Functionalized Diphenyl-Imidazolo-Pyrimidines

Article abstract of DOI:10.1002/jhet.3044

Synthesis of novel imidazopyrimidines has been reported. These systems contain carbethoxy group at C5 of pyrimidine and bromine at C2 of imidazole. Reactivity of these two groups was studied, and the mobility of the carbethoxy group was confirmed by tracing the formation of the amide product and also with isolation of alkyl analogs while bromine did not react with N-nucleophiles under various reaction conditions employed. New conjugates combine the properties of dihydropyrimidine and imidazole and therefore lead to the expansion of original properties of each heterocyclic moiety within the system.

Full text of DOI:10.1002/jhet.3044

Month 2017
Functionalized Diphenyl-Imidazolo-Pyrimidines
a
a
b
c
c
Pavel P. Lyubashov, Vyacheslav M. Povstyanoy, Andrey A. Krysko, Alexander Plotkin, Ilene Lovett,
a
c
Mykhailo V. Povstyaniy, and Iryna O. Lebedyeva *
a
Department of Chemical Technology and Food Safety, Kherson National Technical University, Berislavs’ke Highway 24,
Kherson 73008, Ukraine
b
Department of Medicinal Chemistry, A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of
Ukraine, Lustdorfskaya St., 86, Odessa 65080, Ukraine
c
Department of Chemistry and Physics, Augusta University, 1120 15th Street, Augusta, GA 30912, USA
*
E-mail: ilebedyeva@augusta.edu
Received August 20, 2017
DOI 10.1002/jhet.3044
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
Synthesis of novel imidazopyrimidines has been reported. These systems contain carbethoxy group at C5
of pyrimidine and bromine at C2 of imidazole. Reactivity of these two groups was studied, and the
mobility of the carbethoxy group was confirmed by tracing the formation of the amide product and also with
isolation of alkyl analogs while bromine did not react with N-nucleophiles under various reaction conditions
employed. New conjugates combine the properties of dihydropyrimidine and imidazole and therefore lead to
the expansion of original properties of each heterocyclic moiety within the system.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
historically known for their antifungal [19] and antibacterial
properties [20]. Substituted imidazoles have been presented
on pharmaceutical market with ketocanazole 4 [21],
metronidazole 5 [22], miconazole 6 [23], and clotrimazole
7 [24] (Fig. 2). In addition, imidazole is a part of histidine,
a common building block of proteins [25], bioactive
peptides [26], and natural alkaloids [27,28].
Heterocycles have been known for providing important
building blocks for natural bioactive compounds [1,2] and
pharmaceuticals [3,4]. Dihydropyrimidines (DHPMs),
synthesized via Biginelli reaction, proved to be useful
for both anticancer, for example, Monastrol (1; Fig. 1)
[
3
3,5] and antihypertensive agents, for example, SQ
2547 (2; Fig. 1) [6,7]. Monastrol 1 [3,8–10], the
Combination of pyrimidines and imidazoles with the
possibility of their further functionalization is of
considerable practical interest because of the novelty of
this approach and the therapeutic potential of the new
bisheterosystems. Our group has previously worked with
creating bisconjugates through combination of DHPMs
with theophylline [29]. This approach led to formation of
intermediates with two reactive centers. Difunctionalized
intermediates formed several products that included ring
closure and pyrimidine ring restructuring under
conditions of high pressure and temperatures in presence
of N-nucleophiles. Our previous work on creation of
bisheterocycles [29] has been summarized in Scheme 1.
In this work, the reaction of the potassium salt 2-bromo-
4,5-diphenyl-1H-imidazole 15 with 2-oxo-4-aryl-5-
ethoxycarbonyl-6-bromomethylpyrimidines 16 along
with further reaction ability of the newly formed
imidazopyrimidines has been investigated. It is anticipated
that the combination of substituted imidazoles and
DHPMs will lead to an increase and diversification of the
biological activity of novel conjugates.
inhibitor of mitotic kinesin Eg5 [10], is one of
several successful examples when DHPMs reached
pharmaceutical market. There are also a number of drug
candidates that exhibit calcium channel modulation [11],
inhibition of kinases and G protein–coupled receptors
[12], and DNA intercalation [13] types of activities that
are currently being studied on in vitro and in vivo
models. Besides providing pyrimidines as small
molecules for compound libraries, the three-component
Biginelli reaction has proven to be a convenient
gateway to complex constructs of natural alkaloids such
as crambescidin 800 (3; Fig. 1) [1], Monanchora
arbuscula, Clathria calla [14], (+)-ptilomycalin A [15],
batzelladine F [16], and analogs [17].
