A Catalyst-Free, One-Pot, Three-Component Approach for the Synthesis of 2-[1-Aryl-2-(azaaryl)ethyl]malononitriles via sp3 C-H Activation of 2-Methyl Azaarenes

Article abstract of DOI:10.1055/s-0034-1380212

Combinatorial libraries of 2-[1-aryl-2-(azaaryl)ethyl]malononitriles derivatives have been synthesized by catalyst-free, one-pot, three-component protocol and employing water as a solvent. Simple reaction, open air reaction, and easy isolation are added advantages of this method. The method is applicable for aryl as well as heteroaryl systems and provides a convenient access for the synthesis of novel quinoline derivatives. All the 2-[1-aryl-2-(azaaryl)ethyl]malononitrile derivatives were evaluated for their antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus) and Gram-negative bacteria (Pseudomonas aeruginosa). Eleven compounds exhibited good antibacterial activity against both Gram-positive pathogens and Gram-negative species.

Full text of DOI:10.1055/s-0034-1380212

SYNLETT
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1
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0
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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1808–1814
letter
1808
N. S. Kumar et al.
Letter
Synlett
A Catalyst-Free, One-Pot, Three-Component Approach for the
Synthesis of 2-[1-Aryl-2-(azaaryl)ethyl]malononitriles via sp3 C–H
Activation of 2-Methyl Azaarenes
Nandigama Satish Kumara
L. Chandrasekhara Raoa
N. JagadeeshBabub
V. Dileep Kumarc
U. S. N. Murthyc
R2
R1
R1
R2
H. M. Meshram*a
CN
O
CN
+
+
N
CN
a Medicinal Chemistry and Pharmacology Division,
CSIR-Indian Institute of Chemical Technology,
Uppal Road, Tarnaka, Hyderabad, Telangana 500007, India
hmmeshram@yahoo.com
b Laboratory of X-ray Crystallography, CSIR-Indian Institute
of Chemical Technology, Uppal Road, Tarnaka, Hyderabad,
Telangana 500007, India
c Biology Division, CSIR-Indian Institute of Chemical
Technology, Uppal Road, Tarnaka, Hyderabad, Telangana
500007, India
120 min, 100 °C
N
CN
30 examples
H2O, reflux
open air
zone of inhibition
bacterial culture plate
antibacterial activity
Received: 09.02.2015
Accepted after revision: 20.04.2015
Published online: 18.06.2015
virus (HIV),12 antifungal,13 antitumor,14 and agents. Notably,
2-alkylquinolines have significant importance in medicinal
DOI: 10.1055/s-0034-1380212; Art ID: st-2015-b0088-l
OMe
Abstract Combinatorial libraries of 2-[1-aryl-2-(azaaryl)ethyl]malono-
nitriles derivatives have been synthesized by catalyst-free, one-pot,
three-component protocol and employing water as a solvent. Simple
reaction, open air reaction, and easy isolation are added advantages of
this method. The method is applicable for aryl as well as heteroaryl sys-
tems and provides a convenient access for the synthesis of novel quino-
line derivatives. All the 2-[1-aryl-2-(azaaryl)ethyl]malononitrile deriva-
tives were evaluated for their antimicrobial activity against Gram-
positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, and
Bacillus cereus) and Gram-negative bacteria (Pseudomonas aeruginosa).
Eleven compounds exhibited good antibacterial activity against both
Gram-positive pathogens and Gram-negative species.
N
O
N
N
O
cusparine
COOH
OH
Cl
N
Key words quinoline, multicomponent reaction, medicinal chemistry,
azaarene, antibacterial
CF3
O
O
O
O
N
N
Multicomponent reactions (MCR) are gaining significant
importance in organic synthesis as they offer rapid genera-
tion of series of molecules with multiple-bond formation in
a single step.1 Additionally, in the viewpoint of green chem-
istry the development of new catalyst-free multicompo-
nent reactions in water for the synthesis of privileged bio-
logically active heterocyclic compounds are more prefera-
ble in drug discovery.2,3 Furthermore, quinoline-containing
heterocycles are ubiquitous in many natural products, ac-
tive pharmaceuticals, and functional materials.4 Remark-
ably, quinolines and their derivatives act as antituberculo-
sis,5 antimalarial,6 anti-inflammatory,7,8 anticancer,9 antibi-
otic,10 antihypertensive,11 antihuman immunodeficiency
Me
Me
cuspareine
(–)-galipinine
OH
O
N
Me
(–)-galipeine
Figure 1 Biologically important 2-alkylquinoline derivatives
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1808–1814

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N. S. Kumar et al.
