Reaction of 4-aryl-1-(4-oxo-3,4-dihydrothieno-[2,3-d]pyrimidin-2-yl) thiosemicarbazides with dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1023/B:RUJO.0000045202.20807.f8

4-Aryl-1-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)thiosemicarbazides react with dimethyl acetylenedicarboxylate in methanol to give the corresponding methyl {3-aryl-4-oxo-2-[(4-oxo-3,4-dihydro-thieno[2,3-d]pyrimidin-2-yl) hydrazono]-1,3-thiazolidin-5-ylidene}acetates, whereas in dioxane methyl 5-aryl-amino-2-methoxycarbonylmethyl-3-(4-oxo-3,4-dihydrothieno[2,3-d] pyrimidin-2-yl)-2,3-dihydro-1,3,4-thiadiazole-2-carboxylates are mainly formed.

Full text of DOI:10.1023/B:RUJO.0000045202.20807.f8

Russian Journal of Organic Chemistry, Vol. 40, No. 7, 2004, pp. 1047–1052. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 7, 2004,
pp. 1088–1093.
Original Russian Text Copyright © 2004 by Vas’kevich, Zborovskii, Staninets, Chernega.
Reaction of 4-Aryl-1-(4-oxo-3,4-dihydrothieno-
[2,3-d]pyrimidin-2-yl)thiosemicarbazides with Dimethyl
Acetylenedicarboxylate
R. I. Vas’kevich, Yu. L. Zborovskii, V. I. Staninets, and A. N. Chernega
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02094 Ukraine
Received April 23, 2003
Abstract—4-Aryl-1-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)thiosemicarbazides react with dimethyl
acetylenedicarboxylate in methanol to give the corresponding methyl {3-aryl-4-oxo-2-[(4-oxo-3,4-dihydro-
thieno[2,3-d]pyrimidin-2-yl)hydrazono]-1,3-thiazolidin-5-ylidene}acetates, whereas in dioxane methyl 5-aryl-
amino-2-methoxycarbonylmethyl-3-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)-2,3-dihydro-1,3,4-thiadi-
azole-2-carboxylates are mainly formed.
We previously showed that 1-(4-oxo-3,4-dihydro-
thieno[2,3-d]pyrimidin-2-yl)-4-phenylthiosemicarba-
zides substituted at positions 5 and 6 of the fused
heterocyclic system react with alkyl halides to afford
angular triazolothienopyrimidine derivatives [1]. The
reaction begins with nucleophilic substitution of the
halogen atom in alkyl halide by the thiosemicarbazide
sulfur atom, and the subsequent intramolecular ring
closure is accompanied by elimination of thiolic frag-
ment. Taking into account that dimethyl acetylene-
dicarboxylate tends to participate in nucleophilic
addition processes, in the present work we examined
its reaction with 4-aryl-1-(5,6-dimethyl- and 5,6-tetra-
methylene-4-oxo-3,4-dihydrotieno[2,3-d]pyrimidin-2-
yl)thiosemicarbazides I–III.
acetylenedicarboxylate (XII) to give intermediate A;
the subsequent intramolecular cyclization involves
one of the two possible nucleophilic centers, N1 or
N4 atoms of the thiosemicarbazide fragment. In
methanol, nucleophilic attack by the N4 atom is
directed at the carbonyl carbon atom of the
α-methoxycarbonyl group, resulting in formation of
thiazolidines IV–VI. The presence of protons in the
reaction medium favors elimination of methoxy
group in the final (rate-determining) stage.
The intramolecular cyclization of intermediate A
in dioxane via addition of N1 at the double carbon–
carbon bond follows the Markownikoff rule. In this
case, the major products are thiadiazole derivatives
VII–IX. Dioxane is an aprotic solvent which is
more basic than methanol, and it favors just that
reaction direction. However, introduction of
a methoxy group into the para position of the ben-
zene ring considerably increases the nucleophilicity
of N4; therefore, the cyclization of II can take both
paths simultaneously.
We have found that compounds I–III react with
dimethyl acetylenedicarboxylate in methanol to afford
thiazolidine derivatives IV–VI, which is well consist-
ent with published data [2]. However, when dioxane
was used as solvent, we isolated dihydrothiadiazole
derivatives VII–IX. Here, the nature of substituent in
the benzene ring of the thiosemicarbazide fragment
exerted a strong effect on the cyclization direction.
para-Methoxy-substituted compounds gave rise to
mixtures of products V and VIII, while from para-
ethoxycarbonyl analogs, as well as from unsubstituted
derivatives, dihydrothiadiazoles VII and IX were
formed exclusively (Scheme 1).
