Copper-catalyzed efficient synthesis of 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones from 2-nitrobenzaldehydes

Article abstract of DOI:10.1016/j.tet.2018.03.018

A novel and practical copper-catalyzed approach was developed for the preparation of 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones. The 2-amino-N′-arylbenzohydrazideis easily prepared by a reaction of isatoic anhydride with arylhydrazine. Then, through a con

Full text of DOI:10.1016/j.tet.2018.03.018

Accepted Manuscript
Copper-catalyzed efficient synthesis of 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones
from 2-nitrobenzaldehydes
Zahra Arasteh Fard, Karim Akbari Dilmaghani, Mehdi Soheilizad, Bagher Larijani,
Mohammad Mahdavi
PII:
S0040-4020(18)30261-8
10.1016/j.tet.2018.03.018
TET 29358
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 January 2018
Revised Date: 5 March 2018
Accepted Date: 8 March 2018
Please cite this article as: Arasteh Fard Z, Dilmaghani KA, Soheilizad M, Larijani B, Mahdavi M, Copper-
catalyzed efficient synthesis of 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones from 2-nitrobenzaldehydes,
Tetrahedron (2018), doi: 10.1016/j.tet.2018.03.018.
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Graphical Abstract
Copper-catalyzed efficient synthesis of 5-
arylindazolo[3,2-b]quinazolin-7(5H)-ones
from 2-nitrobenzaldehydes
Leave this area blank for abstract info.
Zahra ArastehFard, Karim Akbari Dilmaghani, Mehdi Soheilizad, Bagher Larijani and Mohammad Mahdavi

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Copper-catalyzed efficient synthesis of 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones
from 2-nitrobenzaldehydes
ZahraArastehFard,a KarimAkbari Dilmaghani
Mahdavic
٭ Mehdi Soheilizad,b Bagher Larijanic and Mohammad
,
a
aDepartment of Chemistry, Faculty of Sciences, Urmia University, Urmia, Iran
bCinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran
cEndocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran,
Iran
ARTICLE INFO
ABSTRACT
Article history:
Received
A novel and practical copper-catalyzed approach was developed for the preparation of 5-
arylindazolo[3,2-b]quinazolin-7(5H)-ones. The 2-amino-N'-arylbenzohydrazideis easily
Received in revised form
Accepted
prepared by a reaction of isatoic anhydride with arylhydrazine. Then, through a
condensation/intramolecular cyclization reaction by 2-nitrobenzaldehydes in the present of CuI,
Available online
the corresponding 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones are produced in good yields.
Keywords:
Indazolo[3,2-b]quinazolinones
Copper-catalyzed
2009 Elsevier Ltd. All rights reserved
.
2-amino-N'-arylbenzohydrazide
2-nitrobenzaldehyde
intramolecular cyclization
———
Corresponding author. Tel.: +98-21-66954708; fax: +98-21-66461178; e-mail: Momahdavi@sina.tums.ac.ir k.adilmaghani@urmia.ac.ir

2
Tetrahedron
ACCEPTED MANUSCRIPT
1. Introduction
amino-N'-arylbenzohydrazide 3 was easily prepared by the
reaction of isatoic anhydride 1 and arylhydrazine 2 in aqueous
media.25 Next, heating an equimolar mixture of 2-amino-N'-
arylbenzohydrazide 3 and 2-nitrobenzaldehydes 4 in the presence
of CuI and K2CO3 in DMSO at 80°C for 8 hours, through a
condensation and intramolecular cyclization by removal of a
nitro group,26 leads to the formation of the corresponding 5-
arylindazolo[3,2-b]quinazolin-7(5H)-ones 5a-l in good yields
(Scheme 2).
