Synthesis of novel 15-aryl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5] pyrimido[6,1-b]quinazoline-1,9-diones

Article abstract of DOI:10.3184/174751916X14527702465295

A new series of 15-aryl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]pyrimido[6,1-b]quinazoline-1,9-diones was synthesised by the cyclisation of methyl anthranilate with ethyl N-(3-cyano-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromen-2-yl)formimidate derivatives, wh

Full text of DOI:10.3184/174751916X14527702465295

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 FEBRUARY, 87–91
RESEARCH PAPER 87
Synthesis of novel 15-aryl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
pyrimido[6,1-b]quinazoline-1,9-diones
a
a
b
a
a,b
Xiu-Xiu Kong , Yong-Nan Cao , Zheng Xing , Li-Zhuang Chen and Guang-Fan Han *
a
School of Environmental & Chemical Engineering, Jiangsu University of Science & Technology, Zhenjiang, Jiangsu 212003, P.R. China
Zhenjiang College, Zhenjiang, Jiangsu 212003, P.R. China
b
A new series of 15-aryl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]pyrimido[6,1-b]quinazoline-1,9-diones was synthesised by the cyclisation
of methyl anthranilate with ethyl N-(3-cyano-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromen-2-yl)formimidate derivatives, which were
obtained by the reactions of 2-amino-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile derivatives and triethyl orthoformate.
The structure of the 2,4-dichlorophenyl derivative was further determined by single crystal X-ray diffraction analysis.
Keywords: cyclisation, substituted quinazolinone, single crystal structure
Over the past decades, the synthesis of nitrogen-containing
heterocycles has become the cornerstone of synthetic organic
chemistry, as a result of a wide variety of applications of these
Results and discussion
Scheme 1 shows the synthesis route of the title compounds.
Compounds
2
were synthesised by the reaction of
1–4
heterocycles in medicinal and pharmaceutical chemistry.
The exploration of heterocycles as privileged structures in drug
triethyl orthoformate with 2‑amino-5-oxo-4-aryl-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile
which were prepared by the reaction of 5-substituted-1,3-
cyclohexanedione with 2‑arylylidenemalononitrile derivatives.
17
derivatives
1,
5,6
discovery is one of the major areas in medicinal chemistry.
It is well known that quinazolinones are the important core
7
units in a number of natural products. Compounds with the
2
-Arylylidenemalononitrile derivatives were obtained by the
quinazoline ring system play important roles in biochemical
18
method reported in the literature. Cyclisation of compounds
with methyl anthranilate afforded compounds 3. The melting
8
,9
processes and have many pharmacological properties, such as
antimicrobial, anti-inflammatory, anti-convulsant, anticancer,
2
10–14
points and yields of compounds 3 are shown in Table 1.
All of the data for MS, IR, H NMR and elemental analysis
antimalarial activity and so on.
Chromeno[2,3-d]pyrimidine
1
and its derivatives have occupied a distinctive place in the field
of medicinal chemistry towards the design of biologically
active compounds, which may be widely used as anticancer,
antibacterial antitubercular, antitumour, anti-inflammatory,
shown in the experimental section are in accordance with the
chemical structures of the target compounds.
1
In the H NMR spectrum of compound 3c, a sharp single
15,16
proton peak at δ 5.52 was the characteristic absorption proton
peak of 15-H. The structure of compound 3c was further proved
by IR spectra through several typical absorption bands of 1661,
antifungal and antileishmanial agents, etc.
In continuation of our previous work, a new series of
1
5-aryl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]pyrimido[6,1-b]
–1
–1
quinazoline-1,9-diones is reported in this paper. Compound
1705 cm (C=O) and 2955, 2867 cm (–CH ).
3
3
d was further determined by single crystal X-ray diffraction
In order to study the optimal reaction conditions for
analysis.
the synthesis of compounds 3, the ethyl N-(3-cyano-4-(4-
R
O
O
R1
R
R
O
CN
NC
CN
CN
CN
R1
CHO
.
KF 2H O/EtOH
2
R1
R1
O
NH2
1
R
R
CH OEt
(
)3
NH2
O
N
N
N
O
COOCH3
CN
N
O
R1
R1
R1
R1
O
O
CHOEt
3
2
Scheme 1
*
Correspondent. E-mail: gf552002@163.com

88 JOURNAL OF CHEMICAL RESEARCH 2016
a
Table 1 The melting points and yields of compounds 3a–o
Table 2 Crystallographic data for compound 3d
b
Product
R
R1
M.p./°C
Yield /%
CCDC No.
