One pot synthesis of pyrrolo[3,4-c]quinolinone/pyrrolo[3,4-c]quinoline derivatives from 2-aminoarylacrylates/2-aminochalcones and tosylmethyl isocyanide (TosMIC)

Article abstract of DOI:10.1039/c4ob01580k

An efficient and practical synthetic approach to access to 2H-pyrrolo[3,4-c]quinolin-4(5H)-one/2H-pyrrolo[3,4-c]quinoline derivatives by the reaction of 2-aminoarylacrylates/2-aminochalcones and tosylmethyl isocyanide (TosMIC) via a one pot van Leusen rea

Full text of DOI:10.1039/c4ob01580k

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One pot synthesis of pyrrolo[3,4-c]quinolinone/
pyrrolo[3,4-c]quinoline derivatives from
2-aminoarylacrylates/2-aminochalcones and
tosylmethyl isocyanide (TosMIC)†
Cite this: Org. Biomol. Chem., 2014,
12, 9471
Xin-Mou Lu, Jian Li, Zhong-Jian Cai, Rong Wang, Shun-Yi Wang* and Shun-Jun Ji*
Received 25th July 2014,
Accepted 1st October 2014
An efficient and practical synthetic approach to access to 2H-pyrrolo[3,4-c]quinolin-4(5H)-one/
2H-pyrrolo[3,4-c]quinoline derivatives by the reaction of 2-aminoarylacrylates/2-aminochalcones and
tosylmethyl isocyanide (TosMIC) via a one pot van Leusen reaction and cyclization under basic conditions
has been reported. The desired products could be obtained in moderate to good yields.
DOI: 10.1039/c4ob01580k
www.rsc.org/obc
construct related compounds, such as pyrrolo[3,4-c]quinolinone
and pyrrolo[3,4-c]quinoline derivatives. In 2012, Di Santo and
Introduction
N-heterocycles have attracted great attention for their impor- co-workers demonstrated a two-step synthesis of pyrrolo[3,4-c]-
tant activities and wide range of applications.1 Among them, quinolinone from (E)-ethyl 3-(2-nitrophenyl)acrylate and tosyl-
pyrroloquinoline derivatives are well known as biologically methyl isocyanide (TosMIC) (Scheme 1).6,7 However, the devel-
active compounds and natural products (Fig. 1).2 Pyrrolo[3,2-c]- opment of a new, general and efficient method to synthesize
quinoline derivative I is an ATP-ase inhibitor.3 Pyrrolo[2,3-c]- them with atom economy and step economy is still a chal-
quinoline derivative II is a natural product with acetylcholin- lenge. More recently, we have reported the synthesis of pyrrole
esterase-inhibiting activity.4 Pyrrolo[3,4-c]quinoline derivative derivatives, 2H-pyrrolo[3,4-c]quinolines8 and 3H-pyrrolo[2,3-c]-
III is a caspase inhibitor.5 Pyrrolo[3,4-c]quinoline derivative IV quinolin-4(5H)-one derivatives9 using TosMICs with 3-phen-
is a potent 5-HT4R antagonist with analgesic action.6
acylideneoxindoles based on the van Leusen reaction10 under
In view of the important biological activities of pyrrolo- basic conditions. As a continuation of our projects8,9,11 on iso-
quinoline derivatives, some methods have been developed to cyanide chemistry,12 herein, we report a general and efficient
Fig. 1 Select biologically active pyrroloquinoline derivatives.
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science & Collaborative Innovation Center of
Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, People’s
Republic of China. E-mail: shunyi@suda.edu.cn, shunjun@suda.edu.cn;
Fax: (+)86-51265880307; Tel: +86-512-65880307
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
Scheme 1 The general strategy for the synthesis of 2H-pyrrolo[3,4-c]-
quinolin-4(5H)-one and pyrrolo[2,3-c]quinoline derivatives.
c4ob01580k
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Table 1 Optimization of the reaction of 1a and 2aa
Table 2 Synthesis of 2H-pyrrolo[3,4-c]quinolin-4(5H)-ones (3)a,b
Entry
Base (equiv.)
