One-pot synthesis of 9H-indolo[3,2-c]pyrazolo[1,5-a]quinolines, 1H-dipyrazolo[1,5-a:4′,3′-c]quinolines and 1H-imidazo[4,5-c] pyrazolo[1,5-a]quinolines: Three new heterocyclic systems

Article abstract of DOI:10.1055/s-0030-1260044

An efficient synthesis of three new kinds of heterocyclic systems, 9H-indolo[3,2-c]pyrazolo[1,5-a]quinolines, 1H-dipyrazolo[ 1,5-a:4′, 3′-c]quinolines and 1H-imidazo[4,5-c]pyrazolo[1,5- a]quinolines, has been achieved by the photochemical oxidative dehydr

Full text of DOI:10.1055/s-0030-1260044

PAPER
1711
One-Pot Synthesis of 9H-Indolo[3,2-c]pyrazolo[1,5-a]quinolines, 1H-Dipyra-
zolo[1,5-a:4¢,3¢-c]quinolines and 1H-Imidazo[4,5-c]pyrazolo[1,5-a]quinolines:
Three New Heterocyclic Systems
O
ne-Pot Synthesis
i
of
N
ew
m
Fused Pyrazolo[1,
i
5-
a
]qui
n
noline Syste
g
ms Zhang, Ren Wang, Zongjun Shi, Wei Zhang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax +86(931)8625657; E-mail: zhangwei6275@lzu.edu.cn
Received 14 February 2011; revised 20 March 2011
one-pot synthesis of three new kinds of polycyclic
Abstract: An efficient synthesis of three new kinds of heterocyclic
systems, 9H-indolo[3,2-c]pyrazolo[1,5-a]quinolines, 1H-dipyrazo-
lo[1,5-a:4¢,3¢-c]quinolines and 1H-imidazo[4,5-c]pyrazolo[1,5-
a]quinolines, has been achieved by the photochemical oxidative de-
compounds, 9H-indolo[3,2-c]pyrazolo[1,5-a]quinolines
2a–d, 1H-dipyrazolo[1,5-a:4¢,3¢-c]quinolines 4a–d and
1H-imidazo[4,5-c]pyrazolo[1,5-a]quinolines 6a,b, by the
hydrogenation and subsequent photocyclization and dehydrochlori- photochemical oxidative dehydrogenation and subse-
nation of 5-(2-chloro-1H-indol-3-yl)-, 5-(5-chloro-1H-pyrazol-4-
quent photocyclization of 5-(2-chloro-1H-indol-3-yl)-,
yl)- and 5-(5-chloro-1H-imidazol-4-yl)-1-phenyl-4,5-dihydro-1H-
pyrazoles in the presence of pyridine in acetone.
5-(5-chloro-1H-pyrazol-4-yl)- and 5-(5-chloro-1H-imida-
zol-4-yl)-1-phenyl-4,5-dihydro-1H-pyrazoles (Schemes 3–
5). These three kinds of polycyclic compounds represent
three new heterocyclic systems, all of them containing a
pyrazolo[1,5-a]quinoline structural unit. The pyrazo-
lo[1,5-a]quinoline unit has been found to possess some in-
teresting biological activities, for example, compounds
with such units are antibacterial agents7a and DNA gyrase
inhibitors.7b
Key words: photodehydrogenation, photocyclization, 9H-indo-
lo[3,2-c]pyrazolo[1,5-a]quinolines,
c]quinolines, 1H-imidazo[4,5-c]pyrazolo[1,5-a]quinolines
1H-dipyrazolo[1,5-a:4¢,3¢-
The oxidative photocyclization of stilbene is the most use-
ful and versatile method for the synthesis of phenan-
threne.1 In this reaction, the unstable intermediate 4a,4b-
dihydrophenanthrene (IIa) could be produced by a photo-
chemically allowed, conrotatory cyclization of cis-stil-
bene (Ia) and then aromatized in situ by an oxidant,
leading to phenanthrene (III) (Scheme 1). This reaction is
equally useful for the synthesis of the heterocyclic ana-
logues of phenanthrene, the so-called ‘phenan-
threnoids’.1e,2 The use of stilbene containing a good
leaving group at one of the ortho positions of the aryl ring
(e.g., Ib) allows the operation of an interesting variant of
the oxidative photocyclization of stilbenes for the synthe-
sis of phenanthrene. For example, the irradiation of stil-
bene Ib leads to a dihydrophenanthrene IIb that can be
aromatized by the action of a base (Scheme 1).1,3
hν
Het
hν
Het
Het
L
L
H
L
trans-Ia, L = H
trans-Ib, L = Cl
cis-Ia, L = H
cis-Ib, L = Cl
IIa, L = H
IIb, L = Cl
O2, hν
– H2O2
Het
L = H
H
H
.
