Synthesis of Substituted Imidazo[1,2-a]Pyridin-3-yl-Acetic Acids by Multicomponent Condensation of 2-Aminopyridines with Arylglyoxals and Meldrum’s Acid

Article abstract of DOI:10.1007/s10593-019-02432-6

[Figure not available: see fulltext.] A simple and effective method for the synthesis of substituted imidazo[1,2-a]pyridin-3-yl-acetic acids has been developed based on the multicomponent condensation of 2-aminopyridines with arylglyoxals and Meldrum's acid.

Full text of DOI:10.1007/s10593-019-02432-6

DOI 10.1007/s10593-019-02432-6
Chemistry of Heterocyclic Compounds 2019, 55(2), 156–159
Synthesis of substituted imidazo[1,2-a]pyridin-3-yl-acetic acids by multi-
component condensation of 2-aminopyridines
with arylglyoxals and Meldrum's acid
Boris V. Lichitsky1, Аleksander D. Tretyakov1,2, Andrey N. Komogortsev1*,
Vitaly S. Mityanov1,2, Arkady А. Dudinov1, Mikhail M. Krayushkin1
1 N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences,
47 Leninsky Ave., Moscow 119991, Russia; e-mail: dna5@mail.ru
2 D. Mendeleev University of Chemical Technology of Russia,
9 Miusskaya Sq., Moscow 125047, Russia; е-mail: mityanovvs@yandex.ru
Submitted November 6, 2018
Accepted after revision January 22, 2019
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(2), 156–159
R
N
O
O
O
R
Ar
1. MeCN, , 4 h
N
OH
+
NH2
+
O
O
Ar
2. AcOH, , 4 h
N
HO
OH
51–74%
Me Me
O
R = H, Me
A simple and effective method for the synthesis of substituted imidazo[1,2-a]pyridin-3-yl-acetic acids has been developed based on the
multicomponent condensation of 2-aminopyridines with arylglyoxals and Meldrum's acid.
Keywords: 2-aminopyridines, arylglyoxals, imidazo[1,2-a]pyridines, imidazo[1,2-a]pyridin-3-yl-acetic acids, Meldrum's acid, multi-
component reaction.
Substituted imidazo[1,2-a]pyridines possess a broad
spectrum of biological activity and can be used as
antibacterial,1 antifungal,2 antiviral,3 and anti-inflammatory
drugs.4 Several studies have proposed the use of imidazo-
[1,2-a]pyridine derivatives for the treatment of cancer5 and
cardiovascular diseases,6 as well as Alzheimer's disease.7 In
medicine, imidazo[1,2-a]pyridin-3-yl-acetic acid derivatives
are most widely used, which include zolpidem 1 and
alpidem 2 (Fig. 1). Zolpidem 1 is used to treat short-term
insomnia, as well as some disorders of brain function.
Similar to classical benzodiazepine tranquilizers, the
hypnotic effect of zolpidem 1 is based on blocking
γ-aminobutyric acid receptors.8 Imidazo[1,2-a]pyridine
compounds, however, are more novel preparations with
fewer side effects.
of substituted 2-aminopyridines 4 with α-halo ketones 5
followed by the introduction of carboxymethyl function
into the structure of the resulting imidazo[1,2-a]pyridine
6.9 A significant disadvantage of this method is the low
total yield of the target product 3, an aspect inherent to a
multistage process (Scheme 1). Methods for the synthesis
of imidazo[1,2-a]pyridin-3-yl-acetic acid derivatives by the
use of nitroalkenes,10 N,N-dimethylglyoxylamide,11 or a
cross-coupling reaction12 have been proposed in the
literature. However, a common shortcoming of the
suggested approaches is the use of specific reagents that are
difficult to source, which significantly reduces the practical
value of the proposed methods.
Scheme 1
The main literature method for the synthesis of imidazo-
[1,2-a]pyridin-3-yl-acetic acids 3 consists of condensation
Figure 1. Medicines zolpidem 1 and alpidem 2.
