Microwave synthesis of 2-[(E)-2-(1H-indol-3-yl)vinyl]hetarenes

Article abstract of DOI:10.1007/s10593-015-1788-0

A new highly efficient method for the condensation of (indol-3-yl)carbaldehydes with 2-methylazoles and 2-methylazines under activation with microwave irradiation is developed. The method provides high yields of structural scaffolds of bishetarylethylene

Full text of DOI:10.1007/s10593-015-1788-0

DOI 10.1007/s10593-015-1788-0
Chemistry of Heterocyclic Compounds 2015, 51(10), 865–868
CHEMISTRY OF
HETEROCYCLIC
COMPOUNDS
Microwave synthesis of
-[(E)-2-(1H-indol-3-yl)vinyl]hetarenes
2
1
1
1
Alexander V. Aksenov *, Oleg N. Nadein , Nicolai A. Aksenov ,
1,2
1
1
Anton A. Skomorokhov, Inna V. Aksenova , Michael A. Rubin *
1
North-Caucasus Federal University,
1
Pushkin St., Stavropol 355009, Russia;
е-mail: alexaks05@rambler.ru
2
University of Kansas,
1
251 Wescoe Hall Drive, Lawrence KS 66045-7582, USA;
е-mail: mrubin@ku.edu
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
015, 51(10), 865–869
Submitted October 15, 2015
Accepted November 3, 2015
2
A new highly efficient method for the condensation of (indol-3-yl)carbaldehydes with 2-methylazoles and 2-methylazines under
activation with microwave irradiation is developed. The method provides high yields of structural scaffolds of bishetarylethylene
fluorescent sensors that found widespread application in medicinal, bioorganic, and pharmaceutical chemistry.
Keywords: benzoxazole, indole, pyridine, quinoline, condensation, microwave synthesis.
2
Clinical treatment of a range of neurological and
psychiatric dysfunctions as well as some cardiovascular
and oncological conditions calls for diagnostic procedures
whose merit strongly depends on efficiency of RNA
visualization.1 Oftentimes the correct choice of RNA-
selective sensors suitable for in vivo applications becomes a
key problem.2 Among available visualization agents the
most commonly used are commercially available cyanine
dyes. However, most of these compounds suffer from
notable photosensitivity and limited RNA selectivity,
which creates certain problems with their utilization for
In his recent work Zheng proposed synthesis of Е36
dye (4) via N-alkylation of heterostilbene 3aa with a previ-
ously protected indolyl nitrogen atom. The overall yield of
the target material according to this scheme did not exceed
21% (Scheme 1). A different synthetic approach suggested
in the same report involved initial quaternization of
quinaldine (2a) and subsequent condensation of the formed
salt with aldehyde 1a. However, this alternative protocol
also did not provide marked improvement and afforded the
yields of about 23–24%.2
,2
,3
Scheme 1
4
frame-by-frame imaging of live cell samples.
Recently, new luminescent probes of type E36, 2-[(E)-2-
4,5
(
1H-indol-3-yl)vinyl]-1-methylquinolinium iodide, were
introduced. These substances proved suitable for
investigation of cell nuclei and identification of particular
fragments of RNA in living cells and demonstrated
significantly improved photostability and selectivity as
compared to traditional cyanine-type sensors, especially for
in vivo analyses. Furthermore, molecules of this structural
type found applications as highly selective contrast
fluorescent probes for analyses of nucleic and pepti-
donucleic acids.6 In addition, important biological
properties were discovered for some of related structures,
7
8
including anticancer and antimalarial activity, as well as
9
inhibiting of HIV. Not surprisingly, there is a great interest
to synthesis of compounds of this structural type.
Here and further the corresponding author is marked with*.