Empirical formula
Formula weight
Wavelength/nm
Crystal system
Space group
a/Å
1426072
C H Cl N O
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
4-OCH3
3,4-(OCH3)2
4-CH3
2,4-Cl2
2-Cl
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
258–260
252–254
260–262
254–256
252–254
282–284
268–270
290–292
264–266
270–272
286–288
> 300
73
74
75
68
69
71
75
72
72
77
70
71
67
72
77
26 19
2 3 3
492.34
0.71073
Monoclinic
P 2 /c
1
6.4098(14)
29.363(6)
11.824(3)
90.00
4-Cl
H
b/Å
c/Å
3-NO2
4-OCH3
4-CH3
2,4-Cl2
2-Cl
4-Cl
H
3-NO2
α/°
β/°
94.316(3)
90.00
2219.1(9)
4
1.474
0.329
γ/°
Volume/Å
3
291–293
284–286
288–290
Z
–
3
H
H
Calculated density/g cm
Absorption coefficient/mm
F (000)
–1
a
1016.0
Reaction condition: 5 mmol compounds 2, 5 mmol methyl anthranilate, 10 mL acetic
acid, reflux.
Isolated yields.
Final R indices [I > 2sigma(I)]
R indices (all data)
R = 0.0392, wR = 0.1312
R = 0.0531, wR = 0.1519
1 2
1
2
b
methoxypheny)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-
chromen-2-yl)formimidate 2a was selected to examine the
reaction with methyl anthranilate under various conditions.
First, ethanol was selected as a solvent at room temperature and
under reflux. However, no reaction was observed. Significantly,
with the presence of acetic acid under reflux in ethanol, the
final compound 3a was obtained with low yield. In order to
increase the yield, excess acetic acid was used. As a result, the
yield of 3a was improved. Encouraged by the aforementioned
results, acetic acid was directly used as a solvent under reflux.
In this way, the yields reached up to about 73%.
Under the optimised conditions, various substituted
compounds 2 were reacted with methyl anthranilate to obtain
the corresponding products (Table 1) and the reactions were
all successful. From these observations, we concluded that the
nature of the substituent on the aromatic rings does not have any
significant role in determining the course of the reaction.
Synthesis of 15-aryl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]pyrimido-
[6,1-b]quinazoline-1,9-dione derivatives (3a–o); general procedure
A mixture of ethyl N-(3-cyano-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-
chromen-2-yl)formimidate 2 (5 mmol) and methyl anthranilate (5 mmol)
was dissolved in acetic acid and heated for 8 h under reflux. The reaction
was monitored by TLC. The mixture was cooled to room temperature,
poured into ice cold water and then neutralised with ammonia and
stirred for 30 min. The precipitate was filtered off, washed with water,
dried, and further purified by column chromatography.
Single crystal X-ray crystallography
Crystallographic data of 3d (Table 2) were obtained on a Bruker
SMART APEX-II CCD with Mo-Kα radiation (λ = 0.71073 Å)
at 296(2) K. The structures were solved by direct methods with
2
the SHELXS-97 program and refinements on F were performed
with the SHELXL-97 program by full-matrix least-squares
19,20
techniques.
CCDC1426072 contains the supplementary data for
this paper. The data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request.
cif. The single crystal structures of 3d are shown in Figs 1 and 2.
Conclusion
1
5- (4-Methoxyphenyl) -3,3-dimethyl-2,3,4,15-tetrahydro-
In summary,
a
series of new 15-aryl-2,3,4,15-
chromeno[2 ′, 3′:4,5]pyrimido[6,1-b]quinazoline-1,9-dione (3a): Yield:
tetrahydrochromeno[2′,3′:4,5]pyrimido[6,1-b]quinazoline-1,9-
dione derivatives were successfully synthesised by the reaction
of methyl anthranilate with ethyl N-(3-cyano-5-oxo-4-aryl-
1
7
7
3%; m.p. 258–260 °C; H NMR (400 MHz, CDCl ): δ 9.41 (s, 1H, C –
3
10 11 13
H), 8.33 (d, J = 8.1 Hz, 1H, C –H), 7.88–7.72 (m, 2H, (C + C )–H), 7.43
12
(
(
2
t, J = 10.2 Hz, 3H, 15–(3′ + 5′)–H, C –H), 6.76 (d, J = 8.0 Hz, 2H), 5.51
5,6,7,8-tetrahydro-4H-chromen-2-yl)formimidate derivatives
1
5
2
s, 1H, C –H), 3.70 (s, 3H, 15–OCH ), 2.65 (d, J = 18.3 Hz, 2H, C –H),
3
in good yields. Systematic characterisations were performed to
investigate the structure of the target compounds. This method
has advantages, such as good yields, neat reaction conditions
and easy workup. The study of the biological activity of these
compounds is in progress.
