Cascade synthesis of azoquinazolinones by Cu(I)-catalyzed C-N coupling/C-H activation/C-N formation reactions under O2

Article abstract of DOI:10.1016/j.tet.2013.05.071

A 'one-pot' method has been developed for the synthesis of azoquinazolinones from substituted 2-halo-benzamides and different N-heterocycles via Cu(I)-catalyzed C-N coupling/C-H activation/C-N formation process under O₂. A number of azoquinazolinones containing different azole rings and substituents were obtained in good yields.

Full text of DOI:10.1016/j.tet.2013.05.071

Tetrahedron 69 (2013) 6461e6467
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cascade synthesis of azoquinazolinones by Cu(I)-catalyzed CeN
coupling/CeH activation/CeN formation reactions under O2
,
b
,
a
b
a
a
Dingben Chen a , Qiufang Chen , Miaochang Liu , Shuangqun Dai , Ling Huang ,
*
Jianguo Yang a, Weiliang Bao c
,
*
a College of Pharmaceutical and Chemical Engineering, Taizhou University, Linhai, Zhejiang 317000, PR China
b Faculty of Chemistry & Material Engineering, Wenzhou University, Wenzhou, Zhejiang 325027 PR China
c Department of Chemistry, Xi Xi Campus, Zhejiang University, Hangzhou, Zhejiang 310028, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A ‘one-pot’ method has been developed for the synthesis of azoquinazolinones from substituted 2-halo-
benzamides and different N-heterocycles via Cu(I)-catalyzed CeN coupling/CeH activation/CeN for-
mation process under O2. A number of azoquinazolinones containing different azole rings and sub-
stituents were obtained in good yields.
Received 1 February 2013
Received in revised form 13 May 2013
Accepted 20 May 2013
Available online 23 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Azoquinazolinones
Copper-catalyzed
Cascade reaction
CeN coupling
CeH Amination
1. Introduction
O
R
N
O
O
N
N
Quinazolinone derivatives have been widely found in nu-
merous biologically active compounds and drug molecules.1
Azoquinazolinone was a combined structure of quinazolinone
and azole, such as imidazole, triazole, pyrazole, benzimidazole,
theophylline, and so on. Azoquinazolinones also exhibit various
biological and medicinal functions.2 For example, as shown in
Fig. 1, imidazole[1,2-a]quinazolinone-7-carboxamide (1) was
disclosed as matrix metalloproteinase inhibitor. 4-Phenyl-1,2,4-
triazolo[4,3-a]quinazolin-5(4H)-one (2) was a class of H1-anti-
histaminic agents. Pyrazolo[1,5-a]quinazolinone-3-carboxylic
acid derivatives (3) could be used as anti-inflammatory, anti-
allergic, and anti-parasitic agents. As potential antitumor
agents, purinoquinazolinone compound (4) was able to form
a complex with DNA and to inhibit the topoisomerase II. In
addition, benzimidazoquinazolinones have also attracted much
attention for their application in antitumor agents and potential
immunosuppressors.
Bn
N
N
H
N
N
N
N
(2)
(1)
O
O
R2
N
N
R3
N
O
N
N
O
N
N
N
CH2CH2N(CH3)2
COOR1
(4)
(3)
Fig. 1. Structures of some pharmaceutically important azoquinazolinone derivatives.
as key intermediates to synthesize 1,2,4-triazolo[4,3-a]quinazolin-
5(4H)-ones via treating with1 hydrazine and followed by ring closure
upon heating in formic acid. Imidazole[1,2-a]quinazolinones could also
be synthesized from intermediates (I), through chlorinating with SOCl2
and reacting with dimethoxyethylamine, followed by cyclization in
acidic media. The other literature had reported that 1,2,4-triazolo[1,
5-a]quinazolin-5(4H)-one and pyrazolo[1,5-a]quinazolin-5(4H)-one
Some approaches have been developed for the syntheses of azo-
quinazolinones.3 For example, mercaptoquinazolones (I) could be used
* Corresponding authors. Tel./fax: þ86 571 88273814; e-mail addresses: chendb@
tzc.edu.cn (D. Chen), wlbao@css.zju.edu.cn (W. Bao).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.071

6462
D. Chen et al. / Tetrahedron 69 (2013) 6461e6467
Table 1
could be synthesized by reacting 2-hydrazinylbenzoic acid with N-
cyanoformimidate or 3-oxoalkanenitrile. Recently, copper-catalyzed
syntheses of azoquinazolinones have been reported. For example,
CuBr-catalyzed condensation between 2-halobenzoic acid and 2-
amniobenzimidazole or 8-aminotheophylline, could afford benzimi-
dazol- and purino-quinazolinone.2d,3d Fu group reported that N-alkyl
substituted benzimidazol- and imidazol-quinazolinones could be
prepared by CuBr/(S)-proline catalyzed intermolecular Ullmann cou-
pling reaction under N2 for 12 h, then intramolecular CeH amidation
under O2 for 48 h. Although these methods are feasible for the syn-
theses of some title heterocycles, they have some disadvantages: (i) the
expansion of the substrate is limited, for example, it is difficult to
synthesize N-aryl substituted azoquinazolinones, and there are no
common approaches for the syntheses of different azoquinazolinone.
(ii) Most of the substituted products were obtained in low yield be-
cause of multi-steps. Therefore, it’s highly desirable to search for
common, convenient and efficient approaches for the title heterocy-
cles, in particular, for N-aryl substituted azoquinazolinones.
In recent years, CeH functionalization strategy for CeC and
Ceheteroatom bond formation has attracted much attention be-
cause of its economic, sustainable, and environmentally benign
features.4 Most CeH activations have been implemented on pal-
ladium, rhodium, ruthenium, and copper catalysis. Recently, more
and more copper-catalyzed/mediated CeH functionalization has
been reported, due to the cheapness and relatively low toxicity of
copper salts.5 In addition, in the past decade, considerable prog-
ress has been made in the area of copper-catalyzed Ullmann
coupling reaction to form CeX (X¼C, N, O, S etc.) bond. More
Recently, Ullmann coupling has been successfully applied to as-
semble various heterocyclic compounds by cascade reaction
strategies.6 Our research group has been engaged in copper-
catalyzed cascade synthesis of heterocycles and has developed
many tandem reactions to synthesize different heterocycles.7 As
the copper salts could catalyze both CeH activation and Ullmann
coupling, we hope to develop new cascade methods to construct
heterocycle. Herein, we report a reaction of azoles with 2-halo-N-
ary(alk)benzamides via Cu(I)-catalyzed CeN coupling/CeH acti-
vation/CeN formation cyclization tandem process to synthesize
azoquinazolinones, which includes different azole rings and sub-
stituents in good yield.
