxo-3,4-dihydroquinoxalin-2-yl)methyl]cyclohexylideno}-
pyrrolidinium chlorides, accompanied by elimination of
pyrrolidinium chloride. In the case of one of the
tetrahydroindolo[1,2-a]quinoxalin-6(5H)-one derivatives,
the possibility for synthesis of 7-arylindolo[1,2-а]quinoxalin-
6(5H)-ones was demonstrated. The analysis of molecular and
crystal structures of the studied compounds showed that the
substituents had no substantial effect on the molecular
conformation and crystal packing. The major factors
affecting the structure were the presence of hydrogen
bonding centers and a large planar ring system.
Preparation of compounds 3a–i (General method).
Equimolar amounts of the appropriate quinoxalin-2(1Н)-
one 1a–h and 1-(1-pyrrolidinо)cyclohexene were refluxed
with dioxane (5–10 ml) in a flask with a reflux condenser
for 6–10 h, until the reaction was complete (control by
TLC method, eluent СH2Cl2–AcOEt, 1:2). The precipitate
that formed during the reaction and additionally upon
maintaining the reaction mixture at room temperature was
filtered off, providing analytically pure samples of
compounds 3a–i. The filtrate was evaporated, the residue
was washed with water (2×5–10 ml), extracted with
chloroform (3×10 ml), dried, evaporated, and recrystallized
from acetic acid, giving an additional crop of analytically
pure compound 3 (Table 1). The synthesis of compound 3i
was performed by using acetonitrile as solvent instead of
dioxane.
7-Phenyl-8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-
6(5H)-one (3а) was obtained from 3-(α-chlorobenzyl)quin-
oxalin-2(1Н)-one (1a) (1.00 g, 3.69 mmol) and 1-(1-pyrro-
lidinо)cyclohexene (2a) (0.55 g, 3.69 mmol). Yield 0.83 g
(71%), white crystals, mp 325–326°С (AcOH). IR spect-
rum, ν, cm–1: 3439, 3108, 3028, 2931, 2853, 1647, 1611,
1514, 1483, 1439, 1394, 1328, 1215, 1120, 1072, 874, 803,
739, 726, 696, 666, 631, 569. 1H NMR spectrum
(400 MHz), δ, ppm (J, Hz): 1.69–1.72 (2H, m) and 1.90–
1.93 (2H, m, 9,10-СН2); 2.47 (2H, dd, J = 6.2, J = 6.0) and
3.24 (2H, dd, J = 6.2, J = 6.0, 8,11-СН2); 7.14 (1H, ddd,
Experimental
IR spectra in the range of 4000–400 cm–1 were recorded
on a Bruker Tensor 27 FT-IR spectrometer with optical reso-
lution of 4 cm–1 and accumulation of 64 scans. The samples
for recording of IR spectra were prepared as KBr pellets.
1H NMR spectra were acquired on a Bruker DRX-400
(400 MHz), DRX-500 (500 MHz), or DRX-600 (600 MHz)
spectrometers, while 13С NMR spectra were acquired on a
Bruker DRX-600 spectrometer (150 MHz) in DMSO-d6,
using the residual solvent signals as internal standard (2.5 ppm
1
for Н nuclei, 39.5 ppm for 13С nuclei). MALDI mass
spectra were recorded on a Bruker Daltonics UltraFlex III
TOF/TOF mass spectrometer. The high-resolution mass
spectra were obtained in reflectron mode (the resolution
was 10000) by using a metallic target and recording the
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Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
J = 7.9, J = 7.7, J = 1.6, Н-2); 7.23 (1H, ddd, J = 7.7,
3-(α-chlorobenzyl)-6,7-dimethylquinoxalin-2(1Н)-one (1e)
(1.00 g, 3.34 mmol) and 1-(1-pyrrolidinо)cyclohexene (2а)
(0.50 g, 3.34 mmol). Yield 0.92 g (80%), light-cream
colored crystals, mp >350°С (AcOH). IR spectrum, ν, cm–1:
3440, 3166, 3045, 2955, 2934, 2843, 1650, 1605, 1517,
1479, 1446, 1410, 1384, 1370, 1332, 1277, 1213, 1022,
880, 807, 768, 638, 590, 503. 1H NMR spectrum (400 MHz),
δ, ppm: 1.69–1.71 (2H, m) and 1.91–1.93 (2H, m,
9,10-СН2); 2.22 (3H, s, CH3); 2.29 (3H, s, CH3); 2.45–2.47
(2H, m) and 3.24–3.26 (2H, m, 8,11-СН2); 7.04 (1H, s,
Н-4); 7.26–7.36 (5H, m, Н Ph); 7.77 (1H, s, H-1); 10.79
(1H, s, NH). Found, m/z: 475.0791 [M+Cs]+. C23H22CsN2O.
