New Multicomponent Synthesis of Functionalized Nitriles and Esters of 6-Alkylsulfanyl-1,4-dihydronicotinic Acids

Article abstract of DOI:10.1134/S1070363220030068

Abstract: The multicomponent condensation of malononitrile, hydrogen sulfide, aryl orhetaryl aldehydes, 1,3-dicarbonyl compounds and alkylating reagents affordedfunctionalized nitriles and esters of 6-alkylsulfanyl-1,4-dihydronicotinicacids, their aromatic analogues and 1,4-dihydrothieno[2,3-b]pyridines.

Full text of DOI:10.1134/S1070363220030068

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 3, pp. 357–366. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Obshchei Khimii, 2020, Vol. 90, No. 3, pp. 371–381.
New Multicomponent Synthesis of Functionalized Nitriles
and Esters of 6-Alkylsulfanyl-1,4-dihydronicotinic Acids
I. N. Kalashnika and V. D. Dyachenkoa,*
a T. Shevchenko Lugansk National University, Lugansk, 91011 Ukraine
*e-mail: dyachvd@mail.ru
Received December 2, 2018; revised December 2, 2018; accepted December 6, 2018
Abstract—The multicomponent condensation of malononitrile, hydrogen sulfide, aryl or hetaryl aldehydes,
1,3-dicarbonyl compounds and alkylating reagents afforded functionalized nitriles and esters of 6-alkylsulfanyl-1,4-
dihydronicotinic acids, their aromatic analogues and 1,4-dihydrothieno[2,3-b]pyridines.
Keywords: malononitrile, (het)aryl aldehydes, 1,3-dicarbonyl compounds, 1,4-dihydrothieno[2,3-b]pyridines,
[3,3]-sigmatropic rearrangement
DOI: 10.1134/S1070363220030068
Nicotinic acid derivatives are promising in the
development of drugs for the treatment of cardiovascular
[1–3], pulmonary [4], antitumor [5] diseases and HIV [6].
They can be used in electron-graphic toners as electric
charge regulators [7] and in positive photosensitive
compositions [8].
The reaction scheme includes the formation of
cyanothioacetamide A, which undergoes Knoevenagel-
type condensation with aldehydes 3a–3c to form the
corresponding alkenes B. Subsequently, the Michael
addition of CH acids 4a–4c to aryl(hetaryl)methylidene
cyanothioacetamides B to form adducts C. The
latter are unstable under the reaction conditions and
chemoselectively transform into salts 5a, 5b. In an
acidic medium, they easily form partially hydrogenated
pyridine-6-thiones 6 and 7. The introduction of an
equimolar amount of 1,2-dibromethane 8 into this reaction
in the presence of a 10% aqueous KOH solution led to
double alkylation of salt 5a. The initially formed thioether
D under the reaction conditions was intramolecularly
alkylated at the nitrogen atom of the dihydropyridine
core, resulting in the formation of a partially hydrogenated
thiazolo[3,2-a]pyridine 9 (Scheme 1).
In continuation of research in the field of nicotinic
acid chemistry [9–11], we investigated a new version
of multicomponent condensation, leading to the
formation of functionalized nitriles and esters of
1,4-dihydronicotinic acid. It was found that the reaction
of malononitrile 1, hydrogen sulfide 2, aryl or hetaryl
aldehydes 3a–3c and 1,3-dicarbonyl compounds
4a–4c produces nicotinic acid derivatives, namely
ammonium 1,4-dihydropyridine-2-thiolates 5a, 5b and
ethyl 5-cyano-2-methyl-4-(3-methylthiophen-2-yl)-6-
thioxo-1,4,5,6-tetrahydropyridinecarboxylate 6 (Scheme 1).
Recrystallization of salt 5a from glacial acetic acid gave
ethyl 2-propyl-6-thioxo-4-(furan-2-yl)-5-cyano-1,6-
dihydropyridine-3-carboxylate 7. Condensation took
place in ethanol at 20°С under catalysis with aliphatic
amines (triethylamine or morpholine).
The involvement into this multicomponent condensa-
tion of 1,2-dibromoethane 8 as an alkylating reagent in
a 0.5 mol amount led to the formation of 1,2-bis(1,4-
dihydropyridin-6-ylsulfanyl)ethanes 10a, 10b and diethyl
6,6'-[ethane-1,2-diylbis(sulfanediyl)]bis[5-cyano-4-
(furan-2-yl)-2-propylnicotinate] 11, respectively (Scheme 2).
An increase in the number of components of
this condensation, in particular, the addition of
1,2-dibromoethane 8 as an alkylating reagent, led to the
formation of ethyl 5-propyl-7-(furan-2-yl)-8-cyano-3,7-
dihydro-2H-thiazolo[3,2-a]pyridine-6-carboxylate 9
(Scheme 1).
The use of monohaloalkylating reagents 12a–12h
in this reaction under the same conditions allows the
synthesis of 6-alkylsulfanyl-1,4-dihydronicotinic acid
esters 13a–13g and nicotinic acid esters 14a, 14b.
Increasing the basicity of the reaction mixture by adding
357

358
KALASHNIK, DYACHENKO
Scheme 1.
O
R3
1
R
R2
O
R1CHO
CN
H2S, B
2
CN
S
CN
S
ꢁɚ–4c
ꢀɚ–3c
CN
ꢀH2O
H2N
H2N
1
Ⱥ
B
S
R1
Me
R1
O
O
CN
S
EtOOC
CN
S
CN
S
R3
R3
H+
R2
O H2N
ꢀH2O
ꢀH2O
R2
N
H
Me
N
BH
H
C
6
ꢂɚ, 5b
B r
B r
8
O
O
O
EtOOC
Pr
CN
S
EtOOC
Pr
CN
S
EtOOC
Pr
CN
S
AcOH, t
ꢀHBr
N
N
H
N
H
Br
7
9
D
B = Et N, morpholine; R1 = furan-2-yl (ꢀɚ), 5-methylfuran-2-yl (3b), 3-methylthiophen-2-yl (3c);
3
R2 = Pr, R3 = OEt (ꢁɚꢀꢁꢂɆɟꢃꢂ2(Wꢂꢄ4b); Me, Me (4c); R1 = furan-2-yl, R2 = Pr, R3 = OEt, B = Et N (ꢂɚ);
3
R1 = 5-methylfuran-2-yl, R2 = R3ꢂ ꢂ0Hꢃꢂȼꢂ ꢂPRUSKROLQHꢂꢄ5b).
a 10% aqueous KOH solution after the stage of adding
alkyl halides 12b, 12i, and 12j led to other reaction
outcome. The intermediately formed thioesters 13
underwent intramolecular cyclization into substituted
1,4-dihydrothieno[2,3-b]pyridines 15a–15d. The latter
are promising intermediates for the development of
antitumor [12–15] and antimicrobial agents [16, 17], as
well as for the treatment of diseases of the central nervous
system [18].
the condensation of malononitrile 1, hydrogen sulfide 2,
benzaldehyde 3i, ethyl benzoylacetate 4d and morpholine
led to the formation of 5-acetyl-1-benzyl-6-methyl-4-
phenyl-1,4-dihydronicotinonitrile 16. It is logical to
assume the formation in the reaction mixture of a fully
substituted 1,4-dihydropyridine E as an intermediate.