T
b (°C)
Yieldc (%)
1
2
3
4
5
6
7
8
Cs2CO3 (2)
K2CO3 (2)
KOH (2)
NaOH (2)
NaHCO3 (2)
DBU (2)
Piperidine (2)
t-BuOK (2)
t-BuOK (1)
t-BuOK (1.5)
t-BuOK (2.5)
t-BuOK (2)
t-BuOK (2)
t-BuOK (2)
t-BuOK (2)
60
60
60
60
60
60
60
60
60
60
60
30
40
50
65
38
Trace
51
57
Trace
Trace
Trace
73 (62d)
38
51
58
45
51
52
60
9
10
11
12
13
14
15
a Reaction conditions: 1 (0.3 mmol), 2 (0.36 mmol) and t-BuOK
(0.6 mmol) , THF (2 ml), rt, 2 h, MeOH (2.5 ml), 60 °C, 9 h. For details,
see the typical experimental procedure (3a–g). b Isolated yield.
a Reaction conditions: 1a (0.3 mmol), 2a (0.36 mmol) and base, THF
(2 ml), rt, 2 h. b The temperature of the cyclization step in MeOH.
c Yields were determined by LC analysis with biphenyl as the internal
standard. d Isolated yield.
With the optimal conditions in hand, we investigated the
substrate scope of 2-aminoarylacrylates. The results are sum-
marized in Table 2. The application of (E)-methyl 3-(2-amino-5-
chlorophenyl)acrylate (1b) provided the desired product 3b in
35% yield. The reaction of (E)-methyl 3-(2-amino-3,5-dichloro-
phenyl)acrylate (1c) led to 3c in 45% yield. The electron-with-
drawing substituent affected the reactivity of 1 and decreased
the yields of 3. When (E)-methyl 3-(2-(benzylamino)phenyl)-
acrylate (1e) and (E)-methyl 3-(2-(methylamino)phenyl)acrylate
(1f) were subjected to the reaction under the optimized con-
ditions, the desired products 3e and 3f could be obtained in
31% and 39% yields, respectively. The reaction of 1-((1-isocyano-
ethyl)sulfonyl)-4-methylbenzene (2b) with 1a could also lead
to the desired product 3g in 30% yield under identical
conditions.
synthetic approach giving access to pyrrolo[3,4-c]quinolinone
and pyrrolo[3,4-c]quinoline derivatives by the reaction of
2-aminoarylacrylates/2-aminochalcones and tosylmethyl iso-
cyanide (TosMIC) via a one pot van Leusen reaction and cycliza-
tion under basic conditions.
Our initial investigations for the construction of 2H-pyrrolo-
[3,4-c]quinolin-4(5H)-one/2H-pyrrolo[3,4-c]quinoline derivatives
focused on the model reaction of methyl 3-(2-aminophenyl)-
acrylate (1a) and tosylmethyl isocyanide (TosMIC) (2a). To our
delight, the reaction of 1a and 2a proceeded well in the pres-
ence of 2 equiv. Cs2CO3 in THF at room temperature and
further cyclization in MeOH after removing THF afforded
2H-pyrrolo[3,4-c]quinolin-4(5H)-one 3a in 38% LC yield without
isolation of the intermediate (Table 1, entry 1). The screening
of different bases revealed that the use of KOH and NaOH
could improve the yield of 3a to moderate yields (Table 1,
entries 3 and 4). When t-BuOK was applied to the reaction,
3a could be formed in 73% LC yield (62% isolated yield)
(Table 1, entry 8). Other bases such as K2CO3, NaHCO3, DBU,
and piperidine only led to trace amounts of 3a (Table 1,
entries 2, 5–7). Reducing or increasing the amount of t-BuOK
could not improve the yield of 3a (Table 1, entries 9–11).
Different reaction temperatures for the cyclization step were
also examined. It was found that 60 °C was the suitable reac-
tion temperature (Table 1, entries 12–15). Thus, the optimal
reaction conditions were: 1a (0.3 mmol), 2a (0.36 mmol) and
t-BuOK (0.6 mmol) were dissolved in THF and stirred at room
temperature for 2 hours, then diluted with ethyl acetate and
washed with brine. The organic layer was combined and dried
over Na2SO4 and concentrated. At last, the product was further
reacted in MeOH at 60 °C for 9 hours.
When (E)-ethyl 3-(2-aminophenyl)acrylate (1h) was applied
to the reaction, the yield of 3a was decreased to 57%
(Scheme 2).