Letter
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chemistry as they show a broad range of biological proper-
ties.15 Synthesis of such 2-alkylquinoline derivatives using
catalyst-free multicomponent reaction is always highly de-
sirable (Figure 1).
have observed that the reaction is sluggish in toluene but
proceeded smoothly, and the product was obtained in very
good yield in water compared to polar organic solvents
such as DMF, DMSO, MeOH, and EtOH. Further attempt to
prepare the compound 4a in neat conditions gave poor
yield (Table 1, entry 12).
Recently, many methods have been developed for the
benzylic addition of 2-methylazaarenes to α,β-unsaturated
carbonyls, azodicarboxylates, aldimines, cyanoalkenes, and
nitro alkenes.16 However, these methods often suffer from
certain limitations, such as harsh reaction conditions, toxic
metals, expensive or air-sensitive catalysts, requirement for
an inert atmosphere, additives, solvents, specialized equip-
ment, tedious workup procedures, longer reaction times,
and multistep syntheses.17 Therefore, the development of a
mild, simple, general, convenient, and efficient method for
the sp3 C–H bond functionalization of 2-methylazaarenes
are still of great value.
The structure of compound 4a was confirmed by 1H
NMR, 13C NMR, and IR spectroscopic and mass spectromet-
ric analysis and unambiguously confirmed by single-crystal
X-ray analysis of its analogous 4f (Figure 2).
Based on our present investigations in establishing new,
eco-friendly, green, and safe protocols18 and developing a
process for the sp3 C–H bond functionalization of
azaarenes,18a herein we wish to report an operationally
simple, one-pot, three-component protocol for the synthe-
sis of 2-[1-aryl-2-(azaaryl)ethyl]malononitrile derivatives.
Initially, we have investigated the reaction of 2-meth-
ylquinoline (1a, 1.0 mmol), benzaldehyde (2a, 1.0 mmol)
and malononitrile (3, 1 mmol) at various temperatures and
times in different solvents without use of catalyst, which
resulted in the formation of compound 4a (Table 1). We
Figure 2 X-ray crystal structure of 4f (ORTEP diagram)21
The optimized reaction conditions are a reaction tem-
perature of 100 °C, a reaction time of 120 minutes, and wa-
ter as solvent (Table 1, entry 7). With the optimum reaction
conditions in hand,22 we investigated the scope of various
Table 1 Optimization of the Reaction Conditionsa
CN
CN
solvent
O
+
+
CN
N
N
CN
1
2a
3
4a
Entry
Solvent
Temp (°C)
Time (min)
Yield (%)b
1
2
toluene
DMSO
MeOH
EtOH
DMF
PEG-400
H2O
100
100
70
300
180
300
300
240
300
120
180
180
180
120
120
300
20
40
50
50
40
70
90
90
80
70
90
90
20
3
4
80
5
100
100
100
100
90
6
7
8
H2O
8
H2O
9
H2O
80
10
11
12
H2O
110
120
100
H2O
–
a All reactions were carried out with 1a (1 mmol), 2a (1 mmol), 3 (1 mmol), and H2O (2 mL).
b Isolated yields of the product 4a after column chromatography.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1808–1814

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N. S. Kumar et al.
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aromatic aldehydes and substituted quinolines. The results
are summarized in Schemes 1 and 2. To our delight, the re-
action of different aromatic aldehydes bearing electron-do-
nating groups (methyl, methoxy) or electron-withdrawing
groups (fluoro, chloro, bromo, nitro) underwent reactions
with 2-methylquinoline and malononitrile in excellent
yields (Scheme 1, 4b–e). Further, we explore the reactivity
of 2-azaarenes bearing electron-donating methyl and me-
thoxy groups or electron-withdrawing fluoro, chloro, and
bromo groups, which underwent reaction with various aro-
matic aldehydes in good to excellent yields (Scheme 2, 5a–l,
6a–f). Additionally, the scope of this method was extended
to heterocyclic aromatic aldehydes such as 2-furanyl, 2-
thiophenyl, 3-pyridyl, and 1,3-diphenyl-1H-pyrazol-4-yl
malononitriles23 (Schemes 1 and 2, 2g–l).
