Synthesis of new derivatives of 5-(3,4-dihydro-2Н-pyrrol-5-yl)-pyrimidine

Article abstract of DOI:10.1134/S1070428016110166

By one-stage condensation of 6-(arylamino)pyrimidine-2,4(1Н,3Н)-diones with pyrrolidin-2-one new potential antiviral compounds were obtained, analogs of pyrrolinylpyrimidine containing structural fragments of known drugs AZT and HEPT used in treating HIV-infections.

Full text of DOI:10.1134/S1070428016110166

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 11, pp. 1646–1653. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © S.P. Gasparyan, М.V. Alexanyan, G.K. Arutyunyan, S.L. Kocharov, А.H. Martirosyan, R.А. Tamazyan, А.G. Ayvazyan, H.А. Panosyan,
G.G. Danagulyan, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 11, pp. 1652–1658.
Synthesis of New Derivatives
of 5-(3,4-Dihydro-2Н-pyrrol-5-yl)-pyrimidine
S. P. Gasparyana,c,* М. V. Alexanyana, G. K. Arutyunyana, S. L. Kocharova,
А. H. Martirosyana, R. А. Tamazyanb, А. G. Ayvazyanb,
H. А. Panosyanb, and G. G. Danagulyanc
R&D Center of Organic and Pharmaceutical Chemistry, National Academy of Sciences, Yerevan, Armenia
a Mndzhoyan Institute of Fine Organic Chemistry, Yerevan, Armenia
b Center of Molecule Structure Research, pr. Azatutyan 26, Yerevan, 0014 Armenia
*e-mail: g_sahak@yahoo.com
c Russian-Armenian (Slavonic) University, Yerevan, Armenia
Received April 6, 2016
Abstract—By one-stage condensation of 6-(arylamino)pyrimidine-2,4(1Н,3Н)-diones with pyrrolidin-2-one
new potential antiviral compounds were obtained, analogs of pyrrolinylpyrimidine containing structural
fragments of known drugs AZT and HEPT used in treating HIV-infections.
DOI: 10.1134/S1070428016110166
Derivatives of pyrimidine and its nucleosides are
vitally important because they exhibit a wide spectrum
of bioactivity, in particular, antitumor, antiviral,
antifungal, antituberculosis, etc. [1]. After appearance
of drugs with antitumor, antiviral, and especially anti-
HIV activity in clinics, the interest to derivatives of
uracyl and pyrimidine, substituted in the position 5 or
6 of pyrimidine ring grew significantly. To the series
of compounds possessing positive effect against HIV
belong 1-(2-hydroxyethoxy)methyl-6-(phenylsulfanyl)-
thymine (HEPT) [2–4], 6-benzyl-5-isopropyl-1-(etho-
xymethyl)-uracyl [5, 6], 2-alkoxy-6-benzyl-3,4-dihyd-
ropyrimidin-4(1Н)-ones (DABOs) [7], 3'-azido-2',3'-
dideoxythymidine (AZT) [8], and others.
antitumor activity [9–11]. In contrast to natural
nucleosides in С-nucleosides the ribofuranosyl residue
is bound with heterocyclic base with a glycoside bond
С‒С, resistant to chemical and enzymatic hydrolysis.
On top of that the replacement of the glycoside oxygen
atom in carbohydrate residue of С-nucleosides for
nitrogen atom is known to result in C-azanucleosides,
capable to inhibit glycohydrolases responsible for
decomposition of glycoside bonds [12–14].
In the literature different methods of synthesis are
described of С-azanucleosides, in particular, using
Heck reaction, 1,3-dipolar cycloaddition, С-nucleo-
sidation by Mannich type, cyclization of γ-azido
ketones by Straudinger–aza-Wittig reaction, etc. [15–
23]. All these methods are labor consuming and
multistage, therefore developing more accessible
methods of synthesis is an actual task.