Heterocycles are represented with many families of
bioactive compounds, and to explore the possibility of
enhancement of biological properties for pyrimidines, we
considered creating a combination of DHPMs with
diphenylsubstituted imidazoles. Imidazoles [18] have been
©
2017 Wiley Periodicals, Inc.

P. P. Lyubashov, V. M. Povstyanoy, A. A. Krysko, A. Plotkin,
I. Lovett, M. V. Povstyaniy, and I. O. Lebedyeva
Vol 000
give 14, which after the addition of KOH formed
potassium salt 15 in situ. Product 17 (Scheme 2) was
synthesized in 74–81% yields by coupling DHPM 16 and
potassium
2-bromo-4,5-diphenyl-1H-imidazole
in
DMF under reflux. Precipitated products 17a–f are
bisheterocycles that contain carbethoxy group and the
bromine atom.
A number of aliphatic and substituted benzyl amines
were then used to explore possibilities for the substitution
of carbethoxy and bromine groups of 17 to take place
followed by subsequent cyclization. The aim was to react
1
7a with a number of N-nucleophiles (Scheme 3) to
explore whether the bromine atom at imidazole moiety
would be substituted with the amino group with the
possibility of the following step of the 7-membered ring
Figure 1. Bioactive DHPMs, products of Biginelli reaction.
cyclization of
a product into a substituted 1H-
imidazo[1,2-a]pyrimido[5,4-e][1,3]diazepine-2,5(3H,6H)-
dione since our previous studies confirmed the possibility
of formation of such products [29]. To facilitate the
reaction, the following reaction conditions were used: (i)
heating of 17a and N-nucleophiles at DMF for 6 h and
(
ii) heating of reagents in alcohol in the high-pressure
tube for 12 h. In this work, the formation of the product
9 was detected at 24.7% (Fig. S4). The product with
1
the molecular mass of 588.0 [M + 1] was detected by the
Scheme 2. Synthesis of pyrimidoimidazoles 17a–f.
Figure 2. Imidazole-based drugs.
RESULTS AND DISCUSSION
DHPMs 16 are reactive compounds functionalized in the
5-carbethoxy and 6-bromomethyl positions. Close
proximity of two reactive centers in the pyrimidine ring
facilitates reactions of cyclization with ethanol as a
leaving group forming 5-, 6-, and 7-membered ring
systems [29,30]. 4,5-Diphenylimidazole was constructed
by condensation of benzoin 12 with formamide to form
1
3. Diphenylimidazole 13 was then brominated at C2 to
Scheme 1. Synthesis of 1,3-diazepinopyrinopyrimidines 11.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Functionalized Diphenyl-Imidazolo-Pyrimidines
Scheme 3. Synthesis of products 18 and 19.
LC/MS after the 12-h reaction of 17a with
monoethanolamine in EtOH in a sealed tube. The
structure of similar amide products was previously
confirmed via X-ray analysis [29]. Reorganization of the
ester moiety up to 30% also took place when the
reaction with N-nucleophiles was conducted for 12 h in
a sealed tube using MeOH as the solvent. Structure of
the product 18 was confirmed with X-ray analysis
broad singlet at around 5.13–5.20 ppm. The signal of an
NH group was identified at around 7.69–7.87 ppm.
Signals of the aromatic moiety of DHPM as well as the
signals for diphenylimidazole part of the molecule were
visible at the aromatic area between 6.43 and 7.89 ppm.
Additional signals of Me group for 17b and OMe group
for 17c were observed as singlets at 2.21 and 3.69 ppm
correspondingly (Fig. 4).
