5-Aryl-2-furaldehydes in the synthesis of tetrahydropyrimidinones by Biginelli reaction

Article abstract of DOI:10.1007/s10593-018-2301-3

5-Aryl-2-furaldehydes, obtained by furfural arylation with arenediazonium salts, react with ethyl acetoacetate or acetylacetone and (thio)- urea in the presence of FeCl3·6H2O as a catalyst. A series of ethyl 4-(5-aryl-2-furyl)-6-methyl-2-oxo(thioxo)-1,2,3,4-tetrahydropyrimidine- 5-carboxylates was obtained.

Full text of DOI:10.1007/s10593-018-2301-3

DOI 10.1007/s10593-018-2301-3
Chemistry of Heterocyclic Compounds 2018, 54(5), 545–549
5-Aryl-2-furaldehydes in the synthesis of tetrahydropyrimidinones
by Biginelli reaction
Andriy R. Vakhula1, Yuriy I. Horak1, Roman Z. Lytvyn1, Alexandra I. Lesyuk1,
Vasyl Kinzhybalo2, Fedor I. Zubkov3, Mykola D. Obushak1*
1 Ivan Franko National University of Lviv,
6 Kyryla i Mefodiya St., Lviv 79005, Ukraine; e-mail: obushak@in.lviv.ua
2 Institute of Low Temperature and Structure Research,
Wroclaw 50-422, Poland; e-mail: v.kinzhybalo@int.pan.wroc.pl
3 RUDN University,
6 Miklukho-Maklaya St., Moscow 117198, Russia; e-mail: fzubkov@sci.pfu.edu.ru
Submitted July 29, 2017
Accepted after revision April 20, 2018
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(5), 545–549
5-Aryl-2-furaldehydes, obtained by furfural arylation with arenediazonium salts, react with ethyl acetoacetate or acetylacetone and (thio)-
urea in the presence of FeCl3·6H2O as a catalyst. A series of ethyl 4-(5-aryl-2-furyl)-6-methyl-2-oxo(thioxo)-1,2,3,4-tetra-
hydropyrimidine-5-carboxylates was obtained.
Keywords: 5-aryl-2-furaldehydes, pyrimidine derivatives, tetrahydropyrimidines, Biginelli reaction, crystal structure, multicomponent reactions.
Multicomponent reactions (MCRs) are extremely useful
organic transformations that are taking place with the
participation of three or more components, which react
with each other consistently to form the desired product.1
MCRs have been widely used in organic and medicinal
chemistry for the generation of diverse compound
libraries,2 demonstrating synthetic efficiency and
significant advantages, reducing time of the reaction, and
increasing reaction rate along with high yields and
reproducibility. Diversity, efficiency, and fast access to
complex functionalized organic molecules make MCRs
favorites among synthetic chemists. The current interest in
the creation of combinatorial libraries and optimization of
chemical processes demonstrates the universality of the
MCR approach.2h,3 These reactions can be an excellent tool
for building diverse and variously oriented compound
libraries of a new generation.
alkaloids, etc.).5 Some recently synthesized tetrahydro-
pyrimidin-2-ones are widely used as therapeutic agents and
possess pharmacological properties including antiviral, anti-
mitotic, anticancer, antihypertensive, anxiolytic, and hypnotic.6
On the other hand, many compounds of the arylfuran
series (in particular, 4-nitrophenylfuran derivatives) exhibit
a broad spectrum of biological activity.7 Some of them are
already used in therapeutic practice (dantrolene,
clodanolene, azimilide, etc.).7a,b Therefore, the combination
of pyrimidine and arylfuran fragments is of great interest
from the point of view of medicinal chemistry, as, for
example, evidenced in particular study of the properties of
the Biginelli reaction products obtained using 5-(3-tri-
fluoromethylphenyl)furan-2-carbaldehyde.8 Here we report
on the series of 5-aryl-2-furaldehydes as starting com-
pounds in a three-component Biginelli cyclization with
(thio)urea and ethyl acetoacetate or acetylacetone.
