A New Version of Multicomponent Synthesis of 4,6-Diaryl-2-sulfanylidene-1,2-dihydropyridine-3-carbonitrile Derivatives

Article abstract of DOI:10.1134/S1070428018090014

Multicomponent condensation of aromatic aldehydes with acetophenones, cyanothioacetamide, and alkylating agents has been shown to provide synthetic routes to various pyridine and thienopyridine derivatives. The structure of some of the synthesized heterocycles has been confirmed by X-ray analysis.

Full text of DOI:10.1134/S1070428018090014

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 9, pp. 1273–1284. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © I.V. Dyachenko, V.D. Dyachenko, E.G. Polupanenko, P.V. Dorovatovskii, V.N. Khrustalev, V.G. Nenajdenko, 2018, published in
Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 9, pp. 1263–1273.
A New Version of Multicomponent Synthesis of 4,6-Diaryl-
2-sulfanylidene-1,2-dihydropyridine-3-carbonitrile Derivatives
I. V. Dyachenkoa, V. D. Dyachenkoa, E. G. Polupanenkoa, P. V. Dorovatovskiib,
V. N. Khrustalevb, c, and V. G. Nenajdenkod*
a Taras Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91000 Ukraine
b National Research Center “Kurchatov Institute,” pl. Akademika Kurchatova 1, Moscow, 123182 Russia
c Peoples’Friendship University of Russia, ul. Miklukho-Maklaya 6, Moscow, 117198 Russia
d Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia
*e-mail: nenajdenko@gmail.com
Received June 8, 2018
Abstract—Multicomponent condensation of aromatic aldehydes with acetophenones, cyanothioacetamide, and
alkylating agents has been shown to provide synthetic routes to various pyridine and thienopyridine derivatives.
The structure of some of the synthesized heterocycles has been confirmed by X-ray analysis.
DOI: 10.1134/S1070428018090014
In recent time, syntheses of heterocyclic com-
pounds by multicomponent condensations have
become more and more popular. Accessibility of initial
reactants, simplicity of experimental procedures, high
yields of the target compounds, and increasing
demands of environmental safety make this approach
quite attractive for the synthesis of complex molecules
[1–3]. By using multicomponent reactions, we
previously synthesized functionalized pyridines [4],
4-spiro-fused 1,4-dihydropyridines [5], 1,4-dihydro-
1,6-naphthyridines [6], pyrido[2,3-d]pyrimidines [7],
5,6,7,8-tetrahydroquinolines [8], and 5,6,7,8-tetra-
hydroisoquinolines [9].
The mechanism of formation of pyridine-3-carbo-
nitrile derivatives 5 includes initial condensation of
aldehyde 1 with acetophenone 2 to give chalcone A
which reacts with cyanothioacetamide (3) to form
Michael adduct B. Intramolecular cyclization of the
latter leads to substituted sodium 1,4,5,6-tetrahydro-
pyridine-2-thiolate C, and its alkylation with halogen
derivative 4 yields sulfide 5. Compounds 5 can be used
as intermediate products in the synthesis of antihyper-
tensive [13–15] and antidiabetic agents [16].
Addition of sodium ethoxide to the reaction mixture
catalyzed intramolecular cyclization of sulfides 5 in
situ to produce 3-amino-4,6-diarylthieno[2,3-b]pyri-
dine derivatives 6a–6p. Compounds of this series can
be used for the treatment of inflammatory [17] and
oncological diseases [18–20]. Functionalized pyridine
and thienopyridine derivatives like 5 and 6 attract
interest as intermediate products for the synthesis of
more complex heterocyclic systems [21–23].
In continuation of our studies of multicomponent
reactions [10–12], herein we report the multicom-
ponent condensation of aromatic aldehydes 1a–1d with
acetophenones 2a and 2b, cyanothioacetamide (3), and
alkylating agents 4a–4q. By varying the reaction
conditions and alkylating agent, we succeeded in
obtaining 2-(alkylsulfanyl)-4,6-diarylpyridine-3-carbo-
nitriles 5a–5h, 3-amino-4,6-diarylthieno[2,3-b]pyri-
dines 6a–6p and 7, 4-(2-methoxyphenyl)-6-phenyl-2-
sulfanylidene-1,2-dihydropyridine-3-carbonitrile (8),
and 2,2′-(disulfanediyl)bis(4,6-diarylpyridine-3-carbo-
nitriles) 9a and 9b (Scheme 1). The reactions were
carried out at 0°C in ethanol in the presence of alkali.
Substituted thieno[2,3-b]pyridine 7 was synthesized
by multicomponent condensation of 4-methoxybenzal-
dehyde (1d) with 4-methoxyacetophenone (2b), cyano-
thioacetamide (3), 4-bromobenzoyl bromide (4g), and
acetic anhydride under analogous conditions. Obvi-
ously, in the final reaction stage the amino group
in intermediate thienopyridine 6 underwent double
1273

DYACHENKO et al.
1274
Scheme 1.
S
Ar
(3)
NC
CN
S
O
O
NH2
NaOH
–H2O
ArCHO
+
Ar'
Me
Ar'
Ar
Ar'
O
NH2
1a–1d
2a, 2b
A
B
Ar
N
CN
S
ZCH2Hlg (4a–4q)
Ar'
Ar'
Z
5a–5h
Ar
NH2
(1) 4a–4q
(2) EtONa
Z
S
N
6a–6p
OMe
Ar
NAc2
CN
(1) 4g; (2) Ac2O, ∆
O
Ar'
N
S– Na+
S
N
HO
H
C
MeO
Br
7
CN
Ph
H+
S
–2H2O
OMe
NH
8
Ar
N
CN
S
OMe
O2, AcOH
–2H2O
S
N
MeO
NC
Ar
9a, 9b
1, Ar = 2-MeOC6H4 (a), Ph (b), 4-O2NC6H4 (c), 4-MeOC6H4 (d); 2, Ar′ = Ph (a), 4-MeOC6H4 (b); 4, Hlg = Cl, Z = PhCH2OC(O) (a),
H2NC(O) (b), Ph (c); Hlg = Br, Z = CH2=CH (d); Hlg = Cl, Z = 2-MeC6H4NHCO (e), 4-BrC6H4NHCO (f); Hlg = Br, Z =
4-BrC6H4CO (g), 4-MeC6H4CO (h); 3,4-Cl2C6H3CO (i); Hlg = Cl, Z = naphthalen-1-ylcarbamoyl (j), EtOC(O) (k), PhNHCO (l);
Hlg = Br, Z = PhCO (m); Hlg = Cl, Z = Me(CH2)7OC(O) (n), Me(CH2)8OC(O) (o), 4-AcC6H4NHCO (p), 1,3-thiazol-2-ylcar-
bamoyl (q); 5, Ar = Ar′ = 4-MeOC6H4, Z = PhCH2OC(O) (a), H2NCO (b); Ar = 4-O2NC6H4, Ar′ = Ph, Z = H2NCO (c); Ar′ = Z =
Ph (d); Ar′ = Ph, Z = CH2=CH (e); Ar = Ar′ = Ph, Z = CH2=CH (f); Ar = 2-MeOC6H4, Ar′ = Ph, Z = CH2=CH (g), 2-MeC6H4NHCO (h);
6, Ar = Ar′ = 4-MeOC6H4, Z = 4-BrC6H4NHCO (a); Ar = 4-O2NC6H4, Ar′ = Ph, Z = H2NCO (b); Ar = 2-MeOC6H4, Ar′ = Ph, Z =
4-BrC6H4CO (c), 4-MeC6H4CO (d), 3,4-Cl2C6H3CO (e), naphthalen-1-ylcarbamoyl (f), EtOC(O) (g), PhNHCO (h), PhCH2OC(O) (i),
H2NCO (j); Ar = Ar′ = Ph, Z = PhCO (k), PhCH2OC(O) (l), Me(CH2)7OC(O) (m), Me(CH2)8OC(O) (n), 4-AcC6H4NHCO (o);
Ar = 4-MeOC6H4, Ar′ = Ph, Z = 1,3-thiazol-2-ylcarbamoyl (p); 9, Ar = Ph (a), 4-MeOC6H4 (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018

A NEW VERSION OF MULTICOMPONENT SYNTHESIS
1275
C16
C14
C15
C19
C18
C17
C20
C21
C16
C13
C20
C19
C18
C21
C22
C17
N3
C3
C2
C12
C4
C3A
C11
C10
C9
N3
C5
O8
O9
C8
C4
C3A
C3
C27
C6
C8
C14
C13
C7A
N7
C15
C5
C23
C10
C26
C25
C22
C23
C6
C7A
O9
C2
C28
C27
O8
C9
S1
C12
C11
N7
S1
C24
C24
C25
C26
Fig. 1. Molecular structure of benzyl 3-amino-4,6-diphenyl-
thieno[2,3-b]pyridine-2-carboxylate (6l) according to the
X-ray diffraction data. Non-hydrogen atoms are shown as
thermal vibration ellipsoids with a probability of 50%.
