Copper-catalyzed intramolecular C-N bond formation reaction of 3-amino-2-(2-bromophenyl)dihydroquinazolinones: Synthesis of indazolo[3,2-b]quinazolinones

Article abstract of DOI:10.1016/j.tet.2013.09.012

A copper-catalyzed intramolecular C-N bond formation reaction of 3-amino-2-(2-bromophenyl)dihydroquinazolinones has been developed for the synthesis of indazolo[3,2-b]quinazolinones in moderate to good yields. The structure of the newly synthesized indazo

Full text of DOI:10.1016/j.tet.2013.09.012

Tetrahedron 69 (2013) 9852e9856
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper-catalyzed intramolecular CeN bond formation reaction
of 3-amino-2-(2-bromophenyl)dihydroquinazolinones: synthesis of
indazolo[3,2-b]quinazolinones
,c,
Weiguang Yang a, Leping Ye b, Dayun Huang a, Miaochang Liu a, Jinchang Ding a
*
,
,
a
Jiuxi Chen a , Huayue Wu
*
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, PR China
b The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, PR China
c Wenzhou Vocational and Technical College, Wenzhou 325035, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 May 2013
Received in revised form 21 August 2013
Accepted 2 September 2013
Available online 19 September 2013
A copper-catalyzed intramolecular CeN bond formation reaction of 3-amino-2-(2-bromophenyl)dihy-
droquinazolinones has been developed for the synthesis of indazolo[3,2-b]quinazolinones in moderate to
good yields. The structure of the newly synthesized indazolo[3,2-b]quinazolinones was unambiguously
confirmed by X-ray single-crystal diffraction analysis. Moreover, a possible mechanism for the formation
of indazolo[3,2-b]quinazolinones is discussed.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Copper
Indazolo[3,2-b]quinazolinones
Intramolecular CeN bond formation
3-Amino-2-(2-bromophenyl)
dihydroquinazolinones
1. Introduction
the palladium-8 or copper-catalyzed9 cascade reaction have been
developed leading to indazolo[3,2-b]quinazolinones. Thus, the
Nitrogen-containing polyheterocycles are present in a wide
variety of bioactive natural products and biological molecules
that may be good drug candidates.1 Specifically, quinazolinone-
based polyheterocycles represent a medicinally and pharmaceu-
tically important class of heterocyclic motifs that are found as the
core structural skeletons in a variety of natural products, such as
luotonin A,2 circumdatins,3 rutaecarpine,4 deoxyvasicinone,5 and
tryptanthrin,6 etc. Therefore, the development of novel methods
for the synthesis of these compounds is important in the field of
synthetic organic and pharmaceutical chemistry. In the past few
years, copper-catalyzed annulation reactions have provided
attractive and valuable routes for the construction of nitrogen-
containing heterocycles or polyheterocycles.7 However, the syn-
thesis of combined quinazolinone and indazole skeletons (Fig. 1),
such as indazolo[3,2-b]quinazolinones are still rarely been in-
vestigated. To the best of our knowledge, only two examples of
development of new synthetic strategies for the preparation of
indazolo[3,2-b]quinazolinones still remain in great demand.
Fig. 1. Structure of indazole-fused quinazolinone skeleton.
This work forms part of the continuing efforts in our laboratory
toward the development of new methods for copper-catalyzed
chemistry10 and the synthesis of quinazolinone derivatives.11
Herein, we report a new method for the synthesis of indazolo
[3,2-b]quinazolinones (2) by copper-catalyzed intramolecular CeN
bond formation reaction of 3-amino-2-(2-bromophenyl)dihy-
droquinazolinones (1) (Scheme 1).
* Corresponding authors. Tel./fax: þ86 57788368280; e-mail addresses: dingjc@
wzu.edu.cn (J. Ding), jiuxichen@wzu.edu.cn (J. Chen).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.012

W. Yang et al. / Tetrahedron 69 (2013) 9852e9856
9853
toluene, THF, and EtOH (Table 1, entries 3, 14e19). According to the
literature,12 one likely reason was that DMSO could act as a mild
oxidant. The choice of base was also vital to the success of the
catalytic reaction. Screening revealed that the use of Cs2CO3 as base
achieved the best result. Other bases, including K2CO3, Na2CO3,
Rb2CO3, NaOH, CsF, KF, NaOAc, and Et3N were less efficient (Table 1,
entries 20e27). Considering ligands always play important roles in
metal-catalyzed chemistry, we were pleased to discover that only
Scheme 1. Synthesis of indazolo[3,2-b]quinazolinones.
when the model reaction was performed in the presence of L-pro-
line13 as the ligand did the yield dramatically increase to 87% yield
(Table 1, entry 30). Other ligands, such as 2-(methylamino)acetic
acid and 2-(dimethylamino)acetic acid, were less efficient (Table 1,
entries 31e32).