The Biginelli reaction is a convenient method for the
synthesis of functionalized tetrahydropyrimidin-2-ones.4
Pyrimidine fragment is an important component of a
variety of biologically active compounds, including com-
pounds with pharmaceutical application (synthetic drugs)
and compounds of natural origin (nucleic acids, vitamins,
One of the most convenient approaches to functionalized
arylfuraldehydes, which are practical and useful reagents,
is arylation of furaldehydes by aryl diazonium salts.9 Using
this methodology, we obtained 5-aryl-2-furaldehydes 3a–l
starting from anilines 1a–l via diazonium salts 2a–l
(Scheme 1).
0009-3122/18/54(5)-0545©2018 Springer Science+Business Media, LLC
545

Chemistry of Heterocyclic Compounds 2018, 54(5), 545–549
Scheme 1
O
O
NH2
N2+Cl–
NaNO2, HCl
CuCl2·2H2O
R1
R1
H2O
0–5°C, 5 min
Me2CO, rt, 0.5–1 h
35–60%
1a–l
2a–l
Me
R2
X
+
O
H2N
NH2
O
O
4a b
,
5a b
O
,
R1
3a l
–
O
R2
Figure 1. Molecular structure of compound 6c with atoms repre-
sented by thermal vibration ellipsoids of 30% probability.
Me
NH
FeCl3·6H2O
EtOH
, 6 h
O
HN
R1
X
6a–l, 7
Table 1. Yields of compounds 6a–l, 7
Compound
R1
R2
X
Yield, %
4-F
4-Сl
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Me
O
O
O
O
O
O
O
O
O
O
O
S
76
59
79
73
69
75
77
68
70
65
68
74
56
6a
6b
6c
6d
6e
6f
6g
6h
6i
4-Br
2-NO2
3-NO2
4-NO2
2,3-Cl2
2,5-Cl2
2-Cl-5-CF3
4-Cl-3-CF3
4-МeO-2-NO2
2,4-Cl2
4-Br
Figure 2. Molecular structure of compound 6f with atoms repre-
sented by thermal vibration ellipsoids of 30% probability.
6j
6k
6l
but in this case, yields of compounds 6a–l were lower. For
instance, application of FeCl3·6H2O as catalyst gave
tetrahydropyrimidine 6а in 76% yield, whereas in the case
of ZnCl2 yield of compound 6a is only 52%.
O
7
We found that aldehydes 3a–l react with ethyl aceto-
acetate (4а) and urea (5a) or thiourea (5b) in the presence
of FeCl3·6H2O as a catalyst forming ethyl 4-(5-aryl-
2-furyl)-6-methyl-2-oxo(thioxo)-1,2,3,4-tetrahydropyrymi-
dine-5-carboxylates 6a–l (Scheme 1, Table 1) with the
yields up to 79%.
We investigated the effect of FeCl3·6H2O catalyst added
in 10 mol % quantity. The reactions were carried out in
EtOH under reflux for 6 h. It should be noted that in the
reaction of 5-aryl-2-furaldehydes 3a–l with ethyl aceto-
acetate (4а) and thiourea (5b), resinification occurred, and
only compound 6l was obtained with sufficient yield and
purity. Probably, the nature of such behavior lies in
oxidizing properties of Fe3+ ion. On the other hand,
reactions with urea (5a) proceeded well and without side
reactions or by-products. The yield of the reactions varied
in the range from 56 to 79%.