0
009-3122/15/5110-0865©2015 Springer Science+Business Media New York
865

Chemistry of Heterocyclic Compounds 2015, 51(10), 865–868
Apparently, the existing synthetic protocols for this
condensation, illustrated with the typical examples
Scheme 2
CHO
2
-Me(Het)2a–c
Het-2
described above, are greatly limited, which lowers their
potential for combinatorial synthesis targeted for building
collections of fluorescent analytical probes or libraries for
bio-medicinal screening. It should be mentioned, that such
condensations involving indol-3-carbaldehydes substituted
at position 2 have never been reported.
Piperidine (cat.)
R
Microvawe
N
N
H
160°C, 4 h
R
H
3
aa–dc
1a–d
1
a R = H, 1b R = Me, 1c R = Ph, 1d R = 2-naphthyl;
2a quinaldine, 2b 2-picoline, 2c 2-methylbezoxazole
In the frame of multidisciplinary research project
10
executed in our laboratories concerning the synthetic and
medicinal11 chemistry of indole derivatives, we became
interested in this challenge. We hypothesized that a general
and highly efficient protocol for condensation of indole-
N
N
HN
HN
HN
3
aa 95%
3ba 91%
Me
3
-carbaldehydes with various methylazines and azoles
could be developed employing microwave activation. To
test this idea, the mixtures of aldehyde 1a and quinaldine
(
2a), without solvent, in the presence of catalytic amounts
N
N
of piperidine were heated in a microwave reactor at varied
temperatures, and the conversions were monitored by
chromatography. Additionally, we found that is was
3da 80%
HN
3
ca 84%
1
convenient to monitor the reaction progress by H NMR
spectroscopy, since the almost equimolar ratio of reactants
allowed for easily assessment of the starting aldehyde
consumption. This method also provides the opportunity to
observe accumulation of well-resolved signals of
condensation product 3aa. Optimized reaction conditions
involved isothermic heating of the neat mixtures of starting
materials in the presence of catalytic amounts of piperidine
O
N
N
HN
3ab 72%*
HN
HN
3ac 86%
O
N
O
(
20 mol %) at 160°С for 4 h. Under these conditions,
N
condensation product 3aa was formed quantitatively, while
HN
3
bc 75%
Me
preparative yield of the purified material was 95%
3cc 90%
(
Scheme 2). The structure and trans-configuration of the
double bond in this molecule were unambiguously assigned
by X-ray crystallography (Fig. 1). Indole-3-carbaldehydes
substituted at position 2, (2-methyl-1H-indol-3-yl)carb-
aldehyde (1b), (2-phenyl-1H-indol-3-yl)carbaldehyde (1c),
and [2-(naphth-2-yl)-1H-indol-3-yl]carbaldehyde (1d), also
reacted with quinaldine (2a) under identical conditions.
Although an increase in steric hindrance causes a notable
decrease of the process efficacy, the corresponding hetero-
stilbenes 3ba, 3ca, and 3da could be obtained in quite high
isolated yields. Similarly, reactions involving 2-methylbenz-
oxazole (2c) proceeded readily under identical conditions
leading to formation of vinyloxazoles 3ac, 3bc, 3cc, and 3dc.
The reaction between 1H-indole-3-carbaldehyde (1a)
and 2-picoline (2b) proceeded very sluggishly under
standard conditions affording complex mixtures of side
products that did not contain a trans-double bond
O
N
HN
3
dc 83%
*
Reaction conditions: DBU, MW, 240°C, 2 h.
chemistry. The synthesis involves condensation of indole-
3-carbaldehydes with 2-methylated nitrogen heterocycles,
and is carried out without solvent in the presence of
catalytic amounts of organic base under microwave
activation. Compared to previously described analogs, the
featured process allowed for significant improvement of
yields and successful utilization of even most stubborn
sterically hindered aldehydes substituted at position 2.
1
according to H NMR spectral analysis. Additional
optimization allowed an alternative protocol involving
heating the reaction at higher temperature over shorter
period of time (2 h at 240°С) in the presence of DBU used
as a base. Such modification allowed for isolation of
product 3ab, albeit in somewhat lower yield due to partial
decomposition of the reaction mixtures (Scheme 2).
