Synthesis of 4-substituted 3-(indol-3-yl)maleimides and azepines with annelated indole and maleimide nuclei

Article abstract of DOI:10.1016/j.tet.2005.06.027

A series of 4-substituted 3-(indole-3-yl)maleimides has been synthesized. Upon the action of CH₃SO₃H in TFA, the 3-(indole-3-yl)-4-(arylalkylamino)-maleimides undergo cyclization to give 12b,13-dihydro-4bH-indolo[3,2-d]pyrrolo[3,4-b][1]benzazepine-5,7(6H,8H)-dione derivatives.

Full text of DOI:10.1016/j.tet.2005.06.027

Tetrahedron 61 (2005) 8241–8248
Synthesis of 4-substituted 3-(indol-3-yl)maleimides and azepines
with annelated indole and maleimide nuclei
*
Sergey A. Lakatosh, Yuri N. Luzikov and Maria N. Preobrazhenskaya
Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, B. Pirogovskaya 11, Moscow 119021, Russian Federation
Received 30 January 2005; revised 31 May 2005; accepted 9 June 2005
Abstract—A series of 4-substituted 3-(indole-3-yl)maleimides has been synthesized. Upon the action of CH3SO3H in TFA, the 3-(indole-3-
yl)-4-(arylalkylamino)-maleimides undergo cyclization to give 12b,13-dihydro-4bH-indolo[3,2-d]pyrrolo[3,4-b][1]benzazepine-5,7(6H,
8H)-dione derivatives.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Bisindolylmaleimide derivatives, their analogues, and
related polycondensed compounds are known to have
valuable biological properties. Some of them are inhibitors
of topoisomerase I (e.g., rebeccamycin 1a and ED110 1b)
and the enzymes of proteinkinase C family (staurosporin 2a,
UCN01 2b, and some bis(indol-3-yl)maleimides, for
example, 3 and 4) as well as other types of protein kinases1
(Scheme 1).
Under the action of protic acids, bis(indol-3-yl)maleimides
5 undergo 2,20-cyclization accompanied by the opening of
one of the indole rings to form aminophenylcarbazoles 7.2
However, in the presence of an oxidant (e.g., DDQ) they are
transformed into indolo[2,3-a]pyrrolo[3,4-c]carbazol-5,7-
diones 8.3 Previously, we showed that bis(indol-1-yl)male-
imides 9 and 3-dialkyl-(3-arylalkyl-)amino-4-(indol-1-
yl)maleimides 11 under the action of protic acids form
diazepine[1,4] derivatives 10 and 12 (Scheme 2).4
The transformation of 11 into 12 proceeds with a hydride
shift followed by an intramolecular electrophilic substi-
tution reaction (Scheme 3).5
Scheme 1.
In this work, the synthesis of 4-substituted 3-(indole-3-yl)
maleimides and new polycondensed heterocyclic systems
derived from them are described.
2. Results and discussion
1-Methyl-3-bromo-4-(indol-3-yl)maleimide and its N-Boc-
derivative were obtained as previously described.6 How-
ever, the bromine atoms in these bromomaleimides were
inert to nucleophilic substitution by primary or secondary
amines in contrast to the easy substitution of bromine atoms
Keywords: Indoles; Bisindolylmaleimides; Cyclization.
*
Corresponding author. Tel.: C7 095 2453753; fax: C7 095 2450295;
e-mail: mnp@space.ru
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.027

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S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
in the presence of Hu¨nig’s base (Scheme 4). Indol-1-
ylacetamide 14f was prepared by dehydrogenation of 14a
with DDQ in boiling toluene. It was also prepared in
lower yield by alkylation of indolyl sodium with
2-chloroacetamide.
Scheme 2.
Scheme 4.
Compounds 14a–f were condensed with methyl indole-3-
glyoxylate 15 to give the corresponding 4-substituted
3-(indol-3-yl)maleimides 16 (Scheme 5).