4
.30 (q, J = 16.5 Hz, 2H, C –H), 1.16 (s, 3H, –CH ), 1.10 (s, 3H, –CH );
IR (KBr, ν, cm ): 2955, 2833, 1708, 1658. Anal. calcd for C H N O :
3
3
–1
27
23
3
4
C, 71.51; H, 5.11; N, 9.27; found: C, 71.62; H, 5.30; N, 9.03%. MS (ESI)
+
m/z: 454.2 [M + H] .
1
5 - ( 3 , 4 - D i m e t h o x y p h e n y l ) - 3 , 3 - d i m e t h y l - 2 , 3 , 4 , 15 -
tetrahydrochromeno[2 ′, 3′:4,5]pyrimido[6,1-b]quinazoline-1,9-dione
Experimental
Melting points were obtained by an Electrothermal apparatus and are
uncorrected. Microanalysis was performed using the PerkinElmer
1
(
3b): Yield: 74%; m.p. 252–254 °C; H NMR (400 MHz, CDCl ):
3
7
10
δ 9.35 (s, 1H, C –H), 8.28 (dd, J = 8.1, 1.5 Hz, 1H, C –H), 7.80–7.67
11 13 12
(m, 2H, (C + C )–H), 7.39 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H, C –H), 7.21
(d, J = 1.8 Hz, 1H, 15–2′–H), 6.82 (dd, J = 8.3, 2.0 Hz, 1H, 15–5′–H),
2
400 Microanalytical Service. IR spectra were determined on a
1
15
PerkinElmer 1700 spectrophotometer. H NMR spectra were recorded
on a Bruker ARX-400 instrument using CDCl as solvent. Electrospray
ionisation mass spectrometry data (ESI-MS) were determined on an
Aglient-6100 instrument. All reactions were monitored by TLC, which
were carried out on 0.2 mm silica GF254 (Merck) plates using UV light
6.65 (d, J = 8.3 Hz, 1H, 15–6′–H), 5.48 (s, 1H, C –H), 3.84 (s, 3H,
15–OCH ), 3.70 (s, 3H, 15–OCH ), 2.62 (s, 2H, C –H), 2.31–2.21
2
3
3
3
4
(m, 2H, C –H), 1.11 (s, 3H, –CH ), 1.06 (s, 3H, –CH ); IR (KBr, ν,
3 3
–1
cm ): 2936, 2856, 1705, 1657. Anal. calcd for C H N O : C, 69.55;
2
8
25
3
5
H, 5.21; N, 8.69; found: C, 69.73; H, 5.34; N, 8.48%. MS (ESI) m/z:
+
(
254 and 365 nm) for detection.
484.2 [M + H] .

JOURNAL OF CHEMICAL RESEARCH 2016 89
Fig. 1 Molecular structure of compound 3d showing 30% probability ellipsoids.
Fig. 2 Packing diagram of compound 3d in unit-cell along a-axis.
1
7
3
,3-Dimethyl-15-(p-tolyl)-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
68%; m.p. 254–256 °C; H NMR (400 MHz, CDCl ): δ 9.43 (s, 1H, C –
3
10
11
pyrimido[6,1-b]quinazoline-1,9-dione (3c): Yield: 75%; m.p. 260–262 °C;
H), 8.32 (d, J = 8.0 Hz, 1H, C –H), 7.83 (t, J = 7.7 Hz, 1H, C –H), 7.70
(d, J = 8.2 Hz, 1H, C –H), 7.44 (t, J = 7.6 Hz, 2H, 15–3′–H, C –H), 7.28
(s, 1H, 15–5′–H), 7.15 (d, J = 8.3 Hz, 1H, 15–6′–H), 5.72 (s, 1H, C –H),
2.65 (s, 2H, C –H), 2.29 (q, J = 16.3 Hz, 2H, C –H), 1.16 (s, 3H, –CH ),
1.08 (s, 3H, –CH ); IR (KBr, ν, cm ): 2960, 2874, 1703, 1662. Anal.
calcd for C H Cl N O : C, 63.43; H, 3.89; N, 8.53; found: C, 63.61; H,
3.62; N, 8.74%. MS (ESI) m/z: 492.1 [M + H] .