Fig. 2. Molecular structure of octyl 3-amino-4,6-diphenyl-
thieno[2,3-b]pyridine-2-carboxylate (6m) according to the
X-ray diffraction data. Non-hydrogen atoms are shown as
thermal vibration ellipsoids with a probability of 50%.
c
a
0
0
a
c
b
b
Fig. 3. Crystal packing of benzyl 3-amino-4,6-diphenyl-
thieno[2,3-b]pyridine-2-carboxylate (6l).
Fig. 4. Crystal packing of octyl 3-amino-4,6-diphenylthieno-
[2,3-b]pyridine-2-carboxylate (6m).
1
acetylation. We previously described analogous acyla-
tion of 2-amino-7-hydroxy-4-(4-hydroxyphenyl)quino-
line-3-carbonitrile [24].
In the H NMR spectra of 5 and 6, the 5-H proton
of the pyridine ring resonated as a singlet at δ 7.25–
8.00 ppm. The H NMR spectra of 5 also contained
1
a singlet in the region δ 4.02–4.72 ppm, which is
typical of SCH2 group [25–28]. Unlike compounds 5,
the H NMR spectra of 6 lacked SCH2 signal, but
a broadened singlet appeared at δ 5.39–6.90 ppm due
to protons of the amino group. The 13C NMR spectra
of 5a–5h and 6a–6p were consistent with the assigned
structures (see Experimental).
The structure of compounds 5 and 6 was confirmed
by spectral data (see Experimental). The IR spectra of
5 characteristically showed an absorption band at
2216–2223 cm–1 due to stretching vibrations of the
conjugated cyano group. No CN stretching band was
observed in the IR spectra of thienopyridines 6;
instead, NH stretching and bending vibration bands
were present at 3275–3398 and 1634–1645 cm–1,
respectively.
1
The structure of thienopyridines 6l and 6m was un-
ambiguously determined by X-ray analysis (Figs. 1, 2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018

DYACHENKO et al.
H · · · O 2.17(2) Å, ∠NHO 129.9(18)° (6m)] and
1276
C13
N3–H3B···π(C17C16C21) [N3···C16 3.106(5), H3B···C16
2.45(5) Å, ∠N3H3BC16 127(4)°] (6l) or N3–H3B···
π(C18C17C22) [N3···C17 3.071(3), H3B···C17 2.45(2) Å,
∠N3H3BC17 130(2)°] (6m). The benzene rings are
turned with respect to the central fragments through
angles of 75.97(10), 21.63(13)° (6l) and 80.38(6),
12.99(9)° (6m). The octyl substituent in molecule 6m
adopts a t–g––t–g––t conformation (“t” stands for trans,
and “g,” for gauche).
C37
C36
C35
O10
C11
C38
C39
C34
C25
C10
C9
N40
C40
C26
C12
C7
C8
C24
C23
C27
C21
C3
N2
S2
C4
C5
Molecules 6l and 6m in crystal are packed in stacks
along the a crystallographic axis (Figs. 3, 4). The dis-
tance between their molecules in a stack corresponds
to van der Waals interactions.
C28
C29
N22
C19
C1
C6
S1
C18
C14
C32
C30
O30
C20
N20
C15
C31
Acidification of the reaction mixture led to the
formation of 4,6-diaryl-2-sulfanylidene-1,2-dihydro-
pyridine-3-carbonitrile 8 which was synthesized
previously by three-component condensation of
2-methoxybenzaldehyde with cyanothioacetamide and
4,4,4-trifluoro-1-phenylbutane-1,3-dione [29]. Inter-
mediate C is readily oxidized with atmospheric oxygen
in the presence of acetic acid to give disulfides 9a
and 9b. The structure of 9a was confirmed by X-ray
analysis (Fig. 5).
C16
C17
C33
Fig. 5. Molecular structure of 2,2′-(disulfanediyl)bis-
[6-(4-methoxyphenyl)-4-phenylpyridine-3-carbonitrile] (9a)
according to the X-ray diffraction data. Non-hydrogen atoms
are shown as thermal vibration ellipsoids with a probability
of 50%.
Disulfide 9a molecule in crystal has a gauche con-
formation [torsion angle C1S1S2C21 79.11(17)°], which
is energetically more favorable due to orbital (gener-
alized anomeric) effect. The pyridine rings are almost
orthogonal to each other: the dihedral angle between
their planes is 82.89(7)°. The benzene rings are turned
with respect to the pyridine ring linked thereto by
21.76(9), 47.21(6)° and 35.51(7), 37.76(6)°. The me-
thoxy groups are almost coplanar to the corresponding
phenyl substituents (the deviations of the non-hydrogen
atoms of the MeO groups from the mean-square planes
are 0.047 and 0.037 Å). Molecules 9a in crystal are
stacked at van der Waals distances from each other
along the a crystallographic axis (Fig. 6).
a
c
0
b
EXPERIMENTAL
Fig. 6. Crystal packing of 2,2′-(disulfanediyl)bis[6-(4-me-
thoxyphenyl)-4-phenylpyridine-3-carbonitrile] (9a).
The X-ray diffraction data for compounds 6l, 6m,
and 9a were obtained on a Belok synchrotron station
with a Rayonix SX165 two-coordinate CCD detector
at the “Kurchatov Institute” National Research Center
(λ 0.96990 Å, ω-scanning with a step of 1.0°). The
data were processed using iMOSFLM program im-
plemented in CCP4 package [30]. A correction for
absorption was applied by SCALA program [31]. The
principal crystallographic and structure refinement
The central 3-aminothieno[2,3-b]pyridine-2-carbox-
ylate fragment in molecules 6l and 6m is planar: the
average deviation of atoms from the mean-square
plane is 0.040 (6l) or 0.020 Å (6m); the planar con-
formation of this fragment is stabilized by intramolec-
ular hydrogen bonds N3–H3A···O9 [N···O 2.836(5),
H···O 2.14(5) Å, ∠NHO 133(4)° (6l); N···O 2.783(2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018

A NEW VERSION OF MULTICOMPONENT SYNTHESIS
Table 1. X-Ray diffraction data for compounds 6l, 6m, and 9a
Parameter
1277
6l
6m
9a
Formula
C27H20N2O2S
436.51
C28H30N2O2S
458.60
C38H26N4O2S2
634.75
Molecular weight
Temperature, K
100(2)
100(2)
100(2)
Single crystal dimensions, mm
0.10×0.20×0.30
Triclinic
0.07×0.15×0.30
Triclinic
0.15×0.20×0.30
Triclinic
Crystal system
Space group
P-1
P-1
P-1
Unit cell parameters:
a, Å
b, Å
08.6690(11)
11.8751(13)
12.1222(14)
68.60(3)
81.42(3)
71.28(3)
1099.7(4)
2
10.400(2)
10.620(2)
12.070(2)
72.74(3)
80.96(3)
70.48(3)
1197.4(5)
2
0008.2601(17)
14.024(3)
14.100(3)
100.11(3)
97.76(3)
101.36(3)
1552.0(6)
2
c, Å
α, deg
β, deg
γ, deg
V, Å3
Z
d
calc, g/cm3
1.318
1.272
1.358
F(000)
456
488
660
μ, mm–1
0.395
0.368
0.492
2θmax, deg
76.84
76.84
76.82
Total number of reflections
Number of independent reflections (Rint)
Number of reflections with I > 2σ(I)
Number of variables
10138
10758
20196
3785 (0.037)
2898
4096 (0.066)
3334
5293 (0.044)
4785
296
306
418
R1, wR2 [reflections with I > 2σ(I)]
R1, wR2 (all independent reflections)
Goodness of fit with respect to F2
Extinction coefficient
0.079, 0.187
0.108, 0.222
1.017
0.048, 0.128
0.066, 0.139
1.083
0.045, 0.115
0.052, 0.123
1.073
0.108(9)
0.880, 0.950
0.012(1)
0.885, 0.968
0.0062(6)
0.860, 0.920
T
min, Tmax
parameters are given in Table 1. The structures were
solved by the direct method and were refined against
F2 by the full-matrix least-squares method in aniso-
tropic approximation for non-hydrogen atoms. Hydro-
gen atoms of the amino groups of 6l and 6m were
localized by the difference Fourier syntheses, and their
positions were refined according to the riding model
with fixed isotropic thermal displacement parameters
[Uiso(H) = 1.2Ueq(N)]. The positions of the other
hydrogen atoms in all compounds were calculated
geometrically and were refined with fixed positional
(riding model) and isotropic thermal parameters
[Uiso(H) = 1.5Ueq(C) for CH3 groups, Uiso(H) =
1.2Ueq(C) for other hydrogens]. All calculations were
performed using SHELXTL software package [32].
