A practical, ligand-free, palladium-catalyzed isocyanide insertion reaction for the construction of novel ring-fused quinazolinones

Article abstract of DOI:10.1055/s-0033-1338936

A high-yielding, ligand-free, palladium-catalyzed isocyanide insertion reaction for the synthesis of phthalazino[1,2-b]quinazolinones from the readily obtainable quinazolinones has been developed. Easily handled and relatively low-cost palladium(II) acetate was used as the catalyst, without an additional ligand. Preparation of the quinazolinones involved the cascade reaction of isatoic anhydrides, phenylhydrazines and 2-bromobenzaldehyde catalyzed by p-toluenesulfonic acid in one pot. This novel protocol may be applicable for the synthesis of other important ring-fused heterocyclic compounds. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1338936

PAPER
▌1965
paper
A Practical, Ligand-Free, Palladium-Catalyzed Isocyanide Insertion Reaction
for the Construction of Novel Ring-Fused Quinazolinones
Synthesis of Ring-Fused Quinazolinones
Fei Ji, Mei-fang Lv, Wen-bin Yi, Chun Cai*
Chemical Engineering College, Nanjing University of Science and Technology, Nanjing 210094, P. R. of China
Fax +86(25)84315030; E-mail: c.cai@mail.njust.edu.cn
Received: 04.03.2013; Accepted after revision: 17.04.2013
and rutaecarpine6b isolated from Evodia rutaecarpa,
Abstract: A high-yielding, ligand-free, palladium-catalyzed isocy-
luotonin A isolated from Peganum nigellastrum,6c trypt-
anide insertion reaction for the synthesis of phthalazino[1,2-b]quin-
anthrin isolated from Couroupita guianensis6d and de-
azolinones from the readily obtainable quinazolinones has been
developed. Easily handled and relatively low-cost palladium(II) ac-
oxyvasicinone isolated from Adhatoda vasica.6e These
etate was used as the catalyst, without an additional ligand. Prepa- quinazolinone alkaloids exhibit a wide range of biological
and medicinal activities.6a,7 In addition, biological assays
have shown that ring-fused quinazolinones containing the
ration of the quinazolinones involved the cascade reaction of isatoic
anhydrides, phenylhydrazines and 2-bromobenzaldehyde catalyzed
by p-toluenesulfonic acid in one pot. This novel protocol may be ap-
–CO–N–N– structural fragment have analgesic proper-
plicable for the synthesis of other important ring-fused heterocyclic
compounds.
ties, and some derivatives exhibit anti-inflammatory ac-
tivities.8 These pharmacological records promoted us to
Key words: ligand-free, palladium catalysis, isocyanide insertion
develop an efficient method for the preparation of ring-
reaction, ring-fused quinazolinones, depropargylation
fused quinazolinones. Some procedures for the synthesis
of ring-fused quinazolinones are known;8,9 however, pre-
vious reported pathways often suffer from the poor avail-
In recent years, isocyanides have emerged as powerful
ability of starting materials, poor regioselectivity, low
building blocks in the construction of medicinally impor-
yields and low functional group diversity. Thus, it is still
tant molecules and natural products.1 Isocyanides have an
necessary to develop an efficient and simple pathway to
isoelectronic relationship with carbon monoxide,2 which
synthesize ring-fused quinazolinones and their analogues.
enables their inclusion into organic synthesis with transi-
tion-metal-catalyzed protocols.3 The use of isocyanides in
place of carbon monoxide in transition-metal-catalyzed
reactions has considerable advantages, such as simple
handling, an extra diversity point and the possibilities of
further elaboration of use of convertible isocyanides.3,4
Moreover, the palladium-catalyzed reaction for the inser-
tion of isocyanides is an efficient but relatively unex-
plored method that offers more possibilities for the
synthesis of heterocyclic compounds. It is therefore not
surprising that interest in this field has recently increased
significantly.2d,5
Herein, we report the development of a novel, ligand-free,
palladium-catalyzed isocyanide insertion reaction for the
synthesis of phthalazino[1,2-b]quinazolinones from the
readily obtainable quinazolinones. As shown in Scheme
1, the cascade reaction of isatoic anhydrides, phenylhy-
drazines and 2-bromobenzaldehyde catalyzed by p-tolu-
enesulfonic acid could be used to prepare the
quinazolinones,10 which provided the starting materials
for the palladium-catalyzed isocyanide insertion reaction.
In the initial phase of the investigation, several kinds of
quinazolinones were synthesized via the cascade reaction
of isatoic anhydrides, phenylhydrazines and 2-bromo-
benzaldehyde catalyzed by p-toluenesulfonic acid, in
moderate to high yields (Table 1).
Ring-fused quinazolinones as considered privileged het-
erocyclic motifs have been found in the core structural
skeletons of many natural products including evodiamine6a
R3
R3
N
R3
N
O
O
O
O
N
R4
R4
R4NC, Pd(OAc)2
1) ArNHNH2, MeCN, reflux
2) 2-bromobenzaldehyde
N
N
N
O
N
H
R2
N
N
R2
R2
R2
or
toluene, Cs2CO3
110 °C
N
R1
O
N
R1
TsOH (10 mol%), one pot
N
R1
Br
1a–h
2a–m
R1 = H, Me, Bn
2n,o
R1 = CH2C≡CH
Scheme 1 General strategy for the synthesis of phthalazino[1,2-b]quinazolinones
SYNTHESIS 2013, 45, 1965–1974
Advanced online publication: 14.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338936; Art ID: SS-2013-H0182-OP
© Georg Thieme Verlag Stuttgart · New York

1966
F. Ji et al.
PAPER
Table 1 Synthesis of Quinazolinones
R3
NH2
NH
O
O
N
6
2-bromobenzaldehyde
TsOH (10 mol%)
MeCN
reflux
O
N
H
R2
R2
+
R3
N
O
N
R1
R1
Br
1a–h
R1
R2
R3
Product
Yielda (%)
Bn
H
H
1a
1b
1c
1d
1e
1f
87
85
82
84
75
89
75
78
Me
H
H
Bn
6-Cl
6-Cl
H
H
Me
H
Me
4-Cl
4-Me
H
Me
H
H
H
1g
1h
CH2C≡CH
H
H
a Isolated yield.