15- (2-Chlorophenyl) -3,3-dimethyl-2,3,4,15-tetrahydro-
1
7
13
12
H NMR (400 MHz, CDCl ): δ 9.39 (s, 1H, C –H), 8.31 (d, J = 8.0 Hz, 1H,
3
10
11
13
15
C –H), 7.84–7.73 (m, 2H, (C + C )–H), 7.42 (dd, J = 16.5, 7.8 Hz, 3H, 15–
12
2
4
(
2′ + 6′)–H, C –H), 7.04 (d, J = 7.6 Hz, 2H, 15–(3′ + 5′)–H), 5.52 (s, 1H,
3
15
2
4
–1
C –H), 2.67 (s, 2H, C –H), 2.30 (q, J = 16.4 Hz, 2H, C –H), 2.22 (s, 3H,
3
–1
1
2
5–CH ), 1.16 (s, 3H, –CH ), 1.09 (s, 3H, –CH ); IR (KBr, ν, cm ): 2955,
867, 1705, 1661. Anal. calcd for C H N O : C, 74.12; H, 5.30; N, 9.60;
3
3
3
26 19
2
3
3
+
27
23
3
3
+
found: C, 74.35; H, 5.12; N, 9.82%. MS (ESI) m/z: 438.2 [M + H] .
5-(2,4-Dichlorophenyl)-3,3-dimethyl-2,3,4,15-tetrahydro-
chromeno[2 ′, 3′:4,5]pyrimido[6,1-b]quinazoline-1,9-dione (3d): Yield:
1
chromeno[2 ′, 3′:4,5]pyrimido[6,1-b]quinazoline-1,9-dione (3e): Yield:
69%; m.p. 252–254 °C; H NMR (400 MHz, CDCl ): δ 9.43 (s, 1H,
1
3

9
0 JOURNAL OF CHEMICAL RESEARCH 2016
7
10
11
C –H), 8.31 (dd, J = 8.1, 1.1 Hz, 1H, C –H), 7.81–7.73 (m, 2H, (C +
15-(2-Chlorophenyl)-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
pyrimido[6,1-b]quinazoline-1,9-dione (3l): Yield: 71%; m.p.
13
12
C )–H), 7.52 (d, J = 9.8 Hz, 1H, 12–3′–H), 7.45–7.41 (m, 1H, C –H),
1
7
7
1
2
2
.28 (s, 1H, 12–4′–H), 7.18–7.15 (m, 1H, 12–5′–H), 7.08–7.04 (m, 1H,
2–6′–H), 5.80 (s, 1H, C –H), 2.65 (s, 2H, C –H), 2.29 (q, J = 16.3 Hz,
H, C –H), 1.16 (s, 3H, –CH ), 1.08 (s, 3H, –CH ); IR (KBr, ν, cm ):
958, 2925, 2858, 1707, 1662. Anal. calcd for C H ClN O : C, 68.20;
> 300 °C; H NMR (400 MHz, CDCl ): δ 9.46 (s, 1H, C –H), 8.33
3
10 11 13
15
2
(dd, J = 8.0, 0.8 Hz, 1H, C –H), 7.84–7.76 (m, 2H, (C + C )–H),
4
–1
12
7.60 (d, J = 7.2 Hz, 1H, 15–3′–H), 7.47–7.43 (m, 1H, C –H), 7.27 (d,
3
3
J = 1.1 Hz, 1H, 15–4′–H), 7.19 (t, J = 6.9 Hz, 1H, 15–5′–H), 7.09 (td,
2
6
20
3
3
15
H, 4.40; N, 9.18; found: C, 68.32; H, 4.65; N, 9.01%. MS (ESI) m/z:
J = 7.7, 1.6 Hz, 1H, 15–6′–H), 5.84 (s, 1H, C –H), 2.90–2.74 (m, 2H,
2 4 3
+
4
58.2 [M + H] .