Calculated, m/z: 475.0781.
J = 7.4, J = 1.0, Н-3); 7.28–7.30 (2H, m, Н-4, Н-4 Ph);
7.35 (2H, dd, J = 7.7, J = 7.3, Н-3,5 Ph); 7.39 (2H, dd,
J = 8.5, J = 1.9, Н-2,6 Ph); 8.01 (1H, br. d, J = 8.3, Н-1);
10.95 (1H, s, NH). Found, m/z: 447.0431 [M+Cs]+.
C21H18CsN2O. Calculated, m/z: 447.0468.
7-(4-Nitrophenyl)-8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-one (3b) was obtained from 3-(α-chloro-
4-nitrobenzyl)quinoxalin-2(1Н)-one (1b) (1.00 g, 3.16 mmol)
and 1-(1-pyrrolidinоcyclohexene (2a) (0.47 g, 3.16 mmol).
Yield 0.93 g (82%), golden brown crystals, mp 318–322°С
(AcOH). IR spectrum, ν, cm-1: 3434, 3176, 2935, 2854,
1654, 1615, 1597, 1515, 1481, 1438, 1392, 1344, 1328,
1205, 1107, 855, 745, 698, 576. 1H NMR spectrum
(600 MHz), δ, ppm (J, Hz): 1.70–1.71 (2H, m) and 1.89–1.90
(2H, m, 9,10-СН2); 2.48 (2Н, dd, J = 5.5, J = 7.1) and 3.20
(2H, dd, J = 5.6, J = 6.2, 8,11-СН2); 7.14 (1H, dd, J = 7.1,
J = 7.4, H-2); 7.25 (1H, dd, J = 7.4, J = 7.4, H-3); 7.31
(1H, d, J = 8.0, H-4); 7.66 (2H, d, J = 8.8, H-3',5' Ar); 7.99
(1H, d, J = 8.4, H-1); 8.18 (2H, d, J = 8.8, H-2',6' Ar);
11.14 (1H, s, NH). 13C NMR spectrum (150 Hz, DMSO-d6),
δ, ppm: 21.8; 22.3; 23.0; 26.3; 116.2; 116.4; 118.1; 122.0;
122.1; 122.4; 123.8; 124.1; 125.0; 128.9; 130.3; 131.8;
141.5; 145.6; 154.6. Found, m/z: 360.1386 [M+H]+.
C21H18N3O3. Calculated, m/z: 360.1343.
7-(4-Chlorophenyl)-8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-one (3с) was obtained from 3-(α,4-di-
chlorobenzyl)quinoxalin-2(1Н)-one (1с) (1.00 g, 3.27 mmol)
and 1-(1-pyrrolidinо)cyclohexene (2а) (0.50 g, 3.27 mmol).
Yield 0.73 g (64%), beige crystals, mp 331–333°С
(AcOH). IR spectrum, ν, cm–1: 3170, 3107, 3026, 2976,
2943, 2855, 1645, 1614, 1515, 1478, 1439, 1391, 1327,
1268, 1216, 1146, 1091, 1016, 998, 867, 839, 792, 734,
711, 666, 576, 539. 1H NMR spectrum (400 MHz), δ, ppm
(J, Hz): 1.70–1.72 (2H, m) and 1.89–1.91 (2H, m, 9,10-СН2);
2.46 (2H, dd, J = 5.8, J = 5.9) and 3.23 (2H, t, J = 5.8,
J = 5.4, 8,11-СН2); 7.14 (1H, dd, J = 8.1, J = 7.2, Н-2);
7.24 (1H, dd, J = 7.3, J = 7.8, Н-3); 7.29 (1H, dd, J = 8.2,
J = 1.6, Н-4); 7.38–7.41 (4H, m, H Ar); 8.00 (1H, d, J = 8.4,
H-1); 11.00 (1H, s, NH). Found, m/z: 481.0071 [M+Cs]+.