.
O-O
Het
– HCl
base
III
phenanthrenoids
L = Cl
Het
H
Cl
As an expansion of the photocyclization of ‘stilbenoids’,
the photocyclization of terphenyl analogues (i.e., IVa and
IVb) supplies an easy entry for the construction of useful
polycyclic compounds similar to triphenylene (VI)
(Scheme 2),1 for example, alkaloids such as arcyriacyanin
A,4a cryptopleurine,4b granulatimide,4c rebeccamycin4d
and staurosporinone,4e and other biological active mole-
cules.5
B:
Scheme 1 Photocyclization of stilbene analogues
Het
Het
Het
O2, h
ν
h
ν
Het
Het
Het
or base
L
H
L
Recently, we reported the synthesis of indolo[3,2-c]quin-
olin-6-ones and pyrazolo[4,3-c]quinolin-4-ones by the
dechlorinative photocyclization of N-aryl-2-chloro-1H-
indole-3-carboxamides and N-aryl-5-chloro-1H-pyra-
zole-4-carboxamides.6 In this paper, we wish to report a
VI
IVa, L = H
IVb, L = Cl
Va, L = H
Vb, L = Cl
triphenylenoids
Scheme 2 Photocyclization of terphenyl analogues
In the initial study, we tried to synthesize 2,9-dimethyl-
9H-indolo[3,2-c]pyrazolo[1,5-a]quinoline (2a) by two
successive photooxidation reactions of 1a: photooxidative
dehydrogenation of the 4,5-dihydropyrazole ring and pho-
SYNTHESIS 2011, No. 11, pp 1711–1716
Advanced online publication: 16.05.2011
DOI: 10.1055/s-0030-1260044; Art ID: F19611SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
1

1712
Y. Zhang et al.
PAPER
R2
room temperature. We found that the desired cyclization
product 2a could be obtained in excellent yield; also, the
intermediate product 1ba could be separated after one
hour of irradiation and it could be smoothly transformed
into the cyclization product 2a after longer irradiation
(Scheme 7).
R2
N
N
N
O2, acetone
pyridine, h
N
ν
Cl
N
N
R1
R1
This photocyclization reaction of 1b could also proceed in
other solvents with the addition of pyridine, for example
in dichloromethane or acetonitrile (Table 1), but the yield
of 2a was higher in acetone, probably because of the sen-
sitization effect of acetone. Therefore, acetone was select-
ed as the solvent in all subsequent photooxidative
dehydrogenation and photocyclization reactions. No great
difference was observed for the photoreaction of 1b under
air versus oxygen.
1b–e
2a–d
Scheme 3 Photoreaction of 5-(2-chloro-1H-indol-3-yl)-1-phenyl-
4,5-dihydro-1H-pyrazoles 1b–e
R2
R2
N
N
N
N
O2, acetone
pyridine, h
ν
N
N
Cl
N
N
R1
R1
Table 1 Photocyclization of 1b in Different Solventsa
4a–d
3a–d
Entry
Solvent
CH2Cl2
MeCN
acetone
Time (h)
Conversionb (%) Yieldc (%)
Scheme 4 Photoreaction of 5-(5-chloro-1H-pyrazol-4-yl)-1-phe-
nyl-4,5-dihydro-1H-pyrazoles 3a–d
1
2
3
5
5
3
72
61
95
60
45
90
R2
R2
N
N
N
N
O2, acetone
pyridine, h
a The solutions were irradiated with Pyrex-filtered light (>300 nm)
from a 500 W medium-pressure Hg lamp at room temperature.
b Conversions are based on 1b.