5- (4-Chlorophenyl) -3,3-dimethyl-2,3,4,15-tetrahydro-
chromeno[2 ′, 3′:4,5]pyrimido[6,1-b]quinazoline-1,9-dione (3f): Yield:
C –H), 2.46–2.43 (m, 2H C –H), 2.18–2.06 (m, 2H, C –H); IR (KBr,
–1
1
ν, cm ): 2942, 1707, 1666. Anal. calcd for C H ClN O : C, 67.06; H,
24 16 3 3
3.75; N, 9.78; found: C, 67.26; H, 3.59; N, 9.90%. MS (ESI) m/z: 430.1
1
7
+
7
1%; m.p. 282–284 °C; H NMR (400 MHz, CDCl ): δ 9.43 (s, 1H, C –
H), 8.34 (dd, J = 8.1, 1.1 Hz, 1H, C –H), 7.87–7.83 (m, 1H, C –H), 7.72
d, J = 8.0 Hz, 1H, C –H), 7.48–7.43 (m, 3H, 15–(3′ + 5′)–H, C –H),
.20 (d, J = 8.5 Hz, 2H, 15–(2′ + 6′)–H), 5.51 (s, 1H, C –H), 2.68 (s,
H, C –H), 2.31 (q, J = 16.3 Hz, 2H, C –H), 1.17 (s, 3H, –CH ), 1.09 (s,
[M + H] .
3
10
11
15-(4-Chlorophenyl)-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
pyrimido[6,1-b]quinazoline-1,9-dione (3m): Yield: 67%; m.p.
13
12
(
7
2
3
15
1
7
291–293 °C; H NMR (400 MHz, CDCl ): δ 9.43 (s, 1H, C –H), 8.34 (d,
3
10 11
2
4
J = 7.9 Hz, 1H, C –H), 7.85 (t, J = 7.5 Hz, 1H, C –H), 7.72 (d, J = 8.3
3
–1
13
12
H, –CH ); IR (KBr, ν, cm ): 2961, 2895, 1710, 1661. Anal. calcd for
Hz, 1H, C –H), 7.45 (t, J = 9.2 Hz, 3H, 15–(3′ + 5′)–H, C –H), 7.20
15
3
C H ClN O : C, 68.20; H, 4.40; N, 9.18; found: C, 67.99; H, 4.69; N,
(d, J = 7.8 Hz, 2H, 15–(2′ + 6′)–H), 5.54 (s, 1H, C –H), 2.89–2.75 (m,
2 4 3
2
6
20
3
3
+
9
.34%. MS (ESI) m/z: 458.1 [M + H] .
,3-Dimethyl-15-phenyl-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
pyrimido[6,1-b]quinazoline-1,9-dione (3g): Yield: 75%; m.p.
2H, C –H), 2.50–2.39 (m, 2H, C –H), 2.20–2.02 (m, 2H, C –H); IR
–1
3
(KBr, ν, cm ): 2949, 2880, 1714, 1662. Anal. calcd for C H ClN O :
24 16 3 3
C, 67.06; H, 3.75; N, 9.78; found: C, 67.21; H, 3.89; N, 9.56%. MS (ESI)
1
7
+
2
(
(
68–270 °C; H NMR (400 MHz, CDCl ): δ 9.37 (s, 1H, C –H), 8.27
d, J = 7.8 Hz, 1H, C –H), 7.79 (d, J = 4.2 Hz, 2H, (C + C )–H), 7.47
d, J = 7.7 Hz, 2H, 15–(3′ + 5′)–H), 7.42–7.38 (m, 1H, C –H), 7.17 (d, J
7.8 Hz, 2H, 15–(2′ + 6′)–H), 7.07 (t, J = 7.6 Hz, 1H, 12–4′-H), 5.61 (s,
H, C –H), 2.63 (s, 2H, C –H), 2.25 (q, J = 16.4 Hz, 2H, C –H), 1.11
m/z: 430.1 [M + H] .