C21H17ClCsN2O. Calculated, m/z: 481.0078.
2-Methyl-7-phenyl-8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-one (3f) was obtained from 3-(α-chloro-
benzyl)-6-methylquinoxalin-2(1Н)-one (1f) (1.00 g,
3.51 mmol) and 1-(1-pyrrolidinо)cyclohexene (2a) (0.53 g,
3.51 mmol). Yield 0.75 g (65%), light-brown crystals,
mp 340–342°С (AcOH). IR spectrum, ν, cm-1: 3435, 3160,
3025, 2939, 2848, 1648, 1625, 1609, 1518, 1483, 1444,
1432, 1392, 1371, 1330, 1214, 1026, 874, 804, 749, 727,
1
696, 635, 569. H NMR spectrum (400 MHz), δ, ppm
(J, Hz): 1.70–1.71 (2H, m) and 1.90–1.91 (2H, m, 9,10-СН2);
2.37 (3H, s, CH3); 2.46 (2H, dd, J = 5.7, J = 5.9) and 3.25
(2H, dd, J = 5.9, J = 6.1, 8,11-СН2); 7.04 (1H, d, J = 8.2, Н-3);
7.17 (1H, d, J = 8.1, Н-4); 7.27 (1H, dd, J = 6.8, J = 6.8,
Н-4 Ph); 7.32–7.38 (4H, m, Н-2,3,5,6 Ph); 7.80 (1H, s,
Н-1); 10.84 (1H, s, NH). 13C NMR spectrum (150 MHz),
δ, ppm: 20.2; 24.7; 28.0; 32.2; 42.0; 45.8; 54.1; 114.8;
126.7; 127.8; 128.3; 128.8; 129.1; 130.4; 131.1; 132.2;
138.6; 153.9; 162.5; 211.1. Found, m/z: 461.0594 [M+Cs]+.
C22H20CsN2O. Calculated, m/z: 461.0625.
6-Oxo-7-phenyl-5,6,8,9,10,11-hexahydroindolo[1,2-а]-
quinoxaline-2(3)-carboxylic acid (3g) was obtained from
3-(α-chlorobenzyl)-2-oxo-1,2-dihydroquinoxaline-6(7)-carb-
oxylic acid (mixture of isomers) (1g) (1.00 g, 3.17 mmol)
and 1-(1-pyrrolidinо)cyclohexene (2а) (0.48 g, 3.17 mmol).
Yield 0.59 g (52%, mixture of isomers), milky crystals,
mp >350°С (AcOH). IR spectrum, ν, cm–1: 3222, 3055,
2935, 2853, 1695, 1689, 1655, 1621, 1519, 1482, 1385, 1330,
1296, 1234, 1215, 911, 806, 766, 698, 678, 589, 516. 1H NMR
spectrum (400 MHz), δ, ppm (J, Hz): 1.71–1.73 (2H, m) and
1.92–1.94 (2H, m, 9,10-СН2); 2.46–2.48 (2H, m) and 3.25–
3.27 (2H, m, 8,11-СН2); 7.29 (1H, dd, J = 6.8, J = 6.7, Н-4
Ph); 7.34–7.41 (5H, m, Н-2,3,5,6 Ph, Н-4*); 7.69 (1H, dd,
J = 8.8, J = 1.9, Н-2); 7.81* (1Н, dd, J = 8.8, J = 1.7,
Н-3*); 7.88 (1H, d, J = 1.9, Н-4); 8.08 (1H, d, J = 8.9,
Н-1); 8.60* (1Н, br. s, Н-1*); 11.12 (1H, s, NH). Found, m/z:
359.1353 [M+H]+. C22H19N2O3. Calculated, m/z: 359.1390.