As expected, the reaction of 2a and 2-aminochalcones (4)
instead of 2-aminoarylacrylates (1) could lead to 2H-pyrrolo
[3,4-c]quinoline derivatives (5) instead of 2H-pyrrolo[3,4-c]qui-
nolin-4(5H)-ones (3) (Table 3). To our delight, the reaction of
4a and 2a provided 5a in 79% yield under the above optimal
conditions. Next, we investigated the scope of 2-aminochal-
cones under identical conditions. The substrate (E)-3-(2-amino-
phenyl)-1-phenylprop-2-en-1-one (4b) gave the desired product
5b in 85% yield. When 4-t-butyl substituted 4c was subjected
Scheme 2 The reaction of 1b and 2a.
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Table 3 Synthesis of 2H-pyrrolo[3,4-c]quinoline derivatives (5)a,b
Scheme 3 Further transformation of 5g.
Scheme 4 (a) Reaction conditions: 1a (0.3 mmol) and 2a (0.36 mmol)
react in THF at room temperature for 2 hours. (b) Isolated yield.
a Reaction conditions: 4 (0.3 mmol), 2a (0.36 mmol) and t-BuOK
(0.6 mmol), THF (2 ml), rt, 2 h, MeOH (2.5 ml), 60 °C, 9 h. For details,
see the typical experimental procedure (5a–j). b Isolated yield.
Scheme 5 (a) Reaction conditions: C (0.3 mmol) reacts in MeOH at
60 °C for 9 hours. (b) Isolated yield.
to the reaction with 2a, the desired product 5c could be
obtained in 72% yield. The reaction of (E)-3-(2-aminophenyl)-
1-arylprop-2-en-1-one bearing an electron-donating group such
as OMe led to the desired product 5f in 78% isolated yield.
When halide substituted (E)-3-(2-aminophenyl)-1-arylprop-2-
en-1-one (4g–i) reacted with 2a, the desired products 5g–i
could be formed in 54%, 62% and 49% yields, respectively.
The chalcones (4) with an electron-withdrawing group on the
aryl ring gave the desired product 5j in 52% yield. However,
the substrates bearing a strong electron-withdrawing group on
the aryl of the chalcones (4), such as (E)-3-(2-aminophenyl)-1-
(4-(methylsulfonyl)phenyl)prop-2-en-1-one and (E)-3-(2-amino-
phenyl)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one, afforded
trace amounts of the desired products.
Based on the above results and van Leusen’s pyrrole syn-
thesis mechanism,8–10,11h a plausible mechanism was pro-
posed, which is shown in Scheme 6. The Michael addition of
2a to 1 or 4 in the presence of t-BuOK in THF leads to the
enolate intermediate A, followed by subsequent intramolecular
cyclization to produce the intermediate B. Elimination of
In addition, 4-(4-bromophenyl)-2H-pyrrolo[3,4-c]quinoline
(5g) could be easily further functionalized by traditional cross
coupling reactions to give its derivatives. For example, 5g can
be transformed to (E)-methyl 3-(4-(2H-pyrrolo[3,4-c]quinolin-4-
yl)phenyl)acrylate (5k) in 52% yield by the Heck reaction.13
The reaction of 5g with phenylboronic acid gave 4-([1,1′-biphe-
nyl]-4-yl)-2H-pyrrolo[3,4-c]quinoline (5l) in 64% yield by the
Suzuki–Miyaura cross coupling reaction (Scheme 3).14
To better understand the mechanism of the reaction, the
reaction of 1a and 2a was carried out only in THF in the pres-
ence of 2 equiv. t-BuOK. It was found that the intermediate 6a
could be isolated in 45% yield (Scheme 4).
When we treated 6a in MeOH at 60 °C for 9 h, 3a could also
be formed in 78% yield (Scheme 5).
Scheme 6 The plausible mechanism.
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tosylic acid from B and hydrogen shift afford the pyrrole inter- was diluted with 10 mL of ethyl acetate and washed with
mediate D. Then intramolecular condensation of the ester and 10 mL of brine. The aqueous layer was extracted with ethyl
ketone with the amine furnish pyrrolo[3,4-c]quinolinone and acetate (10 mL × 2). The organic layer was combined and dried
pyrrolo[3,4-c]quinoline, respectively.
over Na2SO4 and concentrated. Purification of the crude
In conclusion, a general and efficient synthetic approach product with flash column chromatography gave 5a in 79%
giving access to pyrrolo[3,4-c]quinolinone and pyrrolo[3,4-c]- yield as a yellow solid.
quinoline derivatives by the reaction of 2-aminoarylacrylates/2-
aminochalcones and tosylmethyl isocyanide (TosMIC) via a one
pot van Leusen reaction and cyclization under basic conditions
has been developed. The desired products could be obtained
in moderate to good yields. Further studies on extending the
synthetic applications are ongoing in our laboratory.