Scheme 3.
by primary or secondary amines in 3-bromo-4-(indol-1-
yl)maleimides.4 Another known method for the synthesis of
bis(aryl)maleimides is based on condensation of methyl
arylglyoxylates with acetamides using KOtBu.7
2-Substituted acetamides 14 were obtained in a good yield
from the corresponding amines 13a–c, phenol 13d and
4-methoxythiophenole 13e and 2-chloroacetamide in
acetone in the presence of anhydrous K2CO3 or in DMF
Scheme 5.

S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
8243
alkylamino-4-(indol-3-yl)maleimides 16a–c, the hydride
shift was not observed.
The mechanism of this transformation apparently consists
of the following steps: (1) protonation of the indole nucleus
to form the iminium electrophilic center at position-2 (18)
and (2) attack of the electrophile on the position adjacent
(ortho) to the alkylamino substituent in the benzene ring
leading to the formation of azepine ring (19) (Scheme 7).
We failed to obtain a product of the cyclization of 3-(indol-
3-yl)-4-phenoxymaleimide 16d upon the action of
CH3SO3H in TFA. 3-(Indol-3-yl)-4-(4-methoxythio-
phenyl)maleimide 16e under the same conditions gave a
complex mixture.
Dehydrogenation of 17a with an excess of DDQ in THF led
to the corresponding aromatic derivative 20a in 20% yield,
isomeric to the natural antibiotic arcyriacyanine A 21.2
From the reaction mixture, the dimer 22 of 20a was also
isolated in 20% yield (Scheme 8). When 2 equiv of DDQ
were used, a mixture of starting 17a, and the reaction
products 20a and 22 was formed. In the 1H NMR spectrum
of 22 two broad singlets corresponding to two imide
hydrogens (N2–H and N20–H) at d 11.2 and d 11.14 and
only one singlet corresponding to the indole NH hydrogen
(N100–H) at d 11.7 were present. Also present were one
singlet signal for C50–H d 8.06 and two doublet signals
coupled with each other corresponding to C5–H and C6–H.
The signals corresponding to the hydrogens of the benzene
moieties of four indole subfragments (four doublets and 0four
triplets of C11–H, C12–H, C13–H, C14–H, and C11 –H,
C120–H, C130–H, C140–H, as well as four doublets and0two
triplets of C7–H, C8–H, C9–H, and C70–H, C80–H, C9 –H)
were seen. The structure of the dimer 22 was supported by
HRMS and EI MS data. The dehydrogenation of 17a by Pd/
C in boiling toluene proceeded slowly, however, the dimer
22 was not formed. It suggests that the dimerization was
induced by the presence of dichlorodicyanohydroquinone
formed from DDQ in the process of the reaction. The
dehydrogenation of indoline derivatives 17b,c with 1 equiv
of DDQ in EtOAc gave the corresponding indoloazepines
20b,c in good yield (Scheme 8).
Scheme 6.
Maleimides 16a–c were treated with TFA in CH2Cl2.
Although the color of the reaction mixture changed from red
to dark violet, starting materials were recovered after
stirring for 2 h followed by neutralization of the acid by aq
NaHCO3. These compounds were also stable in neat TFA.
However, after treatment with the mixture of TFA/
CH3SO3H (5:1) for w2 h the cyclization products 17a–c
were isolated and purified by crystallization or column
chromatography. The analysis of the NMR spectra of 17a–c
indicated that intramolecular electrophilic substitution
occurred to form azepine derivatives with indoline and
1
maleimide nuclei annelated (Scheme 6). In the H NMR
spectra of cyclization products 17a–c two 1H signals
coupled with each other were present corresponding to the
hydrogens at the positions 2 and 3 of 2,3-disubstituted
indoline subfragment. One of them was coupled with 1H
doublet, in the area d 5–6 ppm, corresponding to the
indoline NH hydrogen. The signals corresponding to four
hydrogens at the positions 4–7 of 2,3-disubstituted indoline
subfragment (two doublets and two triplets) and one
hydrogen singlet of NH imide hydrogen were present in
the low field area of the spectrum. It differs from the earlier
described4 cyclization of 3-dialkyl-(3-arylalkyl-)amino-4-
(indol-1-yl)maleimides 11 (Scheme 3), proceeding with
hydride shift and transfer of electrophilic center from indole
nucleus to alkylamino moiety. In the case of 3-aryl-
Bisindolylmaleimide 16f was obtained by the dehydrogena-
tion of 16a with DDQ in 80% yield or by condensation of
methyl (indol-3-yl)glyoxylate 15 with acetamide 14f in 60%
yield.