13
(
Fig. 4). Overall, the ester group of 17 has been more
C signals for compounds 17a–f were identified with the
prone to structural modifications much easier than the
bromine atom at the imidazole ring of 17 even under
harsh reaction conditions. The fact that imidazole is
substituted with two phenyl groups and can sterically
hinder interactions with the nucleophiles may partially
explain the unexpectedly low reactivity of the halogen
atom at the imidazole ring. Structure of 17a has been
confirmed with X-ray analysis (Fig. 3).
signals of the ethyl group of DHPM between 14.4 ppm for
CH and 60.6–60.8 ppm for CH . NMe group gave a signal
3
2
at around 31.0–31.2 ppm. CH of DHPM was observed at
around 52.1–52.3 ppm. NH–C=O group of DHPM was
observed at 145.3–146.2 ppm, and the carbon peak for the
CO group of the ester part of DHPM was observed
between 153.3 and 153.6 ppm. Two quaternary carbons of
the –C=C– moiety were observed at 138.1 ppm and
between 106.4 and 108.0 ppm correspondingly. Signals of
aromatic carbons for both DHPM and diphenylimidazole
were observed at the aromatic area between 121.0 and
140.4 ppm. Imidazole moiety was also characterized with
the peak for the C–Br at around 121.2–121.7 ppm and two
signals for quaternary carbons at 133 and 127 ppm. Signals
for the 4-Me-Ar for 17b and 4-OMe-Ar of 17c were
identified at 21.1 and 55.5 ppm respectfully.
1
H NMR spectra for compounds of type 17a–f revealed
signals of the ethyl group of DHPM moiety as a triplet
at around 1.14–1.16 ppm and a quartet of a CH group at
2
around 5.13–5.20 ppm. The NMe group was detected
at around 2.68–2.71 as a singlet. CH group of DHPM at
2
C6 was identified with two doublet peaks: a broad singlet
or a multiplet signal at around 3.96–4.04 ppm. CH group
of DHPM was presented either with a doublet or with a
Figure 3. Molecular structure of 17 according to the X-ray analysis.
Figure 4. Molecular structure of 18 according to X-ray analysis.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P. P. Lyubashov, V. M. Povstyanoy, A. A. Krysko, A. Plotkin,
I. Lovett, M. V. Povstyaniy, and I. O. Lebedyeva
Vol 000
The DHPM core acquired boat conformation and the N(1)
and C(2) atoms formed the 0.24(1) and 0.46(1) Å angles
with other atoms within the pyrimidine core. The precision
of measurements was 0.03 Å, and the parameters of the
DHPM core were S = 0.54, θ = 71.6°, ψ = 12.5°, which is
common for compounds with similar structure [31] (see
Supplementary Information for more details).
Analysis of the X-ray data for 18 revealed that the
DHPM cycle acquires boat conformation with the
deviation of N(1) и C(2) atoms from the other atoms
in the ring on 0.26(2) and 0.44(2) Å, correspondingly
crystals of 17 (CCDC 1572960) and 18 (CCDC 1572959)
was performed with an “Xcalibur 3” diffractometer
(graphite-monochromated Mo-Kα radiation, λ = 0.71073)
at 100 K.
Synthesis of 4,5-diphenyl-1H-imidazole 13.
Benzoin
(212 g, 1.0 mol) was dissolved in 350 mL of ethanol, and
the excess of formamide was added to the solution. The
mixture was then kept under reflux for 4 h. After the
reaction mixture cooled to the room temperature, the
precipitate was filtered off and washed with MeOH.
Product 13 was recrystallized from DMF and isolated as
white solid in 95% (209 g).
(the precision of measurements is 0.02 Å, the
parameters of the cycle are S = 0.53, θ = 75.0°,
ψ = 9.4°), which corresponds with the parameters for
the cycles of this type [31] (see Supporting
Information for more details).
Synthesis of 2-bromo-4,5-diphenyl-1H-imidazole 14.
,5-Diphenyl-1H-imidazole 13 (22 g, 0.1 mol) was
suspended in chloroform (250 mL). The mixture was
4
then heated up to 40°C, and Br (8.5 mL) was slowly
2
added dropwise. In 1.5 h, the color of the reaction
mixture turned dark red. The reaction mixture was stirred
for additional 1.5 h at 40°C. After that the reaction
mixture was taken to dryness under vacuum. Product 14
was purified by recrystallization from i-PrOH/H2O 9/1
and isolated as yellow solid in 60% yield (17.9 g).
