Efficient one-step synthesis of pyrrolo[3,4-c]quinoline-1,3-dione derivatives by organocatalytic cascade reactions of isatins and β-ketoamides

Article abstract of DOI:10.1039/c3ob40791h

We describe an efficient one-step synthesis of pyrrolo[3,4-c]quinolinedione derivatives using ethylenediamine diacetate (EDDA)-catalyzed cascade reactions of isatins and β-ketoamides. It is the first direct conversion of isatins to pyrrolo[3,4-c]quinolinedione derivatives via C-N bond cleavage and isatin ring expansion. Furthermore, this reaction provides a one-step synthetic route for the production of biologically interesting complex molecules that are generally prepared using multi-step reactions.

Full text of DOI:10.1039/c3ob40791h

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Efficient one-step synthesis of pyrrolo[3,4-c]quinoline-
1,3-dione derivatives by organocatalytic cascade
reactions of isatins and β-ketoamides†
Cite this: Org. Biomol. Chem., 2013, 11,
5254
Likai Xia and Yong Rok Lee*
We describe an efficient one-step synthesis of pyrrolo[3,4-c]quinolinedione derivatives using ethylenedi-
amine diacetate (EDDA)-catalyzed cascade reactions of isatins and β-ketoamides. It is the first direct con-
version of isatins to pyrrolo[3,4-c]quinolinedione derivatives via C–N bond cleavage and isatin ring
expansion. Furthermore, this reaction provides a one-step synthetic route for the production of biologi-
cally interesting complex molecules that are generally prepared using multi-step reactions.
Received 19th April 2013,
Accepted 11th June 2013
DOI: 10.1039/c3ob40791h
www.rsc.org/obc
Pyrrolo[3,4-c]quinoline-1,3-dione moieties (1) exhibit a broad
spectrum of biologically and pharmacologically important
activities (Fig. 1).1 For instance, compound 2 is a potent
inhibitor of caspase-3 (IC50 = 3 nM),2 which plays a key role in
apoptosis.3 Caspases are attractive targets for therapeutic inter-
vention in cardiovascular, neurodegenerative, infectious and
metabolic disorders.4 In particular, caspase-3 inhibitors have
been described as promising cardioprotectants,5 hepatoprotec-
tants,6 and neuroprotectants.7 Furthermore, compound 3 has
been previously shown to have inhibitory activity against HCV
polymerase in a cell based HCV replication assay with an IC50
of <50 μM, and is currently used to treat and prevent HCV
Scheme 1 General and typical methods for the synthesis of pyrrolo[3,4-c]-
quinoline-1,3-diones.
Scheme 2 Another synthetic approach for pyrrolo[3,4-c]quinoline-1,3-diones.
infection.8 Recently, alpkinidine (4), which bears a pyrrolo[3,4-c]-
quinolinone nucleus, was isolated from Xestospongia cf.
carbonaria and X. cf. exigua,9 and found to be solid tumor
selective in a disk diffusion soft agar colony assay against
murine cell lines.9 Subsequently, it was reported to show
potent therapeutic efficacy in vivo in HCT-116-bearing mice.10
Given the importance of these valuable biological and
pharmacological activities, several synthetic methods have
been reported for the production of pyrrolo[3,4-c]quinoline-
1,3-dione derivatives.11 Of these methods, multi-step reactions
using the Pfitzinger reaction as a key step from isatins are
shown in Scheme 1.11c,d,g,h,l However, these procedures are
limited by their durations, complexities, the harsh reaction
conditions required and their low yields.11c,d,g,h,l
Fig. 1 Pyrrolo[3,4-c]quinoline structure 1 and biologically active molecules 2–4
bearing its skeleton.
School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic
of Korea. E-mail: yrlee@yu.ac.kr; Fax: +82 53-810-4631; Tel: +82 53-810-2529
†Electronic supplementary information (ESI) available: Depiction of 1H, 13C
Recently, a facile procedure was described for the 2-step
syntheses of novel pyrrolo[3,4-c]quinolinedione derivatives via
the cyclocondensation of 2-amino-5-fluorophenyl glyoxylic
acid with β-ketoamides (Scheme 2).12 However, this reaction
NMR and HRMS spectra for all products 7–48, and CIF data for 39. CCDC
934811. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3ob40791h
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Table 1 Reactions of isatin (5a) with 3-oxo-N-phenylbutanamide (6a) using a
number of catalysts
Entry Catalysts
Solvent
Temp.
Time (h) Yield (%)
1
2
3
4
5
6
7
8
MgBr2
FeCl3
InCl3
CuSO4
CaCl2
Ru(PPh3)3Cl2 Toluene
Yb(OTf)3
ZnCl2
BF3·Et2
AcOH
TFA
TEA
L-Proline
PPTS
Pyr·HCl
[DPMA][OTf]
EDDA
EDDA
EDDA
EDDA
EDDA
EDDA
EDDA
Toluene
Toluene
Toluene
Toluene
Toluene
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
40 °C
16
16
16
16
12
12
12
12
12
12
12
12
8
8
8
8
6
16
16
10
16
8
Trace
Trace
Trace
35
55
25
44
16
15
71
10
10
70
65
69
68
80
72
Scheme 3 Three reaction sites (N1, C3 and C4) of β-ketoamides to give biologi-
cally interesting heterocycles.
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
CHCl3
Benzene
Acetonitrile 80 °C
Methanol
DMF
9
depends on temperature, and undergoes decarboxylation at high
temperature to afford other quinoline-3-carboxamide derivatives.
Although these known methods have been widely used for
the synthesis of pyrrolo[3,4-c]quinolinedione derivatives, there
is a need for a simple, cost effective, environmentally benign
method with wide applicability that is capable of producing
more elaborate substitution patterns. This has prompted a
search for a new method of preparing a variety of pyrrolo[3,4-c]-
quinolinedione derivatives using a one-step reaction. We con-
sidered the utilization of isatins13 and β-ketoamides as starting
materials and reagents because they are widely used for the
synthesis of a variety of heterocyclic and fused heterocyclic
compounds. In particular, several important methods of
synthesizing biologically active heterocycles such as
2-pyridones,14 4-pyridones,15 3-acyloxindoles,16 dihydropyr-
imidones,17 and nicotinamides18 starting from β-ketoamides
have already been reported, which involve the two nucleophilic
sites N1 and C3 or one electrophilic site C4 (Scheme 3).
However, no one-step synthesis of pyrrolo[3,4-c]quinolinedione
derivatives from β-ketoamides has been described to date.
Recently, we have reported on new methodologies for
synthesizing a variety of benzopyrans and polycycles by
organocatalytic reactions of 1,3-dicarbonyls or resorcinols with
α,β-unsaturated aldehydes.19 We describe herein ethylenedi-
amine diacetate (EDDA)-catalyzed cascade reactions for the
one-step syntheses of pyrrolo[3,4-c]quinolinedione derivatives
starting from different isatins and β-ketoamides in good yields
(Scheme 4).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
60 °C
80 °C
69
73
65
58
60 °C
100 °C
8
30
(10 mol%) as catalysts in toluene under reflux (Table 1). When
MgBr2, FeCl3, and InCl3 as Lewis acid catalysts were refluxed in
toluene for 16 h, a trace amount of products was produced
(entries 1–3). The use of 10 mol% of other Lewis acid catalysts,
namely CuSO4, CaCl2, Ru(PPh3)3Cl2, Yb(OTf)3, ZnCl2, or
BF3·OEt2, under reflux for 12 h provided 7 in 15–55% yield
(entries 4–9). Using acetic acid, 7 was obtained in 71% yield
(entry 10), whereas reaction in the presence of trifluoroacetic
acid (TFA) (10 mol%) gave 7 in low yield (10%) (entry 11).