9-(tert-Butyl)-7-phenyl-8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-one (3h) was obtained from 3-(α-chloro-
benzyl)quinoxalin-2(1Н)-one (1a) (1.00 g, 3.69 mmol)
and 1-(4-tert-butylcyclohexenyl)piperidine (2b) (0.76 g,
3.69 mmol). Yield 0.92 g (67%), white crystals, mp 328–
332°С (AcOH). IR spectrum, ν, cm–1: 3422, 3177, 3034,
2955, 2865, 1656, 1611, 1505, 1483, 1440, 1387, 1364,
1327, 1246, 1215, 1075, 926, 870, 820, 744, 729, 698, 666,
7-(4-Bromophenyl)-8,9,10,11-tetrahydroindolo[1,2-а]-
quinoxalin-6(5H)-one (3d) was obtained from 3-(4-bromo-
α-chlorobenzyl)quinoxalin-2(1Н)-one (1d) (1.00 g, 2.53 mmol)
and 1-(1-pyrrolidinо)cyclohexene (2a) (0.38 g, 2.53 mmol).
Yield 0.66 g (59%), light-beige crystals, mp 312–315°С
(DMSO). IR spectrum, ν, cm–1: 3437, 3028, 2924, 2857,
1651, 1615, 1511, 1479, 1440, 1397, 1329, 1071, 1013, 997,
1
836, 750, 667, 574. H NMR spectrum (400 MHz), δ, ppm
(J, Hz): 1.72–1.73 (2H, m) and 1.91–1.92 (2H, m,
9,10-СН2); 2.47 (2H, dd, J = 5.8, J = 6.1) and 3.25 (2H, dd,
J = 6.1, J = 5.1, 8,11-СН2); 7.16 (2H, ddd, J = 7.9, J = 7.7,
J = 1.7, Н-2); 7.25 (2Н, ddd, J = 7.9, J = 7.2, J = 1.0, Н-3);
7.30 (2H, dd, J = 8.0, J = 1.7, Н-4); 7.35 (2H, d, J = 8.5,
Н-3',5' Ar); 7.54 (2H, d, J = 8.5, H-2',6' Ar); 8.02 (1H, d,
J = 8.4, H-1); 11.02 (1H, s, NH). Found, m/z: 526.9538
[M+Cs]+. C21H17BrCsN2O. Calculated, m/z: 526.9553.
2,3-Dimethyl-7-phenyl-8,9,10,11-tetrahydroindolo-
[1,2-а]quinoxalin-6(5H)-one (3e) was obtained from
* Signal of the minor isomer.
565

Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
578, 554, 541. 1H NMR spectrum (400 MHz), δ, ppm (J, Hz):
This work received financial support from the Russian
Science Foundation (project No. 14-23-00073-p).
0.90 (9Н, s, (CH3)3); 1.39–1.42 (2H, m) and 2.17–2.20 (1Н,
m, 9,10-СН2); 2.34–2.38 (2H, m) and 3.35–3.39 (2Н, m,
8,11-СН2); 7.14 (1H, ddd, J = 7.8, J = 7.8, J = 1.7, Н-2); 7.23
(1H, dd, J = 7.2, J = 7.1, Н-3); 7.27–7.31 (2H, m, Н-4, Н-4
Ph); 7.37 (2H, dd, J = 7.8, J = 7.2, Н-3,5 Ph); 7.41 (2H, dd,
J = 8.1, J = 1.7, Н-2,6 Ph); 7.99 (1H, d, J = 8.3, Н-1); 10.94
(1H, s, NH). Found, m/z: 371.2097 [M+H]+. C25H27N2O.
Calculated, m/z: 371.2118.
References
1. (a) Mamedov, V. A. Quinoxalines. Synthesis, Reactions,
Mechanisms and Structure; Springer International Publishing,
2016. (b) The Chemistry of Heterocyclic Сompounds:
Condensed Pyrazines; Cheeseman, G. W. H.; Cookson, R. F.,
Eds.; John Wiley & Sons: New York, 1979, Vol. 35.
2. (a) Alleca, S.; Corona, P.; Lorigo, M.; Paglietti, G.; Loddo, R.;
Mascia, V.; Busonera, B.; La Colla, P. Farmaco 2003, 58,
639. (b) Patel, M.; Mc Hugh, R. J.; Cordova, B. C.; Klabe, R. M.;
Erickson-Vitanen, S.; Trainor, G. L.; Rodgers, J. D. Bioorg.