Upon the action of the excess of CH3SO3H in TFA,
bisindolylmaleimide 16f 0 0afforded 8b,9-dihydro-
indolo[40,30:3,4,5]pyrrolo[3 ,4 :6,7]azepino[1,2-a]indol-
Scheme 7.

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S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
Scheme 8.
1,3(2H,5H)dione 23 in 56% yield. In the 1H NMR-spectrum
of 23, the signals corresponding to the hydrogen atoms of
3,4-disubstituted indole and 1,2-disubstituted indoline
fragments are present. It is interesting to note the difference
in reactivity between 1- and 3-subsituted indole fragments
of the bisindolylmaleimide 16f, as the formation of the
azepine derivative 24 isomeric to 23 was not observed
(Scheme 9).
corresponding azepines annelated with maleimide and
indole nuclei.
4. Experimental
Mps were determined on a Buchi SMP-20 apparatus. NMR
spectra were recorded with Varian VXR-400 instrument at
400 MHz (1H NMR) or at 75 MHz (13C NMR) with internal
reference. Chemical shifts are given in ppm and coupling
constants in Hz. Assignment of signals was based on the
decoupling experiments for 1H NMR and APT-experiments
for 13C NMR spectra, signals corresponding to the
quaternary carbon atoms are marked (q). Electron impact
mass-spectra (EI-MS) were obtained on a SAQ 710
Finnigan instrument at 70 eV (direct introduction, ion
source temperature 150 8C). HRMS mass spectra were
registered on a MAT 8430 Finnigan instrument with data
3. Conclusion
3-(Indol-3-yl)maleimides containing an N-alkylaryl sub-
stituent (including N-tetrahydroquinolinyl or N-indolinyl
moiety) in position 4 of the maleimide ring produced
azepines annelated with maleimide, indoline, and arylamine
(including indoline or tetrahydroquinoline) nuclei under
acid treatment. Subsequent dehydrogenation led to the
Scheme 9.

S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
8245
i
operating system SS-300 (EI, 70 eV, direct introduction, ion
source temperature 250 8C). Infrared spectra were recorded
with Nicolet Avatar 330 FTIR spectrometer using KBr
discs. UV–vis spectra were recorded using Hitachi U-2000
spectrophotometer using THF as a solvent. Analytical TLC
was performed on Silica Gel F254 plates (Merck) and
column chromatography on Silica Gel Merck 60. Extracts
were dried over anhydrous Na2SO4 and evaporated under
reduced pressure. Solvents and reagents were obtained from
commercial suppliers unless otherwise specified.
