Synthesis and antibacterial activity of novel pyrano[2,3-d]pyrimidine-4-one–3-phenylisoxazole hybrids

Article abstract of DOI:10.1134/S1070363217040260

A series of ethyl 2,7-dimethyl-4-oxo-5-phenyl-3-[(3-phenylisoxazol-5-yl)methyl]-3,5-dihydro-4H-pyrano[2,3-d]pyrimidine-6-carboxylates was synthesized and screened for antibacterial activity against Gram positive and Gram negative bacterial species. All ne

Full text of DOI:10.1134/S1070363217040260

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 4, pp. 829–836. © Pleiades Publishing, Ltd., 2017.
Synthesis and Antibacterial Activity of Novel
Pyrano[2,3-d]pyrimidine-4-one–3-Phenylisoxazole Hybrids
1
a
a
b
b
B. S. Kumar , P. V. A. Lakshmi *, B. S. Veena , and E. Sujatha
a
Department of Chemistry, University College for Women, Osmania University, Hyderabad, Telangana, 500007 India
e-mail: pvanantha.ou@gmail.com
*
b
Department of Botany, University College of Science, Osmania University, Hyderabad, Telangana, 500007 India
Received December 15, 2016
Abstract—A series of ethyl 2,7-dimethyl-4-oxo-5-phenyl-3-[(3-phenylisoxazol-5-yl)methyl]-3,5-dihydro-4H-
pyrano[2,3-d]pyrimidine-6-carboxylates was synthesized and screened for antibacterial activity against Gram
1
13
positive and Gram negative bacterial species. All new compounds were characterized by H, C NMR, IR, and
mass spectra. The results of the antibacterial study indicated that all compounds exhibited good to excellent
antibacterial activity.
Keywords: antibacterial activity, pyrano[2,3-d]pyrimidine, isoxazole
DOI: 10.1134/S1070363217040260
The chemistry of heterocyclic compounds continues
to be an active field of organic chemistry. Among
nitrogen and oxygen containing heterocyclic com-
pounds, pyranopyrimidine and isoxazole pharmaco-
phores are widely used in medicinal chemistry. Poly-
functionalized 4H-pyran derivative 1 exhibits anti-
bacterial and anti-cancer activity, 2 is an inhibitor of
EAAT1 [1] and their fused derivatives, pyranopyri-
midines, are important synthetic bioactive compounds.
In the recent years the synthesis of pyranopyrimidine
derivatives gained renewed interest in the field of
medicinal chemistry for their wide range of biological
activity including antimicrobial [2, 3], antimalarial [4],
antitumor [5], anti-inflammatory [6], antihistamine [7],
antigenic [8], antiviral [9], antiplatelet [10] and heap-
toprotective [11] properties. Some of these compounds
have been also identified as new HA14-1 analogs [12].
Some of the well-known pyranopyrimidine derivatives
treatment of lepracy [19]. Some of the marked iso-
xazole drugs like Leflunomide 7, Acetysulfisoxazole 8,
Zonisamide 9, Cloxacillin 10, Drazoxol 11, and
Veldecoxib 12 (Scheme 2) show antimicrobial
[20–23], tuberculostatic [24], anticonvulsant [25],
neurotoxic [26], and antiepileptic activity that leads to
the search for new bioactive compounds of these class.
Various biological opportunities of pyranopyrimidine
and isoxazole pharmacophores promoted us to syn-
thesize the title compounds presuming that their
incorporation into a single structural entity could
produce new compounds. Here we report on the
synthesis of a series of new ethyl 2,7-dimethyl-4-oxo-
5-phenyl-3-[(3-phenylisoxazol-5-yl)methyl]-3,5-dihydro-
4H-pyrano[2,3-d]pyrimidine-6-carboxylates 7a–7l and
screening for their antibacterial activity.