Optimization of the reaction conditions of synthesis of 6-p-tolyl-benzimidazo[1,2-a]
quinazolin-5(6H)-onea
O
O
I
N
N
Copper (I)/L, Base
Solvent, 110oC, 24h
N
H
+
N
N
N
H
3a
2a
1a
OH
N
PPh3
N
COOH
L3
NH HN
N
N
L1
L5
L4
L2
Entry
Cat.
Ligand
Base
Solvent
T (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
CuI
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
d
L1
L1
L1
L1
L1
L1
L1
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
EtONa
K2CO3
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
EtONa
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
PhMe
DMSO
NMP
DMF
DMF
DMF
DMF
110
110
110
110
110
110
110
110
110
110
110
110
110
110
120
130
120
120
48
45
28
47
62
30
10
27
12
43
23
29
58
40
81
80
84c
97d
Cu(OAc)2
CuBr
CuCl2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
9
10
11
12
13
14
15
16
17
18
a
Reaction conditions: 2-iodo-N-p-tolylbenzamide 1a (0.5 mmol), 1H-benzo[d]
imidazole 2a (0.5 mmol), copper source (0.05 mmol), ligand (0.1 mmol), and base
(1.0 mmol) in solvent (2.0 mL) under O2 for 24 h.
b
Isolated yield.
CuI (0.1 mmol).
CuI (0.1 mmol), L1 (0.2 mmol).
c
d
was enhanced greatly and the highest yield was obtained (97%,
entry 18).
In our preliminary experiments, the reaction between 2-iodo-
N-p-tolylbenzamide (1a) and 1H-benzo[d]imidazole (2a) was in-
vestigated to optimize the reaction conditions, including cata-
lysts, bases, ligands, solvents, and temperature. The results are
summarized in Table 1. Initially, the following reaction condition
(10 mol % CuI, 20 mol % 1,10-phenanthroline, Cs2CO3 in DMF at
110 ꢀC) was adopted to study the synthesis of 6-p-tolyl-benzi-
midazo[1,2-a]quinazolin-5(6H)-one 3a. However, the yield of
product 3a was only 48%. Then Cu-catalysts were selected (entries
1e4), the others (Cu(OAc)2, CuBr, CuCl2) were worse than CuI.
Different bases were examined, the weak base K2CO3 made the
yield of 3a decreased (30%, entry 6), but the strong base NaOEt
improved the yield (62%, entry 5). Five ligands (L1eL5), including
1,10-phenanthroline, DMEDA, N,N-dimethylglycine, quinolin-8-ol
and PPh3 were evaluated (entries 7e9); 1,10-phenanthroline L1
was proved to be the most effective, DMEDA L2 and quinolin-8-ol
L4 were not suitable for the reaction, only 10% and 12% isolated
yield were obtained. In the absence of ligand, the product was
obtained in 23% yield (entry 11). The effect of solvent, including
PhMe, DMF, DMSO, NMP were tested. The yield was lowest in
toluene (only 29%). When the reaction temperature reached
120 ꢀC, the product yield was increased to 81%. However, when
the reaction temperature was raised to 130 ꢀC, the yield didn’t
improve (entry 16). Subsequently, the dosage of copper-catalyst
was increased to 20%, the yield of product reached 84%. If the
ligand L1 was also increased to 40%, to our delight, the reaction
We then investigated the scope of the copper-catalyzed cascade
reaction of substituted 2-iodo-benzamides and different azoles
(2aed) for the synthesis of azoquinazolinones under the optimized
conditions determined above (20 mol % CuI and 40 mol % L1 in the
presence of NaOEt as base in DMF under O2 at 120 ꢀC). As shown in
Table 2, most benzimidazoquinazolinones and triazolo-quinazoli-
nones were obtained in higher yield than imidazoloquinazolinones
and purinoquinazolinones. The latters must be gained in higher
reaction temperature (in between 130 ꢀC and 140 ꢀC). In N-aryl
benzimidazoquinazolinones, the p-chlorophenyl and tolyl exhibited
higher reactivity than phenyl and methoxyphenyl (Table 2, 3aed).
We also investigated the influence of R1 group on the product yield.
The product with electron-donating R1 group (CH3e) was obtained
in lower yield than those with electron-withdrawing group (Cle) or
H atom (Table 2, 3iek, 3nep). The cascade reaction also produced N-
alkyl products, N-benzyl and butyl triazoloquinazolinones, and
purinoquinazolinones as listed in Table 2. N-Alkyl tri-
azoloquinazolinones were obtained in DMF under N2 for 24 h at
120 ꢀC, then O2 for 24 h at 140 ꢀC. The molecular structure of 3i and
3z were unambiguously elucidated by X-ray crystallography (Fig. 2).
To the best of our knowledge, there was no report about CeH
activation/CeN formation of pyrazole. However, in this work, CeH
amination of pyrazole could occur in the tandem reaction to
synthesize pyrazolo[1,5-a]quinazolinone from the reaction of
substituted 2-iodo-benzamides with pyrazole. The scope of the
reaction was also investigated (Table 3, 3sedd). Most of pyrazolo

D. Chen et al. / Tetrahedron 69 (2013) 6461e6467
6463
Table 2
CuI-catalyzed one-pot synthesis of azoquinazolinones from 2-iodo-benzamides and N-heterocyclesa
O
O
R1
R2
N
R1
R2
CuI/1,10-phen, EtONa
DMF, 120oC, O2, 24h
N
N
H
+ N-heterocycle
2a-2d
N
3a-3r
X
1
R1= H, Me, Cl, NO2
R2= Aryl or alkyl
Compound no. Yieldb [%]
O
N
Cl
OCH3
O
O
N
O
N
N
N
N
N
N
N
N
N
N
3a
3b, 74%
49%c
3c, 90%
3d, 73%
Cl
NO2
O
N
O
O
N
N
3f, 70%d
O
N
Cl
N
N
N
N
N
N
N
N
3e, 81%d
3h, 75%d
3g, 68%d
O
N
O
N
O
N
O
O
Bu-n
N
Bn
N
H3C
Cl
Cl
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
3l, 84%f
3m, 83%f
3i, 89%
3j, 51%
3k, 80%
O
O
O
N
O
N
O
N
Bu-n
Bn
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
O
O
O
N
O
O
N
N
N
O
N
O
N
O
O
O
3q, 62%e
3r, 65%e
3n, 67%e
3o, 52%e
3p, 63%e
aReaction conditions: 2-iodo-benzamide 1 (0.5 mmol), N-heterocycle 2 (0.5 mmol), CuI (0.1 mmol), 1,10-phen (0.2 mmol), and EtONa (1.0 mmol) in DMF (2.0 mL) under O2 for
24 h.
bIsolated yield.
c2-Bromo-N-p-tolylbenzamide (0.5 mmol).
d130 ꢀC.
e140 ꢀC.
fUnder N2 for 24 h in 120 ꢀC, then O2 for 24 h in 140 ꢀC.