colorless crystals (from PrOH) (5.3 g, 25.8 mmol, 80%);
mp 175–177 8C (iPrOH); [Found: C, 70.43; H, 8.03; N,
13.79. C12H16N2O requires C, 70.56; H, 7.90; N, 13.71%];
Rf 0.6 (CHCl3–MeOH 25:1); nmax: 1209, 1243, 1331, 1387,
1403, 1512, 1619, 1655, 2837, 2886, 2924, 3169, 3345 cmK1
;
dH (d6-DMSO) 1.9 (2H, m, –NCH2CH2CH2), 2.14 (3H, s,
PhCH3), 2.67 (2H, t, JZ6.4 Hz, –NCH2CH2CH2), 3.30 (2H,
t, JZ6.2 Hz, –NCH2CH2CH2), 3.69 (2H, s, –CH2-
C(O)NH2), 6.26 (1H, d, JZ8.1 Hz, C8–H), 6.72 (1H, d,
JZ1.9 Hz, C5–H), 6.76 (1H, dd, JZ8.2, 1.9 Hz, C7–H),
7.18 (1H,s, NH), 7.26 (1H, s, NH); dC (d6-DMSO) 20.0,
21.9, 27.4, 50.3, 55.0, 110.6, 122.1 (q), 124.3 (q), 127.1,
129.4, 143.1 (q), 172.3 (C]O); m/z (EI-MS) MC204 (100),
160 MCKCONH2 (33%).
4.1. Acetamides 14
(A) Compound 13 (70 mmol) and an excess of anhydrous
K2CO3 were added to the solution of 2-chloroacetamide
(3 g, 32.2 mmol) in acetone (200 mL). The reaction mixture
was refluxed with intensive stirring for 3 h. After cooling to
rt the reaction mixture was filtered and the filtrate
evaporated. The residue was dissolved in EtOAc
(200 mL), the solution was washed with 1 N HCl (2!
50 mL), 0.5 N Na2CO3 solution (2!50 mL), water (2!
50 mL), dried, and evaporated. The residue was recrystal-
lized from an appropriate solvent.
4.1.4. 2-Phenoxyacetamide (14d). Compound 14d was
obtained by method A as colorless crystals (from PrOH)
i
(3 g, 19.4 mmol, 60%); mp 96–98 8C (iPrOH); [Found: C,
63.65; H, 6.10; N, 9.39. C8H9NO2 requires C, 63.56; H,
6.00; N, 9.27%]; Rf 0.56 (CHCl3–MeOH 10:1); nmax: 1243,
1292, 1354, 1415, 1458, 1497, 1586, 1679, 2923, 3062,
3141, 3457 cmK1; dH (CDCl3) 4.52 (2H, s), 6.65 (2H, br s),
6.96 (2H, d, JZ7.8 Hz), 7.06 (1H, t, JZ7.3 Hz), 7.35 (2H,
m); dC (CDCl3) 67.0, 114.5, 122.0, 129.7, 157.0 (q), 171.3
(C]O); m/z (EI-MS) MC151 (100), 107 MCKCONH2
(75%).
(B) Compound 13 (70 mmol) and Et(iPr)2N (4.5 g,
35 mmol) were added to the solution of 2-chloroacetamide
(3 g, 32.2 mmol) in dry DMF (40 mL). The reaction mixture
was left to stir overnight at 60 8C. After cooling to rt the
reaction mixture was poured into 1 N HCl (100 mL) and
extracted with EtOAc (2!100 mL). The organic layer was
washed with 1 N HCl (100 mL), water (50 mL), dried, and
evaporated. The residue was recrystallized from an
appropriate solvent.
4.1.5. 2-(4-Methoxythiophenyl)acetamide (14e). Com-
pound 14e was obtained by method A as yellowish crystals
(from PrOH) (5.4 g, 27.6 mmol, 86%); mp 100–102 8C
i
(iPrOH); [Found: C, 54.85; H, 5.72; N, 7.18. C9H11NO2S
requires C, 54.80; H, 5.62; N, 7.10%]; Rf 0.4 (CHCl3–
MeOH 10:1); nmax: 1237, 1288, 1383, 1420, 1456, 1496,
1573, 1626, 2919, 2961, 3199, 3383 cmK1; dH (d6-DMSO)
3.49 (2H, s), 3.74 (3H, s), 6.92 (2H, d), 7.11 (1H, br s), 7.36
(2H, d), 7.48 (1H, br s); dC (d6-DMSO) 38.3, 55.2, 114.7
(2C), 126.0 (q), 131.7 (2C), 158.4 (q), 170.1 (C]O); m/z
(EI-MS) MC197 (100), 153 MCKCONH2 (55), 139 MCK
CH2CONH2 (20%).