A series of ethyl 2,7-dimethyl-4-oxo-5-phenyl-3-
[
[
(3-phenylisoxazol-5-yl)methyl]-3,5-dihydro-4H-pyrano-
2,3-d]pyrimidine-6-carboxylates 7a–7l were syn-
3
, 4, 5, and 6 (Scheme 1) were also reported to be anti-
microbial agents [13].
thesized in five steps. In the first step, 4H-pyrans 2a–
d were easily obtained via one-pot reaction of malo-
Isoxazole, an azole with an oxygen atom next to the
nitrogen, exhibits a broad spectrum of biological
activity and also forms a part of various biodynamic
agents [14]. A number of isoxazoles and related
compounds are known as antitumor [15], anti-HIV
2
nonitrile, ethyl acetoacetate, and various substituted
aromatic aldehydes 1a–1d in the presence of catalytic
amount of piperidine in ethanol with stirring for 15–
3
0 min (Scheme 3). Compounds 2a–2d were used as
[16], anti-inflammatory [17], and cytotoxic [18]
precursors for the synthesis of pyrano[2,3-d]pyri-
midine-4-one derivatives 3a–3d by refluxing in acetic
anhydride for 15 min using catalytic amount of sulfuric
acid (Scheme 4). In the third step, the condensation of
agents. Isoxazole derivatives are also employed in the
1
The text was submitted by the authors in English.
8
29

8
30
KUMAR et al.
Scheme 1.
OCH3
HN
S
O
O
O
NC
CN
CN
NH2
NH
O
NH2
O
H N
O
N
H
S
2
1
2
3
F
F
HO
O
O
N
O
O
N
NC
O
NH
NH
N
O
O
N
O
O
N
O
O
H
O
O
4
5
6
Scheme 2.
H N
2
F3C
O
O
SO2
N
N
N
O
H
N
O
SO NH
2 2
O
7
8
9
Cl
N
O
N
O
O
Cl
O
H
H
H
N
N
S
N
N
O
H NO S
2
2
O
OH
1
0
O
11
12
pyrano[2,3-d]pyrimidine-4-one derivatives 3a–3d with
propargyl bromide in the presence of anhydrous
potassium carbonate in dry acetone under reflux for 4–
acetate in ethanol at 80°C for 30 min to form the
corresponding oximes 6a–6e (Scheme 6). In the final
step, N-propargyl pyrano[2,3-d]pyrimidine-4-ones 4a–
4d reacted with various aryl benzaldehyde oximes 6a–
6e in the presence of NaOCl and triethylamine in
CH Cl for 12–14 h to afford new ethyl 2,7-dimethyl-
5
h resulted in the formation of the corresponding N-
propargylated pyrano[2,3-d]pyrimidine-4-one derivatives
a–4d (Scheme 5). In the next step substituted
4
2
2
aromatic aldehydes 5a–5e were treated with hyd-
4-oxo-5-phenyl-3-[(3-phenylisoxazol-5-yl)methyl]-3,5-
roxylamine hydrochloride in the presence of sodium
dihydro-4H-pyrano[2,3-d]pyrimidine-6-carboxylates
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

SYNTHESIS AND ANTIBACTERIAL ACTIVITY
831
Scheme 3.
R
O
NC
O
O
O
CN
CN
Piperidine
EtOH
OEt
+
+
R
H
OEt
H N
O
2
1
2a−2d
R = Ph (a), 3,4,5-(OCH
3
)
3
6
C H
2
(b), 4-CH
3 6 4
C H (c), 2-thienyl (d).
Scheme 4.
R
O
O
R
O
NC
H N
OEt
Ac O, H SO
4
EtO
NH
2
2
O
O
N
2
2a−2d
3a−3d
R = Ph (a), 3,4,5-(OCH
3
)
3
6
C H
2
(b), 4-CH
C H (c), 2-thienyl (d).
3 6 4
Scheme 5.
O
R
O
O
O
R
O
O
K CO , reflux
EtO
N
EtO
NH
2
3
+
Br
acetone
N
N
3
a−3d
R = Ph (a), 3,4,5-(OCH
4a−4d
(c), 2-thienyl (d).
3
)
3
6
C H
2
(b), 4-CH
3 6
C H
4
7
a–7l in quantitative yields (Scheme 7). Yields and
Bacterial growth was detected by optical density. MIC
values were defined as the lowest concentration of
each product, which completely inhibited microbial
growth. The results were expressed in micrograms per
millilitres. The Minimum inhibitory concentration
melting points of the products obtained are given in
Table 1.