Next, the synthesized quinazolinone 1a was chosen as a change of the palladium catalyst did not result in in-
substrate for the optimization of the palladium-catalyzed creased yield (Table 2, entries 3 and 6–10). With palladi-
isocyanide insertion reaction. The model reaction was car- um(II) acetate as a catalyst and toluene as a solvent, bases
ried out using different catalysts, bases, solvents and tem- were screened and cesium carbonate was found to be the
peratures. The reaction failed to proceed when palladium most effective base (Table 2, entries 3 and 11–13). Mean-
catalyst was excluded (Table 2, entries 1 and 2). Among while, decreasing the reaction temperature to 90 °C result-
the three solvents (toluene, MeCN and DMF), toluene was ed in a significantly lower yield of 2a (Table 2, entries 3,
found to be the best choice (Table 2, entries 3–5). A 14 and 15).
Table 2 Optimization of the Palladium-Catalyzed Isocyanide Insertion Reactiona
O
O
NH
N
N
Pd (5 mol%), base (2 equiv)
solvent, 24 h
N
N
N
+
+
–
N
N
Bn
Bn
Br
1a
2a
Entry
Catalyst
Base
Solvent
Temp (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
–
–
toluene
toluene
toluene
MeCN
DMF
110
110
110
80
–
–
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
–
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
85
75
67
72
83
76
110
110
110
110
toluene
toluene
toluene
Pd(PPh3)2Cl2
Pd(dppf)Cl2
Synthesis 2013, 45, 1965–1974
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Ring-Fused Quinazolinones
1967
Table 2 Optimization of the Palladium-Catalyzed Isocyanide Insertion Reactiona (continued)
O
O
NH
N
N
Pd (5 mol%), base (2 equiv)
solvent, 24 h
N
N
N
+
+
–
N
N
Bn
Bn
Br
1a
2a
Entry
Catalyst
Base
Solvent
Temp (°C)
Yieldb (%)
9
10
11
12
13
14
15
Pd(PPh3)4
Pd(Amphos)2Cl2
Pd(OAc)2
Cs2CO3
Cs2CO3
K2CO3
K3PO4
toluene
toluene
toluene
toluene
toluene
toluene
toluene
110
110
110
110
110
100
90
81
79
53
45
78
75
63
Pd(OAc)2
Pd(OAc)2
DIPEA
Cs2CO3
Cs2CO3
Pd(OAc)2
Pd(OAc)2
a Reaction conditions: 1a (0.5 mmol), catalyst (5 mol%), tert-butyl isocyanide (0.75 mmol), base (1 mmol), solvent (2 mL), 24 h, sealed tube.
b Isolated yield.
With this standard protocol in hand, we extended the found to effectively undergo the insertion reaction; how-
method to the synthesis of various substituted phthalazi- ever, when R1 was a propargyl group (R1 = CH2C≡CH),
no[1,2-b]quinazolinones (Table 3). Various substituted the unexpected depropargylation products 2n and 2o were
quinazolinones 1 could be employed in the isocyanide in- isolated. The resulting formation of the C=N double bond
sertion reaction in high yields. Moreover, tert-butyl isocy- led to the further diversity expansion of phthalazino[1,2-
anide and cyclohexyl isocyanide (R4 = t-Bu, Cy) were b]quinazolinones.
Table 3 Synthesis of Phthalazino[1,2-b]quinazolinones
R3
N
R3
N
R3
O
O
N
O
R4
R4
R4NC, Pd(OAc)2
N
N
N
6
N
N
N
H
or
R2
R2
R2
toluene, Cs2CO3
110 °C
N
N
R1
R1
Br
1a–h
2a–m
2n,o
R1
R2
R3
R4
Product
Yielda (%)
Bn
Bn
H
H
t-Bu
Cy
2a
2b
2c
2d
2e
2f
85
83
86
81
78
80
84
87
65
78
H
H
Me
Me
Bn
Bn
Me
Me
H
H
H
t-Bu
Cy
H
H
6-Clb
6-Clb
6-Clb
6-Clb
H
H
t-Bu
Cy
H
H
t-Bu
Cy
2g
2h
2i
H
H
t-Bu
t-Bu
Me
H
4-Cl
2j
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1965–1974

1968
F. Ji et al.
PAPER
Table 3 Synthesis of Phthalazino[1,2-b]quinazolinones (continued)
R3
N
R3
N
R3
O
O
N
O
R4
R4
R4NC, Pd(OAc)2
N
N
N
6
N
N
N
H
or
R2
R2
R2
toluene, Cs2CO3
110 °C
N
N
R1
R1
Br
1a–h
2a–m
2n,o
R1
R2
R3
R4
Product
Yielda (%)
Me
H
H
H
H
H
4-Cl
4-Me
4-Me
H
Cy
2k
2l
75
83
81
66
72
Me
t-Bu
Cy
Me
2m
2n
2o
CH2C≡CH
CH2C≡CH
t-Bu
Cy
H
a Isolated yield.
b Numbering refers to the starting quinazolinone.
To understand the mechanism of the depropargylation re- dergoes nucleophilic attack at the central sp-hybridized
action, control experiments for this reaction were execut- carbon by a water molecule, thereby releasing the desired
ed (Scheme 2). It was found that the base plays a key role compound VI (Scheme 3, route 2). Further investigations
in the reaction, affecting the final product outcome. Fur- on this depropargylation reaction are in progress.
thermore, the presence of isocyanide is favorable for the
The possible mechanism of the isocyanide insertion reac-
formation of the C=N double bond. The presumed mech-
tion is also depicted (Scheme 4).5k,12 The proposed mech-
anism of the palladium-catalyzed depropargylation reac-
anism involves oxidative addition of A and coordination
tion is proposed as follows (Scheme 3):11 Firstly,
of the palladium to the intramolecular nitrogen atom to
compound I reacts with the palladium catalyst, leading to
give species B. This could then undergo an isocyanide in-
the formation of palladium complex II. Under the base
sertion process to give the intermediate C. Next, with the
conditions, C–H bond cleavage triggers an elimination re-
aid of the base, hydrogen bromide is extruded out of C to
action, generating III and IV (Scheme 3, route 1). With-
generate the seven-membered-ring product D. Finally, re-
out a base, C–N bond cleavage directly leads to the
ductive elimination affords E, regenerating the palladi-
um(0) catalyst.