Chemical modification of nucleosides is long
proved as important way to increasing antiviral and
O
Since pyrrolidin-2-ones possessing various bio-
activities are applied in pharmacy [24, 25], it was
desirable to introduce pyrrolidine ring as a substituent
into pyrimidine molecule aiming to investigate
biological properties of obtained compounds.
Previously we suggested and realized a one-stage
synthesis of new C-azanucleosides, derivatives of
pyrrolinylpyrimidine [26], in conditions of Vilsmeier
O
CH3
HN
CH3
HN
O
N
O
O
N
S
HO
HO
O
N3
HEPT
AZT
1646

SYNTHESIS OF NEW DERIVATIVES OF 5-(3,4-DIHYDRO-2Н-PYRROL-5-YL)PYRIMIDINE
1647
Scheme 1.
O
O
O
O
O
N
H
N
HN
R'NH2
HN
HN
HN
RCl
K2CO3
PCl3
O
N
H
Cl
O
N
Cl
O
N
NHR'
O
N
NHR'
R
R
R
2, 3
4_6
7_9
1
R = Bn, R'= Ph (2, 4, 7), 3,5-Me2C6H3 (5, 8); R = (CH2)3Ph, R' = 3,5-Me2C6H3 (3, 6, 9).
reaction, but using pyrrolidin-2-one instead of DMF.
In this study we obtained new analogs of 5-(3,4-
dihydro-2Н-pyrrol-5-yl)pyrimidine 7–9, 13–15, and
20–23.
By the reaction of 6-amino-2-sulfanylidene-2,3-
dihydropyrimidin-4(1Н)-one 10 with propyl bromide
and benzyl chloride were similarly obtained the
corresponding sulfanyl derivatives of pyrimidine 11
and 12 [29]. Compounds 10‒12 were condensed
with pyrrolidin-2-one in the presence of PCl3 to obtain
the corresponding products 13–15 resulting from
the condensation at the position 5 of pyrimidine
(Scheme 2).
As initial compound 6-chloropyrimidine-2,4-
(1H,3H)-dione 1 [27] was used, which by reaction with
benzyl chloride or phenylpropyl bromide in DMF
in the presence of potassium carbonate afforded
the corresponding N1-derivatives 2 [28] and 3.
The reaction of compounds 2 and 3 with aniline
or dimethylaniline results in 6-aniline-substituted
pyrimidines 4–6, by their condensation with pyrrolidin-
2-one in the presence of PCl3 under conditions of
Vilsmeier reaction [26] derivatives of 5-(3,4-dihydro-
2Н-pyrrol-5-yl)pyrimidine-2,4(1Н,3Н)-dione 7–9
(Scheme 1) were synthesized.
The optimum path of producing derivatives of
pyrrolinylpyrimidine is the reaction of N-substituted 5-
hydroxypyrrolidin-2-ones with nucleophiles. Of many
known methods producing 5-hydroxypyrrolidin-2-ones
substituted at the nitrogen atom by the reduction with
sodium borohydride of N-substituted succinimides the
method of pH-controlled reduction turned out to be the
Scheme 2.
O
N
HN
S
N
H
NH2
O
N
H
13
PCl3
O
O
O
O
N
H
N
HN
HN
HN
PrBr
NaOH
PCl3
S
N
H
NH2
PrS
N
NH2
PrS
N
NH2
11
14
10
BnCl
NaOH
O
O
O
N
H
N
HN
HN
PCl3
BnS
N
NH2
BnS
N
NH2
12
15
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

GASPARYAN et al.
1648
Scheme 3.
HO
O
N
O
O
R4
O
R3
O
R3
O
N
N
N
18, 19
R4
NHR2
H+
N
NHR2
N
R1
R1
5, 16, 17
20_23
R1 = Bn, R2 = 3,5-Me2C6H3, R3 = H, R4 = Bn (5, 18, 20); R1 = R2 = R3 = H, R4 = Bn (16, 21); R1 = R3 = Me, R2 = H,
R4 = Bn (17, 22); R1 = R2 = R3 = H, R4 = 4-MeOC6H4 (19, 23).
optimal [30]. Despite wide temperature range recom-
mended by different authors (‒20 to 0°С), only reduction
at ‒30°С allowed the preparation of compounds 18 and
19 and prevented the opening of the pyrrolidine ring
and undesired generation of amidoalcohol.