All synthesized compounds 7a–7l were screened in
vitro for their antibacterial activity against Gram
positive bacterial strains (Staphylococcus aureus,
Pseudomonas aeruginosa) and Gram negative
bacterial strains (Escherichia coli, Klebsiella
pneumonia). The antibacterial activity of the products
obtained was studied by employing a macro dilution
method, using Mueller–Hinton broth. All compounds
were dissolved in DMSO (10% of the final volume)
and diluted with culture broth to a concentration of
(µg/mL) was compared with standard drug ciprofloxacin.
The results are given in Table 2 and Fig. 1. All com-
pounds exhibited good to excellent antibacterial
Scheme 6.
O
H
N
CHO
2
mg/mL. Further 1 : 2 serial dilutions were performed
.
EtOH, NH OH HCl
2
by addition of culture broth to reach concentrations
ranging from 2 to 0.0156 mg/mL. Each test and growth
control well was inoculated with 5 µL of a bacterial
suspension (10 CFU/mL or 10 CFU/well). All
experiments were performed in triplicate and the micro
dilution trays were incubated at 36°C for 18 h.
NaOAc, 80°C
R
R
8
5
5a−5e
R = 4-NO (a), 4-OCH (b), 4-CH (c), 3,4-Cl (d); 2-CH ,
6a−6e
2
3
3
3
3-NO (e).
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

8
32
KUMAR et al.
Scheme 7.
OH
N
O
R1
O
O
N
R1
R2
O
O
EtO
N
NaOCl, Et N
EtO
N
3
+
O
CH Cl2
N
2
O
N
R2
6a−6e
4a−4d
7a−7l
activity. Among all, compounds 7a–7c, 7e–7g, 7i, 7k,
and 7l have shown excellent activity, greater than the
standard, and compounds 7d, 7h and 7j have shown
good activity against bacterial strains, indicating that
compounds with electron-withdrawing substitutions on
the phenyl ring, i.e., –NO and –OCH , show maxi-
mum activity. Compounds with methyl substitutions
on the phenyl ring have shown moderate activity. In
summary we have synthesized a series of novel ethyl
EXPERIMENTAL
Melting points were recorded on a Casia-Siamia
(VMP-AM) melting point apparatus and uncorrected.
IR spectra were registered on a Perkin Elmer FT-IR
240-C spectrometer using KBr optics. H NMR spectra
were taken on a Burker Avance 400 MHz in CDCl
and DMSO-d using TMS as an internal reference.
Electron impact (EI) and chemical ionization mass
spectra were recorded on a VG 7070 H instrument at
70 eV. All reactions were monitored by thin layer
1
2
3
3
6
2
,7-dimethyl-4-oxo-5-phenyl-3-[(3-phenylisoxazol-5-
yl)methyl]-3,5-dihydro-4H-pyrano[2,3-d]pyrimidine-
-carboxylates derivatives and further biological
6
Table 2. Antimicrobial activity of compounds 7a–7l
valuation was done for antibacterial activity against
Gram positive and Gram negative bacterial species.
Among all the derivatives, compounds 7d, 7h, and 7j
have shown better activity against bacterial strains.
Minimum inhibitory concentration, µg/mL
gram positive
bacteria
gram negative
bacteria
Compound
Table 1. Yields and melting points of compounds 7a–7l
Comp.
no.
1
2
Yield,
%
R
R
mp, °C
7
7
a
38
55
36
38
50
38
53
7
7
7
7
7
a
b
c
C
6
C
6
C
6
C
6
C
6
H
H
H
H
H
5
5
5
5
5
4-NO
2
140–142 80
145–146 78
130–132 79
143–144 79
120–122 81
b
58
71
4-OCH
3,4-Cl
3
7
c
70
69
70
7
d
110
68
120
67
100
60
100
65
d
e
4-CH
2-CH
3
7
e
3
,
3
-NO
2
7
f
70
90
85
89
7
7
7
7
7
7
7
f
4-CH
4-CH
4-CH
3
3
3
C
C
C
6
6
6
H
H
H
4
4-NO
2
135–136 80
138–140 81
137–139 76
132–133 82
150–152 80
129–131 75
136–137 76
7
7
g
82
79
80
85
g
h
i
4
4-OCH
3,4-Cl
3
h
120
33
120
28
120
30
120
29
4
7
i
3,4,5-(OCH
3,4,5-(OCH
2-Thienyl
3
)
)
3
C
6
6
H
H
2
2
4-NO
4-CH
4-NO
4-OCH
2
7
j
100
40
92
100
40
100
39
j
3
3
C
3
7
k
32
k
l
2
7l
Ciprofloxacin
60
48
50
52
2-Thienyl
3
100
100
100
100
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

SYNTHESIS AND ANTIBACTERIAL ACTIVITY
833
7
a
7b 7c 7d 7e 7f 7g 7h 7i 7j 7k 7l
Compound
Histogram of antibacterial activity (MIC) of compounds 7a–7l: (1) S. aeureus, (2) P. aeruginosa, (3) E. coli, and (4) K. pneumonia.