Nitrogen-containing heterocyclic compounds and their
analogs are pharmaceutically attractive scaffolds and widely exist
in naturally occurring and synthetic biologically active
molecules.1 Among them, fused polycyclic N-containing
heteroaromatics have received much synthetic attention because
of their wide range of biological activities and their high
therapeutic values.2 For instance, N-fused polycycles witha
quinazolinone scaffold have been shown to possess a broad range
of biological activities, including anticancer,3 anti-microbial,4
anti-inflammatory,5 anticonvulsant,6 anti-ulcer,7 anti-bacterial,8
antidiabetic,9 and anti-viral properties.10 They are also an
important class of alkaloids because they are widely found in the
structure of a number of natural products such as luotonin A,11
circumdatins,12
rutaecarpine,13
deoxyvasicinone,14
and
tryptanthrin.15 Another example of N-containing biologically
active heterocycles are indazole-based derivatives that have been
reported to possess antidepressant,16 anti-inflammatory,16 HIV
protease inhibitory,17 antitumor,18 anti-microbial,19 and
contraceptive activities.20 The indazole core is an important
pharmacophore in medicinal chemistry and has been recognized
as a privileged structure in heterocyclic chemistry.
Scheme 2. Copper-catalyzed preparation of 5-arylindazolo[3,2-
b]quinazolin-7(5H)-ones
To optimizethe reaction conditions, preparation of 5-
Owing to this broad range of properties of N-containing
quinazolinone and indazole heterocycles, it is reasonable to
expect that fused quinazolinone-indazole derivatives, such as
indazolo[3,2-b]quinazolinones, have significant biological
activity. To date, a few synthetic routes have been reported for
the preparation of indazolo[3,2-b]quinazolinones, including: a
one-pot cascade reaction of isatoic anhydride, hydrazines, and 2-
iodo benzaldehyde catalyzed by palladium;21 Cu-catalyzed
domino Ullmann-type coupling reaction of 2-amino-N′-
arylbenzohydrazide and 2-halobenzaldehydes;22 intramolecularC-
Nbondformationreactionof3-amino-2-(2-
phenylindazolo[3,2-b]quinazolin-7(5H)-one
(5a)
was
investigated as a model reaction. First, we observed that heating a
mixture of 2-amino-N'-phenylbenzohydrazide 3a and 2-
nitrobenzaldehyde 4a in the presence of CuBr and Cs2CO3 in
DMF as a solvent at 80°C for 8 hours lead to the desired product
5a in 58% yield (Table 1, entry 1). Next, to evaluate the reaction
medium, the effects of several solvents such as DMSO, xylene,
and THF were investigated (Table 1, entries 2 to 4) and the best
result was obtained in DMSO (65%, Table 1, entry 2). Then, for
the choice of the best base, the model reaction was examined by
various inorganic and organic bases such as K2CO3, K3PO4,
DBU, and NEt3 (Table 1, entries 5 to 8). As shown in Table 1,
among various bases examined, K2CO3 turned out to be the best
choice, while others were less effective. Next, to find the best
copper source, we observed that the use of CuI as a Cu-source
significantly increased the yield of 5a (Table 1, entry 9), while
the other Cu salts like CuCl, CuO, Cu2O, and Cu(OAc)2 could
not enhance the yield of desired product 5a (Table 1, entries 10 to
13). Then, to examine the effect of temperature, the model
reaction in the present of CuI and K2CO3 in DMSO was
investigated at several different temperatures (Table 1, entries 14
to 16). Finally, we observed that in the absence of Cu-catalyst, no
product was formed (Table 1, entry 17). As can be seen in Table
1, the best yield of the product was obtained at 80°C (85%, Table
1, entry 9).
bromophenyl)dihydroquinazolinones by
a
CuCl/L-proline
catalytic system;23 and Pd-catalyzed cascade reaction of 2-amino-
N′-arylbenzohydrazides with triethyl orthobenzoates.24Therefore,
we wished to develop these procedures via intramolecular
cyclization of 2-amino-N'-arylbenzohydrazide with 2-
nitrobenzaldehydes catalyzed by copper(I) iodide (Scheme 1).