[1,5-a]quinazolinones could be obtained in good yield under the
optimized conditions. Among the examination of N-aryl group of
2-iodo-benzamides, the N-aryl substrate with electron-donating
groups (CH3、OCH3) gave lower yield of product than the
others with electron-withdrawing groups (Cl、NO2) (Table 3,
3sew). The products with electron-withdrawing R1 group (Cle,
NO2), 3z, 3aa, and 3bb were obtained in higher yield than the
others (3s, 3x, 3y). N-Alkyl pyrazolo[1,5-a]quinazolinones were
also obtained in moderate yield (Table 3, 3cc,dd).
In summary, a method for the assembly of azoquinazolinones
has been developed, which relied on copper-catalyzed one-pot
reaction of 2-halo-benzamides with azoles via cascade CeN cou-
pling/CeH amination process. Most azoquinazolinones containing
different azole rings and substituents were obtained in good yields.
This method should be valuable for the construction of these kinds
of molecules with biological and medicinal activities, so it may find
application in organic synthesis.
2. Experimental section
2.1. Typical experimental procedures for the Cu(I)-catalyzed
one-pot synthesis of azoquinazolinones
An oven-dried Schlenk tube equipped with a Teflon valve was
charged with a magnetic stir bar, 2-iodo-benzamides 1 (0.5 mmol),
N-heterocycle 2 (0.5 mmol), CuI (20 mg, 0.1 mmol, 20 mol %), 1,10-
phenanthroline (40 mg, 0.10 mmol, 40 mol %), NaOEt (68 mg,
1.0 mmol), and DMF (2.0 mL). The tube was evacuated and back-
filled with O2 balloon. The mixture was stirred at 120 ꢀC for 24 h.
After the reaction was completed, the mixture was extracted with
dichloromethane (3ꢁ15 mL), and then the organic layer was
washed with brine (3ꢁ10 mL) and dried with anhydrous Na2SO4.
Subsequently, the solvent was removed and the product was pu-
rified by column chromatography on silica gel to give the pure
azoquinazolinone.

6464
D. Chen et al. / Tetrahedron 69 (2013) 6461e6467
found: C 77.81, H 4.73, N 12.87; EI-MS: m/z¼325 (Mþ). HRMS (ESI)
for C21H15N3O (MþH)þ: calcd 326.1215, found 326.1219.
2.1.2. 6-Phenyl-benzimidazo[1,2-a]quinazolin-5(6H)-one
(3b). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼1:1) to
give a light yellow solid (115.1 mg, 74%), mp >300 ꢀC; 1H NMR
(500 MHz, CDCl3)
d
8.50 (dd, J¼8.0, 1.0 Hz, 1H), 8.30 (d, J¼8.5 Hz,
1H), 8.08e8.06 (m, 1H), 7.94e7.91 (m, 1H), 7.75e7.72 (m, 1H),
7.64e7.61 (m, 2H), 7.57e7.49 (m, 4H), 7.39e7.35 (m, 2H); 13C NMR
(125 MHz, CDCl3)
d 159.6, 147.5, 142.4, 137.2, 135.4, 135.3, 130.5,
129.8, 129.4, 128.5, 125.0, 124.2, 122.5, 119.8, 117.1, 114.5, 112.3. Anal.
Calcd for C20H13N3O: C 77.16, H 4.21, N 13.50; found: C 76.98, H 4.30,
N 13.67; EI-MS: m/z¼311 (Mþ). HRMS (ESI) for C20H13N3O (MþH)þ:
calcd 312.1059, found 312.1063.
2.1.3. 6-(4-Chlorophenyl)-benzimidazo[1,2-a]quinazolin-5(6H)-one
(3c). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼1:1) to
give a light yellow solid (155.6 mg, 90%); mp >300 ꢀC; 1H NMR
(500 MHz, CDCl3)
d
8.49 (dd, J¼8.0, 1.5 Hz, 1H), 8.30 (d, J¼8.5 Hz,
1H), 8.08e8.06 (m, 1H), 7.95e7.92 (m, 1H), 7.75e7.73 (m, 1H),
7.59e7.57 (m, 2H), 7.52 (t, J¼7.5 Hz, 1H), 7.46e7.43 (m, 2H),
7.40e7.37 (m, 2H); 13C NMR (125 MHz, CDCl3)
d 159.5, 147.2, 142.3,
137.2, 135.5, 135.4, 133.7, 130.6, 130.1, 129.9, 125.2, 124.3, 122.7,
119.8, 116.9, 114.5, 112.4; Anal. Calcd for C20H12ClN3O: C 69.47, H
3.50, N 12.15; found: C 69.30, H 3.62, N 11.88; EI-MS: m/z¼345
(Mþ). HRMS (ESI) for C20H12ClN3O (MþH)þ: calcd 346.0669, found
346.0671.
Fig. 2. X-ray crystallographs for 3i and 3z.
Table 3
CuI-catalyzed one-pot synthesis of pyrazolo[1,5-a]quinazolinones from 2-iodo-benzamides and pyrazolea
O
O
N
R2
R2
CuI/1,10-phen, EtONa
R1
R1
3s-3dd
N
H
N
+
N
N
H
DMF, 120oC, O2, 24h
I
1
N
2e
R1= H, Me, Cl, NO2
R2= Aryl or alkyl
Compound no. Yieldb [%]
OCH3
Cl
NO2
O
N
O
N
O
N
O
N
O
N
O
N
N
N
N
N
N
N
N
N
N
N
N
N
3s, 67%
3t, 74%
3x, 62%
3u, 89%
3v, 82%
3w, 61%
O
O
O
O
O
N
O
N
Bu-n
Bn
Cl
O2N
N
N
N
N
N
N
N
N
N
N
Cl
N
N
N
N
N
N
3dd, 55%c
3cc, 44%c
3y, 59%
3z, 78%
3aa, 80%
3bb, 76%
aReaction conditions: 2-iodo-benzamide 1 (0.5 mmol), pyrazole 2e (0.5 mmol), CuI (0.1 mmol), 1,10-phen (0.2 mmol), and EtONa (1.0 mmol) in DMF (2.0 mL) under O2 for 24 h.
bIsolated yield.
cUnder N2 for 24 h in 120 ꢀC, then O2 for 24 h in 140 ꢀC.