CONCLUSION
A method towards functionalized pyrimidoimidazoles
has been developed. With this approach, two
biologically active systems have been combined to
synthesize a library of substituted pyrimidoimidazole
heterosystems 17a–f in high yields. Further on, the
reactivity of these systems has been tested. It has been
identified that the 2-bromo 4,5-diphenylimidazole part
of the heterosystem was not as highly reactive as the
halogens at C8 of the previously reported theophylline
analogs [29]. Carbethoxy group participated in the alkyl
group rearrangement and also some nucleophile
substitution depending on the reaction conditions. This
work will be translated further on multifunctional
heterocycles to investigate the reactivity and also the
biological activity potential of the polycyclic
heterosystems, which contain pyrimidine fragment.
Synthesis of 2-bromo-4,5-diphenylimidazolopyrimidines
17.
To the solution of 2-bromo-4,5-diphenyl-1H-
imidazole 14 (2.99 g, 0.01 mol) in DMF (10 mL), KOH
(0.56 g, 0.01 mol) was added in H O (2 mL) at room
2
temperature, and the mixture was then stirred for 3 h.
Correspondingly, 6-bromomethyl DHPM 16 was then
added to the mixture that contained potassium 2-bromo-
4,5-diphenyl-1H-imidazole 15 formed in situ and the
mixture was kept under reflux for 60–90 min. After the
reaction mixture cooled to room temperature, it was
poured into cold deionized water (100 mL), and the
precipitated product 17 was filtered off and washed
with cold MeOH. Product 17 was purified with
recrystallization from i-PrOH/H O 9/1 and isolated as
2
white solid with the yields of 74–81%.
Ethyl 6-((2-bromo-4,5-diphenyl-1H-imidazol-1-yl)methyl)-1-
methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (17a).
EXPERIMENTAL
1
13
H NMR spectra were recorded at 400 MHz, and
C
NMR spectra were recorded at 100 MHz at room
temperature using either CDCl or DMSO-d as solvents.
3
6
Chemical shifts are reported in ppm relative either to
TMS as internal standard or to the residual solvent peak.
The following abbreviations are used to describe spin
multiplicity: s (singlet), d (doublet), t (triplet), q (quartet),
m (multiplet), brs (broad singlet), and dd (doublet of
doublets). The LC/MS was recorded on Agilent 1100
1
White solid, yield 74%, mp 180°C; H NMR (400 MHz,
DMSO-d ): δ = 1.15 (t, J = 7.1 Hz, 3 H), 2.71 (s, 3 H),
.99–4.04 (m, 2 H), 4.74 (brs, 1 H), 5.16 (d, J = 17.1 Hz,
H), 6.42 (d, J = 17.1 Hz, 1 H), 7.10–7.12 (d,
6
3
1
with LC/MSD SLMobile Phase: A-H O + 0.1%HCOOH;
2
B-MeCN
+
0.1HCOOH. Elemental analysis was
performed on PerkinElmer analyzer 2400 CHNS/O Series
II System (100 V). X-ray diffraction analysis of single
J = 8.0 Hz, 2 H), 7.16–7.14 (d, J = 8.0 Hz, 1 H),
7.17–7.22 (m, 3 H), 7.25–7.28 (m, 4 H), 7.33 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Functionalized Diphenyl-Imidazolo-Pyrimidines
J = 7.3 Hz, 2 H), 7.42 (t, J = 7.6 Hz, 2 H), 7.50 (t,
J = 7.3 Hz, 1 H), 7.78 (s, 1 H); C (100 MHz,
Ethyl 6-((2-bromo-4,5-diphenyl-1H-imidazol-1-yl)methyl)-4-
4-chlorophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
1
3
(
5
-carboxylate (17d).
DMSO-d ): δ = 164.8, 153.6, 145.7, 143.4, 138.1, 133.9,
6
1
1
1
31.4, 130.8, 129.8, 129.8, 129.3, 129.0, 128.7, 127.9,
27.2, 126.6, 126.3, 121.7, 107.7, 60.6, 52.1, 44.0, 31.1,
4.4. Anal. Calcd for C H BrN O : C, 63.05; H, 4.76;
3
0
27
4 3
N, 9.80. Found: C, 63.41; H, 4.42; N, 9.91.