formation of an allenylpalladium intermediate V at high
temperature. This allenylpalladium intermediate then un-
O
N
O
O
O
N
NH
N
N
N
N
N
3)
N
N
H
1)
N
N
+
+
N
H
N
H
O
N
Br
2p 46%
Br
1g 34%
2i minor
2n 66%
NH
N
Br
O
2)
1h
N
N
4)
H
no reaction
N
H
1) Pd(OAc)2, Cs2CO3, toluene, reflux
2) Cs2CO3, toluene, reflux
Br
3) Pd(OAc)2, Cs2CO3, tert-butyl isocyanide, toluene, reflux
4) Pd(OAc)2, toluene, reflux
1g 63%
Scheme 2 Control experiments for the depropargylation reaction
Synthesis 2013, 45, 1965–1974
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Ring-Fused Quinazolinones
1969
O
O
H
H
PdLn–1
N
N
+
C
••
H
N
IV
N
H
III
O
O
N
LnPd
N
N
H
PdLn
••
N
H
O
O
O
[Pd]+
H
LnPd
H
H
N
H2O
N
N
C
I
II
••
N
H
N
H
N
–
V
VI
LnPd
Scheme 3 Possible mechanism of the depropargylation reaction
R3
N
R3
O
O
N
N
N
N
H
R2
R2
N
N
R1
R1
Br
E
A
Pd(0)
Figure 1 Single-crystal X-ray analysis of 2a
R3
R3
O
O
N
In conclusion, we have described a palladium-catalyzed
isocyanide insertion reaction for the synthesis of phthala-
zino[1,2-b]quinazolinones from the readily obtainable
quinazolinones. Easily handled and relatively low-cost
palladium(II) acetate was used as the catalyst, without an
additional ligand. This methodology has several advan-
tages, such as good yields, accessible materials and high
functional group diversity. Meanwhile, a depropar-
gylation phenomenon was found and the resulting forma-
tion of the C=N double bond led to the further diversity
expansion of phthalazino[1,2-b]quinazolinones. The pos-
sible mechanism of the depropargylation reaction has also
been proposed and further research on this aspect is in
progress.
N
NH
Pd
N
N
R2
R2
N
Pd Br
N
R1
R1
D
B
R3
Pd
O
base
N
+
Br
–
N
H
N
R2
N
N
R1
C
Materials were obtained from commercial suppliers and used with-
out further purification. All melting points are uncorrected. Mass
spectra were recorded on a Shimadzu LCMS-2020 system. 1H and
13C NMR spectra were recorded at 500 MHz and 125 MHz, respec-
tively, in CDCl3 or DMSO-d6, and chemical shifts are reported in
ppm from internal TMS (δ). Elemental analyses were performed on
a Yanagimoto MT3CHN recorder. Infrared spectra were recorded
as thin films on a Thermo Scientific Nicolet IS-10 FT-IR spectrom-
eter.
Scheme 4 Possible mechanism of the isocyanide insertion reaction
The structures of the novel phthalazino[1,2-b]quinazoli-
1
nones were fully characterized by IR, H NMR and 13C
NMR spectroscopy, mass spectrometry and elemental
analysis. The structure of 2a was also confirmed by
single-crystal X-ray analysis (Figure 1).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1965–1974

1970
F. Ji et al.
PAPER
Quinazolinones 1 via the Cascade Reaction; General Procedure
To a soln of an isatoic anhydride (2 mmol) in MeCN (3 mL) was
added a phenylhydrazine (2 mmol) and the mixture was stirred un-
der reflux (progress of the reaction was monitored by TLC). After
the reaction was finished, 2-bromobenzaldehyde (2 mmol) and
TsOH (10 mol%) were added, and the mixture was stirred at 81 °C
overnight. Upon completion of this cascade reaction, the mixture
was concentrated under reduced pressure and the resulting residue
was purified by column chromatography.
IR: 3262, 2986, 2896, 1645, 1601, 1493, 1439, 1385, 1333, 1207,
1179, 1099 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.93 (s, 3 H), 6.44 (s, 1 H), 6.58
(d, J = 9.0 Hz, 1 H), 6.97 (m, 3 H), 7.22 (m, 2 H), 7.29 (m, 2 H),
7.39 (m, 2 H), 7.59 (m, 1 H), 7.98 (d, J = 2.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 34.57, 77.64, 112.40, 113.08,
114.73, 120.88, 122.47, 122.66, 125.88, 127.44, 127.54, 128.37,
129.98, 132.51, 133.41, 135.80, 144.27, 145.04, 160.71.
MS (ESI): m/z = 442 [M + H]+.
1-Benzyl-2-(2-bromophenyl)-3-(phenylamino)-2,3-dihydro-
quinazolin-4(1H)-one (1a)
White solid; yield: 0.840 g (87%); mp 192–194 °C.
Anal. Calcd for C21H17BrClN3O: C, 56.97; H, 3.87; N, 9.49. Found:
C, 56.79; H, 3.85; N, 9.55.
IR: 3244, 3044, 2940, 1653, 1601, 1493, 1385, 1341, 1225, 1153,
1099 cm–1.
1H NMR (500 MHz, CDCl3): δ = 4.38 (d, J = 16.5 Hz, 1 H), 4.70 (d,
J = 16.0 Hz, 1 H), 6.52 (s, 1 H), 6.69 (d, J = 8.5 Hz, 1 H), 6.90 (m,
4 H), 7.22 (m, 4 H), 7.36 (m, 6 H), 7.56 (m, 2 H), 8.07 (d, J = 8.0
Hz, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 50.57, 76.46, 111.70, 112.77,
114.30, 117.66, 118.84, 122.08, 126.58, 127.02, 127.65, 128.20,
128.34, 130.54, 132.63, 133.96, 136.34, 137.84, 145.33, 146.66,
160.76.
2-(2-Bromophenyl)-3-[(4-chlorophenyl)amino]-1-methyl-2,3-
dihydroquinazolin-4(1H)-one (1e)
White solid; yield: 0.662 g (75%); mp 160–162 °C.