2H-Pyrrolo[3,4-c]quinolin-4(5H)-one (3a)
Brown solid. m. p.: 243–245 °C. IR (neat, ν, cm−1): 3277, 3096,
1
1725, 1515, 654 cm−1. H NMR (400 MHz, DMSO) δ 12.11 (s,
1H), 10.68 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.65–7.52 (m, 2H),
7.27–7.17 (m, 2H), 7.11–7.02 (m, 1H). 13C NMR (100 MHz,
DMSO) δ 160.5, 136.6, 126.5, 123.2, 121.9, 121.7, 118.4, 117.7,
116.1, 114.8, 112.1. HRMS (ESI-TOF) calcd for C11H9N2O ([M +
H]+) 185.0715, found 185.0719.
Experimental
General
8-Chloro-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (3b)
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without further purification.
All reactions were carried out in air and using undistilled
solvent, without any precautions to exclude air and moisture
unless otherwise noted. Melting points were recorded on an
Electrothermal digital melting point apparatus and were
uncorrected. IR spectra were recorded on a Varian FT-1000
spectrophotometer using KBr optics. 1H NMR and 13C NMR
spectra were recorded on a BRUKER 400 MHz (1H NMR) and
100 MHz (13C NMR) spectrometer using DMSO-d6 as the
solvent and TMS as an internal standard. High resolution
mass spectra were obtained using a WATERS instrument with
a CI+ source.
Yellow solid. m. p.: 233–235 °C. IR (neat, ν, cm−1): 3153, 3084,
1
1636, 1519, 870, 651 cm−1. H NMR (400 MHz, DMSO) δ 12.18
(s, 1H), 10.79 (s, 1H), 7.96 (s, 1H), 7.73 (s, 1H), 7.56 (s, 1H),
7.27–7.17 (m, 2H). 13C NMR (100 MHz, DMSO) δ 160.3, 135.3,
126.2, 125.9, 122.6, 120.6, 119.4, 118.7, 117.7, 114.6, 113.2.
HRMS (ESI-TOF) calcd for C11H8ClN2O ([M + H]+) 219.0325,
found 219.0331.
6,8-Dichloro-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (3c)
Yellow solid. m. p.: 265–267 °C. IR (neat, ν, cm−1): 3197, 3064,
1
1663, 1520, 869, 658 cm−1. H NMR (400 MHz, DMSO) δ 12.35
(s, 1H), 9.75 (s, 1H), 8.03 (s, 1H), 7.82 (s, 1H), 7.67 (s, 1H), 7.47
(s, 1H). 13C NMR (100 MHz, DMSO) δ 159.9, 131.7, 126.1,
125.9, 121.8, 120.9, 120.1, 120.0, 119.5, 114.3, 114.2. HRMS
(ESI-TOF) calcd for C11H7Cl2N2O ([M + H]+) 252.9935, found
252.9941.
Typical experimental procedure (3a–g)
To a solution of (E)-methyl-3-(2-aminophenyl)acrylate (1a)
(0.3 mmol, 53 mg) and TosMIC 2a (0.36 mmol, 70 mg) in THF
(2 mL) was added t-BuOK (0.6 mmol, 67 mg) and stirred at
25 °C, with monitoring by TLC. After 2a disappeared, the
resulting mixture was diluted with 10 mL of ethyl acetate and
washed with 10 mL of brine. The aqueous layer was extracted
with ethyl acetate (10 mL × 2). The organic layer was combined
and dried over Na2SO4 and concentrated. Then, the crude
mixture was added to 2.5 mL MeOH and stirred for 9 h at
60 °C, with monitoring by TLC. The resulting mixture was
diluted with 10 mL of ethyl acetate and washed with 10 mL of
brine. The aqueous layer was extracted with ethyl acetate
(10 mL × 2). The organic layer was combined and dried over
Na2SO4 and concentrated. Purification of the crude product
with flash column chromatography gave 3a in 62% yield as a
yellow solid.