With the optimized reaction conditions in hand, intramolecular
CeN bond formation reaction was then expanded to various 2-(2-
bromophenyl)-3-(arylamino)dihydroquinazolinones (Table 2). As
shown in Table 2, the electronic properties of the groups on the
phenyl ring of the 2-(2-bromophenyl)-3-(arylamino)dihy-
droquinazolinones (1) had some effect on the reaction.
2. Results and discussion
In initial experiments, 2-(2-bromophenyl)-3-(phenylamino)
dihydroquinazolinone (1a) was chosen as the substrate to screen the
optimal reaction conditions (Table 1). As shown in Table 1, we were
pleased to discover that the desired product 5-phenylindazolo[3,2-
b]quinazolinone (2a) was isolated in 33% yield when CuCl was used
in combination with Cs2CO3 in DMSO (Table 1, entry 1). Encouraged
by this promising result, we further adjusted reaction parameters
including copper catalysts, bases, and solvents.
Table 1
Screening for optimal reaction conditionsa
Table 2
Substrate scope for the synthesis of indazolo[3,2-b]quinazolinonesa
Entry
Cu source
Base
Solvent
Yield (%)b
O
N
CH3
O
N
O
N
Ph
N
Ph
N
Ph
N
1
2
3
4
5
6
7
8
CuCl
CuBr
CuI
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
Na2CO3
Rb2CO3
NaOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
33
38
52
31
29
28
32
30
29
33
24
15
30
27
26
27
22
23
22
45
30
21
Trace
43
28
36
46
82c
81c
87c
67d
64e
H3C
N
N
N
Cu2O
CuOAc
CuSCN
CuF2
CuCl2
CuBr2
Cu(OAc)2
CuSO4
Cu(OTf)2
Cu(acac)2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuBr
CuCl
CuCl
CuCl
2a (87%)
2b (83%)
2c (84 %)
O
O
N
N
O
Ph
N
Ph
N
Ph
N
N
N
9
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
F
N
CH3
Cl
2d (76%)
2e (65%)
2f (71%)
O
Ph
N
O
O
Ph
Ph
N
N
Dioxane
CH3CN
Toluene
THF
N
N
N
N
OCH3
OCH3
N
N
Cl
Br
2g (61%, 77%b)
2h (80%)
2i (75%)
EtOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3
CH3
O
O
O
CH3
CsF
KF
NaOAc
Et3N
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
N
N
N
N
N
N
N
N
N
2j (82%)
OCH3
2k (75 %)
2l (56%)
F
CF3
O
O
O
N
N
N
N
N
N
a
Reaction conditions: 1a (0.2 mmol), Cu source (0.04 mmol), base (0.6 mmol),
N
N
N
undried solvent (2 mL), N2, 90 ꢀC, 12 h.
b
Isolated yield.
2m (88%)
2n (60 %)
2o (51%)
c
L-Proline (0.08 mmol) was used as the ligand.
d
e
2-(Methylamino)acetic acid (0.08 mmol) was used as the ligand.
2-(Dimethylamino)acetic acid (0.08 mmol) was used as the ligand.
a
Reaction conditions: 1 (0.2 mmol), CuCl (0.04 mmol), L-proline (0.08
mmol), Cs2CO3 (0.6 mmol), DMSO (2 mL), N2, 90 oC, 12 h. Isolated yield
was given in parenthesis.
Among the copper sources used (e.g., CuI, CuBr, CuCl, Cu2O,
b For 36 h.