Acetylacetone (4b) can be also successively exploited in
this transformation under found reaction conditions. Thus,
by the reaction of 5-(4-bromophenyl)-2-furaldehyde 3c
with urea (5a) and acetylacetone (4b), compound 7 was
formed in 56% yield. However, in the reactions of
aldehydes 3a–l with urea (5a) and dimedone, the desired
Biginelli products were not isolated. Carrying out the
reactions in highly boiling solvent (acetic acid) did not give
positive results too, proving that 5-aryl-2-furaldehydes are
less active reagents in Biginelli reaction comparing to
benzaldehydes.4c
The structure of compounds 6a–l, 7 was confirmed by
1H and 13C NMR spectroscopy and by X-ray structural
analysis (compounds 6c,f, Fig. 1, 2). The geometrical
parameters of compounds 6c,f are comparable with the
reported in the literature unsubstituted furan derivatives of
methyl and ethyl tetrahydropyrymidine-5-carboxylates.10
Thus, a method for the synthesis of ethyl 4-(5-aryl-
2-furyl)-6-methyl-2-oxo(thioxo)-1,2,3,4-tetrahydropyrimi-
dine-5-carboxylates via the Biginelli reaction has been
developed utilizing 5-aryl-2-furaldehydes as starting com-
pounds.
Several most frequently used Biginelli reaction catalysts
were investigated for this transformation. It was found, that
the hydrochloric acid as a catalyst gave poor results due to
the formation of side products and resinification of the
reaction mixture. ZnCl2 can be utilized as a catalyst as well,
546

Chemistry of Heterocyclic Compounds 2018, 54(5), 545–549
Experimental
Ethyl 4-[5-(4-bromophenyl)furan-2-yl]-6-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (6c). Yield
0.64 g (79%), light-yellow needles, mp 204–205°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.1,
СН3СН2); 2.26 (3H, s, СН3); 4.06 (2H, q, J = 7.1,
СН3СН2); 5.26 (1H, d, J = 3.3, СН); 6.22 (1H, d, J = 3.3,
H Fur); 6.90 (1H, d, J = 3.3, H Fur); 7.57 (2H, d, J = 8.6,
H Ar); 7.62 (2H, d, J = 8.6, H Ar); 7.86 (1H, br. s, NH);
9.32 (1H, s, NH). 13C NMR spectrum, δ, ppm: 14.7; 18.2;
48.4; 59.8; 97.0; 107.8; 108.1; 120.7; 125.5 (2С); 129.9;
132.3 (2C); 150.1; 151.4; 153.0; 156.8; 165.5. Found, %:
С 53.11; Н 3.92; N 6.63. C18H17BrN2O4. Calculated, %:
С 53.35; Н 4.23; N 6.91.
1Н and 13C NMR spectra were acquired on a Bruker
WH-400 spectrometer (400 and 100 MHz, respectively) in
DMSO-d6, using TMS as internal standard. Elemental
analysis was performed on a Carlo Erba 1106 instrument.
Melting points were determined on a Boetius apparatus.
Synthesis of 5-aryl-2-furaldehydes 3a–l (General
method).9 A solution of NaNO2 (15.2 g, 0.22 mol) in H2O
(30 ml) was added dropwise to a stirred and ice-cooled (0–
5°C) mixture of the substituted aniline 1a–l (0.2 mol),
concd HCl (40 ml), and water (30 ml). Then cold
diazonium salt 2a–l solution was slowly added to the
vigorously stirred solution of CuCl2·2H2O (2.0 g, 11.0 mmol)
and furaldehyde (19.2 g, 0.2 mol) in Me2CO (80 ml) at 20–
25°C. The dropping rate was adjusted in a way that
nitrogen was evolved at 2-3 bubbles/s (0.5–1 h). When
bubbling stopped (all nitrogen was removed), the product
was filtered off, washed 3 times with water, and re-
crystallized from EtOH or EtOH–DMF mixture.
Characteristics of compounds 3a–l were in good agreement
with literature data.8,11
Synthesis of compounds 6a–l, 7 (General method).
A mixture of 5-aryl-2-furaldehyde 3a–l (2.0 mmol), ethyl
acetoacetate (4a) or acetylacetone (4b) (2.0 mmol), urea
(5a) or thiourea (5b) (2.0 mmol), and FeCl3·6H2O (0.054 g,
0.2 mmol) in EtOH (10 ml) was heated under reflux for 6 h.