2.1.1. 6-p-Tolyl-benzimidazo[1,2-a]quinazolin-5(6H)-one
(3a). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼1:1) to
give a light yellow solid (157.6 mg, 97%), mp >300 ꢀC; 1H NMR
2.1.4. 6-(4-Methoxyphenyl)-benzimidazo[1,2-a]quinazolin-5(6H)-
one (3d). Synthesized according to the typical procedure and pu-
rified by column chromatography (petroleum ether/ethyl
acetate¼1:1) to give a light yellow solid (124.4 mg, 73%); mp
>300 ꢀC; Yellow solid; mp >300 ꢀC; 1H NMR (500 MHz, CDCl3)
(500 MHz, CDCl3)
1H), 8.07e8.05 (m, 1H), 7.93e7.90 (m, 1H), 7.75e7.73 (m, 1H), 7.50
(t, J¼7.5 Hz, 1H), 7.42e7.41 (m, 2H), 7.37e7.35 (m, 4H), 2.47 (s, 3H);
d
8.50 (dd, J¼8.0, 1.5 Hz, 1H), 8.29 (d, J¼8.5 Hz,
d
8.50 (dd, J¼7.5, 1.5 Hz, 1H), 8.30 (d, J¼8.0 Hz, 1H), 8.07e8.06 (m,
1H), 7.94e7.90 (m, 1H), 7.75e7.74 (m, 1H), 7.51 (t, J¼7.5 Hz, 1H),
13C NMR (125 MHz, CDCl3)
d 159.7, 147.7, 142.6, 139.3, 137.2, 135.2,
7.41e7.36 (m, 4H), 7.13e7.10 (m, 2H), 3.89 (s, 3H); 13C NMR
132.7, 130.6, 130.5, 128.1, 128.1, 125.0, 124.1, 122.4, 119.9, 117.1, 114.4,
112.3, 21.4; Anal. Calcd for C21H15N3O: C 77.52, H 4.65, N 12.91;
(125 MHz, CDCl3)
129.4, 127.9, 125.0, 124.2, 124.1, 122.4, 119.9, 117.1, 115.1, 114.4, 112.3,
d 160.0, 159.7, 147.5, 140.7, 137.2, 135.2, 130.5,

D. Chen et al. / Tetrahedron 69 (2013) 6461e6467
6465
55.5. Anal. Calcd for C21H15N3O2: C 73.89, H 4.43, N 12.31; found: C
74.15, H 4.51, N 12.14; EI-MS: m/z¼341 (Mþ). HRMS (ESI) for
C21H15N3O2 (MþH)þ: calcd 342.1164, found 342.1168.
126.6, 116.7, 115.0, 21.3. HRMS (ESI) for C16H12N4O (MþH)þ:
calcd 277.1011, found 277.1013.
2.1.10. 7-Methyl-4-p-tolyl-[1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one
(3j). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (74.0 mg, 51%); mp >300 ꢀC; 1H NMR
2 .1. 5 . 4 - p -To lyl - i m i d a z o [1, 2 - a ] qu i n az ol i n - 5 ( 4H ) - o ne
(3e). Synthesized according to the typical procedure at 130 ꢀC
and purified by column chromatography (dichloromethane/ethyl
acetate¼3:1) to give a light yellow solid (111.5 mg, 81%); mp
(500 MHz, CDCl3)
7.69 (dd, J¼8.5, 1.5 Hz, 1H), 7.39 (d, J¼8.0 Hz, 2H), 7.32 (d, J¼8.0 Hz,
2H), 2.52 (s, 3H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
159.5,
d
8.19 (s, 1H), 8.03 (d, J¼8.5 Hz, 1H), 7.90 (s, 1H),
229e231 ꢀC; 1H NMR (500 MHz, CDCl3)
d
8.44 (dd, J¼8.0, 1.0 Hz,
1H), 7.82e7.79 (m, 1H), 7.63 (d, J¼8.5 Hz, 1H), 7.52 (d, J¼1.5 Hz,
1H), 7.48 (t, J¼7.5 Hz, 1H), 7.38e7.35 (m, 2H), 7.33e7.31 (m, 2H),
7.10 (d, J¼1.5 Hz, 1H), 2.43 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
151.2, 149.5, 139.6, 136.9, 136.6, 133.6, 132.1, 130.5, 129.4, 127.6,
116.5, 114.9, 21.3, 21.1. HRMS (ESI) for C17H14N4O (MþH)þ:
calcd 291.1168, found 291.1169.
d
159.3, 139.1, 135.2, 134.8, 132.6, 130.4, 130.3, 129.1, 128.0, 126.7,
125.6, 117.3, 114.2, 109.2, 21.3; Anal. Calcd for C17H13N3O: C 74.17,
H 4.76, N 15.26; found: C 74.05, H 4.79, N 15.48; EI-MS: m/
z¼275 (Mþ). HRMS (ESI) for C17H13N3O (MþH)þ: calcd 276.1059,
found 276.1060.
2.1.11. 7-Chloro-4-p-tolyl-[1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one
(3k). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (124.3 mg, 80%); mp 227e229 ꢀC; 1H NMR
2.1.6. 4-(4-Chlorophenyl)-imidazo[1,2-a]quinazolin-5(4H)-one
(3f). Synthesized according to the typical procedure at 130 ꢀC
and purified by column chromatography (dichloromethane/ethyl
acetate¼3:1) to give a light yellow solid (103.5 mg, 70%); mp
(500 MHz, CDCl3)
d
8.37 (d, J¼2.0 Hz,1H), 8.10 (d, J¼9.0 Hz,1H), 7.92
(s, 1H), 7.83 (dd, J¼9.0, 2.5 Hz, 1H), 7.39 (d, J¼8.5 Hz, 2H), 7.32 (d,
J¼8.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 158.4, 151.7,
149.7, 139.9, 135.7, 134.1, 132.7, 131.7, 130.5, 129.2, 127.5, 118.0, 116.7,
21.3; Anal. Calcd for C16H11ClN4O: C 61.84, H 3.57, N 18.03; found: C
61.73, H 3.68, N 17.85; EI-MS: m/z¼310 (Mþ). HRMS (ESI) for
C16H11ClN4O (MþH)þ: calcd 311.0621, found 311.0627.
256e258 ꢀC; 1H NMR (500 MHz, CDCl3)
d
8.43 (d, J¼7.5 Hz, 1H),
7.83 (t, J¼8.0 Hz, 1H), 7.64 (d, J¼8.0 Hz, 1H), 7.55e7.48 (m, 4H),
7.42e7.40 (m, 2H), 7.11 (s, 1H); 13C NMR (125 MHz, CDCl3)
d
159.1, 135.2, 135.1, 133.7, 130.3, 129.9, 129.8, 129.0, 125.8, 117.1,
114.3, 109.5, 107.3; Anal. Calcd for C16H10ClN3O: C 64.98, H 3.41, N
14.21; found: C 64.65, H 3.46, N 13.97; EI-MS: m/z¼295 (Mþ).
HRMS (ESI) for C16H10ClN3O (MþH)þ: calcd 296.0512, found
296.0519.