chromatography (TLC) on precoated M/s Merck silica
gel 60 F254 (mesh); spots were visualized with UV
light. Silica gel (100–200 mesh) used for column
chromatography was purchased from Merck.
concentrated to get product 4. The crude product was
purified by column chromatography.
Ethyl 2,7-dimethyl-4-oxo-3-(prop-2-yn-1-yl)-5-(p-
tolyl)-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-
carboxylate (4c). Yield 90%, white solid, mp 140–
General procedure for the synthesis of 4H-
pyrans 2a–2d. A mixture of aromatic aldehyde 1
0
1
142 C. H NMR spectrum (400 MHz, CDCl ), δ, ppm:
3
(
(
5 mmol), ethyl acetoacetate (5 mmol), malononitrile
5 mmol) and catalytic quantity of piperidine in
7.22 d (2H, J = 8.1 Hz), 7.06 d (2H, J = 7.8 Hz), 4.98
d.d (2H, J = 16.8, 3.2 Hz), 4.49 s (1H), 4.06 q (2H, J =
7.1 Hz), 2.63 s (3H), 2.49 s (3H), 2.27 s (3H), 2.26 s
ethanol (5 mL) was stirred at room temperature for 20–
0 min. After completion of the reaction (monitored by
1
3
3
(1H), 1.18 t (3H, J = 7.1 Hz). C NMR spectrum
(100 MHz, CDCl ), δ , ppm: 166.2, 160.9, 158.6,
158.4, 158.1, 140.7, 136.4, 128.9, 128.4, 108.6, 101.9,
TLC), the separated product was filtered off, washed
with methanol and dried.
3
C
7
6.5, 73.0, 60.5, 36.6, 33.2, 22.5, 21.1, 18.8, 14.0.
General procedure for the synthesis of pyrano-
[
2,3-d]pyrimidines (3a–3d). A mixture of 4H-pyran 2
General procedure for the synthesis of aldehyde
(
5 mmol), acetic anhydride (5 mL), and concentrated
oximes 6a–6e. A solution of substituted benzaldehyde
5 (1 mmol) in ethanol (15 mL) was added to aqueous
solution of hydroxylamine hydrochloride (2 mmol)
and sodium acetate (4 mmol). The reaction mixture
was stirred at 80°C for 30–40 min. After completion of
the reaction (TLC monitoring), the precipitate was
filtered off, recrystallised from methanol to give the
corresponding aldehyde oxime 6 as a solid.
sulfuric acid (0.5 mmol) was refluxed for 10 min,
cooled to room temperature, and kept for one day. A
precipitate formed was filtered off, washed with water
(
3×5 mL), ethanol (5 mL), and light petroleum (5 mL).
The product obtained was recrystallized from ethanol
and dried at 120°C until the constant weight.
General procedure for the synthesis of N-pro-
pargyl pyrano[2,3-d]pyrimidine-4-ones (4a–4d). To
a solution of compound 3 (0.02 mol) in dry acetone
(
(
General procedure for the synthesis of pro-
pargyl pyrano[2,3-d]pyrimidine-4-one-3-phenyliso-
xazole derivarives 7a–7l. To a stirred solution of
oxime 6 (1 mmol) in CH Cl (15 mL) was added
25 mL) was added anhydrous potassium carbonate
0.04 mol). Then propargyl bromide (0.03 mol) was
2
2
added slowly while stirring. The reaction mixture was
refluxed for 4–5 h. After completion of the reaction
dropwise NaOCl (1.5 mmol) within 5 min, and then
Et N was added dropwise (2 mmol) while stirring in
3
(
TLC monitoring), the solvent was removed at a
15–20 min. Next, a solution of propargylated com-
pound 4 (1 mmol) in chloroform (15 mL) was added,
and the reaction mixture was stirred overnight. After
completion of the reaction (TLC monitoring), the
reduced pressure. The residue was diluted with ice
cold distilled water and extracted with chloroform. The
organic layer was dried over anhydrous Na SO and
2
4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

8
34
KUMAR et al.
solvent was removed at a reduced pressure. The
residue was diluted with distilled water and extracted
with chloroform, the organic layer was dried over
anhydrous Na SO and concentrated to get product 7.