At heating the derivatives of pyrimidine 5, 16, and
17 with N-substituted 5-hydroxypyrrolidin-2-ones 18
[31], 19 [32] in glacial acetic acid by method [33]
analogs were obtained of 5-(3,4-dihydro-2Н-pyrrol-5-
yl)pyrimidine-2,4(1Н,3Н)-dione 20–23 (Scheme 3).
N3
O8
S14
C15
C2
C4
C10
C11
N1
C9
C5
The structure of obtained compounds was confir-
C16
C6
1
med by IR and H NMR spectra, and of compound 15
also by 13C NMR spectrum.
C17
C12
N13
N7
1
Signals of protons of NH and NH2 groups in H
NMR spectra are significantly broadened due to the
formation of intermolecular and intramolecular hydrogen
bonds in the solution. In 1H NMR spectra of compounds
13–15 NH2 group appears as two broad signals (of 1Н)
at 7.0 and 11.0 ppm that perhaps follows from the
formation of the hydrogen bond between the nitrogen
atom of pyrrolidine ring and NH2 group.
Fig. 1. Structure of the molecule of 6-amino-5-(3,4-dihydro-
2H-pyrrol-5-yl)-2-propylsulfanylpyrimidin-4(3Н)-one 14
with random atom numeration, ellipsoids of anisotropic
thermal oscillations are shown with 50% probability,
intramolecular hydrogen bond is marked with dashed line.
For compounds 7–9 and 13–15 tautomeric transfor-
mations may occur (Scheme 4).
N13i
H7Bi
Scheme 4.
O8i
N7i
O
O
H3
O8
N3
H7Ai
N3i
H3i
N
H
N
HN
HN
H7A
H
X
N
R
NR1
X
N
R
N
N7
R1
H7B
N13
Structure of compound 14 was confirmed by X-ray
diffraction analysis. Analysis of the conformations of
cyclic fragments showed that deviation of atoms from
the averaged plane of the pyrimidine ring does not
exceed 0.0070(1) Å, and the pyrrolidine ring has a
weakly pronounced envelope conformation, the
Fig. 2. Intermolecular and intramolecular bonds in
structure of compound 14, symmetry code i 1 ‒ x, 1 ‒ y, ‒z,
hydrogen bonds are marked with dashed lines.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

SYNTHESIS OF NEW DERIVATIVES OF 5-(3,4-DIHYDRO-2Н-PYRROL-5-YL)PYRIMIDINE
Table 1. Geometry of hydrogen bonds in crystal of compounds 14
1649
D–H···A
N3‒H3···O8i
N7‒H7A···N13ii
N7‒H7B···N13
D–H, Å
0.892(19)
0.93(2)
H···A, Å
1.867(19)
2.28(2)
D‒A, Å
2.7579(19)
3.196(2)
Angle DHA, deg
178(2)
Symmetry code
i 1 – x, 1 – y, –z
ii 2 – x, 1/2 + y, 1/2 – z
170(2)
0.87(2)
1.96(2)
2.672(2)
138.3(19)
deviation of C9, C10, C12 and N13 atoms from its plane
does not exceed 0.0095(1) Å, of atom C11, 0.1038(1) Å
(Fig. 1). It turned out from the conformational
calculations that cyclic fragments are coplanar, the
dihedral angle between the averaged planes of
pyrimidine and pyrrololidine rings is 1.141(2)°. In the
structure of compound 14 between atoms N7‒H7B···N13
intrarmolecular hydrogen bond exists, the length of the
donor-acceptor bond is 2.672(2) Å (Fig. 1).
geometrical calculations and refined in the rider model
on the following conditions: bonds length C‒H 0.96 Å,
Uiso(H) = 1.5Ueq(C). The structure was refined by full
matrix least-squares method in anisotropic
approximation for nonhydrogen atoms and in isotropic
approximation for hydrogen. All calculations were
performed using software complex SHELXTL [35].