Unlike the above examples, the multicomponent
condensation of malononitrile 1, hydrogen sulfide 2,
3-pyridinecarbaldehyde 3f, ethyl benzoylacetate 4d,
morpholine and allyl bromide 12l proceeded unusually.
It is not possible to isolate the expected corresponding
The consecutive use of two different alkylating
reagents, methyl iodide 12k and benzyl chloride 12h, in
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NEW MULTICOMPONENT SYNTHESIS OF FUNCTIONALIZED NITRILES
359
Scheme 2.
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360
KALASHNIK, DYACHENKO
thioether F due to easy [3,3] sigmatropic rearrangement
into ethyl 5'-allyl-5'-cyano-2'-phenyl-6'-thioxo-1',4',5',6'-
tetrahydro-[3',4'-bipyridine]-3-carboxylate 17 (Scheme 2).
EXPERIMENTAL
IR spectra were recorded on an IKS-40 instrument
1
from liquid paraffin. H and 13C NMR spectra were
Confirmation of the implementation of the above
rearrangement is the presence in the IR spectrum of the
obtained compounds of the characteristic absorption band
of stretching vibrations of the non-conjugated cyano group
at 2244 cm–1. In the 1H NMR spectrum of compound 17,
the NH proton signal is shifted to a weak field compared
with that for 1,4-dihydropyridines 13a–13h and appears
as a broadened singlet in the region of 12.49 ppm. In a
series of functionally substituted 2-allylthio(seleno)-1,4-
dihydropyridines [3,3] sigmatropic rearrangement has
been first reported by us earlier [19].
recorded on a Varian VXR-400 spectrometer (399.97
and 100 MHz, respectively) from DMSO-d6 solutions,
and the internal standard was TMS. Mass spectra were
registered on an Agilent 1100 Series spectrometer with
an Agilent LS/MSDLS selective detector (the sample
was introduced into a CH3COOH matrix, EI, 70 eV).
For compounds 10a and 15b, mass spectra were taken
on an Orbitrap Elite high-resolution mass spectrometer.
Elemental analysis was performed on a PerkinElmer
CHN-analyzer. Melting points were determined on a
Kofler instrument. The reaction progress and the purity
of the obtained compounds were monitored by TLC
on Silufol UV-254 plates in an acetone–hexane system
(3 : 5), developing with iodine vapor and UV irradiation.
Spectral characteristics of the synthesized compounds
5–7, 9–11, 13–16 confirm their structure. In the 1H NMR
spectra of substituted 1,4-dihydropyridines 5a, 5b, 10a,
10b, 13a, 13h, 15a, and 15d there are characteristic proton
signals of the dihydropyridine ring in the regions of
4.64–5.18 (С4Н) and 8.91–11.95 (N1H) ppm disappearing
in the spectra of pyridines 14a–14c. We note the splitting
of proton signals of the SCH2 group into two doublets at
3.58–3.94 and 3.75–3.99 ppm (2J = 14.8–16.7 Hz), which
indicates the absence of free rotation of substituent Z. In
the spectra of 1,4-dihydropyridine derivatives 13a and
13b, the protons of the methyl groups of the isopropyl
substituent appear as two doublets in the ranges of
0.99–1.13 and 1.08–1.24 ppm, which also indicates
the absence of free rotation around the C2Py–CH(Me)2
bond. As a result, the protons of the methyl groups are
magnetically nonequivalent.
Triethylammonium 6-propyl-4-(furan-2-yl)-
3-cyano-5-ethoxycarbonyl-1,4-dihydropyridine-
2-thiolate (5a). A solution of 0.7 g (10 mmol) of
malononitrile 1 and 3 drops of triethylamine in 50 mL
of ethanol at 20°С was bubbled with a moderate flow of
hydrogen sulfide for 1 h before the start of crystallization
of cyanothioacetamide A, after which bubbling was
stopped. Then, 0.83 mL (10 mmol) of furfural 3a was
added to the mixture. The resulting mixture was stirred
for 30 min until crystallization of 2-furfurylidene
cyanothioacetamide B started. Next, 1.6 mL (10 mmol)
of ethyl butylacetate 4a and 1.4 mL (10 mmol) of
triethylamine were successively added. The resulting
mixture was stirred for 15 min and kept for 2 days. The
precipitate formed was filtered off, washed with ethanol
and hexane. Yield 3.9 g (71%), yellow crystalline powder,
mp 96–98°С. IR spectrum, ν, cm–1: 3212, 2960 (NH),
In the 1H NMR spectrum of compound 13f, doubling of
the H4 and NH proton signals of the 1,4-dihydropyridine
moiety is observed in the form of singlets at 4.68 and
4.71 ppm, 10.02 and 10.16 ppm, respectively, which
is probably due to different conformation 1,4-dihydro-
pyridine ring.
1
2179 (C≡N), 1683 (C=O). H NMR spectrum, δ, ppm:
0.87 t (3Н, Ме, J = 6.9 Hz), 1.08 t (3Н, МеСН2О, J =
7.0 Hz), 1.6 t (9Н, Ме, J = 7.3 Hz), 1.33–1.59 m
(2Н, СН2), 2.61 t (2Н, СН2, J = 7.0 Hz), 3.08 q [6Н,
(МеCH2)3N+, J = 7.3 Hz], 3.94 q (2Н, СН2О, J = 6.9 Hz),
4.39 s (1Н, Н4Py), 5.74 d (1Н, Н3Fu, J = 2.9 Hz), 6.23 d.
d (1Н, Н4Fu, J = 4.6 Hz), 7.40 d (1Н, Н5Fu, J = 1.2 Hz),
8.23br.s(1Н,NH).ThesignalsofHN+protonsdonotappear,
apparently, due to fast deutero exchange. Mass spectrum,
In conclusion, multicomponent condensation of
malononitrile, hydrogen sulfide, aryl or hetaryl aldehydes,
1,3-dicarbonyl compounds and alkylating reagents is a
convenient method for the synthesis of functionalized
nitriles and esters of 6-alkylsulfanyl-1,4-dihydronicotinic
acid, as well as their aromatic analogues, such as
thiazolo[2,3-b]pyridine and 1,4-dihydrothieno[2,3-b]-
pyridines.
m/z (Irel, %): 102.2 (10) [Et3NH + 1]+ 319.0 (100) [Мanion
+
1]+. Found, %: C 62.85; H 7.84; N 9.96. C22H33N3O3S.