N
N
ν
Cl
N
N
R1
R1
c Isolated yields.
5a,b
6a,b
Scheme 5 Photoreaction of 5-(5-chloro-1H-imidazol-4-yl)-1-phe-
nyl-4,5-dihydro-1H-pyrazoles 5a,b
Encouraged by these results, three kinds of substrates 1b–e,
3a–d and 5a,b were prepared and their photoreactions
were investigated under similar conditions (Schemes 3–
5). In general, each substrate afforded the corresponding
cyclization product, the 9H-indolo[3,2-c]pyrazolo[1,5-
a]quinolines 2a–d, 1H-dipyrazolo[1,5-a:4¢,3¢-c]quino-
lines 4a–d and 1H-imidazo[4,5-c]pyrazolo[1,5-a]quino-
lines 6a,b, as the sole product in high yield after
irradiation for 3–30 hours (Table 2). All products were
tooxidative 6p-electrocyclization with three different oxi-
dants under an irradiation of l > 300 nm (Scheme 6). We
found, however, only photooxidative aromatization of the
4,5-dihydropyrazole ring took place to give 1aa; no cy-
clization product 2a could be detected.
Then, another reactant 1b with a chloro substituent at the
2-position of the indole ring was prepared and subjected
to the photoreaction in the presence of both air and a base
such as pyridine under an irradiation of l > 300 nm at
1
fully identified by H and 13C NMR spectroscopy and
HRMS.7
N
N
N
N
O2, acetone, h
or I2, THF, h
ν
N
N
ν
or DDQ, MeCN, h
ν
N
N
N
Me
Me
Me
2a
1a
1aa
Scheme 6 Photoreaction of 5-(1H-indol-3-yl)-1-phenyl-4,5-dihydro-1H-pyrazole 1a
N
N
N
N
O2, acetone
, 1 h
N
O2, acetone
pyridine, h
N
ν
h
ν
Cl
N
N
Me
Cl
N
Me
Me
1b
2a
90%
1ba
Scheme 7 Photoreaction of 5-(2-chloro-1H-indol-3-yl)-1-phenyl-4,5-dihydro-1H-pyrazole 1b
Synthesis 2011, No. 11, 1711–1716 © Thieme Stuttgart · New York

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One-Pot Synthesis of New Pyrazolo[1,5-a]quinoline Systems
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Table 2 Photocyclization of 5-(2-Chloro-1H-indol-3-yl)-, 5-(5-Chloro-1H-pyrazol-4-yl)- and 5-(5-Chloro-1H-imidazol-4-yl)-1-phenyl-4,5-
dihydro-1H-pyrazolesa
Entry
Substrate
1b
R1
Me
Me
Ph
Ph
H
R2
Time (h)
Conv.b (%)
Product
2a
Yieldc (%)
Mp (°C)
206–207
200–203
143–145
174–176
208–211
263–264
191–193
197–198
dense oil
dense oil
1
2
Me
Ph
3
5
95
95
98
98
92
87
95
90
95
88
90
85
95
96
90
85
80
72
80
60
1c
2b
3
1d
Me
Ph
4
2c
4
1e
6
2d
5
3a
Me
Ph
24
30
16
24
12
20
4a
6
3b
H
4b
7
3c
Ph
Ph
H
Me
Ph
4c
8
3d
4d
9
5a
Me
6a
10
5b
H
Ph
6b
a Solutions were irradiated with Pyrex-filtered light (> 300 nm) from a 500 W medium-pressure Hg lamp at r.t..
b Based on the amount of substrate used.
c Isolated yields.