2.1.12. 4-Butyl-[1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one
(3l). Synthesized according to the typical procedure under N2 for
24 h at 120 ꢀC, then O2 for 24 h at 140 ꢀC, and purified by column
chromatography (petroleum ether/ethyl acetate¼2:1) to give
a light yellow solid (101.6 mg, 84%); mp 68e70 ꢀC;
d
8.36 (dd, J¼8.0,
2.1.7. 4-(4-Nitrophenyl)-imidazo[1,2-a]quinazolin-5(4H)-
one (3g). Synthesized according to the typical procedure at 130 ꢀC
and purified by column chromatography (dichloromethane/ethyl
acetate¼3:1) to give a light yellow solid (104.1 mg, 68%); mp
1.0 Hz, 1H), 8.07 (d, J¼8.0 Hz, 1H), 7.99 (s, 1H), 7.84e7.81 (m, 1H),
7.52e7.49 (m, 1H), 4.31 (t, J¼7.5 Hz, 2H), 1.85e1.79 (m, 2H),
1.48e1.41 (m, 2H), 0.97 (t, J¼7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d
159.2,151.5,149.2,135.4,135.0,129.3,126.4,116.6,114.8, 43.9, 29.6,
262e264 ꢀC; 1H NMR (500 MHz, CDCl3)
d
8.44e8.43 (m, 3H),
20.1, 13.7; Anal. Calcd for C13H14N4O: C 64.45, H 5.82, N 23.13;
found: C 64.23, H 5.97, N 22.96; EI-MS: m/z¼242 (Mþ). HRMS (ESI)
for C13H14N4O (MþH)þ: calcd 243.1168, found 243.1171.
7.88e7.84 (m, 1H), 7.72e7.70 (m, 2H), 7.66 (d, J¼8.0 Hz, 1H), 7.56 (d,
J¼1.5 Hz, 1H), 7.57e7.50 (m, 1H), 7.11 (d, J¼1.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3)
d 158.7, 147.8, 142.1, 140.7, 135.5, 135.2, 130.4,
129.8, 128.9, 126.0, 124.8, 116.8, 114.4, 109.8; Anal. Calcd for
C16H10N4O3: C 62.74, H 3.29, N 18.29; found: C 62.81, H 3.34, N
18.11; EI-MS: m/z¼306 (Mþ). HRMS (ESI) for C16H10N4O3 (MþH)þ:
calcd 307.0753, found 307.0753.
2.1.13. 4-Benzyl-[1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one
(3m). Synthesized according to the typical procedure under N2 for
24 h at 120 ꢀC, then O2 for 24 h at 140 ꢀC, and purified by column
chromatography (petroleum ether/ethyl acetate¼2:1) to give
a light yellow solid (114.5 mg, 83%); mp 250e252 ꢀC; 1H NMR
2.1.8. 7-Chloro-4-p-tolylimidazo[1,2-a]quinazolin-5(4H)-one
(3h). Synthesized according to the typical procedure at 130 ꢀC
and purified by column chromatography (dichloromethane/ethyl
acetate¼3:1) to give a light yellow solid (116.2 mg, 75%); mp
(500 MHz, CDCl3)
(m,1H), 7.60 (d, J¼7.0 Hz, 2H), 7.48e7.46 (m, 1H), 7.35e7.24 (m, 3H),
5.48 (s, 2H); 13C NMR (125 MHz, CDCl3)
159.2, 151.4, 149.1, 135.6,
d 8.35e8.32 (m,1H), 8.03e7.99 (m, 2H), 7.80e7.76
d
135.3, 135.1, 129.3, 129.1, 128.5, 128.1, 126.4, 116.5, 114.8, 47.0. HRMS
254e256 ꢀC; 1H NMR (500 MHz, CDCl3)
d
8.40 (d, J¼5.0 Hz, 1H),
(ESI) for C16H12N4O (MþH)þ: calcd 277.1011, found 277.1016.
7.76 (dd, J¼9.0, 2.5 Hz, 1H), 7.58 (d, J¼9.0 Hz, 1H), 7.48 (d,
J¼1.5 Hz, 1H), 7.38e7.37 (m, 2H), 7.32e7.30 (m, 2H), 7.11 (d,
2.1.14. 8,10-Dimethyl-6-p-tolylpurino[7,8-a]quinazoline-
5,9,11(6H,8H,10H)-trione (3n). Synthesized according to the typical
procedure at 140 ꢀC and purified by column chromatography
J¼1.5 Hz, 1H), 2.43 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 158.2,
139.4, 134.9, 133.7, 132.4, 131.5, 130.5, 129.8, 129.4, 127.9, 118.6,
115.9, 109.3, 21.3; Anal. Calcd for C17H12ClN3O: C 65.92, H 3.90, N
13.57; found: C 65.67, H 4.03, N 13.31; EI-MS: m/z¼309 (Mþ).
HRMS (ESI) for C17H12ClN3O (MþH)þ: calcd 310.0669, found
310.0675.
(dichloromethane/acetone¼30:1) to give
a
light yellow solid
9.80 (d,
(129.7 mg, 67%); mp >300 ꢀC; 1H NMR (500 MHz, CDCl3)
d
J¼5.0 Hz,1H), 8.40 (d, J¼5.0 Hz,1H), 7.89e7.85 (m,1H), 7.53e7.50 (m,
1H), 7.38 (d, J¼5.0 Hz, 2H), 7.29 (d, J¼10.0 Hz, 2H), 3.50 (s, 3H), 3.46 (s,
3H), 2.48 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 159.1, 154.0, 151.1,
2.1.9. 4-p-Tolyl-[1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one
(3i). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1)
to give a light yellow solid (122.9 mg, 89%); mp 265e267 ꢀC; 1H
150.5,147.2,139.4,135.9,135.5,132.1,130.2,129.4,127.9,126.4,120.1,
116.9, 104.0, 30.2, 29.0, 21.3; Anal. Calcd for C21H17N5O3: C 65.11, H
4.42, N 18.08; found: C 65.32, H 4.45, N 17.91; EI-MS: m/z¼387 (Mþ).
HRMS (ESI) for C21H17N5O3 (MþH)þ: calcd 388.1331, found 388.1335.