In conclusion, a new green method was developed,
allowing for efficient preparative synthesis of compounds
that contain non-symmetrical bishetarylethylene structural
motif, and are of great interest for bioorganic and medicinal
Figure 1. Crystal structure of compound 3aa showing 50%
probability amplitude displacement ellipsoids.
8
66

Chemistry of Heterocyclic Compounds 2015, 51(10), 865–868
Experimental
(1H, m, H Ind); 7.50 (1H, d, J = 3.4, H Ind); 7.41–7.29
2H, m, H Py, H Ind); 7.20–7.14 (2H, m, H Ind); 7.16 (1H,
(
IR spectra were registered on a FT-IR spectrometer
Shimadzu IRTracer-100 with attenuated total reflectance unit
d, J = 15.7, CH=); 6.94 (1H, br. s, H Py); 6.76 (1H, br. s,
H Py). 13C NMR spectrum, δ, ppm: 158.5; 149.2; 136.9;
136.6; 127.7; 127.3; 123.5; 123.4; 122.3; 122.0; 121.9;
1
13
PIKE MIRacle. H and С NMR spectra were recorded on a
Bruker Avance III HD 400 spectrometer (400 or 100 МHz,
+
120.9; 120.2; 115.9; 111.1. Found, m/z: 221.1074 [M+H] .
3
respectively) in CDCl , using TMS as internal standard.
C H N . Calculated, m/z: 221.1073.
15
13
2
High-resolution mass spectra (ESI TOF) were measured on a
Bruker mAxis Impact spectrometer in MeCN–H O solutions,
employing HCO Na–HCO H for calibration. Melting points
2-[(E)-2-(1H-Indol-3-yl)vinyl]-1,3-benzoxazole (3ac).
2
Yield 559 mg (86%), yellow crystals, mp 182–183°C
–
1
2
2
(EtOH), R 0.56. IR spectrum, ν, cm : 3170, 3050, 2934,
f
1
were measured using Stuart SMP30 apparatus. Reaction
progress and purity of isolated compounds was controlled by
TLC on precoated Kavalier SILUFOL UV-254 plates,
eluting with mixture EtOAc–hexane, 1:3. All reactions were
carried out in G10 vessels heated in microwave oven Anton
Paar Monowave 300 with automated temperature control.
The following abbreviations are used to name different
2860, 1628, 1490, 1269, 1168, 740. H NMR, δ, ppm (J, Hz):
8.02 (1H, d, J = 16.4, CH=); 8.01–7.99 (1H, m, H Ind);
7.67–7.64 (1H, m, H Bxl); 7.52–7.50 (1H, m, H Ind); 7.48–
7.46 (1H, m, H Bxl); 7.44–7.42 (1H, m, H Ind); 7.32–7.27
(4H, m, H Bxl, H Ind); 7.06 (1H, d, J = 16.3, CH=). 13
C
NMR spectrum, δ, ppm: 164.5; 151.1; 142.5; 137.4; 136.0;
133.5; 128.1; 125.4; 124.4; 123.4; 123.0; 120.4; 119.4;
1
+
aromatic and heterocyclic cores in H NMR spectra: Qu –
114.3; 112.0; 110.2; 109.4. Found, m/z: 261.1018 [M+H] .
quinoline; Ind – indole, Py – pyridine, Bxl – benzoxazole,
Naph – naphthalene.
C H N O. Calculate, m/z: 261.1022.
17
13
2
2-[(E)-2-(2-Methyl-1H-indol-3-yl)vinyl]quinoline (3ba).