Basic crystallographic characteristics and experimental
data of compound 14 were collected in Table 2.
Crystallographic data in CIF were deposited in
Cambridge Crystallographic Data Centre, deposit
number CCDC 1452678.
In the crystal lattice the molecules connected by
hydrogen bonds (N3‒H3···O8i, N3i‒H3i···O8 and N7‒
H7A···N13ii) form two-dimensional nets parallel to the
plane (1 0 ‒2) (Figs. 2, 3). Parameters of hydrogen
bonds are compiled in Table 1.
1-Benzyl-6-chloropyrimidine-2,4(1H,3H)-dione 2
was obtained by the method [28].
New analogs of pyrrolinylpyrimidine 7–9, 13–15,
and 20–23 obtained in this research are presently
undergoing biological investigations, their result will
be published separately.
1-(3-Phenylpropyl)-6-chloropyrimidine-2,4-
(1H,3H)-dione (3). A mixture of 1.47 g (10 mmol) of
6-chloropyrimidine-2,4(1H,3H)-dione 1 [27], 2.0 g
(10 mmol) of (3-bromopropyl)benzene, 1.4 g (10 mmol)
of K2CO3 in 10 mL of DMF was heated for 8 h at 65°C.
The solvent was distilled off, the residue was triturated
in 10 mL of water, the precipitate was filtered off,
washed with water, dried, and recrystallized. Yield 1.9 g
EXPERIMENTAL
IR spectra were registered on a spectrometer
1
Nicolet Avatar 330 FT-IR from thin layer. Н and 13С
NMR spectra were recorded at 303 K on a Varian
Merсury-300VX instrument at operating frequencies
300 and 75 МHz correspondingly from compounds
solutions in DMSO-d6‒CCl4, 1 : 3. Chemical shifts
were measured with respect to residual signal of
DMSO (2.50 ppm). The reactions progress and
compounds purity was monitored by TLC on Silufol
UV-254 plates using eluent systems acetone–nonane,
2 : 1 (А), 1-butanol–acetic acid–water, 3 : 1 : 1 (B), 1-
butanol saturated with NH3 (C), development with
iodine vapor and phosphorus molybdic acid.
X-ray diffraction analysis of compound 14 was
realized at room temperature on an autodiffractometer
CAD-4 Enraf-Nonius (graphite monochromator, МоKα-
radiation, θ /2θ-scanning). The extinction was taken
into account by the method of psi-scanning [34]. The
structure was solved by the direct method. Coordinates
of hydrogen atoms were partially determined from
differential Fourier synthesis. Coordinates of hydrogen
atoms of methyl group were determined by
Fig. 3. Two-dimensional lattice parallel to the plane (1 0 ‒2)
formed by intermolecular bonds, hydrogen bonds are
marked with dashed lines.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

GASPARYAN et al.
1650
Table 2. Basic crystallographic characteristics of 6-amino-5-
(3,4-dihydro-2H-pyrrol-5-yl)-2-(propylsulfanyl)-pyrimidin-
4(3Н)-one 14
product was triturated, the formed precipitate was
filtered off, washed with water, dried, and
recrystallized.
Empirical formula
М
C11H16N4OS
6-Anilino-1-benzylpyrimidine-2,4(1H,3H)-dione
(4). Yield 2.2 g (75%), mp 301–303°С (2-propanol), Rf
0.42 (А). IR spectrum, ν, cm–1: 3267 (NH), 1681
(C=O). 1Н NMR spectrum, δ, ppm: 4.58 d (1H, =CH, J
1.6 Hz), 5.27 s (2H, NCH2), 7.08–7.38 m (10Harom),
8.24 s (1H, NHPh), 10.59 br.s (1H, NH). Found, %: C
69.81; H 5.33; N 14.02. C17H15N3O2. Calculated, %: C
69.61; H 5.15; N 14.33.