7.35–7.19 m (3H), 7.18–7.13 m (2H), 5.37 s (2H), 4.99
s (1H), 4.07 q (2H, J = 7.1 Hz), 2.84 s (3H), 2.49 s
(3H), 2.36 s (3H), 1.17 t (3H, J = 7.1 Hz). Mass
spectrum (ESI-MS), m/z: 598 [M + 2]. C H N O .
2
4
29 27
3
5
The crude product was purified by column chromato-
graphy.
Ethyl 2,7-dimethyl-3-{[3-(2-methyl-3-nitrophenyl)-
isoxazol-5-yl]methyl}-4-oxo-5-phenyl-3,5-dihydro-4H-
pyrano[2,3-d]pyrimidine-6-carboxylate (7e). Yield
Ethyl 2,7-dimethyl-3-{[3-(4-nitrophenyl)isoxazol-
–
1
8
1
1%, yellow solid. IR spectrum, ν, cm : 3023, 2977,
709, 1672, 1541, 1428, 1244. H NMR spectrum, δ,
5
-yl]methyl}-4-oxo-5-phenyl-3,5-dihydro-4H-pyrano-
1
[
2,3-d]pyrimidine-6-carboxylate (7a). Yield 80%,
–
1
ppm: 8.10–7.97 m (1H), 7.78–7.71 m (2H), 7.56 s
1H), 7.34 d.d (2H, J = 15.8, 6.9 Hz), 7.23 d (2H, J =
yellow solid. IR spectrum, ν, cm : 3088, 2980, 1709,
1
8
1
(
672, 1559, 1428, 1244. H NMR spectrum, δ, ppm:
.25 d (2H, J = 8.7 Hz), 7.86 d (2H, J = 8.5 Hz), 7.53 s
7
4
.6 Hz), 7.13–7.18 m (1H), 5.35 d (2H, J = 10.7 Hz),
.96 s (1H), 4.06 d.d (2H, J = 11.1, 7.1 Hz), 2.87 s
(
1H), 7.46–7.27 m (3H), 7.19–7.02 m (2H), 5.36 d
(
3H), 2.49 s (3H), 2.18 s (3H), 1.15 t (3H, J = 7.1 Hz).
(
2
2H, J = 11.8 Hz), 4.98 s (1H), 4.08 q (2H, J = 6.8 Hz),
.83 s (3H), 2.49 s (3H), 1.17 t (3H, J = 6.9 Hz). C
1
3
13
C NMR spectrum, δ , ppm: 166.1, 161.7, 160.0,
C
1
1
9
58.7, 158.6, 151.1, 143.7, 142.5, 137.8, 130.4, 129.4,
28.5, 128.1, 127.2, 126.8, 126.3, 125.8, 108.3, 101.8,
9.7, 60.5, 39.8, 37.1, 23.3, 18.8, 14.5, 14.0. Mass
NMR spectrum, δ , ppm: 166.0, 161.8, 159.9, 158.6,
C
1
1
1
47.4, 140.8, 135.3, 128.5, 128.1, 126.8, 125.5, 122.4,
20.5, 108.3, 101.8, 99.8, 60.6, 39.8, 37.1, 23.3, 18.8,
4.0. Mass spectrum (ESI-MS), m/z: 529 [M + 1].
spectrum (ESI-MS), m/z: 525 [M + 1]. C H N O .
29 26
4
7
C H N O .