Ethyl 6-((2-bromo-4,5-diphenyl-1H-imidazol-1-yl)methyl)-1-
methyl-2-oxo-4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (17b).
1
White solid, yield 74%, mp 193–195°C; H NMR (400 MHz,
DMSO-d ): δ = 1.14 (t, J = 7.1 Hz, 3 H), 2.68 (s, 3 H), 3.96–
6
(
d, J = 4.4 Hz, 1 H), 5.18 (d, J = 17.1 Hz,
4
.03 (m, 2 H), 4.70
1
H), 6.44 (d, J = 17.1 Hz, 1 H), 7.12–7.14 (d, J = 8.0 Hz,
H), 7.16–7.21 (m, 3 H), 7.25 (d, J = 4.0 Hz, 2 H), 7.34–
.31 (m, 4 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.3 Hz,
2
7
1
H), 7.87 (d, J = 3.9 Hz, 1 H); 13
C (100 MHz, DMSO-d6):
1
White solid, yield 81%, mp 220–223°C; H NMR
δ = 164.7, 153.4, 146.2, 142.3, 138.1, 133.8, 132.5, 131.2,
130.9, 129.8, 129.7, 129.3, 128.9, 128.7, 128.6, 127.2,
126.3, 121.7, 107.0, 60.7, 52.1, 44.0, 31.1, 14.4. Anal. Calcd
for C H BrClN O : C, 59.47; H, 4.33; N, 9.25. Found: C,
(
400 MHz, DMSO-d ): δ = 1.16 (t, J = 7.1 Hz, 3 H),
6
2
5
7
7
2
7
.23 (s, 3 H), 2.71 (s, 3 H), 4.01 (brs, 2 H), 4.72 (s, 1 H),
.13 (d, J = 12.0 Hz, 2 H), 6.40 (d, J = 12.0 Hz, 1 H),
.00 (d, J = 8.0 Hz, 2 H), 7.06 (d, J = 8.0 Hz, 2 H),
.14–7.21 (m, J = 6.8 Hz, 2 H), 7.26 (d, J = 4.0 Hz,
H), 7.33 (d, J = 4.0 Hz, 2 H), 7.42 (t, J = 5.4 Hz, 2 H),
30
26
4 3
59.85; H, 4.12; N, 9.47.
Ethyl 6-((2-bromo-4,5-diphenyl-1H-imidazol-1-yl)methyl)-4-
(4-bromophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (17e).
1
3
.49 (d, J = 6.3 Hz, 1 H), 7.69 (s, 1 H); C (100 MHz,
DMSO-d ): δ = 164.9, 153.6, 145.5, 140.4, 138.1, 137.1,
6
1
1
1
33.9, 131.4, 130.8, 129.8, 129.7, 129.5, 129.3, 128.7,
26.5, 126.3, 121.7, 107.8, 60.6, 52.3, 44.0, 31.1, 21.1,
4.4. Anal. Calcd for C H BrN O : C, 63.59; H, 4.99;
3
1
29
4 3
N, 9.57. Found: C, 63.24; H, 4.76; N, 9.32.
Ethyl 6-((2-bromo-4,5-diphenyl-1H-imidazol-1-yl)methyl)-4-
(
4-methoxyphenyl)-1-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (17c).
1
White solid, yield 78%, mp 205–207°C; H NMR
(
400 MHz, DMSO-d ): δ = 1.15 (t, J = 7.1 Hz, 3 H),
6
2.69 (s, 3 H), 4.01 (q, J = 6.8 Hz, 2 H), 4.72 (brs, 1 H),
5.15 (d, J = 17.1 Hz, 1 H), 6.43 (d, J = 17.1 Hz, 1 H),
7.08 (d, J = 8.3 Hz, 2 H), 7.13–7.21 (m, 3 H), 7.25 (d,
J = 7.3 Hz, 2 H), 7.33 (d, J = 7.3 Hz, 2 H), 7.39–7.51
13
(
m, 5 H), 7.81 (s, 1 H); C (100 MHz, CDCl3):
δ = 164.6, 153.4, 146.2, 142.7, 138.1, 133.8, 131.8,
1
White solid, yield 77%, mp 223–224°C; H NMR
400 MHz, DMSO-d ): δ = 1.15 (t, J = 7.1 Hz, 3 H),
2
(
(
(
1
1
31.3, 130.9, 129.8, 129.7, 129.3, 128.9, 129.6, 127.2,
26.3, 121.2, 121.1, 107.0, 60.7, 52.1, 44.0, 31.1, 14.4.