0009-3122/19/55(2)-0156©2019 Springer Science+Business Media, LLC
156

Chemistry of Heterocyclic Compounds 2019, 55(2), 156–159
Scheme 2
Scheme 3
Thus, the development of new methods for the synthesis
and CO2 molecules by the action of AcOH, leading to the
formation of the final products 3a–n.
of imidazo[1,2-a]pyridin-3-yl-acetic acids 3 which allow to
obtain the target products in one synthetic stage with high
yields is an urgent task. Multicomponent reactions
represent an effective tool for approaching this problem,
the undoubted advantage of which is the possibility of
obtaining a wide range of products, avoiding the complex
sequence of multistage syntheses.13,14
Intermediate imidazo[1,2-a]pyridines 14a–n can be
isolated, however, it is difficult to fully characterize these
compounds due to their low stability. In this regard, the
optimal approach is a one-pot synthesis without isolation of
intermediates 14a–n. The undoubted advantage of this
method lies in the higher total yields of the target
compounds 3a–n, since in this case no losses at the stage of
isolation of imidazo[1,2-a]pyridines 14a–n are incurred.
Synthesized acids 3a–n are solid substances; their
structure was confirmed by NMR spectroscopy and high-
The literature describes a method for producing
substituted imidazo[1,2-a]pyridines
7 based on the
multicomponent condensation of 2-aminopyridines 4,
glyoxals 8, and β-dicarbonyl compounds 9 (Scheme 2).15
At the same time, we proposed a method for the
synthesis of condensed furylacetic acids 10 via the reaction
of heterocyclic enols 11 with arylglyoxals 8 and Meldrum's
acid (12) (Scheme 3).16 It could be assumed that the use of
Meldrum's acid (12) as an analog of β-dicarbonyl
compounds 9 would allow the synthesis of target imidazo-
[1,2-a]pyridin-3-yl-acetic acids 3.
1
resolution mass spectrometry. In the H NMR spectra of
the obtained compounds, the characteristic signals of
protons of the methylene fragment are present in the 4.06–
4.22 ppm range.
To conclude, we have developed a simple and efficient
method for the synthesis of substituted imidazo[1,2-a]-
pyridin-3-yl-acetic acids based on a multicomponent
condensation of 2-aminopyridines with arylglyoxals and
Meldrum's acid.
The purpose of this work was to develop a general
method for the synthesis of substituted [1,2-a]pyridin-3-yl-
acetic acids 3a–n based on the multicomponent
condensation of 2-aminopyridines 4a–c with arylglyoxals
8a–e and Meldrum's acid (12) (Scheme 4).
We have shown that heating 2-aminopyridines 4a–c
with arylglyoxals 8a–e and Meldrum's acid (12) in MeCN
and subsequent treatment with AcOH leads to the target
products 3a–n. It should be noted that the investigated
reaction proceeds in two stages. Initially, the reaction of the
components takes place in MeCN and leads to the
formation of adducts 13a–n, which then undergo
intramolecular cyclization to form imidazo[1,2-a]pyridines
14a–n. In the final stage of the process, the Meldrum's acid
fragment is transformed with the elimination of Me2CO
Experimental
1H and 13C NMR spectra were acquired on a Bruker
AM-300 spectrometer (300 and 75 MHz, respectively) in
DMSO-d6. Chemical shifts were assigned relative to the
residual solvent signal (2.52 ppm for 1H nuclei and
39.5 ppm for 13C nuclei). High-resolution mass spectra
were recorded on
a
Bruker micrOTOF-Q mass
spectrometer with electrospray ionization. Melting points
were determined on a Kofler bench.