The tabulated coordinates of atoms, bond lengths,
bond and torsion angles, and anisotropic thermal
displacement parameters for compounds 6l, 6m, and
9a were deposited to the Cambridge Crystallographic
Data Centre [CCDC entry nos. 1844206 (6l), 1844207
(6m), 1844208 (9a)].
The IR spectra were recorded in mineral oil on
1
an IKS-40 spectrometer. The H and 13C NMR spectra
were measured on a Varian VXR-400 spectrometer at
399.97 and 100 MHz, respectively, using DMSO-d6 as
solvent and tetramethylsilane as internal standard.
The high-resolution mass spectra were obtained on
a Thermo Fischer Scientific Orbitrap Elite instrument;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018

DYACHENKO et al.
1278
samples were dissolved in 1 mL of DMSO, diluted by
a factor of 100 with 1% formic acid in acetonitrile, and
introduced at a flow rate of 40 μL/min into electro-
spray ionization source using a syringe pump, the
source gas flow being turned off (needle voltage
3.5 kV, capillary temperature 275°C; positive and
negative ion detection in the orbital trap, resolution
480 000); the mass scale was calibrated against
[2DMSO + H+] (internal, m/z 157.03515) for positive
ions and dodecyl sulfate anion (m/z 265.14789) for
negative ions. The other mass spectra (electron impact,
70 eV) were recorded on an Agilent 1100 Series
LC/MSD instrument; samples were introduced in
acetic acid. The elemental analyses were obtained with
a Perkin Elmer CHN analyzer. The melting points
were measured on a Kofler hot stage. The progress of
reactions was monitored, and the purity of the isolated
compounds was checked, by TLC on Silufol UV-254
plates using acetone–hexane (3 :5) as eluent; spots
were visualized by treatment with iodine vapor and
under UV light.
(C≡N), 1649 (C=O). 1H NMR spectrum, δ, ppm: 3.81 s
(3H, MeO), 3.82 s (3H, MeO), 4.02 s (2H, SCH2),
7.01 d (2H, Harom, J = 9.0 Hz), 7.10 d (2H, H, Harom
,
J = 8.9 Hz), 7.21 br.s and 7.65 br.s (1H each, NH2),
7.68 d (2H, Harom, J = 8.9 Hz), 7.77 s (1H, 5-H), 8.25 d
(2H, Harom, J = 9.0 Hz). 13C NMR spectrum, δC, ppm:
34.33, 55.82, 55.85, 101.64, 114.64 (2C), 114.75,
115.32, 116.60, 116.63, 128.30, 129.53, 129.94 (2C),
130.66 (2C), 153.97, 158.04, 161.21, 161.88, 162.58,
169.36. Found: m/z 406.1220 [M + H]+. C22H19N3O3S.
Calculated: M + H 406.1147.
2-[3-Cyano-4-(4-nitrophenyl)-6-phenylpyridin-2-
ylsulfanyl]acetamide (5c). Yield 3.1 g (79%), color-
less powder, mp 238–240°C (from AcOH). IR spec-
trum, ν, cm–1: 3325, 3300, 3282 (NH2), 2216 (C≡N),
1
1675 (NO2), 1648 (C=O). H NMR spectrum, δ, ppm:
4.10 s (2H, SCH2), 7.26 br.s (1H, NH2), 7.54 br.s (3H,
Harom), 7.72 br.s (1H, NH2), 7.98 s (1H, 5-H), 8.02 d
(2H, Harom, J = 8.4 Hz), 8.30 d (2H, Ph, J = 7.8 Hz),
8.41 d (2H, Harom, J = 8.4 Hz). 13C NMR spectrum, δC,
ppm: 34.18, 103.6, 115.35, 116.20, 123.90 (2C),
127.92 (2C), 128.97 (2C), 130.43 (2C), 131.05,
136.44, 141.92, 148.39, 152.09, 158.34, 162.55,
168.82. Found: m/z 389.0712 [M – H]+. C20H14N4O3S.
Calculated: M – H 389.0787.
Compounds 5a–5h (general procedure). A mixture
of 0.4 g (10 mmol) of sodium hydroxide, 5 mL of
water, and 5 mL of 95% ethanol was cooled to 0°C,
10 mmol of acetophenone 2 and 10 mmol of aromatic
aldehyde 1 were added, and the mixture was stirred for
1 h at that temperature. A solution of 1 g (10 mmol) of
cyanothioacetamide (3) in 20 mL of ethanol was
added, and the mixture was left to stand for 2 h at 0°C.
Halogen derivative 4, 10 mmol, was then added with
stirring, and the mixture was stirred for 30 min at room
temperature and diluted with an equal volume of water.
The precipitate was filtered off and washed with water,
ethanol, and hexane.
2-(Benzylsulfanyl)-4-(4-nitrophenyl)-6-phenyl-
pyridine-3-carbonitrile (5d). Yield 2.9 g (69%),
yellow powder, mp 211–213°C (from BuOH). IR
1
spectrum, ν, cm–1: 2221 (C≡N), 1670 (NO2). H NMR
spectrum, δ, ppm: 4.72 s (2H, SCH2), 7.24 t (1H, Harom
J = 7.3 Hz), 7.30 t (2H, Harom, J = 7.1 Hz), 7.47 d (2H,
arom, J = 7.3 Hz), 7.52–7.59 m (3H, Harom), 7.95 s
,
H
(1H, 5-H), 7.99 d (2H, Harom, J = 8.6 Hz), 8.21–8.29 m
(2H, Harom), 8.37 d (2H, Harom, J = 8.6 Hz). 13C NMR
spectrum, δC, ppm: 34.47, 103.40, 115.51, 116.87,
124.16 (2C), 127.71, 128.10 (2C), 128.92 (2C), 129.24
(2C), 129.41 (2C), 130.79 (2C), 131.38, 136.99,
137.67, 142.39, 148.93, 152.72, 158.81, 162.86. Mass
spectrum: m/z 424 (Irel 100%) [M + H]+. Found, %:
C 70.80; H 3.96; N 9.81. C25H17N3O2S. Calculated, %:
C 70.91; H 4.05; N 9.92. M 423.49.
Benzyl 2-[3-cyano-4,6-bis(4-methoxyphenyl)-
pyridin-2-ylsulfanyl]acetate (5a). Yield 3.7 g (74%),
yellow powder, mp 182–184°C (from 1,4-dioxane). IR
spectrum, ν, cm–1: 2220 (C≡N), 1715 (C=O). 1H NMR
spectrum, δ, ppm: 3.76 s (3H, MeO), 3.85 s (3H,
MeO), 4.34 s (2H, SCH2), 5.15 s (2H, OCH2), 6.92 d
(2H, Harom, J = 8.8 Hz), 7.13 d (2H, Harom, J = 8.7 Hz),
7.31 br.s (5H, Ph), 7.72 d (2H, Harom, J = 8.7 Hz),
7.81 s (1H, 5-H), 8.16 d (2H, Harom, J = 8.8 Hz). Mass
spectrum: m/z 497 (Irel 100%) [M + H]+. Found, %:
C 70.08; H 4.82; N 5.55. C29H24N2O4S. Calculated, %:
C 70.14; H 4.87; N 5.64. M 496.583.
4-(4-Nitrophenyl)-6-phenyl-2-(prop-2-en-1-yl-
sulfanyl)pyridine-3-carbonitrile (5e). Yield 2.5 g
(68%), yellow powder, mp 189–191°C (from PrOH).
IR spectrum, ν, cm–1: 2223 (C≡N), 1672 (NO2).