Med. Chem. Lett. 2000, 10, 1729. (c) Guillon, J.; Dallemagne, P.;
Pfeiffer, B.; Renard, P.; Manechez, D.; Kervran, A.; Rault, S.
Eur. J. Med. Chem. 1998, 33, 293. (d) Kim, K. S.; Qian, L.;
Bird, J. E.; Dickinson, K. E. J.; Moreland, S.; Schaeffer, T. R.;
Waldron, T. L.; Delaney, C. L.; Weller, H. N.; Miller, A. V.
J. Med. Chem. 1993, 36, 2335.
7-Hexyl-8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-
6(5H)-one (3i) was obtained from 3-(1-chloroheptyl)-
quinoxalin-2(1Н)-one (1h) (1.00 g, 3.58 mmol) and
1-(1-pyrrolidinо)cyclohexene (2a) (0.54 g, 3.58 mmol).
Yield 0.63 g (54%), white crystals, mp 208–210°С (DMF–
2-PrOH, 1:1). IR spectrum, ν, cm–1: 3443, 3168, 3025,
2953, 2922, 2852, 1643, 1613, 1505, 1441, 1399, 1378,
1329, 1245, 1176, 1111, 873, 738, 726, 716, 665, 614, 562,
1
549, 516. H NMR spectrum (500 MHz), δ, ppm (J, Hz):
0.83–0.87 (3H, m, CH3); 1.24–1.31 (6H, m, (СН2)3); 1.48–
1.52 (2H, m, СН2); 1.73–1.77 (2H, m) and 1.85–1.89 (2H,
m, 9,10-СН2); 2.87 (2H, dd, J = 7.4, J = 7.1) and 3.13–3.16
(2H, m, 8,11-СН2); 7.07 (1H, dd, J = 8.0, J = 7.3, Н-2); 7.16
(1H, dd, J = 7.6, J = 6.9, Н-3); 7.23 (1H, d, J = 7.7, Н-4);
7.88 (1H, d, J = 7.9, Н-1); 10.78 (1H, s, NH). Found, m/z:
323.2155 [M+H]+. C21H27N2O. Calculated, m/z: 323.2118.
7-Phenylindolo[1,2-а]quinoxalin-6(5H)-one (6). 7-Phe-
nyl-8,9,10,11-tetrahydroindolo[1,2-а]quinoxalin-6(5H)-one
(3a) (1.00 g, 3.18 mmol) and chloranil (3.12 g, 12.72 mmol)
were refluxed in xylene (30 ml) for 50 h. After the
evaporation of solvent, the residue was purified by silica
gel column chromatography (Silica gel 100/160 μm, eluent
hexane–AcOEt, 4:1→1:1, Rf 0.36). Yield 0.81 g (82%),
pinkish-beige crystals, mp 312–314°С. IR spectrum, ν, cm–1:
3395, 3180, 3030, 2979, 2923, 2859, 1663, 1615, 1601,
1560, 1506, 1493, 1449, 1438, 1405, 1371, 1327, 1242,
1179, 1074, 991, 927, 839, 803, 743, 699, 666, 631, 611,
3. (a) Jacobsen, E. J.; Stelzer, L. S.; Belonga, K. L.; Carter, D. B.;
Im, W. B.; Sethy, V. H.; Tang, A. H.; VonVoigtlander, P. F.;
Petke, J. D. J. Med. Chem. 1996, 39, 3820. (b) Davey, D. D.;
Erhardt, P. W.; Cantor, E. H.; Greenberg, S. S.;
Ingebretsen, W. R.; Wiggins, J. J. Med. Chem. 1991, 34,
2671. (c) Colotta, V.; Cecchi, L.; Catarzi, D.; Filacchioini, G.;
Martini, C.; Tacchi, P.; Lucacchini, A. Eur. J. Med. Chem.
1995, 30, 133.
4. (a) Sakata, G.; Makino, K.; Kurasawa, Y. Heterocycles 1988,
27, 2481. (b) Seitz, L. E.; Suling, W. J.; Reynolds, R. C.
J. Med. Chem. 2002, 45, 5604. (c) Gazit, A.; App, H.;
McMahon, G.; Chen, J.; Levitzki, A.; Bohmer, F. D. J. Med.