NMR (500 MHz, CDCl3)
d
8.41 (d, J¼10.0 Hz, 1H), 8.15 (d, J¼10.0 Hz,
1H), 7.92e7.89 (m, 2H), 7.55 (t, J¼10.0 Hz, 1H), 7.39 (d, J¼5.0 Hz,
2.1.15. 3,8,10-Trimethyl-6-p-tolylpurino[7,8-a]quinazoline-
5,9,11(6H,8H,10H)-trione (3o). Synthesized according to the typical
procedure at 140 ꢀC and purified by column chromatography
2H), 7.33 (d, J¼5.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
159.4, 151.5, 149.8, 139.7, 135.6, 135.5, 132.0, 130.5, 129.7, 127.6,

6466
D. Chen et al. / Tetrahedron 69 (2013) 6461e6467
(dichloromethane/acetone¼30:1) to give
a
light yellow solid
9.67 (d,
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (96.6 mg, 74%); mp 154e155 ꢀC; 1H NMR
(500 MHz, CDCl3)
(104.3 mg, 52%); mp >300 ꢀC; 1H NMR (500 MHz, CDCl3)
d
J¼9.0 Hz, 1H), 8.18 (s, 1H), 7.67 (t, J¼1.5 Hz, 1H), 7.38 (d, J¼8.5 Hz,
d
8.36 (dd, J¼7.5, 1.0 Hz, 1H), 8.23 (d, J¼8.0 Hz,
2H), 7.27 (d, J¼8.5 Hz, 2H), 3.49 (s, 3H), 3.45 (s, 3H), 2.50 (s, 3H), 2.47
1H), 7.84e7.80 (m, 1H), 7.66 (d, J¼2.0 Hz, 1H), 7.59e7.56 (m, 2H),
(s, 3H); 13C NMR (125 MHz, CDCl3)
d 159.1, 154.0, 151.2, 150.4, 146.9,
7.53e7.50 (m, 1H), 7.47e7.44 (m, 3H), 5.49 (d, J¼2.0 Hz, 1H); 13C
139.4, 136.6, 136.5, 133.8, 132.2, 130.2, 129.0, 128.0, 120.1, 116.8,
104.0, 30.2, 29.0, 21.3, 20.9; Anal. Calcd for C22H19N5O3: C 65.83, H
4.77, N 17.45; found: C 66.06, H 4.75, N 17.36; EI-MS: m/z¼401 (Mþ).
HRMS (ESI) for C22H19N5O3 (MþH)þ: calcd 402.1488, found
402.1489.
NMR (125 MHz, CDCl3) d 158.6,141.7,141.6,137.8,136.8,135.0,129.9,
129.4, 129.3, 127.8, 125.5, 116.3, 114.7, 90.9; Anal. Calcd for
C16H11N3O: C 73.55, H 4.24, N 16.08; found: C 73.78, H 4.09, N 16.33;
EI-MS: m/z¼261 (Mþ). HRMS (ESI) for C16H11N3O (MþH)þ:
calcd 262.0902, found 262.0903.
2.1.16. 3-Chloro-8,10-dimethyl-6-p-tolylpurino[7,8-a]quinazoline-
5,9,11(6H,8H,10H)-trione (3p). Synthesized according to the typical
procedure at 140 ꢀC and purified by column chromatography
2.1.21. 4-(4-Chlorophenyl)pyrazolo[1,5-a]quinazolin-5(4H)-one
(3u). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (131.2 mg, 89%); mp 214e216 ꢀC; 1H NMR
(dichloromethane/acetone¼30:1) to give
a
light yellow solid
9.84 (d,
(132.6 mg, 63%); mp >300 ꢀC; 1H NMR (500 MHz, CDCl3)
d
(500 MHz, CDCl3)
d
8.38 (d, J¼7.5 Hz,1H), 8.22 (d, J¼8.5 Hz,1H), 7.83
J¼9.5 Hz,1H), 8.35 (d, J¼2.5 Hz,1H), 7.80 (dd, J¼9.0, 2.5 Hz,1H), 7.38
(t, J¼8.0 Hz, 1H), 7.67 (d, J¼1.5 Hz, 1H), 7.55 (d, J¼9.0 Hz, 2H), 7.46 (t,
(d, J¼8.0 Hz, 2H), 7.28 (d, J¼2.5 Hz, 2H), 3.49 (s, 3H), 3.45 (s, 3H), 2.47
J¼7.5 Hz, 1H), 7.40 (d, J¼8.5 Hz, 2H), 5.51 (d, J¼2.0 Hz, 1H); 13C NMR
(s, 3H); 13C NMR (125 MHz, CDCl3)
d
158.0, 154.0, 151.0, 150.5, 147.0,
(125 MHz, CDCl3) d 158.6, 141.8, 141.2, 137.8, 135.3, 135.2, 130.3,
139.7,135.5, 134.3,132.5, 131.8, 130.3,128.7, 127.8, 122.1, 118.3,104.0,
30.3, 29.0, 21.3; Anal. Calcd for C21H16ClN5O3: C 59.79, H 3.82, N
16.60; found: C 60.01, H 3.96, N 16.37; EI-MS: m/z¼421 (Mþ). HRMS
(ESI) for C21H16ClN5O3 (MþH)þ: calcd 422.0942, found 422.0946.
129.4, 129.2, 125.6, 116.0, 114.8, 90.8; Anal. Calcd for C16H10ClN3O: C
64.98, H 3.41, N 14.21; found: C 65.10, H 3.43, N 14.40; EI-MS: m/
z¼295 (Mþ). HRMS (ESI) for C16H10ClN3O (MþH)þ: calcd 296.0512,
found 296.0515.
2.1.17. 6-Butyl-8,10-dimethylpurino[7,8-a]quinazoline-
5,9,11(6H,8H,10H)-trione (3q). Synthesized according to the typical
procedure at 140 ꢀC and purified by column chromatography
2.1.22. 4-(4-Nitrophenyl)pyrazolo[1,5-a]quinazolin-5(4H)-one
(3v). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (125.5 mg, 82%); mp 223e225 ꢀC; 1H NMR
(dichloromethane/acetone¼30:1) to give
a
light yellow solid
9.76
(109.4 mg, 62%); mp 224e226 ꢀC; 1H NMR (500 MHz, CDCl3)
d
(500 MHz, CDCl3)
d
8.46e8.44 (m, 2H), 8.34 (dd, J¼8.0, 1.0 Hz, 1H),
(d, J¼8.5 Hz, 1H), 8.38 (d, J¼8.0 Hz, 1H), 7.84 (t, J¼7.0 Hz, 1H), 7.50 (t,
J¼7.5 Hz, 2H), 4.41 (t, J¼7.5 Hz, 2H), 3.66 (s, 3H), 3.51 (s, 3H),
1.85e1.79 (m, 2H), 1.46e1.43 (m, 2H), 1.01 (t, J¼7.5 Hz, 3H). 13C NMR
8.25 (d, J¼8.0 Hz, 1H), 7.88e7.85 (m, 1H), 7.71e7.69 (m, 3H),
7.50e7.47 (m,1H), 5.56 (d, J¼2.0 Hz,1H); 13C NMR (125 MHz, CDCl3)
d
158.3, 147.9, 142.2, 141.8, 140.3, 137.8, 135.6, 129.4, 129.2, 125.9,
(125 MHz, CDCl3)
d
158.7, 154.0, 151.2, 150.7, 146.7, 135.7, 135.1,
125.3, 115.7, 115.0, 90.8; Anal. Calcd for C16H10N4O3: C 62.74, H 3.29,
N 18.29; found: C 63.02, H 3.41, N 18.47; EI-MS: m/z¼306 (Mþ).
HRMS (ESI) for C16H10N4O3 (MþH)þ: calcd 307.0753, found
307.0754.