3
10
11
13
15-Phenyl-2,3,4,15-tetrahydrochromeno[2 ′, 3′:4,5]pyrimido[6,1-b]
12
1
quinazoline-1,9-dione (3n): Yield: 72%; m.p. 284–286 °C; H NMR
=
1
(
(400 MHz, CDCl ): δ 9.36 (s, 1H, C –H), 8.26 (dd, J = 8.1, 1.1 Hz, 1H,
7
3
15
2
4
10
11
13
C –H), 7.80–7.76 (m, 1H, C –H), 7.70 (d, J = 7.9 Hz, 1H, C –H), 7.45
(d, J = 7.2 Hz, 2H, 15–(3′ + 5′)–H), 7.40–7.36 (m, 1H, C –H), 7.18 (t,
–1
12
s, 3H, –CH ), 1.03 (s, 3H, –CH ); IR (KBr, ν, cm ): 2957, 2924, 2856,
708, 1659. Anal. calcd for C H N O : C, 73.74; H, 5.00; N, 9.92;
3
3
1
26 21 3 3
J = 7.6 Hz, 2H, 15–(2′ + 6′)–H), 7.07 (t, J = 7.4 Hz, 1H, 15–4′–H), 5.55
+
found: C, 73.86; H, 5.13; N, 9.78.%. MS (ESI) m/z: 424.2 [M + H] .
,3-Dimethyl-15- (3-nitrophenyl) -2,3,4,15-tetrahydro-
chromeno[2 ′, 3′:4,5]pyrimido[6,1-b]quinazoline-1,9-dione (3h): Yield:
15
2
4
(
2
s, 1H, C –H), 2.86–2.68 (m, 2H, C –H), 2.44–2.32 (m, 2H, C –H),
3
3
–1
.12–1.99 (m, 2H, C –H); IR (KBr, ν, cm ): 2948, 2879, 1715, 1664.
Anal. calcd for C H N O : C, 72.90; H, 4.33; N, 10.63; found: C,
2
4
17
3
3
1
7
7
8
7
=
2%; m.p. 290–292 °C; H NMR (400 MHz, CDCl ): δ 9.38 (s, 1H, C –H),
.37 (t, J = 1.9 Hz, 1H, C –H), 8.27 (dd, J = 8.1, 1.1 Hz, 1H, 15–2′–H),
.94–7.92 (m, 1H, 15–4′–H), 7.83–7.78 (m, 2H, (C + C )–H), 7.70 (d, J
+
3
73.05; H, 4.10; N, 10.87%. MS (ESI) m/z: 396.2 [M + H] .
10
1
5-(3-Nitrophenyl)-2,3,4,15-tetrahydrochromeno[2 ′, 3′:4,5]
11 13
pyrimido[6,1-b]quinazoline-1,9-dione (3o): Yield: 77%; m.p.
88–290 °C; H NMR (400 MHz, CDCl ): δ 9.47 (s, 1H, C –H),
.44 (t, J = 1.9 Hz, 1H, C –H), 8.36 (dd, J = 8.1, 1.2 Hz, 1H,
12
7.9 Hz, 1H, 15–6′–H), 7.43–7.33 (m, 2H, 15–5′–H, C –H), 5.57 (s, 1H,
1
7
2
8
15
2
4
3
C –H), 2.67 (q, J = 18 Hz, C –H), 2.26 (q, J = 16.4 Hz, 2H, C –H), 1.12 (s,
10
–1
3
H, –CH ), 1.05 (s, 3H, –CH ); IR (KBr, ν, cm ): 2950, 2868, 1716, 1665.
Anal. calcd for C H N O : C, 66.66; H, 4.30; N, 11.96; found: C, 66.89;
3
3
1
5–2′–H), 8.02 (d, J = 8.0 Hz, 1H, 15–4′–H), 7.90 (dd, J = 15.9,
26
20
4
5
11 13
7
.4 Hz, 2H, (C + C )–H), 7.78 (d, J = 8.3 Hz, 1H, 15–6′–H),
+
H, 4.52; N, 11.74%. MS (ESI) m/z: 469.2 [M + H] .
5-(4-Methoxyphenyl)-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
pyrimido[6,1-b]quinazoline-1,9-dione (3i): Yield: 72%; m.p.
12 15
7.51–7.42 (m, 2H, 15–5′–H, C –H), 5.68 (s, 1H, C –H), 2.99–
1
2
4
2
.81 (m, 2H, C –H), 2.48 (q, J = 5.1 Hz, 2H, C –H), 2.22–2.15
3
–1
1
7
(m, 2H, C –H); IR (KBr, ν, cm ): 2949, 2920, 2877, 1725, 1660.
Anal. calcd for C H N O : C, 65.45; H, 3.66; N, 12.72; found:
C, 65.68; H, 3.80; N, 12.54%. MS (ESI) m/z: 441.1 [M + H] .