(
6
.69 (s, 3 H), 3.69 (s, 3 H), 3.99 (m, 2 H), 4.67
Anal. Calcd for C H Br N O : C, 55.40; H, 4.03; N,
30
26
2 4 3
d, J = 3.4 Hz, 1 H), 5.15 (d, J = 17.1 Hz, 1 H), 6.43
d, J = 17.1 Hz, 1 H), 6.81 (d, J = 8.8 Hz, 2 H), 7.00
d, J = 8.8 Hz, 2 H), 7.12–7.18 (m, 3 H), 7.25 (d,
J = 7.3 Hz, 2 H), 7.33 (d, J = 4.0 Hz, 2 H), 7.41
t, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.1 Hz, 1 H), 7.75
8
.61. Found: C, 55.12; H, 4.00; N, 8.72.
Ethyl 6-((2-bromo-4,5-diphenyl-1H-imidazol-1-yl)methyl)-1-
methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (17f).
(
(
13
brs, 1 H); C (100 MHz, CDCl ): δ = 164.8, 159.0,
3
1
53.5, 145.3, 138.1, 135.5, 133.8, 131.4, 130.8, 129.8,
1
29.7, 129.3, 128.6, 127.8, 127.2, 126.2, 121.6,
114.2, 108.0, 60.5, 55.5, 52.1, 44.0, 31.0, 14.4. Anal.
Calcd for C H BrN O : C, 61.90; H, 4.86; N, 9.31.
31
29
4 4
Found: C, 61.74; H, 4.56; N, 9.48.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P. P. Lyubashov, V. M. Povstyanoy, A. A. Krysko, A. Plotkin,
I. Lovett, M. V. Povstyaniy, and I. O. Lebedyeva
Vol 000
1
White solid, yield 80%, mp 204–206°C; H NMR
[12] Schneider, P.; Stutz, K.; Kasper, L.; Haller, S.; Reutlinger,
M.; Reisen, F.; Geppert, T.; Schneider, G. Pharmaceuticals 2011, 4,
(
(
400 MHz, DMSO-d ): δ = 1.16 (t, J = 7.1 Hz, 3 H), 2.69
s, 3 H), 4.04 (q, J = 7.2 Hz, 2 H), 4.85 (d, J = 3.9 Hz,
H), 5.20 (d, J = 17.1 Hz, 1 H), 6.48 (d, J = 17.1 Hz,
H), 7.13–7.21 (m, 3 H), 7.25 (d, J = 6.3 Hz, 2 H), 7.32
d, J = 7.8 Hz, 2 H), 7.42 (t, J = 7.6 Hz, 2 H), 7.50 (t,
J = 7.3 Hz, 1 H), 7.58 (d, J = 4.9 Hz, 2 H), 7.94 (s, 1 H),
.01 (d, J = 3.9 Hz, 1 H), 8.08–8.11 (m, 1 H);
100 MHz, DMSO-d ): δ = 164.5, 153.3, 148.3, 147.0,
6
1
236.
13] Lebedyeva, I. A.; Povstyanoy, M. V.; Zubatyuk, R. I.;
Shishkin, O. V.; Ihmels, H. Acta Crystallogr Sect E 2010, 66, o1762.
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20] Sutherland, L.; Singleton, J.; Sessions, J.; Hanauer, S.; Krawitt,
[
1
1
(
[
[
13
8
C
[
(
6
5
1
1
1
45.5, 138.1, 133.8, 133.1, 131.3, 130.9, 130.8, 129.9,
29.7, 129.3, 128.7, 127.2, 126.3, 123.0, 121.7, 121.4,
06.4, 60.8, 52.1, 44.0, 31.2, 14.4. Anal. Calcd for
[
[
C H BrN O : C, 58.45; H, 4.25; N, 11.36. Found: C,
30
26
5 5
[
58.29; H, 4.36; N, 11.68.
E.; Rankin, G.; Summers, R.; Mekhjian, H.; Greenberger, N.; Kelly, M.
Gut 1991, 32, 1071.
[
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet