Palladium-Catalyzed Oxidative Three-Component Coupling of Anthranilamides with Isocyanides and Arylboronic Acids: Access to 2,3-Disubstituted Quinazolinones

Article abstract of DOI:10.1021/acs.joc.8b01218

A novel palladium-catalyzed oxidative three-component coupling of easily accessible N-substituted anthranilamides with isocyanides and arylboronic acids is achieved. This protocol offers an alternative approach toward 2,3-disubstituted quinazolinones with a wide substrate scope and good functional group tolerance.

Full text of DOI:10.1021/acs.joc.8b01218

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Article
Palladium-Catalyzed Oxidative Three-Component Coupling
of Anthranilamides with Isocyanides and Arylboronic
Acids: Access to 2,3-Disubstituted Quinazolinones
Chun Qian, Kui Liu, Shou-Wei Tao, Fang-Ling Zhang, Yong-Ming Zhu, and Shi-Lin Yang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 02 Jul 2018
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Palladium-Catalyzed Oxidative Three-Component Coupling
of Anthranilamides with Isocyanides and Arylboronic Acids:
Access to 2,3-Disubstituted Quinazolinones
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†,‡
†
†
†
Chun Qian, Kui Liu, Shou-Wei Tao, Fang-Ling Zhang,
*,†
*,†, ‡
Yong-Ming Zhu, and Shi-Lin Yang
†College of Pharmaceutical Sciences, Soochow University, Suzhou,
2
‡
15123, China
School of Pharmaceutical Sciences, Guizhou University, Guiyang,
550000, China
ABSTRACT: A novel palladium-catalyzed oxidative three-component
coupling of easily accessible N-substituted anthranilamides with
isocyanides and arylboronic acids is achieved. This protocol offers an
alternative approach toward 2,3-disubstituted quinazolinones with wide
substrate scope and good functional group tolerance.
INTRODUCTION
Quinazolinones are an important class of fused heterocyclic compounds
that attracted significant attention in recent organic and medicinal
chemistry. In particular, 2,3-disubstituted quinazolinones show a broad
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range of biological and pharmacological activities, including
anti-inflammatory, anticancer, antifungal, antibacterial, antidiabetic,
1
anticonvulsant and antiviral properties. Moreover, their wide presence in
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natural products as well as clinical drugs has also been reported (Figure
1
).2 In view of their importance, various methods to synthesize these
compounds have been developed. As shown in Scheme 1, representative
examples of these approaches include (a) condensation of
3
4
5
anthranilamides with aldehydes, benzyl halides, benzyl alcohols, or
6
orthoesters; (b) dehydrative cyclization of the diamide derivatives of
7
2
2
-aminobenzoic acids; (c) Cu-catalyzed aryl amidation of N-substituted
8
-bromobenzamides with amides; (d) arylation of quinazolinones with
9
aryl halides catalyzed by metal catalyst; (e) condensation of methyl
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anthranilate with amides with the aid of the Ph
3
P-I system; Although
2
these methodologies have their own advantages, most of them suffer from
a variety of limitations including multistep procedures, limited substrate
scopes as well as relatively harsh reaction conditions in the process.
Notably, carbon monoxide (CO) has emerged as valuable C1 building
block to synthesize 2-aryl quinazolinones from anthranilamides and
11
bromobenzenes (Scheme 1, f). To overcome the problems associated
with high pressure, long reaction time and manipulation complexity, in
2
014, our group reported that 2-aryl quinazolinones could be efficiently
synthesized from anthranilamides and aryl halides via isocyanides
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1
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insertion (Scheme 1, g). However, the approach needs at least one
equivalent of base, which is not compatible with base sensitive functional
groups in the substrates. On the other hand, only trace amount of
2,3-disubstituted quinazolinones could be obtained by this route. For C1
source, many applications of isocyanide have been reported. Especially,
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palladium-catalyzed isocyanide insertion into carbon-halogen bonds and
1
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carbon-hydrogen bonds . Nevertheless, palladium-catalyzed isocyanide
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insertion into the C-B bond has rarely been described. Very recently,
Gao et al.15c discovered an oxidative cross-coupling reaction of
arylboronic acids and isocyanides for the synthesis of amides and diaryl
ketones. In a continuation of our efforts on isocyanides chemistry and
oxidative cross-couplings, we considered that 2,3-disubstituted
quinazolinones could be synthesized by building a C−N bond between
readily available N-substituted 2-aminobenzamides and arylboronic acids.
We envisioned that palladium-catalyzed oxidative coupling of
anthranilamides with isocyanides and arylboronic acids would be of
interest, considering that arylboronic acids hold great promise due to their
commercially available and also air-stable. In addition, using arylboronic
acids, isocyanides and N-substituted 2-aminobenzamides for the
formation of 2,3-disubstituted quinazolinones would extend the reported
methods and also develop a new path to form potentially bioactive
nitrogen heterocycles. To our knowledge, palladium catalyst has never
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been applied in oxidative coupling of anthranilamides with arylboronic
acids and isocyanides. Thus, we illustrate the first palladium-catalyzed
oxidative three-component coupling of arylboronic acids, isocyanides and
N-substituted 2-aminobenzamides to construct 2,3-disubstituted
quinazolinones.
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Figure 1. Selected quinazolinone drugs and natural products.
Scheme 1. Classical Routes and the Present Method To Synthesize
Quinazolinones
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RESULTS AND DISCUSSION
Initially, we performed a reaction using phenylboronic acid 1a,
-amino-N-methylbenzamide 2a and tert-butyl isocyanide in the presence
2
of Pd(OAc)
2
and Cu(OAc)
2
. When the reaction was carried out in DMF as
o
a solvent under nitrogen at 100 C for 8 h, we could isolate the desired
product 3a in 37% yield (Table 1, entry 1). Meanwhile, various catalytic
systems were examined and Pd(PPh
reaction giving 3a in an optimised yield of 95% (Table 1, entries 2-8). Of
all the oxidants we tested, Cu(OAc) performed best indicating that
acetates could have a promoting effect on the reaction (Table 1, entries
-14). When the reaction was carried out under free air and oxygen
atmospheres, respectively, but no desired product could be detected.