Using 10 mol% of triethylamine (TEA) as a Brønsted base, 7
was produced in only 10% yield (entry 12). Using 10 mol% of
Brønsted acids and bases as bifunctional catalysts, the desired
product was produced in increased yield. For example, reac-
tions with L-proline and several salts, namely pyridinium
p-toluenesulfonate (PPTS), pyridine hydrochloride (Pyr·HCl),
or diphenylmethanaminium trifluoromethanesulfonate ([DPMA]-
[OTf]), gave 7 in 70, 65, 69, and 68% yield, respectively (entries
13–16). Importantly, the use of 10 mol% of ethylenediamine
diacetate (EDDA) as a catalyst improved yields. These reactions
were solvent dependent and the best yield (80%) was obtained
in toluene under reflux for 6 h. The structure of 7 was deter-
mined by 1H NMR and by comparison with previously reported
data for pyrrolo[3,4-c]quinolinedione.20,12b
To afford pyrrolo[3,4-c]quinolinedione 7, we first reacted
isatin (5a) with 3-oxo-N-phenylbutanamide (6a) in the presence
of a number of Lewis acids (10 mol%) or Brønsted acids
To prepare pyrrolo[3,4-c]quinoline-1,3(2H)-dione derivatives
with a variety of different substituents on the benzene ring of
the quinoline nucleus, several isatins bearing an electron-
donating or -withdrawing group on the benzene ring were
Scheme 4
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reacted with a number of β-ketoamides under optimized reac-
tion conditions (10 mol% of EDDA, toluene, reflux 6 h). To
investigate the influences of substituents on reactivities of
β-ketoamides, the effects of a number of N-aryl-3-oxobutan-
amides (6b–6g) bearing electron-donating or -withdrawing
groups on the benzene ring were also examined. Results are
summarized in Table 2. Reactions between isatin and 3-oxo-N-
o-tolylbutanamide (6b), 3-oxo-N-p-tolylbutanamide (6c), or
N-(4-methoxyphenyl)-3-oxobutanamide (6d), which all possess
an electron-donating group on the benzene ring, afforded pro-
ducts 8–10 in 70, 72, and 80% yield, respectively, whereas
those with N-(4-bromophenyl)-3-oxobutanamide (6e), N-(2-
chlorophenyl)-3-oxobutanamide (6f), or N-(4-chlorophenyl)-3-
oxobutanamide (6g), possessing electron-withdrawing groups,
provided 11–13 in 68, 66, and 68% yield, respectively. Treat-
ment of 5-methylisatin (5b) with 3-oxo-N-phenylbutanamide
(6a) or several N-aryl-3-oxobutanamides (6b–6g) produced com-
pounds 14–20 in 63–84% yield. Using 5-bromoisatin (5c),
Fig. 2 X-ray structure of compound 39.
5-chloroisatin (5d), and 5-nitroisatin (5e), the desired products
21–36 were also produced in 60–86% yield. Reactions between
7-bromoisatin (5f) or 7-chloroisatin (5g) and 3-oxo-N-phenyl-
butanamide (6a) or N-aryl-3-oxobutanamides (6d and 6g) were
also successful. When 7-bromoisatin (5f) was treated with
3-oxo-N-phenylbutanamide (6a) or N-(4-methoxyphenyl)-3-oxo-
butanamide (6d), products 37 and 38 were produced in 63 and
67% yield, respectively. Using 7-chloroisatin (5g) and N-(4-
methoxyphenyl)-3-oxobutanamide (6d) or N-(4-chlorophenyl)-
3-oxobutanamide (6g), compounds 39 and 40 were obtained in
66 and 62%, respectively. These results show that isatins with
substituents at the 5-position on the benzene ring provide pro-
ducts in somewhat higher yields than isatins substituted at the
7-position. Reactions of N-aryl-3-oxobutanamides possessing
an electron-donating group on the N-phenyl ring afford pro-
ducts in better yields than their counterparts with an electron-
withdrawing group. The structures of the synthesized com-
pounds 8–40 were unambiguously confirmed by X-ray diffrac-
tion analysis of compound 3921 (Fig. 2).
Table 2 A variety of pyrrolo[3,4-c]quinolinediones 8–40 synthesized
by EDDA-catalyzed cascade reactions
In order to examine the utilities of these reactions, further
reactions between isatins and N-benzyl-3-oxobutanamide (6h)
and 3-oxo-N,3-diphenylpropanamide (6i) were investigated.
Results are presented in Table 3. Reactions between isatin (5a),
5-methylisatin (5b), 5-bromoisatin (5c), or 5-chloroisatin (5d)
and N-benzyl-3-oxobutanamide (6h) in the presence of 10 mol%
of EDDA in refluxing toluene for 12 h provided the desired
products 41–44 in 35–46% yield, whereas reactions between
these and 3-oxo-N,3-diphenylpropanamide (6i) afforded pro-
ducts 45–48 in 36–45% yield.
A proposed mechanism of the EDDA-catalyzed cascade reac-
tion for 7 through Knoevenagel type condensation and cycliza-
tion is depicted in Scheme 5.22 We suppose that the carbonyl
group of isatin (5a) is protonated by EDDA to give intermediate
49, which facilitates a nucleophilic attack of the enol form 50
of β-ketoamide (6a) followed by dehydration and proton trans-
fer to give 51. Intermediate 51 then undergoes intramolecular
cyclization by N1 nucleophilic attack of the β-ketoamide group
followed by proton transfer to form intermediate 52, and ring-
opening of intermediate 52 followed by proton transfer gives
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300 MHz, Varian VNS 300 MHz, or Varian VNS-600 MHz
spectrometers in CDCl3, DMSO-d6 or CD2Cl2 as the solvent. IR
Table 3 Synthesis of other pyrrolo[3,4-c]quinolinedione derivatives 41–48
spectra were recorded on
a Jasco FTIR 5300 spectro-
photometer. All melting points were obtained on a Fisher-
Johns melting point apparatus and are uncorrected. HRMS
was carried out at the Korea Basic Science Institute.
General procedure for the synthesis of pyrrolo[3,4-c]quino-
line-1,3-dione derivatives: 7–48. To a solution of isatins 5
(1.0 mmol) in toluene (8 mL) was added β-ketoamides
(1.1 mmol) and ethylenediamine diacetate (18 mg, 0.1 mmol)
at room temperature. The reaction mixture was refluxed for
6–12 h. After completion of the reaction as indicated by TLC
(hexane–EtOAc, 6 : 1, v/v), the solvent was evaporated, and the
residue was purified by flash column chromatography on silica
gel using hexane–EtOAc (4 : 1, v/v) to give 1H-pyrrolo[3,4-c]-
quinoline-1,3(2H)-dione derivatives 7–48.
4-Methyl-2-phenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
1
(7).12b,20 Brown solid; yield 230 mg; 80%; mp 163–164 °C; H
NMR (300 MHz, CDCl3) δ 8.83 (dd, J = 8.1, 0.6 Hz, 1H), 8.15 (d,
J = 8.4 Hz, 1H), 7.89 (td, J = 8.7, 1.5 Hz, 1H), 7.71 (td, J = 8.1,
0.9 Hz, 1H), 7.55–7.52 (m, 2H), 7.47–7.41 (m, 3H), 3.08 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 167.41, 167.20, 155.30, 151.60,
135.67, 132.90, 131.23, 129.26, 129.22, 129.14, 128.35, 126.66,
125.00, 121.56, 120.67, 22.21; IR (KBr): 3064, 2924, 1718, 1597,
1499, 1377, 1113, 871, 776, 691, 629, 577, 509, cm−1; HRMS
(EI+): m/z: calcd for C18H12N2O2: 288.0899, Found: 288.0898.
4-Methyl-2-(o-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(8).20a,23a,b Brown solid; yield 211 mg; 70%; mp 198–199 °C;
1H NMR (300 MHz, CDCl3) δ 8.77 (d, J = 8.4 Hz, 1H), 8.10 (d,
J = 8.4 Hz, 1H), 7.86–7.81 (m, 1H), 7.66 (dd, J = 8.4, 7.2 Hz,
1H), 7.34–7.25 (m, 3H), 7.17 (d, J = 8.4 Hz, 1H), 3.03 (s, 3H),
2.17 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.45, 167.20,
155.28, 151.54, 136.59, 135.94, 132.90, 131.22, 130.10, 129.63,
129.19, 129.10, 128.76, 126.95, 125.03, 121.85, 120.73, 22.18,
18.08; IR (KBr): 3063, 2926, 1718, 1626, 1497, 1377, 1115, 871,
Scheme 5 Proposed mechanism of the formation of 7 via cascade reactions.
the free aromatic amine 53. Subsequently, the NH2 group of 53
attacks a carbonyl group by intramolecular cyclization to form
intermediate 54, which on elimination of water and deprotona-
tion results in 7.
Conclusions
769, 632, 583, 514 cm−1
;
HRMS (EI+): m/z: calcd for
C19H14N2O2: 302.1055, Found: 302.1051.
In summary, an efficient and facile one-step synthesis of
pyrrolo[3,4-c]quinolinedione derivatives has been developed
using ethylenediamine diacetate (EDDA)-catalyzed cascade
reactions of isatins and β-ketoamides. Using this methodology,
a variety of pyrrolo[3,4-c]quinolinediones have been synthesized.
This methodology has the advantages of mild reaction con-
ditions, inexpensive non-metal catalyst, and straightforward.
In particular, this reaction solves the problems posed by the
need for multi-step reactions to synthesize pyrrolo[3,4-c]quino-
linedione derivatives.
4-Methyl-2-(p-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(9).20a,23c Brown solid; yield 218 mg; 72%; mp 194–195 °C; H
1
NMR (300 MHz, CDCl3) δ 8.83 (d, J = 7.8 Hz, 1H), 8.14 (d, J =
8.7 Hz, 1H), 7.88 (t, J = 7.8 Hz, 1H), 7.71 (dd, J = 7.8, 7.5 Hz,
1H), 7.32 (brs, 4H), 3.07 (s, 3H), 2.41 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 167.57, 167.34, 155.26, 151.58, 138.45,
135.72, 132.85, 129.88, 129.24, 129.08, 128.50, 126.52, 125.02,
121.61, 120.68, 22.23, 21.24; IR (KBr): 3063, 2924, 1720, 1628,
1515, 1386, 1119, 873, 817, 777, 641, 557, 508 cm−1; HRMS
(EI+): m/z: calcd for C19H14N2O2: 302.1055, Found: 302.1055.
2-(4-Methoxyphenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3-
(2H)-dione (10).20a Brown solid; yield 254 mg; 80%; mp
Experimental section
General experimental details
1
231–232 °C; H NMR (300 MHz, CDCl3) δ 8.81 (d, J = 8.4 Hz,
1H), 8.15 (d, J = 8.7 Hz, 1H), 7.87 (dd, J = 8.1, 7.2 Hz, 1H), 7.70
All experiments were carried out under a nitrogen atmosphere. (dd, J = 7.8, 7.5 Hz, 1H), 7.34 (d, J = 8.7 Hz, 2H), 7.02 (d, J =
Merck pre-coated silica gel plates (Art. 5554) with a fluorescent 9.0 Hz, 2H), 3.84 (s, 3H), 3.07 (s, 3H); 13C NMR (75 MHz,
indicator were used for analytical TLC. Flash column chromato- CDCl3) δ 167.61, 167.38, 159.39, 155.20, 151.37, 135.76, 132.90,
graphy was performed using silica gel 9385 (Merck). 1H and 129.10, 128.00, 124.99, 123.72, 121.59, 120.65, 114.53, 55.50,
13C NMR spectra were recorded at 25 °C on Bruker Avance DPX 22.10; IR (KBr): 2986, 2840, 1711, 1514, 1395, 1260, 1175, 1119,
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1094, 1032, 739 cm−1; HRMS (EI+): m/z: calcd for C19H14N2O3:
318.1004, Found: 318.1003.
4,8-Dimethyl-2-(p-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (16). Brown solid; yield 231 mg; 73%; mp 197–198 °C;
1H NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.01 (d, J = 8.7 Hz,
1H), 7.70 (d, J = 8.7 Hz, 1H), 7.32 (brs, 4H), 3.04 (s, 3H), 2.58
(s, 3H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.66,
167.49, 154.15, 150.37, 139.65, 138.32, 135.26, 134.78, 129.82,
128.83, 128.60, 126.47, 123.55, 121.50, 120.76, 22.04, 21.87,
21.23; IR (KBr): 3043, 2921, 2860, 1716, 1604, 1513, 1376, 1124,
1088, 1023, 812, 745, 657, 596, 552, 508 cm−1; HRMS (EI+):
m/z: calcd for C20H16N2O2: 316.1212, Found: 316.1212.
2-(4-Bromophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3-
(2H)-dione (11). Brown solid; yield 249 mg; 68%; mp
1
226–227 °C; H NMR (300 MHz, CDCl3) δ 8.83 (d, J = 8.4 Hz,
1H), 8.16 (d, J = 8.7 Hz, 1H), 7.91 (td, J = 8.4, 1.5 Hz, 1H), 7.73
(td, J = 8.1, 0.9 Hz, 1H), 7.65 (d, J = 8.7 Hz, 2H), 7.36 (d, J =
8.7 Hz, 2H), 3.85 (s, 3H), 3.12 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 167.01, 166.83, 155.31, 151.59, 135.67, 133.11, 132.41,
130.34, 129.31, 129.28, 128.02, 124.98, 122.13, 121.47, 120.65,
22.17; IR (KBr): 3098, 2925, 2856, 1719, 1625, 1491, 1392,
1116, 824, 805, 773, 639, 589 cm−1; HRMS (EI+): m/z: calcd for
C18H11BrN2O2: 366.0004, Found: 366.0000.