After cooling to room temperature, the reaction mixture was
poured into distilled water (50 ml). The precipitate was
filtered off and washed several times with distilled water.
The crude product was recrystallized from EtOH–DMF
(1:2) mixture.
Ethyl 6-methyl-4-[5-(2-nitrophenyl)furan-2-yl]-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (6d). Yield
0.54 g (73%), yellow-brown powder, mp 230–231°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.1,
СН3СН2); 2.26 (3H, s, СН3); 4.05 (2H, q, J = 7.1,
СН3СН2); 5.22 (1H, d, J = 3.2, СН); 6.29 (1H, d, J = 3.3,
H Fur); 6.79 (1H, d, J = 3.3, H Fur); 7.53 (1H, t, J = 7.8,
H Ar); 7.70 (1H, t, J = 7.8, H Ar); 7.75 (1H, br. s, NH);
7.78 (1H, d, J = 7.8, H Ar); 7.83 (1H, d, J = 7.8, H Ar);
9.27 (1H, s, NH). 13C NMR spectrum, δ, ppm: 14.6; 18.2;
48.3; 59.7; 96.7; 108.1; 111.0; 123.1; 124.4; 128.7; 129.4;
132.8; 147.2 (2C); 150.3; 152.8; 158.3; 165.3. Found, %:
С 58.01; Н 4.79; N 11.00. C18H17N3O6. Calculated, %:
С 58.22; Н 4.61; N 11.32.
Ethyl 6-methyl-4-[5-(3-nitrophenyl)furan-2-yl]-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (6e). Yield
0.51 g (69%), light-yellow powder, mp 249–250°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.19 (3H, t, J = 7.1,
СН3СН2); 2.30 (3H, s, СН3); 4.11 (2H, q, J = 7.1,
СН3СН2); 5.37 (1H, d, J = 3.1, СН); 6.30 (1H, d, J = 3.3,
H Fur); 7.12 (1H, d, J = 3.3, H Fur); 7.72 (1H, t, J = 8.0,
H Ar); 7.88 (1H, br. s, NH); 8.08–8.12 (2H, m, H Ar); 8.44
(1H, s, H Ar); 9.33 (1H, s, NH). 13C NMR spectrum,
δ, ppm: 14.3; 17.9; 48.4; 59.6; 96.9; 108.1; 109.2; 117.6;
121.9; 129.5; 130.8; 132.3; 148.9; 150.3 (2C); 153.0;
157.7; 165.4. Found, %: С 58.44; Н 4.37; N 11.04.
C18H17N3O6. Calculated, %: С 58.22; Н 4.61; N 11.32.
Ethyl 6-methyl-4-[5-(4-nitrophenyl)furan-2-yl]-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (6f). Yield
0.56 g (75%), light-yellow crystals, mp 231–232°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.0,
СН3СН2); 2.27 (3H, s, СН3); 4.07 (2H, q, J = 7.0,
СН3СН2); 5.31 (1H, d, J = 3.0, СН); 6.34 (1H, d, J = 3.3,
H Fur); 7.20 (1H, d, J = 3.3, H Fur); 7.86 (2H, d, J = 8.8,
H Ar); 7.92 (1H, br. s, NH); 8.28 (2H, d, J = 8.8, H Ar);
9.36 (1H, s, NH). 13C NMR spectrum, δ, ppm: 14.7; 18.2;
48.4; 59.9; 96.7; 108.8; 111.6; 124.1 (2С); 125.0 (2С);
136.5; 146.3; 150.4; 150.5; 152.9; 158.8; 165.4. Found, %:
С 57.98; Н 4.79; N 11.57. C18H17N3O6. Calculated, %:
С 58.22; Н 4.61; N 11.32.
