Efficient synthesis of a novel series of indeno-fused pyrido[2,3-d]pyrimidines using a deep eutectic solvent system comprised of choline chloride/urea

Article abstract of DOI:10.3184/175815517X14981249895596

A series of 13 aryl indeno[2',1':5,6]pyrido[2,3-d]pyrimidine-2,4,6-(3H,5H,11H)-triones, eight of which are new, were synthesised regioselectively in high yields by a three-component reaction of 1,3-indanedione, an araldehyde and 6-aminopyrimidin-2,4(1H,3H

Full text of DOI:10.3184/175815517X14981249895596

430 RESEARCH PAPER
VOL. 41 JULY, 430–433
JOURNAL OF CHEMICAL RESEARCH 2017
Efficient synthesis of a novel series of indeno-fused pyrido[2,3-d]pyrimidines
using a deep eutectic solvent system comprised of choline chloride/urea
Mohammad Hakimi Roknabadi, Mohammad Hossein Mosslemin* and Razieh Mohebat
Department of Chemistry, Yazd Branch, Islamic Azad University, PO Box 89195-155, Yazd, Iran
A series of 13 aryl indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6-(3H,5H,11H)-triones, eight of which are new, were synthesised
regioselectively in high yields by a three-component reaction of 1,3-indanedione, an araldehyde and 6-aminopyrimidin-2,4(1H,3H)-dione
in the presence of a deep eutectic solvent comprised of choline chloride/urea (1:2) as the catalyst. The reaction conditions were mild and
did not require additional catalysts. Given the inexpensive, nontoxic and recyclable nature of the deep eutectic solvent, these reaction
conditions are simple to carry out and environmentally friendly.
Keywords: three-component reaction, aromatic aldehydes, 1,3-indanedione, 6-aminopyrimidin-2,4(1H,3H)-dione, deep eutectic solvent
Deep eutectic solvents (DESs) are attractive alternatives to
room temperature ionic liquids, as they are less expensive, more
synthetically accessible, nontoxic and biodegradable. In general,
DESs are formed by complexation of the halide salt of a quaternary
ammonium or phosphonium cation with a hydrogen bond donor,
cases, the catalysts used are harmful to the environment and cannot
be reused. Therefore, an efficient method for the preparation of
pyrido[2,3-d]pyrimidine derivatives is still desirable.
In continuation of our ongoing programme for the synthesis
of heterocyclic compounds,32–36 here we report an efficient one-
pot regioselective synthesis of indeno[2′,1′:5,6]pyrido[2,3-d]
pyrimidine-2,4,6(3H,5H,11H)-trione derivatives 4.
for example, urea, a sugar, a carboxylic acid or ethylene glycol.1–3
A
characteristic property of DESs is that they exhibit a lower melting
point compared with the halide salt of a quaternary ammonium and
a hydrogen bond donor because the strong interactions prevent the
parent components from crystallising.4 Therefore, many chemical
processes, such as extraction,5 materials synthesis, biomass
processing and applications in metal electrodeposition,6 have
recently employed DESs in organic synthesis.7
In multicomponent approaches, complex products and
biologically active molecules are synthesised from readily available
starting materials in a single step process. From this point of view,
multicomponent reactions (MCRs) have emerged as green and
powerful tools in organic synthesis and drug discovery.8,9 Also,
in MCRs, by selecting different starting materials, new classes
of compounds can be synthesised that may show interesting
properties.10
Results and discussion
Our proposed route to the pentacyclic target compounds 4
involved a base-catalysed condensation b′etween 1,3-indanedione
1, an araldehyde 2 and 6-aminopyrimidin-2,4(1H,3H)-dione
3, a three-component reaction we hoped would occur in one pot
(Scheme 1). Initially, the yields of a model three-component reaction
using 4-nitrobenzaldehyde (2; Ar = 4-NO2–C6H4) in reaction with
1,3-indanedione 1 and 6-aminopyrimidin-2,4(1H,3H)-dione 3
catalysed by various base/solvent combinations at 80 °C were
determined and the results are shown in Table 1.
