General and efficient copper-catalyzed aerobic oxidative synthesis of N-fused heterocycles using amino acids as the nitrogen source

Article abstract of DOI:10.1039/c3ra41644e

A general and efficient copper-catalyzed aerobic oxidative method for the synthesis of N-fused heterocycles has been developed by using readily available α-amino acids as the nitrogen source. The reactions underwent N-arylation, aerobic oxidative dehydrogenation, intramolecular cyclization and dissociation of formic acid. This method should provide a general and practical strategy for the construction of N-fused heterocycles.

Full text of DOI:10.1039/c3ra41644e

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General and efficient copper-catalyzed aerobic
oxidative synthesis of N-fused heterocycles using amino
acids as the nitrogen source3
Cite this: DOI: 10.1039/c3ra41644e
Qing Liu,a Haijun Yang,a Yuyang Jiang,b Yufen Zhaoa and Hua Fu*ab
A general and efficient copper-catalyzed aerobic oxidative method for the synthesis of N-fused
heterocycles has been developed by using readily available a-amino acids as the nitrogen source. The
reactions underwent N-arylation, aerobic oxidative dehydrogenation, intramolecular cyclization and
dissociation of formic acid. This method should provide a general and practical strategy for the
construction of N-fused heterocycles.
Received 5th April 2013,
Accepted 28th June 2013
DOI: 10.1039/c3ra41644e
www.rsc.org/advances
Introduction
Results and discussion
N-Heterocycles widely found in natural products are ubiqui-
tous subunits of a variety of biologically active substances,1
and they have been assigned as privileged structures in drug
development.2 Transition metal-catalyzed C–H functionaliza-
tion has emerged as a sustainable and intriguing strategy,3
and some N-heterocyclic compounds have been assembled
through this method, in which expensive palladium-, rho-
dium-, and ruthenium-based catalysts are usually required.4
Recently, copper-catalyzed reactions have been widely used in
organic synthesis because of the low-cost and low toxicity of
copper catalysts and good functional group tolerance in the
substrates.5 In particular, some N-heterocycles have been
efficiently synthesized via copper-catalyzed aerobic oxidative
C–H functionalization by us6 and other groups.7 The efficient
synthesis of N-heterocycles from simple and readily available
starting materials is an important task for chemists.8 a-Amino
acids are readily available substances in nature and fine
chemicals and are one of the most attractive nitrogen
sources,6a,9 so it is of value to develop efficient methods for
the assembly of N-heterocycles from these substrates. Herein,
we report a general and efficient copper-catalyzed domino
aerobic oxidative synthesis of some N-fused heterocycles by
using a-amino acids as the nitrogen source.
2-(2-Bromophenyl)-1H-indole (1a) and valine (2e) were used as
model substrates to optimize the reaction conditions includ-
ing catalyst, base, solvent and reaction temperature. As shown
in Table 1, the reaction was divided into two steps: copper-
catalyzed N-arylation of valine under air and aerobic oxidative
cyclization under oxygen (1 atm). First, various copper-
catalysts were screened in DMF in the presence of 2 equiv.
of K2CO3 (relative to amount of 1a) at 90 uC (entries 1–7), and
CuI showed the best activity (entry 3). No target product was
observed in the absence of copper-catalyst (entry 8). The use of
other bases was attempted (entries 9–11), and K2CO3 provided
the highest yield (compare entries 3, 9–11). The effect of
solvent was also investigated (compare entries 3, 12–15), and
DMF was optimum (entry 3). When the temperature was
changed, yields decreased (entries 16 and 17). No better results
were observed when the N-arylation of valine and aerobic
oxidative cyclizations were performed under the same atmo-
sphere for both steps: air (entry 18) or oxygen (entry 19).
The scope of copper-catalyzed reactions of substituted 2-(2-
bromophenyl)-1H-indoles (1) with a-amino acids was investi-
gated under the optimized conditions (using 20 mol% of CuI
as the catalyst, 2 equiv. of K2CO3 as the base, and DMF as the
solvent at 90 uC under air for the first step, under oxygen for
the second step). As shown in Table 2, the corresponding
H-indolo[1,2-c]quinazoline derivatives were obtained in mod-
erate to good yields for the various substrates examined. For
substituted 2-(2-bromophenyl)-1H-indoles (1), the electronic
effect of the substrates did not show an evident difference in
reactivity. For a-amino acids, their reactivity depended on their
side chains. When 2-amino-3,3-dimethylbutanoic acid (2h)
was used as the substrate, the tert-butyl group was removed in
the form of iso-butene (entry 8). The copper-catalyzed reactions
of substituted 2-(2-bromophenyl)-1H-indoles with a-amino
aKey Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry
of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R.
China. E-mail: fuhua@mail.tsinghua.edu.cn
bKey Laboratory of Chemical Biology (Guangdong Province), Graduate School of
Shenzhen, Tsinghua University, Shenzhen 518057, P. R. China
Electronic supplementary information (ESI) available: Copies of 1H and 13C
3
NMR spectra of compounds 3a–y, 5a–l, 7a–d. See DOI: 10.1039/c3ra41644e
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Table 3. The reactions provided the desired target products
in moderate to good yields. For substituted 2-(2-halophenyl)-
1H-benzo[d]imidazoles, aryl iodides exhibited higher reactivity
than aryl bromides. The reactions in Table 3 showed a similar
tolerance of functional groups to those shown in Table 2.
Copper-catalyzed reactions of 5-(2-bromophenyl)-3-phenyl-
1H-pyrazole (6) with representative a-amino acids (2) were also
investigated as shown in Scheme 3. To our pleasure, the
reactions provided good results. Therefore, the present
strategy using a-amino acids as the nitrogen source shows
wide application for the synthesis of N-fused heterocycles.
Table 1 Copper-catalyzed reaction of 2-(2-bromophenyl)-1H-indole (1a) with
valine (2e) leading to 6-isopropyl H-indolo[1,2-c]quinazoline (3e): optimization
of conditionsa
Entry
Cat.
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
CuCl
CuBr
CuI
Cu2O
CuBr2
Cu(OAc)2
Cu
—
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMA
DMSO
1,4-dioxane
toluene
DMF
DMF
DMF
33
45
58
32
52
32
40
0
15
12
17
19
29
Trace
Conclusions
We have developed a general and efficient copper-catalyzed
aerobic oxidative method for the synthesis of N-fused hetero-
cycles including H-indolo[1,2-c]quinazolines, benzo[4,5]imi-
dazo[1,2-c]quinazolines and pyrazolo[1,5-c]quinazolines. The
protocol uses cheap and readily available CuI as the catalyst,
readily available a-amino acids as the nitrogen source, and
economical and environmentally friendly oxygen as the
oxidant, and the corresponding N-fused heterocycles were
prepared in moderate to good yields. The reactions underwent
copper-catalyzed N-arylation, aerobic oxidative dehydrogena-
tion, intramolecular cyclization and dissociation of formic
acid. This method shows simple and practical advantages, so it
will find wide application for the construction of other N-fused
heterocycles.