3
)Cl proved the best catalyst for this
2
2
9
(Table 1, entries 15-16). Subsequent screening of other solvents including
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DMSO, DCE, and toluene did not give better results (Table 1, entries
1
7-19). Overall, the optimized reaction conditions include Pd(PPh
3
)
2
Cl
2
(
5 mol%) as the catalyst and Cu(OAc) (2.0 equiv.) as the oxidant under a
2
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o
nitrogen atmosphere at 100 C for 8 hours in DMF.
Table 1. Conditions for Optimization of the Reactiona
Entry
Catalyst
Oxidant
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Yield [%]
1
2
3
4
5
6
7
8
9
Pd(OAc)
2
2
2
2
2
2
2
37
69
81
80
72
89
95
0
Pd(OAc)
Pd(dppf)Cl
Pd(CH CN) Cl
Pd(dppp)Cl
Pd(PPh
2
/PPh
3
2
3
2
2
2
)
3 4
Pd(PPh
3
)
2
Cl
2
Cu(OAc)
Cu(OAc)
Cu(TFA)
2
—
2
Pd(PPh
Pd(PPh
Pd(PPh
Pd(PPh
Pd(PPh
Pd(PPh
3
)
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
2
2
72
0
1
0
3
)
3
)
3
)
3
)
3
)
)
2
Cu(OTf)
2
11
12
2
2
2
2
AgOAc
12
trace
0
CuBr
2
1
1
1
3
4
5
CuCl
2
—
0
Pd(PPh
3
2
Cl
2
—
0b
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Pd(PPh
3
)
2
Cl
2
2
2
2
—
DMF
DMSO
Toluene
DCE
0c
61
70
80
1
1
1
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Pd(PPh
Pd(PPh
Pd(PPh
3
)
)
)
2
2
2
Cl
Cl
Cl
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
3
3
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a
General conditions: the reactions were carried out under a nitrogen atmosphere
with 1a (0.5 mmol), 2a (1.1 equiv.), tert-butyl isocyanide (1.2 equiv.), catalyst (5
o
mol%), oxidant (2.0 equiv.) in 2 mL of the solvent at 100 C for 8 h in a sealed
tube. Under air without Cu(OAc)2. cUnder O
b
without Cu(OAc)2.
2
With the optimum reaction conditions established, we evaluated the
substrate scope of the reaction. As depicted in Table 2, a wide variety of
arylboronic acids bearing either electron-withdrawing or electron-
donating substituents on the aryl ring could be transformed into the
corresponding compounds in moderate to excellent yields. In addition,
ester, ketone, cyano and vinyl groups were well-tolerated in this system,
and provided the desired products over 63% yield (3f, 3h, 3k, and 3q).
2
-Naphthylboronic acid and (4-(methylthio)phenyl)boronic acid were
also compatible with the method under the standard conditions (3l, 3m).
Unfortunately, the effect of steric hindrance was obvious,
1
-naphthylboronic acid provided the product 3r in low yield .
Table 2. Reactions of Different Arylboronic Acids with
2
-Amino-N-methylbenzamide and tert-Butyl Isocyanide To
Synthesize Various Quinazolinonesa
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a
General conditions: the reactions were carried out under a nitrogen atmosphere with
arylboronic acids (0.5 mmol), 2a (1.1 equiv.), tert-butyl isocyanide ( 1.2 equiv.),
o
Pd(PPh
)
3 2
Cl
2
(5 mol%), Cu(OAc) (2.0 equiv.) in 2 mL of DMF at 100 C for 8 h in a
2
sealed tube.
To further explore the application of this oxidative coupling reaction, a
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series of anthranilamides were investigated, and the results are illustrated
in Table 3. Most N-alkyl anthranilamide substrates could be converted
into the corresponding products in excellent yields (4a, 4b). However,
2-amino-N-cyclopropylbenzamide, as an N-alkyl functional groups, gave
a moderate yield (Table 3, 4e). In addition, this process could also be
applied to general N-aryl anthranilamides. Meanwhile, the influence of
substituents on the N-aryl ring of the anthranilamides was assessed.
Compared to the substrates having electron-poor groups, such as p-F,
p-Cl and p-Br, on N-aryl substituent (4f-4h), the substrates having
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electron-rich groups , such as m-CH
3
and p-CH , provided lower yields of
3
products (4c, 4d). Remarkably, N-methyl anthranilamide bearing
electron-donating group on the aromatic ring obtained preferable result
(
4k). As for electron-withdrawing substituents, such as p-chloro and
p-fluoro groups, the targeted products were generated in 61−66% yields
Table 3, 4i, 4j). Unfortunately, 2-aminobenzamide, used as the substrate,
(
was tested in our model system but no desired product could be detected.
Table 3. Reactions of Various Arylboronic Acids with Different
Anthranilamides and tert-Butyl Isocyanide To Construct Various
Quinazolinones
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aGeneral conditions: the reactions were carried out under a nitrogen atmosphere with
arylboronic acids (0.5 mmol), anthranilamides (1.1 equiv.), tert-butyl isocyanide ( 1.2
o
equiv.), Pd(PPh
3
2
) Cl
2
(5 mol%), Cu(OAc)
2
(2.0 equiv.) in 2 mL of DMF at 100 c for
8
h in a sealed tube.
Next, to extend the scope of the oxidative coupling reaction, we
examined other isocyanides and aromatic borides. Since arylboronic acids
can be varied quite well in this reaction, the compatability of the
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conditions with aromatic borides was investigated. As shown in Scheme 2,
pinacol phenylboronate 1s provided trace amount of the product 3a
possibly due to the effect of the steric hindrance. However, this process to
form the product 3a is compatible with potassium phenyltrifluoroborate
1
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t. Other isocyanides were examined in this reaction to extend the scope
of isocyanide as valuable C1 building block. Satisfactorily, cyclohexyl
isocyanide and benzyl isocyanide could proceed smoothly to give the
product 3a in reasonably yields.
Scheme 2. Oxidative Coupling Reactions of Other Aromatic Borides
and Isocyanides
On the basis of the above experimental results and previous literature
investigation,16-18a plausible reaction mechanism is delineated in Scheme
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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5
5
5
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5
6
3
. Initial, arylboronic acid 1 faces two pathways. On the one hand,
transmetalation of arylboronic acid 1 with Cu(OAc) leads to a copper
2
complex B, which could be exchanged with palladium to form the
0
1
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8
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2
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4
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8
9
0
II
intermediate C. On the other hand, arylboronic acid 1 and Pd L
n
X (A)
2
can undergo a direct transmetalation process to generate intermediate C,
followed by isocyanide insertion to get the complex D. Then, D could
0
further reductive elimination to deliver Pd species and react with
anthranilamide 3 to form the intermediate E. At this point, E undergoes a
tautomerization process to generate complex F, which is followed by
further cyclization with losing amine to form the product 4. At last, the
presence of Cu(OAc) allows the oxidation of the Pd(0) to Pd(II) and
2
completes the catalytic cycle.19-25It is worth noting that although amines
are formed during the reaction process, the reaction system still remains
neutral, and base-sensitive functional group substituted substrates could
work smoothly.
Scheme 3. Plausible Mechanism for the Synthesis of 4
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8
9
0
CONCLUSION
In conclusion, we have demonstrated a palladium-catalyzed oxidative
three-component coupling of easily accessible N-substituted
anthranilamides with isocyanides and arylboronic acids for synthesis of
2
,3-disubstituted quinazolinones. The protocol constructs a C−N bond
without requiring basic reaction conditions, which is beneficial to the
usage of base-sensitive functional group substituted substrates.
Furthermore, this strategy offers an alternative approach toward
2
,3-disubstituted quinazolinones with broad substrate scope and good
functional group tolerance.
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6
EXPERIMENTAL SECTION
General Information. Reactants and reagents were purchased from
commercial suppliers. All solvents were dried and freshly distilled. TLC
was performed on silica HSGF254 plates. Melting points were
0
1
2
3
4
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8
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0
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
13
determined with a digital melting-point apparatus. H and C NMR
spectra were obtained from a solution in deuterated chloroform (CDCl
3
)
1
13
with TMS as internal standard using a 400/101 MHz ( H/ C) or
1
13
6
00/151MHz ( H/ C) spectrometer. Chemical shifts (δ) are given in ppm
and J in Hz. High-resolution mass spectra (HRMS) analyses were carried
out on a chemical ionization (CI) apparatus using time-of-flight (TOF)
mass spectrometry.
2
7b
Synthesis of 2-Amino-N-alkylbenzamide. Isatoic anhydride (5 mmol)
and alkylamine (5 mmol) were added to DMF (25 mL) and the mixture
o
was stirred at 50 C in air for 3 h. Upon completion, the solution was
diluted with EtOAc, and then washed by brine. The organic layer was
dried over anhydrous Na
2
SO , concentrated and then purified by flash
4
column chromatography on silica gel to afford the desired substrate.
27b
Synthesis of 2-Amino-N-arylbenzamide. Isatoic anhydride (5 mmol),
aniline (5 mmol), and iodine (0.5 mmol) were added to EtOH (10 mL)
and the mixture was heated at reflux in air. The progress of the reaction
was monitored by TLC. Upon completion, the solvent was distilled off
and the residue was diluted with EtOAc. The mixture was quenched by
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8
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saturated Na
2
S
2
O
3
solution and then washed by brine. The organic layer
was dried over anhydrous Na
2
SO , concentrated and then purified by
4
flash column chromatography on silica gel to afford the desired substrate.
Synthesis of 2-Amino-4-fluoro(chloro,methoxy)-N-methylbenzamide.
27cA suspension of CDI (1.2 eq.) and the appropriate 2-amino-benzoic
acid (1 eq.) in THF (1M) was stirred under a hydrogen atmosphere at
room temperature over-night. A 1N solution of methylamine in THF (2
eq.) was added dropwise. The resulting solution was stirred for 3h. The
reaction mixture was concentrated in vacuo, and the residue was
dissolved in EtOAc and washed with a saturated aqueous sodium
bicarbonate solution, water, and brine. The organic phase was dried over
magnesium sulfate and concentrated in vacuo. The crude product was
purified by flash chromatography on silica gel (30% EtOAc=DCM) to
give the expected product .
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
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3
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6
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8
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2
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2
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2
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8
9
0
General Procedure for the Synthesis of 2,3-Disubstituted
Quinazolinones. 1 (0.5 mmol, 1 equiv.), 2 (0.55 mmol, 1.1 equiv.),
tert-butyl isocyanide (0.6 mmol, 68 μL, 1.2 equiv.), Pd(PPh
3
)
2
Cl (0.025
2
mmol, 18 mg, 5 mol %), Cu(OAc) (1.0 mmol, 2 equiv) and anhydrous
2
DMF (2 mL) were added into a 15 mL sealed tube equipped with a
magnetic stirring bar. The tube was purged with nitrogen gas and stirred
at 100 °C for 8 h. After completion of the reaction indicated by TLC, it
was poured into brine (30 mL) and extracted using ethyl acetate (3 × 30
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1
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1
1
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2
2
2
2
2
2
2
2
3
3
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5
6
mL). The combined organic layers were dried (Na
2
SO ) and evaporated.
4
The residue was purified on a silica gel column using petroleum
ether/EtOAc as the eluent to give the pure target product .
0
1
2
3
4
5
6
7
8
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2
3
4
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3-Methyl-2-phenylquinazolin-4(3H)-one (3a).26a White solid (112 mg,
1
9
5% yield). Mp: 148–151 °C. EtOAc/petroleum ether =1/30. H NMR
(
400 MHz, CDCl
3
) δ 8.45 (s, 1H), 7.87 (s, 2H), 7.64 (d, J = 2.0 Hz, 6H),
1
3
1
3
1
.61 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ 162.7, 156.1, 147.3,
35.4, 134.3, 130.1, 128.9, 128.0, 127.5, 127.0, 126.7, 120.5, 34.3.
+
HRMS (CI): m/z calcd for C15
H
13
N
2
O [M + H] , 237.1029; found,
2
37.1034.
-(4-Chlorophenyl)-3-methylquinazolin-4(3H)-one (3b).26a White solid
2
o
1
(
118 mg, 88% yield). Mp: 166–168 C. EtOAc/petroleum ether =1/40. H
NMR (400 MHz, CDCl ) δ 8.33 (dd, J = 8.0, 0.8 Hz, 1H), 7.80–7.71 (m,
2H), 7.60–7.46 (m, 5H), 3.51 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
1
3
1
3
) δ
1
1
2
3
62.6, 155.0, 147.2, 136.4, 134.4, 133.8, 129.6, 129.2, 127.5, 127.2,
26.7, 120.5, 34.3. HRMS (CI): m/z calcd for C15
71.0639; found, 271.0633.