Ethyl 4-[5-(4-fluorophenyl)furan-2-yl]-6-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (6a). Yield
0.52 g (76%), white powder, mp 225–226°С. H NMR
1
spectrum, δ, ppm (J, Hz): 1.16 (3H, t, J = 7.1, СН3СН2);
2.26 (3H, s, СН3); 4.06 (2H, q, J = 7.1, СН3СН2); 5.25 (1H,
d, J = 3.2, СН); 6.20 (1H, d, J = 3.3, H Fur); 6.81 (1H, d,
J = 3.3, H Fur); 7.27 (2H, dd, JHH = 8.8, JHF = 8.8, H Ar);
7.66 (2H, dd, JHH = 8.8, JHF = 5.5, H Ar), 7.84 (1H, br. s,
NH); 9.31 (1H, s, NH). 13C NMR spectrum, δ, ppm (J, Hz):
14.7; 18.2; 48.3; 59.8; 97.1; 106.7; 107.9; 116.4 (2C, d,
J = 22.0); 125.7 (2C, d, J = 8.2); 127.5; 150.1; 151.6;
153.0; 156.4; 161.9 (d, J = 244.6); 165.5. Found, %:
С 62.54; Н 4.77; N 7.92. C18H17FN2O4. Calculated, %:
С 62.79; Н 4.98; N 8.14.
Ethyl 4-[5-(4-chlorophenyl)furan-2-yl]-6-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (6b). Yield
0.43 g (59%), light-brown powder, mp 254–255°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.0,
СН3СН2); 2.26 (3H, s, СН3); 4.06 (2H, q, J = 7.0,
СН3СН2); 5.26 (1H, d, J = 2.8, СН); 6.22 (1H, d, J = 3.1,
H Fur); 6.89 (1H, d, J = 3.1, H Fur); 7.49 (2H, d, J = 8.0,
H Ar); 7.64 (2H, d, J =8.0, H Ar); 7.84 (1H, br. s, NH);
9.32 (1H, s, NH). 13C NMR spectrum, δ, ppm: 14.7; 18.2;
48.4; 59.8; 97.0; 107.7; 108.1; 125.2 (2С); 129.4 (2С);
129.6; 132.2; 150.1; 151.3; 153.0; 156.8; 165.5. Found, %:
С 59.74; Н 4.51; N 7.92. C18H17ClN2O4. Calculated, %:
С 59.92; Н 4.75; N 7.76.
Ethyl 4-[5-(2,3-dichlorophenyl)furan-2-yl]-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (6g).
Yield 0.61 g (77%), white powder, mp 233–234°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.16 (3H, t, J = 7.1,
СН3СН2); 2.26 (3H, s, СН3); 4.07 (2Н, q, J = 7.1,
СН3СН2); 5.29 (1H, d, J = 2.8, СН); 6.31 (1H, d, J = 3.3,
547

Chemistry of Heterocyclic Compounds 2018, 54(5), 545–549
H Fur); 7.11 (1H, d, J = 3.3, H Fur); 7.45 (1H, t, J = 7.8,
59.7; 96.8; 107.9; 109.4 (2C); 115.7; 118.9; 130.0; 147.3;
148.1; 150.2; 152.8; 157.5; 159.5; 165.4. Found, %:
С 56.61; Н 4.94; N 10.12. C19H19N3O7. Calculated, %:
С 56.86; Н 4.77; N 10.47.
H Ar); 7.59 (1H, d, J = 7.8, H Ar); 7.72 (1H, d, J = 7.8,
H Ar); 7.88 (1H, br. s, NH); 9.35 (1H, s, NH). 13C NMR
spectrum, δ, ppm: 14.7; 18.2; 48.3; 59.8; 96.9; 108.0;
113.4; 126.6; 127.4; 128.9; 129.6; 131.1; 133.7; 148.1; 150.3;
153.0; 157.2; 165.5. Found, %: С 54.52; Н 3.92; N 6.88.