2-(4-Methoxyphenyl)-4,8-dimethyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (17). Brown solid; yield 279 mg; 84%; mp
1
194–195 °C; H NMR (300 MHz, CDCl3) δ 8.54 (s, 1H), 7.99 (d,
J = 8.7 Hz, 1H), 7.68 (dd, J = 8.7, 1.8 Hz, 1H), 7.34 (d, J =
9.0 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 3.84 (s, 3H), 3.01 (s, 3H),
2.56 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.76, 167.57,
159.31, 154.09, 150.30, 139.65, 135.24, 134.74, 128.79, 127.98,
123.86, 123.51, 121.45, 120.71, 114.49, 55.50, 22.00, 21.86; IR
(KBr): 2925, 2842, 1715, 1514, 1394, 1249, 1174, 1126, 1032,
821, 560 cm−1; HRMS (EI+): m/z: calcd for C20H16N2O3:
332.1161, Found: 332.1162.
2-(2-Chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3-
(2H)-dione (12).20a Brown solid; yield 213 mg; 66%; mp
155–156 °C; H NMR (300 MHz, CDCl3) δ 8.86 (d, J = 8.1 Hz,
1
1H), 8.24 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 7.2, 6.9 Hz, 1H), 7.76
(d, J = 7.8, 7.5 Hz, 1H), 7.61–7.58 (m, 1H), 7.49–7.44 (m, 2H),
7.40–7.34 (m, 1H), 3.13 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
166.75, 166.54, 155.42, 151.67, 135.94, 133.33, 133.03, 130.90,
130.76, 130.51, 129.28, 129.23, 129.21, 127.82, 125.11, 121.86,
120.78, 22.23; IR (KBr): 3071, 2924, 1715, 1594, 1540, 1374,
1059, 1033, 763, 592, 538 cm−1; HRMS (EI+): m/z: calcd for
C18H11ClN2O2: 322.0509, Found: 322.0511.
2-(4-Bromophenyl)-4,8-dimethyl-1H-pyrrolo[3,4-c]quinoline-1,3-
(2H)-dione (18). Brown solid; yield 247 mg; 65%; mp
1
227–228 °C; H NMR (300 MHz, CDCl3) δ 8.60 (s, 1H), 8.06 (d,
J = 8.7 Hz, 1H), 7.74 (dd, J = 8.7, 1.8 Hz, 1H), 7.65 (d, J =
8.4 Hz, 2H), 7.36 (d, J = 8.7 Hz, 2H), 3.06 (s, 3H), 2.60 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 167.09, 166.96, 154.14, 150.38,
139.91, 135.46, 134.55, 132.33, 130.34, 128.87, 127.95, 123.44,
121.98, 121.25, 120.64, 22.03, 21.88; IR (KBr): 3010, 2919, 2854,
1723, 1604, 1495, 1382, 1121, 1080, 1012, 813, 778, 748, 644,
590, 501 cm−1; HRMS (EI+): m/z: calcd for C19H13BrN2O2:
380.0160, Found: 380.0160.
2-(4-Chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3-
(2H)-dione (13). Brown solid; yield 219 mg; 68%; mp
224–225 °C; H NMR (300 MHz, CDCl3) δ 8.81 (d, J = 7.8 Hz,
1
1H), 8.14 (d, J = 8.7 Hz, 1H), 7.89 (dd, J = 8.4, 6.9 Hz, 1H), 7.71
(dd, J = 8.1, 7.2 Hz, 1H), 7.49 (d, J = 8.7 Hz, 2H), 7.42 (d, J =
8.7 Hz, 2H), 3.07 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.12,
166.92, 155.28, 151.67, 135.52, 134.08, 133.02, 129.75, 129.42,
129.09, 127.74, 124.93, 121.40, 120.58, 116.34, 22.25; IR (KBr):
3064, 2925, 2855, 1722, 1625, 1495, 1387, 1117, 1089, 806, 771,
637, 588, 502 cm−1; HRMS (EI+): m/z: calcd for C18H11ClN2O2:
322.0509, Found: 322.0507.
2-(2-Chlorophenyl)-4,8-dimethyl-1H-pyrrolo[3,4-c]quinoline-1,3-
(2H)-dione (19). Brown solid; yield 212 mg; 63%; mp
1
231–232 °C; H NMR (300 MHz, CDCl3) δ 8.56 (s, 1H), 8.02 (d,
J = 8.4 Hz, 1H), 7.70 (d, J = 8.7 Hz, 1H), 7.59–7.56 (m, 1H),
7.44–7.39 (m, 3H), 3.04 (s, 3H), 2.57 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 166.86, 166.67, 154.22, 150.44, 139.72, 135.35, 134.83,
133.22, 130.79, 130.72, 130.42, 129.21, 128.86, 127.76, 123.55,
121.64, 120.75, 22.07, 21.88; IR (KBr): 3209, 3017, 2923, 1721,
1597, 1484, 1379, 1100, 1064, 834, 755, 695, 588 cm−1; HRMS
(EI+): m/z: calcd for C19H13ClN2O2: 336.0666, Found: 336.0665.
2-(4-Chlorophenyl)-4,8-dimethyl-1H-pyrrolo[3,4-c]quinoline-1,3-
4,8-Dimethyl-2-phenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(14).12b Brown solid; yield 224 mg; 74%; mp 194–195 °C; 1H
NMR (300 MHz, CDCl3) δ 8.58 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H),
7.70 (dd, J = 8.7, 1.8 Hz, 1H), 7.55–7.50 (m, 2H), 7.47–7.39 (m,
3H), 3.04 (s, 3H), 2.58 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
167.49, 167.34, 154.17, 150.37, 139.74, 135.32, 134.73, 131.31,
129.17, 128.84, 128.25, 126.62, 123.54, 121.44, 120.75, 22.03,
21.88; IR (KBr): 3061, 2960, 2922, 1719, 1600, 1498, 1375, 1103,
825, 754, 686, 624, 580 cm−1; HRMS (EI+): m/z: calcd for (2H)-dione (20). Brown solid; yield 222 mg; 66%; mp
1
C19H14N2O2: 302.1055, Found: 302.1057.