H
12ClN
O [M + H]+,
2
-Methyl-2-(p-tolyl)quinazolin-4(3H)-one (3c).26a White solid (117 mg,
o
1
94% yield). Mp: 137–139 C. EtOAc/petroleum ether =1/40. H NMR
400 MHz, CDCl ) δ 8.33 (d, J = 7.9 Hz, 1H), 7.75 (d, J = 3.7 Hz, 2H),
.49 (dd, J = 13.2, 5.8 Hz, 3H), 7.33 (d, J = 7.7 Hz, 2H), 3.51 (s, 3H),
(
3
7
2
1
3
1
.44 (s, 3H). C{ H}NMR (101 MHz, CDCl ) δ 162.8, 156.3, 147.4,
3
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1
40.3, 134.3, 132.6, 129.5, 128.0, 127.5, 126.9, 126.7, 120.5, 34.3, 21.4.
+
HRMS (CI): m/z calcd for C16
H
15
N
2
O [M + H] , 251.1185; found,
2
51.1186.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
6
0
1
2
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
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7
8
9
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1
2
3
4
5
6
7
8
9
0
2-(4-Fluorophenyl)-3-methylquinazolin-4(3H)-one (3d).27b White solid
1
(123 mg, 97% yield). Mp: 186–189 °C. EtOAc/petroleum ether =1/30. H
NMR (400 MHz, CDCl
3
) δ 8.25 (d, J = 7.1 Hz, 1H), 7.68 (d, J = 11.4 Hz,
2
H), 7.56–7.39 (m, 3H), 7.17 (dd, J = 15.3, 7.7 Hz, 2H), 3.43 (s, 3H).
13
1
C{ H}NMR (101 MHz, CDCl
3
) δ 164.4, 162.0 (d, JC-F = 31.3 Hz),
154.7, 146.7, 133.9, 131.1 (d, JC-F = 3.5 Hz), 129.8 (d, JC-F = 8.6 Hz),
1
27.0, 126.7, 126.2, 120.0, 115.6 (d, JC-F = 22.0 Hz), 33.8. HRMS (CI):
+
m/z calcd for C15
H
12FN
2
O [M+ H] , 255.0934; found, 255.0937.
2
-([1,1'-Biphenyl]-4-yl)-3-methylquinazolin-4(3H)-one (3e).28b White
solid (124 mg, 80% yield). Mp: 176–178 °C. EtOAc/petroleum ether
1
=1/30. H NMR (400 MHz, CDCl
3
) δ 8.27 (d, J = 7.9 Hz, 1H), 7.69 (dd, J
=
=
9.7, 6.1 Hz, 4H), 7.58 (dd, J = 11.1, 8.2 Hz, 4H), 7.42 (s, 3H), 7.33 (t, J
1
3
1
7.2 Hz, 1H), 3.50 (s, 3H). C{ H}NMR (101 MHz, CDCl ) δ 162.7,
3
1
1
56.0, 147.2, 143.1, 140.1, 134.4, 134.0, 129.0, 128.6, 128.0, 127.6,
27.4, 127.2, 127.1, 126.7, 120.5, 34.4. HRMS (CI): m/z calcd for
+
C
21
17
H N
2
O [M + H] , 313.1342; found, 313.1343.
Methyl4-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)benzoate(3f). White
solid (108 mg, 74% yield). Mp: 173–175 °C. EtOAc/petroleum ether
1
=
1/10. H NMR (400 MHz, CDCl
3
) δ 8.35 (d, J = 7.8 Hz,1H), 8.22 (d, J
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
=
7.5 Hz, 2H), 7.78 (s, 2H), 7.68 (d, J = 7.5 Hz, 2H), 7.54 (s, 1H), 3.98 (s,
1
3
1
3
1
H), 3.49 (s, 3H). C{ H}NMR (101 MHz, CDCl ) δ 166.2, 162.5, 155.2,
3
47.0, 139.2, 134.5, 131.7, 130.2, 128.2, 127.5, 127.4, 126.8, 120.6, 52.4,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
34.3. HRMS (CI): m/z calcd for C17
H
15
N
2
O
3
[M + H] , 295.1083; found,
2
95.1087.
3
-Methyl-2-(m-tolyl)quinazolin-4(3H)-one (3g). White solid (98mg, 79%
1
yield). Mp: 126–128 °C. EtOAc/petroleum ether =1/30. H NMR (400
MHz, CDCl
7.39 (dd, J = 20.4, 13.2 Hz, 4H), 3.50 (s, 3H), 2.44 (s, 3H). C{ H}NMR
101 MHz, CDCl ) δ 162.7, 156.4, 147.3, 138.9, 135.3, 134.3, 130.8,
28.7, 128.5, 127.5, 126.9, 126.7, 125.0, 120.5, 34.3, 21.5. HRMS (CI):
3
) δ 8.33 (d, J = 7.9 Hz, 1H), 7.75 (s, 2H), 7.54–7.46 (m, 1H),
1
3
1
(
3
1
+
m/z calcd for C16
H
15
N O [M + H] , 251.1185; found, 251.1186.
2
2
-(4-Acetylphenyl)-3-methylquinazolin-4(3H)-one (3h). White solid (114
1
mg, 82% yield). Mp: 218–220 °C. EtOAc/petroleum ether =1/5. H NMR
(400 MHz, CDCl
3
) δ 8.35 (d, J = 7.8 Hz, 1H), 8.13 (d, J = 8.0 Hz, 2H),
7
.76 (dd, J = 14.8, 7.7 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 7.54 (t, J = 7.1
1
3
1
Hz, 1H), 3.50 (s, 3H), 2.68 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ
1
96.7, 162.0, 154.6, 146.7, 139.0, 137.6, 134.0, 128.3, 128.0, 127.1,
126.9, 126.3, 120.2, 33.7, 26.3. HRMS (CI): m/z calcd for C17
H
15
N
O
2 2
+
[M + H] , 279.1134; found, 279.1141.