IR: 3272, 2986, 2888, 1646, 1601, 1493, 1385, 1341, 1261, 1207,
1163, 1091 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.92 (s, 3 H), 6.33 (s, 1 H), 6.43
(s, 1 H), 6.64 (d, J = 8.5 Hz, 1 H), 6.91 (m, 3 H), 7.21 (m, 4 H), 7.42
(m, 2 H), 7.58 (m, 1 H), 8.01 (d, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 34.29, 77.67, 110.81, 113.26,
114.36, 117.42, 122.50, 125.52, 125.97, 127.54, 127.97, 128.28,
129.89, 132.41, 133.90, 135.93, 144.02, 145.80, 161.83.
MS (ESI): m/z = 484 [M + H]+.
MS (ESI): m/z = 442 [M + H]+.
Anal. Calcd for C27H22BrN3O: C, 66.95; H, 4.58; N, 8.67. Found: C,
66.77; H, 4.55; N, 8.75.
Anal. Calcd for C21H17BrClN3O: C, 56.97; H, 3.87; N, 9.49. Found:
C, 56.74; H, 3.95; N, 9.45.
2-(2-Bromophenyl)-1-methyl-3-(phenylamino)-2,3-dihydro-
quinazolin-4(1H)-one (1b)
White solid; yield: 0.692 g (85%); mp 162–164 °C.
2-(2-Bromophenyl)-1-methyl-3-(p-tolylamino)-2,3-dihydro-
quinazolin-4(1H)-one (1f)
White solid; yield: 0.749 g (89%); mp 178–180 °C.
IR: 3244, 3012, 2940, 1663, 1601, 1493, 1403, 1333, 1261, 1197,
1099 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.94 (s, 3 H), 6.37 (s, 1 H), 6.47
(s, 1 H), 6.64 (d, J = 8.0 Hz, 1 H), 6.91 (m, 1 H), 6.99 (m, 3 H), 7.20
(m, 2 H), 7.29 (m, 2 H), 7.44 (m, 2 H), 7.58 (m, 1 H), 8.03 (d, J = 8.0
Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 34.41, 77.69, 110.89, 113.09,
113.59, 117.36, 120.73, 122.46, 126.03, 127.49, 127.93, 128.34,
129.79, 132.39, 133.72, 136.16, 145.39, 145.77, 161.80.
IR: 3226, 2986, 2888, 1645, 1609, 1485, 1395, 1349, 1261, 1207,
1163, 1099 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.94 (s, 3 H), 6.32
(s, 1 H), 6.46 (s, 1 H), 6.63 (d, J = 8.5 Hz, 1 H), 6.92 (m, 3 H), 7.09
(d, J = 8.5 Hz, 2 H), 7.20 (m, 2 H), 7.44 (m, 2 H), 7.58 (m, 1 H),
8.03 (d, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 19.70, 34.38, 77.63, 110.86,
113.49, 113.64, 117.32, 122.45, 126.02, 127.48, 127.89, 128.85,
129.75, 130.21, 132.36, 133.64, 136.24, 142.97, 145.73, 161.72.
MS (ESI): m/z = 408 [M + H]+.
MS (ESI): m/z = 422 [M + H]+.
Anal. Calcd for C21H18BrN3O: C, 61.78; H, 4.44; N, 10.29. Found:
C, 61.97; H, 4.51; N, 10.25.
Anal. Calcd for C22H20BrN3O: C, 62.57; H, 4.77; N, 9.95. Found: C,
62.44; H, 4.85; N, 9.98.
1-Benzyl-2-(2-bromophenyl)-6-chloro-3-(phenylamino)-2,3-di-
hydroquinazolin-4(1H)-one (1c)
White solid; yield: 0.848 g (82%); mp >230 °C.
2-(2-Bromophenyl)-3-(phenylamino)-2,3-dihydroquinazolin-
4(1H)-one (1g)
White solid; yield: 0.590 g (75%); mp 184–186 °C.
IR: 3272, 3226, 2926, 1645, 1601, 1493, 1395, 1341, 1251, 1179,
1019 cm–1.
IR: 3216, 2986, 2881, 1645, 1605, 1481, 1385, 1301, 1256, 1157,
1085 cm–1.
1H NMR (500 MHz, CDCl3): δ = 5.36 (s, 1 H), 6.26 (s, 1 H), 6.63
(d, J = 8.0 Hz, 1 H), 6.87 (m, 1 H), 6.98 (m, 1 H), 7.04 (d, J = 7.5
Hz, 2 H), 7.22 (m, 1 H), 7.29 (m, 5 H), 7.61 (d, J = 7.5 Hz, 1 H),
7.98 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 72.55, 113.01, 113.59, 113.89,
118.46, 120.91, 121.17, 126.03, 126.96, 127.66, 128.39, 129.44,
132.71, 133.35, 136.57, 143.88, 145.38, 163.23.
1H NMR (500 MHz, CDCl3): δ = 4.39 (d, J = 16.5 Hz, 1 H), 4.64 (d,
J = 16.5 Hz, 1 H), 6.35 (s, 1 H), 6.50 (s, 1 H), 6.62 (d, J = 8.5 Hz, 1
H), 6.83 (d, J = 8.0 Hz, 2 H), 6.94 (m, 1 H), 7.23 (m, 4 H), 7.29 (m,
1 H), 7.34 (m, 5 H), 7.51 (m, 1 H), 7.57 (m, 1 H), 8.02 (d, J = 1.5
Hz, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 50.69, 76.44, 111.68, 114.94,
115.47, 118.95, 121.46, 122.03, 126.58, 126.66, 127.13, 128.26,
128.37, 130.69, 132.68, 133.54, 135.92, 137.46, 144.14, 146.37,
159.66.
MS (ESI): m/z = 394 [M + H]+.
MS (ESI): m/z = 518 [M + H]+.
Anal. Calcd for C20H16BrN3O: C, 60.93; H, 4.09; N, 10.66. Found:
C, 60.84; H, 4.15; N, 10.78.
Anal. Calcd for C27H21BrClN3O: C, 62.50; H, 4.08; N, 8.10. Found:
C, 62.67; H, 4.05; N, 8.15.
2-(2-Bromophenyl)-3-(phenylamino)-1-(prop-2-ynyl)-2,3-dihy-
droquinazolin-4(1H)-one (1h)
White solid; yield: 0.672 g (78%); mp 165–167 °C.