Calculated, %: C 62.98; H 7.93; N 10.02. М 419.6.
Morpholin-4-ium 5-acetyl-6-methyl-4-(5-
methylfuran-2-yl)-3-cyano-1,4-dihydropyridine-
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NEW MULTICOMPONENT SYNTHESIS OF FUNCTIONALIZED NITRILES
361
2-thiolate (5b) was prepared similarly from 1 mL
(10 mmol) of 5-methylfurfural 3b, 1.23 mL(10 mmol) of
acetylacetone 4c and 0.87 mL (10 mmol) of morpholine.
Yield 2.8 g (77%), colorless powder, mp 118–120°С. IR
spectrum, ν, cm–1: 3316 (NH), 2170 (C≡N), 1714 (C=O).
1H NMR spectrum, δ, ppm: 2.11 s (3Н, Ме), 2.43 s (3Н,
Ме), 2.52 s (3Н, Ме), 3.08 t (4Н, CH2N+CH2, J = 4.4 Hz),
3.74 t (4Н, СН2ОСН2, J = 4.4 Hz), 4.36 s (1Н, Н4Py), 5.68 d
(1Н, Н3Fu, J = 2.9 Hz), 5.88 d (1Н, Н4Fu, J = 2.9 Hz),
8.31 br. s (1Н, NH). The signals of H2N+ protons do not
appear, apparently, due to fast deutero exchange. Mass
spectrum, m/z (Irel, %): 274.0 (100) [Мanion + 1]+. Found,
%: C 59.72; H 6.35; N 11.52. C18H23N3O3S. Calculated,
%: C 59.81; H 6.41; N 11.63. М 361.5.
1]+. Found, %: C 61.01; H 5.10; N 8.84. C16H16N2O3S.
Calculated, %: C 61.13; H 5.13; N 8.91. М 314.4.
Ethyl 5-propyl-7-(furan-2-yl)-8-cyano-3,7-dihydro-
2Н-thiazolo[3,2-a]pyridine-6-carboxylate (9) was
prepared from salt 5a. The formed salt 5a was filtered
off and dissolved in 25 mL of DMF. To the prepared
solution 0.9 mL (10 mmol) of 1,2-dibromoethane 8 and
5.6 mL (10 mmol) of a 10% aqueous KOH solution were
successively added. The resulting mixture was stirred
for 1 h and kept for 2 days, then diluted with an equal
volume of water. The precipitate formed was filtered
off, washed with water, ethanol and hexane. Yield 2.7 g
(78%), colorless powder, mp 112–114°С (EtОН). IR
spectrum, ν, cm–1: 2191 (C≡N), 1694 (C=O). 1H NMR
spectrum, δ, ppm: 0.94 t (3Н, Ме, J = 7.2 Hz), 1.11 t (3Н,
Ме, J = 7.1 Hz), 1.39–1.64 m (2Н, СН2), 2.58–2.77 m
(1Н, СН2), 2.79–2.92 m (1Н, СН2), 3.42 t (2Н, СН2,
J = 7.4 Hz), 4.05 q (2Н, СН2О, J = 7.2 Hz), 4.08–4.12
m (1Н, СН2), 4.19–4.26 m (1Н, СН2), 4.74 s (1Н, Н7Py),
6.02 d (1Н, Н3Fu, J = 2.9 Hz), 6.35 s (1Н, Н4Fu), 7.53 s
(1Н, Н5Fu). 13С NMR spectrum, δС, ppm: 13.77, 14.00,
21.53, 28.27, 31.21, 35.13, 51.95, 59.83, 74.84, 100.76,
105.39, 110.61, 119.52, 142.39, 149.79, 153.74, 156.74,
166.14. Mass spectrum, m/z (Irel, %): 345.2 (100) [М +
1]+. Found, %: C 62.61; H 5.70; N 7.97. C18H20N2O3S.
Calculated, %: C 62.77; H 5.85; N 8.13. М 344.4.
Ethyl 2-methyl-4-(3-methylthiophen-2-yl)-
6-thioxo-5-cyano-1,4,5,6-tetrahydropyridine-3-
carboxylate (6) was prepared similarly from 1.1 mL
(10 mmol) of 3-methylthiophen-2-ylcarbaldehyde 3c
and 1.3 mL (10 mmol) of acetoacetate 4b. Before filtra-
tion, the reaction mixture was diluted with 10%
hydrochloric acid to pH = 5 and kept for a day. The
precipitate formed was filtered off, washed successively
with water, ethanol and hexane. Yield 2.2 g (68%),
yellow powder, mp 135–137°С (EtOH). IR spectrum,
ν, cm–1: 3335 (NH), 2247 (C≡N), 1711 (C=O),
1
1188 (C=S). H NMR spectrum, δ, ppm: 1.20 t (3Н,
Diethyl 6,6'-[ethane-1,2-diylbis(sulfanediyl)]-
bis[5-cyano-2-methyl-4-(3-methylyhiophen-2-yl)-1,4-
dihydropyridine-3-carboxylate] (10a) was prepared
similarly to compound 9 from 1.1 mL (10 mmol) of
3-methylthiophen-2-ylcarbaldehyde 3c and 0.45 mL
(5 mmol) of 1,2-dibromoethane 8. Yield 2.3 g (68%),
yellow powder, mp 263–265°С (BuOH). IR spectrum,
ν, cm–1: 3330 (NH), 2198 (C≡N), 1716 (C=O). 1H NMR
spectrum, δ, ppm: 1.06 t (6Н, Ме, J = 7.1 Hz), 2.18 s
(6Н, Ме), 2.21 s (6Н, Ме), 2.98 t (2Н, СН2, J = 7.3 Hz),
3.14 t (2Н, СН2, J = 7.3 Hz), 3.95 q (4Н, СН2О, J =
7.1 Hz), 4.89 s (2Н, Н4Py), 6.75 d (2Н, Н4thiophene, J =
5.1 Hz), 7.19 d (2Н, Н5thiophene, J = 5.1 Hz), 9.65 br. s
(2Н, NH). 13С NMR spectrum, δC, ppm: 13.73 (2С),
14.42 (2С), 18.11 (2С), 32.76 (2С), 35.75 (2С), 59.96
(2С), 92.51 (2С), 101.17 (2С), 119.50 (2С), 123.92 (2С),
130.25 (2С), 132.35 (2С), 141.14 (2С), 144.46 (2С),
145.93 (2С), 166.36 (2С). Mass spectrum, m/z: 665.1392
[М – Н]+ (calculated for C32H34N4O4S4: 665.1463).