CuOAc, CuSCN, CuF2, CuCl2, CuBr2, Cu(OAc)2, CuSO4, Cu(OTf)2, and
Cu(acac)2), CuI exhibited the highest catalytic reactivity in 52% yield
(Table 1, entries 1e13). Subsequently, we studied the solvent effect
and found that DMSO was superior to DMF, dioxane, CH3CN,
In general, substrates bearing electron-donating substituents
(R1) at the ‘right’ side phenyl part produced the corresponding

9854
W. Yang et al. / Tetrahedron 69 (2013) 9852e9856
products (Table 2, 2b and 2c) in slightly higher yields than those
analogs bearing electron-withdrawing substituents (Table 2, 2d
and 2e). On the other hand, it was observed that the reactivity
pattern of the ‘left’ bromo-containing aryl part was opposite to that
of the ‘right’ phenyl side, and electron-withdrawing substituents on
that portion facilitate the cyclization (Table 2, 2fei). For example,
moderate yield was observed when substrate 1g bearing two
methoxy groups was used (Table 2, 2g). However, prolonging re-
action time to 36 h resulted in 77% yield of 2g. Finally, we also
examined the electronic properties of amino-containing aryl part of
substrates 1 (Table 2, 2jeo). Substrates having an electron-donating
substituent on the aryl group (Table 2, 2j, 2k and 2m) afforded the
corresponding products in slightly higher yields than those analogs
bearing electron-withdrawing substituents (Table 2, 2n and 2o).
For example, substrates 1m and 1o, bearing a methoxy or tri-
fluoromethyl group, give the corresponding products in 88% and
51% yields, respectively. On the other hand, steric effects of sub-
stituents had an obvious impact on the yields of the reaction. For
example, substrate bearing a para-, meta-, and ortho-methyl group
was examined, 82% yield of 2j and 75% yield of 2k were isolated,
while the yield of 2l was decreased to 56%.
To elucidate the mechanism, some control experiments were
carried out under the standard conditions as shown in Scheme 3.
2-(2-Bromophenyl)-3-(phenylamino)quinazolinone (3) was pre-
pared from dehydrogenation of 2-(2-bromophenyl)-3-(phenyl-
amino)dihydroquinazolinone (1a) in the presence of DDQ (Scheme
3a). Under the standard conditions, the desired product 2a in 88%
yield could be obtained smoothly with good results by intra-
molecular CeN bond formation reaction of compound 3 (Scheme
3b). However, intramolecular cyclization reaction of 2-(2-
bromophenyl)-3-(phenylamino)dihydroquinazolinone (1a) failed
to deliver the corresponding dihydroindazolo[3,2-b]quinazolinone
(4) under different reaction conditions (Scheme 3c). There is
no detection of compound 4 by GCeMS analysis. This result
confirmed that compound
3 is a key intermediate in this
transformation.
To confirm the structures of the newly synthesized products,
single crystals of 2a was prepared as a representative example, and
its structure was unambiguously confirmed by X-ray single-crystal
diffraction analysis (Fig. 2).14
Scheme 3. Control experiments.
A possible formation mechanism of indazolo[3,2-b]quinazoli-
none derivatives was proposed in Scheme 4. First, coordination of
L-proline with CuCl in the presence of Cs2CO3 forms CuL
(I). Dehydrogenation of 2-(2-bromophenyl)-3-(arylamino)dihy-
droquinazolinone (1) affords 2-(2-bromophenyl)-3-(phenylamino)
quinazolinone (3) in DMSO, and treatment of compound 3 with CuL
(I) gives complex II, in which one nitrogen of the hydrazine group
may coordinate with the copper center to provide additional sta-
bilization. Oxidation addition of II provides coordinate III, which
undergoes reductive elimination to give the desired product 2 re-
leasing the copper catalyst.
Fig. 2. X-ray analysis of 5-phenylindazolo[3,2-b]quinazolinone (2a).
Furthermore, we investigated a cascade reaction of 2-amino-N0-
phenylbenzohydrazide with 2-bromobenzaldehyde as a represen-
tative example is shown in Scheme 2. Under the optimized reaction
conditions, the corresponding desired product (2a) was obtained in
39% yield.
Scheme 2. Cascade reaction of 2-amino-N0-phenylbenzohydrazide with 2-
bromobenzaldehyde.
Scheme 4. Possible formation mechanism of 2.

W. Yang et al. / Tetrahedron 69 (2013) 9852e9856
9855
3. Conclusion
HRMS (ESI) calcd for C20H12N3OCl [MþH]þ: 347.0775, found
346.9736.