1H NMR spectrum, δ, ppm: 4.09 d (2H, SCH2, J =
6.8 Hz), 5.13 d (1H, =CH2, Jcis = 8.4 Hz), 5.36 d (1H,
=CH2, Jtrans = 17.0 Hz), 5.96–6.06 m (1H, CH=), 7.49–
7.58 m (3H, Ph), 8.00 s (1H, 5-H), 8.02 d (2H, C6H4,
J = 8.8 Hz), 8.22–8.29 m (2H, Ph), 8.39 d (2H, C6H4,
2-[3-Cyano-4,6-bis(4-methoxyphenyl)pyridin-2-
ylsulfanyl]acetamide (5b). Yield 3.4 g (83%), color-
less powder, mp 253–255°C (from 1,4-dioxane). IR
spectrum, ν, cm–1: 3318, 3295, 3204 (NH2), 2218
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A NEW VERSION OF MULTICOMPONENT SYNTHESIS
1279
J = 8.8 Hz). 13C NMR spectrum, δC, ppm: 32.97,
103.59, 115.71, 116.71, 118.92, 124.25 (2C), 128.03
(2C), 129.50 (2C), 130.86 (2C), 134.48, 133.75,
136.87, 142.34, 148.77, 152.67, 158.58, 162.56. Mass
spectrum: m/z 374 (Irel 100%) [M + H]+. Found, %:
C 67.42; H 3.96; N 11.15. C21H15N3O2S. Calculated,
%: C 67.54; H 4.05; N 11.25. M 373.43.
ppm: 18.24, 34.94, 56.00, 112.32 (2C), 115.90, 117.83
(2C), 121.29 (2C), 125.04, 125.66, 126.38, 128.12
(2C), 129.30 (2C), 130.78, 130.87, 131.20, 132.09,
136.66, 137.07, 152.67, 156.43, 158.58, 161.55,
166.31. Found: m/z 466.1582 [M + H]+. C28H23N3O2S.
Calculated: M + H 466.1511.
2-Substituted 3-amino-4,6-diarylthieno[2,3-b]-
pyridines 6a–6p were synthesized as described above
for compounds 5, but instead of dilution of the reaction
mixture with water a solution of 0.1 g (5 mmol) of
metallic sodium in 15 mL of ethanol was added. The
mixture was then stirred for 2 h at room temperature
and diluted with an equal volume of water, and the
precipitate was filtered off and washed with water,
ethanol, and hexane.
4,6-Diphenyl-2-(prop-2-en-1-ylsulfanyl)pyridine-
3-carbonitrile (5f). Yield 2.1 g (65%), light yellow
needles, mp 91–93°C (from AcOH). IR spectrum:
ν 2219 cm–1 (C≡N). 1H NMR spectrum, δ, ppm: 4.10 d
(2H, SCH2, J = 6.8 Hz), 5.15 d (1H, =CH2, Jcis
=
10.0 Hz), 5.39 d (1H, =CH2, Jtrans = 17.0 Hz), 5.81–
6.16 m (1H, CH=), 7.52–7.60 m (6H, Harom), 7.69–
7.72 m (2H, Harom), 7.93 s (1H, 5-H), 8.23–8.28 m (2H,
Harom). 13C NMR spectrum, δC, ppm: 32.95, 103.52,
116.10, 116.65, 118.81, 127.95 (2C), 129.12 (2C),
129.28 (2C), 129.43 (2C), 130.54, 131.25, 133.83,
136.11, 137.07, 154.74, 158.35, 162.49. Mass spec-
trum: m/z 329 (Irel 100%) [M + H]+. Found, %:
C 76.71; H 4.88; N 8.40. C21H16N2S. Calculated, %:
C 76.80; H 4.91; N 8.53. M 328.43.
3-Amino-N-(4-bromophenyl)-4,6-bis(4-methoxy-
phenyl)thieno[2,3-b]pyridine-2-carboxamide (6a).
Yield 4.3 g (77%), bright yellow powder fluorescing
under UV irradiation, mp 120–122°C (from AcOH). IR
spectrum, ν, cm–1: 3345, 3312, 3275 (NH, NH2), 1664
1
(CONH), 1642 (δNH2). H NMR spectrum, δ, ppm:
3.87 s (3H, MeO), 3.91 s (3H, MeO), 6.04 br.s (2H,
NH2), 6.70 d (2H, Harom, J = 8.5 Hz), 7.06 d (2H, Harom
,
4-(2-Methoxyphenyl)-6-phenyl-2-(prop-2-en-
1-ylsulfanyl)pyridine-3-carbonitrile (5g). Yield 2.5 g
(69%), colorless lustrous crystals, mp 89–91°C (from
J = 8.6 Hz), 7.25 s (1H, 5-H), 7.31–7.49 m (6H, Harom),
8.07 d (2H, Harom, J = 8.8 Hz), 8.10 s (1H, NH). Mass
spectrum: m/z 561 (Irel 100%) [M + H]+. Found, %:
C 59.87; H 3.82; N 7.38. C28H22BrN3O3S. Calculated,
%: C 60.00; H 3.96; N 7.50. M 560.468.
1
MeOH). IR spectrum: ν 2216 cm–1 (C≡N). H NMR
spectrum, δ, ppm: 3.78 s (3H, MeO), 4.07 d (2H,
SCH2, J = 6.8 Hz), 5.14 d (1H, =CH2, Jcis = 8.3 Hz),
5.36 d (1H, =CH2, Jtrans = 17.0 Hz), 5.79–6.11 m (1H,
3-Amino-4-(4-nitrophenyl)-6-phenylthieno-
[2,3-b]pyridine-2-carboxamide (6b). Yield 3.3 g
(84%), yellow powder, mp 307–309°C (from 1,4-di-
oxane), sublimes at 240°C. IR spectrum, ν, cm–1: 3340,
3300, 3281, 3250 (NH2), 1666 (C=O), 1642 (δNH2).
1H NMR spectrum, δ, ppm: 5.95 br.s (2H, NH2),
7.31 br.s (2H, CONH2), 7.42–7.54 m (3H, Harom),
7.83 s (1H, 5-H), 7.86 d (2H, Harom, J = 8.7 Hz), 8.22 d
(2H, Harom, J = 8.0 Hz), 8.39 d (2H, Harom, J = 8.7 Hz).
13C NMR spectrum, δC, ppm: 99.86, 118.52, 121.24,
124.07 (2C), 127.62 (2C), 129.39 (2C), 130.39, 131.06
(2C), 137.81, 143.57, 145.79, 145.95, 148.30, 156.02,
160.23, 167.36. Mass spectrum: m/z 391 (Irel 100%)
[M + H]+. Found, %: C 61.40; H 3.55; N 14.21.
C20H14N4O3S. Calculated, %: C 61.53; H 3.61;
N 14.35. M 390.423.
CH=), 7.09 t (1H, Harom, J = 7.6 Hz), 7.21 d (1H, Harom
,
J = 7.8 Hz), 7.40 d (1H, Harom, J = 7.6 Hz), 7.45–
7.53 m (4H, Harom), 7.82 s (1H, 5-H), 8.19–8.22 m (2H,
H
arom). 13C NMR spectrum, δC, ppm: 32.85, 55.98,
105.69, 112.27, 115.81, 117.70, 118.81, 121.22,
125.08, 127.85 (2C), 129.46 (2C), 130.84, 131.18,
132.01, 133.91, 137.13, 152.71, 156.36, 158.33,
161.34. Found: m/z 359.1214 [M + H]+. C22H18N2OS.
Calculated: M + H 359.1140.
2-[3-Cyano-4-(2-methoxyphenyl)-6-phenylpyri-
din-2-ylsulfanyl]-N-(4-methylphenyl)acetamide
(5h). Yield 3.7 g (79%), colorless lustrous crystals,
mp 198–200°C (from 1,4-dioxane). IR spectrum, ν,
1
cm–1: 3310 (NH), 2218 (C≡N), 1675 (C=O). H NMR
spectrum, δ, ppm: 2.13 s (3H, Me), 3.81 s (3H, MeO),
4.40 s (2H, SCH2), 7.01–7.15 m (3H, Harom), 7.17 d
(1H, Harom, J = 7.3 Hz), 7.23 d (1H, Harom, J = 8.4 Hz),
7.37 d (1H, Harom, J = 7.6 Hz), 7.39–7.44 m (3H,
[3-Amino-4-(2-methoxyphenyl)-6-phenylthieno-
[2,3-b]pyridin-2-yl](4-bromophenyl)methanone
(6c). Yield 3.8 g (73%), yellow powder, mp 129–
131°C (from BuOH). IR spectrum, ν, cm–1: 3338,
3304, 2291 (NH2), 1697 (C=O), 1635 (δ NH2).
1H NMR spectrum, δ, ppm: 3.75 s (3H, Me), 6.84 br.s
Harom), 7.47 d (1H, Harom, J = 7.2 Hz), 7.54 t (1H, Harom,
J = 8.3 Hz), 7.84 s (1H, 5-H), 8.26 d (2H, Harom, J =
7.3 Hz), 9.71 br.s (1H, NH). 13C NMR spectrum, δC,
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DYACHENKO et al.