2-(2-Bromophenyl)-6-chloro-1-methyl-3-(phenylamino)-2,3-di-
hydroquinazolin-4(1H)-one (1d)
White solid; yield: 0.741 g (84%); mp 190–192 °C.
Synthesis 2013, 45, 1965–1974
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Ring-Fused Quinazolinones
1971
IR: 3272, 2986, 2896, 1653, 1601, 1493, 1395, 1323, 1243, 1163,
1099 cm–1.
(d, J = 7.5 Hz, 2 H), 7.27 (m, 1 H), 7.32 (m, 3 H), 7.38 (m, 1 H),
7.91 (m, 1 H), 8.33 (m, 1 H).
1H NMR (500 MHz, CDCl3): δ = 2.11 (m, 1 H), 4.22 (m, 2 H), 6.34
(s, 1 H), 6.55 (s, 1 H), 6.88 (d, J = 8.0 Hz, 1 H), 6.99 (m, 4 H), 7.19
(m, 2 H), 7.27 (m, 2 H), 7.42 (m, 1 H), 7.49 (m, 1 H), 7.58 (m, 1 H),
8.08 (d, J = 8.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 29.33, 39.44, 56.49, 71.24,
113.33, 115.64, 118.26, 120.13, 121.77, 123.14, 127.40, 128.10,
128.25, 128.33, 128.95, 130.95, 133.44, 137.71, 140.27, 143.70,
145.50, 163.77.
13C NMR (125 MHz, CDCl3): δ = 38.02, 72.36, 77.15, 112.64,
113.20, 114.97, 118.69, 120.78, 122.76, 126.50, 127.19, 128.03,
128.28, 129.78, 132.32, 133.53, 136.30, 143.83, 145.31, 161.90.
MS (ESI): m/z = 411 [M + H]+.
Anal. Calcd for C26H26N4O: C, 76.07; H, 6.38; N, 13.65. Found: C,
76.31; H, 6.35; N, 13.77.
MS (ESI): m/z = 432 [M + H]+.
5-(Cyclohexylimino)-13-methyl-6-phenyl-5,6,13,13a-tetra-
hydro-8H-phthalazino[1,2-b]quinazolin-8-one (2d)
White solid; yield: 0.177 g (81%); mp 189–190 °C.
Anal. Calcd for C23H18BrN3O: C, 63.90; H, 4.20; N, 9.72. Found: C,
63.74; H, 4.15; N, 9.75.
IR: 2922, 2852, 1689, 1637, 1601, 1493, 1449, 1367, 1297, 1225,
1163, 1091, 1027 cm–1.
Phthalazino[1,2-b]quinazolinones 2 via the Isocyanide Insertion
Reaction; General Procedure
To a soln of a quinazolinone 1 (0.5 mmol) in toluene (2 mL) was
successively added an isocyanide (0.75 mmol), Pd(OAc)2 (5 mol%)
and Cs2CO3 (1 mmol). The mixture was stirred in a sealed tube at
110 °C for 24 h. Upon completion of the reaction, the mixture was
concentrated under reduced pressure and the resulting residue was
purified by column chromatography.
1H NMR (500 MHz, CDCl3): δ = 1.05 (m, 1 H), 1.24 (m, 2 H), 1.52
(m, 3 H), 1.72 (m, 3 H), 2.04 (m, 1 H), 3.33 (s, 3 H), 3.58 (m, 1 H),
5.80 (s, 1 H), 6.79 (m, 2 H), 7.06 (d, J = 7.5 Hz, 1 H), 7.10 (m, 1 H),
7.17 (m, 2 H), 7.30 (m, 4 H), 7.39 (m, 1 H), 7.89 (m, 1 H), 8.37 (m,
1 H).
13C NMR (125 MHz, CDCl3): δ = 23.41, 23.61, 24.97, 31.70, 32.49,
39.29, 56.99, 72.50, 112.93, 115.12, 118.04, 118.99, 121.69,
122.91, 127.51, 128.24, 128.47, 129.15, 129.93, 133.63, 137.47,
142.03, 143.35, 145.47, 164.51.
13-Benzyl-5-(tert-butylimino)-6-phenyl-5,6,13,13a-tetrahydro-
8H-phthalazino[1,2-b]quinazolin-8-one (2a)
White solid; yield: 0.206 g (85%); mp 188–190 °C.
MS (ESI): m/z = 437 [M + H]+.
IR: 2965, 2899, 1681, 1645, 1601, 1493, 1454, 1349, 1261, 1233,
1073, 1019 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 1.28 (s, 9 H), 4.74 (d, J = 16.0
Hz, 1 H), 5.06 (d, J = 16.0 Hz, 1 H), 5.87 (s, 1 H), 6.77 (m, 1 H),
7.07 (m, 4 H), 7.28 (m, 11 H), 7.67 (d, J = 6.5 Hz, 1 H), 8.18 (d,
J = 6.5 Hz, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 29.56, 53.82, 56.41, 69.27,
115.50, 115.60, 118.57, 119.57, 122.86, 123.41, 126.81, 127.64,
127.81, 127.99, 128.85, 129.81, 130.55, 134.19, 136.82, 138.26,
140.33, 143.35, 145.00, 163.96.
Anal. Calcd for C28H28N4O: C, 77.04; H, 6.46; N, 12.83. Found: C,
76.91; H, 6.55; N, 12.81.
13-Benzyl-5-(tert-butylimino)-10-chloro-6-phenyl-5,6,13,13a-
tetrahydro-8H-phthalazino[1,2-b]quinazolin-8-one (2e)
White solid; yield: 0.203 g (78%); mp 196–198 °C.
IR: 2968, 2852, 1671, 1637, 1601, 1493, 1439, 1359, 1251, 1189,
1091, 1019 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.38 (s, 9 H), 4.45 (d, J = 15.0 Hz,
1 H), 4.80 (d, J = 15.0 Hz, 1 H), 5.68 (s, 1 H), 6.96 (d, J = 8.5 Hz, 1
H), 7.13 (m, 5 H), 7.28 (m, 9 H), 7.96 (m, 1 H), 8.32 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 29.33, 56.52, 56.64, 68.54,
118.13, 119.11, 120.16, 121.86, 123.24, 125.31, 126.93, 127.01,
127.46, 127.82, 128.22, 129.01, 130.77, 133.19, 135.02, 136.96,
140.08, 143.38, 143.64, 162.73.