In summary, we have developed a new protocol for the syn-
thesis of indazolo[3,2-b]quinazolinones in moderate to good yields
by copper-catalyzed intramolecular CeN bond formation reaction
of 3-amino-2-(2-bromophenyl) dihydroquinazolinones. Further
efforts to expand the scope of the chemistry are currently un-
derway in our laboratories.
4.2.4. 10-Fluoro-5-phenylindazolo[3,2-b]quinazolinone (2e). Solid;
mp 214e215 ꢀC. 1H NMR (DMSO-d6, 500 MHz):
d
7.35e7.52 (m, 8H),
7.63e7.67 (m, 1H), 7.75e7.78 (m, 1H), 8.20e8.24 (m, 2H); 13C NMR
(DMSO-d6, 500 MHz): 111.4, 111.5, 112.3, 113.9, 114.1, 116.4, 117.9,
d
123.0, 123.8, 124.7, 127.9, 128.9, 129.0, 129.2, 134.1, 141.3, 148.4,
148.9, 150.3, 150.4, 164.5, 166.5. IR (KBr): 3169, 2979, 1726, 1437,
1081 cmꢁ1. HRMS (ESI) calcd for C20H12FN3O [MþH]þ: 330.1037,
found 330.1045.
4. Experimental section
4.1. General
4.2.5. 3-Methyl-5-phenylindazolo[3,2-b]quinazolinone (2f). Solid;
mp 248e250 ꢀC. 1H NMR (CDCl3, 500 MHz):
d 2.46 (s, 3H), 6.98 (s,
Chemicals and solvents were either purchased or purified by
standard techniques. Melting points were uncorrected and
recorded on Digital Melting Point Apparatus WRS-1B. IR
spectra were recorded on an AVATAR 370 FI-Infrared Spectro-
photometer. NMR spectroscopy was performed on both a Bruck
1H), 7.24 (d, J¼7.5 Hz, 1H), 7.35 (d, J¼7.5 Hz, 2H), 7.41e7.50 (m, 4H),
7.80 (t, J¼7.5 Hz, 1H), 7.89 (d, J¼8.5 Hz, 1H), 8.15 (d, J¼8.5 Hz, 1H),
8.32 (d, J¼8 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d 22.3, 112.2, 116.3,
119.6, 122.8, 124.5, 125.1, 126.0, 126.6, 126.8, 128.4, 129.4, 133.9,
141.9, 144.7, 148.2, 148.7, 149.5, 156.4. IR (KBr): 3171, 2981, 1730,
1436, 1081 cmꢁ1. HRMS (ESI) calcd for C21H15N3O [MþH]þ:
327.1321, found 327.1296.
spectrometer operating at 500 MHz (1H NMR) and 125 MHz (13
C
NMR). TMS (tetramethylsilane) was used as an internal
standard and CDCl3 or DMSO-d6 was used as the solvent. IR
spectra were obtained using a Nicolet iS10 spectrophotometer
(Thermo Scientific). High-resolution mass spectra (HRMS)
were recorded on Bruker micro TOF QII ESI-Q-TOF mass spec-
trometer. Column chromatography was performed using Al2O3
(200e300 mesh).
4.2.6. 2,3-Dimethoxy-5-phenylindazolo[3,2-b]quinazolinone
(2g). Solid; mp 223e225 ꢀC. 1H NMR (DMSO-d6, 500 MHz):
d 3.88
(s, 3H), 4.02 (s, 3H), 6.56 (s, 1H), 7.33e7.50 (m, 7H), 7.61 (s, 1H),
7.75e7.80 (m, 1H), 7.85 (d, J¼12.5 Hz, 1H), 8.29 (d, J¼8 Hz, 1H); 13
C
NMR (DMSO-d6, 500 MHz):
d 56.10, 56.13, 95.0, 102.8, 109.4, 118.5,
123.5, 124.5, 125.9, 128.4, 127.7, 129.2, 133.9, 141.9, 144.4, 147.7,
148.0, 148.4, 154.8, 155.2. IR (KBr): 3169, 2979, 1727, 1437,
1082 cmꢁ1. HRMS (ESI) calcd for C22H17N3O3 [MþH]þ: 372.1343,
found 372.1351.