Preparation of 2-[(E)-2-(1H-indol-3-yl)vinyl]hetare-
nes 3aa–dc (General method). A reaction vessel was
charged with 1H-indole-3-carbaldehyde 1a–d (2.5 mmol),
Yield 645 mg (91%), dark-red oil, R 0.46. IR spectrum, ν,
f
–1
cm : 3403, 3163, 3055, 2965, 1593, 1456, 1422, 1329,
1222, 949, 816, 741. H NMR spectrum, δ, ppm (J, Hz):
1
2
-methylhetarene 2a–c (3.0 mmol), and piperidine
8.09–8.06 (1H, m, H Ind); 8.05–8.02 (2H, m, H Qu); 7.95
(1H, d, J = 16.4, CH=); 7.77 (1H, d, J = 8.0, H Qu); 7.69–
7.66 (2H, m, H Qu); 7.50–7.46 (1H, m, H Qu); 7.44–7.40
(1H, m, H Ind); 7.38 (1H, d, J = 16.4, CH=); 7.29–7.27
(
0.05 ml, 0.5 mmol), and the mixture was stirred and
heated in microwave reactor at 160°С for 4 h. Then, the
reaction mixture was cooled down and quantitatively
1
3
transferred to another vessel employing CH
2
Cl
2
(3×10 ml).
(2H, m, H Ind); 2.75 (3H, s, CH ). C NMR spectrum, δ,
3
Solutions of compounds 3aa and 3ac were evaporated in
vacuum and the residual solids were recrystallized from
EtOH. Solutions of other products were concentrated and
the residues were purified by flash column chromatography
on silica gel eluting with 5% solution of isopropanol in
ppm: 157.8; 148.5; 136.8; 136.2; 129.7; 129.3; 127.9;
127.6; 127.1; 126.3; 125.9; 125.5; 124.3; 121.0; 120.8;
120.2; 119.4; 115.5; 111.0; 25.4. Found, m/z: 285.1389
+
[M+H] . C H N . Calculated, m/z: 285.1386.
20
17
2
2
-[(E)-2-(2-Methyl-1H-indol-3-yl)vinyl]-1,3-benzoxa-
CH
2
Cl . Note: DBU (0.075 ml, 0.5 mmol) was used as a
2
zol (3bc). Yield 514 mg (75%), light-yellow oil, R
f
0.58. IR
3249, 3054, 2967, 2861, 1616, 1456,
242, 952, 737. H NMR spectrum, δ, ppm (J, Hz): 8.02
–1
base to perform reaction between 1H-indole-3-carb-
aldehyde (1a) and 2-methylpyridine (2b); the mixture was
microwaved at 240°С for 2 h.
spectrum, ν, cm :
1
1
(
1H, d, J = 16.4, CH=); 7.96–7.94 (1H, m, H Ind); 7.66–
2
-[(E)-2-(1H-Indol-3-yl)vinyl]quinoline (3aa). Yield
41 mg (95%), orange crystals, mp 209–210°C (EtOH)
7
7
2
1
1
1
.65 (1H, m, H Bxl); 7.47 (2H, m, H Bxl, H Ind); 7.30–
6
.26 (4H, m, H Bxl, H Ind); 7.05 (1H, d, J = 16.4, CH=);
o
12
–1
1
3
(
mp 212–213 C ), R
f
0.45. IR spectrum, ν, cm : 3403,
.64 (3H, s, CH ). C NMR spectrum, δ, ppm: 163.8;
3
3
1
161, 3053, 2921, 2854, 4600, 1505, 1455, 1423, 1337,
50.5; 146.7; 140.7; 137.2; 135.8; 135.0; 126.1; 124.2;
1
312, 1221, 1141, 1009, 820, 740. H NMR spectrum, δ,
23.9; 123.6; 123.0; 121.0; 118.9; 115.0; 110.8; 109.9;
+
ppm (J, Hz): 8.49 (1H, br. s, NH); 8.14–8.12 (1H, m,
H Ind); 8.11 (1H, d, J = 8.5, H Qu); 8.08 (1H, d, J = 9.0,
H Qu); 7.95 (1H, d, J = 16.4, CH=); 7.77 (1H, d, J = 7.9,
H Qu); 7.71–7.68 (1H, m, H Qu); 7.68 (1H, d, J = 8.5,
H Qu); 7.53 (1H, d, J = 2.5, H Ind); 7.47–7.45 (1H, m,
H Qu); 7.44 (1H, d, J = 16.4, CH=); 7.44–7.42 (1H, m,
H Ind); 7.28–7.26 (2H, m, H Ind). 1 C NMR spectrum, δ,
ppm: 157.3; 148.4; 137.2; 136.4; 129.8; 129.0; 128.1;
2.4. Found, m/z: 275.1184 [M+H] (1.1 ppm). C18
H
15
N O.