8-Fluoro-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (3d)
Yellow solid. m. p.: 291–293 °C. IR (neat, ν, cm−1): 3144, 3068,
1
1708, 1523, 861, 652 cm−1. H NMR (400 MHz, DMSO) δ 12.16
(s, 1H), 10.72 (s, 1H), 7.78–7.65 (m, 2H), 7.55 (s, 1H), 7.22 (dd,
J = 8.9, 5.1 Hz, 1H), 7.06 (td, J = 8.8, 2.8 Hz, 1H). 13C NMR
(100 MHz, DMSO) δ 160.2, 157.8 (d, JC–F = 234.9 Hz), 133.1,
121.1 (d, JC–F = 2.8 Hz), 118.9 (d, JC–F = 9.1 Hz), 118.6, 117.4 (d,
JC–F = 8.7 Hz), 114.6, 113.6 (d, JC–F = 23.4 Hz), 113.2, 108.9 (d,
JC–F = 23.3 Hz). HRMS (ESI-TOF) calcd for C11H8FN2O ([M +
H]+) 203.0621, found 203.0625.
5-Benzyl-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (3e)
Yellow solid. m. p.: 245–247 °C. IR (neat, ν, cm−1): 3152, 2968,
Typical experimental procedure (5a–j)
1
1721, 1523, 849, 660 cm−1. H NMR (400 MHz, DMSO) δ 12.22
To
a solution of (E)-4-(2-aminophenyl)but-3-en-2-one (4a) (s, 1H), 7.95 (d, J = 7.3 Hz, 1H), 7.68 (dd, J = 4.1, 2.7 Hz, 2H),
(0.3 mmol, 53 mg) and TosMIC (2a) (0.36 mmol, 70 mg) in 7.36–7.08 (m, 8H), 5.56 (d, J = 37.8 Hz, 2H). 13C NMR
THF (2 mL) at 25 °C was added t-BuOK (0.6 mmol, 67 mg). (100 MHz, DMSO) δ 160.1, 138.3, 136.6, 129.0, 127.6, 127.3,
After stirring for 2 h, the resulting mixture was concentrated to 127.0, 123.7, 122.3, 120.9, 119.4, 119.1, 116.4, 113.8, 112.3,
remove the solvent. The crude mixture was added to 2.5 mL 44.4. HRMS (ESI-TOF) calcd for C18H15N2O ([M
MeOH and stirred for 9 h at 60 °C, and the resulting mixture 275.1184, found 275.1193.
+
H]+)
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5-Methyl-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (3f)
123.3, 123.0, 121.4, 118.3, 114.7, 110.5, 20.2. HRMS (ESI-TOF)
calcd for C18H15N2 ([M + H]+) 259.1203, found 259.1211.
White solid. m. p.: 212–214 °C. IR (neat, ν, cm−1): 3168, 3014,
1
1725, 1519, 894, 647 cm−1. H NMR (400 MHz, DMSO) δ 12.12
(s, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.61 (d, J = 22.6 Hz, 2H),
7.42–7.31 (m, 2H), 7.18 (t, J = 7.0 Hz, 1H), 3.58 (s, 3H). 13C
NMR (100 MHz, DMSO) δ 159.8, 137.6, 126.9, 123.5, 122.2,
120.7, 118.9, 118.8, 115.8, 114.2, 112.1, 28.9. HRMS (ESI-TOF)
calcd for C12H11N2O ([M + H]+) 199.0871, found 199.0875.
4-(p-Tolyl)-2H-pyrrolo[3,4-c]quinolone (5e)
Yellow solid. m. p.: 159–161 °C. IR (neat, ν, cm−1): 3125, 3050,
1
1565, 1501, 645 cm−1. H NMR (400 MHz, DMSO) δ 12.63 (s,
1H), 8.26–8.13 (m, 1H), 8.07–7.83 (m, 4H), 7.74 (s, 1H),
7.51–7.32 (m, 4H), 2.43 (s, 3H). 13C NMR (100 MHz, DMSO) δ
155.6, 139.3, 137.6, 129.6, 128.8, 126.2, 126.2, 123.1, 123.0,
122.0, 116.5, 114.9, 110.6, 21.4. HRMS (ESI-TOF) calcd for
C18H15N2 ([M + H]+) 259.1235, found 259.1239.