9
10
11
12
13
14
15
16
17
18
19
0c
11d
42e
25f
DMF
a
Reaction conditions: 2-(2-bromophenyl)-1H-indole (1a) (0.2 mmol),
valine (2e) (0.4 mmol), catalyst (0.04 mmol), base (0.4 mmol), solvent
(3 mL), reaction temperature (90 uC), reaction time (12 h under air;
24 h under oxygen (1 atm)). DMA = N,N-dimethylacetamide.
b
c
d
Isolated yield. Reaction temperature (60 uC). Reaction
e
temperature (110 uC). The two-step reaction was performed under
f
air at 90 uC for 36 h. The two-step reaction was performed under
oxygen (1 atm) at 90 uC for 36 h.
Experimental section
General methods
acids showed tolerance of some functional groups in the
substrates including C–Cl bond, ether bond and S-heterocycle.
We attempted the copper-catalyzed reaction of 2-(2-bromo-
phenyl)-1H-indole (1a) with pipecolinic acid (2k) under the
standard conditions (Scheme 1), and the target product 3y was
obtained in 64% yield.
All reactions were carried out under air or oxygen atmosphere.
Proton and carbon magnetic resonance spectra (1H NMR and
13C NMR) were recorded using tetramethylsilane (TMS) in a
solvent of CDCl3-d or DMSO-d6 as the internal standard (1H
NMR: TMS at 0.00 ppm, CDCl3 at 7.26 ppm, DMSO at 2.50
ppm; 13C NMR: CDCl3 at 77.16 ppm, DMSO at 40.00 ppm).
A possible mechanism for the copper-catalyzed reaction of
substituted 2-(2-bromophenyl)-1H-indoles with a-amino acids
is suggested in Scheme 2 according to the results above and
previous research.6a First, N-arylation of a-amino acid (2) with
substituted 2-(2-bromophenyl)-1H-indole (1) affords I, and
then intermediate I performs two domino pathways (pathways
A and B). Pathway A: dissociation of formic acid from I gives II,
intramolecular cyclization of II provides III, and copper-
catalyzed aerobic oxidative dehydrogenation of III affords the
target product (3). Pathway B: copper-catalyzed aerobic
oxidative dehydrogenation of I provides IV, intramolecular
cyclization of IV leads to V, and desorption of formic acid from
V gives 3.
General procedure for the synthesis of N-fused heterocycles
(3a–y, 5a–l and 7a–d)
A 25 mL flask equipped with a magnetic stirring bar was
charged with substituted 2-(2-bromophenyl)-1H-indole (1) or 2-
(2-halophenyl)-1H-benzo[d]imidazole (4) or 5-(2-bromophenyl)-
3-phenyl-1H-pyrazole (6) (0.2 mmol), a-amino acid (2) (0.4
mmol), K2CO3 (0.4 mmol, 55 mg), CuI (0.04 mmol, 7.6 mg) and
DMF (3 mL). The mixture was allowed to stir under air at 90 or
105 uC for 12 or 36 h, then under oxygen (1 atm) at the same
temperature for 24 or 36 h (see Tables 2 and 3, Schemes 1 and
3 for details). After completion of the reaction, the resulting
solution was cooled to room temperature and filtered, and the
solid was washed with ethyl acetate (3 6 3 mL). The combined
filtrate was concentrated with the aid of a rotary evaporator,
and the residue was purified by column chromatography on
Inspired by the excellent results above, we investigated the
copper-catalyzed reactions of substituted 2-(2-halophenyl)-
1H-benzo[d]imidazoles with a-amino acids as shown in
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Table 2 Copper-catalyzed synthesis of H-indolo[1,2-c]quinazoline derivativesa
Table 2 (Continued)
3 (Yield)b
Entry
1
1
2
3 (Yield)b
Entry
13
1
2
1b
2b
2
3
4
5
1a
1a
1a
1a
14
15
16
1b
1b
1b
2c
2g
2h
17
18
1b
2i
2g
6
7
1a
1a
19
20
1c
1c
2h
2i
8
9
1a
1a
3a (91%)
21
22
23
1c
2j
10
11
12
1a
1a
2d
2h
1d
2a
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Table 2 (Continued)
Entry
24
1
2
3 (Yield)b
1d
2i
Scheme 2 Possible mechanism for the synthesis of H-indolo[1,2-c]quinazoline
derivatives.
25
1d
2j
139.1, 135.4, 131.3, 130.7, 129.0, 127.4, 126.9, 123.4, 122.8,
122.2, 120.9, 120.5, 115.3, 95.6, 30.4, 10.8. ESI-MS [M + H]+ m/z
247.2.
6-Propylindolo[1,2-c]quinazoline (3d)11. Eluent: petroleum
ether–ethyl acetate (50 : 1). Yield 31 mg (60%). Light yellow
solid, m.p. 109–110 uC. 1H NMR (CDCl3, 300 MHz) d 8.06–7.98
(m, 2H), 7.84–7.81 (dd, 1H, J = 6.6 Hz, J = 1.9 Hz), 7.75–7.72
(dd, 1H, J = 8.1 Hz, J = 1.2 Hz), 7.54–7.34 (m, 4H), 7.21 (s, 1H),
3.37 (t, 2H, J = 7.8 Hz), 2.13–2.01 (m, 2H), 1.22 (t, 3H, J = 7.6
Hz). 13C NMR (CDCl3, 75 MHz) d 151.5, 139.0, 135.4, 131.3,
130.7, 129.0, 127.3, 126.9, 123.4, 122.7, 122.2, 120.9, 120.5,
115.1, 95.5, 38.9, 19.8, 14.1. ESI-MS [M + H]+ m/z 261.2.
6-Isopropylindolo[1,2-c]quinazoline (3e). Eluent: petroleum
ether–ethyl acetate (50 : 1). Yield 30 mg (58%). Light yellow
solid, m.p. 90–91 uC. 1H NMR (CDCl3, 300 MHz) d 8.07 (dd, 2H,
J = 7.5 Hz, J = 1.6 Hz), 7.84 (dd, 1H, J = 6.6 Hz, J = 2.4 Hz), 7.77
(d, 1H, J = 7.6 Hz), 7.55–7.38 (m, 4H), 7.27 (s, 1H), 4.07–3.93 (s,
1H), 1.59 (d, 6H, J = 3.6 Hz). 13C NMR (CDCl3 75 MHz) d 155.9,
139.0, 135.8, 139.0, 130.8, 129.0, 127.5, 126.8, 123.2, 122.7,
122.2, 120.9, 120.5, 115.7, 95.6, 32.8, 20.7. ESI-MS [M + H]+ m/z
261.2.
a
Reaction conditions: 2-(2-bromophenyl)-1H-indole (1) (0.2 mmol),
amino acid (2) (0.4 mmol), CuI (0.04 mmol), K2CO3 (0.4 mmol),
DMF (3 mL), reaction temperature (90 uC), reaction time (12 h under
b
air; 24 h under oxygen (1 atm)). Isolated yield.
silica gel using petroleum ether–ethyl acetate as eluent to
provide the desired product (3, 5 and 7).