2
8
24
4
7
Ethyl 2,7-dimethyl-3-{[3-(4-nitrophenyl)isoxazol-
5
-yl]methyl}-4-oxo-5-(p-tolyl)-3,5-dihydro-4H-pyrano-
Ethyl 3-{[3-(4-methoxyphenyl)isoxazol-5-yl]methyl}-
,7-dimethyl-4-oxo-5-phenyl-3,5-dihydro-4H-pyrano-
2,3-d]pyrimidine-6-carboxylate (7b). Yield 78%,
[
2,3-d]pyrimidine-6-carboxylate (7f). Yield 80%,
2
[
–
1
yellow solid. IR spectrum, ν, cm : 3111, 2970, 1735,
1677, 1597, 1346, 1034. H NMR spectrum, δ, ppm:
8.41 d (2H, J = 8.9 Hz), 7.91 d (2H, J = 8.9 Hz), 7.52 s
1
–
1
yellow solid. IR spectrum, ν, cm : 3025, 2976, 1712,
1
1
8
676, 1559, 1428, 1242. H NMR spectrum, δ, ppm:
.11 d (2H, J = 8.7 Hz), 7.78 d (2H, J = 8.6 Hz), 7.59 s
(
1H), 7.22 d (2H, J = 7.8 Hz), 7.08 d (2H, J = 7.5 Hz),
5
7
.38 s (2H), 4.95 s (1H), 4.07 d.d (2H, J = 11.1,
(
1H), 7.34 d (2H, J = 7.2 Hz), 7.28 d (2H, J = 9.1 Hz),
.18 t (1H, J = 7.3 Hz), 5.35 s (2H), 4.99 s (1H), 4.07 q
2H, J = 7.1 Hz), 3.76 s (3H), 2.84 s (3H), 2.49 s (3H),
.0 Hz), 2.83 s (3H), 2.47 s (3H), 2.28 s (3H), 1.19 t
7
1
3
(
3H, J = 7.0 Hz). C NMR spectrum, δ , ppm: 166.0,
C
(
1
1
1
61.8, 159.9, 158.6, 147.4, 146.9, 143.7, 140.8, 136.1,
30.0, 129.6, 128.2, 127.0, 123.9, 121.9, 108.3, 101.8,
00.0, 60.6, 39.8, 37.1, 23.1, 28.8, 18.1, 14.0. Mass
1
5
.17 t (3H, J = 7.1 Hz). Mass spectrum (ESI-MS), m/z:
14 [M + 1]. C H N O .
2
9
27
3
6
spectrum (ESI-MS), m/z: 543 [M + 1]. C H N O .
Ethyl 3-{[3-(3,4-dichlorophenyl)isoxazol-5-yl]-
29 26
4
7
methyl}-2,7-dimethyl-4-oxo-5-phenyl-3,5-dihydro-4H-
pyrano[2,3-d]pyrimidine-6-carboxylate (7c). Yield
Ethyl 3-{[3-(4-methoxyphenyl)isoxazol-5-yl]
methyl}-2,7-dimethyl-4-oxo-5-(p-tolyl)-3,5-dihydro-
–
1
7
1
9%, yellow solid. IR spectrum, ν, cm : 3085, 2930,
710, 1672, 1559, 1429, 1245. H NMR spectrum, δ,
4
H-pyrano[2,3-d]pyrimidine-6-carboxylate (7g).
1
–1
Yield 81%, yellow solid. IR spectrum, ν, cm : 2977,
ppm: 8.00 d.d (1H, J = 9.1, 7.0 Hz), 7.81–7.76 m (2H),
1
2
927, 1710, 1674, 1558, 1428, 1241. H NMR spect-
rum, δ, ppm: 8.12 d (2H, J = 8.9 Hz), 7.81 d (2H, J =
.9 Hz), 7.50 s (1H), 7.24 d (2H, J = 8.6 Hz), 7.08 d
2H, J = 7.5 Hz), 5.38 s (2H), 4.95 s (1H), 4.07 q (2H,
7
8
4
.51 s (1H), 7.34 d (2H, J = 7.2 Hz), 7.29 d (2H J =
.5 Hz), 7.19–7.12 m (1H), 5.37 d (2H, J = 11.9 Hz),
.99 s (1H), 4.07 q (2H, J = 7.1 Hz), 2.83 s (3H), 2.49
8
(
s (3H), 1.17 t (3H, J = 7.1 Hz). Mass spectrum (ESI-
MS), m/z: 551 [M + 1]. C H Cl N O .