МеСН2, J = 7.0 Hz), 2.31 s (3Н, Ме), 2.36 s (3Н,
Ме), 4.11 q (2Н, СН2О, J = 7.0 Hz), 4.29–4.44 m
(2Н, Н3 + Н4Py), 6.76 d (1Н, Н4thiophene, J = 5.2 Hz),
Py
7.11 d (1Н, Н5thiophene, J = 5.2 Hz), 12.08 br. s (1Н, NH).
Mass spectrum, m/z (Irel, %): 321.0 (100) [М + 1]+. Found,
%: C 56.02; H 4.96; N 8.66. C15H16N2O2S2. Calculated,
%: C 56.23; H 5.03; N 8.74. М 320.4.
Ethyl 2-propyl-6-thioxo-4-(furan-2-yl)-5-cyano-
1,6-dihydropyridine-3-carboxylate (7) was obtained
by recrystallization of 1 g (2.4 mmol) of salt 5a from
25 mL of glacial acetic acid. Yield 2.4 g (75%), yellow
crystals, mp 183–185°С (АсОН). IR spectrum, ν, cm–1:
3157 (NH), 2223 (C≡N), 1724 (C=O), 1029 (C=S).
1H NMR spectrum, δ, ppm: 0.88 t (3Н, МеСН2О, J =
7.3 Hz), 1.09 t (3Н, Ме, J = 7.0 Hz), 1.51–1.56 m (2Н,
СН2), 2.67 t (2Н, СН2, J = 7.0 Hz), 4.14 q (2Н, СН2О, J =
7.3 Hz), 6.80 s (1Н, Н3Fu), 7.38 s (1Н, Н4Fu), 8.03 s (1Н,
Н5Fu), 14.24 br. s (1Н, NH). 13С NMR spectrum, δС, ppm:
13.60, 13.83, 22.95, 32.78, 61.92, 109.74, 113.03, 115.58,
116.30, 117.16, 140.85, 145.88, 147.25, 155.83, 164.96,
179.10. Mass spectrum, m/z (Irel, %): 315.0 (100) [М +
Diethyl 6,6'-[ethane-1,2-diethylbis(sulfandiyl)]-
bis[4-(2-methoxyphenyl)-2-phenyl-5-cyano-1,4-
dihydropyridine-3-carboxylate] (10b) was prepared
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KALASHNIK, DYACHENKO
similarly to compound 9 from 1.21 mL (10 mmol)
o-methoxybenzaldehyde 3d, 1.73 mL (10 mmol) of
ethylbenzoylacetate 4d and 0.45 mL (5 mmol) of
1,2-dibromoethane 8. Yield 2.8 g (70%), yellow crystals,
mp 225–227°С (i-PrOH). IR spectrum, ν, cm–1: 3311
was filtered off, washed successively with water, ethanol
and hexane.
Methyl 2-isopropyl-4-(2-methyl-4-fluorophenyl)-
6-[2-(4-chlorophenyl)-2-oxoethylthio)]-5-cyano-1,4-
dihydropyridine-3-carboxylate (13a). Yield 4.1 g
(82%), yellow crystals, mp 134–136°С (АсОН). IR
spectrum, ν, cm–1: 3310 (NH), 2200 (C≡N), 1719
(ОС=О), 1698 (C=O). 1H NMR spectrum, δ, ppm: 1.09 d
(3Н, МеСН, J = 6.8 Hz), 1.23 d (3Н, МеСН, J = 6.8 Hz),
2.40 s (3Н, Ме), 3.48 s (3Н, МеО), 4.01–4.18 m (1Н,
CHМе2), 4.70 s (2Н, СН2), 4.78 s (1Н, Н4Py), 6.82–6.95 m
(2Н, НAr), 7.02–7.05 m (1Н, НAr), 7.61 d (2Н, НAr,
J = 8.4 Hz), 7.99 d (2Н, НAr, J = 8.4 Hz), 8.92 br. s (1Н,
NH). Mass spectrum, m/z (Irel, %): 500.2 (100) [М + 1]+.
Found, %: C 62.41; H 4.77; N 5.58. C26H24FClN2O3S.
Calculated, %: C 62.58; H 4.85; N 5.61. М 499.0.
1
(NH), 2202 (C≡N), 1707 (C=O). H NMR spectrum,
δ, ppm: 0.68 t (6Н, Ме, J = 7.0 Hz), 2.91–3.02 m (2Н,
СН2), 3.24–3.29 m (2Н, СН2), 3.65 q (4Н, СН2О, J =
7.0 Hz), 3.76 s (6Н, МеО), 4.97 s (2Н, Н4Py), 6.93 t (2Н,
НAr, J = 7.4 Hz), 7.02 d (2Н, НAr, J = 8.2 Hz), 7.20 d
(3Н, НAr, J = 7.4 Hz), 7.23 t (2Н, НAr, J = 7.8 Hz), 7.34 d
(4Н, НAr, J = 7.0 Hz), 7.38–7.47 m (5Н, НAr), 9.86 br. s
(2Н, NH). 13С NMR spectrum, δC, ppm: 13.77 (2С),
32.43 (2С), 36.72 (2С), 55.88 (2С), 59.62 (2С), 90.23
(2С), 100.40 (2С), 111.81 (2С), 119.43 (2С), 121.07 (2С),
128.40 (4С), 128.49 (2С), 128.88 (2С), 129.24 (4С),
129.50 (2С), 132.77 (2С), 136.10 (2С), 143.09 (2С),
148.06 (2С), 156.73 (2С), 166.31 (2С). Mass spectrum,
m/z (Irel, %): 811.2 (100) [М + 1]+. Found, %: C 68.02;
H 5.14; N 6.78. C46H42N4O6S2. Calculated, %: C 68.13;
H 5.22; N 6.91. М 810.991.