4,8-Dimethyl-2-(o-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
235–236 °C; H NMR (300 MHz, CDCl3) δ 8.52 (s, 1H), 7.99 (d,
J = 9.0 Hz, 1H), 7.69 (dd, J = 8.7, 1.8 Hz, 1H), 7.48 (d, J =
dione (15). Brown solid; yield 215 mg; 68%; mp 213–214 °C; 8.7 Hz, 2H), 7.41 (d, J = 9.0 Hz, 2H), 3.01 (s, 3H), 2.56 (s, 3H);
1H NMR (300 MHz, CDCl3) δ 8.51 (s, 1H), 7.97 (d, J = 8.7 Hz, 13C NMR (75 MHz, CDCl3) δ 167.15, 167.02, 154.11, 150.39,
1H), 7.65 (dd, J = 8.7, 1.5 Hz, 1H), 7.31–7.26 (m, 3H), 7.16 (d, 139.86, 135.41, 134.47, 133.93, 129.78, 129.35, 128.87, 127.67,
J = 7.8 Hz, 1H), 2.99 (s, 3H), 2.51 (s, 3H), 2.16 (s, 3H); 13C NMR 123.40, 121.21, 120.59, 22.05, 21.88; IR (KBr): 2967, 2925, 1721,
(75 MHz, CDCl3) δ 167.56, 167.35, 154.14, 150.32, 139.67, 1607, 1497, 1384, 1277, 1191, 1121, 1091, 1019, 817, 748, 597,
136.57, 135.30, 134.99, 131.17, 130.17, 129.54, 128.76, 126.90, 535, 506 cm−1; HRMS (EI+): m/z: calcd for C19H13ClN2O2:
123.54, 121.74, 120.80, 22.00, 21.84, 18.06; IR (KBr): 3051, 336.0666, Found: 336.0664.
2923, 1714, 1603, 1497, 1377, 1102, 834, 750, 631, 589 cm−1
;
8-Bromo-4-methyl-2-phenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
HRMS (EI+): m/z: calcd for C20H16N2O2: 316.1212, Found: dione (21).12b Brown solid; yield 293 mg; 80%; mp 187–188 °C;
316.1209.
1H NMR (300 MHz, CDCl3) δ 8.98 (d, J = 2.1 Hz, 1H), 8.00 (d,
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J = 9.0 Hz, 1H), 7.93 (dd, J = 9.3, 2.1 Hz, 1H), 7.55–7.50 (m, 128.95, 127.86, 127.15, 123.83, 122.38, 121.54, 22.27; IR (KBr):
2H), 7.45–7.43 (m, 3H), 3.05 (s, 3H); 13C NMR (75 MHz, CDCl3) 3072, 2925, 2855, 1720, 1589, 1484, 1382, 1148, 1097, 825, 756,
δ 166.98, 166.69, 155.74, 150.02, 136.39, 134.58, 131.04, 672, 625, 581, 509 cm−1
;
HRMS (EI+): m/z: calcd for
130.74, 129.24, 128.45, 127.08, 126.54, 123.80, 122.14, 121.47, C18H10BrClN2O2: 399.9614, Found: 399.9613.
22.20; IR (KBr): 3063, 2924, 1717, 1592, 1498, 1388, 1129, 830,
8-Bromo-2-(4-chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
745, 680, 579 cm−1; HRMS (EI+): m/z: calcd for C18H11BrN2O2:
366.0004, Found: 366.0001.
1,3(2H)-dione (27). Brown solid; yield 280 mg; 70%; mp
1
245–246 °C; H NMR (300 MHz, CDCl3) δ 8.98 (d, J = 1.8 Hz,
8-Bromo-4-methyl-2-(o-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (22). Brown solid; yield 274 mg; 72%; mp 209–210 °C;
1H NMR (300 MHz, CDCl3) δ 8.92 (d, J = 2.1 Hz, 1H), 7.95 (d,
J = 9.0 Hz, 1H), 7.88 (dd, J = 9.0, 1.2 Hz, 1H), 7.34–7.25 (m,
3H), 7.15 (d, J = 7.5 Hz, 1H), 3.00 (s, 3H), 2.16 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 167.07, 166.71, 155.74, 150.05, 136.52,
136.36, 134.83, 131.26, 130.73, 129.91, 129.71, 128.68, 127.10,
126.98, 123.73, 122.44, 121.55, 22.20, 18.07; IR (KBr): 3076,
3021, 2969, 1714, 1590, 1495, 1375, 1123, 837, 753, 674,
581 cm−1; HRMS (EI+): m/z: calcd for C19H13BrN2O2: 380.0160,
Found: 380.0159.
8-Bromo-4-methyl-2-(p-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (23). Brown solid; yield 277 mg; 73%; mp 253–254 °C;
1H NMR (300 MHz, CDCl3) δ 8.99 (d, J = 2.1 Hz, 1H), 7.99 (d,
J = 9.0 Hz, 1H), 7.93 (dd, J = 9.3, 1.5 Hz, 1H), 7.31 (brs, 4H),
3.05 (s, 3H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.18,
166.86, 155.73, 150.10, 138.55, 136.30, 134.62, 130.79, 129.89,
128.35, 127.10, 126.41, 123.70, 122.20, 121.50, 22.24, 21.24; IR
(KBr): 3047, 2924, 1723, 1594, 1515, 1376, 1130, 1090, 890,
838, 749, 675, 563, 503 cm−1; HRMS (EI+): m/z: calcd for
C19H13BrN2O2: 380.0160, Found: 380.0158.
1H), 8.00 (d, J = 9.3 Hz, 1H), 7.94 (dd, J = 9.0, 2.1 Hz, 1H), 7.50
(d, J = 8.7 Hz, 2H), 7.41 (d, J = 8.7 Hz, 2H), 3.05 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 166.74, 166.47, 155.75, 150.16, 136.54,
134.48, 134.23, 130.84, 129.57, 129.48, 127.66, 127.05, 123.95,
122.02, 121.43, 22.26; IR (KBr): 3094, 2927, 1725, 1594, 1498,
1389, 1141, 1089, 887, 831, 812, 780, 750, 672, 594, 550,
508 cm−1
;
HRMS (EI+): m/z: calcd for C18H10BrClN2O2:
399.9614, Found: 399.9612.
8-Chloro-4-methyl-2-phenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (28). Brown solid; yield 261 mg; 81%; mp 181–182 °C;
1H NMR (300 MHz, CDCl3) δ 8.80 (d, J = 2.1 Hz, 1H), 8.07 (d,
J = 9.3 Hz, 1H), 7.80 (dd, J = 9.0, 2.4 Hz, 1H), 7.55–7.50 (m,
2H), 7.45–7.42 (m, 3H), 3.06 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 167.01, 166.70, 155.57, 149.84, 135.51, 134.74, 133.86,
131.04, 130.69, 129.25, 128.45, 126.55, 123.71, 122.20, 121.05,
22.14; IR (KBr): 3062, 2924, 1723, 1596, 1499, 1383, 1134, 1103,
830, 747, 683, 624, 581 cm−1; HRMS (EI+): m/z: calcd for
C18H11ClN2O2: 322.0509, Found: 322.0508.
8-Chloro-4-methyl-2-(o-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (29). Brown solid; yield 245 mg; 73%; mp 197–198 °C;
1H NMR (300 MHz, CDCl3) δ 8.72 (d, J = 2.1 Hz, 1H), 8.01 (d,
J = 9.3 Hz, 1H), 7.73 (dd, J = 9.0, 2.1 Hz, 1H), 7.33–7.24 (m,
3H), 7.15 (d, J = 7.5 Hz, 1H), 3.00 (s, 3H), 2.16 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 167.08, 166.70, 155.55, 149.83, 136.50,
135.41, 134.95, 133.79, 131.24, 130.66, 129.91, 129.69, 128.67,
126.97, 123.71, 122.47, 121.08, 22.13, 18.06; IR (KBr): 3077,
3022, 2970, 1715, 1593, 1496, 1374, 1124, 839, 754, 695, 631,
582 cm−1; HRMS (EI+): m/z: calcd for C19H13ClN2O2: 336.0666,
Found: 336.0664.