4.2. General procedure for the synthesis of indazolo[3,2-b]
quinazolinones
ToaSchlenkreactiontubewasadded3-amino-2-(2-bromophenyl)
dihydroquinazolinones (1) (0.2 mmol), CuCl (0.04 mmol), Cs2CO3
4.2.7. 2-Chloro-5-phenylindazolo[3,2-b]quinazolinone (2h). Solid;
(0.6 mmol),
L-proline (0.08 mmol), and DMSO (2 mL). The reaction
mp 255e256 ꢀC. 1H NMR (DMSO-d6, 500 MHz):
d
7.13 (d, J¼8.5 Hz,
1H), 7.34e7.56 (m, 7H), 7.82e7.90 (m, 2H), 8.26e8.33 (m, 2H); 13C
NMR (DMSO-d6, 500 MHz): 113.6, 119.8, 120.1, 122.7, 124.5, 125.7,
tube was placed under high vacuum, backfilled with nitrogen and
repeated three times. The mixture was stirred vigorously at 90 ꢀC for
12 h. After the completion of the reaction, as monitored by TLC, the
solvent was removed under reduced pressure, and the resulting res-
idue was purified by column chromatography to provide the desired
product 2.
d
126.6, 127.1, 128.8, 129.6, 130.0, 133.6, 134.1, 141.4, 147.0, 147.3, 148.4,
156.1. IR (KBr): 3171, 2979, 1728, 1439, 1082 cmꢁ1. HRMS (ESI) calcd
for C20H12ClN3O [MþH]þ: 346.0742, found 346.0765.
4.2.8. 2-Bromo-5-phenylindazolo[3,2-b]quinazolinone (2i). Solid;
4.2.1. 8-Methyl-5-phenylindazolo[3,2-b]quinazolinone (2b). Solid;
mp 244e246 ꢀC. 1H NMR (CDCl3, 500 MHz):
d
7.07 (d, J¼8.5 Hz, 1H),
mp 232e233 ꢀC. 1H NMR (CDCl3, 500 MHz):
d
2.85 (s, 3H), 7.20 (d,
7.34e7.48 (m, 6H), 7.68e7.89 (m, 3H), 8.32 (d, J¼7 Hz, 1H), 8.43 (d,
J¼13.5 Hz, 2H), 7.33e7.42 (m, 4H), 7.47 (t, J¼12.0 Hz, 2H),
J¼2 Hz, 1H); 13C NMR (CDCl3, 125 MHz):
d 113.9, 117.1, 119.8, 120.6,
124.6,125.7,125.8,126.7,127.1,128.8,129.6,124.1,136.2,141.3,146.8,
7.57e7.66 (m, 2H), 7.75 (d, J¼13.5 Hz, 1H), 8.25 (d, J¼13.5 Hz, 1H);
13C NMR (CDCl3, 125 MHz):
d
23.2, 112.3, 118.3, 118.8, 123.1, 123.8,
147.7, 148.4, 156.1. IR (KBr): 3167, 2978, 1728, 1435, 1081 cmꢁ1
.
124.2, 125.2, 128.0, 128.2, 129.5, 133.0, 133.2, 141.3, 142.2, 148.1,
HRMS (ESI) calcd for C20H12BrN3O [MþH]þ: 390.0237, 392.0217,
149.3, 150.3, 157.0. IR (KBr): 3167, 2977, 1728, 1437, 1082 cmꢁ1
.
found 390.0250, 392.0242.
HRMS (ESI) calcd for
326.1279.