1-Methyl-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (3g)
Yellow solid. m. p.: 239–242 °C. IR (neat, ν, cm−1): 3275, 3091,
1
1720, 1513, 650 cm−1. H NMR (400 MHz, DMSO) δ 11.93 (s,
1H), 10.62 (s, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 2.8 Hz,
1H), 7.26–7.15 (m, 2H), 7.09 (t, J = 7.3 Hz, 1H), 2.63 (s, 3H). 13
C
4-(4-Methoxyphenyl)-2H-pyrrolo[3,4-c]quinoline (5f)
Yellow solid. m. p.: 168–170 °C. IR (neat, ν, cm−1): 2997, 2969,
936, 835, 655 cm−1. 1H NMR (400 MHz, DMSO) δ 12.62 (s, 1H),
8.22–8.15 (m, 1H), 8.10 (d, J = 8.8 Hz, 2H), 7.96 (s, 1H), 7.91
(dd, J = 6.1, 3.3 Hz, 1H), 7.76 (s, 1H), 7.50–7.41 (m, 2H), 7.12
(d, J = 8.8 Hz, 2H), 3.86 (s, 3H). 13C NMR (100 MHz, DMSO) δ
NMR (100 MHz, DMSO) δ 160.5, 136.6, 125.6, 122.9, 122.6,
121.9, 119.0, 116.2, 116.1, 115.5, 115.4, 13.9. HRMS (ESI-TOF)
calcd for C12H11N2O ([M + H]+) 199.0871, found 199.0874.
4-Methyl-2H-pyrrolo[3,4-c]quinoline (5a)
Yellow solid. m. p.: 164–166 °C. IR (neat, ν, cm−1): 3122, 2955, 160.7, 155.1, 142.7, 132.9, 130.2, 129.4, 126.2, 126.0, 123.1,
1530, 854, 653 cm−1 1H NMR (400 MHz, DMSO) δ 12.43 (s, 122.9, 122.0, 116.4, 114.8, 114.3, 110.6, 55.7. HRMS (ESI-TOF)
.
1H), 8.10 (dd, J = 6.0, 3.4 Hz, 1H), 7.82 (s, 1H), 7.79–7.75 (m, calcd for C18H15N2O ([M + H]+) 275.1184, found 275.1194.
1H), 7.70 (s, 1H), 7.44–7.35 (m, 2H), 2.67 (s, 3H). 13C NMR
(100 MHz, DMSO) δ 156.1, 142.7, 128.7, 125.8, 125.5, 123.2,
4-(4-Bromophenyl)-2H-pyrrolo[3,4-c]quinolone (5g)
123.0, 120.7, 118.8, 114.0, 110.3, 22.9. HRMS (ESI-TOF) calcd
Yellow solid. m. p.: 229–231 °C. IR (neat, ν, cm−1): 3075, 3056,
1586, 1508, 934, 835, 703, 637 cm−1 1H NMR (400 MHz,
for C12H11N2 ([M + H]+) 183.0922, found 183.0928.
.
4-Phenyl-2H-pyrrolo[3,4-c]quinoline (5b)
DMSO) δ 12.71 (s, 1H), 8.24–8.18 (m, 1H), 8.10–8.03 (m, 2H),
8.01–7.97 (m, 1H), 7.96–7.89 (m, 1H), 7.81–7.72 (m, 4H),
7.53–7.45 (m, 2H). 13C NMR (100 MHz, DMSO) δ 154.4, 142.4,
139.4, 132.0, 130.9, 129.6, 126.6, 126.3, 123.2, 123.2, 123.1,
122.0, 116.2, 114.7, 110.8. HRMS (ESI-TOF) calcd for
C17H12BrN2 ([M + H]+) 323.0184, found 323.0188.
Yellow solid. m. p.: 173–175 °C. IR (neat, ν, cm−1): 3140, 3051,
1
1591, 1503, 873, 650 cm−1. H NMR (400 MHz, DMSO) δ 12.65
(s, 1H), 8.21 (dd, J = 6.1, 3.2 Hz, 1H), 8.10 (dd, J = 8.0, 1.5 Hz,
2H), 7.95 (m, 2H), 7.74 (dd, J = 2.8, 1.7 Hz, 1H), 7.62–7.51 (m,
3H), 7.51–7.44(m, 2H). 13CNMR (100 MHz, DMSO) δ 155.7,
142.6, 140.4, 129.7, 129.7, 129.0, 128.8, 126.4, 126.2, 123.1,
123.06, 122.0, 116.5, 114.8, 110.6. HRMS (ESI-TOF) calcd for
C17H13N2 ([M + H]+) 245.1079, found 245.1083.