2
Calculated, m/z: 275.1179.
14
2
-[(E)-2-(2-Phenyl-1H-indol-3-yl)vinyl]quinoline (3ca).
Yield 728 mg (84%), dark-red oil, R
f
0.52. IR spectrum, ν,
–1
cm : 3156, 3058, 2963, 1597, 1450, 1311, 1245, 1073,
1
9
8
52, 743, 695. H NMR spectrum, δ, ppm (J, Hz): 8.20–
3
.18 (1H, m, H Ind); 8.05–8.02 (2H, m, H Qu); 7.93 (1H,
d, J = 16.4, CH=); 7.78–7.73 (1H, m, H Qu); 7.70–7.65
1
1
C
27.6; 127.2; 126.1; 125.8; 125.3; 123.1; 121.1; 120.7;
(
2H, m, H Qu); 7.63–7.61 (2H, m, H Ph); 7.50–7.46 (3H,
+
19.2; 115.4, 111.7. Found, m/z: 271.1234 [M+H] .
m, H Ph); 7.43–7.40 (3H, m, H Qu, H Ind, CH=); 7.28–
7
1
1
1
3
.24 (2H, m, H Ind). 13C NMR spectrum, δ, ppm: 159.0;
50.1; 148.2; 146.9; 137.5; 136.7; 135.1; 135.3; 131.3;
30.1; 129.6; 129.3; 128.5; 127.5; 126.3; 125.8; 125.0;
19
H
3
15
N . Calculated, m/z: 271.1230.
2
-[(E)-2-(Pyridin-2-yl)vinyl]-1H-indole (3ab). Yield
3
(
3
8
8
96 mg (72%), orange crystals, mp 190–191°C (MeOH)
o
13
–1
mp 190–191 C ), R
f
0.34. IR spectrum, ν, cm : 3425,
24.3; 123.0; 122.1; 121.2; 115.0; 111.1. Found, m/z:
+
121, 3078, 3060, 1583, 1506, 1342, 1236, 1160, 985, 930,
47.1540 [M+H] . C25
H
19
N . Calculated, m/z: 347.1543.
2
1
02, 738, 693. H NMR spectrum, δ, ppm (J, Hz): 8.50–
.49 (1H, m, H Py); 7.93 (1H, d, J = 15.3, CH=); 7.91–7.89
2
-[(E)-2-(2-Phenyl-1H-indol-3-yl)vinyl]-1,3-benzoxa-
zole (3cc). Yield 757 mg (90%), light-yellow oil, R 0.63.
f
8
67

Chemistry of Heterocyclic Compounds 2015, 51(10), 865–868
–
1
IR spectrum, ν, cm : 3442, 3230, 3063, 2937, 2858, 2360,
Federation for Support of Young Russian Scientists with
PhD degree (MK-5733.2015.3).
1
1
616, 1451, 1241, 741, 696. H NMR spectrum, δ, ppm
(
J, Hz): 8.00 (1H, d, J = 16.3, CH=); 7.99–7.96 (1H, m,
References
H Ind); 7.63–7.61 (3H, m, H Bxl, H Ph); 7.56–7.51 (3H, m,
H Ph); 7.38–7.36 (2H, m, H Bxl, H Ind); 7.32–7.28 (4H, m,
1
. (a) MacLaren, D. C.; Toyokuni, T.; Cherry, S. R.; Barrio, J. R.;
Phelps, M. E.; Herschman, H. R.; Gambhir, S. S. Biol.