R2
R2
H2O
CN
CN
O
+
+
CN
reflux, 100 °C
N
N
CN
4a–l
1
2a–l
3
OMe
CN
CN
CN
CN
N
N
N
CN
CN
4a, 90%c
4b, 85%c
4c, 80%c
O
NO2
O
Cl
CN
CN
CN
CN
N
N
N
CN
CN
4d, 75%c
4e, 70%c
4f, 80%c
N
N
O
S
CN
CN
CN
CN
CN
N
N
4i, 80%c
N
CN
4g, 65%c
4h, 60%c
N
N
N N
N
N
S
F
CN
CN
CN
N
N
N
CN
CN
CN
4j, 80%c
4k, 75%c
4l, 80%c
Scheme 1 Catalyst-free, one-pot, three-component synthesis of 2-[1-aryl-2-(azaaryl)ethyl]malononitriles.a,b a Unless otherwise specified, the reaction
was carried out with 1 (1 mmol), 2a–l (1 mmol), 3 1 mmol), and H2O (2 mL). b Isolated yields of the products 4a–l after column chromategraphy.
c Reaction conditions: 100 °C, 120 min.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1808–1814

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R2
R1
R1
R2
H2O
CN
CN
O
+
+
N
CN
reflux, 100 °C
N
1b–f
CN
2a–k
3
5a–l, 6a–e
OMe
N
N
N
Br
F
F
Br
CN
CN
O
CN
CN
N
N
N
N
CN
CN
O
5a, 90%c
CN
5c, 75%c
5b, 70%c
CN
5d, 75%c
Br
Br
N
N
Br
S
Cl
Br
CN
CN
N
N
CN
CN
N
CN
CN
CN
N
5e, 70%c
5f, 80%c
CN
5g, 65%c
5h, 75%c
O
O
O
O
F
MeO
S
CN
MeO
N
CN
CN
Cl
CN
N
N
CN
CN
N
CN
Cl
CN
5i, 75%c
5j, 80%c
5k, 75%c
5l, 75%c
OMe
CH3
N
F
CN
CN
N
N
CN
CN
CN
N
N
CN
CN
6a, 65%d
6b, 75%d
6c, 65%d
6d, 80%d
CN
N
N
N
N
F
CN
CN
N
6e, 65%d
N
CN
CN
6f, 75%d
Scheme 2 Catalyst-free, one-pot, three-component synthesis of 2-[1-aryl-2-(azaaryl)ethyl]malononitriles.a,b a Unless otherwise specified, the reaction
was carried out with 1b–f (1 mmol), 2a–i (1 mmol), 3 (1 mmol), and H2O (2 mL). b Isolated yields of the products 5a–l, 6a–f after column chromatog-
raphy. c Reaction conditions: 100 °C, 120 min. d Reaction conditions: 100 °C, 180 min.
Then we were interested to develop this protocol in a
gram scale. So we have carried out the reaction of 2-meth-
ylquinoline (1a, 50 mmol), 4-methoxy benzaldehyde (2b,
50 mmol). and malononitrile (3, 50 mmol) in water (50 mL)
under optimized reaction conditions. After completion of
the reaction, the solid compound was filtered and purified
by silica gel column chromatography (Scheme 3).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1808–1814

1812
N. S. Kumar et al.
Letter
Synlett
OMe
O
CN
CN
H2O
+
+
reflux, 100 °C
CN
MeO
N
N
CN
1
2b
3
4b
41 mmol
50 mmol
50 mmol
50 mmol
Scheme 3
All the newly synthesized scaffolds were screened for
their in vitro antimicrobial activity against the bacterial
strains Staphylococcus aureus (MTCC 96, Gram-positive or-
ganism), Staphylococcus epidermidis (MTCC 9041, Gram-
positive organism), Bacillus subtilis (MTCC 441), Pseudomo-
nas aeruginosa (MTCC 741, Gram-negative organism) by
agar well diffusion method.19
The minimum inhibitory concentrations (MIC) of the
synthetic derivatives, by microdilution method recom-
mended by CLSI standard protocol20 in liquid medium (nu-
trient agar) distributed in 96-well plates, serial dilutions of
the tested compounds were performed (concentrations
from 150 μg/mL to 0.97 μg/mL) in a 200 μL culture medium
final volume, afterwards each well was seeded with a 50 μL
microbial suspension of 0.5 MacFarland density. Penicillin
and streptomycin were used as reference drugs. The MIC
values are presented in Table 2.