2
64–266 °C; H NMR (400 MHz, CDCl ): δ 9.42 (s, 1H, C –H), 8.33
3
10 11
(
d, J = 8.1 Hz, 1H, C –H), 7.84 (t, J = 7.7 Hz, 1H, C –H), 7.76 (d,
24 16
4
5
+
13
J = 8.3 Hz, 1H, C –H), 7.44 (dd, J = 13.4, 7.8 Hz, 3H, 15–(2′ + 6′)–H,
12
15
C –H), 6.77 (d, J = 8.4 Hz, 2H, 15–(3′ + 5′)–H), 5.54 (s, 1H, C –H),
2
Electronic Supplementary Information
3
.71 (s, 3H, 15–OCH ), 2.90–2.78 (m, 2H, C –H,), 2.50–2.42 (m, 2H,
3
4
3
–1
1
C –H), 2.14–2.08 (m, 2H, C –H); IR (KBr, ν, cm ): 2949, 2834, 1708,
The ESI ( H NMR spectra and IR spectra) is available through:
1
7
660. Anal. calcd for C H N O : C, 70.58; H, 4.50; N, 9.88; found: C,
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
2
5
19
3
4
+
0.80; H, 4.23; N, 9.75%. MS (ESI) m/z: 426.2 [M + H] .
5- (p-Tolyl) -2 , 3,4 ,15-tetrahydrochromeno [2 ′, 3 ′: 4 , 5]
pyrimido[6,1-b]quinazoline-1,9-dione (3j): Yield: 77%; m.p.
1
Received 25 November 2015; accepted 16 December 2015
Paper 1503733 doi: 10.3184/174751916X14527702465295
Published online: 20 January 2016
1
7
2
70–272 °C; H NMR (400 MHz, CDCl ): δ 9.43 (s, 1H, C –H), 8.34
3
10 11 13
(
(
d, J = 8.0 Hz, 1H, C –H), 7.88–7.77 (m, 2H, (C + C ) –H), 7.48–7.41
12
m, 3H, 15–(3′ + 5′)–H, C –H), 7.06 (d, J = 7.9 Hz, 2H, 15–(3′ + 5′)–
References
15
2
H), 5.58 (s, 1H, C –H), 2.93–2.75 (m, 2H, C –H), 2.52–2.39 (m, 2H,
1
S. Gupta, P. Gupta, A. Sacher and R.L. Sharma, J. Heterocyclic Chem.,
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4
3
C –H), 2.25 (s, 3H, 15–CH ), 2.19–2.08 (m, 2H, C –H); IR (KBr, ν,
3
–1
cm ): 2944, 2874, 1710, 1662. Anal. calcd for C H N O : C, 73.34;
H, 4.68; N, 10.26; found: C, 73.15; H, 4.81; N, 10.03%. MS (ESI) m/z:
2
3
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2
5
19
3
3
+
4
10.2 [M + H] .
5-(2,4-Dichlorophenyl)-2,3,4,15-tetrahydrochromeno[2′,3′:4,5]
pyrimido[6,1-b]quinazoline-1,9-dione (3k): Yield: 70%; m.p.
4
5
6
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1
1
7
2
86–288 °C; H NMR (400 MHz, CDCl ) δ 9.45 (s, 1H, C –H), 8.34
3
10 11
(
8
dd, J = 8.1, 1.2 Hz, 1H, C –H), 7.87–7.83 (m, 1H, C –H), 7.72 (d, J =
13
12
.2 Hz, 1H, C –H), 7.54–7.45 (m, 2H, 15–4′–H, C –H), 7.29 (d, J = 2.1
7
8
9
J.P. Michael, Nat. Prod. Rep., 2001, 18, 543.
Hz, 1H, 15–5′–H), 7.17 (dd, J = 8.4, 2.1 Hz, 1H, 15–6′–H), 5.75 (s, 1H,
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15
2
4
C –H), 2.88–2.78 (m, 2H, C –H), 2.47–2.43 (m, 2H, C –H), 2.17–2.06
3
–1
(
m, 2H, C –H); IR (KBr, ν, cm ): 2936, 2888, 1708, 1664. Anal. calcd
for C H Cl N O : C, 62.08; H, 3.26; N, 9.05; found: C, 61.89; H, 3.52;
N, 9.23%. MS (ESI) m/z: 464.1 [M + H] .
10
2
4
15
2
3
3
11 L.-M. Yang, C.-F. Chen and K.-H. Lee, Bioorg. Med. Chem. Lett., 1995,
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15
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