Table 1 Yields of aryl tetracyclic product (4a; Ar = 4-NO2-C6H4) prepared
from the reaction of 4-nitrobenzaldehyde (2; Ar = 4-NO -C6H4) with
1,3-indanedione 1 and 6-aminopyrimidin-2,4(1H,3H)-dion2e 3 in the
presence of a base catalyst (Scheme 1)a
Pyridopyrimidines
are
nitrogen-bearing
heterocyclic
compounds that have various pharmaceutical applications. In
particular, pyrido[2,3-d]pyrimidine derivatives show a wide
variety of biological activities, such as anticancer agents inhibiting
dihydrofolate reductases or tyrosine kinases,11–13 and antitumour,14,15
Entry Conditions
Time (min)
Yield (%)
95
62
59
36
53
70
29
1
2
3
4
5
6
7
ChCl (1 mmol)–urea (2 mmol)
15
70
80
65
55
90
60
Et3N (50 mol%)–EtOH (5 mL)
piperine (50 mol%)–EtOH (5 mL)
l-proline (50 mol%)–EtOH (5 mL)
DBU (50 mol%)–EtOH (5 mL)
DABCO (50 mol%)–EtOH (5 mL)
(EtOH)3N (50 mol%)–EtOH (5 mL)
18
antiviral,16 antihistaminic,17 anti-inflammatory and antibacterial
agents,19–22 as well as acting as cyclin-dependent kinase 4
inhibitors.23 This structural moiety is present in ramastine (anti-
allergic)24 and pirenperone (tranquiliser).25 As a result, this class has
attracted considerable interest and several MCR methods have been
reported for their synthesis.26–31 Although most of these methods
offer distinct advantages, some of them still have limitations in
terms of yields, longer reaction times and difficult work-up. In some
aReaction conditions: an araldehyde 2 (1 mmol) was reacted with 1,3-indanedione
1 and 6-aminopyrimidin-2,4(1H,3H)-dione 3 in the presence of various base/solvent
combinations as a catalyst at 80 °C.
O
NH
-
OH
N+
Cl
O
Ar
O
O
O
H2N
N
H
O
3
NH
H2N
NH2
2
+
o C
O
80
N
H
N
H
O
O
1
Ar
H
4
2
Scheme 1
* Correspondent. E-mail: mhmosslemin@iauyazd.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2017 431
When the reaction was carried out in the presence of a DES
comprised of choline chloride/urea (1:2), the product was the
desired pentacyclic compound (4b; Ar = 4-NO2–C6H4) and
the reaction had occurred in excellent yield (95%) (Table 1,
entry 1). None of the other catalysts (Table 1, entries 2–7) gave
equivalent yields, the best giving only 70% (Table 1, entry 6).
It was thus clear that our one-pot method had worked very well
and the DES catalyst was thus adopted as the optimum catalyst.
Using the optimum conditions, 12 other aldehydes 2 were
reacted with 1,3-indanedione
1 and 6-aminopyrimidin-
2,4(1H,3H)-dione to afford the corresponding aryl
3
Table 2 Yields of aryl tetracyclic products 4a–m prepared from the
reaction of 1,3-indanedione 1 and 6-aminopyrimidin-2,4(1H,3H)-dione
3 with various araldehydes 2 in the presence of a deep eutectic solvent
comprising choline chloride/urea (1:2) as a catalyst (Scheme 1)a
indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H,5H,11H)-
trione derivatives (4a,c–m) and the results are shown in Table
2. As can be seen, very good yields of products were obtained
for aldehydes bearing either electron-withdrawing or electron
donating groups.
Time Yield
Entry Ar group
Product
M.p. (°C)
(min) (%)b
1
1
2
3
4
5
6
7
8
4-OCH3 C6H4
4-NO2 C6H4
4-Br C6H4
2,4-Cl C6H3
3-NO2 C6H4
3-Cl-4-NO2 C6H3
4-F C6H4
2-OH-3-OCH3 C6H3 4h
4-OH C6H4
2-Br C6H4
4-CN C6H4
4a
4b
4c
4d
4e
4f
40
25
30
30
35
28
37
55
45
40
35
42
50
89 323–325 (lit.37 324–326)
95 325–327 (lit.37 328–330)
92 328–330 (lit.37 327–329)
92 320–322
The structures of products were deduced from their IR, H
NMR, 13C NMR and mass spectra, and CHN analysis data.