252.34
Crystal system
Space group
а, b, c, Å
β, deg
Monoclinic
P21/c
10.623(2), 6.5812(13), 18.475(4)
105.93(3)
1242.0(5)
4
1-Benzyl-6-(3,5-dimethylanilino)pyrimidine-2,4-
(1H,3H)-dione (5). Yield 2.5 g (80%), mp 273–275°С
(2-propanol), Rf 0.79 (B). IR spectrum, ν, cm–1: 3277
V, Å3
Z
1
(NH); 1690, 1638 (C=O). Н NMR spectrum, δ, ppm:
Dcalc, g/cm3
1.349
2.29 s (6H, CH3), 4.60 d (1H, =CH, J 1.4 Hz), 5.25 s
(2H, NCH2), 6.70 d (2H, C6H3, J 1.4 Hz), 6.77 br.t
(1H, C6H3, J 1.4 Hz), 7.20–7.36 m (5Harom), 8.07 s
(1H, NHPh), 10.44 br.s (1H, NH). Found, %: C 71.28;
H 5.69; N 13.24. C19H19N3O2. Calculated, %: C 71.01;
H 5.96; N 13.08.
μ(MoKα) mm–1, Tmin, Tmax0.251, 0.30591, 0.33438
F(000)
536
Crystal size, mm
Temperature, K
0.22 × 0.30 × 0.35
293
6-(3,5-Dimethylanilino)-1-(3-phenylpropyl)-pyri-
midine-2,4(1H,3H)-dione (6). Yield 2.4 g (69%), mp
240–242°С (2-propanol), Rf 0.74 (B). IR spectrum, ν,
Radiation wavelength, Å 0.71073
θmin, θmax, deg
2.0, 30.0
1
cm–1: 3240, 3178 (NH); 1693, 1653 (C=O). Н NMR
Scanning range
Measured reflections
0 ≤ h ≤ 14, 0 ≤ k ≤ 9, –25 ≤ l ≤ 24
spectrum, δ, ppm: 1.90–2.02 m (2H, CH2), 2.33 s (6H,
CH3), 2.65–2.72 m (2H, CH2Ph), 3.98–4.05 m (2H,
NCH2), 4.50 d (1H, =CH, J 2.0 Hz), 6.82 s (3H, C6H3),
7.09–7.14 m (1Harom), 7.19–7.26 m (4Harom), 8.08 s
(1H, NHPh), 10.25 br.d (1H, NH, J 2.0 Hz). Found, %:
C 72.43; H 6.31; N 12.25. C21H23N3O2. Calculated, %:
C 72.18; H 6.63; N 12.03.
3786
Reflections with
[I>2.0σ(I)]
2755
Nref, Npar
3609, 207
R, WR2, S
0.0422, 0.1223, 1.05
W = 1/[σ2(Fo2) + (0.0609P)2 +
0.2601P], where P = (Fo2 +
2Fc2)/3
Compounds (7–9 and 13–15). General method.
To 1.9 g (20 mmol) of pyrrolidin-2-one in 5 mL of 1,4-
dioxane at 0–5°С while vigorously stirring was added
dropwise 2.74 g (20 mmol) of PCl3. The reaction
mixture was stirred for 15 min at 30°С and during 10
min was gradually added 10 mmol of compounds 4–6
or 10–12 dissolved in minimal amount of 1,4-dioxane.
The reaction mixture was stirred for 3 h at 60°С, the
temperature was raised to 100°С and the stirring
continued for 15 min more. After cooling 50 mL of ice
cold water was added, the solution was filtered from a
little amount of precipitate, the filtrate was neutralized
with 30% NH4OH and held for one day at 5°С. The
formed precipitate was filtered off and dried in air.