1280
(2H, NH2), 7.20 t (1H, Harom, J = 7.5 Hz), 7.28 d (1H,
7.08 d (1H, Harom, J = 8.1 Hz), 7.11–7.18 m (1H,
arom), 7.25 s (1H, 5-H), 7.33 d (1H, Harom, J = 7.4 Hz),
7.35–7.56 m (7H, Harom), 7.59 s (1H, NH), 7.73 d (1H,
arom, J = 7.7 Hz), 7.81–7.89 m (3H, Harom), 7.97 d
(1H, Harom, J = 7.4 Hz), 8.13 d (1H, Harom, J = 6.0 Hz).
Mass spectrum: m/z 502 (Irel 100%) [M + H]+. Found,
%: C 74.12; H 4.55; N 8.21. C31H23N3O2S. Calculated,
%: C 74.23; H 4.62; N 8.38. M 501.606.
H
arom, J = 8.3 Hz), 7.42 d (1H, Harom, J = 7.5 Hz),
H
7.46–7.53 m (3H, Harom), 7.60 t (1H, Harom, J = 6.8 Hz),
7.63–7.71 m (4H, Harom), 7.79 s (1H, 5-H), 8.20 d (2H,
H
H
arom, J = 6.8 Hz). 13C NMR spectrum, δC, ppm: 56.31,
113.11, 118.89 (2C), 121.16 (2C), 124.32, 127.30,
127.75, 128.64, 129.44 (2C), 129.79 (2C), 129.96
(2C), 130.30, 130.59, 131.00, 131.97, 132.04, 144.68,
149.30, 154.63, 157.44, 162.33, 188.23. Found:
m/z 515.0422 [M + H]+. C27H19BrN2O2S. Calculated:
M + H 515.0351.
Ethyl 3-amino-4-(2-methoxyphenyl)-6-phenyl-
thieno[2,3-b]pyridine-2-carboxylate (6g). Yield 2.7 g
(68%), light yellow needles, mp 183–185°C (from
BuOH). IR spectrum, ν, cm–1: 3333, 3307, 2281 (NH2),
1704 (C=O), 1645 (δNH2). 1H NMR spectrum, δ, ppm:
1.28 t (3H, MeCH2, J = 6.8 Hz), 3.72 s (3H, MeO),
4.25 q (2H, OCH2, J = 6.8 Hz), 5.71 br.s (2H, NH2),
7.16 t (1H, Harom, J = 7.2 Hz), 7.24 d (1H, Harom, J =
8.1 Hz), 7.38 d (1H, Harom, J = 6.4 Hz), 7.41–7.52 m
(3H, Harom), 7.58 t (1H, Harom, J = 7.2 Hz), 7.73 s (1H,
5-H), 8.18 d (2H, Harom, J = 5.6 Hz). 13C NMR spec-
trum, δC, ppm: 15.02, 56.34, 60.64, 112.35, 118.98
(2C), 121.43 (2C), 124.72, 127.64 (2C), 129.39 (2C),
130.44, 130.55, 131.70, 137.52, 145.59, 147.72,
156.56, 156.96, 160.68, 165.31. Found: m/z 405.1272
[M + H]+. C23H20N2O3S. Calculated: M + H 405.1195.
[3-Amino-4-(2-methoxyphenyl)-6-phenylthieno-
[2,3-b]pyridin-2-yl](4-methylphenyl)methanone
(6d). Yield 3.1 g (68%), bright yellow powder,
mp 203–205°C (from AcOH). IR spectrum, ν, cm–1:
3352, 3303, 3276 (NH2), 1694 (C=O), 1644 (δNH2).
1H NMR spectrum, δ, ppm: 2.39 s (3H, Me), 3.75 s
(3H, MeO), 6.79 br.s (2H, NH2), 7.13–7.52 m (8H,
H
H
arom), 7.54–7.76 m (4H, Harom), 8.14–8.22 m (2H,
arom). 13C NMR spectrum, δC, ppm: 22.14, 53.84,
113.14 (2C), 118.74 (2C), 119.13 (2C), 119.47, 121.11,
123.15, 125.96, 127.17, 127.81 (2C), 128.98, 129.05,
129.53, 129.80, 130.15, 130.46, 131.08, 131.66,
132.14, 145.57, 148.49, 154.72, 186.15. Found:
m/z 451.1474 [M + H]+. C28H22N2O2S. Calculated:
M + H 451.1402.
3-Amino-4-(2-methoxyphenyl)-N,6-diphenyl-
thieno[2,3-b]pyridine-2-carboxamide (6h). Yield
3.7 g (82%), bright yellow powder, mp 206–208°C
(from 1,4-dioxane). IR spectrum, ν, cm–1: 3338, 3302,
[3-Amino-4-(2-methoxyphenyl)-6-phenylthieno-
[2,3-b]pyridin-2-yl](3,4-dichlorophenyl)methanone
(6e). Yield 4 g (80%), bright yellow powder, mp 128–
130°C (from AcOH). IR spectrum, ν, cm–1: 3341,
3300, 3288 (NH2), 1711 (C=O), 1635 (δ NH2).
1H NMR spectrum, δ, ppm: 3.77 s (3H, Me), 6.88 br.s
(2H, NH2), 7.21 t (1H, Harom, J = 7.4 Hz), 7.30 d (1H,
1
3290 (NH, NH2), 1669 (C=O), 1634 (δNH2). H NMR
spectrum, δ, ppm: 3.73 s (3H, Me), 5.92 br.s (2H,
NH2), 7.07 t (1H, Harom, J = 7.3 Hz), 7.17 t (1H, Harom
,
J = 7.4 Hz), 7.24 d (1H, Harom, J = 8.4 Hz), 7.31 t
(2H, Harom, J = 8.1 Hz), 7.40 d (1H, Harom, J = 7.4 Hz),
7.46–7.59 m (4H, Harom), 7.66 d (2H, Harom, J =
8.2 Hz), 7.74 s (1H, 5-H), 8.21 d (2H, Harom, J =
8.1 Hz), 9.52 br.s (1H, NH). 13C NMR spectrum, δC,
ppm: 56.14, 98.01, 112.29, 119.06 (2C), 121.35,
121.77 (2C), 122.58, 124.04, 125.41, 127.58 (2C),
128.88 (2C), 129.39 (2C), 130.31, 130.57, 131.58,
137.91, 139.25, 144.96, 147.42, 156.50, 159.99,
164.26. Found: m/z 452.1428 [M + H]+. C27H21N3O2S.
Calculated: M + H 452.1354.
Harom, J = 8.4 Hz), 7.43 d (1H, Harom, J = 7.3 Hz),
7.48–7.54 m (3H, Harom), 7.62 t (1H, Harom, J = 7.9 Hz),
7.77–7.84 m (3H, Harom), 7.98 s (1H, 5-H), 8.22 d (2H,
H
arom, J = 5.4 Hz). 13C NMR spectrum, δC, ppm: 56.24,
103.30, 112.55, 119.34, 121.38, 121.66, 124.82,
127.77, 128.02 (2C), 129.44, 129.89 (2C), 130.47
(2C), 130.76, 131.38, 131.96, 132.01, 134.39, 137.52,
146.53, 151.59, 156.23, 158.29, 162.39, 186.26. Mass
spectrum: m/z 506 (Irel 100%) [M + H]+. Found, %:
C 64.01; H 3.42; N 5.44. C27H18Cl2N2O2S. Calculated,
%: C 64.16; H 3.59; N 5.54. M 505.426.
Benzyl 3-amino-4-(2-methoxyphenyl)-6-phenyl-
thieno[2,3-b]pyridine-2-carboxylate (6i). Yield 3.9 g
(84%), bright yellow powder, mp 156–158°C (from
BuOH). IR spectrum, ν, cm–1: 3338, 3305, 2907 (NH2),
1713 (C=O), 1636 (δNH2). 1H NMR spectrum, δ, ppm:
3.78 s (3H, Me), 5.30 s (2H, CH2), 5.78 br.s (2H,
3-Amino-4-(2-methoxyphenyl)-N-(naphthalen-
1-yl)-6-phenylthieno[2,3-b]pyridine-2-carboxamide
(6f). Yield 4 g (79%), yellow powder, mp 199–201°C
(from AcOH). IR spectrum, ν, cm–1: 3354, 3300, 3286
1
(NH2, NH), 1666 (C=O), 1640 (δNH2). H NMR spec-
NH2), 7.17 t (1H, Harom, J = 7.4 Hz), 7.24 d (1H, Harom
J = 8.4 Hz), 7.26–7.50 m (8H, Harom), 7.59 t (2H, Harom
,
,
trum, δ, ppm: 3.73 s (3H, Me), 5.93 br.s (2H, NH2),
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A NEW VERSION OF MULTICOMPONENT SYNTHESIS
1281
J = 7.5 Hz), 7.75 s (1H, 5-H), 8.18 d (2H, Harom, J =
5.7 Hz). 13C NMR spectrum, δC, ppm: 56.15, 65.81,
112.36, 119.03, 121.44, 122.11, 125.06, 127.66 (2C),
128.27 (2C), 129.40, 130.48 (2C), 130.55 (2C), 131.73
(2C), 135.12, 136.03, 137.06, 137.72, 145.49, 148.77,
156.42, 157.60, 161.08, 164.51. Found: m/z 467.1422
[M + H]+. C28H22N2O3S. Calculated: M + H 467.1351.
cubic crystals fluorescing under UV irradiation,
mp 106–108°C (from AcOH). IR spectrum, ν, cm–1:
3330, 3295, 3287 (NH2), 1712 (C=O), 1645 (δNH2).