C18H16Cl2N2O4. Calculated, %: С 54.70; Н 4.08; N 7.09.
Ethyl 4-[5-(2,5-dichlorophenyl)furan-2-yl]-6-methyl-
2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (6h).
Yield 0.54 g (68%), yellow-brown powder, mp 232–233°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.17 (3H, t, J = 7.1,
СН3СН2); 2.26 (3H, s, СН3); 4.08 (2H, q, J = 7.1,
СН3СН2); 5.30 (1H, d, J = 3.4, СН); 6.30 (1H, d, J = 3.6,
H Fur); 7.14 (1H, d, J = 3.6, H Fur); 7.37 (1H, dd, J = 8.6,
J = 2.6, H Ar); 7.56 (1H, d, J = 8.6, H Ar); 7.80 (1H, d, J = 2.6,
H Ar); 7.94 (1H, br. s, NH); 9.37 (1H, d, J = 1.4, NH).
13C NMR spectrum, δ, ppm: 14.7; 18.2; 48.3; 59.9; 96.7;
108.1; 113.4; 126.9; 127.7; 128.7; 130.2; 132.7; 133.0; 147.3;
150.4; 153.0; 157.2; 165.5. Found, %: С 54.87; Н 4.26; N 7.23.
C18H16Cl2N2O4. Calculated, %: С 54.70; Н 4.08; N 7.09.
Ethyl 4-{5-[2-chloro-5-(trifluoromethyl)phenyl]furan-
2-yl}-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carb-
oxylate (6i). Yield 0.60 g (70%), white powder, mp 219–
Ethyl 4-[5-(2,4-dichlorophenyl)furan-2-yl]-6-methyl-
2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (6l).
Yield 0.61 g (74%), light-yellow powder, mp 231–232°С.
1H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.1,
СН3СН2); 2.30 (3H, s, СН3); 4.08 (2H, q, J = 7.1,
СН3СН2); 5.31 (1H, d, J = 3.7, СН); 6.34 (1H, d, J = 3.4,
H Fur); 7.08 (1H, d, J = 3.4, H Fur); 7.54 (1H, dd, J = 8.6,
J = 2.1, H Ar); 7.71 (1H, d, J = 2.1, H Ar); 7.74 (1H, d,
J = 8.6, H Ar); 9.74 (1H, br. s, NH); 10.51 (1H, s, NH).
13C NMR spectrum, δ, ppm: 14.6; 17.6; 48.3; 60.2; 98.4;
108.9; 112.8; 127.7; 128.3; 129.0; 130.2; 130.7; 132.9; 146.8;
148.2; 155.6; 165.2; 175.7. Found, %: С 52.32; Н 4.15; N 6.64.
C18H16Cl2N2O3S. Calculated, %: С 52.56; Н 3.92; N 6.81.
5-Acetyl-4-[5-(4-bromophenyl)furan-2-yl]-6-methyl-
1,2,3,4-tetrahydropyrimidin-2-one (7). Yield 0.40 g
(56%), light-brown powder, mp 265–266°С. 1H NMR
spectrum, δ, ppm (J, Hz): 2.19 (3H, s, СН3); 2.24 (3H, s,
СН3); 5.33 (1H, s, СН); 6.20 (1H, d, J = 3.3, H Fur); 6.86
(1H, d, J = 3.3, H Fur); 7.55–7.70 (4H, m, H Ar); 7.92 (1H,
s, NH); 9.28 (1H, s, NH). 13C NMR spectrum, δ, ppm:
19.5; 30.6; 48.4; 107.9; 108.4; 120.8; 125.6 (2С); 126.7;
129.8; 132.4 (2C); 149.6; 151.6; 153.0; 156.6; 194.2.
Found, %: С 54.23; Н 3.89; N 7.25. C17H15BrN2O3.
Calculated, %: С 54.42; Н 4.03; N 7.47.