It can be observed from Table 2 that the type of chloro- cyclization of intermediate 1ba is just a 6p-electrocycliza-
substituted heterocyclic unit, 5-(2-chloro-1H-indol-3-yl), tion reaction and that pyridine helps the
5-(5-chloro-1H-pyrazol-4-yl) or 5-(5-chloro-1H-imida- dehydrochlorination; however, from the comparison of
zol-4-yl), has a great effect on the photocyclization reac- the photoreactions of 1a and 1b (Schemes 6 and 7), it
tions. Comparatively, the photoreaction efficiency of the seems that the presence of a chloro substituent in the sub-
substrates 1b–e containing the 5-(2-chloro-1H-indol-3-yl) strate is necessary for aromatization of the intermediate of
unit is much higher than that of those substrates contain- a 6p-electrocyclization reaction. According to these re-
ing the 5-(5-chloro-1H-pyrazol-4-yl) or 5-(5-chloro-1H- sults, a mechanism for the formation of 2a is proposed as
imidazol-4-yl) unit. The substituent R2 in substrates 1b–e, follows (Scheme 9): oxidative dehydrogenation of 1b
3a–d and 5a,b also has some effect on the photoreaction gives the intermediate product 1ba; the subsequent 6p-
efficiency; the substrates with R2 = Me react faster and the electrocyclization reaction of 1ba gives the unstable cy-
yields of the corresponding products are higher than those clization intermediate 1bb which undergoes dehydrochlo-
with R2 = Ph.
rination with the help of pyridine to afford the product 2a.
In our previous work,6 we found that N-aryl-2-chloro-1H- In summary, an efficient one-pot synthesis of three kinds
indole-3-carboxamides could couple with the solvent ben- of new heterocyclic compounds, 9H-indolo[3,2-c]pyrazo-
zene under irradiation; thus, a radical mechanism was pro- lo[1,5-a]quinolines, 1H-dipyrazolo[1,5-a:4¢,3¢-c]quino-
posed to explain the dechlorinative photocyclization. In lines and 1H-imidazo[4,5-c]pyrazolo[1,5-a]quinolines,
contrast, we found that the irradiation of 1b in benzene has been achieved by the photochemical oxidative dehy-
only gives the cyclization product 2a; no solvent-incorpo- drogenation and subsequent photocyclization and dehy-
rated product, the 5-(2-phenyl-1H-indol-3-yl)-1-phenyl- drochlorination of 5-(2-chloro-1H-indol-3-yl)-, 5-(5-
1H-pyrazole 7, was detected (Scheme 8).
chloro-1H-pyrazol-4-yl)- and 5-(5-chloro-1H-imidazol-
4-yl)-1-phenyl-4,5-dihydro-1H-pyrazoles in the presence
of pyridine in acetone.
N
N
N
N
O2, acetone
All reagents were purchased from commercial suppliers and used
without further purification. All solvents were dried and redistilled
before use. Flash chromatography was carried out with silica gel
(200–300 mesh). Analytical TLC was performed with silica gel
GF254 plates, and the products were visualized by UV detection.
Melting points were determined on a Yanagimoto melting point ap-
paratus and are uncorrected. 1H and 13C NMR spectra were recorded
in CDCl3 with TMS as an internal standard on a Bruker AM-400 or
a Bruker DRX-300 NMR spectrometer. HRMS data were measured
on a Bruker Daltonics APEX II 47e spectrometer by ESI.
benzene, h
ν
Ph
Cl
N
N
Me
Me
7
1b
Scheme 8 Photoreaction of 5-(2-chloro-1H-indol-3-yl)-1-phenyl-
4,5-dihydro-1H-pyrazole 1b in benzene
In other words, no C–Cl bond fission takes place in the
photoreaction of 1b. It could be supposed that the photo-
Synthesis 2011, No. 11, 1711–1716 © Thieme Stuttgart · New York

1714
Y. Zhang et al.
PAPER
hν
*
N
N
N
N
Me2CO
N
N
Me2CO
O2
– H2O2
Cl
Cl
Cl
N
N
N
Me
Me
Me
1ba
1b
1b
N–
N
+
N
hν
N
– HCl
N
N
Cl
H
Me
Me
B:
2a
1bb
Scheme 9 Proposed mechanism for the formation of 2a
1-Methyl-3-(3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl)-
1H-indole (1a)
13C NMR (100 MHz, CDCl3): d = 13.03 (CH3), 30.23 (NCH3),
103.18 (C), 109.43 (CH), 109.56 (CH), 109.60 (CH), 119.33 (CH),
121.01 (CH), 122.65 (CH), 123.80 (CH), 125.57 (C), 126.23 (C),
126.69 (C), 128.88 (CH), 135.27 (C), 135.79 (C), 140.87 (CH),
149.74 (C).