tive and Gram-negative bacterial strains with zones of inhi-
bition ranging to a maximum of 21 mm. Derivatives 4f,h,l
and 5a,c,e,f,h–j,l were identified as potent antibacterial
agent against Gram-positive bacterial strains, and deriva-
tives 4f,h,l and 5c,e,i were identified as potent antibacterial
agent against Gram-negative bacterial strains (Table 2). The
MIC values for derivatives 4f,h,l and 5a,c,e,f,h–j,l and the
positive control drugs penicillin and streptomycin were
also determined against the four bacterial strains.
Mechanistically, the tandem process might be rational-
ized as follows: Most probably, there are two parallel reac-
tions occurring with the formation of arylidenemalononi-
trile 7 and enamine intermediate 8. The enamine interme-
diate 8 itself is generated from 2-methylquinoline (1) via
1,3-H shift from the sp3 carbon to nitrogen. The arylidene-
malononitrile 7 was formed by the Knoevenagel condensa-
tion of aromatic aldehyde 2 and malononitrile (3) in the
presence of water. The two intermediates 7 and 8 undergo
intermolecular Michael addition (TS-A) and furnish product
4 (Scheme 4).
The compounds in Schemes 2 and 3 exhibited different
antibacterial activities for all four bacterial strains. Com-
pounds exhibited antibacterial activity against Gram-posi-
Table 2 MIC (in μg mL–1) of Synthesized Derivatives 4f,h,l and 5a,c,e,f,h–j,l) by Using the Modified Agar Well Diffusion Method
Minimum inhibitory concentration
Gram-positive organisms
Gram-negative organism
Staphylococcus epidermidis (MTCC9041) Bacillus subtilis (MTCC441) Pseudomonas aeruginosa (MTCC741)
Compd
Staphylococcus aureus (MTCC96)
4f
37.5
18.75
18.75
>150
37.5
37.5
75
18.75
9.37
37.5
37.5
37.5
37.5
37.5
>150
>150
>150
>150
37.5
18.75
37.5
4h
4l
5a
>150
5c
18.75
37.5
>150
18.75
>150
37.5
37.5
5e
5f
>150
5h
>150
37.5
37.5
37.5
1.562
6.25
>150
>150
>150
>150
>150
5i
37.5
5j
18.75
37.5
>150
>150
5l
penicillin
streptomycin
3.125
3.125
1.562
6.25
12.5
1.562
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1808–1814

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R
NC
CN
Ar
R
N
H
R
R
N
H
N
N
NC
Ar
1
4
8
CN
7
TS-B
CN
CN
3
+
ArCHO
2
Scheme 4 Plausible mechanism for the formation of 2-[1-aryl-2-(azaaryl)ethyl]malonitriles
In summary, we have developed a one-pot, three com-
ponent, and catalyst-free methodology for the sp3 C–H
bond functionalization of 2-methyl azaarenes with aromat-
ic aldehydes and malononitrile, affording the corresponding
products in good to excellent yields. It is a versatile method
for the synthesis of biologically active heterocyclic com-
pounds from a point of view of cost-effectiveness and in-
dustrial feasibility. The compounds were screened for their
in vitro antibacterial activity. First time we reported the an-
tibacterial activity of these quinoline derivatives. Among
the series, compounds 4f,h,l and 5a,c,e,f,h–j,l show good to
moderate antibacterial activity against Staphylococcus au-
reus, Staphylococcus epidermidis, Bacillus subtilis (Gram-
positive organisms), Pseudomonas aeruginosa (Gram-nega-
tive organism). The result shows that these quinoline deriv-
atives will be suitable for further investigations in this field
for research of potent antimicrobial agents.