8-Bromo-2-(4-methoxyphenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (24). Brown solid; yield 333 mg; 84%; mp
1
251–252 °C; H NMR (300 MHz, CDCl3) δ 9.00 (d, J = 2.1 Hz,
1H), 8.02 (d, J = 9.0 Hz, 1H), 7.94 (dd, J = 9.3, 2.1 Hz, 1H), 7.34
(d, J = 9.3 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H), 3.85 (s, 3H), 3.06 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 167.49, 167.18, 159.84,
155.97, 150.27, 136.62, 135.07, 130.97, 128.17, 127.43, 124.03,
122.57, 121.85, 114.89, 55.77, 22.30; IR (KBr): 2924, 2842, 1714,
1517, 1396, 1253, 1143, 1095, 1036, 824, 569 cm−1; HRMS
(EI+): m/z: calcd for C19H13BrN2O3: 396.0110, Found: 396.0110.
8-Bromo-2-(4-bromophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (25). Brown solid; yield 311 mg; 70%; mp
8-Chloro-4-methyl-2-(p-tolyl)-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (30). Brown solid; yield 252 mg; 75%; mp 244–245 °C;
1H NMR (300 MHz, CDCl3) δ 8.81 (d, J = 1.8 Hz, 1H), 8.06 (d,
J = 8.7 Hz, 1H), 7.82–7.78 (m, 1H), 7.31 (brs, 4H), 3.06 (s, 3H),
2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.21, 166.89,
155.56, 149.91, 138.56, 135.42, 134.79, 133.78, 130.74, 129.90,
128.35, 126.42, 123.75, 122.27, 121.08, 22.18, 21.24; IR (KBr):
3086, 3045, 2925, 1723, 1595, 1514, 1376, 1136, 1087, 839,
790, 748, 695, 576, 504 cm−1; HRMS (EI+): m/z: calcd for
C19H13ClN2O2: 336.0666, Found: 336.0664.
1
244–245 °C; H NMR (300 MHz, CDCl3) δ 9.04 (d, J = 2.1 Hz,
1H), 8.22 (d, J = 9.0 Hz, 1H), 8.02 (dd, J = 9.0, 2.1 Hz, 1H), 7.67
(d, J = 4.5 Hz, 2H), 7.35 (d, J = 4.8 Hz, 2H), 3.14 (s, 3H); 13C
NMR (75 MHz, CDCl3 + DMSO-d6) δ 165.30, 165.13, 154.27,
148.72, 134.77, 133.39, 130.90, 129.85, 129.42, 127.25, 125.47,
122.04, 121.13, 120.50, 120.14, 20.80; IR (KBr): 3082, 2924,
2855, 1721, 1590, 1493, 1393, 1125, 1072, 1007, 831, 809, 773,
685, 586 cm−1; HRMS (EI+): m/z: calcd for C18H10Br2N2O2:
443.9109, Found: 443.9111.
8-Chloro-2-(4-methoxyphenyl)-4-methyl-1H-pyrrolo[3,4-c]-
quinoline-1,3(2H)-dione (31). Brown solid; yield 303 mg; 86%;
mp 213–214 °C; 1H NMR (300 MHz, CDCl3) δ 8.79 (d, J =
8-Bromo-2-(2-chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (26). Brown solid; yield 268 mg; 67%; mp 2.1 Hz, 1H), 8.07 (d, J = 9.0 Hz, 1H), 7.80 (dd, J = 9.3, 2.4 Hz,
1
213–214 °C; H NMR (300 MHz, CDCl3) δ 8.98 (d, J = 2.1 Hz, 1H), 7.33 (d, J = 9.0 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 3.85 (s,
1H), 8.01 (d, J = 9.0 Hz, 1H), 7.95 (d, J = 9.3, 2.1 Hz, 1H), 3H), 3.05 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.29, 166.96,
7.61–7.58 (m, 1H), 7.50–7.41 (m, 2H), 7.39–7.35 (m, 1H), 3.06 159.47, 155.52, 149.76, 135.48, 134.85, 133.84, 130.63, 127.94,
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 166.39, 166.06, 155.84, 123.73, 123.56, 122.26, 121.08, 114.56, 55.52, 22.09; IR (KBr):
150.17, 136.48, 134.74, 133.19, 131.01, 130.80, 130.65, 130.52, 2968, 2841, 1712, 1517, 1397, 1254, 1144, 1093, 1036, 820,
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518 cm−1; HRMS (EI+): m/z: calcd for C19H13ClN2O3: 352.0615, 502 cm−1; HRMS (EI+): m/z: calcd for C18H10BrN3O4: 410.9855,
Found: 352.0612.
Found: 410.9855.
6-Bromo-4-methyl-2-phenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (37). Brown solid; yield 231 mg; 63%; mp 200–202 °C;
1H NMR (300 MHz, CDCl3) δ 8.84 (dd, J = 8.1, 0.9 Hz, 1H), 8.22
(dd, J = 7.5, 1.2 Hz, 1H), 7.58–7.51 (m, 3H), 7.46–7.42 (m, 3H),
3.14 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 166.94, 166.65,
156.36, 148.37, 136.33, 136.13, 131.15, 129.40, 129.26, 128.47,
126.64, 125.04, 124.73, 122.38, 122.00, 22.56; IR (KBr): 3075,
2923, 2853, 1721, 1596, 1498, 1378, 1106, 890, 788, 756, 700,
631, 587 cm−1; HRMS (EI+): m/z: calcd for C18H11BrN2O2:
366.0004, Found: 366.0002.
2-(4-Bromophenyl)-8-chloro-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (32). Brown solid; yield 284 mg; 71%; mp
259–260 °C; H NMR (300 MHz, CDCl3) δ 8.81 (d, J = 2.4 Hz,
1
1H), 8.11 (d, J = 9.0 Hz, 1H), 7.83 (dd, J = 9.3, 2.4 Hz, 1H), 7.65
(d, J = 8.7 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 3.07 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 166.62, 166.36, 155.57, 149.76, 145.43,
135.80, 134.16, 132.47, 130.63, 130.09, 127.94, 123.73, 122.28,
122.14, 121.07, 22.08; IR (KBr): 3084, 2924, 2855, 1713, 1596,
1497, 1374, 1129, 1074, 1008, 831, 812, 776, 700, 587 cm−1
;
HRMS (EI+): m/z: calcd for C18H10BrClN2O2: 399.9614, Found:
6-Bromo-2-(4-methoxyphenyl)-4-methyl-1H-pyrrolo[3,4-c]-
quinoline-1,3(2H)-dione (38). Brown solid; yield 265 mg; 67%;
mp 198–199 °C; 1H NMR (300 MHz, CDCl3) δ 8.77 (d, J =
8.4 Hz, 1H), 8.17 (d, J = 7.2 Hz, 1H), 7.50 (dd, J = 8.7, 7.8 Hz,
1H), 7.34 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 3.85 (s,
3H), 3.10 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.20, 166.87,
159.47, 156.26, 148.20, 136.21, 136.06, 129.30, 127.99, 124.93,
124.70, 123.62, 122.36, 121.89, 114.56, 55.52, 22.54; IR (KBr):
2976, 2841, 1716, 1512, 1386, 1259, 1168, 1122, 1096, 828, 786,
740, 573 cm−1; HRMS (EI+): m/z: calcd for C19H13BrN2O3:
396.0110, Found: 396.0113.