Indolo[1,2-c]quinazoline (3a)10. Eluent: petroleum ether–
ethyl acetate (5 : 1). Yield 31 mg (72%). Light yellow solid, m.p.
200–202 uC. 1H NMR (CDCl3, 300 MHz) d 9.02 (s, 1H), 8.05 (dd,
1H, J = 7.5 Hz, J = 1.8 Hz), 7.95 (dd, 1H, J = 6.9 Hz, J = 0.9 Hz),
7.84–7.79 (m, 2H), 7.58–7.47 (m, 2H), 7.44–7.40 (m, 2H), 7.13
(s, 1H). 13C NMR (CDCl3, 75 MHz) d 139.6, 137.2, 133.1, 130.5,
129.9, 129.3, 128.3, 127.9, 124.2, 123.3, 122.4, 121.5, 121.1,
110.0, 94.8. ESI-MS [M + H]+ m/z 219.2.
6-Methylindolo[1,2-c]quinazoline (3b)11. Eluent: petroleum
ether–ethyl acetate (5 : 1). Yield 21 mg (45%). Light yellow
solid, m.p. 112–114 uC. H NMR (CDCl3, 300 MHz) d 8.10 (d,
6-(sec-Butyl)indolo[1,2-c]quinazoline (3f). Eluent: petroleum
ether–ethyl acetate (50 : 1). Yield 36 mg (66%). Light yellow
1
1
viscous solid. H NMR (CDCl3, 300 MHz) d 8.09–8.04 (m, 2H),
1H, J = 7.9 Hz), 8.04 (d, 1H, J = 7.9 Hz), 7.82 (d, 1H, J = 9.3 Hz),
7.72 (d, 1H, J = 9.5 Hz), 7.53–7.35 (m, 4H), 7.24 (d, 1H, J = 8.4
Hz), 3.16 (s, 3H). 13C NMR (CDCl3, 75MHz) d 148.6, 139.0,
135.0, 131.8, 130.6, 129.1, 127.0, 126.9, 123.5, 122.7, 122.6,
120.9, 120.3, 114.9, 95.6, 25.6. ESI-MS [M + H]+ m/z 233.2.
7.85 (dd, 1H, J = 6.3 Hz, J = 2.1 Hz), 7.76 (d, 1H, J = 7.8 Hz),
7.55–7.37 (m, 4H), 7.27 (s, 1H), 3.82–3.72 (m, 1H), 2.35–2.22
(m, 1H), 1.89–1.76 (m, 1H), 1.59–1.55 (m, 3H), 1.10 (t, 3H, J =
7.2 Hz). 13C NMR (CDCl3, 75 MHz) d 155.2, 138.9, 135.8, 131.0,
130.8, 129.0, 127.5, 126.8, 123.3, 122.7, 122.2, 121.0, 120.4,
115.6, 95.6, 39.5, 27.5, 18.2, 12.0. ESI-MS [M + H]+ m/z 275.2.
6-iso-Butylindolo[1,2-c]quinazoline (3g). Eluent: petroleum
ether–ethyl acetate (50 : 1). Yield 51 mg (93%). Light yellow
solid, m.p. 89–91 uC. 1H NMR (CDCl3, 300 MHz) d 8.06 (dd, 1H,
J = 8.1 Hz, J = 1.4 Hz), 8.00 (d, 1H, J = 7.8 Hz), 7.83 (dd, 1H, J =
6.9 Hz, J = 2.4 Hz), 7.75 (d, 1H, J = 8.1 Hz), 7.55–7.35 (m, 4H),
7.23 (t, 1H, J = 7.5 Hz), 3.30 (d, 2H, J = 7.2 Hz), 2.63–2.49 (m,
1H), 1.17 (d, 6H, J = 6.3 Hz). 13C NMR (CDCl3, 75 MHz) d 150.7,
139.0, 135.5, 131.3, 130.7, 129.0, 127.4, 126.9, 123.4, 122.7,
122.1, 121.0, 120.5, 115.1, 95.6, 45.6, 25.6, 22.7. ESI-MS [M +
H]+ m/z 275.2.
6-Ethylindolo[1,2-c]quinazoline (3c)11
. Eluent: petroleum
ether–ethyl acetate (50 : 1). Yield 24 mg (48%). Light yellow
solid, m.p. 97–99 uC. 1H NMR (CDCl3, 300 MHz) d 8.07 (m, 2H),
7.84 (dd, 1H, J = 6.9 Hz, J = 1.8 Hz), 7.75 (dd, 1H, J = 7.8 Hz, J =
1.2 Hz), 7.55–7.34 (m, 4H), 7.23 (s, 1H), 3.45 (m, 2H, J = 7.2 Hz),
3.45 (t, 3H, J = 7.5 Hz). 13C NMR (CDCl3, 75 MHz) d 152.5,
6-Phenylindolo[1,2-c]quinazoline (3h)11. Eluent: petroleum
ether–ethyl acetate (10 : 1). Yield 41 mg (70%). Light yellow
solid, m.p. 197–199 uC. 1H NMR (CDCl3, 300 MHz) d 8.11–8.08
(m, 1H), 7.85–7.82 (m, 1H), 7.76 (d, 1H, J = 7.8 Hz), 7.68–7.56
(m, 5H), 7.53–7.48 (m, 2H), 7.31–7.23 (m, 2H) 6.97 (dt, 1H, J =
Scheme 1 Copper-catalyzed reaction of 2-(2-bromophenyl)-1H-indole (1a) with
pipecolinic acid (2k) leading to 3y under the standard conditions.
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Table 3 Copper-catalyzed synthesis of benzo[4,5]imidazo[1,2-c]quinazoline
derivativesa
Table 3 (Continued)
Entry
12
4
2
5 (Temp., yield)b
Entry
1
4
2
5 (Temp., yield)b
2i
2
3
4a
4a
a
Reaction conditions: 2-(2-halophenyl)-1H-benzo[d]imidazole (3) (0.2
mmol), amino acid (2) (0.4 mmol), CuI (0.04 mmol), K2CO3 (0.4
mmol), DMF (3 mL), reaction temperature (90 or 105 uC), reaction
b
time (36 h under air; 36 h under oxygen (1 atm)). Isolated yield.
8.4 Hz, J = 1.8 Hz), 6.45 (d, 1H, J = 8.7 Hz). 13C NMR (CDCl3, 75
MHz) d 149.4, 139.3, 136.1, 135.3, 131.7, 130.5, 129.4, 129.2,
128.3, 128.0, 127.5, 123.5, 122.8, 121.6, 120.7, 120.6, 115.0,
95.8. ESI-MS [M + H]+ m/z 295.1.
4
5
4a
4a
6-(4-Chlorophenyl)indolo[1,2-c]quinazoline (3i)12
. Eluent:
petroleum ether–ethyl acetate (20 : 1). Yield 50 mg (77%).