1H NMR spectrum, δ, ppm: 0.81 t (3H, Me, J =
6.6 Hz), 1.17–1.34 m (10H, CH2), 1.54–1.60 m (2H,
CH2), 4.17 t (2H, OCH2, J = 6.6 Hz), 5.77 br.s (2H,
NH2), 7.38–7.51 m (3H, Harom), 7.57 s (5H, Ph), 7.76 s
(1H, 5-H), 8.18 d (2H, Harom, J = 8.0 Hz). 13C NMR
spectrum, δC, ppm: 14.38, 22.50, 25.83, 28.69, 29.02,
29.04, 31.62, 64.50, 95.32, 118.65, 120.71, 127.66,
129.05 (2C), 129.33 (2C), 129.75 (4C), 130.43,
136.72, 137.69, 147.92, 148.48, 156.80, 161.37,
164.75. Found: m/z 459.2105 [M + H]+. C28H30N2O2S.
Calculated: M + H 459.2028.
3-Amino-4-(2-methoxyphenyl)-6-phenylthieno-
[2,3-b]pyridine-2-carboxamide (6j). Yield 2.9 g
(77%), bright yellow powder fluorescing under UV
irradiation, mp 208–210°C (from EtOAc). IR spec-
trum, ν, cm–1: 3388, 3012, 2285 (NH2), 1666 (C=O),
1
1639 (δNH2). H NMR spectrum, δ, ppm: 3.76 s
(3H, Me), 5.39 br.s (2H, NH2), 5.86 br.s (2H, CONH2),
7.06 d (1H, Harom, J = 8.2 Hz), 7.12 t (1H, Harom, J =
7.0 Hz), 7.30 d (1H, Harom, J = 7.4 Hz), 7.39–7.50 m
(4H, Harom), 7.55 s (1H, 5-H), 8.09 d (2H, Harom, J =
6.6 Hz). Mass spectrum: m/z 376 (Irel 100%) [M + H]+.
Found, %: C 76.01; H 4.44; N 11.00. C21H17N3O2S.
Calculated, %: C 67.18; H 4.56; N 11.19. M 375.448.
(3-Amino-4,6-diphenyltieno[2,3-b]pyridin-2-yl)-
(phenyl)methanone (6k). Yield 3.2 g (79%), bright
yellow powder fluorescing under UV irradiation,
mp 156–158°C (AcOH). IR spectrum, ν, cm–1: 3333,
3015, 2284 (NH2), 1697 (C=O), 1641 (δ NH2).
1H NMR spectrum, δ, ppm: 6.90 br.s (2H, NH2), 7.34–
Nonyl 3-amino-4,6-diphenylthieno[2,3-b]pyri-
dine-2-carboxylate (6n). Yield 2.9 g (67%), bright
yellow powder fluorescing under UV irradiation,
mp 67–68°C (from EtOH). IR spectrum, ν, cm–1: 3337,
3302, 3000 (NH2), 1712 (C=O), 1636 (δ NH2).
1H NMR spectrum, δ, ppm: 0.82 t (3H, Me, J =
6.7 Hz), 1.14–1.38 m (12H, CH2), 1.63 t (2H, CH2, J =
6.9 Hz), 4.18 t (2H, OCH2, J = 6.3 Hz), 5.79 br.s (2H,
NH2), 7.49 d (3H, Harom, J = 7.2 Hz), 7.60 s (5H, Ph),
7.77 s (1H, 5-H), 8.20 d (2H, Harom, J = 7.2 Hz).
13C NMR spectrum, δC, ppm: 14.36, 22.56, 25.88,
28.74, 29.10, 29.37, 31.73, 33.40, 64.54, 95.61,
108.92, 118.62, 120.76 (2C), 127.68 (2C), 129.07
(2C), 129.32 (2C), 129.35, 129.77, 136.83, 137.81,
147.94, 148.46, 156.84, 161.50, 164.82. Mass spec-
trum: m/z 473 (Irel 100%) [M + H]+. Found, %:
C 73.60; H 6.71; N 5.85. C29H32N2O2S. Calculated, %:
C 73.70; H 6.82; N 5.93. M 472.65.
7.58 m (6H, Harom), 7.61 s (5H, Ph), 7.75 d (2H, Harom
,
J = 6.6 Hz), 7.81 s (1H, 5-H), 8.20 d (2H, Harom, J =
7.0 Hz). 13C NMR spectrum, δC, ppm: 103.90, 116.63,
118.90, 120.26, 127.76 (4C), 128.96 (4C), 129.38
(2C), 129.54, 129.95, 130.68, 131.68, 136.60, 137.56,
141.17, 149.40, 150.56, 157.76, 162.60, 189.45.
Found: m/z 407.1214 [M + H]+. C26H18N2OS. Calculat-
ed: M + H 407.1140.
Benzyl 3-amino-4,6-diphenylthieno[2,3-b]pyri-
dine-2-carboxylate (6l). Yield 3.5 g (81%), light
yellow powder fluorescing under UV irradiation,
mp 176–178°C (from BuOH). IR spectrum, ν, cm–1:
3342, 3307, 3288 (NH2), 1713 (C=O), 1644 (δNH2).
1H NMR spectrum, δ, ppm: 5.29 s (2H, CH2), 5.85 br.s
(2H, NH2), 7.31 d (1H, Harom, J = 6.7 Hz), 7.36–7.44 m
(3H, Harom), 7.46–7.53 m (4H, Harom), 7.58 s (5H, Ph),
7.78 s (1H, 5-H), 8.20 d (2H, Harom, J = 7.8 Hz).
13C NMR spectrum, δC, ppm: 65.81, 118.74, 120.66,
127.70 (2C), 128.23 (4C), 128.48 (2C), 128.96 (4C),
129.06, 129.37, 129.81, 130.50, 136.67, 136.85,
137.66, 148.42, 148.60, 156.98, 161.45, 164.48.
Found: m/z 437.1322 [M + H]+. C27H20N2O2S. Calcu-
lated: M + H 437.1245.
N-(4-Acetylphenyl)-3-amino-4,6-diphenylthieno-
[2,3-b]pyridine-2-carboxamide (6o). Yield 3.3 g
(72%), yellow powder, mp 210–212°C (from BuOH).
IR spectrum, ν, cm–1: 3398, 3330, 3284 (NH, NH2),
1707 (MeC=O), 1669 (CONH), 1635 (δ NH2).
1H NMR spectrum, δ, ppm: 2.51 s (3H, Me), 6.44 br.s
(2H, NH2), 7.41–7.54 m (3H, Harom), 7.60 s (5H, Ph),
7.78 s (1H, 5-H), 7.82 d (2H, C6H4, J = 8.8 Hz), 7.89 d
(2H, C6H4, J = 8.8 Hz), 8.21 d (2H, Harom, J = 7.7 Hz),
12.41 br.s (1H, CONH). 13C NMR spectrum, δC, ppm:
26.85, 118.75, 120.67 (2C), 127.64 (4C), 129.15 (4C),
129.29 (4C), 129.36 (4C), 129.53, 137.03, 137.91,
148.04, 156.28, 160.57, 164.86, 196.90. Found:
m/z 464.1425 [M + H]+. C28H21N3O2S. Calculated:
M + H 464.1354.
3-Amino-4-(2-methoxyphenyl)-6-phenyl-
N-(1,3-thiazol-2-yl)thieno[2,3-b]pyridine-2-carbox-
amide (6p). Yield 3.2 g (70%), yellow powder,
Octyl 3-amino-4,6-diphenylthieno[2,3-b]pyri-
dine-2-carboxylate (6m). Yield 3.2 g (70%), yellow
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018

DYACHENKO et al.