6-Chloro-2-(4-methoxyphenyl)-4-methyl-1H-pyrrolo[3,4-c]-
quinoline-1,3(2H)-dione (39). Brown solid; yield 232 mg; 66%;
mp 218–219 °C; 1H NMR (300 MHz, CDCl3) δ 8.73 (d, J =
8.1 Hz, 1H), 7.95 (d, J = 6.6 Hz, 1H), 7.58 (dd, J = 8.1, 7.8 Hz,
1H), 7.34 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 9.0 Hz, 2H), 3.84 (s,
3H), 3.10 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.21, 166.93,
159.47, 156.09, 147.44, 136.01, 133.71, 132.63, 128.88, 127.98,
123.97, 123.60, 122.36, 121.96, 114.56, 55.52, 22.54; IR (KBr):
2979, 2846, 1715, 1513, 1388, 1249, 1107, 1013, 900, 829, 792,
703, 573, 531 cm−1; HRMS (EI+): m/z: calcd for C19H13ClN2O3:
352.0615, Found: 352.0612.
399.9618.
8-Chloro-2-(2-chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (33). Brown solid; yield 235 mg; 66%; mp
200–201 °C; H NMR (300 MHz, CDCl3) δ 8.80 (d, J = 2.1 Hz,
1
1H), 8.08 (d, J = 9.0 Hz, 1H), 7.82 (d, J = 9.0, 2.4 Hz, 1H),
7.61–7.58 (m, 1H), 7.49–7.41 (m, 2H), 7.38–7.34 (m, 1H), 3.07
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 166.43, 166.09, 155.68,
150.01, 135.54, 134.90, 133.94, 133.20, 131.00, 130.77, 130.66,
130.52, 128.96, 127.86, 123.79, 122.44, 121.12, 22.23; IR (KBr):
3208, 3074, 2964, 1720, 1592, 1484, 1377, 1149, 1096, 826, 756,
688, 583 cm−1; HRMS (EI+): m/z: calcd for C18H10Cl2N2O2:
356.0119, Found: 356.0119.
8-Chloro-2-(4-chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (34). Brown solid; yield 242 mg; 68%; mp
241–242 °C; H NMR (300 MHz, CDCl3) δ 8.75 (d, J = 1.8 Hz,
1
1H), 8.05 (d, J = 9.0 Hz, 1H), 7.79 (dd, J = 9.0, 2.1 Hz, 1H), 7.49
(d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 3.04 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 166.74, 166.45, 155.56, 149.95, 135.61,
134.54, 134.18, 133.95, 130.79, 129.54, 129.45, 127.64, 123.62,
122.02, 120.93, 22.20; IR (KBr): 3085, 2926, 2856, 1721, 1593,
1497, 1394, 1264, 1237, 1129, 1091, 887, 810, 777, 748, 703,
647, 590, 559, 503 cm−1
C18H10Cl2N2O2: 356.0119, Found: 356.0118.
;
HRMS (EI+): m/z: calcd for
6-Chloro-2-(4-chlorophenyl)-4-methyl-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (40). Brown solid; yield 221 mg; 62%; mp
1
2-(4-Methoxyphenyl)-4-methyl-8-nitro-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (35). Brown solid; yield 236 mg; 65%; mp
211–212 °C; H NMR (300 MHz, CDCl3) δ 9.69 (d, J = 2.4 Hz,
266–267 °C; H NMR (600 MHz, CD2Cl2) δ 8.81 (d, J = 4.2 Hz,
1H), 8.05 (d, J = 3.9 Hz, 1H), 7.69 (dd, J = 4.2, 3.9 Hz, 1H), 7.56
(d, J = 4.2 Hz, 2H), 7.47 (d, J = 4.2 Hz, 2H), 3.13 (s, 3H); 13C
NMR (150 MHz, CD2Cl2) δ 167.08, 166.89, 156.44, 148.00,
136.43, 134.48, 134.23, 133.21, 130.35, 129.74, 129.48, 128.35,
124.33, 122.81, 122.44, 22.65; IR (KBr): 3099, 2970, 2928, 1718,
1620, 1494, 1386, 1172, 1096, 1013, 902, 824, 788, 758, 675,
596, 504 cm−1; HRMS (EI+): m/z: calcd for C18H10Cl2N2O2:
356.0119, Found: 356.0122.
1
1H), 8.62 (d, J = 9.3, 2.4 Hz, 1H), 8.27 (d, J = 9.3 Hz, 1H), 7.34
(d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz, 2H), 3.85 (s, 3H), 3.12 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 166.79, 166.36, 159.61,
159.29, 152.84, 147.05, 137.48, 131.13, 127.86, 125.94, 123.28,
121.80, 119.48, 114.63, 55.54, 22.62; IR (KBr): 3091, 2924, 2844,
1723, 1622, 1513, 1394, 1343, 1256, 1119, 1095, 1033, 919, 824,
789, 750, 679 cm−1; HRMS (EI+): m/z: calcd for C19H13N3O5:
363.0855, Found: 363.0855.
2-Benzyl-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (41).
Brown solid; yield 106 mg; 35%; mp 206–207 °C; 1H NMR
(300 MHz, CDCl3) δ 8.78 (d, J = 8.1 Hz, 1H), 8.14 (dd, J =
2-(4-Bromophenyl)-4-methyl-8-nitro-1H-pyrrolo[3,4-c]quinoline-
1,3(2H)-dione (36). Brown solid; yield 247 mg; 60%; mp 8.7 Hz, 1H), 7.89–7.83 (m, 1H), 7.69 (dd, J = 8.1, 7.2 Hz, 1H),
1
217–218 °C; H NMR (300 MHz, CDCl3) δ 9.71 (d, J = 2.4 Hz, 7.47–7.44 (m, 2H), 7.35–7.27 (m, 3H), 4.87 (s, 2H), 3.05 (s, 3H);
1H), 8.64 (dd, J = 9.3, 2.4 Hz, 1H), 8.30 (d, J = 9.6 Hz, 1H), 7.67 13C NMR (75 MHz, CDCl3) δ 168.03, 167.82, 158.94, 154.92,
(d, J = 9.0 Hz, 2H), 7.37 (d, J = 8.7 Hz, 2H), 3.14 (s, 3H); 136.29, 135.95, 132.93, 129.06, 128.77, 128.67, 128.03, 124.89,
13C NMR (150 MHz, CDCl3) δ 166.16, 165.79, 159.35, 152.95, 121.98, 120.64, 41.76, 29.67, 21.86; IR (KBr): 3063, 2924, 2854,
147.22, 137.36, 132.56, 131.26, 129.91, 127.84, 126.16, 123.16, 1710, 1625, 1432, 1391, 1339, 1112, 1075, 775, 704, 631, 549,
122.51, 121.74, 119.45, 22.66; IR (KBr): 3086, 2923, 2853, 1729, 502 cm−1; HRMS (EI+): m/z: calcd for C19H14N2O2: 302.1055,
1632, 1537, 1495, 1382, 1348, 1076, 1014, 814, 750, 644, 589, Found: 302.1054.