Chem. 1996, 39, 2170. (d) Ali, M. M.; Ismail, M. M. F.;
El-Gaby, M. S. A.; Zahran, M. A.; Ammar, Y. A. Molecules
2000, 5, 864. (e) Campiani, G.; Nacci, V.; Corelli, F.; Anzini, M.
Synth. Commun. 1991, 21, 1567. (f) Kher, S. S.; Penzo, M.;
Fulle, S.; Ebejer, J. P.; Finn, P. W.; Blackman, M. J.;
Jirgensons, A. Chem. Heterocycl. Compd. 2015, 50, 1457.
[Khim. Geterotsikl. Soedin. 2014, 1583.]
5. (a) Mamedov, V. A.; Kalinin, A. A. Chem. Heterocycl.
Compd. 2010, 46, 641. [Khim. Geterotsikl. Soedin. 2010, 803.]
(b) Kalinin, A. A.; Mamedov, V. A. Chem. Heterocycl. Compd.
2011, 46, 1423. [Khim. Geterotsikl. Soedin. 2010, 1763.]
6. Mamedov, V. A.; Zhukova, N. A. In Progress in Heterocyclic
Chemistry; Gribble, G. W.; Joule, J. A., Ed.; Elsevier: Oxford,
2012, Vol. 24, p. 55.
7. Mamedov, V. A.; Zhukova, N. A. In Progress in Heterocyclic
Chemistry; Gribble, G. W.; Joule, J. A., Ed.; Elsevier: Oxford,
2013, Vol. 25, p. 1.
8. Corona, P.; Vitale, G.; Loriga, M.; Paglietti, G.; La Colla, P.;
Collu, G.; Sanna, G.; Loddo, R. Eur. J. Med. Chem. 2006, 41, 1102.
9. (а) Mamedov, V. A.; Kalinin, A. A. Russ. Chem. Rev. 2014,
83, 820. [Usp. Khim. 2014, 83, 820.] (b) Mamedov, V. A.;
Kalinin, A. A., Balandina A. A., Rizvanov, I. Kh.; Latypov, Sh. K.
Tetrahedron 2009, 65, 9412. (c) Kalinin, A. A.; Voloshina, A. D.;
Kulik, N. V.; Zobov, V. V.; Mamedov, V. A. Eur. J. Med.
Chem. 2013, 66, 345.
10. (а) Somei, M.; Yamada, F. Nat. Prod. Rep. 2003, 20, 216.
(b) Gupta, L.; Talwar, A.; Chauhan, P. M. S. Curr. Med.
Chem. 2007, 14, 1789.
11. (а) Xu, H.; Lv, M. Curr. Pharm. Des. 2009, 15, 2120.
(b) Ran, J. Q.; Huang, N.; Xu, H.; Yang, L. M.; Lv, M.;
Zheng, Y. T. Bioorg. Med. Chem. Lett. 2010, 20, 3534.
(c) Williams, J. D.; Chen, J. J.; Drach, J. C.; Townsend, L. B.
J. Med. Chem. 2004, 47, 5753.
1
566. H NMR spectrum (400 MHz), δ, ppm (J, Hz): 7.29–
7.33 (2H, m, H Ar); 7.36–7.42 (3H, m, H Ar); 7.46–7.49
(2H, m, H Ar); 7.55–7.62 (3H, m, H Ar); 7.70 (1H, d,
J = 8.0, H Ar); 8.51–8.54 (1H, m, H Ar); 8.59 (1H, d,
J = 8.8, H Ar); 11.40 (1H, s, NH). Found, m/z: 443.0157
[M+Cs]+. C21H14CsN2O. Calculated, m/z: 443.0155.
X-ray structural studies of crystals were performed on
Bruker SMART Apex II (compounds 3a,e,f) and Bruker
KAPPA Apex (compounds 3d,h,i) diffractometers, using
MoKα radiation at 0.71073 Å. The structure was solved by
direct method with the SHELXS software.34 The non-
hydrogen atom positions were refined in isotropic and then
anisotropic approximations using SHELXL-97 program.34
The amino group hydrogen atoms were revealed from
electron density difference maps (except for compounds
3d,h), the rest of the atoms were placed in the calculated
positions. All calculations were performed with WinGX35
and APEX236 software. Graphical representations were
prepared by using the PLATON software.37
Supplementary information file containing X-ray crystallo-
graphy data for compounds 3a,d–f,h,i is available from the
journal website at http://link.springer.com/journal/10593.