C
21H15N3O [MþH]þ: 326.1288, found
4.2.9. 5-p-Tolylindazolo[3,2-b]quinazolinone
(2j). Solid;
mp
184e185 ꢀC. 1H NMR (CDCl3, 500 MHz):
d 2.39 (s, 3H), 7.15 (d,
4.2.2. 9-Methyl-5-phenylindazolo[3,2-b]quinazolinone (2c). Solid;
mp 236e238 ꢀC. 1H NMR (CDCl3, 500 MHz):
2.49 (s, 3H), 7.21 (d,
J¼10.5 Hz, 1H), 7.23e7.27 (m, 4H), 7.40 (t, J¼7.5 Hz, 1H), 7.45 (t,
J¼8 Hz, 1H), 7.61 (t, J¼6 Hz, 1H), 7.81 (t, J¼6 Hz, 1H), 7.90 (d, J¼9 Hz,
1H), 8.28 (d, J¼9 Hz, 1H), 8.33 (d, J¼8.5 Hz, 1H); 13C NMR (CDCl3,
d
J¼13.5 Hz, 1H), 7.33e7.49 (m, 6H), 7.58e7.65 (m, 2H), 7.82 (d,
J¼13.5 Hz, 1H), 8.11 (s, 1H), 8.27 (d, J¼13 Hz, 1H); 13C NMR (CDCl3,
125 MHz):
d 21.2, 99.9, 112.3, 119.8, 123.1, 124.1, 124.6, 125.2, 126.6,
125 MHz):
d
21.3, 122.3, 118.9, 119.5, 123.1, 124.2, 124.4, 125.9, 126.8,
126.9, 130.1, 133.2, 133.8, 138.6, 139.2, 148.1, 148.6, 149.2, 156.5. IR
128.4, 129.4, 133.1, 135.5, 135.6, 142.0, 146.6, 147.6, 149.0, 156.3. IR
(KBr): 3170, 2980, 1728, 1438, 1082 cmꢁ1. HRMS (ESI) calcd for
(KBr): 3166, 2975, 1729, 1437, 1084 cmꢁ1. HRMS (ESI) calcd for
C
21H15N3O [MþH]þ: 326.1288, found 326.1279.
C
21H12N3O [MþH]þ: 327.1321, found 327.1336.
4.2.10. 5-m-Tolylindazolo[3,2-b]quinazolinone
(2k). Solid;
mp
4.2.3. 11-Chloro-5-phenylindazolo[3,2-b]quinazolinone (2d). Solid;
mp 235e236 ꢀC. 1H NMR (CDCl3, 500 MHz):
7.19e7.51 (m, 9H),
7.62e7.67 (m, 1H), 7.89e7.90 (m, 1H), 8.23e8.41 (m, 2H); 13C
NMR (CDCl3, 125 MHz): 122.2, 118.6, 121.2, 123.8, 124.3, 124.6,
125.1, 125.6, 128.7, 129.5, 131.3, 133.7, 134.2, 141.3, 145.4, 148.5,
149.1, 155.8. IR (KBr): 3170, 2981, 1726, 1436, 1081 cmꢁ1
241e242 ꢀC. 1H NMR (CDCl3, 500 MHz):
d
2.37 (s, 3H), 7.1 (s, 1H),
d
7.17 (d, J¼8 Hz, 1H), 7.19e7.21 (m, 2H), 7.35 (t, J¼7.5 Hz, 1H), 7.41 (t,
J¼7.5 Hz, 1H), 7.46 (t, J¼7.5 Hz, 1H), 7.62 (t, J¼7.5 Hz, 1H), 7.82 (t,
J¼8 Hz, 1H), 7.91 (d, J¼8.5 Hz, 1H), 8.29 (d, J¼8 Hz, 1H), 8.34 (d,
d
J¼8 Hz, 1H); 13C NMR (DMSO-d6, 500 MHz):
d 21.7, 112.4, 119.3,
120.8, 122.8, 123.9, 124.5, 125.2, 125.9, 126.8, 128.2, 128.5, 129.0,
.

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W. Yang et al. / Tetrahedron 69 (2013) 9852e9856
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McInnes, C.; Griffiths, G.; Barnett, A. L.; Kontopidis, G.; Slawin, A. M. Z.; Jackson,
W.; Thomas, M.; Zheleva, D. I.; Wang, S.; Blake, D. G.; Westwood, N. J.; Fischer,
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12754.
133.7, 133.9, 139.0, 141.6, 147.8, 148.2, 148.5, 155.2. IR (KBr): 3173,
2978, 1728, 1437, 1081 cmꢁ1. HRMS (ESI) calcd for C21H15N3O
[MþH]þ: 326.1288, found 326.1283.
4.2.11. 5-o-Tolylindazolo[3,2-b]quinazolinone
221e223 ꢀC. 1H NMR (CDCl3, 500 MHz):
(2l). Solid;
2.47 (s, 3H), 6.95 (t,
mp
d
2. (a) Cagir, A.; Jones, S. H.; Gao, R.; Eisenhauer, B. M. J. Am. Chem. Soc. 2003, 125,
13628; (b) Tseng, M.-C.; Chu, Y.-W.; Tsai, H.-P.; Lin, C.-M.; Hwang, J.; Chu, Y.-H.