The starting arylglyoxals 8а–е were obtained according
to
a
published method from the corresponding
acetophenones.17–19
Scheme 4
R1
R1
R1
N
N
R2
O
R2
O
O
O
+
N
–
AcOH
N
O
N
NH2
R2
MeCN
OH
R1
+
R2
+
O
O
, 4 h
51–74%
, 4 h
O
O
N
NH2
HO
OH
8a e
Me
Me
O
Me
Me
4a c
–
12
–
O
Me
14a–n
O
O
O
O
3a n
–
Me
13a n
4 a R1 = H, b R1 = 4-Me, c R1 = 5-Me;
–
8 a R2 = Ph, b R2 = 4-MeC6H4, c R2 = 4-MeOC6H4, d R2 = 4-ClC6H4, e R2 = 2-thienyl
3 a R1 = H, R2 = Ph; b R1 = 7-Me, R2 = Ph; c R1 = 6-Me, R2 = Ph; d R1 = H, R2 = 4-MeC6H4; e R1 = 7-Me, R2 = 4-MeC6H4;
f R1 = 6-Me, R2 = 4-MeC6H4; g R1 = H, R2 = 4-MeOC6H4; h R1 = 7-Me, R2 = 4-MeOC6H4; i R1 = H, R2 = 4-ClC6H4;
j R1 = 7-Me, R2 = 4-ClC6H4; k R1 = 6-Me, R2 = 4-ClC6H4; l R1 = H, R2 = 2-thienyl; m R1 = 7-Me, R2 = 2-thienyl; n R1 = 6-Me, R2 = 2-thienyl
157

Chemistry of Heterocyclic Compounds 2019, 55(2), 156–159
Synthesis of compounds 3a–n (General method). A
[6-Methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-
3-yl]acetic acid (3f). Yield 560 mg (67%), white powder,
mp 233–234°C (mp 227–229°C20). 1H NMR spectrum,
δ, ppm (J, Hz): 2.31 (3H, s, CH3); 2.33 (3H, s, CH3); 4.08
(2H, s, CH2); 7.15 (1H, d, J = 6.9, Н Ar); 7.27 (2H, d,
J = 8.4, Н Ar); 7.51 (1H, d, J = 6.9, Н Ar); 7.63 (2H, d,
J = 8.4, Н Ar); 8.20 (1H, s, Н Ar); 12.77 (1H, br. s, CO2H).
13C NMR spectrum, δ, ppm: 17.8; 20.8; 30.0; 113.9; 116.0;
121.0; 122.2; 127.4; 127.5; 129.2; 131.6; 136.7; 142.4;
142.9; 171.1. Found, m/z: 281.1289 [M+H]+. C17H17N2O2.
Calculated, m/z: 281.1285.
mixture of 2-aminopyridine 4a–c (3 mmol), arylglyoxal 8a–e
(3.3 mmol), and Meldrum's acid (12) (600 mg, 4.2 mmol)
in MeCN (8 ml) was heated under reflux for 4 h. The reaction
mixture was concentrated under reduced pressure, AcOH
(8 ml) was added to the residue. The obtained mixture was
heated for 4 h. AcOH was then evaporated under reduced
pressure, and the residue was recrystallized from i-PrOH.
The formed precipitate was filtered off and washed on the
filter with i-PrOH.
(2-Phenylimidazo[1,2-a]pyridin-3-yl)acetic
acid
(3a). Yield 560 mg (74%), brown powder, mp 240–241°C
(mp 231–233°C20). 1H NMR spectrum, δ, ppm (J, Hz): 4.15
(2H, s, CH2); 6.92–7.01 (1H, m, H Ar); 7.25–7.34 (1H, m,
H Ar); 7.35–7.43 (1H, m, H Ar); 7.44–7.54 (2H, m, H Ar);
7.55–7.66 (1H, m, H Ar); 7.73–7.82 (2H, m, H Ar); 8.41
(1H, d, J = 6.9, Н Ar); 12.88 (1H, br. s, CO2H). 13C NMR
spectrum, δ, ppm: 30.0; 112.1; 114.6; 116.6; 124.7; 125.0;
127.6; 127.8; 128.7; 134.3; 142.5; 143.9; 171.1. Found, m/z:
253.0977 [M+H]+. C15H13N2O2. Calculated, m/z: 253.0972.
(7-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)acetic acid
(3b). Yield 480 mg (60%), brown powder, mp 236–237°C.