4.1.1. 2-(2,3-Dihydroindol-1-yl)acetamide (14a). Com-
pound 14a was obtained by method A as colorless crystals
(from EtOAc) (4.8 g, 27.4 mmol, 85%); mp 146–147 8C
(EtOAc); [Found: C, 68.26; H, 7.97; N, 15.75. C10H12N2O
requires C, 68.16; H, 7.86; N, 15.90%]; Rf 0.61 (CHCl3–
MeOH 10:1); nmax: 1242, 1305, 1335, 1385, 1398, 1458,
1473, 1489, 1605, 1653, 2842, 2897, 3185, 3377 cmK1; dH
(d6-DMSO) 2.92 (2H, t, JZ8.3 Hz), 3.41 (2H, t, JZ8.3 Hz),
3.61 (2H, s), 6.44 (1H, d, JZ7.6 Hz), 6.60 (1H, t, JZ
7.4 Hz), 6.98 (1H, t, JZ7.4 Hz), 7.04 (1H, d, JZ7.1 Hz),
7.16 (1H, s), 7.44 (1H, s); dC (d6-DMSO) 28.1, 52.1, 53.6,
106.5, 117.3, 124.1, 127.0, 129.4 (q), 152.0 (q), 171.4 (C]O);
m/z (EI-MS) MC176 (35), 132 MCKCONH2 (100%).
4.1.6. Indol-1-ylacetamide (14f). (A) The solution of 14a
(500 mg, 2.8 mmol) in the mixture of toluene and THF (2:1,
150 mL) was treated with DDQ (770 mg, 3.4 mmol), and
the reaction mixture was refluxed for 2 h. The cooled to rt
reaction mixture was diluted with EtOAc (50 mL), washed
with aq NaHSO3 (2!30 mL), aq Na2CO3 (2!30 mL),
water (50 mL), brine (30 mL), dried and evaporated. The
residue was purified by flash chromatography (CHCl3). The
product was obtained as a grey colored solid (453 mg,
2.6 mmol, 93%); mp 158–160 8C (CHCl3); [Found: C,
69.06; H, 5.84; N, 16.19. C10H10N2O requires C, 68.95; H,
5.79; N, 16.08%]; Rf 0.51 (CHCl3–MeOH 10:1); nmax: 1311,
4.1.2. 2-(N-Ethylphenylamino)acetamide (14b). Com-
pound 14b was obtained by method B as colorless crystals
i
(from PrOH) (5.05 g, 28.3 mmol, 88%); mp 104–106 8C
(iPrOH); [Found: C, 67.26; H, 7.97; N, 15.78. C10H14N2O
requires C, 67.39; H, 7.92; N, 15.72%]; Rf 0.62 (CHCl3–
MeOH 25:1); nmax: 1239, 1257, 1340, 1405, 1502, 1654,
2976, 3182, 3417 cmK1; dH (d6-DMSO) 1.10 (3H, m,
–CH2CH3), 3.42 (2H, m, –CH2CH3), 3.78 (2H, s,
–CH2C(O)NH2), 6.59–6.64 (3H, m), 7.13 (1H, s, NH),
7.15–7.19 (2H, m), 7.32 (1H, s, NH); dC (d6-DMSO) 11.8,
45.4, 53.5, 111.7, 115.8, 147.9 (q), 172.3 (C]O); m/z
(EI-MS) MC178 (55), 134 MCKCONH2 (100%).