4-(3-Chlorophenyl)-2H-pyrrolo[3,4-c]quinoline (5h)
Yellow solid. m. p.: 154–156 °C. IR (neat, ν, cm−1): 3082, 3051,
1585, 1509, 934, 837, 701, 642 cm−1 1H NMR (400 MHz,
.
4-(4-(tert-Butyl)phenyl)-2H-pyrrolo[3,4-c]quinolone (5c)
DMSO) δ 12.71 (s, 1H), 8.22 (dd, J = 6.0, 3.2 Hz, 1H), 8.14–8.04
(m, 2H), 8.03–7.92 (m, 2H), 7.79 (dd, J = 2.8, 1.6 Hz, 1H),
7.66–7.57 (m, 2H), 7.55–7.44 (m, 2H). 13C NMR (100 MHz,
DMSO) δ 154.0, 142.4, 142.3, 133.8, 131.0, 129.8, 129.6, 128.3,
127.5, 126.7, 126.3, 123.2, 122.1, 116.2, 114.6, 110.9. HRMS
(ESI-TOF) calcd for C17H12ClN2 ([M + H]+) 279.0689, found
279.0694.
Yellow solid. m. p.: 203–205 °C. IR (neat, ν, cm−1): 3134, 3068,
1
1592, 1501, 839, 655 cm−1. H NMR (400 MHz, DMSO) δ 12.65
(s, 1H), 8.20 (dd, J = 6.0, 3.3 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H),
7.96 (s, 1H), 7.92 (dd, J = 6.1, 3.3 Hz, 1H), 7.77 (s, 1H), 7.58 (d,
J = 8.4 Hz, 2H), 7.50–7.44 (m, 2H), 1.36 (s, 9H). 13C NMR
(100 MHz, DMSO) δ 155.5, 152.3, 142.7, 137.6, 129.5, 128.6,
126.2, 126.2, 125.7, 123.1, 123.0, 122.0, 116.5, 114.8, 110.6,
35.0, 31.6. HRMS (ESI-TOF) calcd for C21H21N2 ([M + H]+)
301.1705, found 301.1712.
4-(4-Chlorophenyl)-2H-pyrrolo[3,4-c]quinolone (5i)
Yellow solid. m. p.: 245–247 °C. IR (neat, ν, cm−1): 3080, 3052,
4-(o-Tolyl)-2H-pyrrolo[3,4-c]quinolone (5d)
1581, 1507, 937, 835, 706, 639 cm−1 1H NMR (400 MHz,
.
Yellow solid. m. p.: 209–211 °C. IR (neat, ν, cm−1): 3121, 3056, DMSO) δ 12.70 (s, 1H), 8.25–8.18 (m, 1H), 8.14 (d, J = 8.2 Hz,
1561, 1508, 648 cm−1. H NMR (400 MHz, DMSO) δ 12.57 (s, 2H), 7.99 (s, 1H), 7.96–7.90 (m, 1H), 7.78 (s, 1H), 7.63 (d, J =
1
1H), 8.25–8.19 (m, 1H), 7.93 (s, 1H), 7.89 (dd, J = 5.8, 3.5 Hz, 8.2 Hz, 2H), 7.54–7.44 (m, 2H). 13C NMR (100 MHz, DMSO) δ
1H), 7.54–7.44 (m, 3H), 7.37 (dt, J = 7.2, 5.1 Hz, 3H), 7.23 (s, 154.3, 142.5, 139.0, 134.4, 130.6, 129.7, 129.1, 126.6, 126.3,
1H), 2.28 (s, 3H). 13C NMR (100 MHz, DMSO) δ 157.7, 142.5, 123.2, 123.1, 122.0, 116.2, 114.7, 110.8. HRMS (ESI-TOF) calcd
139.8, 136.1, 131.0, 129.5, 129.2, 128.7, 126.3, 126.1, 126.0, for C17H12ClN2 ([M + H]+) 279.0689, found 279.0693.