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Acknowledgement
N. S. K and L. C. R thank the CSIR-India for award of a fellowship and
Dr. A. Kamal, Outstanding scientist and Head of MCP Division, for his
support and encouragement. The authors thank CSIR-India for finan-
cial support as part of XII five year plan programme under title ACT
(CSC-0301)
Supporting Information
Supporting information for this article is available online at
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http://dx.doi.org/10.1055/s-0034-1380212.
S
u
p
p
ortiInfogrmoaitn
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p
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ortioInfgrmoaitn
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(22) General Procedure
A 5 mL round-bottom-flask containing 2-methylquinoline (1a,
1 mmol), benzaldehyde (2a, 1.0 mmol), and malononitrile (3, 1
mmol), and H2O (2 mL) was placed in an oil bath and refluxed
for the appropriate time at 100 °C (temperature monitored by a
thermometer). The progress of reaction was monitored by TLC.
After completion of the reaction, the flask was removed from
the oil bath, and the solid product obtained was filtered,
washed with H2O (2 × 10 mL) and n-hexane (3 × 10 mL). The
reaction mixture was diluted with H2O and extracted with
EtOAc. The combined EtOAc extracts were then dried over
Na2SO4, and after removal of the solvent the mixture was puri-
fied by column chromatography (silica gel; hexane–EtOAc,
90:10) to give pure products.
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Franck, X.; Hocquemiller, R.; Figadere, B. Bioorg. Med. Chem.
2003, 11, 5013. (g) Chang, F. S.; Chen, W. C.; Wang, C. H.; Tzeng,
C. C.; Chen, Y. L. Bioorg. Med. Chem. 2010, 18, 124.
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2011, 13, 1706. (b) Li, H.-Y.; Xing, L.-J.; Xu, T.; Wang, P.; Liu, R.-
H.; Wang, B. Tetrahedron Lett. 2013, 54, 858. (c) Yan, Y.; Xu, K.;
Fang, Y.; Wang, Z. J. Org. Chem. 2011, 76, 6849. (d) Qian, B.; Shi,
D.; Yang, L.; Huang, H. Adv. Synth. Catal. 2012, 354, 2146.
(e) Qian, B.; Guo, S.; Shao, J.; Zhu, Q.; Yang, L.; Xia, C.; Huang, H.
J. Am. Chem. Soc. 2010, 132, 3650. (f) Qian, B.; Xie, P.; Xie, Y.;
Huang, H. Org. Lett. 2011, 13, 2580. (g) Qian, B.; Guo, S.; Xie, C.;
Huang, H. Adv. Synth. Catal. 2010, 352, 3195.
(23) Analytical Data for a Few Typical Compounds
2-[1-(1,3-Diphenyl-1H-pyrazol-4-yl)-2-(quinolin-2-
yl)ethyl]malononitrile (4i)
Pale grey solid; yield 75%; mp 149–151 °C. IR (KBr): νmax = 3443,
3063, 2867, 2258, 1745, 1597, 1546, 1503, 1450, 1418, 1362,
1312, 1245, 1153, 1062, 960, 914, 829, 753, 695, 514 cm–1 1H
.
NMR (500 MHz, CDCl3): δ = 3.53 (m, 2 H), 4.48 (m, 1 H), 4.93 (d,
J = 4.8 Hz, 1 H), 7.21 (d, J = 8.3 Hz, 1 H), 7.29 (t, J = 7.4 Hz, 1 H),
7.39 (m, 5 H), 7.52 (t, J = 7.9 Hz, 1 H), 7.61 (d, J = 6.7 Hz, 2 H),
7.71 (t, J = 8.0 Hz, 3 H), 7.78 (d, J = 8.2 Hz, 1 H), 8.00 (d, J = 8.3
Hz, 1 H), 8.08 (d, J = 8.3 Hz, 1 H), 8.27 (s, 1 H). 13C NMR (125
MHz, CDCl3): δ = 29.15, 35.40, 41.40, 112.47, 112.74, 118.73,
119.42, 121.85, 126.05, 126.77, 127.07, 127.16, 127.82, 128.72,
128.94, 129.01, 129.08, 129.63, 130.12, 132.46, 137.17, 139.80,
147.81, 152.69, 157.02. ESI-MS: m/z = 440 [M + H]+. HRMS: m/z
calcd for C29H22N5: 440.18697 [M + H]+; found: 440.18478.