MS (ESI): m/z = 487 [M + H]+.
Anal. Calcd for C32H30N4O: C, 78.98; H, 6.21; N, 11.51. Found: C,
78.87; H, 6.15; N, 11.65.
13-Benzyl-5-(cyclohexylimino)-6-phenyl-5,6,13,13a-tetra-
hydro-8H-phthalazino[1,2-b]quinazolin-8-one (2b)
White solid; yield: 0.212 g (83%); mp >230 °C.
MS (ESI): m/z = 521 [M + H]+.
IR: 2958, 2904, 1681, 1645, 1609, 1493, 1449, 1377, 1269, 1225,
1073, 1019 cm–1.
Anal. Calcd for C32H29ClN4O: C, 73.76; H, 5.61; N, 10.75. Found:
C, 73.51; H, 5.76; N, 10.87.
1H NMR (500 MHz, CDCl3): δ = 1.25 (m, 1 H), 1.42 (m, 2 H), 1.52
(m, 3 H), 1.71 (m, 3 H), 2.04 (m, 1 H), 3.58 (m, 1 H), 4.49 (d,
J = 15.0 Hz, 1 H), 4.87 (d, J = 15.0 Hz, 1 H), 5.73 (s, 1 H), 6.88 (m,
1 H), 7.00 (d, J = 8.0 Hz, 1 H), 7.06 (m, 1 H), 7.23 (m, 12 H), 7.38
(m, 1 H), 7.93 (m, 1 H), 8.34 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 23.39, 23.61, 24.97, 31.65, 32.47,
56.54, 56.97, 69.74, 116.53, 117.62, 118.73, 119.81, 122.03,
122.75, 126.90, 127.33, 127.50, 127.78, 128.42, 129.13, 129.84,
133.45, 135.47, 137.06, 141.88, 143.58, 145.34, 164.42.
13-Benzyl-10-chloro-5-(cyclohexylimino)-6-phenyl-5,6,13,13a-
tetrahydro-8H-phthalazino[1,2-b]quinazolin-8-one (2f)
White solid; yield: 0.218 g (80%); mp >230 °C.
IR: 2922, 2842, 1689, 1645, 1601, 1475, 1431, 1367, 1251, 1189,
1127, 1081, 1027 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.05 (m, 1 H), 1.28 (m, 2 H), 1.55
(m, 3 H), 1.72 (m, 3 H), 2.05 (m, 1 H), 3.58 (m, 1 H), 4.50 (d,
J = 15.0 Hz, 1 H), 4.88 (d, J = 15.0 Hz, 1 H), 5.76 (s, 1 H), 6.96 (d,
J = 8.5 Hz, 1 H), 7.09 (m, 1 H), 7.27 (m, 13 H), 7.93 (m, 1 H), 8.38
(m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 23.34, 23.54, 24.95, 31.60, 32.49,
56.56, 56.99, 69.84, 117.90, 118.72, 121.90, 122.87, 125.23,
126.83, 127.07, 127.55, 127.62, 127.87, 127.98, 129.22, 129.76,
133.34, 135.01, 136.62, 141.65, 143.28, 143.71, 161.32.
MS (ESI): m/z = 513 [M + H]+.
Anal. Calcd for C34H32N4O: C, 79.66; H, 6.29; N, 10.93. Found: C,
79.57; H, 6.45; N, 10.85.
5-(tert-Butylimino)-13-methyl-6-phenyl-5,6,13,13a-tetrahydro-
8H-phthalazino[1,2-b]quinazolin-8-one (2c)
White solid; yield: 0.176 g (86%); mp 188–190 °C.
MS (ESI): m/z = 547 [M + H]+.
IR: 2958, 2904, 1689, 1645, 1601, 1493, 1449, 1377, 1287, 1225,
1197, 1163, 1091, 1055 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.36 (s, 9 H), 3.25 (s, 3 H), 5.70
(s, 1 H), 6.76 (d, J = 8.0 Hz, 1 H), 6.82 (m, 1 H), 7.09 (m, 2 H), 7.15
Anal. Calcd for C34H31ClN4O: C, 74.64; H, 5.71; N, 10.24. Found:
C, 74.41; H, 5.76; N, 10.17.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1965–1974

1972
F. Ji et al.
PAPER
5-(tert-Butylimino)-10-chloro-13-methyl-6-phenyl-5,6,13,13a-
tetrahydro-8H-phthalazino[1,2-b]quinazolin-8-one (2g)
White solid; yield: 0.186 g (84%); mp >230 °C.
Anal. Calcd for C26H25ClN4O: C, 70.18; H, 5.66; N, 12.59. Found:
C, 70.31; H, 5.56; N, 12.67.
6-(4-Chlorophenyl)-5-(cyclohexylimino)-13-methyl-5,6,13,13a-
tetrahydro-8H-phthalazino[1,2-b]quinazolin-8-one (2k)
White solid; yield: 0.176 g (75%); mp 151–153 °C.
IR: 2968, 2896, 1682, 1645, 1609, 1493, 1421, 1359, 1305, 1215,
1117, 1099, 1037 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.38 (s, 9 H), 3.28 (s, 3 H), 5.72
(s, 1 H), 6.73 (d, J = 8.5 Hz, 1 H), 7.07 (m, 1 H), 7.16 (m, 3 H), 7.28
(m, 1 H), 7.35 (m, 4 H), 7.90 (s, 1 H), 8.37 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 29.30, 39.52, 56.57, 71.22,
114.75, 116.77, 120.07, 121.61, 123.29, 123.67, 127.59, 127.87,
128.22, 128.32, 129.02, 130.85, 133.25, 137.24, 139.93, 143.46,
143.97, 162.70.
IR: 2967, 2921, 1678, 1645, 1602, 1453, 1365, 1245, 1162, 1087,
1026 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.05 (m, 1 H), 1.27 (m, 2 H), 1.45
(m, 1 H), 1.54 (m, 2 H), 1.72 (m, 3 H), 2.04 (m, 1 H), 3.36 (s, 3 H),
3.56 (m, 1 H), 5.77 (s, 1 H), 6.81 (m, 2 H), 7.10 (m, 3 H), 7.30 (m,
4 H), 7.42 (m, 1 H), 7.90 (m, 1 H), 8.37 (d, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 23.40, 23.58, 24.92, 31.63, 32.50,
39.33, 57.12, 72.58, 113.00, 114.93, 118.16, 121.77, 127.58,
127.88, 128.31, 128.48, 129.35, 129.62, 133.81, 137.30, 140.71,
142.92, 145.43, 164.52.