1H NMR spectrum, δ, ppm (J, Hz): 2.37 (3H, s, СН3); 4.10
(2H, s, СН2); 6.81 (1H, d, J = 7.0, Н Ar); 7.31–7.41 (2H, m,
H Ar); 7.43–7.52 (2H, m, H Ar); 7.70–7.79 (2H, m, H Ar);
8.29 (1H, d, J = 7.0, Н Ar); 12.76 (1H, br. s, CO2H). 13C NMR
spectrum, δ, ppm: 20.8; 30.0; 113.9; 114.5; 114.8; 124.2; 127.4;
127.7; 128.6; 134.4; 135.1; 142.0; 144.3; 171.1. Found, m/z:
267.1137 [M+H]+. C16H15N2O2. Calculated, m/z: 267.1128.
(6-Methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)acetic acid
(3c). Yield 510 mg (64%), white powder, mp 230–231°C
[2-(4-Methoxyphenyl)imidazo[1,2-a]pyridin-3-yl]acetic
acid (3g). Yield 590 mg (70%), white powder, mp 220–
221°C (mp 219–222°C20). 1H NMR spectrum, δ, ppm
(J, Hz): 3.80 (3H, s, OCH3); 4.11 (2H, s, CH2); 6.90–6.99
(1H, m, H Ar); 7.06 (2H, d, J = 8.3, Н Ar); 7.22–7.33 (1H, m,
H Ar); 7.59 (1H, d, J = 9.0, Н Ar); 7.70 (2H, d, J = 8.3,
Н Ar); 8.38 (1H, d, J = 6.9, Н Ar); 12.92 (1H, br. s, CO2H).
13C NMR spectrum, δ, ppm: 30.1; 55.2; 111.9; 113.7; 114.1;
116.4; 124.5; 124.8; 126.7; 129.0; 142.4; 143.8; 158.9;
171.2. Found, m/z: 283.1066 [M+H]+. C16H15N2O3.
Calculated, m/z: 283.1077.
[2-(4-Methoxyphenyl)-7-methylimidazo[1,2-a]pyridin-
3-yl]acetic acid (3h). Yield 650 mg (73%), white powder,
mp 238–239°C (mp 234–236°C21). 1H NMR spectrum,
δ, ppm (J, Hz): 2.37 (3H, s, CH3); 3.80 (3H, s, OCH3); 4.06
(2H, s, CH2); 6.79 (1H, d, J = 7.0, Н Ar); 7.04 (2H, d,
J = 8.3, Н Ar); 7.34 (1H, s, Н Ar); 7.68 (2H, d, J = 8.3,
Н Ar); 8.25 (1H, d, J = 7.0, Н Ar); 12.65 (1H, br. s, CO2H).
13C NMR spectrum, δ, ppm: 20.8; 30.1; 55.2; 113.1; 114.1;
114.3; 114.6; 124.1; 126.9; 128.9; 134.9; 142.0; 144.1;
158.8; 171.2. Found, m/z: 297.1236 [M+H]+. C17H18N2O3.
Calculated, m/z: 297.1234.
1
(mp 223–224°C20). H NMR spectrum, δ, ppm (J, Hz):
2.32 (3H, s, CH3); 4.11 (2H, s, CH2); 7.15 (1H, d, J = 9.1,
Н Ar); 7.31–7.41 (1H, m, H Ar); 7.42–7.56 (3H, m, H Ar);
7.74 (2H, d, J = 7.6, Н Ar); 8.22 (1H, s, H Ar); 12.82 (1H,
br. s, CO2H). 13C NMR spectrum, δ, ppm: 17.8; 30.0;
114.2; 116.1; 121.2; 122.3; 127.4; 127.5; 127.6; 128.6;
134.5; 142.3; 143.0; 171.1. Found, m/z: 267.1126 [M+H]+.
C16H15N2O2. Calculated, m/z: 267.1128.