1H NMR (300 MHz, CDCl3): d = 2.083 (s, 3 H, CH3), 2.844 (q,
J = 1.7 Hz, 1 H), 3.441 (q, J = 1.7 Hz, 1 H), 3.689 (s, 3 H, NCH3),
5.285 (q, J = 1.7 Hz, 1 H), 6.727 (q, J = 4.5 Hz, 1 H), 6.917 (s, 1 H),
7.046 (d, J = 7.5 Hz, 2 H, 2 CH), 7.051–7.063 (m, 3 H), 7.231 (d,
J = 5.1 Hz, 1 H), 7.303 (d, J = 8.1 Hz, 1 H), 7.587 (d, J = 7.2 Hz, 1
H).
2,9-Dimethyl-9H-indolo[3,2-c]pyrazolo[1,5-a]quinoline (2a);
Typical Procedure for the Photochemical Reactions
To acetone (50 mL) in a reaction flask was added 1b (162 mg, 0.5
mmol); then, pyridine (0.1 mL) was added after dissolution of the
solid. The resulting colorless solution was irradiated with a 500 W
medium-pressure Hg lamp with stirring at r.t. for 3 h. After comple-
tion of the reaction, as monitored by TLC, the solvent was removed
under reduced pressure and the product was separated by silica gel
column chromatography [hexane–acetone, 10:1 (v/v)] to afford 2a.
The solid was further purified by recrystallization (EtOH) to give
pure 2a.
13C NMR (75 MHz, CDCl3): d = 16.11 (CH3), 32.76 (NCH3), 46.58
(CH2), 57.92 (CH), 109.52 (CH), 113.26 (CH), 115.87 (CH), 118.40
(CH), 119.03 (CH), 121.85 (CH), 125.55 (C), 126.29 (CH), 128.76
(CH), 137.51 (C), 146.57 (C), 149.52 (C).
1-Methyl-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-1H-indole
(1aa)
1H NMR (300 MHz, CDCl3): d = 2.417 (s, 3 H, CH3), 3.685 (s, 3 H,
NCH3), 6.409 (s, 1 H), 6.687 (s, 1 H), 7.112 (t, J = 4.5 Hz, 1 H),
7.216–7.372 (m, 5 H), 7.400 (d, J = 7.2 Hz, 2 H), 7.840 (d, J = 8.4
Hz, 1 H).
Yield: 128 mg (90%); colorless needles; mp 206–207 °C.
1H NMR (400 MHz, CDCl3): d = 2.602 (s, 3 H, CH3), 4.135 (s, 3 H,
NCH3), 6.603 (s, 1 H), 7.010 (t, J = 7.6 Hz, 1 H), 7.120–7.320 (m,
8 H).
13C NMR (100 MHz, CDCl3): d = 14.53 (CH3), 33.71 (NCH3),
96.35 (CH), 106.80 (C), 109.52 (CH), 115.46 (C), 117.10 (CH),
120.45 (CH), 120.79 (CH), 122.03 (C), 122.80 (CH), 123.79 (CH),
124.33 (CH), 128.02 (CH), 131.35 (C), 134.10 (C), 136.00 (C),
140.09 (C), 151.74 (C).
13C NMR (75 MHz, CDCl3): d = 13.64 (CH3), 31.69 (NCH3), 32.87
(CH), 53.67 (CH), 105.14 (C), 107.06 (CH), 109.34 (CH), 119.98
(CH), 120.06 (CH), 122.12 (CH), 125.08 (CH), 126.36 (CH),
126.95 (CH), 128.06 (CH), 128.69 (CH), 136.53 (C), 137.66 (C),
140.56 (C), 149.43 (C).
2-Chloro-1-methyl-3-(3-methyl-1-phenyl-4,5-dihydro-1H-
pyrazol-5-yl)-1H-indole (1b)
Yellow solid; mp 129–130 °C.
ESI-HRMS: m/z [M + H]+ calcd for C19H16N3: 286.1339; found:
286.1341.