Previous works:
CHO
O
O
I
H
N
O
Pd(PPh3
)
3
Ar
N
CuCl
L-proline
ref. 23
+
BINAP
ref. 21
N
H
O
N
H
ArNHNH2
O
N
Ar
Br
N
N
O
O
CH(OEt)3
CHO
NHAr
+
NHAr
+
X
N
H
NH2
N
Pd(OAc)2
CuBr
H
Cs2CO3
AgOAc
ref. 24
NH2
ref. 22
Table 1. Optimization of conditions for the synthesis of 5aa
This study:
CHO
O
O
Ar
N
NO2
NHAr
N
N
CuI
K2CO3
H
+
N
NH2
Scheme 1. Synthesis of 5-arylindazolo[3,2-b]quinazolin-7(5H)-ones
Cu
source
Temp.
(°C)
Yield
(%)b
Entry
Base
Solvent
1
2
3
4
5
6
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CsCO3
CsCO3
CsCO3
CsCO3
K2CO3
K3PO4
DMF
80
80
80
80
80
80
58
DMSO
Xylene
THF
65
NRc
2. Results and discussion
In continuation of our efforts toward the efficient synthesis of
biologically active target molecules,25 herein we would like to
32
DMSO
DMSO
68
introduce
a
new approach to the preparation of 5-
arylindazolo[3,2-b]quinazolin-7(5H)-ones. Thus, initially 2-
48

3
7
CuBr
CuBr
CuI
DBU
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
80
42
ACCEPTED MANUSCRIPT
8
NEt3
80
80
80
80
80
80
120
60
25
80
37
85
46
18
38
22
78
74
15
NR
9
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
10
11
12
13
14
15
16
17
CuCl
CuO
Cu2O
Cu(OAc)2
CuI
CuI
CuI
‒
Scheme 3. Proposed mechanism for the preparation of 5-
arylindazolo[3,2-b]quinazolin-7(5H)-ones
a Reaction condition: 3a (2 mmol), 4a (2.1 mmol), Cu-source (0.2 mmol),
Base (2 mmol), Solvent (4 mL) at reflux for 8 h. b Isolated yield. c NR=
no reaction
3. Conclusion
In conclusion, we developed a new and efficient copper-
catalyzed approach for the synthesis of 5-arylindazolo[3,2-
b]quinazolin-7(5H)-ones through a condensation/intramolecular
cyclization reaction of 2-amino-N'-arylbenzohydrazide with 2-
nitrobenzaldehydes in the present of CuI. The simplicity of the
starting materials, ligand-free metal catalysis and good yields of
the products are the main advantages of this method.
Table 2. Substrate scope of Cu-catalyzed synthesis of
5-arylindazolo[3,2-b]quinazolin-7(5H)-ones 5a–l
4. Experimental
4.1. Material and methods
All chemicals were purchased from Merck and Fluka
companies. All yields refer to isolated products. Melting points
were determined in a capillary tube and have not been corrected.
The progress of the reaction was followed with TLC using silica
gel SILG/UV 254 and 365 plates. The IR spectra of the
compounds were obtained on Nicolet FT-IR Magna 550
1
spectrographs (KBr disks) (Nicolet, Madison, WI, USA). H and
13C NMR spectra were recorded at 500 and 125 MHzon a
BruckerNMR spectrometer(Rheinstetten, Germany) using
tetramethylsilane (TMS) as the internal standard. Products 5e, 5f,
5h, 5i, 5j, 5k, and 5l are novel compounds. All products were
characterized by melting point, IR, 1H, and 13C NMR
spectroscopic data.
4.2. General procedure for the preparation of 2-amino-N'-
arylbenzohydrazide (3)
A mixture of isatoic anhydride (2.0 mmol) and arylhydrazine
(2.0 mmol) in H2O (4.0 mL) was stirred for 4 hours at room
temperature. After completion of the reaction as indicated by
TLC, the resulting precipitate was filtered, washed with cold
water, dried, and recrystallized from ethanol to produce the
desired compound 3.