Psychiatr. 2000, 48, 337. (b) Bartlett, D. W.; Su, H.;
Hildebrandt, I. J.; Weber, W. A.; Davis, M. E. Proc. Natl.
Acad. Sci. 2007, 104, 15549. (c) Tian, X.; Aruva, M. R.;
Zhang, K.; Shanthly, N.; Cardi, C. A.; Thakur, M. L.;
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1
3
H Bxl, H Ind); 7.04 (1H, d, J = 16.3, CH=). C NMR
spectrum, δ, ppm: 165.0; 152.3; 149.0; 147.7; 142.1; 138.4;
1
1
3
37.2; 135.5; 130.3; 129.7; 129.4; 126.3; 124.6; 124.0;
23.4; 123.0; 122.6; 120.5; 115.2; 111.2. Found, m/z:
+
37.1340 [M+H] . C23
H
17
N O. Calculated, m/z: 337.1335.
2
2
-{(E)-2-[2-(Naphth-2-yl)-1H-indol-3-yl]vinyl}quino-
line (3da). Yield 793 mg (80%), dark-red oil, R 0.68.
IR spectrum, ν, cm : 3180, 3054, 2967, 1597, 1426, 1304,
f
–
1
1
1
8
7
237, 950, 818, 745. H NMR spectrum, δ, ppm (J, Hz):
.29–8.27 (1H, m, H Ind); 8.11 (1H, br. s, H Naph); 8.06–
.99 (4H, m, H Naph, H Qu, CH=); 7.94–7.91 (2H, m,
2. Wang, M.; Gao, M.; Miller, K. D.; Sledge, G. W; Hutchins, G. D.;
Zheng, Q.-H. Eur. J. Med. Chem. 2009, 44, 2300.
3
4
. Li, Q. Chang, Y.-T. Nat. Protoc. 2006, 1, 2922.
. (a) Ballou, B.; Fisher, G.W.; Deng, J. S.; Hakala, T. R.;
Srivastava, M.; Farkas, D. L. Cancer Detect. Prev. 1998, 22,
H Naph); 7.79–7.74 (2H, m, H Naph, H Qu); 7.70–7.63
(
2H, m, H Qu); 7.58–7.55 (2H, m, H Naph); 7.50–7.42
3H, m, H Qu, H Ind, CH=); 7.31–7.27 (2H, m, H Ind).
(
2
51. (b) Bogdanov, A. A., Jr.; Lin, C. P.; Simonova, M.;
1
3
C NMR spectrum, δ, ppm: 157.8; 148.4; 140.0; 136.4;
Matuszewski, L.; Weissleder, R. Neoplasia 2002, 4, 228.
1
1
1
3
29.8; 129.6; 128.9; 128.7; 128.1; 127.9; 127.1; 126.8; 126.7;
5. Li, Q.; Kim, Y.; Namm, J.; Kulkarni, A.; Rosania, G. R.;
Ahn, Y.-H.; Chang, Y.-T. Chem. Biol. 2006, 13, 615.
26.1; 125.8; 125.6; 124.0; 123.3; 123.2; 122.4; 122.1;
6
. (a) Bohländer, P. R.; Vilaivan, T.; Wagenknecht, H. A. Org.
Biomol. Chem. 2015, 13, 9223. (b) Bohländer, P. R.;
Wagenknecht, H.-A. Org. Biomol. Chem. 2013, 11, 7458.
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BioSystems 2013, 9, 2426.
21.3; 121.2; 120.7; 120.2; 118.6; 111.8; 111.1. Found, m/z:
+
97.1705 [M+H] . Calculated for C29
H
21
N , m/z: 397.1699.
2
2
-{(E)-2-[2-(Naphth-2-yl)-1H-idol-3-yl]vinyl}-1,3-benz-
oxazole (3dc). Yield 802 mg (83%), light-yellow oil, R 0.75.