X-ray structural study of compounds 6c,f was per-
formed on a four-circle Oxford Diffraction Xcalibur diffracto-
meter. Crystal structures were solved by direct methods
using the SHELXT program.12 Full-matrix least-square
refinement of atomic coordinates and anisotropic thermal
parameters (for non-hydrogen atoms) was done on F2 using
the SHELXL program.13 The positions of hydrogen atoms
were found on difference Fourier maps, but in final refinement
cycles were restrained geometrically to the idealized
positions. Complete bond lengths and angles, coordinates,
and displacement parameters have been deposited at the
Cambridge Crystallographic Data Center (deposits CCDC
1534517 for compound 6c, CCDC 1534516 for compound 6f).
1
220°С. H NMR spectrum, δ, ppm (J, Hz): 1.16 (3H, t,
J = 7.1, СН3СН2); 2.26 (3H, s, СН3); 4.07 (2H, q, J = 7.1,
СН3СН2); 5.33 (1H, d, J = 3.4, СН); 6.33 (1H, d, J = 3.5,
H Fur); 7.21 (1H, d, J = 3.5, H Fur); 7.66 (1H, dd, J = 8.4,
J = 2.0, H Ar); 7.79 (1H, d, J = 8.4, H Ar); 7.97 (1H, br. s,
NH); 8.07 (1H, d, J = 2.0, H Ar); 9.37 (1H, s, NH).
13C NMR spectrum, δ, ppm: 14.6; 18.2; 48.3; 59.8; 96.7;
108.2; 113.9; 124.0 (q, J = 3.7); 124.1 (q, J = 270.0); 125.3
(q, J = 3.9); 128.9 (q, J = 32.5); 129.5; 132.6; 133.1 (q,
J = 0.8); 147.2; 150.4; 153.0; 157.6; 165.5. Found, %:
С 52.95; Н 3.58; N 6.76. C19H16CIF3N2O4. Calculated, %:
С 53.22; Н 3.76; N 6.53.
Ethyl 4-{5-[4-chloro-3-(trifluoromethyl)phenyl]furan-
2-yl}-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carb-
oxylate (6j). Yield 0.56 g (65%), yellow-brown powder,
1
mp 226–227°С. H NMR spectrum, δ, ppm (J, Hz): 1.16
(3H, t, J = 7.1, СН3СН2); 2.26 (3H, s, СН3); 4.07 (2H, q,
J = 7.1, СН3СН2); 5.29 (1H, d, J = 3.3, СН); 6.27 (1H, d,
J = 3.4, H Fur); 7.12 (1H, d, J = 3.4, H Fur); 7.78 (1H, d,
J = 8.5, H Ar); 7.88–7.93 (2H, m, H Ar, NH); 8.01 (1H, d,
J = 1.7, H Ar); 9.35 (1H, s, NH). 13C NMR spectrum,
δ, ppm: 14.6; 18.2; 48.3; 59.8; 96.8; 108.3; 109.6; 122.3 (q,
J = 5.3); 123.2 (q, J = 271.3); 127.8 (q, J = 30.7); 128.6;
129.3 (q, J = 1.5); 130.2; 132.8; 149.9; 150.3; 153.0; 157.6;
This publication was supported by the Ministry of
Education and Science of Ukraine (project 0118U003610)
and by the Ministry of Education and Science of the
Russian Federation (project 4.1154.2017/4.6).
References
165.5. Found, %:
С
53.47;
Н
3.82;
N
6.86.
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thyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(6k). Yield 0.55 g (68%), yellow-brown powder, mp 206–
207°С. 1H NMR spectrum, δ, ppm (J, Hz): 1.15 (3H, t, J = 7.1,
СН3СН2); 2.25 (3H, s, СН3); 3.86 (3H, s, ОСН3); 4.05 (2H,
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NH). 13C NMR spectrum, δ, ppm: 14.6; 18.2; 48.2; 56.6;
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