2
6a
3
-Methyl-2-(4-(trifluoromethyl)phenyl)quinazolin-4(3H)-one(3i). White
solid (109 mg, 72% yield). Mp: 119−121 °C. EtOAc/petroleum ether
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5
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7
8
9
1
=
1/30. H NMR (400 MHz, CDCl
18.4, 7.9 Hz, 6H), 7.45 (t, J = 7.3 Hz, 1H), 3.41 (s, 3H). C{ H}NMR
) δ 161.9, 154.2, 146.6, 138.3, 134.0, 131.6 (d, JC-F
32.9 Hz), 128.2, 127.0 (d, JC-F = 11.5 Hz), 126.3, 125.5 (d, JC-F = 3.7 Hz),
3
) δ 8.26 (d, J = 7.9 Hz, 1H), 7.69 (dt, J
1
3
1
=
(
101 MHz, CDCl
3
=
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
24.5, 121.8, 120.1, 33.7. HRMS (CI): m/z calcd for C16
H
12
F
3
N O [M +
2
+
H] , 305.0902; found, 305.0911.
2
8b
2
-(4-Bromophenyl)-3-methylquinazolin-4(3H)-one (3j). White solid (68
1
mg, 43% yield). Mp: 165–166 °C. EtOAc/petroleum ether =1/75. H
NMR (400 MHz, CDCl ) δ 8.34 (d, J = 7.8 Hz, 1H), 7.81–7.64 (m, 4H),
3
1
3
1
7
1
1
3
.56–7.44 (m, 3H), 3.52 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ
62.6, 155.1, 147.1, 134.5, 134.1, 132.2, 129.8, 127.4, 127.3, 126.8,
24.7, 120.5, 34.3. HRMS (CI): m/z calcd for C15
15.0134; found, 315.0132.
H
12BrN
O [M + H]+,
2
4-(3-Methyl-4-oxo-3,4-dihydroquinazolin-2-yl)benzonitrile (3k).26b White
solid (87 mg, 67% yield). Mp: 216–218 °C. EtOAc/petroleum ether =1/5.
1H NMR (400 MHz, CDCl
) δ 8.35 (d, J = 7.8 Hz, 1H), 7.92–7.68 (m,
3
1
3
1
6
H), 7.55 (t, J = 7.3 Hz, 1H), 3.49 (s, 3H). C{ H}NMR (101 MHz,
CDCl ) δ 162.3, 154.1, 146.9, 139.4, 134.6, 132.7, 129.1, 127.7, 127.6,
3
126.8, 120.6, 117.9, 114.1, 34.2. HRMS (CI): m/z calcd for C16
H
12
N O
3
+
[
M + H] , 262.0981; found, 262.0985.
3
-Methyl-2-(4-(methylthio)phenyl)quinazolin-4(3H)-one (3l). White solid
1
(
90 mg, 64% yield). Mp: 144–145 °C. EtOAc/petroleum ether =1/10. H
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
NMR (400 MHz, CDCl
3
) δ 8.32 (d, J = 7.9 Hz, 1H), 7.75 (s, 2H), 7.51 (d,
J = 7.8 Hz, 3H), 7.37 (d, J = 8.0 Hz, 2H), 3.53 (s, 3H), 2.54 (s, 3H).
13
1
C{ H}NMR (101 MHz, CDCl ) δ 162.7, 155.8, 147.1, 141.9, 134.4,
3
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5
6
7
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9
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9
0
131.4, 128.6, 127.3, 127.0, 126.7, 126.1, 120.4, 34.4, 15.3. HRMS (CI):
+
m/z calcd for C16
H
15
N
2
OS [M + H] , 283.0906; found, 283.0909.
3
-Methyl-2-(naphthalen-2-yl)quinazolin-4(3H)-one (3m). White solid
1
(
105 mg, 74% yield). Mp: 161–162 °C. EtOAc/petroleum ether =1/40. H
NMR (400 MHz, CDCl ) δ 8.34 (d, J = 7.9 Hz, 1H), 8.08 (s, 1H), 7.95 (t,
J = 9.1 Hz, 1H), 7.89 (d, J = 6.9 Hz, 2H), 7.76 (s, 2H), 7.63–7.47 (m, 4H),
3
1
3
1
3
1
1
.52 (s, 3H). C{ H}NMR (101 MHz, CDCl ) δ 162.7, 156.3, 147.2,
3
34.4, 133.7, 132.9, 132.4, 128.8, 128.7, 128.3, 127.9, 127.6, 127.4,
27.14, 127.08, 126.8, 124.8, 120.6, 34.6. HRMS (CI): m/z calcd for
+
C
19
15
H N
2
O [M + H] , 287.1185; found, 287.1185.
2-(Benzo[d][1,3]dioxol-5-yl)-3-methylquinazolin-4(3H)-one (3n). White
solid (93 mg, 67% yield). Mp: 158–160 °C. EtOAc/petroleum ether =1/10.
1H NMR (400 MHz, CDCl
Hz, 2H), 7.50 (t, J = 5.9 Hz, 1H), 7.12 – 7.01 (m, 2H), 6.94 (d, J = 7.9 Hz,
) δ 8.32 (d, J = 7.9 Hz, 1H), 7.75 (d, J = 5.5
3
13
1
1
H), 6.06 (s, 2H), 3.53 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ 162.3,
155.2, 148.7, 147.5, 146.7, 133.9, 128.4, 126.9, 126.5, 126.2, 122.1,
119.9, 108.25, 108.19, 101.2, 33.9. HRMS (CI): m/z calcd for
+
C
16
13
H N
2
O
3
[M + H] , 281.0927; found, 281.0932.
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-(3-Methoxyphenyl)-3-methylquinazolin-4(3H)-one (3o).28b White solid
1
(104 mg, 78% yield). Mp: 110–111 °C. EtOAc/petroleum ether =1/40. H
NMR (400 MHz, CDCl
3
) δ 8.34 (d, J = 7.8 Hz, 1H), 7.78–7.72 (m, 2H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7.53–7.47 (m, 1H), 7.44 (d, J = 7.9 Hz, 1H), 7.14–7.04 (m, 3H), 3.88 (s,
1
3
1
3
1
1
2
H), 3.51 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ 162.7, 159.9, 155.9,
47.3, 136.5, 134.3, 130.1, 127.5, 127.0, 126.7, 120.6, 120.1, 115.9,
13.5, 55.5, 34.2. HRMS (CI): m/z calcd for C16
H
15
N
2
O
[M + H]+,
2
67.1134; found, 267.1142.