566

Chemistry of Heterocyclic Compounds 2017, 53(5), 560–567
12. (а) Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.;
24. Huang, A.; Liu, F.; Zhan, C.; Liu,Y.; Ma, C. Org. Biomol.
Locatelli, A.; Morigi, R.; Rambaldi, M.; Varoli, L.; Landi, L.;
Prata, C.; Berridge, M. V.; Grasso, C.; Fiebig, H. H.;
Kelter, G.; Burger, A. M.; Kunkel, M. W. J. Med. Chem.
2008, 51, 4563. (b) Mahboobi, S.; Sellmer, A.; Eichhorn, E.;
Beckers, T.; Fiebig, H. H.; Kelter, G. Eur. J. Med. Chem.
2005, 40, 85. (с) Girgis, A. S. Eur. J. Med. Chem. 2009, 44,
1257.
Chem. 2011, 9, 7351.
25. (a) Biswas, S.; Singh, V.; Batra, S. Tetrahedron 2010, 66,
7781. (b) Zhao, F.; Zhang, L.; Liu, H.; Zhou, S.; Liu, H.
Beilstein J. Org. Chem. 2013, 9, 2463.
26. Chicharro, R.; Castro, S.; Reino, J. L.; Arán, V. J. Eur. J. Org.
Chem. 2003, 2314.
27. Samala, S.; Arigela, R. K.; Kant, R.; Kundu, B. J. Org. Chem.
2014, 79, 2491.
28. Shvedov, V. I.; Altukhova, L. B.; Alekseev, V. V.; Grinev, A. N.
Chem. Heterocycl. Compd. 1970, 6, 1255. [Khim. Geterotsikl.
Soedin. 1970, 1348.]
29. Atfah, A.; Abu-Shuheil, M. Y.; Hill, J. Tetrahedron 1990, 46,
6483.
13. Mathada, B. S. D.; Mathada, M. B. H. Chem. Pharm. Bull.
2009, 57, 557.
14. (а) Bhati, S. K.; Kumar, A. Eur. J. Med. Chem. 2008, 43,
2323. (b) Fakhr, I. M. I.; Radwan, M. A. A.; El-Batran, S.;
Abd El-Salam, O. M. E.; El-Shenawy, S. M. Eur. J. Med.
Chem. 2009, 44, 1718.
15. (а) Xu, H.; Fan, L. L. Eur. J. Med. Chem. 2011, 46, 1919.
(b) Verma, A. K.; Jha, R. R.; Sankar, V. K.; Aggarwal, T.;
Singh, R. P.; Chandra, R. Eur. J. Org. Chem. 2011, 6998.
(c) Agarwal, P. K.; Sawant, D.; Sharma, S.; Kundu, B. Eur. J.
Org. Chem. 2009, 292. (d) Lin, P. T; Salunke, D. B.;
Chen, L. H.; Sun, C. M. Org. Biomol. Chem. 2011, 9, 2925.
(e) Sokolova, E. A; Festa, A. A. Chem. Heterocycl. Compd.
2016, 52, 219. [Khim. Geterotsikl. Soedin. 2016, 52, 219.]
16. (а) Maiti, B.; Sun, C. M. New J. Chem. 2011, 35, 1385.
(b) Lai, J. J.; Salunke, D. B.; Sun, C. M. Org. Lett. 2010, 12, 2174.
17. Fan, Y. S.; Jiang, Y. J.; An, D.; Sha, D.; Antilla, J. C.; Zhang, S.
Org. Lett. 2014, 16, 6112.
30. (a) Mamedov, V. A.; Kalinin, A. A.; Gubaidullin, A. T.;
Nurkhametova, I. Z.; Litvinov, I. A.; Levin, Ya. A. Chem.
Heterocycl. Compd. 1999, 35, 1459. [Khim. Geterotsikl.