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2-Benzyl-4,8-dimethyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione NMR (300 MHz, CDCl3) δ 9.13 (s, 1H), 8.12 (d, J = 9.0 Hz, 1H),
(42). Brown solid; yield 133 mg; 42%; mp 183–184 °C; 1H
NMR (300 MHz, CDCl3) δ 8.48 (s, 1H), 7.92 (d, J = 8.7 Hz, 1H),
7.61 (d, J = 8.7 Hz, 1H), 7.40 (d, J = 7.8 Hz, 2H), 7.29–7.21 (m,
3H), 4.81 (s, 2H), 2.94 (s, 3H), 2.51 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 168.26, 168.17, 153.84, 150.19, 139.53, 136.08, 135.20,
128.76, 128.69, 127.98, 123.41, 121.85, 120.70, 41.69, 21.82; IR
(KBr): 3034, 2938, 1710, 1598, 1396, 1344, 1109, 1070, 933,
832, 753, 702, 629, 508 cm−1; HRMS (EI+): m/z: calcd for
C20H16N2O2: 316.1212, Found: 316.1209.
7.99–7.97 (m, 3H), 7.53–7.49 (m, 5H), 7.45–7.43 (m, 3H); 13C
NMR (75 MHz, CDCl3) δ 166.51, 166.11, 155.64, 150.22, 136.70,
136.08, 135.94, 131.55, 130.99, 130.29, 130.09, 129.18, 128.44,
128.13, 127.14, 126.60, 124.51, 121.54, 121.23; IR (KBr): 3062,
2926, 1721, 1585, 1497, 1381, 1143, 1108, 970, 832, 744, 685,
625, 540 cm−1; HRMS (EI+): m/z: calcd for C23H13BrN2O2:
428.0160, Found: 428.0163.
8-Chloro-2,4-diphenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(48). Brown solid; yield 173 mg; 45%; mp 229–230 °C; 1H
NMR (300 MHz, CDCl3) δ 8.96 (d, J = 2.4 Hz, 1H), 8.21 (d, J =
9.0 Hz, 1H), 7.99–7.96 (m, 2H), 7.86 (dd, J = 9.3, 2.4 Hz, 1H),
7.54–7.47 (m, 5H), 7.45–7.42 (m, 3H); 13C NMR (75 MHz,
CDCl3) δ 166.55, 166.16, 155.53, 150.08, 136.15, 136.10, 134.19,
131.55, 131.02, 130.27, 130.11, 129.19, 128.96, 128.46, 128.14,
126.63, 123.79, 121.13, 121.18; IR (KBr): 3060, 2925, 1721,
1592, 1497, 1381, 1144, 1108, 973, 831, 746, 686, 625,
541 cm−1; HRMS (EI+): m/z: calcd for C23H13ClN2O2: 384.0666,
Found: 384.0664.
2-Benzyl-8-bromo-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (43). Brown solid; yield 156 mg; 41%; mp 192–193 °C;
1H NMR (300 MHz, CDCl3) δ 8.93 (d, J = 1.8 Hz, 1H), 7.95 (d,
J = 9.0 Hz, 1H), 7.88 (dd, J = 9.0, 2.1 Hz, 1H), 7.44 (d, J = 6.9
Hz, 2H), 7.35–7.27 (m, 3H), 4.86 (s, 2H), 3.00 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 167.74, 167.49, 155.41, 149.86, 136.25,
135.82, 135.03, 130.61, 128.81, 128.75, 128.12, 126.98, 123.60,
122.56, 121.43, 41.86, 22.03; IR (KBr): 3078, 2922, 2850, 1708,
1587, 1390, 1334, 1072, 924, 838, 750, 699, 625, 556 cm−1
;
HRMS (EI+): m/z: calcd for C19H13BrN2O2: 380.0160, Found:
380.0158.
2-Benzyl-8-chloro-4-methyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-
dione (44). Brown solid; yield 155 mg; 46%; mp 190–191 °C;
1H NMR (300 MHz, CDCl3) δ 8.77 (d, J = 1.8 Hz, 1H), 8.07 (d,
J = 9.3 Hz, 1H), 7.78 (dd, J = 9.3, 2.4 Hz, 1H), 7.45 (d, J =
7.5 Hz, 2H), 7.35–7.27 (m, 3H), 4.87 (s, 2H), 3.03 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 167.82, 167.59, 155.46, 149.54,
136.02, 135.78, 135.71, 134.20, 130.55, 129.05, 128.98, 128.36,
123.93, 122.97, 121.35, 42.17, 22.07; IR (KBr): 3074, 2925, 2854,
1711, 1497, 1394, 1335, 1079, 925, 838, 749, 696, 625, 563,
501 cm−1; HRMS (EI+): m/z: calcd for C19H13ClN2O2: 336.0666,
Found: 336.0663.
2,4-Diphenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (45).
Brown solid; yield 126 mg; 36%; mp 246–247 °C; 1H NMR
(300 MHz, CDCl3) δ 8.98 (dd, J = 8.4 Hz, 1H), 8.28 (d, J =
8.4 Hz, 1H), 8.01–7.98 (m, 2H), 7.93 (td, J = 8.4, 1.5 Hz, 1H),
7.76 (td, J = 8.1, 0.9 Hz, 1H), 7.53–7.51 (m, 4H), 7.48–7.38 (m,
4H); 13C NMR (150 MHz, CDCl3) δ 167.00, 166.49, 155.43,
151.85, 137.09, 136.60, 133.10, 131.38, 130.21, 130.18, 130.04,
129.72, 129.14, 128.32, 128.08, 126.77, 125.10, 120.87, 120.74;
IR (KBr): 3060, 1721, 1593, 1501, 1382, 1116, 779, 744,
687 cm−1; HRMS (EI+): m/z: calcd for C23H14N2O2: 350.1055,
Found: 350.1057.
8-Methyl-2,4-diphenyl-1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione
(46). Brown solid; yield 146 mg; 40%; mp 256–257 °C; 1H
NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 8.17 (d, J = 8.7 Hz, 1H),
7.98–7.95 (m, 2H), 7.77 (dd, J = 8.7, 1.8 Hz, 1H), 7.55–7.41 (m,
8H), 2.63 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.21,
166.64, 154.42, 150.68, 140.50, 136.66, 136.04, 135.62,
131.34, 130.08, 129.88, 129.81, 129.11, 128.26, 128.06,
126.72, 123.59, 120.96, 120.60, 22.04; IR (KBr): 3061, 2924,
1720, 1595, 1496, 1377, 1135, 1108, 831, 753, 694, 624,
506 cm−1; HRMS (EI+): m/z: calcd for C24H16N2O2: 364.1212,
Found: 364.1215.
Acknowledgements
This research was supported by the Nano Material Technology
Development Program through the Korean National Research
Foundation (NRF) funded by the Korean Ministry of
Education, Science, and Technology (2012M3A7B4049675).
Notes and references
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