MS (ESI): m/z = 445 [M + H]+.
Anal. Calcd for C26H25ClN4O: C, 70.18; H, 5.66; N, 12.59. Found:
C, 70.42; H, 5.71; N, 12.47.
MS (ESI): m/z = 471 [M + H]+.
10-Chloro-5-(cyclohexylimino)-13-methyl-6-phenyl-5,6,13,13a-
tetrahydro-8H-phthalazino[1,2-b]quinazolin-8-one (2h)
White solid; yield: 0.204 g (87%); mp 140–142 °C.
Anal. Calcd for C28H27ClN4O: C, 71.40; H, 5.78; N, 11.90. Found:
C, 71.21; H, 5.76; N, 11.97.
IR: 2986, 2904, 1717, 1671, 1601, 1457, 1359, 1323, 1287, 1243,
1189, 1145, 1027 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.05 (m, 1 H), 1.28 (m, 3 H), 1.55
(m, 2 H), 1.72 (m, 3 H), 2.05 (m, 1 H), 3.34 (s, 3 H), 3.58 (m, 1 H),
5.82 (s, 1 H), 6.74 (d, J = 8.5 Hz, 1 H), 7.05 (d, J = 7.5 Hz, 1 H),
7.17 (m, 3 H), 7.34 (m, 5 H), 7.89 (d, J = 2.5 Hz, 1 H), 8.41 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 23.36, 23.56, 24.95, 31.64, 32.50,
39.37, 57.01, 72.44, 114.42, 116.26, 118.88, 121.56, 123.05,
123.51, 127.65, 127.96, 128.32, 129.23, 129.84, 133.45, 137.00,
141.80, 143.09, 143.97, 163.43.
5-(tert-Butylimino)-13-methyl-6-p-tolyl-5,6,13,13a-tetrahydro-
8H-phthalazino[1,2-b]quinazolin-8-one (2l)
White solid; yield: 0.176 g (83%); mp 198–200 °C.
IR: 2976, 2914, 1681, 1642, 1609, 1493, 1449, 1367, 1269, 1215,
1163, 1081, 1037 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.38 (s, 9 H), 2.35 (s, 3 H), 3.28
(s, 3 H), 5.74 (s, 1 H), 6.77 (d, J = 8.5 Hz, 1 H), 6.83 (m, 1 H), 7.08
(m, 3 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.29 (m, 2 H), 7.41 (m, 1 H),
7.93 (m, 1 H), 8.35 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 19.89, 29.39, 39.34, 56.29, 70.93,
113.08, 115.52, 118.11, 120.67, 121.67, 127.37, 128.09, 128.32,
128.82, 128.90, 130.97, 133.06, 133.41, 137.82, 140.90, 141.16,
145.42, 163.72.
MS (ESI): m/z = 471 [M + H]+.
Anal. Calcd for C28H27ClN4O: C, 71.40; H, 5.78; N, 11.90. Found:
C, 71.21; H, 5.66; N, 12.01.
MS (ESI): m/z = 425 [M + H]+.
5-(tert-Butylimino)-6-phenyl-5,6,13,13a-tetrahydro-8H-
phthalazino[1,2-b]quinazolin-8-one (2i)
White solid; yield: 0.129 g (65%); mp 185–186 °C.
Anal. Calcd for C27H28N4O: C, 76.39; H, 6.65; N, 13.20. Found: C,
76.21; H, 6.56; N, 13.27.
IR: 2988, 2845, 1674, 1632, 1601, 1456, 1356, 1245, 1135, 1091,
1025 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.34 (s, 9 H), 5.89 (s, 1 H), 6.81
(d, J = 7.5 Hz, 2 H), 6.88 (m, 1 H), 7.14 (m, 3 H), 7.46 (m, 3 H),
7.79 (m, 1 H), 7.85 (d, J = 8.0 Hz, 1 H), 8.33 (m, 1 H), 8.45 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 29.40, 50.34, 72.59, 116.62,
121.20, 122.06, 124.72, 125.51, 125.63, 126.15, 126.52, 126.66,
127.78, 128.39, 131.38, 133.22, 136.25, 144.92, 146.05, 148.11,
158.35.
5-(Cyclohexylimino)-13-methyl-6-p-tolyl-5,6,13,13a-tetra-
hydro-8H-phthalazino[1,2-b]quinazolin-8-one (2m)
White solid; yield: 0.182 g (81%); mp 188–190 °C.
IR: 2922, 2852, 1681, 1637, 1609, 1493, 1449, 1377, 1297, 1225,
1163, 1099, 1037 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.05 (m, 1 H), 1.27 (m, 2 H), 1.54
(m, 3 H), 1.75 (m, 3 H), 2.07 (m, 1 H), 2.37 (s, 3 H), 3.34 (s, 3 H),
3.58 (m, 1 H), 5.83 (s, 1 H), 6.80 (m, 2 H), 7.12 (m, 5 H), 7.29 (m,
2 H), 7.42 (m, 1 H), 7.92 (m, 1 H), 8.39 (d, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 19.85, 23.46, 23.63, 25.01, 31.83,
32.39, 39.18, 56.75, 72.26, 112.80, 115.11, 117.96, 119.46, 121.61,
127.43, 127.52, 128.46, 128.81, 129.08, 130.03, 132.76, 133.59,
137.52, 139.58, 143.78, 145.44, 164.45.
MS (ESI): m/z = 397 [M + H]+.
Anal. Calcd for C25H24N4O: C, 75.73; H, 6.10; N, 14.13. Found: C,
75.81; H, 6.15; N, 14.01.
5-(tert-Butylimino)-6-(4-chlorophenyl)-13-methyl-5,6,13,13a-
tetrahydro-8H-phthalazino[1,2-b]quinazolin-8-one (2j)
White solid; yield: 0.173 g (78%); mp 164–166 °C.
MS (ESI): m/z = 451 [M + H]+.