The structure of the products was confirmed by
elemental analysis and 1H and IR spectra. The struc-
ture of VIIb was unambiguously proved by the
X-ray diffraction method. The principal bond
lengths and bond angles are given in table, and
Figure 1 shows the general view of the molecule.
The bicyclic system S1C1C2C3C4N1C5N2C6 is almost
planar: deviations of atoms from the mean-square
plane do not exceed 0.056 Å, and the dihedral angle
between the S1C1C2C3C4 and C3C4N1C5N2C6 rings is
These results led us to presume that the initial
reaction step is nucleophilic addition of the thiosemi-
carbazide sulfur atom at the triple bond of dimethyl
1070-4280/04/4007-1047 © 2004 MAIK “Nauka/Interperiodica”

VAS’KEVICH et al.
1048
Scheme 1.
O
N
R1
O
N
NH
NH
R1
R2
MeOCO
C
XII
C
COOMe
S
NH
N
C
S
NH R3
R2
NHNHC(S)NHR3
S
MeOCO
C
O
C
H
C
OMe
Ia, Ib, IIa, IIb, IIIa, IIIb
A
O
R1
R3
NH
R2
N
N
Methanol
S
N
N
O
H
S
CHCOOMe
IVa, IVb, Va, Vb, VIa, VIb
O
R1
NH
R2
N
Dioxane
S
N
N
NHR3
S
MeOCO
CH2COOMe
VIIa, VIIb, VIIIa, VIIIb, IXa, IXb
R1R2 = (CH2)4 (a), R1 = R2 = Me (b); I, IV, VII, R3 = Ph; II, V, VIII, R3 = 4-MeOC6H4; III, VI, IX, R3 = 4-EtOCOC6H4.
as small as 4.3°. The five-membered ring S2C9N4N3C10
is not planar: it has an envelope conformation. The
bond system S2–C9=N4–N3 is almost ideally planar; the
C10 atom deviates from that plane by –0.423 Å; and
the S2C10N3 fragment with the S2–C9=N4–N3 plane
forms an angle of 24.0°. The C16C17C18C19C20C21
benzene ring is almost coplanar to the S2C9N4N3
fragment: the corresponding dihedral angle is 2.3°. The
N2 and N5 atoms have planar–trigonal bond configura-
tion, and the N3 atom is slightly pyramidal; the sum of
the bond angles at these atoms is 360.0, 359.9, and
349.2°, respectively. The N5–C9 bond is shortened to
1.365(4) Å against the standard N(sp2)–C(sp2) bond
length (1.43–1.45 Å [3, 4]) due to effective n(N5)–
π(C9=N4) conjugation. Likewise, the n(N3)–π(C5=N1)
interaction makes the N3–C5 bond shorter [to
1.394(4) Å], and the N2–C6 bond is shortened to
1.404(4) Å as a result of n(N2)–π(C6=O1) conjugation.
Repulsion between the spatially close N4 and C17
atoms [the N4–C17 distance is 2.974 (4) Å which is
considerably shorter than the sum of the corresponding
van der Waals radii, 3.20 Å] leads to increase of the
N5C16C17 bond angle to 124.3(3)° relative to the
N5C16C21 bond angle [116.3(3)°].
Molecules of VIIb in crystal give rise to centro-
symmetric dimers (Fig. 2) via medium-strength hydro-
gen bonds N2–H2···O1 [5] with the following param-
eters: N2 ···O1 2.927(4), H2 · ·· O1 2.09(4), N2–H2
0.85(4) Å; ∠N2H2O1 164(2)°. The dimers are linked
through hydrogen bonds N5–H5 ···O4 [N5 · ·· O4
2.918(4), H5···O4 2.06(3), N5–H5 0.86(3) Å, ∠N5H5O4
179(2)°] to form an infinite network.
1
The H NMR spectra of IV–VI contain a singlet at
δ 3.76–3.78 ppm from the methoxy group and a singlet
at δ 6.93–6.99 ppm typical of the C5=CH proton. The
positions of other signals insignificantly differ from
those present in the spectra of the initial compounds.
Compounds VII–IX characteristically give rise to two
singlets from the ester methoxy groups at δ 3.61–3.63
and 3.66–3.67 ppm and two doublets from the C2–CH2
protons at δ 3.43–3.48 and 3.96–4.00 ppm.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

REACTION OF 4-ARYL-1-(4-OXO-3,4-DIHYDROTHIENO-...
1049
Principal bond lengths (d, Å) and bond angles (ω, deg) in
the molecule of (VIIb)
EXPERIMENTAL
The IR spectra were measured on a UR-20 spec-
trometer from samples prepared as KBr pellets. The
1H NMR spectra were recorded on a Varian VXR-300
instrument (300 MHz) in DMSO-d6 using TMS as
internal reference.
Bond
S1–C1
S1–C4
S2–C9
S2–C10
N1–C4
N1–C5
N2–C5
N2–C6
d
Angle
C1S1C4
C9S2C10
C4N1C5
C5N2C6
N4N3C5
N4N3C10
C5N3C10
N3N4C9
ω
1.752(4)
1.714(4)
1.779(4)
1.840(3)
1.374(4)
1.296(4)
1.367(4)
1.404(4)
00091.12(17)
00089.38(15)
114.0(3)
023.1(3)
The X-ray diffraction data for a single crystal of
VIIb (0.22×0.34×0.37 mm) were acquired at room
temperature on an Enraf–Nonius CAD-4 automatic
four-circle diffractometer (MoKα irradiation, λ =
0.71069 Å, scan rate ratio 2θ/ω = 1.2, θmax = 25°,
spherical segment 0 ≤ h ≤ 11, 0 ≤ k ≤ 23, –11 ≤ l ≤ 11).
Total of 4358 reflections were measured, 3804
of which were symmetry-independent (Rint = 0.026).
Monoclinic crystal system with the following unit cell
parameters: a = 8.224(2), b = 9.183(3), c = 30.439(11) Å;
β = 90.47(2)°; V = 2299(1) Å3; M = 487.5; Z = 4;
dcalc = 1.41 g/cm3; µ = 2.62 cm–1; F(000) = 1017.1;
space group P21/c. The structure was solved by the
direct method and was refined by the least-squares
procedure in full-matrix anisotropic approximation
using CRYSTALS software package [6]; 2187 reflec-
tions with I > 3(I) were used in the refinement
(306 parameters, number of reflections per parameter
7.1). All hydrogen atoms were visualized from the
difference synthesis of electron density and were
included into the calculation with fixed positional and
thermal parameters (only the H2 and H5 atoms in-
volved in hydrogen bonding were refined in isotropic
approximation). The Chebyshev weight scheme [7]
with five parameters: 0.86, 0.74, 0.82, 0.25, and 0.21
was applied. The final divergence factors were R =
0.041 and RW = 0.041, GOF = 1.153. The residual
electron density from the Fourier difference series was
0.24 and –0.21 e/Å3. Absorption by the crystal was
taken into account using the azimuthal scanning
technique [8]. The complete set of crystallographic
data for compound VIIb was deposited to the
Cambridge Structural Database (entry no. CCDC
205977).
114.8(3)
116.4(2)
118.0(3)
109.4(3)
N3–N4
1.419(4)
C9N5C16
128.9(3)
N3–C5
N3–C10
N4–C9
N5–C9
N5–C16
C1–C2
C2–C3
C3–C4
1.394(4)
1.489(4)
1.283(4)
1.365(4)
1.410(5)
1.340(5)
1.454(4)
1.382(4)
S1C1C2
C1C2C3
C2C3C4
C4C3C6
S1C4C3
N1C4C3
N1C5N2
N2C6C3
012.8(3)
111.9(3)
112.2(3)
118.1(3)
012.0(2)
126.5(3)
125.1(3)
113.1(3)
C3–C6
1.441(5)
S2C9N4
S2C10N3
117.3(3)
101.2(2)
0.01 mol of 4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-
2-ylhydrazine in 50 ml of ethanol. The mixture was
heated for 2 h under reflux and cooled, and the
precipitate was filtered off and washed with ethanol
and diethyl ether.
4-(p-Methoxyphenyl)-1-(4-oxo-3,4,5,6,7,8-hexa-
hydro[1]benzothieno[2,3-d]pyrimidin-2-yl)thio-
semicarbazide (IIa). Yield 3.97 g (99%), mp >350°C.
IR spectrum, ν, cm–1: 3340, 3285, 3160, 2950 (NH);
1660 (C=O); 1610 (C=N). 1H NMR spectrum, δ, ppm:
1.75 m (4H, CH2), 2.64–2.79 m (4H, CH2), 3.74 s (3H,
CH3), 6.89 d (2H, Harom, J = 8.7 Hz), 7.35 d (2H, Harom
,
J = 9.0 Hz), 8.61 br.s (1H, NH), 9.51 s (1H, NH),
9.77 s (1H, NH), 11.15 br.s (1H, NH). Found, %:
C 53.69; H 4.63; N 17.39; S 15.91. C18H19N5O2S2.
Calculated, %: C 53.85; H 4.77; N 17.44; S 15.97.
Initial 1-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-
2-yl)-4-phenylthiosemicarbazides (I) were described
previously [1].
1-(5,6-Dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]-
pyrimidin-2-yl)-4-(p-methoxyphenyl)thiosemicar-
bazide (IIb). Yield 3.49 g (93%), mp >330°C.
IR spectrum, ν, cm–1: 3340, 3160, 2980 (NH); 1660
4-(p-Methoxyphenyl)- and 4-(p-ethoxycarbonyl-
phenyl)-1-(4-oxo-3,4-dihydrothieno[2,3-d]pyrimi-
din-2-yl)thiosemicarbazides II and III (general
procedure). A solution of 0.015 mol of p-methoxy-
phenyl or p-ethoxycarbonylphenyl isothiocyanate in
20 ml of ethanol was added to a suspension of
1
(C=O); 1605 (C=N). H NMR spectrum, δ, ppm:
2.26 s and 2.31 s (6H, CH3), 3.74 s (3H, CH3O), 6.89 d
(2H, Harom, J = 9.0 Hz), 7.34 d (2H, Harom, J = 8.7 Hz),
8.62 br.s (1H, NH), 9.53 s (1H, NH), 9.79 s (1H, NH),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

VAS’KEVICH et al.
1050
C8
C2
(4H, CH2), 2.64–2.79 m (4H, CH2), 4.30 q (2H, CH2O,
J = 7.2 Hz), 7.80 d (2H, Harom, J = 8.7 Hz), 7.91 d (2H,
arom, J = 8.7 Hz), 8.73 br.s (1H, NH), 9.84 br.s (1H,
NH), 10.13 s (1H, NH), 11.31 br.s (1H, NH). Found,
%: C 54.06; H 4.01; N 15.63; S 14.38. C20H21N5O3S2.
Calculated, %: C 54.16; H 4.77; N 15.79; S 14.46.
O1
C6
C7
C18
H
C19
C20
C21
C3
C1
N2
C17
C16
C5
C4
N4
1-(5,6-Dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]-
pyrimidin-2-yl)-4-(p-ethoxycarbonylphenyl)thio-
semicarbazide (IIIb). Yield 2.96 g (71%),
mp >330°C. IR spectrum, ν, cm–1: 3280, 3150, 2900
(NH); 1710, 1665 (C=O); 1615 (C=N). 1H NMR spec-
trum, δ, ppm: 1.32 t (3H, CH3, J = 7.2 Hz), 2.27 s and
2.32 s (6H, CH3), 4.30 q (2H, CH2O, J = 7.2 Hz),
7.80 d (2H, Harom, J = 8.7 Hz), 7.91 d (2H, Harom, J =
8.7 Hz), 8.72 br.s (1H, NH), 9.87 br.s (1H, NH),
10.14 s (1H, NH), 11.33 br.s (1H, NH). Found, %:
C 51.67; H 4.48; N 16.61; S 15.23. C18H19N5O3S2.
Calculated, %: C 51.78; H 4.59; N 16.77; S 15.36.
S1
N3
N1
C9
N5
O3
C12
C10
C11
S2
C13
O2
C14
O5
O4
C15
Fig. 1. Structure of the molecule of methyl 3-(5,6-dimethyl-4-
oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)-2-methoxycar-
bonylmethyl-5-phenylamino-2,3-dihydro-1,3,4-thiadiazole-2-
carboxylate (VIIb) according to the X-ray diffraction data
(hydrogen atoms are not shown).
Methyl {3-aryl-4-oxo-2-[(4-oxo-3,4-dihydro-
thieno[2,3-d]pyrimidin-2-yl)hydrazono]-1,3-thiazo-
lidin-5-ylidene}acetates IV–VI (general procedure).
A mixture of 2 mmol of compound I–III and 0.37 ml
(3 mmol) of dimethyl acetylenedicarboxylate (XII) in
30 ml of methanol was heated for 1 h under reflux and
was left to stand for crystallization. The precipitate
was filtered off and washed on a filter with methanol
and diethyl ether.
b
Methyl {4-oxo-2-[(4-oxo-3,4,5,6,7,8-hexahydro-
[1]benzothieno[2,3-d]pyrimidin-2-yl)hydrazono]-3-
phenyl-1,3-thiazolidin-5-ylidene}acetate (IVa). Yield
0.73 g (76%), mp 258–260°C (from metanol). IR spec-
trum, ν, cm–1: 3340, 3085 (NH); 1730, 1660 (C=O);
0
1
a
c
1600 (C=N). H NMR spectrum, δ, ppm: 1.75 m (4H,
CH2), 2.65–2.80 m (4H, CH2), 3.77 s (3H, CH3O),
6.92 d (2H, Harom, J = 7.5 Hz), 6.95 s (1H, CH), 7.22 t
(1H, Harom, J = 7.5 Hz), 7.43 t (2H, Harom, J = 8.1 Hz),
9.92 br.s (1H, NH), 12.10 br.s (1H, NH). Found, %:
C 54.77; H 3.81; N 14.47; S 13.26. C22H19N5O4S2.
Calculated, %: C 54.87; H 3.98; N 14.54; S 13.32.
Fig. 2. Packing of molecules VIIb in crystal (projection onto
the ac plane). Intermolecular hydrogen bonds are shown as
dotted lines.
Methyl {2-[(5,6-dimethyl-4-oxo-3,4-dihydro-
thieno[2,3-d]pyrimidin-2-yl)hydrazono]-4-oxo-3-
phenyl-1,3-thiazolidin-5-ylidene}acetate (IVb).
Yield 0.65 g (71%), mp 269–271°C (from methanol).
IR spectrum, ν, cm–1: 3340, 3080 (NH); 1720, 1660
11.21 br.s (1H, NH). Found, %: C 51.03; H 4.49;
N 18.57; S 17.05. C16H17N5O2S2. Calculated, %:
C 51.18; H 4.56; N 18.65; S 17.08.
1
(C=O); 1600 (C=N). H NMR spectrum, δ, ppm:
4-(p-Ethoxycarbonylphenyl)-1-(4-oxo-3,4,5,6,7,8-
hexahydro[1]benzothieno[2,3-d]pyrimidin-2-yl)-
thiosemicarbazide (IIIa). Yield 3.19 g (72%),
mp >330°C. IR spectrum, ν, cm–1: 3330, 3300, 3170
(NH); 1710, 1665 (C=O); 1610 (C=N). 1H NMR spec-
trum, δ, ppm: 1.31 t (3H, CH3, J = 7.2 Hz), 1.76 m
2.27 s and 2.32 s (6H, CH3), 3.77 s (3H, CH3O), 6.92 d
(2H, Harom, J = 7.8 Hz), 6.95 s (1H, CH), 7.22 t (1H,
Harom, J = 7.2 Hz), 7.43 t (2H, Harom, J = 7.8 Hz),
9.88 br.s (1H, NH), 12.10 br.s (1H, NH). Found, %:
C 52.68; H 3.75; N 15.32; S 14.05. C20H17N5O4S2.
Calculated, %: C 52.74; H 3.76; N 15.37; S 14.08.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

REACTION OF 4-ARYL-1-(4-OXO-3,4-DIHYDROTHIENO-...
1051
Methyl {3-(p-methoxyphenyl)-4-oxo-2-[(4-oxo-
3,4,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimi-
din-2-yl)hydrazono]-1,3-thiazolidin-5-ylidene}
acetate (Va). Yield 0.74 g (72%), mp 222–224°C
(from methanol–dioxane). IR spectrum, ν, cm–1: 3330,
2940 (NH); 1730, 1660 (C=O); 1600 (C=N). 1H NMR
spectrum, δ, ppm: 1.74 m (4H, CH2), 2.64–2.79 m (4H,
CH2), 3.76 s (3H, CH3O), 3.77 s (3H, CH3), 6.88 d
(2H, Harom, J = 8.4 Hz), 6.93 s (1H, CH), 6.99 d
(2H, Harom, J = 8.7 Hz), 9.88 br.s (1H, NH), 12.07 br.s
(1H, NH). Found, %: C 53.89; H 4.02; N 13.56;
S 12.47. C23H21N5O5S2. Calculated, %: C 54.00; H 4.14;
N 13.69; S 12.54.
NH), 12.11 br.s (1H, NH). Found, %: C 53.30; H 3.98;
N 13.19; S 12.09. C23H21N5O6S2. Calculated, %:
C 53.36; H 4.01; N 13.27; S 12.16.
Reaction of 4-aryl-1-(4-oxo-3,4-dihydrothieno-
[2,3-d]pyrimidin-2-yl)thiosemicarbazides (I–III)
with dimethyl acetylenedicarboxylate (XII) in di-
oxane (general procedure). A mixture of 2 mmol of
compound I–III and 3 mmol (0.37 ml) of compound
XII in 30 ml of dioxane was heated for 20 min. The
resulting solution was evaporated under reduced pres-
sure, the residue was dissolved in 50–75 ml of acetone
(if an undissolved material remained, it was separated),
and the solvent was allowed to evaporate. The residue
was treated with diethyl ether, and the precipitate was
filtered off. The product was additionally purified by
recrystallization from methanol. In the reaction of
compounds IIa and IIb with dimethyl acetylene-
dicarboxylate, apart from thiadiazolidine derivatives
VIIIa and VIIIb, we also isolated compounds Va
(yield 0.39 g, 38%) and Vb (yield 0.20 g, 21%). For
this purpose, the reaction mixture was evaporated by
2/3, and the precipitate (Va or Vb) was filtered off.
Methyl {2-[(5,6-dimethyl-4-oxo-3,4-dihydro-
thieno[2,3-d]pyrimidin-2-yl)hydrazono]-3-(p-meth-
oxyphenyl)-4-oxo-1,3-thiazolidin-5-ylidene}acetate
(Vb). Yield 0.74 g (76%), mp 254–256°C (from
methanol–dioxane). IR spectrum, ν, cm–1: 3340, 3070
(NH); 1720, 1660 (C=O); 1600 (C=N). 1H NMR spec-
trum, δ, ppm: 2.27 s and 2.32 s (6H, CH3), 3.76 s
(3H, CH3O), 3.78 s (3H, CH3O), 6.88 d (2H, Harom, J =
9.0 Hz), 6.92 s (1H, CH), 6.99 d (2H, Harom, J =
9.0 Hz), 9.81 br.s (1H, NH), 12.01 br.s (1H, NH).
Found, %: C 51.86; H 3.89; N 14.35; S 13.20.
C21H19N5O5S2. Calculated, %: C 51.95; H 3.94;
N 14.42; S 13.21.
Methyl 2-methoxycarbonylmethyl-3-(4-oxo-
3,4,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimi-
din-2-yl)-5-phenylamino-2,3-dihydro-1,3,4-thiadi-
azole-2-carboxylate (VIIa). Yield 0.43 g (42%),
mp 182–184°C (from methanol). IR spectrum, ν, cm–1:
3380, 3290, 2950 (NH); 1730, 1680, 1650 (C=O);
Methyl {3-(p-ethoxycarbonylphenyl)-4-oxo-2-
[(4-oxo-3,4,5,6,7,8-hexahydro[1]benzothieno[2,3-d]-
pyrimidin-2-yl)hydrazono]-1,3-thiazolidin-5-
ylidene}acetate (VIa). Yield 0.69 g (62%), mp 253–
255°C (from methanol). IR spectrum, ν, cm–1: 3330,
3065, 2950, 2860 (NH); 1745, 1720, 1660 (C=O);
1
1600 (C=N). H NMR spectrum, δ, ppm: 1.76 m (4H,
CH2), 2.63–2.80 m (4H, CH2), 3.44 d (1H, CH, J =
16.5 Hz), 3.61 s and 3.67 s (6H, CH3O), 3.98 d (1H,
CH, J = 16.5 Hz), 7.02 t (1H, Harom, J = 7.8 Hz), 7.34 t
(2H, Harom, J = 7.8 Hz), 7.61 d (2H, Harom, J = 8.1 Hz),
9.70 s (1H, NH), 10.88 s (1H, NH). Found, %:
C 53.64; H 4.41; N 13.56; S 12.39. C23H23N5O5S2. Cal-
culated, %: C 53.79; H 4.51; N 13.64; S 12.49.
1
1600 (C=N). H NMR spectrum, δ, ppm: 1.32 t (3H,
CH3, J = 7.2 Hz), 1.79 m (4H, CH2), 2.65–2.80 m (4H,
CH2), 3.77 s (3H, CH3), 4.31 q (2H, CH2, J = 7.2 Hz),
6.99 s (1H, CH), 7.05 d (2H, Harom, J = 8.4 Hz), 8.02 d
(2H, Harom, J = 8.4 Hz), 9.96 br.s (1H, NH), 12.12 br.s
(1H, NH). Found, %: C 54.14; H 4.17; N 15.13;
S 11.47. C25H23N5O6S2. Calculated, %: C 54.24; H 4.19;
N 15.18; S 11.58.
Methyl 3-(5,6-dimethyl-4-oxo-3,4-dihydrothieno-
[2,3-d]pyrimidin-2-yl)-2-methoxycarbonylmethyl-5-
phenylamino-2,3-dihydro-1,3,4-thiadiazole-2-car-
boxylate (VIIb). Yield 0.26 g (27%), mp 202–204°C
(from methanol). IR spectrum, ν, cm–1: 3345 (NH):
Methyl {2-[(5,6-dimethyl-4-oxo-3,4-dihydro-
thieno[2,3-d]pyrimidin-2-yl)hydrazono]-3-(p-ethoxy-
carbonylphenyl)-4-oxo-1,3-thiazolidin-5-ylidene}
acetate (VIb). Yield 0.61 g (58%), mp 227–229°C
(from methanol). IR spectrum, ν, cm–1: 3340, 3070
(NH); 1720, 1660 (C=O); 1590 (C=N). 1H NMR spec-
trum, δ, ppm: 1.33 t (3H, CH3, J = 7.2 Hz), 2.27 s and
2.32 s (6H, CH3), 3.78 s (3H, CH3O), 4.32 q (2H, CH2,
J = 7.2 Hz), 6.99 s (1H, CH), 7.06 d (2H, Harom, J =
8.4 Hz), 8.02 d (2H, Harom, J = 8.4 Hz), 9.93 br.s (1H,
1
1730, 1700, 1660 (C=O); 1595 (C=N). H NMR spec-
trum, δ, ppm: 2.26 s and 2.32 s (6H, CH3), 3.44 d
(1H, CH, J = 16.5 Hz), 3.61 s and 3.67 s (6H, CH3O),
3.98 d (1H, CH, J = 16.8 Hz), 7.02 t (1H, Harom, J =
7.5 Hz), 7.34 t (2H, Harom, J = 7.8 Hz), 7.62 d (2H,
Harom, J = 8.1 Hz), 9.70 s (1H, NH), 10.89 s (1H, NH).
Found, %: C 51.67; H 4.31; N 14.32; S 13.03.
C21H21N5O5S2. Calculated, %: C 51.73; H 4.34;
N 14.36; S 13.15.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004

VAS’KEVICH et al.
1052
NH), 11.02 s (1H, NH). Found, %: C 53.23; H 4.56;
Methyl 2-methoxycarbonylmethyl-5-(p-methoxy-
N 11.81; S 10.87. C26H27N5O7S2. Calculated, %:
C 53.32; H 4.65; N 11.96; S 10.95.
phenylamino)-3-(4-oxo-3,4,5,6,7,8-hexahydro[1]-
benzothieno[2,3-d]pyrimidin-2-yl)-2,3-dihydro-
1,3,4-thiadiazole-2-carboxylate (VIIIa). Yield 0.32 g
(29%), mp 227–228°C (from methanol). IR spectrum,
ν, cm–1: 3380, 2940 (NH); 1735, 1670 (C=O). 1H NMR
spectrum, δ, ppm: 1.75 m (4H, CH2); 2.62–2.80 m
(4H, CH2); 3.44 d (1H, CH, J = 16.5 Hz); 3.62 s,
3.66 s, and 3.74 s (9H, CH3); 3.96 d (1H, CH, J =
16.2 Hz), 6.91 d (2H, Harom, J = 9.0 Hz), 7.53 d (2H,
Harom, J = 8.4 Hz), 9.53 s (1H, NH), 10.62 s (1H, NH).
Found, %: C 52.97; H 4.53; N 12.78; S 11.67.
C24H25N5O6S2. Calculated, %: C 53.03; H 4.64;
N 12.88; S 11.80.
Methyl 3-(5,6-dimethyl-4-oxo-3,4-dihydrothieno-
[2,3-d]pyrimidin-2-yl)-5-(p-ethoxycarbonylphenyl-
amino)-2-methoxycarbonylmethyl-2,3-dihydro-
1,3,4-thiadiazole-2-carboxylate (IXb). Yield 0.35 g
(31%), mp 147–149°C (from methanol). IR spectrum,
ν, cm–1: 3310 (NH); 1730–1710, 1680–1650 (C=O);
1
1600 (C=N). H NMR spectrum, δ, ppm: 1.33 t (3H,
CH3, J = 7.2 Hz), 2.27 s and 2.33 s (6H, CH3), 3.48 d
(1H, CH, J = 16.5 Hz), 3.62 s and 3.67 s (6H, CH3O),
4.00 d (1H, CH, J = 16.5 Hz), 4.29 q (2H, CH2O, J =
6.9 Hz), 7.75 d (2H, Harom, J = 8.7 Hz), 7.86 d (2H,
Methyl 3-(5,6-dimethyl-4-oxo-3,4-dihydrothieno-
[2,3-d]pyrimidin-2-yl)-2-methoxycarbonylmethyl-5-
(p-methoxyphenylamino)-2,3-dihydro-1,3,4-thiadi-
azole-2-carboxylate (VIIIb). Yield 0.30 g (29%),
mp 116–118°C (from methanol). IR spectrum, ν, cm–1:
H
arom, J = 8.7 Hz), 10.12 s (1H, NH), 11.07 s (1H,
NH). Found, %: C 51.46; H 4.46; N 12.49; S 11.39.
C24H25N5O7S2. Calculated, %: C 51.51; H 4.50;
N 12.51; S 11.46.
1
3300 (NH); 1735, 1660 (C=O). H NMR spectrum, δ,
REFERENCES
ppm: 2.26 s and 2.32 s (6H, CH3); 3.43 d (1H, CH,
J = 16.5 Hz); 3.62 s, 3.66 s, and 3.74 s (9H, CH3O);
3.97 d (1H, CH, J = 16.8 Hz); 6.91 d (2H, Harom, J =
9.0 Hz); 7.53 d (2H, Harom, J = 9.0 Hz); 9.54 s (1H,
NH); 10.65 s (1H, NH). Found, %: C 50.97; H 4.37;
N 13.47; S 12.26. C22H23N5O6S2. Calculated, %:
C 51.05; H 4.48; N 13.53; S 12.39.
1. Khripak, S.M., Vas’kevich, R.I., Zborovskii, Yu.L., and
Staninets, V.I., Russ. J. Org. Chem., 2000, vol. 36, p. 430.
2. Kauss, V.Ya., Liepin’sh, E.E., Kalvin’sh, I.Ya., and
Lukevits, E., Khim. Geterotsikl. Soedin., 1990, p. 120.
3. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Tailor, R., J. Chem. Soc., Perkin
Trans. 2, 1987, p. S1.
Methyl 5-(p-ethoxycarbonylphenylamino)-2-
methoxycarbonylmethyl-3-(4-oxo-3,4,5,6,7,8-hexa-
hydro[1]benzothieno[2,3-d]pyrimidin-2-yl)-2,3-di-
hydro-1,3,4-thiadiazole-2-carboxylate (IXa). Yield
0.41 g (35%), mp 192–195°C (from methanol). IR
spectrum, ν, cm–1: 3320, 2940 (NH); 1735, 1670
(C=O); 1590 (C=N). 1H NMR spectrum, δ, ppm: 1.33 t
(3H, CH3, J = 7.2 Hz), 1.77 m (4H, CH2), 2.63–2.81 m
(4H, CH2), 3.48 d (1H, CH, J = 16.5 Hz), 3.63 s and
3.67 s (6H, CH3O), 3.99 d (1H, CH, J = 16.5 Hz),
4.30 q (2H, CH2O, J = 7.2 Hz), 7.74 d (2H, Harom, J =
9.0 Hz), 7.94 d (2H, Harom, J = 8.4 Hz), 10.12 s (1H,
4. Burke-Laing, M. and Laing M., Acta Crystallogr.,
Sect. B, 1976, vol. 32, p. 3216.
5. Kuleshova, L.N. and Zorkii, P.M., Acta Crystallogr.,
Sect. B, 1981, vol. 37, p. 1363.
6. Watkin, D.J., Prout, C.K., Carruthers, J.R., and Bet-
teridge, P.W., CRYSTALS, Issue 10, Chemical Crystal-
lography Laboratory, Univ. of Oxford, 1996.
7. Carruthers, J.R. and Watkin, D.J., Acta Crystallogr.,
Sect. A, 1979, vol. 35, p. 698.
8. North, A.C.T., Phillips, D.C., and Mathews, F.S., Acta
Crystallogr., Sect. A, 1968, vol. 24, p. 351.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 7 2004