1282
mp 165–167°C (from AcOH). IR spectrum, ν, cm–1:
(Irel 100%) [M + H]+. C19H14N2OS. Calculated:
M 318.396.
3339, 3325, 3300 (NH, NH2), 1662 (C=O), 1635
1
(δNH2). H NMR spectrum, δ, ppm: 3.87 s (3H, Me),
2,2′-(Disulfanediyl)bis[6-(4-methoxyphenyl)-4-
phenylpyridine-3-carbonitrile] (9a) was synthesized
as described above for compound 8 before the dilution
with aqueous HCl. Instead, the mixture was diluted
with 10 mL of glacial acetic acid and was left to stand
for 48 h at 20°C. The mixture was then diluted with
an equal volume of water, and the precipitate was
filtered off. Yield 2.1 g (66%), colorless fine plates,
mp 171–173°C (from EtOH). IR spectrum: ν 2219 cm–1
6.16 br.s (2H, NH2), 7.02 d (1H, 5′-H, J = 3.5 Hz),
7.15 d (2H, Harom, J = 8.4 Hz), 7.44 d (1H, 4′-H, J =
3.5 Hz), 7.46–7.66 m (5H, Harom), 7.72 s (1H, 5-H),
8.22 d (2H, Harom, J = 8.7 Hz), 12.63 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 55.82, 105.14, 112.03,
114.18, 114.70 (2C), 117.32, 118.67, 123.19, 127.59
(2C), 129.14, 129.34 (2C), 130.19, 130.64 (2C),
138.12, 147.89, 152.06, 157.14, 158.93, 160.38,
161.36. Mass spectrum: m/z 459 (Irel 100%) [M + H]+.
Found, %: C 62.73; H 3.81; N 12.08. C24H18N4O2S.
Calculated, %: C 62.86; H 3.96; N 12.22. M 458.564.
1
(C≡N). H NMR spectrum, δ, ppm: 3.73 s (6H, Me),
6.86 d (4H, Harom, J = 7.0 Hz), 7.56–7.62 m (6H,
Harom), 7.73–7.79 m (4H, Harom), 7.98 s (2H, 5-H),
8.03 d (4H, Harom, J = 7.0 Hz). 13C NMR spectrum, δC,
ppm: 55.79 (2C), 102.97 (2C), 114.67 (4C), 116.09
(2C), 117.79 (2C), 128.90 (2C), 129.21 (4C), 129.38
(4C), 129.66 (4C), 130.75 (2C), 135.79 (2C), 154.84
(2C), 158.53 (2C), 159.33 (2C), 162.10 (2C). Found:
m/z 635.1570 [M + H]+. C38H26N4O2S2. Calculated:
M + H 635.1497.
N-Acetyl-N-[2-(4-bromobenzoyl)-4,6-bis(4-me-
thoxyphenyl)thieno[2,3-b]pyridin-3-yl]acetamide
(7) was synthesized as described above for compounds
6 from aldehyde 1d, acetophenone 2b, cyanothioacet-
amide (3), and 4-bromobenzoyl bromide (4d). The
precipitate was separated and heated in acetic anhy-
dride for 5 min under reflux. After 24 h, the precipitate
was filtered off and washed with diethyl ether. Yield
4.7 g (75%), bright yellow powder fluorescing under
UV irradiation, mp 170–172°C (from AcOH). IR spec-
2,2′-(Disulfanediyl)bis[4,6-bis(4-methoxyphenyl)-
pyridine-3-carbonitrile] (9b) was synthesized in
a similar way from 4-methoxybenzaldehyde 1a. Yield
2.1 g (60%), yellow wool-like material, mp 123–
125°C (from PrOH). IR spectrum: ν 2220 cm–1 (C≡N).
1H NMR spectrum, δ, ppm: 3.73 s (6H, Me), 3.83 s
(6H, Me), 6.85 d (2H, Harom, J = 8.7 Hz), 6.94 t (2H,
Harom, J = 8.9 Hz), 7.01 d (2H, Harom, J = 8.5 Hz),
7.14 d (1H, Harom, J = 8.6 Hz), 7.32 d (1H, Harom, J =
8.3 Hz), 7.44 d (2H, Harom, J = 8.6 Hz), 7.74 d (2H,
1
trum, ν, cm–1: 1692, 1665 (C=O). H NMR spectrum,
δ, ppm: 3.33 s (6H, MeCO), 3.82 s (3H, MeO), 3.88 s
(3H, MeO), 7.04 d (2H, Harom, J = 8.6 Hz), 7.17 d (2H,
Harom, J = 8.5 Hz), 7.55 d (2H, Harom, J = 8.4 Hz),
7.68–7.77 m (5H, 5-H, Harom), 8.18 d (2H, Harom, J =
8.7 Hz). 13C NMR spectrum, δC, ppm: 55.78 (2C),
55.84 (2C), 103.14, 114.75, 115.03 (2C), 118.36,
119.63, 125.24, 128.68, 129.33 (2C), 129.91 (4C),
130.03, 130.43, 131.98 (4C), 140.26, 149.16, 151.39,
157.66, 160.59, 161.56, 162.88, 187.85. Mass spec-
trum: m/z 630 (Irel 100%) [M + H]+. Found, %:
C 60.92; H 3.88; N 4.35. C32H25BrN2O5S. Calculated,
%: C 61.05; H 4.00; N 4.45. M 629.53.
Harom, J = 8.3 Hz), 7.93 s (2H, 5-H), 8.01 d (2H, Harom
,
J = 8.7 Hz), 8.13 d (1H, Harom, J = 8.7 Hz), 8.24 d (1H,
Harom, J = 8.5 Hz). 13C NMR spectrum, δC, ppm: 55.69,
55.79, 55.88, 55.91, 102.53 (2C), 109.98 (4C), 114.45,
114.51, 114.64 (4C), 116.37, 117.42, 127.74, 127.84
(2C), 129.02, 129.46 (2C), 129.60 (4C), 130.64 (2C),
130.86 (4C), 154.45, 158.34, 159.41, 161.24, 161.44,
162.03. Found: m/z 695.1778 [M + H]+. C40H30N4O4S2.
Calculated: M + H 695.1708.
4-(2-Methoxyphenyl)-6-phenyl-2-sulfanylidene-
1,2-dihydropyridine-3-carbonitrile (8). The proce-
dure was the same as described above for compounds
5 before the addition of alkyl halide 4. Instead, the
mixture was diluted with 10% aqueous HCl to pH 5
and was left to stand for 24 h. The precipitate was
filtered off and washed with water, ethanol, and
hexane. Yield 2.2 g (68%), yellow powder, mp 141–
143°C (from BuOH); published data [29]: mp 138–
140°C. 13C NMR spectrum, δC, ppm: 56.12, 112.40,
114.54, 115.73, 116.93, 121.14, 125.76, 127.76, 129.22
(2C), 129.35 (2C), 131.66, 131.92, 132.30, 152.49,
155.01, 156.49, 179.32. Mass spectrum: m/z 319
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (program 5-100 for increasing the
rating of PFUR) and by the Russian Foundation for
Basic Research (project nos. 18-53-06006 Az_a, 16-
29-10669 ofi_m). The X-ray diffraction data were
obtained using the unique Kurchatov Synchrotron
Radiation Source under financial support by the
Ministry of Education and Science of the Russian
Federation (project ID RFMEFI61917X0007).
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A NEW VERSION OF MULTICOMPONENT SYNTHESIS
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19. Cywin, C.L., Chen, Z., Fleck, K.W., Hao, M.-H.,
Hickey, E., Liu, W., Marshall, D.R., Nemoto, P.,
Sorcek, R.J., Sun, S., Wu, J.-P., Morwick, N., and
Emeigh, J., US Patent no. 6964956, 2005; Ref. Zh.,
Khim., 2006, no. 06.14-19O.69P.
REFERENCES
1. Ugi, I., Abstracts of Papers, III Vserossiiskii simpozium
po organicheskoi khimii “Strategiya i taktika organi-
cheskogo sinteza” (IIIrd All-Russian Symp. on Organic
Chemistry “Strategy and Tactics of Organic Synthesis”),
March 3–6, 2001, Yaroslavl, 2001, p. 2.
20. Reichelt, C., Ludwig, A., and Leistner, S., EP Patent
Appl. no. 1683799, 2006; Ref. Zh., Khim., 2007,
no. 07.20-19O.115P.
2. Litvinov, V.P., Russ. Chem. Rev., 2003, vol. 72, p. 69.
21. Dyachenko, V.D., Dyachenko, I.V., and Nenajden-
3. Orru, R.V.A., Book of Abstracts, Chemistry of Nitrogen-
Containing Heterocycles. CNCH-2012, Kharkiv:
Ekskluziv, 2012, L-1.
ko, V.G., Russ. Chem. Rev., 2018, vol. 87, p. 1.