A possible reaction pathway for the Cu-catalyzed formation of
5-arylindazolo[3,2-b]quinazolin-7(5H)-ones 5 is suggested in
Scheme 3. The initial condensation of the 2-amino-N'-
arylbenzohydrazide 3 with 2-nitrobenzaldehyde 4, followed by
aerobic oxidation generate the compound 6,27 which undergo
coordination with Cu generates intermediate 7. Then,
nucleophilic attack of iodide ion to this intermediate followed by
intramolecular cyclization and libration of KNO2, leads to the
4.3. General procedure for the preparation of 5-
arylindazolo[3,2-b]quinazolin-7(5H)-ones (5a-i)
A mixture of 2-amino-N'-arylbenzohydrazide 3 (2.0 mmol), 2-
nitrobenzaldehyde 4 (2.1 mmol), CuI (0.2 mmol), and K2CO3
(2.0 mmol) in dry DMSO (4.0 mL) was heated in a sealed vessel
under air for 8 hours at 80°C. After reaction completion (checked
by TLC), the reaction mixture was cooled, quenched with water
(20 mL), and extracted with EtOAc (3 × 20 mL). The extract was
washed with 20% NaCl solution (W/V), dried (Na2SO4) and
concentrated under reduced pressure. The residue was purified by
formation
5-arylindazolo[3,2-b]quinazolin-7(5H)-ones
5
(Scheme 3).

4
Tetrahedron
ACCEPTED MANUSCRIPT
column chromatography using petroleum ether/ethyl acetate
4.3.6.
2-chloro-5-(4-methoxyphenyl)indazolo[3,2-
b]quinazolin-7(5H)-one (5f). Yield 85% (319 mg); White solid;
M.p = 238–240 °C; IR (KBr, cm-1): 3046, 1681, 1627, 1466,
1060; 1H NMR (CDCl3, 500 MHz): δ = 3.84 (s, 3H), 6.97 (d, J =
8.0 Hz, 2H), 7.05 (d, J = 9.0 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H),
7.46 (t, J = 7.5 Hz, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.81 (t, J = 7.5
Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 8.25 (s, 1H), 8.32 (d, J = 7.5
Hz, 1H); 13C NMR (CDCl3, 125 MHz): δ =55.5, 113.7, 114.7,
117.5, 121.3, 125.0, 125.3, 125.6, 126.8, 126.9, 128.7, 129.8,
133.6, 134.0, 147.7, 156.7, 157.0, 157.3; Anal. Calcd for
C21H14ClN3O2: C, 67.12; H, 3.76; N, 11.18. Found: C, 66.87; H,
3.48; N, 10.93.
(4:1) as the eluent to produce the pure product 5a–l.
4.3.1.
5-phenylindazolo[3,2-b]quinazolin-7(5H)-one
(5a).
Yield 85% (264 mg); White solid; M.p = 246–248 °C (Lit. 230–
231 °C)24; IR (KBr, cm-1): 3052, 1672, 1623, 1469, 1054; H
1
NMR (CDCl3, 500 MHz): δ = 7.19 (d, J = 8.0 Hz, 1H), 7.36 (d, J
= 7.5 Hz, 2H), 7.4 (t, J = 7.5 Hz, 2H), 7.44 (m, 3H), 7.59 (t, J =
7.5 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.9 (d, J = 8.0 Hz, 1H),
8.27 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 7.5 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): δ = 112.3, 118.8, 119.7, 123.2, 124.2, 124.5,
125.3, 126.6, 126.9, 128.5, 129.4, 133.3, 133.9, 141.8, 148.1,
148.6, 149.0, 156.3; Anal. Calcd for C20H13N3O: C, 77.16; H,
4.21; N, 13.50. Found: C, 76.12; H, 4.17; N, 13.12.
4.3.7.
5-(4-fluorophenyl)indazolo[3,2-b]quinazolin-7(5H)-one
(5g). Yield 83% (273 mg); White solid; M.p = 213–215 °C (Lit.