Light yellow solid, m.p. 199–201 uC. 1H NMR (CDCl3, 300 MHz)
d 8.09 (dd, 1H, J = 7.5 Hz, J = 1.8 Hz), 7.83 (dd, 1H, J = 7.2 Hz, J
= 1.2 Hz), 7.71–7.48 (m, 8H), 7.18 (s, 1H), 6.92 (dd, 1H, J = 8.9
Hz, J = 2.1 Hz) 6.34 (d, 1H, J = 9.0 Hz). 13C NMR (CDCl3, 75
MHz) d 149.0, 139.4, 136.6, 135.7, 130.7, 130.1, 129.7, 129.5,
129.4, 129.2, 128.3, 128.1, 127.8, 123.0, 121.8, 120.3, 119.8,
115.9, 95.2. ESI-MS [M + H]+ m/z 329.2.
6-(Thiophen-2-yl)indolo[1,2-c]quinazoline (3j)13. Eluent: pet-
roleum ether–ethyl acetate (20 : 1 to 15 : 1). Yield 36 mg
(60%). Yellow solid, m.p. 199–201 uC. 1H NMR (CDCl3, 300
MHz) d 8.10 (dd, 1H, J = 6.9 Hz, J = 2.4 Hz), 7.85–7.77 (m, 2H),
7.64 (d, 1H, J = 5.4 Hz), 7.55–7.49 (m, 3H), 7.34 (t, 1H, J = 7.8
Hz), 7.28–7.27 (m, 2H), 7.08 (t, 1H, J = 5.5 Hz), 6.71 (d, 1H, J =
5.7 Hz). 13C NMR (CDCl3, 100 MHz) d 143.6, 139.1, 136.0,
135.4, 131.7, 130.4, 129.3, 129.2, 128.4, 128.1, 127.9, 127.6,
123.7, 122.8, 121.8, 120.8, 120.7, 114.9, 96.1. ESI-MS [M + H]+
m/z 301.1.
6
7
4a
2e
8
9
4b
4b
2i
2j
10
11
4b
4b
2k
Scheme 3 Copper-catalyzed
reaction
of
5-(2-bromophenyl)-3-phenyl-
1H-pyrazole (6) with amino acids (2) leading to pyrazolo[1,5-c]quinazolines
(7a–d) under the same conditions as in Table 1.
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3-Methoxyindolo[1,2-c]quinazoline (3k). Eluent: petroleum
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d 8.03 (dd, 1H, J = 7.8 Hz, J = 0.9 Hz), 7.88 (d, 1H, J = 8.7 Hz),
7.77–7.74 (m, 2H), 7.58–7.44 (m, 2H), 7.32 (dd, 1H, J = 9.3 Hz, J
= 2.1 Hz) 7.14 (s, 1H), 3.23 (d, 2H, J = 7.8 Hz), 2.57–2.45 (m,
1H), 1.16 (d, 6H, J = 6.6 Hz). 13C NMR (CDCl3, 75 MHz) d 150.2,
139.0, 136.8, 131.8, 129.6, 129.5, 129.1, 127.5, 127.1, 122.8,
122.2, 120.1, 120.0, 116.0, 94.9, 45.4, 25.5, 22.7. ESI-MS [M +
H]+ m/z 309.1.
ether–ethyl acetate (3 : 1). Yield 32 mg (65%). Light yellow
1
solid, m.p. 222–224 uC. H NMR (CDCl3, 300 MHz) d 8.99 (s,
1H), 7.93 (t, 2H, J = 8.7 Hz), 7.78 (d, 1H, J = 8.6 Hz), 7.45–7.34
(m, 2H), 7.27 (d, 1H, J = 8.3 Hz), 7.10 (dd, 1H, J = 8.9 Hz, J = 2.7
Hz), 6.97 (s, 1H), 3.92 (s, 3H). 13C NMR (CDCl3, 75 MHz) d
160.6, 141.2, 137.7, 133.3, 130.3, 130.2, 124.5, 124.2, 121.8,
120.8, 116.9, 114.8, 110.3, 109.9, 93.1, 55.7. ESI-MS [M + H]+ m/
z 249.2.
3-Methoxy-6-methylindolo[1,2-c]quinazoline (3l). Eluent:
petroleum ether–ethyl acetate (1 : 1). Yield 27 mg (51%).
Light yellow solid, m.p. 130–132 uC. 1H NMR (CDCl3, 300 MHz)
d 8.08 (d, 1H, J = 8.1 Hz), 7.96 (d, 1H, J = 8.4 Hz), 7.79 (d, 1H, J =
8.0 Hz), 7.42–7.30 (m, 2H), 7.19 (d, 1H, J = 2.4 Hz), 7.09–7.06
(m, 2H), 3.91 (s, 3H), 3.15 (s, 3H). 13C NMR (CDCl3, 75 MHz) d
160.7, 149.3, 140.7, 135.4, 131.7, 131.0, 124.1, 123.6, 121.6,
120.6, 116.4, 114.8, 113.8, 108.8, 93.9, 55.7, 25.6. ESI-MS [M +
H]+ m/z 263.2.
6-Ethyl-3-methoxyindolo[1,2-c]quinazoline (3m). Eluent: pet-
roleum ether–ethyl acetate (3 : 1). Yield 40 mg (73%). Light
yellow solid, m.p. 126–127 uC. 1H NMR (CDCl3, 300 MHz) d
8.05 (d, 1H, J = 8.4 Hz), 7.96 (d, 1H, J = 8.4 Hz), 7.80 (dd, 1H, J =
8.7 Hz, J = 1.8 Hz), 7.45–7.31 (m, 2H), 7.24 (d, 1H, J = 2.2 Hz),
7.10 (s, 1H), 7.07 (dd, 1H, J = 8.7 Hz, J = 2.7 Hz), 3.93 (s, 3H),
3.46 (q, 2H, J = 7.2 Hz), 1.60 (t, 3H, J = 7.2 Hz). 13C NMR (CDCl3,
75 MHz) d 160.6, 153.2, 140.6, 135.7, 131.1, 131.0, 124.0, 123.4,
121.6, 120.5, 116.4, 115.2, 113.8, 108.9, 93.9, 55.7, 30.4, 10.9.
ESI-MS [M + H]+ m/z 277.2.
6-Isobutyl-3-methoxyindolo[1,2-c]quinazoline (3n). Eluent:
petroleum ether–ethyl acetate (15 : 1). Yield 27 mg (44%).