2-(3,4-Dichlorophenyl)-3-methylquinazolin-4(3H)-one (3p). White solid
1
(80 mg, 64% yield). Mp: 160–161 °C. EtOAc/petroleum ether =1/80. H
NMR (400 MHz, CDCl
3
) δ 8.33 (dd, J = 8.0, 1.3 Hz, 1H), 7.80–7.69 (m,
3
H), 7.63 (d, J = 8.3 Hz, 1H),7.53 (dd, J = 10.9, 4.1 Hz, 1H), 7.44 (dd, J
13
1
=
8.3, 2.0 Hz, 1H), 3.52 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ
162.4, 153.7, 147.0, 135.0, 134.7, 134.5, 133.5, 130.9, 130.3, 127.52,
1
27.48, 127.3, 126.8, 120.6, 34.2. HRMS (CI): m/z calcd for
+
C
15
H11Cl
2
N
2
O [M + H] , 305.0249; found, 305.0251.
3
-methyl-2-(4-vinylphenyl)quinazolin-4(3H)-one (3q). White solid (82 mg,
1
6
3% yield). Mp: 151–152 °C. EtOAc/petroleum ether =1/40. H NMR
(400 MHz, CDCl
3
) δ 8.36 (d, J = 7.9 Hz, 1H), 7.79 (d, J = 3.4 Hz, 2H),
7
1
.63–7.50 (m, 5H), 6.81 (dd, J = 17.6, 10.9 Hz, 1H), 5.89 (d, J = 17.6 Hz,
1
3
1
H), 5.41 (d, J = 10.9 Hz, 1H), 3.55 (s, 3H). C{ H}NMR (101 MHz,
CDCl
3
) δ 162.7, 155.9, 147.2, 139.4, 135.9, 134.4, 134.3, 128.4, 127.4,
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1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
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4
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4
4
4
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4
5
5
5
5
5
5
5
5
5
5
6
1
27.0, 126.7, 126.6, 120.5, 115.9, 34.3. HRMS (CI): m/z calcd for
+
C
17
15
H N
2
O [M + H] , 263.1185; found, 263.1193.
3
-Methyl-2-(naphthalen-1-yl)quinazolin-4(3H)-one (3r) White solid (29
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
mg, 20% yield). Mp: 251–253 °C. EtOAc/petroleum ether =1/80. H
NMR (400 MHz, CDCl
3
) δ 8.40 (d, J = 7.9 Hz, 1H), 8.00 (dd, J = 5.9, 2.6
Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.78 (s, 2H), 7.60 (d, J = 5.8 Hz, 2H),
1
3
1
7
1
.57–7.46 (m, 4H), 3.30 (s, 3H). C{ H}NMR (151 MHz, CDCl
3
) δ
62.4, 155.4, 147.4, 134.4, 133.5, 132.7, 130.3, 130.2, 128.7, 128.0,
127.6, 127.2, 126.8, 126.7, 126.1, 125.4, 124.2, 120.8, 33.1. HRMS (CI):
+
m/z calcd for C19
H
15
N
2
O [M + H] , 287.1185; found, 287.1183.
2
6a
3
-Ethyl-2-phenylquinazolin-4(3H)-one (4a). White solid (121 mg, 97%
1
yield). Mp: 155−156 °C. EtOAc/petroleum ether =1/50. H NMR (400
MHz, CDCl ) δ 8.34 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 5.9 Hz, 2H), 7.53 (s,
6H), 4.05 (dd, J = 13.6, 6.7 Hz, 2H), 1.22 (t, J = 6.9 Hz, 3H).
3
1
3
1
C{ H}NMR (101 MHz, CDCl ) δ 162.0, 156.2, 147.1, 135.5, 134.3,
3
1
29.8, 128.8, 127.7, 127.4, 127.0, 126.7, 121.0, 41.2, 14.1. HRMS (CI):
+
m/z calcd for C16
H
15
N
2
O [M + H] , 251.1185; found, 251.1188.
3
-Benzyl-2-phenylquinazolin-4(3H)-one (4b).26a White solid (125 mg,
1
94% yield). Mp: 167–169 °C. EtOAc/petroleum ether =1/50. H NMR
400 MHz, CDCl ) δ 8.38 (d, J = 7.9 Hz, 1H), 7.78 (s, 2H), 7.59–7.50 (m,
H), 7.48–7.30 (m, 5H), 7.24–7.13 (m, 3H), 6.93 (d, J = 3.4 Hz, 2H),
(
3
1
5
1
3
1
.28 (s, 2H). C{ H}NMR (101 MHz, CDCl ) δ 162.0, 155.9, 146.8,
3
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36.1, 134.8, 134.1, 129.4, 128.12 , 128.05, 127.6, 127.1, 127.0, 126.7,
26.6, 126.5, 120.4, 48.3. HRMS (CI): m/z calcd for C21
H
17
N O [M +
2
+
H] , 313.1342; found, 313.1345.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
a
2-Phenyl-3-(p-tolyl)quinazolin-4(3H)-one (4c). White solid (115 mg,
1
7
4% yield). Mp: 177–179 °C. EtOAc/petroleum ether =1/40. H NMR
(400 MHz, CDCl
3
) δ 8.35 (d, J = 7.8 Hz, 1H), 7.81 (s, 2H), 7.53 (t, J =
6
=
.2 Hz, 1H), 7.35 (d, J = 7.0 Hz, 2H), 7.24 (t, J = 7.6 Hz, 3H), 7.11 (d, J
13
1
7.7 Hz, 2H), 7.02 (d, J = 7.8 Hz, 2H), 2.30 (s, 3H). C{ H}NMR (101
) δ 162.4, 155.4, 147.5, 138.3, 135.6, 135.0, 134.7, 129.7,
29.2, 129.0, 128.8, 128.0, 127.7, 127.23, 127.20, 121.0, 21.2. HRMS
MHz, CDCl
3
1
+
(CI): m/z calcd for C21
H
17
N O [M + H] , 313.1342; found, 313.1344.