Methyl 6-(2-amino-2-oxoethylthio)-2-isopropyl-
4-(2-methyl-4-fluorophenyl)-5-cyano-1,4-
dihydropyridine-3-carboxylate (13b). Yield 3.2 g
(79%), colorless powder, mp 198–200°С (i-PrOH). IR
spectrum, ν, cm–1: 3412–3290 (NH, NH2), 2204 (C≡N),
1719 (С=О), 1666 (CONH). 1H NMR spectrum, δ, ppm:
1.13 d (3Н, МеСН, J = 6.6 Hz), 1.24 d (3Н, МеСН, J =
6.6 Hz), 2.42 s (3Н, Ме), 3.48 s (3Н, МеО), 3.58 d (1H,
SCH2, J = 15.5 Hz), 3.75 d (1H, SCH2, J = 15.5 Hz),
4.02–4.19 m (1Н, CHМе2), 4.81 s (1Н, Н4Py), 6.84–7.01 m
(2Н, НAr), 7.03–7.15 m (1Н, НAr), 7.85 br. s (1Н, NH2),
8.14 br. s (1Н, NH2), 10.57 br. s (1Н, NH). 13С NMR
spectrum, δC, ppm: 19.21, 20.04, 21.44, 28.13, 35.14,
37.45, 51.55, 86.04, 100.50, 114.23, 116.81, 119.48,
130.27, 137.20, 141.64, 144.43, 154.38, 159.84, 167.10,
173.40. Mass spectrum, m/z (Irel, %): 404.2 (100) [М +
1]+. Found, %: C 59.44; H 5.39; N 10.32. C20H22FN3O3S.
Calculated, %: C 59.54; H 5.50; N 10.41. М 403.5.
Diethyl 6,6'-[ethane-1,2-diylbis(sulfanediyl)]-
bis[2-propyl-4-(furan-2-yl)-5-cyanonicotinate] (11)
was prepared similarly to compound 9 from 0.45 mL
(5 mmol) of 1,2-dibromoethane. Yield 2.2 g (66%),
colorless powder, mp 148–150°С (АсОН). IR spectrum,
ν, cm–1: 2222 (C≡N), 1739 (C=O). 1H NMR spectrum, δ,
ppm: 0.88 t (6Н, Ме, J = 7.2 Hz), 1.18 t (6Н, МеСН2О,
J = 7.3 Hz), 1.57–1.76 m (4Н, СН2), 2.69 t (4Н, SСН2,
J = 7.0 Hz), 3.72 t (4Н, СН2, J = 7.3 Hz), 4.28 q (4Н,
СН2О, J = 7.3 Hz), 6.77 s (2Н, Н3Fu), 7.25 s (2Н, Н4Fu),
7.99 s (2Н, Н5Fu). 13С NMR spectrum, δС, ppm: 13.64
(2С), 13.88 (2С), 21.36 (2С), 29.82 (2С), 37.39 (2С),
61.95 (2С), 100.01 (2С), 112.91 (2С), 115.03 (2С), 115.54
(2С), 122.09 (2С), 138.35 (2С), 145.44 (2С), 146.75 (2С),
161.82 (2С), 163.01 (2С), 166.34 (2С). Mass spectrum,
m/z (Irel, %): 659.2 (100) [М + 1]+. Found, %: C 61.85;
H 5.07; N 8.41. C34H34N4O6S2. Calculated, %: C 61.99;
H 5.20; N 8.50. М 658.8.
Methyl 6-[2-oxo-(2-oxo-2Н-chromen-3-yl)-
ethylthio]-2-isopropyl-4-(2-methyl-4-fluorophenyl)-5-
cyano-1,4-dihydropyridine-3-carboxylate (13c). Yield
3.9 g (74%), yellow crystals, mp 250–252°С (dioxane).
IR spectrum, ν, cm–1: 3320 (NH), 2205 (C≡N), 1715,
1
1695 (С=О). H NMR spectrum, δ, ppm: 1.29 d (6Н,
Substituted 2-alkylsulfanyl-1,4-dihydropyridines
(13a–13h) and pyridines (14a–14c) were obtained
analogously to compounds 5 from the corresponding
aldehydes 3a–3h and CH acids 4a–4f. After the step of
salt 5 precipitate formation, the alkyl halide 12a–12h
was added with stirring. The mixture was stirred for 2 h
and kept for a day, then diluted with an equal volume of
water and again kept for a day. The precipitate formed
2Ме, J = 6.6 Hz), 2.76 s (3Н, Ме), 3.56 br. s (5Н, МеО +
SCH2), 4.18–4.26 m (1Н, CHМе2), 5.37 s (1Н, Н4Py),
6.72–6.81 m (2Н, НAr), 7.10 br. s (1Н, НAr), 7.24–7.33 m
(2Н, НAr), 7.49 br. s (1Н, НAr), 8.24 br. s (1Н, НAr), 9.85 s
(1Н, Н4coumarin), 11.68 br. s (1Н, NH). 13С NMR spectrum,
δC, ppm: 20.09 (2С), 20.63, 22.80, 28.32, 51.16, 66.81,
86.13, 87.12, 103.01, 113.25, 116.03, 117.14, 119.02,
124.86, 125.07, 132.16, 133.04, 137.09, 143.98, 147.12,
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150.96, 152.17, 153.10, 158.96, 161.12, 162.15, 165.05,
168.17. Mass spectrum, m/z (Irel, %): 533.0 (100) [М +
1]+. Found, %: C 65.37; H 4.68; N 5.22. C29H25FN2O5S.
Calculated, %: C 65.40; H 4.73; N 5.30. М 532.6.
1H NMR spectrum, δ, ppm: 0.71 t (3Н, Ме, J = 7.2 Hz),
1.49–2.18 m (6Н, НCy), 3.71 q (2Н, CH2О, J = 7.2 Hz),
4.22–4.29 m (1Н, SCH), 4.68 s and 4.71 s (1Н, Н4Py),
5.15–5.23 m (1Н, =СН), 5.28–6.01 m (1Н, СН=), 7.32 d
(2Н, НAr, J = 6.8 Hz), 7.38–7.53 m (4Н, НAr), 7.71 q (1Н,
НAr, J = 8.0 Hz), 8.50 s (1Н, Н2Py), 8.54 d (1Н, Н6Py, J =
5.2 Hz), 10.02 br. s and 10.16 br. s (1H, NH). 13С NMR
spectrum, δC, ppm: 13.73, 18.05, 19.64, 24.70, 28.22,
43.69, 59.87, 90.55, 91.96, 100.53, 119.33 (2С), 124.71,
126.34, 128.46 (2С), 129.20, 131.57, 140.64, 143.71,
144.32, 147.94, 148.08, 148.56, 148.97, 166.13. Mass
spectrum, m/z (Irel, %): 444.0 (100) [М + 1]+. Found, %:
C 70.29; H 5.54; N 9.33. C26H25N3O2S. Calculated, %:
C 70.40; H 5.68; N 9.47. М 443.6.
Allyl 6-{[2-oxo-(o-tolylamino)ethyl]thio}2-
propyl-4-furan-2-yl-5-cyano-1,4-dihydropyridine-3-
carboxylate (13d). Yield 3.8 g (84%), colorless powder,
under UV irradiation fluoresces, mp 160–162°С (BuOH).