129.0,126.3,120.0,116.7,104.1, 43.7, 30.2, 29.5, 29.0, 20.0,13.7; Anal.
Calcd for C18H19N5O3: C 61.18, H 5.42, N 19.82; found: C 61.05, H
5.43, N 20.03; EI-MS: m/z¼353 (Mþ). HRMS (ESI) for C18H19N5O3
(MþH)þ: calcd 354.1488, found 354.1490.
2.1.23. 4-(4-Methoxyphenyl)pyrazolo[1,5-a]quinazolin-5(4H)-one
(3w). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (88.7 mg, 61%); mp 179e180 ꢀC; 1H NMR
2.1.18. 6-Benzyl-8,10-dimethylpurino[7,8-a]quinazoline-
5,9,11(6H,8H,10H)-trione (3r). Synthesized according to the typical
procedure at 140 ꢀC and purified by column chromatography
(dichloromethane/acetone¼30:1) to give
a
light yellow solid
9.74 (d,
(500 MHz, CDCl3)
d
8.35 (dd, J¼8.0, 1.0 Hz, 1H), 8.22 (d, J¼8.0 Hz,
(125.8 mg, 65%); mp 209e211 ꢀC; 1H NMR (500 MHz, CDCl3)
d
1H), 7.83e7.80 (m, 1H), 7.66 (d, J¼2.0 Hz, 1H), 7.46e7.43 (m, 1H),
J¼8.5 Hz,1H), 8.40 (dd, J¼8.0,1.5 Hz,1H), 7.85e7.81 (m,1H), 7.61e7.60
7.36e7.33 (m, 2H), 7.08e7.05 (m, 2H), 5.50 (d, J¼2.0 Hz, 1H), 3.88 (s,
(m, 2H), 7.51e7.48 (m,1H), 7.33e7.27 (m, 3H), 5.58 (s, 2H), 3.68 (s, 3H),
3H); 13C NMR (125 MHz, CDCl3)
d 160.0, 158.9, 141.9, 141.7, 137.8,
3.49 (s, 3H). 13C NMR (125 MHz, CDCl3)
d
158.8, 153.9, 151.1, 150.5,
135.0, 129.4, 128.9, 125.5, 116.3, 115.2, 115.2, 114.7, 90.9, 55.6; Anal.
Calcd for C17H13N3O2: C 70.09, H 4.50, N 14.42; found: C 69.95, H
4.58, N 14.37; EI-MS: m/z¼291 (Mþ). HRMS (ESI) for C17H13N3O2
(MþH)þ: calcd 292.1008, found 292.1010.
146.5, 135.6, 135.3, 129.3, 129.1, 128.5, 128.2, 126.9, 126.3, 120.1, 116.7,
104.2, 46.8, 30.2, 29.0; Anal. Calcd for C21H17N5O3: C 65.11, H 4.42, N
18.08; found: C 64.98, H 4.46, N 17.82; EI-MS: m/z¼387 (Mþ). HRMS
(ESI) for C21H17N5O3 (MþH)þ: calcd 388.1331, found 388.1331.
2.1.24. 7-Methyl-4-p-tolylpyrazolo[1,5-a]quinazolin-5(4H)-one
(3x). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (89.6 mg, 62%); mp 140e142 ꢀC; 1H NMR
(500 MHz, CDCl3)
2H), 7.36 (d, J¼8.0 Hz, 2H), 7.30 (d, J¼8.5 Hz, 2H), 5.47 (d, J¼2.0 Hz,
1H), 2.48 (s, 3H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
158.8,
141.4, 141.3, 139.3, 136.0, 135.7, 135.5, 134.3, 130.6, 129.0, 127.5, 116.1,
114.6, 90.7, 21.3, 21.0; Anal. Calcd for C18H15N3O: C 74.72, H 5.23, N
14.52; found: C 74.67, H 5.06, N 14.67; EI-MS: m/z¼289 (Mþ). HRMS
(ESI) for C18H15N3O (MþH)þ: calcd 290.1215, found 290.1219.
2.1.19. 4-p-Tolylpyrazolo[1, 5-a]quinazolin-5(4H)-one
(3s). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼1:1) to
give a light yellow solid (92.2 mg, 67%); mp 157e158 ꢀC; 1H NMR
d
8.13 (s, 1H), 8.10 (d, J¼8.0 Hz, 1H), 7.63e7.61 (m,
(500 MHz, CDCl3)
d
8.36 (dd, J¼8.0, 1.0 Hz, 1H), 8.22 (d, J¼8.5 Hz,
1H), 7.84e7.80 (m, 1H), 7.66 (d, J¼1.5 Hz, 1H), 7.47e7.44 (m, 1H),
7.37 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.5 Hz, 2H), 5.49 (d, J¼2.0 Hz, 1H),
d
2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 158.7, 141.7, 139.3, 137.7,
134.9, 134.1, 130.6, 129.4, 127.4, 125.4, 116.3, 114.7, 90.9, 21.3; Anal.
Calcd for C17H13N3O: C 74.17, H 4.76, N 15.26; found: C 74.10, H 4.63,
N 15.40; EI-MS: m/z¼275 (Mþ). HRMS (ESI) for C17H13N3O (MþH)þ:
calcd 276.1059, found 276.1066.
2.1.25. 9-Methyl-4-p-tolylpyrazolo[1,5-a]quinazolin-5(4H)-one
(3y). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (85.2 mg, 59%); mp 137e139 ꢀC; 1H NMR
2.1.20. 4-Phenylpyrazolo[1, 5-a]quinazolin-5(4H)-one
(3t). Synthesized according to the typical procedure and purified

D. Chen et al. / Tetrahedron 69 (2013) 6461e6467
6467
(500 MHz, CDCl3)
7.37e7.29 (m, 5H), 5.48 (s, 1H), 3.01 (s, 3H), 2.45 (s, 3H); 13C NMR
(125 MHz, CDCl3) 159.0, 142.2, 140.6, 139.3, 138.5, 136.5, 134.4,
d
8.28 (d, J¼7.5 Hz, 1H), 7.65e7.60 (m, 3H),
J¼1.0 Hz, 1H), 7.68 (d, J¼2.0 Hz, 1H), 7.44e7.41 (m, 1H), 7.36 (d,
J¼7.5 Hz, 2H), 7.32e7.25 (m, 3H), 5.89 (d, J¼2.0 Hz, 1H), 5.29 (s, 2H);
d
13C NMR (125 MHz, CDCl3)
d 158.8, 141.9, 140.3, 137.5, 135.2, 134.8,
130.6, 127.5, 127.5, 125.0, 117.6, 90.1, 23.3, 21.3; HRMS (ESI) for
129.2, 128.7, 127.9, 127.5, 125.4, 115.8, 114.6, 90.0, 48.1; Anal. Calcd
for C17H13N3O: C 74.17, H 4.76, N 15.26; found: C 73.89, H 4.68, N
15.47; EI-MS: m/z¼275 (Mþ). HRMS (ESI) for C17H13N3O (MþH)þ:
calcd 276.1059, found 276.1060.