2
5
a
2
-Phenyl-3-(m-tolyl)quinazolin-4(3H)-one (4d). White solid (110 mg,
1
7
1% yield). Mp: 155–157 °C. EtOAc/petroleum ether =1/30. H NMR
) δ 8.42 (d, J = 7.4 Hz, 1H), 7.88 (s, 2H), 7.60 (s, 1H),
.41 (d, J = 5.7 Hz, 2H), 7.26 (dd, J = 20.6, 7.4 Hz, 4H), 7.17–7.02 (m,
(400 MHz, CDCl
3
7
2
1
3
1
H), 6.99 (d, J = 7.0 Hz, 1H), 2.34 (s, 3H). C{ H}NMR (101 MHz,
) δ 161.9, 154.8, 147.0, 138.5, 137.0, 135.0, 134.2, 129.2, 128.8,
28.7, 128.5, 128.3, 127.5, 127.2, 126.8, 126.7, 125.6, 120.5, 20.7.
CDCl
3
1
+
HRMS (CI): m/z calcd for C21
H
17
N O [M + H] , 313.1342; found,
2
3
3
5
13.1344.
9
a
-Cyclopropyl-2-phenylquinazolin-4(3H)-one (4e). White solid (77 mg,
1
9% yield). Mp: 112–114 °C. EtOAc/petroleum ether =1/20. H NMR
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1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
4
4
4
4
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5
5
5
5
5
5
5
5
6
(
400 MHz, CDCl
3
) δ 8.31 (d, J = 7.5 Hz, 1H), 7.72 (dd, J = 8.4, 2.2 Hz,
4
H), 7.50 (s, 4H), 3.14 (d, J = 3.2 Hz, 1H), 0.93 (d, J = 6.2 Hz, 2H), 0.50
13
1
(s, 2H). C{ H}NMR (101 MHz, CDCl ) δ 164.0, 156.9, 147.1, 136.2,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
134.3, 129.8, 128.4, 128.3, 127.4, 126.9, 126.5, 120.9, 30.3, 11.3. HRMS
+
(CI): m/z calcd for C17
H
15
N
2
O [M + H] , 263.1185; found, 263.1191.
3
-(4-Fluorophenyl)-2-phenylquinazolin-4(3H)-one (4f).5a White solid
1
(
137 mg, 87% yield). Mp: 148-150 °C. EtOAc/petroleum ether =1/30. H
NMR (400 MHz, CDCl ) δ 8.35 (d, J = 7.7 Hz, 1H), 7.84 (s, 2H), 7.54 (d,
J = 5.7 Hz, 1H), 7.30 (dd, J = 20.0, 8.5 Hz, 4H), 7.25 (s, 1H), 7.12 (d, J =
3
1
3
1
4
1
1
1
.2 Hz, 2H), 7.01 (t, J = 8.2 Hz, 2H). C{ H}NMR (101 MHz, CDCl ) δ
3
62.8, 161.0 (d, JC-F = 149.0 Hz), 154.6 , 146.8, 134.7, 134.4, 133.1,
30.4 (d, JC-F = 8.8 Hz), 129.0, 128.5, 127.7, 127.3, 127.0, 126.7, 120.3,
15.6 (d, JC-F = 23.0 Hz). HRMS (CI): m/z calcd for C20
H
14FN O [M +
2
+
H] , 317.1091; found, 317.1094.
3
-(4-Chlorophenyl)-2-phenylquinazolin-4(3H)-one (4g).5a White solid
1
(142mg, 86% yield). Mp: 188–190 °C. EtOAc/petroleum ether =1/20. H
NMR (400 MHz, CDCl
3
) δ 8.33 (d, J = 7.7 Hz, 1H), 7.81 (d, J = 2.5 Hz,
2
H), 7.57–7.47 (m, 1H), 7.37–7.23 (m, 7H), 7.09 (d, J = 8.1 Hz, 2H).
1
3
1
C{ H}NMR (101 MHz, CDCl ) δ 162.1, 154.8, 147.4, 136.2, 135.2,
3
1
1
34.9, 134.3, 130.5, 129.6, 129.2, 129.0, 128.2, 127.8, 127.4, 127.2,
+
20.8. HRMS (CI): m/z calcd for C20
H
14ClN
2
O [M + H] , 333.0795;
found, 333.0794.
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-(4-Bromophenyl)-2-phenylquinazolin-4(3H)-one (4h).5a White solid
1
(169 mg, 90% yield). Mp: 228–230 °C. EtOAc/petroleum ether =1/30. H
NMR (400 MHz, CDCl
3
) δ 8.35 (d, J = 7.7 Hz, 1H), 7.82 (d, J = 2.5 Hz,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2H), 7.58–7.50 (m, 1H), 7.45 (d, J = 8.2 Hz, 2H), 7.37–7.25 (m, 5H),
1
3
1
7
1
1
.03 (d, J = 8.2 Hz, 2H). C{ H}NMR (101 MHz, CDCl
3
) δ 162.1, 154.7,
47.4, 136.7, 135.1, 134.9, 132.2, 130.7, 129.6, 129.0, 128.2, 127.8,
27.5, 127.2, 122.5, 120.8. HRMS (CI): m/z calcd for C20
H
14BrN O [M +
2
+
H] , 377.0290; found, 377.0290.
2
7a
7-Fluoro-3-methyl-2-phenylquinazolin-4(3H)-one (4i). White solid (77
o
1
mg, 61% yield). Mp: 127–130 C. EtOAc/petroleum ether =1/70. H
NMR (400 MHz, CDCl ) δ 8.33 (dd, J = 8.5, 6.4 Hz, 1H), 7.54 (d, J = 4.6
Hz, 5H), 7.40–7.33 (m, 1H), 7.21 (dd, J = 12.0, 4.9 Hz, 1H), 3.49 (s, 3H).
3
13
1
C{ H}NMR (101 MHz, CDCl
3
) δ 166.5 (d, JC-F = 254.1 Hz), 162.0,
157.4, 149.3, 135.1, 130.3, 129.5 (d, JC-F = 10.6 Hz), 128.9, 127.9, 117.3,
1
15.9 (d, JC-F = 23.6 Hz), 112.7 (d, JC-F = 21.9 Hz), 34.3. HRMS (CI):
+
m/z calcd for C15
H
12FN
2
O [M + H] , 255.0934; found, 255.0939.