197–198 °C)23; IR (KBr, cm-1): 3076, 1674, 1626, 1467, 1059; 1H
NMR (CDCl3, 500 MHz): δ = 7.15 (m, 3H), 7.37 (d, J = 8.0 Hz,
2H), 7.43 (t, J = 7.0 Hz, 1H), 7.46 (t, J = 7.0 Hz, 1H), 7.63 (t, J =
7.5 Hz, 1H), 7.82 (t, J = 7.5 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H),
8.29 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): δ = 112.3, 116.4, 116.5, 118.9, 123.5, 124.4,
125.5, 126.6, 127.0, 127.1, 130.3, 133.4, 134.0, 143.7, 148.6,
153.6, 155.3; Anal. Calcd for C20H12FN3O: C, 72.94; H, 3.67; N,
12.76. Found: C, 72.52; H, 3.44; N, 12.35.
4.3.2.
5-(p-tolyl)indazolo[3,2-b]quinazolin-7(5H)-one (5b).
Yield 87% (283 mg); White solid; M.p = 196–198 °C (Lit. 184–
185 °C)24; IR (KBr, cm-1): 3030, 1688, 1619, 1464, 1057; H
1
NMR (DMSO-d6, 500 MHz): δ = 2.36 (s, 3H), 7.27 (d, J = 7.5
Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.48
(t, J = 7.5 Hz, 1H), 7.52 (m, 2H), 7.73 (t, J = 7.5 Hz, 1H), 7.87
(d, J = 6.5 Hz, 1H), 8.16 (d, J = 7.5 Hz,1H), 8.23 (d, J = 7.5
Hz,1H); 13C NMR (DMSO-d6, 125 MHz): δ = 20.5, 112.5, 118.2,
119.4, 122.9, 123.7, 123.9, 124.4, 124.6, 125.1, 125.3, 125.8,
125.9, 129.8, 133.7, 133.9, 137.4, 139.2, 148.2, 148.6, 155.2;
Anal. Calcd for C21H15N3O: C, 77.52; H, 4.65; N, 12.91. Found:
C, 77.47; H, 4.52; N, 12.82.
4.3.8.
2-chloro-5-(4-fluorophenyl)indazolo[3,2-b]quinazolin-
7(5H)-one (5h). Yield 77% (281 mg); White solid; M.p = 222–
224 °C; IR (KBr, cm-1): 3056, 1683, 1625, 1465, 1057; H NMR
1
(CDCl3, 500 MHz): δ = 7.06 (d, J = 8.5 Hz, 1H), 7.17 (d, J = 7.5
Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.48 (t, J = 7.5 Hz, 1H), 7.57
(d, J = 8.5 Hz, 1H), 7.82 (t, J = 7.5 Hz, 1H), 7.89 (d, J = 8.0 Hz,
1H), 8.26 (s, 1H), 8.31 (d, J = 8.0 Hz, 1H);13C NMR (CDCl3, 125
MHz): δ = 113.6, 116.5, 116.7, 125.3, 125.4, 125.8, 125.8,
127.0, 127.1, 127.2, 130.9, 133.7, 134.3, 134.3, 136.0, 143.9,
153.1, 155.3; Anal. Calcd for C20H11ClFN3O: C, 66.04; H, 3.05;
N, 11.55. Found: C, 65.72; H, 2.87; N, 11.23.
4.3.3.
5-(4-methoxyphenyl)indazolo[3,2-b]quinazolin-7(5H)-
one(5c). Yield 88% (301 mg); White solid; M.p = 216–218 °C
(Lit. 209–210 °C)23; IR (KBr, cm-1): 3053, 1674, 1624, 1468,
1055; 1H NMR (CDCl3, 500 MHz): δ = 3.84 (s, 3H), 6.96 (d, J =
8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 1H), 7.3 (d, J = 8.0 Hz, 2H),
7.39 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 7.59 (t, J = 7.5
Hz, 1H), 7.79 (t, J = 7.5 Hz, 1H), 7.89 (d, J = 7.5 Hz, 1H), 8.27
(d, J = 7.5 Hz,1H), 8.32 (d, J = 7.5 Hz, 1H); 13C NMR (CDCl3,
125 MHz): δ = 55.5, 112.4, 114.5, 118.6, 119.8, 123.1, 124.0,
125.2, 126.6, 127.0, 133.2, 133.8, 134.4, 148.0, 148.6, 149.5,
156.4, 159.6; Anal. Calcd for C21H15N3O2: C, 73.89; H, 4.43; N,
12.31. Found: C, 73.68; H, 4.22; N, 12.13.
4.3.9.