1325, 1405, 1466, 1484, 1515, 1626, 1668, 3183, 3382 cmK1
;
dH (d6-acetone) 4.87 (2H, s), 6.50 (1H, d, JZ3.1 Hz, C3–H),
6.63 (2H, br s), 7.06 (1H, t, JZ7.5 Hz), 7.17 (1H, t, JZ
7.6 Hz), 7.31(1H, d,JZ3.1 Hz), 7.39(1H, d, JZ8.2 Hz), 7.59
(1H, d, JZ7.9 Hz); dC (d6-acetone) 49.6, 102.3, 110.3, 120.2,
121.4, 122.2, 129.7 (q), 130.0, 137.5 (q), 170.4 (C]O); m/z
(EI-MS) MC174 (90), MCKCONH2 130 (100%).
(B) A solution of indole (580 mg, 5 mmol) in DMF (3 mL)
was added to the stirred suspension of NaH (60% in mineral
oil, 200 mg, 5 mmol) in DMF (4 mL), the mixture was left
4.1.3. 2-(6-Methyl-3,4-dihydroquinolin-1-yl)acetamide
(14c). Compound 14c was obtained by method B as

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S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
to stir at rt for 30 min. The reaction mixture was then treated
with the solution of 2-chloroacetamide (470 mg, 5 mmol) in
DMF (5 mL) and left to stir overnight. The reaction mixture
was poured into ice and extracted with EtOAc (2!50 mL).
The organic layer was washed with water (3!30 mL), dried
and evaporated. The residue was purified by flash
chromatography (CHCl3) to give 14f (435 mg, 50%). The
obtained product was identical to 14f, obtained by method A
according to TLC and NMR data.
2.8 Hz, indole NH); dC (d6-DMSO) 13.5 (ethyl CH3), 44.7
(ethyl CH2), 104.1 (q), 112.0, 118.1 (2C, Ph), 119.2 (q),
120.0, 120.4, 120.8, 121.7, 126.3 (q), 128.4, 128.7 (2C, Ph),
135.7 (q), 136.0 (q), 145.1 (q), 169.7 (C]O), 171.6 (C]O);
m/z (EI-MS) MC331 (100) MCK NH 316 (20%).
4.2.3. 3-(1H-Indol-3-yl)-4-(3,4-dihydro-6-methylquino-
lin-1-yl)maleimide (16c). Compound 16c was obtained
from 14c (220 mg, 1.08 mmol) and 15 (220 mg, 1.08 mmol)
as dark red crystals (308 mg, 0.86 mmol, 80%); mp 260–
262 8C (EtOH); [Found: C, 73.81; H, 5.49; N, 11.87.
C22H19N3O2 requires C, 73.93; H, 5.36; N, 11.76]; Rf 0.36
(CHCl3–MeOH 20:1); nmax: 1243, 1299, 1329, 1398, 1433,
4.2. 4-Substituted 3-(indol-3-yl)maleimides 16
The stirred solution or suspension of acetamide 14 (200–
500 mg) and equimolar amount of methyl (indol-3-
yl)glyoxylate 15 in THF (20 mL) was treated with KOtBu
(1.5 equiv). The reaction mixture was left to stir for 2.5–3 h
at 50 8C, cooled to 0 8C, and concd HCl (3 equiv) was
added. The mixture was stirred for 15 min, diluted with
water (50 mL), and extracted with EtOAc (2!50 mL). The
organic layer was separated, washed with water up to
neutral pH, dried, and evaporated. The residue was worked
up as indicated below.
1502, 1522, 1613, 1630, 1674, 1760, 2920, 3186, 3342 cmK1
;
dH (d6-DMSO) 1.73 (2H, m, CH2CH2CH2), 2.18 (3H, s,
PhCH3),2.67(2H,t,JZ6.2 Hz, PhCH2CH2–), 3.25(2H, t, JZ
5.9 Hz, NCH2CH2), 6.70 (1H, d, JZ8.2 Hz, Ph C6–H), 6.77
(1H, dd, JZ8.2, 1.5 Hz, Ph C5–H), 6.82 (1H, d, JZ1.5 Hz, Ph
C3–H), 6.91(1H, t, JZ7.6 Hz, indole), 7.10(1H, t, JZ7.6 Hz,
indole), 7.32 (1H, d, JZ8.2 Hz, indole), 7.45 (1H, d, JZ
8.2 Hz, indole), 7.70 (1H, d, JZ2.8 Hz, indole C2–H), 10.64
(1H, s, imide NH), 11.7 (1H, br s, indole N1–H); dC (d6-
DMSO) 20.2, 21.9, 26.4, 48.6, 104.2 (q), 112.0, 118.5 (q),
119.6 (q), 119.9, 120.4, 121.8, 124.8 (q), 126.1 (q), 126.8,
128.3, 128.9 (q), 129.4, 136.1 (q), 136.4 (q), 138.3 (q), 169.2
(C]O), 171.6 (C]O); m/z (EI-MS) MC357 (100) MCK
C(O)NHC(O) 286 (15%).