IR spectrum, ν, cm : 3213, 3055, 2941, 2858, 1616, 1446,
7
f
–
1
1
1
(
(
241, 820, 743. H NMR spectrum, δ, ppm (J, Hz): 8.95
8. Teguh, S. C.; Klonis, N; Duffy, S.; Lucantoni, L.; Avery, V. M.;
Hutton, C. A. Baell, J. B.; Tilley, L. J. Med. Chem. 2013, 56,
6200.
1H, br. s, NH); 8.12 (1H, d, J = 16.3, CH=); 8.08–8.06
2H, m, H Ind, H Naph); 7.98–7.95 (1H, m, H Naph); 7.91–
9
. Hinkov, A.; Yosifova, L.; Todorova, E.; Raleva, S.; Pavlov, A.;
Chervenkov, S.; Dundarova, D.; Argirova, R. Auton. Autacoid
Pharmacol. 2010, 30, 107.
7
7
7
.82 (3H, m, H Naph); 7.66–7.64 (1H, m, H Bxl); 7.57–
.55 (2H, m, H Naph); 7.50–7.42 (2H, m, H Bxl, H Ind);
.33–7.25 (4H, m, H Bxl, H Ind); 7.13 (1H, d, J = 16.3,
13
10. (a) Aksenov, A. V.; Smirnov, A. N.; Aksenov, N. A.;
CH=). C NMR spectrum, δ, ppm: 161.7; 151.6; 149.0;
Aksenova, I. V.; Matheny, J. P.; Rubin, M. RCS Adv. 2015, 5,
1
1
1
41.9; 138.0; 137.2; 135.8; 133.8; 133.2; 129.8; 129.3;
8647. (b) Aksenov, A. V.; Smirnov, A. N.; Aksenov, N. A.;
28.6; 128.1; 127.7; 127.5; 127.4; 126.8; 126.4; 126.3;
Aksenova, I. V.; Bijieva, A. S.; Rubin, M. Org. Biomol.
Chem. 2014, 12, 9786. (c) Aksenov, A. V.; Smirnov, A. N.;
Aksenov, N. A.; Aksenova, I. V.; Frolova, L. V.; Kornienko, A.;
Magedov, I. V.; Rubin, M. Chem. Commun. 2013, 49, 9305.
1. Aksenov, A.; Smirnov, A.; Magedov, I.; Reisenauer, M.;
Aksenov, N.; Aksenova, I.; Pendleton, A.; Nguyen, G.;
Johnston, R.; Rubin, M.; De Carvalho, A.; Kiss, R.; Mathieu, V.;
Lefranc, F.; Correa, J.; Cavazos, D.; Brenner, A.; Bryan, B.;
Rogelj, S.; Kornienko, A.; Frolova, L. J. Med. Chem. 2015,
24.7; 123.5; 122.6; 122.1; 121.3; 115.4; 112.0; 111.2.
+
Found, m/z: 387.1495 [M+H] . C27
H
19
N O. Calculated, m/z:
2
387.1492.
1
X-ray structural analysis of compound 3aa was
performed on an Agilent SuperNova diffractometer
equipped with AtlasS2 CCD detector, using Cu X-ray
source (CuKα 1.54184 Å), scanning at 291.86 K. The
structure was solved by the SHELXS software and refined
5
8, 2206.
2
15
by full-matrix least-squares on all F data using SHELXL
1
2. Bahner, C. T.; Kinder, H.; Gutman, L. J. Med. Chem. 1965, 8,
in conjunction with the OLEX2 graphical user interface.
Full crystallographic data are deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 1431568).
397.
13. De Silva, S. O.; Snieckus, V. Can. J. Chem. 1974, 52, 1294.
14. Wang, S.; Kim, Y. K.; Chang, Y.-T. J. Comb.
Chem. 2008, 10, 460.
Financial support to this program was provided by the
Council for Grants of the President of the Russian
15. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2008, A64, 112.
8
68