IR spectrum, ν, cm–1: 3380–3295 (NH), 2196 (C≡N),
1715 (С=О), 1668 (NHCO). 1H NMR spectrum, δ, ppm:
2.20 s (3Н, Ме), 2.31 s (3Н, Ме), 3.94 d (1Н, SCH2, J =
14.8 Hz), 3.99 d (1Н, SCH2, J = 14.8 Hz), 3.91–4.62 m
(2Н, ОСН2), 4.69 s (1Н, Н4Py), 5.13 d (1Н, СН2=, Jcis
=
9.2 Hz), 5.17 d (1Н, СН2=, Jtrans = 15.9 Hz), 5.77–5.98 m
(1Н, =СН), 6.05 d (1Н, Н3Fu, J = 3.0 Hz), 6.34 t (1Н,
Н4Fu, J = 1.8 Hz), 7.08 t (1Н, НAr, J = 8.2 Hz), 7.10 t (1Н,
НAr, J = 8.0 Hz), 7.13 d (1Н, НAr, J = 8.2 Hz), 7.32 d
(1Н, НAr, J = 7.8 Hz), 7.52 s (1Н, Н5Fu), 9.80 br. s (1Н,
NH), 10.15 br. s (1H, CONH). 13С NMR spectrum, δC,
ppm: 18.18, 18.26, 36.02, 36.38, 64.54, 85.41, 97.85,
105.99, 111.05, 119.31, 119.94, 125.60, 126.35, 126.58,
130.90, 132.53, 135.94, 136.59, 142.92, 144.87, 147.70,
156.47, 166.05, 167.94. Mass spectrum, m/z (Irel, %):
448.0 (100) [М – 1]+. Found, %: C 64.02; H 5.04; N
9.19. C24H23N3O4S. Calculated, %: C 64.13; H 5.16; N
9.35. М 449.5.
5-Acetyl-6-methyl-4-(2-chlorophenyl)-2-(cyclohex-
2-en-1-ylthio)-1,4-dihydropyridine-3-carboxylate
(13g).Yield 2.9 g (76%), red powder, under UV irradiation
fluoresces, mp 157–159°С (EtOH). IR spectrum, ν, cm–1:
3300 (NH), 2202 (C≡N), 1714 (С=О). 1H NMR spectrum,
δ, ppm: 1.51–1.72 m (2Н, НAlk), 1.76–1.81 m (2Н, НAlk),
1.83–1.99 m (2Н, НAlk), 2.04 s (3Н, Ме), 2.37 s (3Н,
МеСО), 4.18–4.26 m (1Н, SCH), 5.18 s (1Н, Н4Py),
5.61–5.66 m (1Н, =СН), 5.84–5.93 m (1Н, =СН), 7.20 d
(1Н, НAr, J = 7.7 Hz), 7.23 t (1Н, НAr, J = 7.7 Hz), 7.33 t
(1Н, НAr, J = 7.4 Hz), 7.40 d (1Н, НAr, J = 8.0 Hz),
9.72 br. s (1H, NH). 13С NMR spectrum, δC, ppm: 18.20,
19.36, 24.69, 24.85, 28.31, 30.34, 43.90, 92.27, 109.75,
119.01, 124.92, 128.72, 129.37, 129.86, 130.48, 142.70,
142.99, 143.08, 143.12, 146.51, 196.80. Mass spectrum,
m/z (Irel, %): 385.0 (100) [М + 1]+. Found, %: C 65.48;
H 5.44; N 7.16. C21H21ClN2OS. Calculated, %: C 65.60;
H 5.50; N 7.29. М 384.5.
Ethyl 4-(2-methoxyphenyl)-6-[(3-methyl-1-
oxo-1-phenylbut-2-yl)thio]-2-phenyl-5-cyano-1,4-
dihydropyridine-3-carboxylate (13e). Yield 4.8 g
(86%), yellow powder, mp 156–158°С (EtОН). IR
spectrum, ν, cm–1: 3306 (NH), 2222 (C≡N), 1714, 1698
(С=О). 1H NMR spectrum, δ, ppm: 0.76 t (3Н, Ме, J =
7.0 Hz), 0.99 d (3Н, Ме, J = 6.5 Hz), 1.08 d (3Н, Ме,
J = 6.5 Hz), 2.19–2.25 m (1Н, CHМе2), 3.66 q (2Н,
CH2О, J = 7.0 Hz), 3.85 s (3Н, МеО), 4.94 s (1Н, Н4Py),
5.07 d (1Н, SCH, J = 7.0 Hz), 6.81–6.92 m (2Н, НAr),
7.10–7.18 m (2Н, НAr), 7.23 d (2Н, НAr, J = 7.5 Hz), 7.34 t
(2Н, НAr, J = 7.5 Hz), 7.38 d (1Н, НAr, J = 7.0 Hz), 7.47 d
(2Н, НAr, J = 7.5 Hz), 7.61 t (1Н, НAr, J = 7.0 Hz), 7.95 d
(2Н, НAr, J = 7.5 Hz), 9.35 br. s (1H, NH). Mass spectrum,
m/z (Irel, %): 551.2 (100) [М – 1]+. Found, %: C 71.65;
H 5.72; N 4.96. C33H32N2O4S. Calculated, %: C 71.72;
H 5.84; N 5.07. М 552.7.
Ethyl 4-(pyridin-3-yl)-6-(prop-2-yn-1-ylthio)-
2-phenyl-5-cyano-1,4-dihydropyridinenicotinate
(13h). Yield 2.8 g (70%), pale yellow crystals, under
UV irradiation fluoresces, mp 145–147°С (EtOH). IR
spectrum, ν, cm–1: 3333 (NH, ≡С–Н), 2244 (С≡С), 2203
(C≡N), 1722 (С=О). 1H NMR spectrum, δ, ppm: 0.77 t
(3Н, Ме, J = 7.2 Hz), 3.02 s (1Н, ≡С–Н), 3.74 q (2Н,
ОСН2, J = 7.2 Hz), 3.77 d (1Н, SCH2, J = 16.7 Hz), 4.10 d
(1Н, SCH2, J = 16.7 Hz), 4.64 s (1Н, Н4Py), 7.26–7.38 m
(6Н, НAr), 7.67 d (1Н, НAr, J = 7.2 Hz), 8.43–8.51 m
(2Н, НAr), 9.93 br. s (1H, NH). Mass spectrum, m/z (Irel,
%): 402.0 (100) [М + 1]+. Found, %: C 68.72; H 4.65;
N 10.38. C23H19N3O2S. Calculated, %: C 68.81; H 4.77;
N 10.47. М 401.5.
Ethyl 2'-phenyl-5'-cyano-6'-(cyclohex-2-en-1-
ylthio)-1',4'-dihydro-(3,4'-bipyridine)-3'-carboxylate
(13f). Yield 3.5 g (78%), pale yellow crystals, under
UV irradiation fluoresces, mp 165–167°С (EtOH). IR
spectrum, ν, cm–1: 3318 (NH), 2205 (C≡N), 1719 (С=О).