5-(4-bromophenyl)-2-chloroindazolo[3,2-b]quinazolin-
7(5H)-one (5i). Yield 80% (340 mg); White solid; M.p = 244–
1
246 °C; IR (KBr, cm-1): 3061, 1678, 1629, 1465, 1052; H NMR
(DMSO-d6, 500 MHz): δ = 7.39 (d, J = 9.0 Hz, 1H), 7.49 (d, J =
8.0 Hz, 2H), 7.55 (t, J = 7.5 Hz, 1H), 7.68 (d, J = 8.0 Hz, 2H),
7.78 (d, J = 8.5 Hz, 1H), 7.89 (t, J = 7.5 Hz, 1H), 7.93 (d, J = 8.0
Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.27 (s, 1H);13C NMR (CDCl3,
125 MHz): δ = 114.0, 120.8, 122.2, 124.3, 124.6, 124.7, 125.6,
126.0, 126.0, 126.4, 128.9, 132.2, 133.7, 140.4, 146.4, 147.9,
155.5; Anal. Calcd for C20H11BrClN3O: C, 56.56; H, 2.61; N,
9.89. Found: C, 56.31; H, 2.42; N, 9.48.
4.3.4.
2-chloro-5-phenylindazolo[3,2-b]quinazolin-7(5H)-one
(5d). Yield 83% (287 mg); White solid; M.p = 241–243 °C (Lit.
272–273 °C)22; IR (KBr, cm-1): 3184, 1679, 1627, 1465, 1053; 1H
NMR (CDCl3, 500 MHz): δ = 7.12 (d, J = 8.5 Hz, 1H), 7.35 (d, J
= 7.5 Hz, 2H), 7.42 (t, J = 7.0 Hz, 1H), 7.47 (m, 3H), 7.55 (d, J =
8.5 Hz, 1H), 7.82 (t, J = 7.5 Hz, 1H), 7.9 (d, J = 8.0 Hz, 1H),
8.26 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 7.5 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): δ =113.6, 119.9, 120.2, 122.8, 124.5, 125.7,
126.7, 127.1, 128.8, 129.6, 130.0, 133.6, 134.1, 141.4, 147.1,
147.7, 148.4, 148.9, 155.2, 156.2; Anal. Calcd for C20H12ClN3O:
C, 69.47; H, 3.50; N, 12.15. Found: C, 69.25; H, 3.21; N, 11.94.
4.3.10. 5-(4-methoxyphenyl)indazolo[3,2-b]quinazolin-7(5H)-
one (5j). Yield 83%(283 mg); White solid; M.p = 220–224 °C;
IR (KBr, cm-1): 3048, 1680, 1616, 1468, 1050; 1H NMR (DMSO-
d6, 500 MHz): δ = 3.77 (s, 3H), 6.78 (d, J = 7.0 Hz, 1H), 6.98 (d,
J = 7.5 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H),
7.40 (d, J = 7.0 Hz, 1H), 7.46 (d, J = 7.5 Hz, 1H), 7.53-7.77 (m,
5H-ph), 8.14 (d, J = 7.5 Hz, 1H); 13C NMR (DMSO-d6, 125
MHz): δ = 56.4, 111.9, 115.2, 115.6, 115.7, 116.1, 117.7, 121.6,
126.1, 128.0, 128.2, 129.0, 133.5, 140.3, 146.0, 147.1, 154.3,
163.4; Anal. Calcd for C21H15N3O2: C, 73.89; H, 4.43; N, 12.31.
Found: C, 74.09; H, 4.66; N, 12.48.