For example, the IR spectrum of 4a showed absorptions at
3173–3485 cm−1 for NH groups and 1708 and 1672 cm−1 for
carbonyl groups, indicating the presence of these functional
groups in the proposed structure. The 1H NMR spectrum of 4a
exhibited a singlet for the OCH3 group at δ = 3.84 ppm and a
singlet at δ = 4.85 for the methine group in dihydropyridine.
Two doublets at δ = 6.92 and 6.95 (3JHH = 12 Hz) and multiplet
signals at 7.61–7.88 ppm are due to the aromatic hydrogens.
Finally, three singlet signals at δ = 10.27–11.25 ppm are NH
91 318–320 (lit.37 320–322)
90 333–335
4g
88 327–329 (lit.37 325–327)
87 319–321
85 320–322
89 315–317
91 326–328
9
4i
4j
4k
4l
4m
10
11
12
13
1
groups. The H decoupled 13C NMR spectrum of 4a showed
2-OH-5-NO2 C6H3
2-OH-5-Br C6H3
89 331–333
90 314–316
19 resonances. Elemental analysis confirmed the molecular
structures. Compounds 4a–m gave M+ ions, as expected.
The reusability of the catalyst was studied through a selected
model reaction of 1,3-indanedione, 4-nitrobenzaldehyde and
6-aminopyrimidin-2,4(1H,3H)-dione. The reaction mixture,
including DES and products, was dissolved in water and the
aReaction conditions: a mixture of 1,3-indanedione 1 (0.25 mmol), an araldehyde 2
(0.25 mmol) and 6-aminopyrimidin-2,4(1H,3H)-dione 3 was stirred in a deep eutectic
solvent for the appropriate time.
bIsolated yield.
-
Cl
N+
O
O
2
O
NH2
H2N
OH
O
-
OH
N+
Cl
H2N
+
2
NH2
+
Ar
H
HN
NH
H
H
-
O
Cl
N+
OH
Ar
H
O
(a)
O
NH2
H2N
O
(b)
OH
O
O
HN
NH
_
H
H2O
H
Ar
Ar
(c) O
O
O
Ar
O
O
Ar
NH
O
O
H2N
N
H
O
3
_
NH
NH
O
O
2HN
+
O
N
2HN
N
O
H
H
(d)
Ar
O
H
O
_
H2O
NH
4
N
N
H
O
H
HO
(e)
Scheme 2

432 JOURNAL OF CHEMICAL RESEARCH 2017
129.5, 129.6, 130.8, 131.0, 132.7, 132.8, 136.1, 145.6, 146.4, 150.2, 153.0
(aromatic and olefinic carbons), 154.4, 163.3, 191.0 (3C=O); MS m/z
(%): 388 (38). Anal. calcd for C20H12N4O5: C, 61.86; H, 3.11; N, 14.43;
found: C, 61.83; H, 3.09; N, 14.41%.
crude product obtained by extraction with EtOAc. The DES
was recovered from the aqueous phase by evaporation at 80 °C
under vacuum and was recycled for the next reaction. It was
recycled four consecutive times with almost unaltered catalytic
activity (the yield decreased from 92% to 87% after four runs).
We propose the following mechanism for the reaction
(Scheme 2). The DES may play a dual role in this reaction as
a solvent and catalyst, which in the latter case is by activation
of the carbonyl group via hydrogen bonding. The aldehyde,
which is activated by the DES and the activated carbonyl (a),
undergoes a Knoevenagel condensation with 1,3-indandione
(b) to afford intermediate (c). Then, 6-aminopyrimidin-
2,4(1H,3H)-dione 3 attacks the intermediate (c) and affords
intermediate (d) via Michael addition. The intermediate (d)
undergoes intramolecular cyclisation with participation of the
amino function and one of the 1,3-indandione carbonyl group to
form (e). Then the elimination of water from (e) forms the aryl
indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H,5H,11H)-
trione derivatives (4a–m) as the target molecules.
5- (4-Bromophenyl) -5,11-dihydro-1H-indeno [2 ′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4c): Red powder; m.p.