1H NMR (400 MHz, CDCl3): d = 2.016 (s, 3 H, CH3), 2.901 (d,
J = 1.8 Hz, 1 H), 3.354 (m, J = 1.8 Hz, 1 H), 3.724 (s, 3 H, NCH3),
5.343 (d, J = 1.3 Hz, 1 H), 6.676 (t, J = 7.2 Hz, 1 H), 6.979–7.119
(m, 5 H), 7.180 (t, J = 7.6 Hz, 1 H), 7.273 (d, J = 6.0 Hz, 1 H), 7.508
(d, J = 8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 15.79 (CH3), 29.84 (NCH3),
45.23 (CH2), 57.00 (CH), 109.29 (CH), 111.10 (C), 113.00 (CH),
118.50 (CH), 119.18 (C), 120.24 (CH), 122.20 (CH), 123.15 (C),
124.28 (CH), 128.81 (CH), 136.15 (C), 146.36 (C), 148.78 (C).
9-Methyl-2-phenyl-9H-indolo[3,2-c]pyrazolo[1,5-a]quinoline
(2b)
Yield: 147 mg (85%); colorless needles; mp 200–203 °C.
1H NMR (400 MHz, CDCl3): d = 3.837 (s, 3 H, NCH3), 6.846 (s, 1
H), 7.195–7.523 (m, 8 H), 7.802 (d, J = 7.6 Hz, 1 H), 8.026 (d, J = 8
Hz, 1 H), 8.82 (d, J = 7.2 Hz, 2 H), 8.635 (d, J = 4.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 29.68 (NCH3), 33.08 (CH), 93.03
(CH), 106.31 (C), 109.13 (CH), 115.32 (C), 117.01 (CH), 120.03
(CH), 120.37 (CH), 121.53 (C), 122.27 (CH), 123.72 (CH), 123.91
(CH), 126.40 (CH), 127.48 (CH), 128.08 (CH), 130.68 (C), 133.66
(C), 133.72 (C), 135.88 (C), 139.56 (C), 152.79 (C).
2-Chloro-1-methyl-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-1H-
indole (1ba)
1H NMR (400 MHz, CDCl3): d = 2.442 (s, 3 H, CH3), 3.703 (s, 3 H,
NCH3), 6.379 (s, 1 H), 7.179–7.327 (m, 9 H).
ESI-HRMS: m/z [M + H]+ calcd for C24H18N3: 348.1495; found:
348.1499.
Synthesis 2011, No. 11, 1711–1716 © Thieme Stuttgart · New York

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One-Pot Synthesis of New Pyrazolo[1,5-a]quinoline Systems
1715
2-Methyl-9-phenyl-9H-indolo[3,2-c]pyrazolo[1,5-a]quinoline
(2c)
Yield: 165 mg (95%); pale yellow powder; mp 143–145 °C.
1H NMR (400 MHz, CDCl3): d = 2.637 (s, 3 H, CH3), 6.787 (s, 1 H),
7.058 (t, J = 8 Hz, 1 H), 7.139 (d, J = 7.2 Hz, 1 H), 7.322–7.393 (m,
3 H), 7.487–7.510 (m, 3 H), 7.637–7.644 (m, 3 H), 8.089 (t, J = 7.6
Hz, 1 H), 8.676 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.14 (CH3), 14.21 (CH3), 97.18
(CH), 113.02 (C), 116.85 (CH), 122.98 (CH), 123.67 (CH), 127.13
(CH), 129.11 (CH), 129.43 (CH), 129.72 (CH), 133.98 (C), 134.16
(C), 134.51 (C), 140.86 (C), 143.87 (C), 151.51 (C).
ESI-HRMS: m/z [M + H]+ calcd for C20H17N4: 313.1448; found:
313.1452.
3-Methyl-1,5-diphenyl-1H-dipyrazolo[1,5-a:4¢,3¢-c]quinoline
(4d)
Yield: 134 mg (72%); colorless needles; mp 197–198 °C.
13C NMR (100 MHz, CDCl3): d = 14.5 (CH3), 29.85 (CH), 96.75
(CH), 107.71 (C), 110.90 (CH), 114.79 (C), 116.80 (CH), 120.31
(CH), 121.52 (CH), 122.38 (C), 123.10 (CH), 123.44 (CH), 124.69
(CH), 128.09 (CH), 129.19 (CH), 130.40 (CH), 131.54 (C), 134.27
(C), 135.98 (C), 139.06 (C), 141.62 (C), 151.79 (C).