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8-Chloro-4-phenyl-2H-pyrrolo[3,4-c]quinoline (5j)
Notes and references
Yellow solid m. p.: 265–247 °C. IR (neat, ν, cm−1): 3079, 3048,
151, 1507, 934, 831, 706, 641 cm−1. HNMR (400 MHz, DMSO) δ
12.74 (s, 1H), 8.33 (s, 1H), 8.09 (d, J = 7.6 Hz, 3H), 7.93 (d, J =
8.6 Hz, 1H), 7.78 (s, 1H), 7.57 (d, J = 7.3 Hz, 3H), 7.48 (d, J =
8.6 Hz, 1H). 13C NMR (DMSO, 100 MHz) δ 156.1, 141.1, 139.9,
131.3, 130.5, 129.9, 128.9, 128.8, 126.2, 124.4, 122.4, 121.0,
116.3, 115.1, 111.6. HRMS (ESI-TOF) calcd for C17H12ClN2
([M + H]+) 279.0684, found 279.0687.
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(E)-Methyl 3-(4-(2H-pyrrolo[3,4-c]quinolin-4-yl)phenyl)acrylate
(5k)
.
Yellow solid. m. p.: 178–180 °C. IR (neat, ν, cm−1): cm−1 1H
NMR (400 MHz, DMSO) δ 12.70 (s, 1H), 8.26–8.19 (m, 1H), 8.16
(d, J = 8.2 Hz, 2H), 7.99 (s, 1H), 7.94 (t, J = 7.5 Hz, 3H),
7.85–7.72 (m, 2H), 7.54–7.44 (m, 2H), 6.77 (d, J = 16.1 Hz, 1H),
3.77 (s, 3H). 13C NMR (100 MHz, DMSO) δ 167.1, 154.7, 144.5,
135.3, 129.3, 129.1, 127.0, 126.6, 126.3, 123.2, 123.1, 122.0,
118.9, 116.3, 110.7, 52.0. HRMS (ESI-TOF) calcd for
C21H17N2O2 ([M + H]+) 329.1290, found 329.1292.
4-([1,1′-Biphenyl]-4-yl)-2H-pyrrolo[3,4-c]quinolone (5l)
Yellow solid. m. p.: 184–186 °C. IR (neat, ν, cm−1): 3078, 3051,
1584, 1503, 937, 838, 701, 634 cm−1 1H NMR (400 MHz,
.
DMSO) δ 12.77 (s, 1H), 8.22 (d, J = 8.1 Hz, 2H), 8.08–7.72 (m,
7H), 7.60–7.47 (m, 3H), 7.47–7.36 (m, 2H), 7.36–7.28 (m, 1H).
13C NMR (100 MHz, DMSO) δ 155.2, 140.1, 134.5, 130.5, 129.6,
128.3, 127.8, 127.3, 127.2, 126.4, 123.2, 123.0, 122.0, 116.3,
110.9. HRMS (ESI-TOF) calcd for C23H17N2 ([M
321.1392, found 321.1397.
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+
H]+)
8 R. Wang, X.-P. Xu, H. Meng, S.-Y. Wang and S.-J. Ji, Tetra-
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Methyl 4-(2-aminophenyl)-1H-pyrrole-3-carboxylate (6a)
9 R. Wang, S.-Y. Wang and S.-J. Ji, Tetrahedron, 2013, 69,
10836.
White solid. m. p.: 198–200 °C. IR (neat, ν, cm−1): cm−1 1H
.
NMR (400 MHz, DMSO) δ 11.53 (s, 1H), 7.54–7.43 (m, 1H), 6.93
(ddd, J = 20.9, 7.9, 3.8 Hz, 2H), 6.77 (t, J = 2.0 Hz, 1H), 6.65 (d,
J = 7.8 Hz, 1H), 6.51 (t, J = 7.3 Hz, 1H), 4.47 (s, 2H), 3.56 (s,
3H). 13C NMR (100 MHz, DMSO) δ 164.7, 146.7, 131.6, 127.6,
125.5, 122.2, 120.9, 119.6, 116.2, 114.7, 113.3, 50.8. HRMS
(ESI-TOF) calcd for C12H13N2O2 ([M + H]+) 217.0977, found
217.0984.
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Acknowledgements
We gratefully acknowledge the Natural Science Foundation of
China (no. 21172162, 21372174), the Young National Natural
Science Foundation of China (no. 21202111), the PhD Pro-
grams Foundation of Ministry of Education of China
(2013201130004), the Young Natural Science Foundation of
Jiangsu Province (BK2012174), Key Laboratory of Organic Syn-
thesis of Jiangsu Province (KJS1211), PAPD, and Soochow Uni-
versity for financial support.
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Paper
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This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 9471–9477 | 9477