328–330 °C; yield 92%; IR (KBr) (νmax cm−1): 3420, 3215, 3135 (NH),
1698, 1668, 1657 (C=O); 1H NMR: δ 4.67 (1H, s, CH), 7.24, 7.44 (2H,
2d, 3JHH = 12 Hz, aromatic), 7.28–7.66 (4H, m, aromatic), 10.27–10.97
(3H, s, 3NH); 13C NMR: δ 33.8 (CH), 91.0, 109.4, 119.6, 121.3, 130.4,
130.9, 131.0, 131.3, 132.6, 132.9, 133.4, 135.9, 136.4, 145.0, 145.2, 150.2
(aromatic and olefinic carbons), 154.0, 163.3, 191.2 (3C=O); MS m/z
(%): 388 (38). Anal. calcd for C20H12N3O3Br: C, 56.89; H, 2.86; N, 9.95;
found: C, 56.80; H, 2.59; N, 10.03%.
5- (2,4-Dichlorophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4d): Red powder;
m.p. 320–322 °C; yield 92%; IR (KBr) (νmax cm−1): 3450, 3165, 3150
1
(NH), 1703, 1687, 1627 (C=O); H NMR: δ 5.08 (1H, s, CH), 7.34
(1H, s, aromatic), 7.48 (1H, dd, JHH = 8.4, 2.0 HZ, aromatic), 7.64 (1H,
s, aromatic), 7.66 (1H, s, aromatic), 7.70 (1H, d, J = 2.0 Hz, 1H), 7.79
(1H, dt, J = 8.2, 2.0 Hz, aromatic), 7.87 (1H, s, aromatic), 7.96 (1H,
s, aromatic), 10.38–10.92 (3H, s, 3NH); 13C NMR: δ 29.2 (CH), 90.7,
107.2, 119.6, 124.1, 128.6, 128.8, 130.8, 131.0, 132.1, 132.6, 132.9,
133.4, 136.4, 141.9, 142.1, 150.2 (aromatic and olefinic carbons),
154.4, 163.0, 190.9 (3C=O); MS m/z (%): 411 (33). Anal. calcd for
C20H11N3O3Cl2: C, 58.27; H, 2.69; N, 10.19; found: C, 58.23; H, 2.65;
N, 10.16%.
In this study, we have developed a rapid, efficient and versatile
procedure for the synthesis of indeno-fused pyrido[2,3-d]
pyrimidine derivatives 4a–m in a regiochemical manner by
using an eco-friendly and biodegradable deep eutectic solvent
based on a choline chloride/urea mixture. The advantages of
this method are operational simplicity, green medium, DES
recoverability, short reaction times and high yields.
5-(3-Nitrophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]pyrido[2,3-d]
pyrimidine-2,4,6(3H)-trione (4e): Red powder; m.p. 318–320 °C;
yield 91%; IR (KBr) (νmax cm−1): 3510, 3330, 3180 (NH), 1711, 1655,
Experimental
All melting points were determined with an Electrothermal 9100
apparatus. Elemental analyses were performed using a Costech ECS
4010 CHNS-O analyser at the analytical laboratory of Islamic Azad
University, Yazd branch. Mass spectra were recorded on a Finnigan-
Mat 8430 mass spectrometer operating at an ionisation potential of
70 eV. IR spectra were recorded on a Shimadzu IR-470 spectrometer.
1
1617 (C=O), 1519, 1339 (NO2); H NMR: δ 4.86 (1H, s, CH), 7.29
(1H, d, J = 7.2 Hz, aromatic), 7.38 (1H, dt, J = 7.2, 1.6 Hz, aromatic),
7.49 (1H, s, aromatic), 7.56 (1H, t, J = 8.0 Hz, aromatic), 7.78 (1H, t,
J = 8.0 Hz, aromatic), 8.04 (1H, dd, J = 8.0, 1.2 Hz, aromatic), 8.09 (1H,
s, aromatic), 10.35–11.01 (3H, s, 3NH); 13C NMR: δ 34.3 (CH), 90.6,
108.7, 119.8, 121.0, 121.8, 122.6, 130.0, 131.1, 132.7, 132.8, 133.5, 135.1,
136.4, 145.5, 147.6, 150.2 (aromatic and olefinic carbons), 154.4, 163.3,
191.2 (3C=O); MS m/z (%): 388 (35). Anal. calcd for C20H12N4O5: C,
61.86; H, 3.11; N, 14.43; found: C, 61.77; H, 3.08; N, 14.52%.