Light yellow solid, m.p. 140–142 uC. 1H NMR (CDCl3, 300 MHz)
d 7.95 (d, 2H, J = 8.7 Hz), 7.78 (dd, 1H, J = 7.9 Hz), 7.43–7.30 (m,
2H), 7.22 (d, 1H, J = 2.4 Hz), 7.08–7.05 (m, 2H), 3.92 (s, 3H),
3.28 (d, 2H, J = 7.2 Hz), 2.60–2.45 (m,1H), 1.16 (d, 6H, J = 6.6
Hz). 13C NMR (CDCl3, 75 MHz) d 160.6, 151.3, 140.5, 135.8,
131.1, 131.0, 124.0, 123.4, 121.5, 120.6, 116.4, 115.0, 113.8,
109.0, 93.8, 55.7, 45.6, 25.6, 22.6. ESI-MS [M + H]+ m/z 305.2.
3-Methoxy-6-phenylindolo[1,2-c]quinazoline (3o). Eluent:
petroleum ether–ethyl acetate (10 : 1). Yield 44 mg (67%).
Light yellow solid, m.p. 170–172 uC. 1H NMR (CDCl3, 300 MHz)
d 8.01 (d, 1H, J = 9.0 Hz), 7.73 (d, 1H, J = 8.4 Hz), 7.69–7.59 (m,
5H), 7.32–7.28 (m, 2H), 7.14–7.11 (m, 2H), 6.94 (dt, 1H, J = 7.5
Hz, J = 1.5 Hz), 6.44 (d, 1H, J = 8.7 Hz), 3.91 (s, 3H). 13C NMR
(CDCl3, 75 MHz) d 160.7, 150.1, 140.9, 136.1, 135.7, 131.5,
130.9, 130.5, 129.5, 128.3, 124.1, 123.6, 121.0, 120.1, 117.1,
114.9, 114.0, 109.7, 94.1, 55.7. ESI-MS [M + H]+ m/z 325.2.
6-(4-Chlorophenyl)-3-methoxyindolo[1,2-c]quinazoline (3p).
Eluent: petroleum ether–ethyl acetate (20 : 1). Yield 52 mg
(73%). Yellow solid, m.p. 219–222 uC. 1H NMR (CDCl3, 300
MHz) d 8.00 (d, 1H, J = 8.4 Hz), 7.74 (d, 1H, J = 7.8 Hz), 7.65–
7.58 (m, 4H), 7.34–7.28 (m, 2H), 7.15–7.10 (m, 2H), 7.04–6.96
(m, 1H), 6.56 (d, 1H, J = 8.1 Hz), 3.90 (s, 3H). 13C NMR (CDCl3,
75 MHz) d 148.9, 140.7, 136.7, 135.6, 134.5, 131.3, 130.9, 129.9,
129.7, 124.1, 123.7, 121.2, 120.5, 117.2, 114.7, 114.0, 109.6,
94.3, 55.7. ESI-MS [M + H]+ m/z 359.1.
10-Chloro-6-phenylindolo[1,2-c]quinazoline (3r)12
. Eluent:
petroleum ether–ethyl acetate (20 : 1). Yield 41 mg (63%).
Light yellow solid, m.p. 207–209 uC. 1H NMR (CDCl3, 300 MHz)
d 8.09 (dd, 1H, J = 7.5 Hz, J = 1.8 Hz), 7.84 (dd, 1H, J = 7.2 Hz, J
= 1.0 Hz), 7.71 (m, 8H), 7.18 (s, 1H), 6.92 (dd, 1H, J = 9.0 Hz, J =
2.1 Hz), 6.34 (d, 1H, J = 9.0 Hz). 13C NMR (CDCl3, 75 MHz) d
149.0, 139.4, 136.6, 135.7, 131.6, 130.7, 130.1, 129.7, 129.6,
129.4, 128.3, 128.1, 127.8, 123.0, 121.8, 120.3, 119.8, 116.0,
95.2. ESI-MS [M + H]+ m/z 329.2.
10-Chloro-6-(4-chlorophenyl)indolo[1,2-c]quinazoline (3s).
Eluent: petroleum ether–ethyl acetate (20 : 1). Yield 44 mg
(61%). Light yellow solid, m.p. 250–251 uC. 1H NMR (CDCl3,
400 MHz) d 8.08 (d, 1H, J = 7.6 Hz), 7.81 (d, 1H, J = 8.0 Hz), 7.72
(d, 1H, J = 1.6 Hz), 7.63–7.52 (m, 6H), 7.19 (s, 1H), 6.98 (dd, 1H,
J = 8.8 Hz, J = 1.6 Hz), 6.48 (d, 1H, J = 9.2 Hz). 13C NMR (CDCl3,
100 MHz) d 147.8, 139.2, 136.9, 136.6, 134.0, 131.6, 129.90,
129.83, 129.75, 129.51, 128.1, 128.0, 123.0, 122.0, 120.3, 120.0,
115.7, 95.4. ESI-MS [M + H]+ m/z 363.1.
10-Chloro-6-(thiophen-2-yl)indolo[1,2-c]quinazoline (3t)12
.
Eluent: petroleum ether–ethyl acetate (20 : 1–15 : 1). Yield 43
mg (64%). Light yellow solid, m.p. 235–237 uC. 1H NMR
(CDCl3, 400 MHz) d 8.08 (d, 1H, J = 11.2 Hz), 7.84 (d, 1H, J =
11.0 Hz), 7.73 (d, 1H, J = 2.0 Hz), 7.66 (d, 1H, J = 4.8 Hz), 7.57–
7.52 (m, 2H), 7.49 (d, 1H, J = 3.6 Hz), 7.27 (d, 1H, J = 4.0 Hz),
7.20 (s, 1H), 7.20 (dd, 1H, J = 8.8 Hz, J = 2.4 Hz), 6.60 (d, 1H, J =
9.2 Hz). 13C NMR (CDCl3, 100 MHz) d 143.2, 139.2, 136.7,
135.6, 131.5, 130.0, 129.7, 129.5, 128.7, 128.3, 128.1, 127.7,
123.0, 122.0, 120.4, 119.9, 115.8, 95.4. ESI-MS [M + H]+ m/z
335.2.
10-Methyl-6-propylindolo[1,2-c]quinazoline (3u)11. Eluent:
petroleum ether–ethyl acetate (50 : 1). Yield 41 mg (75%).
Light yellow solid, m.p. 134–136 uC. 1H NMR (CDCl3, 300 MHz)
d 8.04 (dd, 1H, J = 7.5 Hz, J = 1.5 Hz), 7.87 (d, 1H, J = 8.4 Hz),
7.73 (dd, 1H, J = 8.7 Hz, J = 1.0 Hz), 7.61 (s, 1H), 7.53–7.40 (m,
2H), 7.20 (dd, 1H, J = 7.8 Hz, J = 1.8 Hz), 7.15 (s, 1H), 3.66 (t,
2H, J = 7.5 Hz), 2.54 (s, 3H), 2.06 (m, 2H), 1.21 (t, 3H, J = 7.2
Hz). 13C NMR (CDCl3, 75 MHz) d 151.6, 139.1, 135.5, 133.1,
131.0, 129.7, 129.0, 127.3, 126.8, 123.9, 122.7, 120.6, 120.5,
114.8, 95.2, 38.9, 21.6, 19.8, 14.1. ESI-MS [M + H]+ m/z 275.2.