4.3.5.
2-chloro-5-(p-tolyl)indazolo[3,2-b]quinazolin-7(5H)-
one (5e). Yield 86% (309 mg); White solid; M.p = 226–228 °C;
IR (KBr, cm-1): 3020, 1682, 1626, 1466, 1054; 1H NMR (CDCl3,
500 MHz): δ =2.40 (s, 3H), 7.09 (d, J = 8.5 Hz, 1H), 7.23 (d, J =
7.5 Hz, 2H), 7.27 (d, J = 9.0 Hz, 2H), 7.46 (t, J = 7.5 Hz, 1H),
7.54 (d, J = 9.0 Hz, 1H), 7.81 (t, J = 7.5 Hz, 1H), 7.89 (d, J = 8.0
Hz, 1H), 8.25 (s, 1H), 8.32 (d, J = 8.0 Hz, 1H); 13C NMR
(CDCl3, 125 MHz): δ =21.2, 113.6, 119.9, 122.7, 124.7, 125.6,
126.7, 126.7, 127.0, 127.1, 130.2, 133.5, 134.0, 138.8, 139.0,
147.6, 148.6, 156.3; Anal. Calcd for C21H14ClN3O: C, 70.10; H,
3.92; N, 11.68. Found: C, 69.91; H, 3.58; N, 11.35.
4.3.11. 5-(4-bromophenyl)-4-methoxyindazolo[3,2-
b]quinazolin-7(5H)-one (5k). Yield 78%(328 mg); White solid;
M.p = 215–219 °C; IR (KBr, cm-1): 3068, 1674, 1625, 1468,
1
1068; H NMR (DMSO-d6, 500 MHz): δ = 3.82 (s, 3H), 7.01 (t,
J = 7.5 Hz, 1H), 7.43 (d, J = 7.5 Hz, 2H), 7.52 (t, J = 8.0 Hz,

5
10. Li, H.; Huang, R.; Qiu, D.; Yang, Z.; Liu, X.; Ma, J.; Ma, Z. Prog.
1H), 7.70 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 7.5 Hz, 2H), 7.84 (d, J
= 7.0 Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 8.01 (d, J = 7.5 Hz, 1H),
8.30 (d, J = 7.0 Hz, 1H); 13C NMR (DMSO-d6, 125 MHz): δ =
56.7, 112.0, 113.8, 114.0, 115.0, 117.9, 118.9, 120.6, 126.2,
126.9, 128.0, 129.2, 131.0, 133.7, 136.7, 146.7, 154.2, 162.8;
Anal. Calcd for C21H14BrN3O2: C, 60.02; H, 3.36; N, 10.00.
Found: C, 6.28; H, 3.54; N, 10.18.
ACCEPTED MANUSCRIPT
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4.3.12. 4-methoxy-5-(4-methoxyphenyl)indazolo[3,2-
b]quinazolin-7(5H)-one (5l). Yield 69%(256 mg); White solid;
M.p = 206-212 °C; IR (KBr, cm-1): 3048, 1665, 1625, 1455,
1066; 1H NMR (DMSO-d6, 500 MHz): δ = 3.71 (s, 3H), 3.84 (s,
3H), 6.72 (t, J = 7.5 Hz, 1H), 7.00 (dd, J1= 8.5 Hz, J2= 3.0 Hz,
2H), 7.05 (d, J = 7.5 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.21-7.24
(m, 4H), 7.88 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 7.5 Hz, 1H); 13C
NMR (DMSO-d6, 125 MHz): δ = 55.3, 109.9, 113.9, 114.6,
117.4, 117.8, 122.1, 127.6, 128.2, 128.8, 132.2, 133.6, 134.6,
146.7, 149.6, 149.9, 154.2, 158.5, 162.8; Anal. Calcd for
C22H17N3O3: C, 71.15; H, 4.61; N, 11.31. Found: C, 71.34; H,
4.83; N, 11.60.
Acknowledgment
This research was supported by a grant from Iran National
Science Foundation (INSF).
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