ESI-HRMS: m/z [M + H]+ calcd for C24H18N3: 348.1495; found:
348.1497.
1H NMR (400 MHz, CDCl3): d = 2.735 (d, J = 1.2 Hz, 3 H, CH3),
6.984 (s, 1 H), 7.108 (t, J = 3.8 Hz, 1 H), 7.318–7.412 (m, 3 H), 7.49
(q, J = 7.6 Hz, 2 H), 7.544–7.582 (m, 5 H), 8.090 (d, J = 8 Hz, 2 H),
8.725 (d, J = 8.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.33 (CH3), 94.42 (CH), 94.48
(C), 110.71 (C), 113.49 (CH), 117.38 (CH), 123.02 (CH), 124.20
(C), 126.47 (CH), 127.25 (CH), 128.47 (CH), 128.83 (CH), 129.23
(CH), 129.57 (CH), 133.40 (CH), 134.31 (C), 135.04 (C), 140.91
(CH), 144.03 (C), 153.28 (C).
2,9-Diphenyl-9H-indolo[3,2-c]pyrazolo[1,5-a]quinoline (2d)
Yield: 197 mg (96%); pale yellow powder; mp 174–176 °C.
1H NMR (400 MHz, CDCl3): d = 7.123 (t, J = 8 Hz, 1 H), 7.178 (d,
J = 8 Hz, 1 H), 7.233 (d, J = 8.2 Hz, 1 H), 7.316 (s, 1 H), 7.371–
7.456 (m, 3 H), 7.513–7.595 (m, 5 H), 7.675 (d, J = 2.4 Hz, 3 H),
8.204 (t, J = 7.2 Hz, 3 H), 8.872 (d, J = 8.2 Hz, 1 H).
ESI-HRMS: m/z [M + H]+ calcd for C25H19N4: 375.1604; found:
375.1613.
13C NMR (100 MHz, CDCl3): d = 94.05 (CH), 107.91 (C), 111.06
(CH), 115.31 (CH), 117.35 (CH), 120.44 (CH), 121.70 (C), 122.45
(CH), 123.16 (CH), 123.98 (CH), 124.89 (CH), 126.72 (CH),
128.24 (CH), 128.47 (CH), 128.93 (CH), 129.18 (CH), 129.59
(CH), 130.51 (CH), 131.64 (C), 133.90 (C), 134.49 (C), 136.52 (C),
139.08 (C), 141.74 (C), 153.58 (C).
2-Butyl-5-methyl-1H-imidazo[4,5-c]pyrazolo[1,5-a]quinoline
(6a)
Yield: 111 mg (80%); yellow dense oil.
1H NMR (400 MHz, CDCl3): d = 0.794 (t, J = 4.8 Hz, 3 H, CH3),
1.127–1.280 (m, 2 H, CH2), 1.679–1.755 (m, 2 H, CH2), 2.467 (s, 3
H, CH3), 2.925 (t, J = 7.6 Hz, 2 H, CH2), 6.504 (s, 1 H), 7.286 (t,
J = 8 Hz, 1 H), 7.457–7.499 (m, 1 H), 8.210 (d, J = 8 Hz, 1 H),
8.572 (d, J = 8.2 Hz, 1 H).
ESI-HRMS: m/z [M + H]+ calcd for C29H20N3: 410.1652; found:
410.1648.
3,5-Dimethyl-1H-dipyrazolo[1,5-a:4¢,3¢-c]quinoline (4a)
13C NMR (100 MHz, CDCl3): d = 13.66 (CH3), 14.32 (CH3), 22.49
(CH2), 29.03 (CH2), 30.96 (CH2), 96.25 (CH), 116.45 (CH, C),
122.29 (CH, C), 124.68 (CH, C), 127.52 (C), 132.71 (CH, C),
151.51 (C), 154.05 (C).
Yield: 106 mg (90%); colorless needles; mp 208–211 °C.