Soedin. 1999, 1664.] (b) Mamedov, V. A.; Zhukova, N. A.;
Balandina, A. А.; Kharlamov, S. V.; Beschastnova, T. N.;
Rizvanov, I. Kh.; Latypov, Sh. K. Tetrahedron 2012, 68, 7363.
31. (a) Mamedov, V. A.; Nuretdinov, I. A.; Sibgatullina, F. G. Bull.
Acad. Sci. USSR, Div. Chem. Sci. 1989, 38, 1292. [Izv. Akad.
Nauk SSSR, Ser. Khim. 1988, 1412.] (b) Saifina, D. F.; Ganieva,
V. R.; Mamedov, V. A. Russ. J. Org. Chem. 2009, 45, 1244. [Zh.
Org. Khim. 2009, 45, 1252.] (c) Kalinin, A. A.; Mamedov, V. A.
Chem. Heterocycl. Compd. 2004, 40, 129. [Khim. Geterotsikl.
Soedin. 2004, 133.] (d) Mamedov, V. A.; Kalinin, A. A.;
Azancheev, N. M.; Levin, Ya. A. Russ. J. Org. Chem. 2003, 39,
125. [Zh. Org. Khim. 2003, 39, 135.]
32. (a) Bagal, S. K.; Adlington, R. M.; Baldwin, J. E.; Marquez, R. J.
Org. Chem. 2004, 69, 9100. (b) Maiti, S.; Achari, B.;
Mukhopadhyay, R.; Banerjee, A. K. J. Chem. Soc., Perkin
Trans. 1 2002, 1769. (c) McNally, J. J.; Youngman, M. A.;
Lovenberg, T. W.; Nepomuceno, D. H.; Wilson, S. J.; Dax, S. L.
Bioorg. Med. Chem. Lett. 2000, 10, 213.
18. Wang, L.; Guo, W.; Zhang, X. X.; Xia, X. D.; Xiao, W. D.
Org. Lett. 2012, 14, 740.
19. (а) Yi, C. S.; Yun, S. Y. J. Am. Chem. Soc. 2005, 127, 17000.
(b) Patil, N. T.; Lakshmi, P. G. V. V.; Singh, V. Eur. J. Org.
Chem. 2010, 4719.
20. (а) Zhou, Y.; Ji, X.; Liu, G.; Zhang, D.; Zhao, L.; Jiang, H.;
Liua, H. Adv. Synth. Catal. 2010, 352, 1711. (b) Patil, N. T.;
Kavthe, R. D.; Shinde, V. S.; Sridhar, B. J. Org. Chem. 2010,
75, 3371.
21. (а) Rustagi, V.; Tiwari, R.; Verma, A. K. Eur. J. Org. Chem.
2012, 4590. (b) Rustagi, V.; Aggarwal, T.; Verma, A. K.
Green Chem. 2011, 13, 1640.
22. (а) Luo, X.; Chenard, E.; Martens, P.; Cheng, Y. X.;
Tomaszewski, M. J. Org. Lett. 2010, 12, 3574. (b) Abbiati, G.;
Beccalli, E. M.; Broggini, G.; Paladino, G,; Rossia, E.
Synthesis 2005, 2881.
23. (а) Maddirala, S. J.; Basanagoudar, L. D. Synth. Commun.
2003, 33, 851. (b) Beach, M. J.; Hope, R.; Klaubert, D. H.;
Russel R. K. Synth. Commun. 1995, 25, 2165. (с) Yuan, Q.;
Ma, D. J. Org. Chem. 2008, 73, 5159.
33. (a) Overman, L. E.; Wolfe, J. P. J. Org. Chem. 2002, 67,
6421. (b) Mitschke, U.; Osteritz, E. M.; Debaerdemaeker, T.;
Sokolowski, M.; Bauerle, P. Chem.–Eur. J. 1998, 4, 2211.
(c) Ma, Li-J., Inokuchi, T. Chem. Commun. 2010, 46, 7037.
34. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2008, A64, 112.
35. Farrugia, L. J. J. Appl. Crystallogr. 1999, 32(4), 837.
36. APEX (Version 2.1). SAINTPlus. Data Reduction and
Correction Program. Version 7.31A. Bruker Advansed X-Ray
Solutions; BrukerXS Inc.: Madison, 2006.
37. Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7.
567