Org. Lett. 2011, 13, 920; (c) Servais, A.; Azzouz, M.; Lopes, D.; Courillon, C.;
Malacria, M. Angew. Chem., Int. Ed. 2007, 46, 576.
J¼8.5 Hz, 2H), 7.20 (t, J¼8 Hz, 1H), 7.35 (t, J¼7.5 Hz, 1H), 7.38e7.45
(m, 3H), 7.61 (t, J¼7.5 Hz, 1H), 7.81 (t, J¼8 Hz, 1H), 7.91 (d, J¼8.5 Hz,
1H), 8.31 (t, J¼8 Hz, 2H); 13C NMR (CDCl3, 125 MHz):
d 18.0, 111.7,
ꢀ
3. (a) Dai, J.-R.; Carte, B. K.; Sidebottom, P. J.; Yew, A. L. S.; Ng, S.-B.; Huang, Y.;
118.3,119.6,123.2,123.6,125.1, 125.3,126.5,126.9,127.1, 129.3,131.3,
133.4, 133.8, 136.5, 139.9, 147.8, 148.4, 148.6, 156.2. IR (KBr): 3171,
2979, 1727, 1439, 1082 cmꢁ1. HRMS (ESI) calcd for C21H15N3O
[MþH]þ: 326.1288, found 326.1307.
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J.; Beifuss, U. Chem.dEur. J. 2012, 18, 8882.
4.2.12. 5-(4-(Trifluoromethyl)phenyl)indazolo[3,2-b]quinazolinone
(2o). Solid; mp 210e212 ꢀC. 1H NMR (DMSO-d6, 500 MHz):
d 7.49
(d, J¼8.5 Hz, 1H), 7.51e7.56 (m, 2H), 7.74e7.78 (m, 3H), 7.86 (d,
J¼8.5 Hz, 2H), 7.89e7.91 (m, 2H), 8.18 (d, J¼8.5 Hz, 1H), 8.26 (d,
J¼8.5 Hz, 1H); 13C NMR (DMSO-d6, 500 MHz):
d 111.7, 118.1, 118.8,
122.6, 123.7, 124.5, 124.6, 125.0, 125.5, 125.8, 125.9, 126.4, 127.2,
127.4, 133.4, 133.7, 144.3, 146.9, 147.2, 147.7, 154.8. IR (KBr): 3172,
2976, 1727, 1438, 1081 cmꢁ1. HRMS (ESI) calcd for C21H12F3N3O
[MþH]þ: 380.1005, found 380.1012.
8. Kumar, K. S.; Kumar, P. M.; Rao, V. S.; Jafar, A. A.; Meda, C. L. T.; Kapavarapu, R.;
Parsac, K. V. L.; Pal, M. Org. Biomol. Chem. 2012, 10, 3098.
9. During the preparation of this manuscript, copper-catalyzed synthesis of 5-
arylindazolo[3,2-b]quinazolin-7(5H)-one via cascade reaction of 2-amino-
N0-arylbenzohydrazide and o-halogenated benzaldehyde was reported, see:
Chen, D.-S.; Dou, G.-L.; Li, Y.-L.; Liu, Y.; Wang, X.-S. J. Org. Chem. 2013, 78,
5700.
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Synlett 2011, 1626; (d) Peng, Y.; Chen, J.; Ding, J.; Liu, M.; Gao, W.; Wu, H.
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Acknowledgements
We thank the National Natural Science Foundation of China
(Nos. 21102105 and 21172175) and Natural Science Foundation of
Zhejiang Province (No. LY12B02011) for financial support.
Supplementary data
11. (a) Chen, J.; Su, W.; Wu, H.; Liu, M.; Jin, C. Green Chem. 2007, 9, 972; (b) Chen, J.;
Wu, D.; He, F.; Liu, M.; Wu, H.; Ding, J.; Su, W. Tetrahedron Lett. 2008, 49, 3814.
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M.; Rascher, L.; Chiang, Y. H.; Oroshnik, W. Tetrahedron Lett. 1968, 9, 6201; (b)
Tsuji, T. Tetrahedron Lett. 1966, 7, 2413; (c) Deligeorgiev, T. C. Dyes Pigm. 1990,
12, 243.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.09.012.
References and notes
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14. CCDC-939946 contains the supplementary crystallographic data for compound
2a, which is available free of charge via www.ccdc.cam.ac.uk/data_request/cif.
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