Anal. Calcd for C29H30N4O: C, 77.30; H, 6.71; N, 12.43. Found: C,
77.11; H, 6.66; N, 12.57.
IR: 2976, 2914, 1689, 1653, 1609, 1475, 1349, 1269, 1225, 1163,
1091, 1037 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.39 (s, 9 H), 3.30 (s, 3 H), 5.69
(s, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 6.85 (m, 1 H), 7.11 (d, J = 9.0 Hz,
3 H), 7.34 (m, 4 H), 7.42 (m, 1 H), 7.93 (m, 1 H), 8.34 (m, 1 H).
13C NMR (125 MHz, CDCl3): δ = 29.32, 39.47, 56.63, 71.35,
113.40, 115.49, 118.37, 121.17, 121.84, 127.51, 128.14, 128.36,
129.13, 130.64, 133.59, 137.51, 139.69, 142.43, 145.47, 163.76.
5-(tert-Butylimino)-6-phenyl-5,6-dihydro-8H-phthalazino[1,2-
b]quinazolin-8-one (2n)
White solid; yield: 0.130 g (66%); mp 154–156 °C.
IR: 2987, 2887, 1675, 1632, 1601, 1445, 1375, 1245, 1176, 1095,
1025 cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.59 (s, 9 H), 6.72 (d, J = 8.0 Hz,
2 H), 6.92 (m, 1 H), 7.15 (m, 2 H), 7.58 (m, 3 H), 7.84 (m, 2 H), 7.96
(d, J = 8.0 Hz, 1 H), 8.34 (d, J = 8.5 Hz, 1 H), 8.45 (d, J = 7.5 Hz, 1
H).
MS (ESI): m/z = 445 [M + H]+.
Synthesis 2013, 45, 1965–1974
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Ring-Fused Quinazolinones
1973
13C NMR (125 MHz, CDCl3): δ = 29.66, 57.29, 114.87, 120.79,
121.99, 125.63, 126.05, 126.34, 126.77, 127.04, 127.65, 128.12,
129.81, 131.49, 133.66, 133.84, 143.18, 143.92, 145.82, 147.73,
158.44.
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MS (ESI): m/z = 395 [M + H]+.
Anal. Calcd for C25H22N4O: C, 76.12; H, 5.62; N, 14.20. Found: C,
76.21; H, 5.66; N, 14.07.
5-(Cyclohexylimino)-6-phenyl-5,6-dihydro-8H-phthalazi-
no[1,2-b]quinazolin-8-one (2o)
White solid; yield: 0.151 g (72%); mp 210–211 °C.
IR: 2985, 2892, 1685, 1632, 1613, 1435, 1356, 1243, 1125, 1099
cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.30 (m, 1 H), 1.43 (m, 1 H), 1.55
(m, 2 H), 1.69 (m, 1 H), 1.78 (m, 3 H), 1.87 (m, 1 H), 1.95 (m, 1 H),
4.42 (m, 1 H), 6.67 (d, J = 8.5 Hz, 2 H), 6.97 (m, 1 H), 7.20 (m, 2
H), 7.59 (m, 3 H), 7.85 (d, J = 4.0 Hz, 2 H), 8.04 (m, 1 H), 8.44 (m,
2 H).
13C NMR (125 MHz, CDCl3): δ = 23.22, 23.56, 24.69, 28.71, 32.21,
33.32, 58.38, 113.68, 120.58, 122.23, 125.71, 125.82, 126.31,
126.75, 127.02, 127.77, 128.62, 130.29, 131.51, 133.80, 142.65,
145.69, 147.53, 158.09.
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Ed. 2000, 39, 4156.
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(b) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104,
2127. (c) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108,
3395.
MS (ESI): m/z = 421 [M + H]+.
Anal. Calcd for C27H24N4O: C, 77.12; H, 5.75; N, 13.32. Found: C,
77.31; H, 5.86; N, 13.17.
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Takemoto, Y. Org. Lett. 2012, 14, 4270. (h) Liu, B.; Li, Y.;
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2288. (i) Hu, Z.; Liang, D.; Zhao, J.; Huang, J.; Zhu, Q.
Chem. Commun. 2012, 48, 7371. (j) Zhu, C.; Xie, W.; Falck,
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Kuijer, S.; Rýček, L.; Sergeyev, S.; Janssen, E.; De Kanter,
F. J. J.; Maes, B. U. W.; Ruijter, E.; Orru, R. V. A. Chem.
Eur. J. 2011, 17, 15039. (l) Cai, Q.; Zhou, F.; Xu, T.; Fu, L.;
Ding, K. Org. Lett. 2011, 13, 340. (m) Tobisu, M.; Kitajima,
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Sasayama, D.; Kawabata, T.; Takehira, K.; Takaki, K.
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2-(2-Bromophenyl)-3-(phenylamino)quinazolin-4(3H)-one (2p)
White solid; yield: 0.090 g (46%); mp 190–191 °C.
IR: 3201, 2976, 2865, 1657, 1605, 1465, 1375, 1254, 1089, 1032
cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.24 (d, J = 8.0 Hz, 1 H), 7.39 (m,
2 H), 7.43 (m, 2 H), 7.48 (m, 3 H), 7.65 (m, 1 H), 7.85 (m, 1 H), 7.95
(m, 1 H), 8.34 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 111.35, 117.64, 118.71, 122.34,
123.39, 124.46, 125.73, 125.84, 127.62, 128.55, 132.50, 133.08,
140.74, 147.16, 147.42, 148.08, 155.32.
MS (ESI): m/z = 392 [M + H]+.
Anal. Calcd for C20H14BrN3O: C, 61.24; H, 3.60; N, 10.71. Found:
C, 61.41; H, 3.56; N, 10.77.
Acknowledgment
We are thankful for financial support by NUST research funding
(2011ZDJH07). We also acknowledge the Analysis and Testing
Center of Nanjing University of Science and Technology for NMR
analyses.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
Primary Data for this article are available online at
http://www.thieme-connect.com/ejournals/toc/synthesis and can be
cited using the following DOI: 10.4125/pd0046thDaryaiPmatPriiDy
m
rp4hd1a.0r2D6t/5y4.aZteanh1l01
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hemrysti
© Georg Thieme Verlag Stuttgart · New York
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F. Ji et al.
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