[2-(4-Methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetic
acid (3d). Yield 530 mg (66%), white powder, mp 240–
241°C (mp 230–232°C20). 1H NMR spectrum, δ, ppm (J, Hz):
2.36 (3H, s, CH3); 4.13 (2H, s, CH2); 6.88–7.02 (1H, m,
H Ar); 7.18–7.37 (3H, m, H Ar); 7.53–7.73 (3H, m, H Ar);
8.39 (1H, d, J = 6.9, Н Ar); 12.86 (1H, br. s, CO2H).
13C NMR spectrum, δ, ppm: 20.8; 30.0; 111.9; 114.2;
116.5; 124.5; 124.9; 127.7; 129.2; 131.5; 136.9; 142.6;
143.8; 171.1. Found, m/z: 267.1128 [M+H]+. C16H15N2O2.
Calculated, m/z: 267.1128.
[7-Methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-
3-yl]acetic acid (3e). Yield 610 mg (73%), white powder,
mp 229–230°C (mp 220–224°C21). 1H NMR spectrum,
δ, ppm (J, Hz): 2.36 (3H, s, CH3); 2.37 (3H, s, CH3); 4.08
(2H, s, CH2); 6.79 (1H, d, J = 7.0, Н Ar); 7.19–7.43 (3H,
m, H Ar); 7.66 (2H, d, J = 8.2, Н Ar); 8.24 (1H, d, J = 7.0,
Н Ar); 12.88 (1H, br. s, CO2H). 13C NMR spectrum, δ, ppm:
20.8; 30.0; 113.6; 114.3; 114.7; 124.1; 127.6; 129.2; 131.6;
134.9; 136.7; 142.1; 144.2; 171.2. Found, m/z: 281.1286
[M+H]+. C17H17N2O2. Calculated, m/z: 281.1285.
[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]acetic
acid (3i). Yield 500 mg (58%), brown powder, mp 230–
231°C (mp 223–225°C20). 1H NMR spectrum, δ, ppm
(J, Hz): 4.16 (2H, s, CH2); 6.89–7.07 (1H, m, H Ar); 7.23–
7.38 (1H, m, H Ar); 7.46–7.69 (3H, m, H Ar); 7.79 (2H, d,
J = 8.2, Н Ar); 8.40 (1H, d, J = 6.9, Н Ar); 12.94 (1H, br. s,
CO2H). 13C NMR spectrum, δ, ppm: 30.0; 112.2; 114.9;
116.7; 124.9; 125.0; 128.7; 129.4; 132.3; 133.2; 141.3;
144.0; 170.9. Found, m/z: 287.0587 [M+H]+.
C15H12ClN2O2. Calculated, m/z: 287.0582.
[2-(4-Chlorophenyl)-7-methylimidazo[1,2-a]pyridin-
3-yl]acetic acid (3j). Yield 490 mg (54%), brown powder,
1
mp 233–234 °C (mp 229–231 °C21). H NMR spectrum,
δ, ppm (J, Hz): 2.37 (3H, s, CH3); 4.11 (2H, s, CH2); 6.82
(1H, d, J = 6.9, Н Ar); 7.37 (1H, s, Н Ar); 7.53 (2H, d,
J = 8.4, Н Ar); 7.76 (2H, d, J = 8.4, Н Ar); 8.28 (1H, d,
J = 6.9, Н Ar); 12.81 (1H, br. s, CO2H). 13C NMR
spectrum, δ, ppm: 20.8; 30.0; 114.3; 114.6; 114.9; 124.2;
128.6; 129.2; 132.1; 133.4; 135.4; 140.8; 144.3; 171.0.
Found, m/z: 301.0752 [M+H]+. C16H14ClN2O2. Calculated,
m/z: 301.0738.