5-Acetyl-6-methyl-4-(5-methylfuran-2-yl)-2-(prop-
2-yn-1-ylthio)nicotinonitrile (14a). Yield 2.4 g (77%),
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KALASHNIK, DYACHENKO
yellow powder, under UV irradiation fluoresces, mp 93–
solution of KOH was added. The mixture was stirred
for 2 h. Next day, the mixture was diluted with an equal
volume of water. The precipitate formed was filtered off
and washed with water, ethanol and hexane.
95°С (i-PrOH). IR spectrum, ν, cm–1: 3330 (≡С–Н), 2222
1
(C≡N), 2150 (С≡С), 1712 (С=О). H NMR spectrum,
δ, ppm: 2.25 s (3Н, Ме), 2.34 s (3Н, Ме), 2.49 s (3Н,
Ме), 3.18 t (1Н, ≡СН, J = 2.4 Hz), 4.13 d (2Н, СН2, J =
Ethyl 3-amino-2-carbamoyl-4-(pyridin-3-yl)-
6-phenyl-4,7-dihydrothieno[2,3-b]pyridine-5-
carboxylate (15a). Yield 3.0 g (72%), pale yellow
powder, mp 190–192°С (PrOH). IR spectrum, ν, cm–1:
3400–3295 (NH, NH2), 1722 (С=О), 1668 (CONH2),
1635 [δ(NH2)]. 1H NMR spectrum, δ, ppm: 0.69 t (3Н,
Ме, J = 6.4 Hz), 3.66 q (2Н, ОСН2, J = 6.4 Hz), 5.17 s
(1Н, Н4dihydropyridine), 6.46 br. s (2H, NH2), 6.57 br. s
(2H, NH2), 7.24–7.49 m (6Н, НAr), 7.72 d (1Н, НAr, J =
6.8 Hz), 8.27 br. s (1Н, НAr), 8.64 s (1Н, Н2Py), 10.03 br. s
(1H, NH). 13С NMR spectrum, δС, ppm: 13.84, 36.78,
59.25, 91.43, 99.87, 111.19, 124.04, 128.38 (2С), 128.70
(2С), 129.13, 135.37, 137.47, 139.56, 142.56, 147.81,
149.17, 149.21, 150.73, 167.05, 167.19. Mass spectrum,
m/z (Irel, %): 421.0 (100) [М + 1]+. Found, %: C 62.70;
H 4.68; N 13.25. C22H20N4O3S. Calculated, %: C 62.84;
H 4.79; N 13.32. М 420.5.
2.4 Hz), 6.45 d (1Н, Н4Fu, J = 3.4 Hz), 7.24 d (1Н, Н3
,
Fu
J = 3.4 Hz). 13С NMR spectrum, δC, ppm: 13.66, 18.80,
23.54, 31.34, 74.14, 80.01, 98.96, 110.22, 115.65, 117.86,
129.55, 137.28, 143.96, 156.95, 157.85, 161.31, 202.81.
Mass spectrum, m/z (Irel, %): 311.0 (100) [М + 1]+. Found,
%: C 65.64; H 4.39; N 10.22. C17H14N2O2S. Calculated,
%: C 65.79; H 4.55; N 10.33. М 310.4.
5-Acetyl-2-benzylthio-6-methyl-4-(4-chlorophenyl)-
nicotinonitrile (14b). Yield 3.3 g (84%), yellow powder,
mp 130–132°С (АсOH). IR spectrum, ν, cm–1: 2225
(С≡N), 1717 (С=О). 1H NMR spectrum, δ, ppm: 1.99 s
(3Н, Ме), 2.54 s (3Н, Ме), 4.57 s (2Н, СН2), 7.25 d (1Н,
НAr, J = 6.5 Hz), 7.32 t (2Н, НAr, J = 6.5 Hz), 7.41 d
(2Н, НAr, J = 8.0 Hz), 7.47 d (2Н, НAr, J = 7.0 Hz), 7.60 d
(2Н, НAr, J = 8.0 Hz). Mass spectrum, m/z (Irel, %):
393.3 (100) [М + 1]+. Found, %: C 67.18; H 4.25; N
7.02. C22H17ClN2OS. Calculated, %: C 67.25; H 4.36;
N 7.13. М 392.9.
Ethyl 3-amino-2-carbamoyl-6-methyl-4-(3-
methylthiophen-2-yl)-4,7-dihydrothieno[2,3-b]-
pyridine-5-carboxylate (15b). Yield 2.9 g (77%), yellow
crystals, mp 225–227°С (BuOH). IR spectrum, ν, cm–1:
3400–3011 (NH, NH2), 1718 (ОС=О), 1665 (CONH2),
1635 [δ(NH2)]. 1H NMR spectrum, δ, ppm: 1.11 t (3Н,
Ме, J = 7.1 Hz), 2.18 s (3Н, Ме), 2.23 s (3Н, Ме), 3.99 q
(2Н, СН2, J = 7.1 Hz), 5.25 s (1Н, Н4Py), 5.91 br. s (2H,
Ethyl 6-[2-oxo-2-(2-oxo-2Н-chromen-3-yl)ethyl-
thio]-2-propyl-4-(furan-2-yl)-5-cyanonicotinate (14c).
Yield 3.6 g (71%), colorless powder, mp 180–182°С
(BuOH). IR spectrum, ν, cm–1: 2227 (С≡N), 1733
(С=О). 1H NMR spectrum, δ, ppm: 0.66 t (3Н, Ме, J =
7.2 Hz), 1.17 t (3Н, Ме, J = 7.3 Hz), 1.38–1.62 m (2Н,
СН2), 2.56 t (2Н, СН2, J = 7.3 Hz), 4.26 q (2Н, СН2О,
J = 7.2 Hz), 4.89 s (2Н, SCH2), 6.78 d. d (1Н, Н4Fu, J =
1.7, 3.5 Hz), 7.26 d (1Н, Н3Fu, J = 3.5 Hz), 7.43 t (1Н,
НAr, J = 6.7 Hz), 7.50 d (1Н, НAr, J = 8.3 Hz), 7.79 t
(1Н, НAr, J = 8.3 Hz), 7.98 br. s (2Н, Н5Fu + НAr), 8.77 s
(1Н, Н4coumarin). 13С NMR spectrum, δC, ppm: 13.46,
13.87, 21.52, 24.48, 37.33, 61.98, 99.39, 112.95, 115.14,
115.65, 116.30, 118.15, 121.89, 123.63, 125.28, 131.06,
135.10, 138.17, 145.36, 146.79, 148.44, 154.74, 158.61,
161.72, 162.78, 166.29, 190.66. Mass spectrum, m/z (Irel,
%): 503.2 (100) [М + 1]+. Found, %: C 64.41; H 4.38;
N 5.45. C27H22N2O6S. Calculated, %: C 64.53; H 4.41;
N 5.57. М 502.5.