C18H15N3O (MþH)þ: calcd 290.1215, found 290.1216.
2.1.26. 7-Chloro-4-p-tolylpyrazolo[1,5-a]quinazolin-5(4H)-one
(3z). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (120.5 mg, 78%); mp 132e134 ꢀC; 1H NMR
Acknowledgements
(500 MHz, CDCl3)
J¼8.5 Hz, 1H), 7.65 (s, 1H), 7.37 (d, J¼7.5 Hz, 2H), 7.30 (d, J¼8.0 Hz,
2H), 5.51 (s, 1H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
157.7,
142.0, 141.6, 139.6, 136.2, 135.1, 133.9, 131.3, 130.6, 128.8, 127.3, 117.5,
116.5, 91.2, 21.3; Anal. Calcd for C17H12ClN3O: C 65.92, H 3.90, N
13.57; found: C 66.12, H 3.83, N 13.43; EI-MS: m/z¼309 (Mþ). HRMS
(ESI) for C17H12ClN3O (MþH)þ: calcd 310.0669, found 310.0670.
d
8.30 (s, 1H), 8.16 (d, J¼9.0 Hz, 1H), 7.75 (d,
This work was financially supported by the Natural Science
Foundation of Zhejiang (No. Y4110491), the Natural Science Foun-
dation of China (Nos. 21072168, 21272169), the Opening Founda-
tion of Zhejiang Provincial Top Key Discipline (No. 100061200102),
and Taizhou Science & Technology Program (No. 111ZD02).
d
Supplementary data
2.1.27. 8-Chloro-4-p-tolylpyrazolo[1,5-a]quinazolin-5(4H)-one
(3aa). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (123.5 mg, 80%); mp 177e179 ꢀC; 1H NMR
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.05.071.
References and notes
(500 MHz, CDCl3)
d
8.26 (d, J¼8.5 Hz, 1H), 8.22 (d, J¼2.0 Hz, 1H),
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Dastbaravardeh, N.; Ghobrial, M. Curr. Org. Chem. 2011, 15, 2694e2730; (d)
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7.65 (d, J¼1.5 Hz, 1H), 7.40e7.36 (m, 3H), 7.30 (d, J¼8.5 Hz, 2H), 5.49
(d, J¼2.0 Hz, 1H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 158.1,
142.2, 142.0, 141.6, 139.5, 138.3, 133.8, 130.9, 130.6, 127.3, 125.9,
114.9, 114.6, 91.2, 21.3; HRMS (ESI) for C17H12ClN3O (MþH)þ:
calcd 310.0669, found 310.0676.
2.1.28. 7-Nitro-4-p-tolylpyrazolo[1,5-a]quinazolin-5(4H)-one
(3bb). Synthesized according to the typical procedure and purified
by column chromatography (petroleum ether/ethyl acetate¼2:1) to
give a light yellow solid (121.6 mg, 76%); mp 210e212 ꢀC; 1H NMR
(500 MHz, CDCl3)
d
9.20 (d, J¼2.5 Hz, 1H), 8.64 (dd, J¼9.0, 2.5 Hz,
1H), 8.35 (d, J¼9.0 Hz, 1H), 7.74 (d, J¼2.0 Hz, 1H), 7.39 (d, J¼8.0 Hz,
2H), 7.31 (d, J¼8.5 Hz, 2H), 5.56 (d, J¼2.0 Hz, 1H), 2.46 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 157.2,144.9,143.8,142.5,141.1,139.9,133.4,
130.8, 129.6, 127.2, 126.0, 116.7, 116.2, 92.0, 21.3; Anal. Calcd for
C17H12N4O3: C 63.75, H 3.78, N 17.49; found: C 63.60, H 3.82, N
17.43; EI-MS: m/z¼320 (Mþ). HRMS (ESI) for C17H12N4O3 (MþH)þ:
calcd 321.0909, found 321.0915.
5. (a) Wendlandt, A. E.; Success, A. M.; Stahl, S. S. Angew. Chem., Int. Ed. 2011, 50,
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Y. Y.; Zhao, Y. F. Org. Lett. 2009, 11, 2469e2472; (d) Huang, C.; Fu, Y.; Fu, H.; Jiang,
Y. Y.; Zhao, Y. F. Chem. Commun. 2008, 6333e6335; (e) Liu, X. W.; Fu, H.; Jiang, Y.
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2.1.29. 4-Butylpyrazolo[1,5-a]quinazolin-5(4H)-one (3cc). Synthe-
sized according to the typical procedure under N2 for 24 h at 120 ꢀC,
then O2 for 24 h at 140 ꢀC, and purified by column chromatography
(petroleum ether/ethyl acetate¼2:1) to give a light yellow solid
(53.0 mg, 44%); mp 57e59 ꢀC; 1H NMR (500 MHz, CDCl3)
d 8.32 (dd,
J¼8.0, 1.0 Hz, 1H), 8.17 (d, J¼8.5 Hz, 1H), 7.77 (d, J¼2.0 Hz, 2H),
7.44e7.41 (m, 1H), 5.94 (d, J¼2.0 Hz, 1H), 4.09 (t, J¼7.5 Hz, 2H),
1.82e1.75 (m, 2H), 1.46e1.42 (m, 2H), 0.98 (t, J¼7.5 Hz, 3H); 13C
NMR (125 MHz, CDCl3)
d 158.6, 148.6, 142.0, 140.5, 134.6, 129.0,
125.4, 115.0, 114.6, 89.1, 44.9, 29.7, 20.2, 13.7; Anal. Calcd for
C14H15N3O: C 69.69, H 6.27, N 17.41; found: C 69.60, H 6.41, N 17.23;
EI-MS: m/z¼241 (Mþ). HRMS (ESI) for C14H15N3O (MþH)þ:
calcd 242.1215, found 242.1217.
7. (a) Lv, X.; Liu, Y. Y.; Qian, W. X.; Bao, W. L. Adv. Synth. Catal. 2008, 350,
2507e2512; (b) Bao, W. L.; Liu, Y. Y.; Lv, X.; Qian., W. X. Org. Lett. 2008, 10,
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2.1.30. 4-Benzylpyrazolo[1,5-a]quinazolin-5(4H)-one
(3dd). Syn-
thesized according to the typical procedure under N2 for 24 h at
120 ꢀC, then O2 for 24 h at 140 ꢀC, and purified by column chro-
matography (petroleum ether/ethyl acetate¼2:1) to give a light
yellow solid (75.6 mg, 55%); mp 153e155 ꢀC; 1H NMR (500 MHz,
CDCl3)
d
8.36 (dd, J¼8.0, 1.5 Hz, 1H), 8.16 (d, J¼8.5 Hz, 1H), 7.77 (d,