J = 6.8 Hz), 3.76 s (3H), 2.83 s (3H), 2.47 s (3H), 2.28
s (3H), 1.19 t (3H, J = 7.0 Hz). Mass spectrum (ESI-
MS), m/z: 528 [M + 1]. C H N O .
2
8
23
2
3
5
3
0
29
3
6
Ethyl 2,7-dimethyl-4-oxo-5-phenyl-3-{[3-(p-tolyl)-
isoxazol-5-yl]methyl}-3,5-dihydro-4H-pyrano[2,3-d]-
pyrimidine-6-carboxylate (7d). Yield 79%, yellow
Ethyl 3-{[3-(3,4-dichlorophenyl)isoxazol-5-yl]-
methyl}-2,7-dimethyl-4-oxo-5-(p-tolyl)-3,5-dihydro-
4H-pyrano[2,3-d]pyrimidine-6-carboxylate (7h).
–
1
solid. IR spectrum, ν, cm : 3072, 2929, 1705, 1670,
1
–1
1
557, 1423, 1238. H NMR spectrum, δ, ppm: 8.11 d
Yield 76%, yellow solid. IR spectrum, ν, cm : 3050,
1
(
2H, J = 8.7 Hz), 7.78 d (2H, J = 8.6 Hz), 7.49 s (1H),
2977, 1710, 1674, 1559, 1428, 1241. H NMR spec-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

SYNTHESIS AND ANTIBACTERIAL ACTIVITY
835
1
trum, δ, ppm: 7.84 d (1H, J = 2.0 Hz), 7.60 t (1H, J =
.6 Hz), 7.52 s (1H), 7.41 d (1H, J = 8.8 Hz), 7.22 d
2H, J = 7.9 Hz), 7.07 d (2H, J = 7.7 Hz), 5.37 s (2H),
.95 s (1H), 4.07 d.d (2H, J = 12.2, 7.1 Hz), 2.82 s
3H), 2.47 s (3H), 2.28 s (3H), 1.19 t (3H, J = 7.1 Hz).
2927, 1713, 1665, 1555, 1433, 1216. H NMR spec-
trum, δ, ppm: 7.91 d (2H, J = 8.9 Hz), 7.65 d (2H, J =
8.8 Hz), 7.51 s (1H), 7.15 d (1H, J = 4.8 Hz), 6.95 d
(1H, J = 4.8 Hz), 6.90–6.83 m (1H), 5.41 s (2H), 5.35 s
(1H), 4.15 q (2H, J = 7.1 Hz), 3.79 s (3H), 2.86 s (3H),
2.48 s (3H), 1.23 t (3H, J = 7.1 Hz). Mass spectrum
(ESI-MS), m/z: 520 [M + 1]. C H N O S.
8
(
4
(
Mass spectrum (ESI-MS), m/z: 566 [M + 1].
C H Cl N O .
2
9
25
2
3
5
27 25
3
6
Ethyl 2,7-dimethyl-3-{[3-(4-nitrophenyl)isoxazol-
-yl]methyl}-4-oxo-5-(3,4,5-trimethoxyphenyl)-3,5-
dihydro-4H-pyrano[2,3-d]pyrimidine-6-carboxylate
ACKNOWLEDGMENTS
5
We express our thanks to DST-FIST Program of
India (SR/FST/CSI-213/2010) for infra structural
facilities and the Director, CFRD, Osmania University,
Hyderabad for providing spectral analysis. One of the
authors, B. S. Kumar, is grateful to UGC-New Delhi
for Research Fellowship.
–
1
(
3
7i). Yield 82%, yellow solid. IR spectrum, ν, cm :
095, 2971, 1716, 1672, 1559, 1425, 1233. H NMR
1
spectrum, δ, ppm: 8.38 d (2H, J = 9.1 Hz), 7.89 d (2H,
J = 9.1 Hz), 7.50 s (1H), 6.55 s (2H), 5.29 s (2H), 4.96
s (1H), 4.13 q (2H, J = 7.1 Hz), 3.81 s (6H), 3.79 s
(
3H), 2.84 s (3H), 2.49 s (3H), 1.22 t (3H, J = 7.1 Hz).
1
3
C NMR spectrum, δ , ppm: 166.1, 161.9, 158.8,
C
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3
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9
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 4 2017

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