2-[2-(6-Bromoquinolin-2-yl)-1-phenylethyl]malononitrile
(5c)
Pale grey solid; yield 75%; mp 118–120 °C. IR (KBr): νmax = 3422,
3032, 2901, 2853, 2252, 1592, 1488, 1451, 1324, 1190, 1054,
831, 771, 698 cm–1 1H NMR (500 MHz, CDCl3): δ = 3.48 (dd,
.
J = 4.8, 16.1 Hz, 1 H), 3.66 (dd, J = 9.7, 16.1 Hz, 1 H), 4.09 (m, 1
H), 5.05 (d, J = 5.0 Hz, 1 H), 7.24 (d, J = 5.3 Hz, 1 H), 7.33 (m, 3 H),
7.45 (d, J = 8.2 Hz, 2 H), 7.79 (dd, J = 2.2, 9.0 Hz, 1 H), 7.92 (d,
J = 8.8 Hz, 1 H), 7.95 (d, J = 2.1 Hz, 1 H), 7.99 (d, J = 8.3 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 28.52, 39.35, 44.02, 111.81,
112.28, 120.07, 122.46, 127.76, 127.86, 128.69, 128.92, 129.42,
130.40, 133.00, 135.61, 136.78, 145.90, 157.59. ESI-MS: m/z =
376 [M + H]+. HRMS: m/z calcd for C21H15N3Br: 376.0444 [M +
H]+; found: 376.0445.
(17) (a) Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Buriol, L.;
Machado, P. Chem. Rev. 2009, 109, 4140. (b) Cave, G. W. V.;
Raston, C. L.; Scott, J. L. Chem. Commun. 2001, 2159. (c) Cheng,
C.; Jiang, B.; Tu, S.-J.; Li, G. Green Chem. 2011, 13, 2107.
(18) (a) Meshram, H. M.; Ngeswara Rao, N.; Chandrasekhara Rao, L.;
Satish Kumar, N. Tetrahedron Lett. 2012, 53, 3963. (b) Meshram,
H. M.; SatishKumar, N.; Jagadeesh Babu, N.; Chandrasekhara
Rao, L.; Ngeswara Rao, N. Tetrahedron Lett. 2013, 54, 5941.
(19) Linday, M. E. Practical Introduction to Microbiology; E. and F. N.
Spon: U.K., 1962, 177.
2-{1-[3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2-(6-
methylpyridin-2-yl)ethyl}malononitrile (6f)
White solid; yield 70%; mp 89–91 °C. IR (KBr): νmax = 3447,
3138, 3066, 2926, 1592, 1500, 1453, 1410, 1340, 1228, 1152,
1070, 963, 843, 749, 686, 588, 550, 494 cm–1 1H NMR (300
.
(20) P Clinical And Laboratory Standards Institute. Performance
Standards for Antimicrobial Susceptibility Tests; Eighteen infor-
mational supplement M100-S18 (2008).
(21) CCDC number of the 4f is 952999. These data can be obtained
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or
from the Cambridge Crystallographic Data Centre (CCDC), 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223336033;
email: deposit@ccdc.cam.ac.uk].
MHz, CDCl3): δ = 2.51 (s, 3 H), 3.33 (m, 2 H), 4.25 (m, 1 H), 4.56
(d, J = 4.7 Hz, 1 H), 6.90 (d, J = 7.5 Hz, 1 H), 7.02 (d, J = 7.5 Hz, 1
H), 7.15 (t, J = 8.6 Hz, 1 H), 7.33 (t, J = 7.3 Hz, 1 H), 7.47 (m, 3 H),
7.56 (m, 2 H), 7.71 (d, J = 7.7 Hz,), 8.21 (s, 1 H). 13C NMR (75
MHz, CDCl3): δ = 21.35, 24.50, 29.08, 35.89, 40.93, 112.20,
112.46, 117.74, 119.22, 120.84, 121.85, 125.74, 126.83, 128.66,
129.31, 129.47, 137.08, 138.39, 139.69, 152.58, 155.85, 158.52.
ESI-MS: m/z = 422 [M + H]+. HRMS: m/z calcd for C27H23N5:
422.17755 [M + H]+; found: 422.17680.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1808–1814