10-Methyl-6-phenylindolo[1,2-c]quinazoline (3v)11
. Eluent:
petroleum ether–ethyl acetate (20 : 1). Yield 37 mg (60%).
Light yellow solid, m.p. 195–197 uC. 1H NMR (CDCl3, 400 MHz)
d 8.10 (dd, 1H, J = 7.2 Hz, J = 1.2 Hz), 7.82 (dd, 1H, J = 7.2 Hz, J
= 1.2 Hz), 7.68–7.58 (m, 5H), 7.55–7.48 (m, 3H), 7.20 (s, 1H),
6.80 (dd, 1H, J = 8.8 Hz, J = 1.2 Hz), 6.31 (d, 1H, J = 8.8 Hz), 2.44
(s, 3H). 13C NMR (CDCl3, 100 MHz) d 149.4, 139.4, 136.1, 135.5,
133.2, 130.8, 130.5, 130.1, 129.4, 129.1, 128.4, 128.0, 127.4,
123.3, 122.8, 120.8, 120.2, 114.6, 95.5, 21.5. ESI-MS [M + H]+ m/
z 309.2.
10-Chloro-6-isobutylindolo[1,2-c]quinazoline (3q). Eluent:
petroleum ether–ethyl acetate (3 : 1). Yield 42 mg (67%).
Light yellow solid, m.p. 141–143 uC. 1H NMR (CDCl3, 300 MHz)
6-(4-Chlorophenyl)-10-methylindolo[1,2-c]quinazoline (3w).
Eluent: petroleum ether–ethyl acetate (20 : 1). Yield 48 mg
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(71%). Light yellow solid, m.p. 220–221 uC. 1H NMR (CDCl3,
300 MHz) d 8.08 (dd, 1H, J = 6.9 Hz, J = 2.4 Hz), 7.79 (dd, 1H, J =
7.2 Hz, J = 2.4 Hz), 7.64–7.59 (m, 4H), 7.57–7.49 (m, 3H), 7.19
(s, 1H), 6.86 (dd, 1H, J = 8.7 Hz, J = 2.1 Hz), 6.44 (d, 1H, J = 8.7
Hz), 2.46 (s, 3H). 13C NMR (CDCl3, 75 MHz) d 149.0, 139.2,
136.6, 135.4, 134.5, 133.4, 130.8, 129.95, 129.86, 129.67, 129.2,
128.0, 127.6, 123.4, 122.8, 120.7, 120.4, 114.4, 95.7, 21.6. ESI-
MS [M + H]+ m/z 343.1.
solid, m.p. 246–247 uC. H NMR (CDCl3, 400 MHz) d 8.76 (d,
1H, J = 8.4 Hz), 8.00 (t, 2H, J = 8.0 Hz), 7.81 (dt, 1H, J = 8.0 Hz, J
= 1.4 Hz), 7.75–7.65 (m, 6H), 7.47 (t, 1H, J = 8.0 Hz), 7.12 (t, 1H,
J = 8.4 Hz), 6.61 (d, 1H, J = 8.4 Hz). 13C NMR (CDCl3, 100 MHz)
d 148.7, 148.2, 144.6, 142.5, 134.4, 132.0, 131.1, 129.5 (2C),
128.49, 128.46, 128.38, 125.8, 124.3, 112.7, 120.1, 118.6, 114.5.
ESI-MS [M + H]+ m/z 296.0.
6-(4-Chlorophenyl)benzo[4,5]imidazo[1,2-c]quinazoline
(5e)16. Eluent: petroleum ether–ethyl acetate (10 : 1–5 : 1).
Yield 51 mg (78%). White solid, m.p. 241–242 uC. 1H NMR
(CDCl3, 400 MHz) d 8.73 (d, 1H, J = 8.0 Hz, J = 1.2 Hz), 8.00–
7.98 (m, 2H), 7.82–7.64 (m, 6H), 7.48 (t, 1H, J = 7.6 Hz), 7.16 (t,
1H, J = 7.6 Hz), 6.73 (d, 1H, J = 8.0 Hz). 13C NMR (CDCl3, 100
MHz) d 148.1, 147.5, 144.5, 142.3, 137.4, 132.8, 132.1, 130.1,
129.7, 129.2, 128.6, 128.3, 125.9, 124.3, 122.8, 120.3, 118.5,
114.2. ESI-MS [M + H]+ m/z 330.1.
10-Methyl-6-(thiophen-2-yl)indolo[1,2-c]quinazoline (3x)12
.
Eluent: petroleum ether–ethyl acetate (15 : 1). Yield 40 mg
(64%). Light yellow solid, m.p. 218–219 uC. 1H NMR (CDCl3,
400 MHz) d 8.08 (d, 1H, J = 7.2 Hz), 7.82 (d, 1H, J = 6.8 Hz), 7.63
(d, 1H, J = 6.2 Hz), 7.56 (s, 1H), 7.53–7.48 (m, 3H), 7.27–7.25
(m, 1H), 7.19 (s, 1H), 6.90 (d, 1H, J = 8.8 Hz), 6.58 (d, 1H, J = 8.8
Hz), 2.47 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 143.6, 139.2,
136.1, 135.5, 133.4, 130.8, 130.0, 129.3, 129.1, 128.3, 128.1,
127.8, 127.6, 123.5, 122.8, 120.8, 120.3, 114.5, 95.7, 21.6. ESI-
MS [M + H]+ m/z 315.2.
7,8-Dihydro-6H-indolo[1,2-c]pyrido[1,2-a]quinazoline (3y).
Eluent: petroleum ether–ethyl acetate (50 : 1). Yield 35 mg
(64%). Light yellow waxy solid. 1H NMR (CDCl3, 300 MHz) d
7.69 (dd, 1H, J = 7.5 Hz, J = 1.4 Hz), 7.61 (d, 1H, J = 7.8 Hz), 7.25
(s, 1H), 7.22–7.10 (m, 3H), 6.91–6.83 (m, 2H), 6.75 (s, 1H), 5.66
(dd, 1H, J = 8.1 Hz, J = 2.1 Hz), 4.19 (d, 1H, J = 10.2 Hz), 3.27–
3.21 (m, 1H), 2.30–2.11 (m, 1H), 2.00–1.61 (m, 3H). 13C NMR
(CDCl3, 75 MHz) d 140.2, 135.0, 134.2, 132.6, 129.3, 129.3,
124.8, 121.4, 120.6, 120.2, 118.8, 117.2, 113.2, 108.6, 94.7, 70.6,
47.9, 28.8, 24.7, 20.4. ESI-MS [M + H]+ m/z 273.1.
6-(Thiophen-2-yl)benzo[4,5]imidazo[1,2-c]quinazoline (5f)17
.