Weight scheme
1
(72%), mp 140–142°С (2-propanol), Rf 0.73 (А). Н
NMR spectrum, δ, ppm: 1.88–1.99 m (2H, CH2), 2.65 t
(2H, CH2Ph, J 7.5 Hz), 3.71–3.78 m (2H, NCH2), 5.71
d (1H, =CH, J 1.9 Hz), 7.09–7.24 m (5Harom), 11.41
br.d (1H, NH, J 1.9 Hz). Found, %: C 58.80; H 4.73; N
10.29. C13H13ClN2O2. Calculated, %: C 58.99; H 4.95;
N 10.58.
Compounds (4–6). General method. A mixture of
10 mmol of 1-R-pyrimidine-2,4(1H,3H)-dione 2 [28]
or 3 and 20 mmol of aniline or dimethylaniline was
boiled until reaction was completed (control with
TLC). Then 10 mL of water was added, the reaction
6-Anilino-1-benzyl-5-(3,4-dihydro-2H-pyrrol-5-
yl)pyrimidine-2,4(1H,3H)-dione (7). Yield 2.1 g
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

SYNTHESIS OF NEW DERIVATIVES OF 5-(3,4-DIHYDRO-2Н-PYRROL-5-YL)PYRIMIDINE
1651
(60%), mp 173–175°С, Rf 0.63 (B). IR spectrum, ν,
6-Amino-5-(3,4-dihydro-2H-pyrrol-5-yl)-2-sul-
1
cm–1: 3320, 3204 (NH); 1698, 1637 (C=O). Н NMR
fanylidene-1,2-dihydropyrimidin-4(3Н)-one (13).
Yield 0.6 g (30%), mp 285°С (with decomposition), Rf
0.27 (B). IR spectrum, ν, cm–1: 3529, 3370 (NH); 1636
spectrum, δ, ppm: 1.82–1.95 m (2H, CH2), 2.44–2.83
m (2H, CH2), 3.55 br.t (2H, CH2, J 7.2 Hz), 4.95 br.s
(2H, NCH2Ph), 6.65–6.69 m (2Harom), 6.82–6.88 m
(1Harom), 7.00–7.23 m (7Harom), 10.31 br.s (1H, NH),
11.08 br (1H, NH). Found, %: C 69.74; H 5.83; N
15.33. C21H20N4O2. Calculated, %: C 69.98; H 5.59; N
15.55.
1
(C=O). Н NMR spectrum, δ, ppm: 1.75–1.87 m (2H,
CH2), 3.06 br.t (2H, =CCH2, J 8.0 Hz), 3.77 t (2H,
NCH2, J 7.4 Hz), 6.74 br.s (1H, =NH), 11.03 br.s (1H,
NH), 11.39 br.s (2H, 2NH). Found, %: C 45.88; H
4.52; N 26.44. C8H10N4OS. Calculated, %: C 45.70; H
4.79; N 26.65.
1-Benzyl-5-(3,4-dihydro-2H-pyrrol-5-yl)-6-(3,5-
dimethylanilino)pyrimidine-2,4(1H,3H)-dione (8).
Yield 2.5 g (64%), mp 198–199°С, Rf 0.71 (B). IR
6-Amino-5-(3,4-dihydro-2H-pyrrol-5-yl)-2-(pro-
pylsulfanyl)pyrimidin-4(3Н)-one (14). Yield 1.3 g
(52%), mp 176°С (with decomposition), Rf 0.58 (B).
IR spectrum, ν, cm–1: 3351 (NH), 1642 (C=O). 1Н NMR
spectrum, δ, ppm: 1.04 t (3H, CH3, J 7.3 Hz), 1.72
sextet (2H, CH2CH3, J 7.3 Hz), 1.75–1.87 m (2H,
NCH2CH2CH2), 3.04–3.12 m (4H, SCH2, =CCH2),
3.81 br.t (2H, NCH2, J 7.4 Hz), 6.83 br.s (1H, =NH),
10.51 br.s (1H, NH), 11.65 br.s (1H, NH). Found, %:
C 52.61; H 6.12; N 22.52. C11H16N4OS. Calculated, %:
C 52.36; H 6.39; N 22.20.