NMR spectra were obtained on
a Bruker DRX-400 Avance
spectrometer (1H NMR at 400 Hz, 13C NMR at 100 Hz) in DMSO-d6
using TMS as an internal standard. Chemical shifts (δ) are given in
ppm and coupling constants (J) are given in Hz. The chemicals used in
this work were purchased from Fluka (Buchs, Switzerland) and were
used without further purification.
5-(4-Chloro-3-nitrophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4f): Red powder; m.p.
333–335 °C; yield 90%; IR (KBr) (νmax cm−1): 3445, 3215, 3165 (NH),
1
Synthesis of indeno fused pyrido[2,3-d]pyrimidine derivatives
(4a–m); general procedure
1706, 1684, 1663 (C=O), 1526, 1337 (NO2); H NMR: δ 4.83 (1H, s,
CH), 7.30–7.95 (7H, aromatic), 10.44–11.01 (3H, s, 3NH); 13C NMR:
δ 30.5 (CH), 90.1, 108.2, 119.9, 124.9, 127.6, 131.1, 131.4, 132.7, 132.9,
133.7, 136.0, 136.5, 142.1, 146.5, 147.9, 150.2 (aromatic and olefinic
carbons), 154.5, 163.3, 191.2 (3C=O); MS m/z (%): 422 (30). Anal.
calcd for C20H11N4O5Cl: C, 56.82; H, 2.62; N, 13.25; found: C, 56.70;
H, 2.55; N, 13.3%.
1,3-indanedione 1 (0.25 mmol), an aromatic aldehyde 2 (0.25 mmol)
and 6-aminopyrimidin-2,4(1H,3H)-dione 3 (0.25 mmol) were added to
a DES (choline chloride/urea, 1 mmol:2 mmol). The resulting mixture
was stirred for the specified time (Table 2) at 80 °C. After reaction
completion, (TLC, ethyl acetate/n-hexane, 2:1), the reaction mixture
was washed with water (10 mL) and the solid residue recrystallised
from ethanol to obtain the pure product.
5- (4-Fluorophenyl) -5,11-dihydro-1H-indeno [2 ′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4g): Red powder;
m.p. 327–329 °C; yield 88%; IR (KBr) (νmax
cm−1): 3440, 3220, 3125
5- (4-Methoxyphenyl) -5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4a): Red powder; m.p.
323–325 °C; yield 89%; IR (KBr) (νmax cm−1): 3485, 3370, 3173 (3NH),
(NH), 1697, 1673, 1659 (C=O); 1H NMR: 4.70 (1H, s, CH), 7.07 (2H,
t, J = 8.4Hz, aromatic), 7.22 (1H, d, J = 8.8 Hz, aromatic), 7.36 (1H,
t, J = 8.4 Hz, aromatic), 7.44 (2H, d, J = 8.0 Hz, aromatic), 7.65 (1H,
d, J = 7.2 Hz, aromatic), 10.23–10.96 (3H, s, 3NH); 13C NMR: 33.4
(CH), 91.3, 109.8, 115.2 (JCF = 21 Hz, Cortho), 119.6, 129.9, 129.9, 130.5
(JCF = 9 Hz, Cmeta), 130.9, 132.6, 133.4, 136.2, 140.6 (JCF = 2 Hz, Cortho),
145.1, 150.2, 157.9 (JCF = 246 Hz, Cipso) (aromatic and olefinic carbons),
153.9, 163.3, 191.3 (3C=O); MS m/z (%): 361 (41). Anal. calcd for
C20H12N3O3F: C, 66.48; H, 3.35; N, 11.63; found: C, 66.41; H, 3.29; N,
11.59%.
1
1708, 1680, 1672 (3C=O); H NMR: δ 3.84 (3H, s, OCH3), 4.85 (1H,
3
s, CH), 6.92, 6.95 (4H, 2d, JHH = 12 Hz, aromatic), 7.61–7.88 (4H,
m, aromatic), 10.27–11.25 (3H, s, 3NH); 13C NMR: δ 28.9 (CH), 55.2
(OCH3), 91.9, 110.6, 115.1, 115.6, 121.2, 128.9, 129.8, 130.7, 132.5,
133.1, 133.3, 136.2, 136.3, 144.7, 150.3, 153.5 (aromatic and olefinic
carbons), 156.1, 163.3, 191.4 (3C=O); MS m/z (%): 373 (34). Anal.
calcd for C21H15N3O4: C, 67.56; H, 4.05; N, 11.25; found: C, 67.44; H,
3.99; N, 11.36%.