Eluent: petroleum ether–ethyl acetate (5 : 1). Yield 42 mg
(70%). White solid, m.p. 232–233 uC. 1H NMR (CDCl3, 400
MHz) d 8.73 (d, 1H, J = 7.6 Hz), 8.00 (d, 1H, J = 7.6 Hz), 7.80 (t,
1H, J = 7.6 Hz), 7.72–7.69 (m, 2H), 7.61 (d, 1H, J = 8.0 Hz), 7.53–
7.45 (m, 2H), 7.33–7.19 (m, 2H), 6.96 (d, 1H, J = 8.8 Hz). 13C
NMR (CDCl3, 100 MHz) d 148.2, 144.5, 142.9, 142.3, 134.3,
132.0, 130.0, 129.2, 128.8, 128.4, 127.7, 126.7, 125.9, 124.3,
122.8, 120.2, 118.6, 114.4. ESI-MS [M + H]+ m/z 302.1.
6-Isopropyl-2-methylbenzo[4,5]imidazo[1,2-c]quinazoline
(5g). Eluent: petroleum ether–ethyl acetate (5 : 1). Yield 25 mg
(46%). White solid, m.p. 164–165 uC. 1H NMR (CDCl3, 400
MHz) d 8.50 (s, 1H), 8.03 (dd, 2H, J = 8.4 Hz, J = 1.4 Hz), 7.82 (d,
1H, J = 8.0 Hz), 7.58–7.55 (m, 2H), 7.46 (dt, 1H, J = 8.4 Hz, J =
1.2 Hz), 4.00–3.90 (m, 1H), 2.58 (s, 3H), 1.61 (d, 6H, J = 6.8 Hz).
13C NMR (CDCl3, 100 MHz) d 154.3, 148.5, 144.7, 140.3, 137.9,
133.2, 128.9, 127.7, 125.4, 123.8, 123.1, 120.4, 118.1, 115.0,
32.7, 21.6, 20.3. ESI-MS [M + H]+ m/z 276.2.
6-Isobutyl-2-methylbenzo[4,5]imidazo[1,2-c]quinazoline
(5h). Eluent: petroleum ether–ethyl acetate (10 : 1). Yield 47
mg (81%). White solid, m.p. 139–141 uC. H NMR (CDCl3, 400
MHz) d 8.50 (s, 1H), 8.03 (d, 1H, J = 7.8 Hz), 7.97 (d, 1H, J = 8.1
Hz), 7.82 (d, 1H, J = 8.2 Hz), 7.60–7.55 (m, 2H), 7.47 (dt, 1H, J =
9.2 Hz, J = 1.2 Hz). 13C NMR (CDCl3, 100 MHz) d 149.3, 148.3,
144.6, 140.3, 138.1, 133.3, 129.2, 127.6, 125.5, 123.8, 123.0,
120.4, 118.0, 114.4, 44.6, 25.7, 22.6, 21.6. ESI-MS [M + H]+ m/z
290.2.
Benzo[4,5]imidazo[1,2-c]quinazoline (5a)14. Eluent: CH2Cl2–
MeOH (20 : 1). Yield 37 mg (85%). white solid, m.p. 229–231
uC. 1H NMR (CDCl3, 300 MHz) d 9.17 (s, 1H), 8.70 (d, 1H, J = 8.1
Hz), 8.04–7.99 (m, 3H), 7.81 (t, 1H, J = 8.4 Hz), 7.74 (t, 1H, J =
7.8 Hz), 7.60 (t, 1H, J = 8.4 Hz), 7.51 (t, 1H, J = 7.8 Hz). 13C NMR
(CDCl3, 100 MHz) d 146.5, 144.2, 142.7, 136.3, 131.9, 128.8,
128.7, 128.3, 126.3, 124.4, 123.5, 120.5, 119.5, 110.2. ESI-MS [M
+ H]+ m/z 220.1.
1
6-Propylbenzo[4,5]imidazo[1,2-c]quinazoline (5b)15. Eluent:
petroleum ether–ethyl acetate (5 : 1). Yield 29 mg (56%). white
1
solid, m.p. 102–104 uC. H NMR (CDCl3, 600 MHz) d 8.65 (d,
1H, J = 8.4 Hz), 8.01 (d, 1H, J = 8.4 Hz), 7.93 (d, 1H, J = 8.4 Hz),
7.88 (d, 1H, J = 7.2 Hz), 7.74 (t, 1H, J = 7.8 Hz), 7.61 (t, 1H, J =
7.2 Hz), 7.54 (t, 1H, J = 7.8 Hz), 7.44 (t, 1H, J = 7.8 Hz), 3.39 (t,
2H, J = 7.8 Hz), 2.11–2.08 (m, 2H), 1.23 (t, 3H, J = 7.6 Hz). 13C
NMR (CDCl3, 100 MHz) d 150.7, 148.1, 144.5, 142.3, 131.7,
129.1, 127.7, 127.6, 125.5, 124.2, 123.2, 120.3, 118.2, 114.4,
37.9, 19.4, 14.0. ESI-MS [M + H]+ m/z 262.2.
2-Methyl-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline
(5i)15. Eluent: petroleum ether–ethyl acetate (5 : 1). Yield 38
mg (61%). White solid, m.p. 252–253 uC. H NMR (CDCl3, 400
1
6-Isopropylbenzo[4,5]imidazo[1,2-c]quinazoline (5c). Eluent:
petroleum ether–ethyl acetate (10 : 1). Yield 24 mg (47%).
White solid, m.p. 196–197 uC. 1H NMR (CDCl3, 400 MHz) d
8.69 (dd, 1H, J = 7.6 Hz, J = 1.2 Hz), 8.06–8.03 (m, 2H), 7.93 (d,
1H, J = 8.0 Hz), 7.76 (dt, 1H, J = 7.6 Hz, J = 1.2 Hz), 7.65–7.55
(m, 2H), 7.48 (dt, 1H, J = 8.4 Hz, J = 1.2 Hz), 4.02–3.90 (m, 1H),
1.62 (d, 6H, J = 6.0 Hz). 13C NMR (CDCl3, 100 MHz) d 155.2,
148.5, 144.7, 142.3, 131.7, 128.8, 127.9, 127.7, 125.5, 124.2,
123.2, 120.4, 118.4, 115.0, 32.8, 20.3. ESI-MS [M + H]+ m/z
262.2.
MHz) d 8.56 (s, 1H), 7.98 (d, 1H, J = 8.4 Hz), 7.90 (d, 1H, J = 8.0
Hz), 7.74–7.60 (m, 6H), 7.46 (t, 1H, J = 7.2 Hz), 7.10 (t, 1H, J =
7.2 Hz), 6.61 (d, 1H, J = 8.4 Hz), 2.62 (s, 3H). 13C NMR (CDCl3,
100 MHz) d 148.2, 147.8, 144.5, 140.6, 138.8, 134.5, 133.5,
131.0, 129.5, 129.4, 128.6, 128.1, 125.7, 123.9, 122.6, 120.1,
118.3, 114.5, 21.7. ESI-MS [M + H]+ m/z 310.1.