1
spectrum, ν, cm–1: 3149 (NH), 1695 (C=O). Н NMR
spectrum, δ, ppm: 1.88–2.01 m (2H, CH2), 2.18 s (6H,
CH3), 2.72–3.00 m (2H, CH2), 3.54–3.65 m (2H,
NCH2), 4.87 br.s (2H, NCH2Ph), 6.22 br.d (2H, C6H3,
J 1.4 Hz), 6.49 br.t (1H, C6H3, J 1.4 Hz), 6.83–7.02 m
(2Harom), 7.10–7.23 m (3Harom), 10.28 br.s (1H, NH),
11.55 br (1H, NH). Found, %: C 70.85; H 6.02; N
14.74. C23H24N4O2. Calculated, %: C 71.11; H 6.23; N
14.42.
6-Amino-2-benzylsulfanyl-5-(3,4-dihydro-2H-
pyrrol-5-yl)pyrimidin-4(3Н)-one (15). Yield 1.3 g
(45%), mp 203°С (with decomposition), Rf 0.53 (B).
IR spectrum, ν, cm–1: 3347, 3135 (NH), 1636 (C=O).
1Н NMR spectrum, δ, ppm: 1.76–1.88 m (2H, CH2),
3.09 br.t (2H, =CCH2, J 8.0 Hz), 3.81 br.t (2H, NCH2,
J 7.4 Hz), 4.37 s (2H, SCH2), 7.17–7.31 m (3Harom),
7.38–7.43 m (2Harom), 7.29 br.s (1H, =NH), 10.51 br.s
(1H, NH), 11.62 br.s (1H, NH). 13С NMR spectrum, δ,
ppm: 21.6 (CH2), 33.3 (CH2), 38.1 (CH2), 57.6
(NCH2), 89.2 (CCO), 126.6 (Сp), 127.9 and 128.7
(Со,о', Cm,m'), 137.0 (Ci), 160.4 br.s (N=C), 161.9, 171.2
br.s (N=C). Found, %: C 59.65; H 5.54; N 18.90.
C15H16N4OS. Calculated, %: C 59.98; H 5.37; N 18.65.
5-(3,4-Dihydro-2H-pyrrol-5-yl)-6-(3,5-dimethyl-
anilino)-1-(3-phenylpropyl)pyrimidine-2,4(1H,3H)-
dione (9). Yield 2.4 g (58%), mp 224–225°С, Rf 0.66
(B). IR spectrum, ν, cm–1: 3240, 3180 (NH); 1693
1
(C=O). Н NMR spectrum, δ, ppm: 1.63–1.77 m (2H,
CH2), 1.92–2.05 m (2H, CH2), 2.16–2.34 m (2H, CH2),
2.26 s (6H, CH3), 3.11 br (2H, CH2), 3.58–3.69 m
(4H, NCH2), 6.40 br.s (2H, H2,2', C6H3), 6.56 br.s (1H,
H4, C6H3), 7.00–7.20 m (5Harom), 10.12 s (1H, NH),
11.96 br (1H, NH). Found, %: C 72.39; H 6.65; N
13.14. C25H28N4O2. Calculated, %: C 72.09; H 6.78; N
13.45.