[2-(4-Chlorophenyl)-6-methylimidazo[1,2-a]pyridin-
3-yl]acetic acid (3k). Yield 580 mg (64%), brown powder,
1
mp 230–231 °C (mp 222–224 °C20). H NMR spectrum,
δ, ppm (J, Hz): 2.32 (3H, s, CH3); 4.11 (2H, s, CH2); 7.16
(1H, d, J = 9.2, Н Ar); 7.45–7.61 (3H, m, H Ar); 7.77 (2H,
158

Chemistry of Heterocyclic Compounds 2019, 55(2), 156–159
4. Rupert, K. C.; Henry, J. R.; Dodd, J. H.; Wadsworth, S. A.;
d, J = 8.2, Н Ar); 8.22 (1H, s, Н Ar); 12.88 (1H, br. s,
CO2H). 13C NMR spectrum, δ, ppm: 17.8; 30.0; 114.6;
116.1; 121.4; 122.3; 127.8; 128.6; 129.2; 132.1; 133.4;
141.1; 143.0; 171.0. Found, m/z: 301.0752 [M+H]+.
C16H14ClN2O2. Calculated, m/z: 301.0738.
Cavender, D. E.; Olini, G. C.; Fahmy, B.; Siekierka, J.
Bioorg. Med. Chem. Lett. 2003, 13, 347.
5. Hamdouchi, C.; Zhong, B.; Mendoza, J.; Collins, E.;
Jaramillo, C.; De Diego, J. E.; Robertson, D.; Spencer, C. D.;
Anderson, B. D.; Watkins, S. A.; Zhang, F.; Brooks, H. B.
Bioorg. Med. Chem. Lett. 2005, 15, 1943.
6. Tully, W. R.; Gardner, C. R.; Gillespie, R. J.; Westwood, R.
J. Med. Chem. 1991, 34, 2060.
[2-(Thiophen-2-yl)imidazo[1,2-a]pyridin-3-yl]acetic
acid (3l). Yield 470 mg (61%), black powder, mp 234–
1
235°C. H NMR spectrum, δ, ppm (J, Hz): 4.22 (2H, s,
7. Goodacre, S. C.; Street, L. J.; Hallett, D. M.; Crawforth, J. M.;
Kelly, S.; Owens, A. P.; Blackaby, W. P.; Lewis, R. T.;
Stanley, J.; Smith, A. J.; Ferris, P.; Sohal, B.; Cook, S. M.;
Pike, A.; Brown, N.; Wafford, K. A.; Marshall, G.; Castro, J. L.;
Atack, J. R. J. Med. Chem. 2006, 49, 35.
CH2); 6.91–7.01 (1H, m, H Ar); 7.13–7.21 (1H, m, H Ar);
7.22–7.35 (1H, m, H Ar); 7.39–7.44 (1H, m, Н Ar); 7.52–
7.63 (2H, m, H Ar); 8.42 (1H, d, J = 6.9, Н Ar); 12.89 (1H,
br. s, CO2H). 13C NMR spectrum, δ, ppm: 29.8; 112.2; 113.8;
116.3; 124.2; 124.9; 126.1; 128.1; 137.3; 137.6; 143.8;
170.7. Found, m/z: 259.0546 [M+H]+. C13H11N2O2S.
Calculated, m/z: 259.0536.
8. Lemmer, B. Physiol. Behav. 2007, 90, 285.
9. Kaplan, J.-P.; George, P. US Patent 4382938; Chem. Abstr.
1982, 97, 92280.
10. Nair, D. K.; Mobin, S. M.; Namboothiri, I. N. N. Org. Lett.
2012, 14, 4580.
[7-Methyl-2-(thiophen-2-yl)imidazo[1,2-a]pyridin-3-yl]-
acetic acid (3m). Yield 460 mg (56%), brown powder,
1
11. Marcinkowska, M.; Kołaczkowski, M.; Kaminski, K.; Bucki, A.;
Pawłowski, M.; Siwek, A.; Karcz, T.; Mordyl, B.; Starowicz, G.;
Kubowicz, P.; Pekala, E.; Wesołowska, A.; Samochowiec, J.;
Mierzejewski, P.; Bienkowski, P. Eur. J. Med. Chem. 2016, 124, 456.