5-(4-Nitrophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]pyrido[2,3-d]
pyrimidine-2,4,6(3H)-trione (4b): Red powder; m.p. 325–327 °C;
yield 95%; IR (KBr) (νmax cm−1): 3465, 3220, 3130 (NH), 1700, 1663,
5-(2-Hydroxy-3-methoxyphenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4h): Red powder; m.p.
319–321 °C; yield 87%; IR (KBr) (νmax cm−1): 3485, 3275, 3185 (NH),
3215 (OH), 1704, 1674, 1657 (C=O); 1H NMR: δ 4.88 (1H, s, CH), 6.65
(2H, d, J = 7.6Hz, aromatic), 6.73 (1H, t, J = 8.8 Hz, aromatic), 7.27
(1H, d, J = 8.8 Hz, aromatic), 7.37 (1H, dt, J = 7.2, 1.2 Hz, aromatic),
1
1539, 1336 (NO2); H NMR: δ 4.84 (1H, s, CH), 7.30–7.52 (4H, m,
3
aromatic) 7.58, 8.12 (4H, 2d, JHH = 12 Hz, aromatic), 10.42–11.01
(3H, 3s, 3NH); 13C NMR: δ 34.5 (CH), 90.5, 108.6, 119.8, 122.8, 123.7,

JOURNAL OF CHEMICAL RESEARCH 2017 433
7.49 (3H, m, aromatic), 8.78 (1H, br, OH), 10.24–11.04 (3H, s, 3NH);
13C NMR: δ 28.9 (CH), 91.4, 109.6, 110.4, 119.3, 119.3, 121.2, 121.8,
130.7, 132.4, 132.5, 133.1,136.4, 144.3, 145.5, 148.7, 150.0 (aromatic
and olefinic carbons), 154.6, 164.4, 191.2 (C=O); MS m/z (%): 389
(44). Anal. calcd for C21H15N3O5: C, 64.78; H, 3.88; N, 10.79; found: C,
64.89; H, 3.79; N, 10.68%.
Received 22 May 2017; accepted 7 June 2017
Paper 1704787
https://doi.org/10.3184/175815517X14981249895596
Published online: 2 July 2017
References
5- (4-Hydroxyphenyl) -5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4i): Red powder; m.p.
320–322 °C; yield 85%; IR (KBr) (νmax cm−1): 3470, 3281, 3150 (NH),
3211 (OH), 1707, 1682, 1645 (C=O); 1H NMR: δ 4.57 (1H, s, CH), 6.62
(2H, d, J = 12 Hz, aromatic), 7.11 (2H, d, J = 12 Hz, aromatic), 7.28
(2H, d, J = 6.8 Hz, aromatic), 7.37 (1H, dt, J = 8.8, 0.8 Hz, aromatic),
7.40 (1H, d, J = 6.8 Hz, aromatic), 7.47 (1H, dt, J = 8.8, 0.8 Hz,
aromatic), 9.19 (1H, s, OH), 10.12–10.91 (3H, s, 3NH); 13C NMR: δ
32.9 (CH), 91.9, 110.6, 115.1, 115.6, 121.2, 129.0, 129.9, 130.7, 132.6,
133.0, 133.2, 136.3, 136.4, 144.7, 150.3, 153.5 (aromatic and olefinic
carbons), 156.2, 163.3, 191.4 (C=O); MS m/z (%): 359 (43). Anal.
calcd for C20H13N3O4: C, 66.85; H, 3.65; N, 11.69; found: C, 66.71; H,
3.59; N, 11.73%.
5- (2-Bromophenyl) -5,11-dihydro-1H-indeno [2 ′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4j): Red powder; m.p.