1H NMR (400 MHz, CDCl3): d = 2.540 (s, 3 H, CH3), 2.655 (s, 3 H,
CH3), 6.450 (s, 1 H), 7.395 (t, J = 7.2 Hz, 1 H), 7.607 (t, J = 7.2 Hz,
1 H), 8.111 (d, J = 7.6 Hz, 1 H), 8.490 (d, J = 8.2 Hz, 1 H).
ESI-HRMS: m/z [M + H]+ calcd for C17H19N4: 279.1604; found:
279.1606.
13C NMR (100 MHz, CDCl3): d = 13.99 (CH3), 29.63 (CH3), 97.51
(C), 116.08 (CH), 119.23 (C), 122.91 (CH), 123.60 (C), 124.65
(CH), 128.63 (C), 133.13 (C), 134.52 (CH), 150.60 (C).
ESI-HRMS: m/z [M + H]+ calcd for C14H13N4: 237.1135; found:
237.1137.
2-Butyl-5-phenyl-1H-imidazo[4,5-c]pyrazolo[1,5-a]quinoline
(6b)
Yield: 102 mg (60%); yellow dense oil.
1H NMR (400 MHz, CDCl3): d = 0.768 (t, J = 7.2 Hz, 3 H, CH3),
0.848–0.887 (m, 2 H, CH2), 1.734–1.800 (m, 2 H, CH2), 2.922 (t,
J = 8 Hz, 2 H, CH2), 7.011 (s, 1 H), 7.308–7.426 (m, 5 H), 7.550 (t,
J = 8 Hz, 1 H), 7.978 (d, J = 7.6 Hz, 2 H), 8.130 (d, J = 8 Hz, 1 H),
8.747 (d, J = 8.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.79 (CH3), 22.56 (CH2), 29.04
(CH2), 30.98 (CH2), 93.36 (CH), 116.98 (CH, C), 122.00 (C),
124.89 (2 CH, C), 124.95 (C), 126.54 (CH), 127.44 (CH), 128.47
(CH), 128.87 (2 CH), 132.87 (CH, C), 133.50 (C), 153.15 (C),
153.76 (C).
3-Methyl-5-phenyl-1H-dipyrazolo[1,5-a:4¢,3¢-c]quinoline (4b)
Yield: 126 mg (85%); colorless needles; mp 263–264 °C.
1H NMR (400 MHz, DMSO–CDCl3): d = 3.188 (s, 3 H, CH3), 6.906
(s, 1 H), 7.234–7.410 (m, 4 H), 7.535–7.971 (m, 1 H), 7.980 (t,
J = 7.6 Hz, 2 H), 8.222 (d, J = 7.2 Hz, 1 H), 8.529 (d, J = 8.4 Hz, 1
H).
13C NMR (100 MHz, CDCl3): d = 28.93 (CH3), 93.61 (C), 107.71
(C), 115.95 (2 CH), 122.41 (C), 124.12 (C), 125.52 (4 CH), 127.65
(C), 128.09 (3 CH), 129.26 (C), 132.72 (CH), 135.07 (C), 151.93
(C).
ESI-HRMS: m/z [M + H]+ calcd for C22H21N4: 341.1761; found:
341.1763.
ESI-HRMS: m/z [M + H]+ calcd for C19H15N4: 299.1291; found:
299.1289.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
3,5-Dimethyl-1-phenyl-1H-dipyrazolo[1,5-a:4¢,3¢-c]quinoline
(4c)
Yield: 124 mg (80%); white powder; mp 191–193 °C.
Acknowledgment
1H NMR (300 MHz, CDCl3): d = 2.577 (s, 3 H, CH3), 2.702 (s, 3 H,
CH3), 6.547 (s, 1 H), 7.123 (t, J = 7.5 Hz, 1 H), 7.343 (d, J = 7.8 Hz,
1 H), 7.535–7.598 (m, 6 H), 8.581 (d, J = 8.4 Hz, 1 H).
We are grateful to the National Natural Science Foundation of
China (Grant No. 20872056) for financial support.
Synthesis 2011, No. 11, 1711–1716 © Thieme Stuttgart · New York

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Y. Zhang et al.
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Synthesis 2011, No. 11, 1711–1716 © Thieme Stuttgart · New York