22. Antipin, I.S., Kazymova, M.A., Kuznetsov, M.A.,
Vasilyev, A.V., Ishchenko, M.A., Kiryushkin, A.A.,
Kuznetsova, L.M., Makarenko, S.V., Ostrovskii, V.A.,
Petrov, M.L., Solod, O.V., Trishin, Yu.G., Yakovlev, I.P.,
Nenaidenko, V.G., Beloglazkina, E.K., Beletskaya, I.P.,
Ustynyuk, Yu.A., Solov’ev, P.A., Ivanov, I.V.,
Malina, E.V., Sivova, N.V., Negrebetskii, V.V.,
Baukov, Yu.I., Pozharskaya, N.A., Traven’, V.F., Shche-
kotikhin, A.E., Varlamov, A.V., Borisova, T.N., Lesina,
Yu.A., Krasnokutskaya, E.A., Rogozhnikov, S.I., Shu-
rov, S.N., Kustova, T.P., Klyuev, M.V., Khelevina, O.G.,
Stuzhin, P.A., Fedorov, A.Yu., Gushchin, A.V.,
Dodonov, V.A., Kolobov, A.V., Plakhtinskii, V.V.,
Orlov, V.Yu., Kriven’ko, A.P., Fedotova, O.V., Pchelin-
tseva, N.V., Charushin, V.N., Chupakhin, O.N.,
Klimochkin, Yu.N., Klimochkina, A.Yu., Kuryatni-
kov, V.N., Malinovskaya, Yu.A., Levina, A.S., Zhurav-
lev, O.E., Voronchikhina, L.I., Fisyuk, A.S., Akse-
nov, A.V., Aksenov, N.A., and Aksenova, I.V., Russ. J.
Org. Chem., 2017, vol. 53, p. 1275.
4. Dyachenko, I.V. and Dyachenko, V.D., Russ. J. Org.
Chem., 2015, vol. 51, p. 629.
5. Dyachenko, V.D., Nesterov, V.N., and Dyachenko, I.V.,
Russ. J. Gen. Chem., 2011, vol. 81, p. 751.
6. Dyachenko, V.D., Roman, S.V., and Litvinov, V.P., Russ.
Chem. Bull., Int. Ed., 2000, vol. 49, p. 125.
7. Dyachenko, V.D., Tkacheva, V.P. Dyachenko, A.D., and
Tkachev, R.P., Russ. J. Gen. Chem., 2010, vol. 80,
p. 1034.
8. Dyachenko, V.D., Nesterov, V.N., Dyachenko, S.V., and
Chernykh, A.V., Russ. J. Org. Chem., 2015, vol. 51,
p. 864.
9. Sukach, S.M. and Dyachenko, V.D., Russ. J. Org.
Chem., 2015, vol. 51, p. 1020.
10. Dyachenko, I.V. and Dyachenko, V.D., Russ. J. Gen.
Chem., 2015, vol. 85, p. 1668.
11. Dyachenko, I.V. and Dyachenko, V.D., Russ. J. Gen.
Chem., 2015, vol. 85, p. 1447.
23. Konovalov, A.I., Antipin, I.S., Burilov, V.A., Madzhi-
dov, T.I., Kurbangalieva, A.R., Nemtarev, A.V., Solovie-
va, S.E., Stoikov, I.I., Mamedov, V.A., Zakharo-
va, L.Ya., Gavrilova, E.L., Sinyashin, O.G.,
Balova, I.A., Vasilyev, A.V., Zenkevich, I.G., Krasa-
vin, M.Yu., Kuznetsov, M.A., Molchanov, A.P.,
Novikov, M.S., Nikolaev, V.A., Rodina, L.L.,
Khlebnikov, A.F., Beletskaya, I.P., Vatsadze, S.Z.,
Gromov, S.P., Zyk, N.V., Lebedev, A.T., Lemenov-
skii, D.A., Petrosyan, V.S., Nenaidenko, V.G.,
Negrebetskii, V.V., Baukov, Yu.I., Shmigol’, T.A., Kor-
lyukov, A.A., Tikhomirov, A.S., Shchekotikhin, A.E.,
Traven’, V.F., Voskresenskii, L.G., Zubkov, F.I.,
Golubchikov, O.A., Semeikin, A.S., Berezin, D.B.,
Stuzhin, P.A., Filimonov, V.D., Krasnokutskaya, E.A.,
Fedorov, A.Yu., Nyuchev, A.V., Orlov, V.Yu., Begu-
nov, R.S., Rusakov, A.I., Kolobov, A.V., Kofanov, E.R.,
Fedotova, O.V., Egorova, A.Yu., Charushin, V.N.,
Chupakhin, O.N., Klimochkin, Yu.N., Osyanin, V.A.,
Reznikov, A.N., Fisyuk, A.S., Sagitullina, G.P., Akse-
nov, A.V., Aksenov, N.A., Grachev, M.K., Maslenni-
kova, V.I., Koroteev, M.P., Brel’, A.K., Lisina, S.V.,
Medvedeva, S.M., Shikhaliev, Kh.S., Suboch, G.A.,
Tovbis, M.S., Mironovich, L.M., Ivanov, S.M., Kurba-
tov, S.V., Kletskii, M.E., Burov, O.N., Kobrakov, K.I.,
12. Dyachenko, I.V., Karpov, E.N., and Dyachenko, V.D.,
Russ. J. Gen. Chem., 2015, vol. 85, p. 1063.
13. Nell, P., Hübsch, W., Albrecht, B., Keldenich, J., and
Kaorr, A., FRG Patent Appl. no. 102006042143, 2008;
Ref. Zh., Khim., 2009, no. 09.13-19O.72P.
14. Rosentreter, U., Krämer, T., Vaupel, A., Hübsch, W.,
Diedrichs, N., Krahn, T., Dembowsky, K., Sfasch, V.-P.,
and Shimoda, M., FRG Patent Appl. no. 10115922,
2002; Ref. Zh., Khim., 2003, no. 03.14-19O.81P.
15. Ergüden, J.-K., Karig, G., Rosentreter, U., Albrecht, B.,
Henninger, K., Hütter, J., and Diedrichs, N., FRG Patent
Appl. no. 102004042607, 2006; Ref. Zh., Khim., 2007,
no. 07.06-19O.163P.
16. Nell, P., Albrecht, B., Hübsch, W., Wuttke, M.,
Krahn, T., Diedrichs, N., and Bischaff, H., FRG Patent
Appl. no. 102006009813, 2007; Ref. Zh., Khim., 2008,
no. 08.20-19O.97P.
17. Leistner, S., Ludwig, A., Reichelt, C., and Schulze, A.,
EP Patent Appl. no. 1681292, 2006; Ref. Zh., Khim.,
2007, no. 07.20-19.116P.
18. Chen, Z., Cirillo, P.F., Disalvo, D., Liu, W.,
Marshall, D.R., Wu, L., and Young, E.R.R., US Patent
no. 7119102, 2006; Ref. Zh., Khim., 2007, no. 07.12-
19O.79P.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018

DYACHENKO et al.
1284
28. Dyachenko, V.D. and Dyachenko, A.D., Russ. J. Org.
and Kuznetsov, D.N., Russ. J. Org. Chem., 2018,
vol. 54, p. 157.
Chem., 2008, vol. 44, p. 412.
24. Dyachenko, V.D. and Kudryavtseva, A.G., Chem.
Heterocycl. Compd., 2004, vol. 40, p. 1495.
29. Dyachenko, V.D., Russ. J. Org. Chem., 2011, vol. 47,
p. 1535.
25. Dyachenko, V.D., Ryl’skaya, T.A., Dyachenko, I.V.,
Kalashnik, I.N., and Chernykh, A.V., Russ. J. Gen.
Chem., 2015, vol. 85, p. 1069.
30. Battye, T.G., Kontogiannis, L., Johnson, O.,
Powell, H.R., and Leslie, A.G.W., Acta Crystallogr.,
Sect. D, 2011, vol. 67, p. 271.
26. Dyachenko, V.D., Russ. J. Org. Chem., 2007, vol. 43,
31. Evans, P., Acta Crystallogr., Sect. D, 2006, vol. 62,
p. 271.
p. 72.
27. Dyachenko, V.D. and Dyachenko, A.D., Russ. J. Org.
Chem., 2007, vol. 43, p. 280.
32. Sheldrick, G.M., Acta Crystallogr., Sect. C, 2015,
vol. 71, p. 3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 9 2018