6-Amino-2-(propylsulfanyl)pyrimidin-4(3Н)-one
(11). A mixture of 1.43 g (10 mmol) of 6-amino-2-
sulfanylidene-2,3-dihydropyrimidin-4(1Н)-one 10,
1.25 g (10 mmol) of 1-bromopropane, and 0.4 g
(10 mmol) of NaOH in a mixture of 10 mL of water and
2 ml of 2-propanol was boiled for 16 h. The reaction
mixture was filtered from small amount of precipitate,
the filtrate was neutralized with diluted acetic acid, the
formed precipitate was filtered off and recrystallized
from 2-propanol. Yield 1.5 g (82%), mp 201–203°С,
Compounds (20–23). General method. A mixture
of 10 mmol of N-substituted 5-hydroxypyrrolidin-2-
one 18 [31], 19 [32] and 10 mmol of compounds 5, 16,
and 17 in 15 mL of glacial acetic acid was heated at
115–130°С for 2 h after the dissolution of reagents.
After cooling the reaction mixture was diluted with
water and neutralized with sodium carbonate. The
formed precipitate was separated, dried, and
recrystallized.
1
Rf 0.80 (B). Н NMR spectrum, δ, ppm: 1.03 t (3H,
CH3, J 7.3 Hz), 1.70 sextet (2H, CH2, J 7.3 Hz), 3.03 t
(2H, SCH2, J 7.3 Hz), 4.89 s (1H, =CH), 5.91 br.s (2H,
NH2), 11.34 br.s (1H, NH). Found, %: C 45.21; H
5.65; N 22.47. C7H11N3OS. Calculated, %: C 45.39; H
5.99; N 22.68.
1-Benzyl-5-(1-benzyl-5-oxotetrahydro-1H-pyrrol-
2-yl)-6-(3,5-dimethylanilino)pyrimidine-2,4(1H,3H)-
dione (20). Yield 3.1 g (63%), mp 252–253.5°С (butan-
1-ol), Rf 0.74 (C). IR spectrum, ν, cm–1: 3260 (NH),
1
1699 (С=О). Н NMR spectrum, δ, ppm: 1.82–1.94 m
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 11 2016

GASPARYAN et al.
1652
(2Н, СНСН2), 2.03–2.18 m (1Н, О=ССНB), 2.14 s
(6Н, 2СН3), 2.52–2.68 m (1Н, О=ССНA), 3.76 d (1Н,
NCH2, J 14.8 Hz), 4.24–4.32 m (1Н, NСН), 4.41 d (1Н,
NCH2, J 14.8 Hz), 4.85 d (1Н, NCH2, J 15.6 Hz), 5.13
d (1Н, NCH2, J 15.6 Hz), 6.07 br.s (2Н, Нo,o', С6Н3),
6.38 br.s (1Н, Нp, С6Н3), 6.97–7.02 m (2Н) and 7.08–
7.25 m (8Н, 2С6Н5), 7.53 br.s (1Н, NH), 11.03 s (1Н,
NH). Found, %: C 72.48; H 6.25; N 11.23.
C30H30N4O3. Calculated, %: C 72.85; H 6.11; N 11.33.
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3.78 d (0.3Н, J 14.0 Hz), 4.05 d (0.7Н, J 14.0 Hz),
4.23 d (0.7Н, J 14.0 Hz) and 4.53 d (0.3Н, NCH2,
J 14.0 Hz), 4.59–4.68 m (0.7Н) and 4.98–5.08 m
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6-Amino-5-[1-(4-methoxyphenyl)-5-oxotetra-
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(С=О). Н NMR spectrum, δ, ppm: 2.00–2.70 m (4Н,
СН2СН2), 3.71 s (3Н, ОСН3), 5.19 br.s (0.7Н)
and 5.44 br.s (0.3Н, СН), 5.88 br.s (0.6Н) and
6.23 br.s (1.4Н, NH2), 6.80–6.86 m (2Н) and 7.13–
7.19 m (2Н, С6Н4), 9.68–9.86 br.s (1Н, NH), 10.01–
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17.87. C15H16N4O4. Calculated, %: C 56.96; H 5.10; N
17.71.
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SYNTHESIS OF NEW DERIVATIVES OF 5-(3,4-DIHYDRO-2Н-PYRROL-5-YL)PYRIMIDINE
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