315–317 °C; yield 89%; IR (KBr) (νmax cm−1): 3441, 3215, 3185 (NH),
1708, 1680, 1659 (C=O); 1H NMR: δ 5.10 (1H, s, CH), 7.07–7.54 (8H,
m, aromatic), 10.24–10.88 (3H, s, 3NH); 13C NMR: δ 35.0 (CH), 91.4,
107.2, 119.5, 124.1, 127.4, 128.0, 129.9, 130.9, 131.8, 132.6, 132.8,
133.6, 136.4, 140.7, 145.4, 150.2 (aromatic and olefinic carbons),
161.2, 163.0, 190.9 (3C=O); MS m/z (%): 421 (41). Anal. calcd for
C20H12N3O3Br: C, 56.89; H, 2.86; N, 9.95; found: C, 56.77; H, 2.82; N,
10.02%.
1
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5- (4- Cyanophenyl) -5,11-dihydro-1H-indeno [2 ′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4k): Red powder; m.p.
326–328 °C; yield 91%; IR (KBr) (νmax cm−1): 3473, 3232, 3151 (NH),
1
2224 (CN), 1703, 1679, 1650 (C=O); H NMR: δ 4.78 (1H, s, CH),
7.23–7.71 (4H, m, aromatic), 7.72, 7.87 (4H, 2dm, J = 12 Hz, aromatic),
10.38–10.99 (3H, s, 3NH); 13C NMR: δ 34.6 (CH), 90.5, 107.0, 109.4,
119.5, 119.7 (CN), 129.3, 130.6, 131.0, 131.5, 132.5, 132.7, 132.9, 133.5,
136.4, 145.5, 149.6, 150.2 (aromatic and olefinic carbons), 154.4, 163.3,
191.1 (3C=O); MS m/z (%): 368 (37). Anal. calcd for C21H12N4O3: C,
68.48; H, 3.28; N, 15.21; found: C, 68.37; H, 3.22; N, 15.30%.
5-(2-Hydroxy-5-nitrophenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4l): Red powder; m.p.
331–333 °C; yield 89%; IR (KBr) (νmax cm−1): 3480, 3270, 3110 (NH),
1
2216 (OH), 1708, 1662, 1621 (C=O), 1540, 1340 (NO2); H NMR: δ
4.60 (1H, s, CH), 7.62–8.33 (7H, m, aromatic), 10.93 (1H, s, OH),
11.45–12.36 (3H, s, 3NH); 13C NMR: δ 19.0 (CH), 96.6, 107.2, 121.0,
122.1, 123.2, 124.0, 124.5, 129.2, 129.8, 130.6, 133.5, 136.4, 140.5,
147.3, 150.2, 161.8 (aromatic and olefinic carbons), 157.9, 168.7, 188.7
(C=O); MS m/z (%): 404 (33). Anal. calcd for C20H12N4O6: C, 59.41; H,
2.99; N, 13.86; found C, 59.31; H, 3.07; N, 13.74%.
5-(5-Bromo-2-hydroxyphenyl)-5,11-dihydro-1H-indeno[2′,1′:5,6]
pyrido[2,3-d]pyrimidine-2,4,6(3H)-trione (4m); Red powder; m.p.
314–316 °C; yield 90%; IR (KBr) (νmax cm−1): 3475, 3290, 3117 (NH),
32 M. Anary-Abbasinejad, N. Shams and M. Heidari, ARKIVOC., 2012, ix,
13.
1
3214 (OH), 1699, 1674, 1644 (C=O); H NMR: δ 4.85 (1H, s, CH),
6.69 (1H, d, J = 8.4 Hz, aromatic), 7.03 (1H, m, aromatic), 7.11 (1H, dd,
J = 8.4, 2.8 Hz, aromatic), 7.25 (1H, d, J = 6.8 Hz, aromatic), 7.37 (1H,
dt, J = 8.8, 0.8 Hz, aromatic), 7.43 (1H, dt, J = 8.8, 0.8 Hz, aromatic),
7.64 (1H, m, aromatic), 9.26 (1H, s, OH), 10.62–11.12 (3H, s, 3NH);
13C NMR: δ 29.1 (CH), 90.4, 107.8, 111.3, 117.3, 119.3, 122.0, 124.6,
130.0, 130.4, 131.9, 133.4, 135.9, 136.4, 140.7, 150.2, 157.7 (aromatic
and olefinic carbons), 154.7, 161.3,188.6 (3C=O); MS m/z (%): 437
(35). Anal. calcd for C20H12N3O4Br: C, 54.82; H, 2.76; N, 9.59; found:
C, 54.72; H, 2.67; N, 9.63%.
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