2
6c
7
-Chloro-3-methyl-2-phenylquinazolin-4(3H)-one (4j). White solid (89
1
mg, 66% yield). Mp: 159–161 °C. EtOAc/petroleum ether =1/60. H
NMR (400 MHz,CDCl ) δ 8.23 (d, J = 8.5 Hz, 1H), 7.71 (s, 1H), 7.53 (s,
3
1
3
1
5
H), 7.43 (d, J = 8.4 Hz, 1H), 3.48 (s, 3H). C{ H}NMR (101 MHz,
CDCl
3
) δ 162.1, 157.4, 148.2, 140.5, 135.1, 130.3, 128.9, 128.2, 128.0,
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
27.6, 127.0, 119.0, 34.4. HRMS (CI): m/z calcd for C15
H
12ClN O [M +
2
+
H] , 271.0639; found, 271.0642.
-Methoxy-3-methyl-2-phenylquinazolin-4(3H)-one (4k).26a White solid
7
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
(114 mg, 86% yield). Mp: 177–178 °C. EtOAc/petroleum ether =1/10. H
NMR (400 MHz, CDCl ) δ 8.15 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.0 Hz,
3
1
3
1
5
H), 7.08–6.96 (m, 2H), 3.83 (s, 3H), 3.41 (s, 3H). C{ H}NMR (101
MHz, CDCl ) δ 164.6, 162.2, 156.9, 149.5, 135.5, 130.0, 128.9, 128.2,
3
1
27.9, 117.3, 114.1, 107.9, 55.7, 34.1. HRMS (CI): m/z calcd for
+
C
16
15
H N
2
O [M + H] , 267.1134; found, 267.1133.
2
2
,3-Diphenylquinazolin-4(3H)-one (4l).28a White solid (114 mg, 76%
1
yield). Mp: 158–159 °C. EtOAc/petroleum ether =1/40. H NMR (400
MHz, CDCl ) δ 8.36 (d, J = 7.8 Hz, 1H), 7.83 (s, 2H), 7.54 (s, 1H),
3
13
1
7
.36–7.20 (m, 8H), 7.15 (d, J = 7.3 Hz, 2H). C{ H}NMR (101 MHz,
CDCl
3
) δ 162.3, 155.2, 147.5, 137.7, 135.5, 134.7, 129.3, 129.1, 129.0,
1
28.4, 128.0, 127.8, 127.3, 127.2, 121.0. HRMS (CI): m/z calcd for
+
C
20
H
15
N O [M + H] , 299.1185; found, 299.1190.
2
5
a
3
-Phenyl-2-(p-tolyl)quinazolin-4(3H)-one (4m). White solid (117 mg,
o
1
7
5% yield). Mp: 174–176 C. EtOAc/petroleum ether =1/20. H NMR
) δ 8.35 (d, J = 7.7 Hz, 1H), 7.81 (s, 2H), 7.52 (s, 1H),
.37–7.28 (m, 3H), 7.26–7.20 (m, 2H), 7.16 (d, J = 7.1 Hz, 2H), 7.01 (d,
(400 MHz, CDCl
3
7
1
3
1
J = 7.5 Hz, 2H), 2.27 (s, 3H). C{ H}NMR (101 MHz, CDCl
3
) δ 162.3,
1
55.4, 147.4, 139.6, 137.8, 134.7, 132.4, 129.1, 129.04, 128.99, 128.7,
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28.4, 127.6, 127.21, 127.19, 120.8, 21.3. HRMS (CI): m/z calcd for
+
C
21
17
H N
2
O [M + H] , 313.1342; found, 313.1345.
2
-(4-Fluorophenyl)-3-phenylquinazolin-4(3H)-one (4n).5a White solid
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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2
3
4
5
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7
8
9
0
1
(137 mg, 87% yield). Mp: 163−165 °C. EtOAc/petroleum ether =1/30. H
NMR (400 MHz, CDCl
3
) δ 8.36 (d, J = 7.3 Hz, 1H), 7.81 (s, 2H), 7.55 (s,
1
H), 7.34 (d, J = 6.2 Hz, 5H), 7.15 (d, J = 5.6 Hz, 2H), 6.92 (d, J = 7.9
1
3
1
Hz, 2H). C{ H}NMR (101 MHz, CDCl
Hz), 154.0, 147.2, 137.4, 134.6, 131.4 (d, JC-F = 3.5 Hz), 131.0 (d, JC-F
8.6 Hz), 128.9 (d, JC-F = 6.7 Hz), 128.8, 128.4, 127.5, 127.2, 127.1, 120.8,
3
) δ 164.0, 161.8 (d, JC-F = 49.4
=
1
15.0 (d, JC-F = 22.0 Hz). HRMS (CI): m/z calcd for C20
H
14FN O [M +
2
+
H] , 317.1091; found, 317.1091.
2
-(4-Chlorophenyl)-3-phenylquinazolin-4(3H)-one (4o).5a White solid
1
(132 mg, 80% yield). Mp: 169−170 °C. EtOAc/petroleum ether =1/20. H
NMR (400 MHz, CDCl
3
) δ 8.37 (d, J = 7.8 Hz, 1H), 7.84 (dd, J = 4.2, 2.0
Hz, 2H), 7.56 (ddd, J = 8.2, 5.5, 2.9 Hz, 1H), 7.40–7.30 (m, 5H),
1
3
1
7
1
1
.23–7.15 (m, 4H). C{ H}NMR (101 MHz, CDCl
3
) δ 161.7, 153.6,
46.9, 137.0, 135.1, 134.4, 133.4, 130.0, 128.7, 128.6, 128.2, 127.8,
27.3, 127.0, 126.8, 120.5. HRMS (CI): m/z calcd for C20
H
14ClN O [M +
2
+
H] , 333.0795; found, 333.0792.
ASSOCIATED CONTENT
AUTHOR INFORMATION
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Corresponding Authors
*
*
E-mail: zhuyongming@suda.edu.cn.
E-mail: yangshilin@suda.edu.cn.
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NOTES
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge the financial support by PAPD (A Project
Funded by the Priority Academic Program Development of Jiangsu
Higher Education Institutions).
Supporting Information
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Supporting Information Figures giving H, C NMR spectra.
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