12. Su, H.; Wang, L.; Rao, H.; Xu, H. Org. Lett. 2017, 19, 2226.
13. Ruijter, E.; Scheffelaar, R.; Orru, R. V. A. Angew. Chem., Int.
Ed. 2011, 50, 6234.
mp 240–241°C. H NMR spectrum, δ, ppm (J, Hz): 2.36
(3H, s, CH3); 4.18 (2H, s, CH2); 6.82 (1H, d, J = 7.0, Н Ar);
7.12–7.20 (1H, m, H Ar); 7.34 (1H, s, Н Ar); 7.38–7.41
(1H, m, Н Ar); 7.55–7.60 (1H, m, Н Ar); 8.30 (1H, d,
J = 7.0, Н Ar); 12.88 (1H, br. s, CO2H). 13C NMR
spectrum, δ, ppm: 20.8; 29.8; 113.2; 114.6; 123.9; 124.1;
125.9; 128.0; 135.5; 137.0; 137.8; 144.2; 170.8. Found, m/z:
273.0698 [M+H]+. C14H13N2O2S. Calculated, m/z: 273.0692.
[6-Methyl-2-(thiophen-2-yl)imidazo[1,2-a]pyridin-3-yl]-
acetic acid (3n). Yield 420 mg (51%), brown powder, mp 236–
237°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.31 (3H, s, CH3);
4.18 (2H, s, CH2); 7.12–7.19 (2H, m, H Ar); 7.37–7.41 (1H,
m, H Ar); 7.49 (1H, d, J = 9.2, Н Ar); 7.53–7.60 (1H, m,
H Ar); 8.24 (1H, s, Н Ar); 12.82 (1H, br. s, CO2H). 13C NMR
spectrum, δ, ppm: 17.8; 29.8; 113.5; 115.7; 121.4; 122.2; 123.9;
125.8; 127.8; 128.0; 137.2; 137.8; 142.9; 170.7. Found, m/z:
273.0696 [M+H]+. C14H13N2O2S. Calculated, m/z: 273.0692.
14. Rotstein, B. H.; Zaretsky, S.; Rai, V.; Yudin, A. K. Chem.
Rev. 2014, 114, 8323.
15. Peshkov, V. A.; Peshkov, A. A.; Pereshivko, O. P.; Van
Hecke, K.; Zamigaylo, L. L.; Van der Eycken, E. V.;
Gorobets, N. Yu. ACS Comb. Sci. 2014, 16, 535.
16. Gorbunov, Yu. O.; Lichitsky, B. V.; Komogortsev, A. N.;
Mityanov, V. S.; Dudinov, A. A.; Krayushkin, M. M. Chem.
Heterocycl. Compd. 2018, 54, 692. [Khim. Geterotsikl.
Soedin. 2018, 54, 692.]
17. Wang, P.; Tao, W.-J.; Sun, X.-L.; Liao, S.; Tang, Y. J. Am.
Chem. Soc. 2013, 135, 16849.
18. Kutsunugi, Y.; Kawai, S.; Nakashima, T.; Kawai, T. New
J. Chem. 2009, 33, 1368.
19. Tafelska-Kaczmarek, A.; Prewysz-Kwinto, A.; Skowerski, K.;
Pietrasiak, K.; Kozakiewicz, A.; Zaidlewicz, M. Tetrahedron:
Asymmetry 2010, 21, 2244.
References
1. Rival, Y.; Grassy, G.; Michel, G. Chem. Pharm. Bull. 1992,
40, 1170.
2. Fisher, M. H.; Lusi, A. J. Med. Chem. 1972, 15, 982.
3. Hamdouchi, C.; Blas, J.; del Prado, M.; Gruber, J.; Heinz, B. A.;
Vance, L. J. Med. Chem. 1999, 42, 50.
20. Lange, J.; Karolak-Wojciechowska, J.; Wejroch, K.; Rump, S.
Acta Pol. Pharm. 2001, 58, 43.
21. Yang, R. F.; Li, Yu. F.; Li, Yo. Z.; Zhao, N.; Yun, L. H.;
Qin, J. J.; Feng, Z. Y.; Zhang, Y. Z. EP Patent 2586780.
159