С3NH2), 6.56 br. s (2H, СОNH2), 6.61 d (1Н, Н4
,
thiophene
J = 5.1 Hz), 7.08 d (1Н, Н5thiophene, J = 5.1 Hz), 9.86 br. s
(1H, NH). 13С NMR spectrum, δC, ppm: 14.12, 14.68,
19.69, 32.44, 59.37, 91.39, 99.61, 111.95, 122.95, 129.92,
131.94, 138.86, 145.52, 146.62, 150.93, 167.05, 167.37.
Mass spectrum, m/z 378.0941 [М + Н]+ (calculated for
C17H19N3O3S2: 378.0878).
3-Amino-2-benzyl-4-(pyridin-3-yl)-6-phenyl-
5-ethyl-4,7-dihydrothieno[2,3-b]pyridine-2,5-
carboxylate (15c). Yield 3.8 g (74%), yellow crystals, mp
282–284°С (BuOH). IR spectrum, ν, cm–1: 3400–3312
(NH, NH2), 1724, 1716 (С=О), 1645 [δ(NH2)]. 1H NMR
spectrum, δ, ppm: 0.65 t (3Н, Ме, J = 7.1 Hz), 3.62 q
(2Н, МеCH2, J = 7.1 Hz), 5.09 d (1Н, CH2Ph, J =
12.8 Hz), 5.12 d (1Н, CH2Ph, J = 12.8 Hz), 5.20 s (1Н,
Н4thienopyridine), 6.49 br. s (2H, NH2), 7.23–7.46 m (11Н,
НAr), 7.68 d (1Н, Н4Py, J = 6.0 Hz), 8.34 d (1Н, Н6Py, J =
1.6 Hz), 8.61 s (1Н, Н2Py), 10.11 br. s (1H, NH). 13С NMR
spectrum, δС, ppm: 13.79, 36.48, 59.36, 64.66, 100.66,
Substituted 4,7-dihydrothieno[2,3-b]pyridines
(15a–15d) were obtained similarly to compounds 5.After
the precipitate formation, to the mixture 10 mmol of the
corresponding alkylating agent 12b, 12i or 12j was added.
The resulting mixture was stirred for 2 h, diluted with
20 mL of DMF, and 5.6 mL (10 mmol) of a 10% aqueous
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NEW MULTICOMPONENT SYNTHESIS OF FUNCTIONALIZED NITRILES
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109.68, 110.34, 124.10, 128.02, 128.23 (2С), 128.40,
128.61 (2С), 128.85 (4С), 129.18, 135.34, 137.17, 137.47,
142.12, 143.43, 147.93, 148.62, 149.14, 163.86, 166.82.
Mass spectrum, m/z 512.1647 [М + 1]+ (calculated for
C29H25N3O4S: 512.1566).
12l was added. The mixture was stirred for 2 h and kept
for 2 days, then diluted with an equal volume of water.
The precipitate formed was filtered off, washed with
water, ethanol and hexane. Yield 2.7 g (68%), pale yellow
crystals, under UV irradiation fluoresces, mp 125–127°С
(EtOH). IR spectrum, ν, cm–1: 3060 (NH), 2244 (С≡N),
1699(С=О), 1229(C=S). 1HNMRspectrum, δ, ppm:0.72t
(3Н, Ме, J = 7.1 Hz), 2.73–2.99 m (2Н, СН2), 3.75 q
(2Н, ОСН2, J = 7.1 Hz), 4.31 s (1Н, Н4dihydropyridine), 5.31 d
Allyl 3-amino-6-propyl-2-(thiazol-2-ylcarbamoyl)-
4-(furan-2-yl)-4,7-dihydrothieno[2,3-b]pyridine-
2,5-carboxylate (15d). Yield 3.5 g (81%), pale yellow
crystals, under UV irradiation fluoresces, mp 223–225°С
(BuOH). IR spectrum, ν, cm–1: 3400–3296 (NH, NH2),
(1Н, =СН2, Jtrans = 17.1 Hz), 5.35 d (1Н, =СН2, Jcis
=
1
10.4 Hz), 5.42–6.06 m (1Н, СН=), 7.46 br. s (6Н, НAr),
7.65 d (1Н, НAr, J = 8.0 Hz), 8.51 s (1Н, Н2Py), 8.53 d
(1Н, Н6Py, J = 8.0 Hz), 12.49 br. s (1H, NH). 13С NMR
spectrum, δC, ppm: 13.70, 41.22, 43.34, 59.36, 60.60,
108.61, 118.11, 122.11, 124.47, 128.43, 129.04 (2С),
129.91 (2С), 131.15, 133.87, 133.98, 136.02, 145.55,
149.87, 150.02, 165.56, 194.51. Mass spectrum, m/z (Irel,
%): 404.1 (100) [М + 1]+. Found, %: C 68.32; H 5.11;
N 10.35. C23H21N3O2S. Calculated, %: C 68.46; H 5.25;
N 10.41. М 403.5.
1713 (С=О), 1666 (NHCO), 1644 [δ(NH2)]. H NMR
spectrum, δ, ppm: 2.87 s (3Н, Ме), 4.36–4.61 m (2Н,
СН2О), 5.11 d (1Н, СН2=, Jcis = 10.6 Hz), 5.18 d (1Н,
СН2=, Jtrans = 17.3 Hz), 5.23 s (1Н, Н4thienopyridine),
5.76–5.84 m (1Н, =СН), 5.85 d (1Н, Н3Fu, J = 2.9 Hz),
6.25 br. s (1Н, Н4Fu), 6.77 br. s (3H, NH2 + Н5thiazole),
6.98 d (1Н, Н4thiazole, J = 3.5 Hz), 7.34 d (1Н, Н5Fu, J =
1.2 Hz), 7.38 br. s (1Н, N7H), 10.06 br. s (1H, СОNH).
13С NMR spectrum, δС, ppm: 19.83, 32.40, 64.00, 97.15,
103.02, 105.02, 107.11, 110.12, 117.23, 119.16, 122.11,
124.45, 133.98, 142.16, 143.07, 146.16, 148.81, 158.96,
167.05. Mass spectrum, m/z (Irel, %): 431.1 (100) [М +
1]+. Found, %: C 52.91; H 4.07; N 12.88. C19H18N4O4S2.
Calculated, %: C 53.01; H 4.22; N 13.01. М 430.5.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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