6-(4-Chlorophenyl)-2-methylbenzo[4,5]imidazo[1,2-c]quina-
zoline (5j). Eluent: petroleum ether–ethyl acetate (5 : 1). Yield
1
45 mg (66%). White solid, m.p. 242–244 uC. H NMR (DMSO-
d6, 300 MHz) d 8.43 (s, 1H), 7.93–7.76 (m, 6H), 7.68 (d, 1H, J =
8.1 Hz), 7.46 (t, 1H, J = 7.8 Hz), 7.19 (t, 1H, J = 7.2 Hz), 6.54 (d,
1H, J = 8.4 Hz), 2.58 (s, 3H). 13C NMR (DMSO-d6, 75 MHz) d
6-Phenylbenzo[4,5]imidazo[1,2-c]quinazoline (5d)15. Eluent:
petroleum ether–ethyl acetate (5 : 1). Yield 48 mg (81%). white
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147.8, 147.1, 144.5, 140.6, 138.8, 136.0, 133.8, 133.6, 131.1,
129.6, 129.5, 128.2, 125.8, 123.7, 122.9, 120.1, 118.4, 114.3,
21.7. ESI-MS [M + H]+ m/z 344.1.
127.8, 127.2, 127.0, 123.1, 119.1, 95.2. ESI-MS [M + H]+ m/z
328.1.
2-Methyl-6-(thiophen-2-yl)benzo[4,5]imidazo[1,2-c]quinazo-
line (5k). Eluent: petroleum ether–ethyl acetate (10 : 1–5 : 1).
Yield 43 mg (68%). White solid, m.p. 255–256 uC. 1H NMR
(CDCl3, 400 MHz) d 8.54 (s, 1H), 7.99 (d, 1H, J = 8.0 Hz), 7.89
(d, 1H, J = 8.0 Hz), 7.70 (dd, 1H, J = 5.2 Hz, J = 1.2 Hz), 7.63–
7.59 (m, 2H), 7.50 (t, 1H, J = 7.2 Hz), 7.32–7.30 (m, 1H), 7.19 (t,
1H, J = 7.2 Hz), 6.93 (d, 1H, J = 8.4 Hz), 2.61 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d 148.1, 144.5, 142.0, 140.4, 139.2, 134.6,
133.5, 129.9, 129.4, 129.1, 128.2, 127.7, 125.8, 123.9, 122.7,
120.1, 118.3, 114.4, 21.8. ESI-MS [M + H]+ m/z 316.1.
Acknowledgements
The authors wish to thank the National Natural Science
Foundation of China (Grant Nos. 21172128, 21105054 and
21221062), the Ministry of Science and Technology of China
(Grant No. 2012CB722605) and the Doctoral Program of
Higher Education (No. 20090002110058) for financial support.
2-Chloro-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline
(5l)15. Eluent: petroleum ether–ethyl acetate (10 : 1). Yield 28
mg (42%). White solid, m.p. 249–250 uC. H NMR (CDCl3, 400
MHz) d 8.73 (s, 1H), 7.98 (d, 1H, J = 8.4 Hz), 7.93 (d, 1H, J = 8.8
Hz), 7.75–7.65 (m, 6H), 7.48 (t, 1H, J = 8.0 Hz), 7.13 (t, 1H, J =
8.4 Hz), 6.63 (d, 1H, J = 8.4 Hz). 13C NMR (CDCl3, 100 MHz) d
148.8, 147.0, 144.4, 140.9, 134.2, 134.1, 132.4, 131.3, 129.9,
129.5, 129.4, 128.4, 126.0, 123.8, 123.1, 120.3, 119.6, 114.6. ESI-
MS [M + H]+ m/z 330.1.
Notes and references
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1
5-Ethyl-2-phenylpyrazolo[1,5-c]quinazoline (7a). Eluent: pet-
roleum ether–ethyl acetate (50 : 1). Yield 30 mg (55%). Light
1
yellow solid, m.p. 89–90 uC. H NMR (CDCl3, 400 MHz) d 8.06
(m, 3H), 7.91 (d, 1H, J = 8.0 Hz), 7.63 (t, 1H, J = 8.4 Hz), 7.56–
7.48 (m, 3H), 7.43 (d, 1H, J = 7.6 Hz), 7.27 (s, 1H), 3.48 (m, 2H, J
= 7.6 Hz), 1.57 (t, 3H, J = 7.6 Hz). 13C NMR (CDCl3, 100 MHz) d
154.6, 152.5, 140.7, 140.0, 132.8, 129.7, 129.2, 129.0, 128.2,
127.1, 126.9, 123.2, 119.6, 95.4, 26.5, 10.7. ESI-MS [M + H]+ m/z
274.2.
¨
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2-Phenyl-5-propylpyrazolo[1,5-c]quinazoline (7b). Eluent:
petroleum ether–ethyl acetate (50 : 1). Yield 46 mg (81%).
1
white solid, m.p. 78–80 uC. H NMR (CDCl3, 300 MHz) d 8.07–
7.98 (m, 3H), 7.90 (d, 1H, J = 7.8 Hz), 7.62 (dt, 1H, J = 7.8 Hz, J =
1.2 Hz), 7.55–7.47 (m, 3H), 7.43 (d, 1H, J = 7.2 Hz), 7.25 (s, 1H),
3.41 (t, 2H, J = 8.1 Hz), 2.16–1.99 (m, 2H), 1.15 (t, 3H, J = 7.5
Hz). 13C NMR (CDCl3, 100 MHz) d 154.6, 151.6, 140.7, 140.0,
132.8, 129.7, 129.1, 129.0, 128.2, 127.1, 126.9, 123.2, 119.6,
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leum ether–ethyl acetate (50 : 1). Yield 40 mg (62%). Light
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4H), 7.49–7.46 (m, 2H), 7.42 (d, 1H, J = 7.2 Hz), 7.35 (s, 1H). 13
C
NMR (CDCl3, 100 MHz) d 154.8, 147.7, 142.0, 140.2, 132.9,
132.6, 131.1, 130.7, 129.9, 129.2, 128.9, 128.3, 127.7, 126.9,
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2-Phenyl-5-(thiophen-2-yl)pyrazolo[1,5-c]quinazoline (7d).
Eluent: petroleum ether–ethyl acetate (20 : 1). Yield 42 mg
(64%). Light yellow solid, m.p. 146–148 uC. 1H NMR (CDCl3,
400 MHz) d 8.93 (dd, 1H, J = 3.6 Hz, J = 1.6 Hz), 8.14–8.12 (m,
2H), 8.05 (dd, 1H, J = 8.0 Hz, J = 1.6 Hz), 7.97 (d, 1H, J = 8.0 Hz),
7.69 (dd, 1H, J = 3.6 Hz, J = 0.9 Hz), 7.65 (dt, 1H, J = 8.0 Hz, J =
1.2 Hz), 7.56–7.50 (m, 3H), 7.45 (d, 1H, J = 7.2 Hz), 7.33 (s 1H),
7.30–7.28 (m, 1H). 13C NMR (CDCl3, 100 MHz) d 154.7, 142.2,
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