4.2.1. 3-(2,3-Dihydroindol-1-yl)-4-(indol-3-yl)maleimide
(16a). Compound 16a was obtained from 14a (240 mg,
1.4 mmol) and 15 (280 mg, 1.4 mmol) as a red colored oil,
that crystallized upon storage to give dark violet crystals
(440 mg, 1.3 mmol. 95%); mp 198–200 8C (EtOH); [Found:
C, 73.04; H, 4.51; N, 12.80. C20H15N3O2 requires C, 72.94;
4.2.4. 3-(Indol-3-yl)-4-phenyloxymaleimide (16d). The
residue after solvent evaporation was chromatographed
(CHCl3–MeOH 20:1), the fractions containing 16d were
pooled and evaporated, the residue was purified by the
preparative TLC (CHCl3–MeOH 20:1), to give 16d as a
yellow solid (52 mg, 0.17 mmol, 10% from 14d, 250 mg,
1.7 mmol); Rf 0.5 (CHCl3–MeOH 10:1), EI HRMS, found
MC304.0837 (100%). C18H12N2O3 requires 304.0848;
nmax: 1221, 1251, 1318, 1353, 1379, 1444, 1488, 1590,
1642, 1671, 1716, 2925, 3170, 3359 cmK1; dH (d6-DMSO)
6.99 (2H, d, JZ8.5 Hz), 7.1 (1H, t JZ7.6 Hz), 7.15 (1H, t,
JZ7.6 Hz), 7.19 (1H, m), 7.28–7.32 (2H, m), 7.46 (1H, d,
JZ8.0 Hz), 7.9 (1H, d, JZ8.2 Hz), 8.13 (1H, d, JZ2.9 Hz),
11.0 (1H, s), 11.92 (1H, br d).
H, 4.59; N, 12.76%]; Rf 0.61 (CHCl3–MeOH 10:1); nmax
:
1214, 1239, 1320, 1340, 1429, 1461, 1486, 1517, 1599,
1634, 1680, 1754, 3051, 3356 cmK1; dH (d6-DMSO) 3.10
(2H, t, JZ8.2 Hz, indoline C3–H), 4.16 (2H, t, JZ8.2 Hz,
indoline C2–H), 6.21 (1H, dd, JZ8.2 Hz, indoline C4–H),
6.59–6.63 (2H, two triplets, indoline C5–H and C6–H), 6.84
(1H, t, JZ7.4 Hz, indole C6–H or C5–H), 7.00 (1H, t, JZ
8.1 Hz, indole C6–H or C5–H), 7.07 (1H, dd, JZ8.3 Hz,
indoline C7–H), 7.31 (1H, d, JZ8.0 Hz, indole C4–H or
C7–H), 7.33 (1H, d, JZ8.2 Hz, indole C4–H or C7–H), 7.42
(1H, d, JZ2.6 Hz, indole C2–H), 10.72 (1H, s, imide NH),
11.49 (1H, br d, JZ2.5 Hz, indole NH); dC (d6-DMSO) 28.7
(indoline C3), 52.2 (indoline C2), 104.7 (q), 111.59, 111.61
(q), 112.0, 119.4, 120.1, 120.6, 121.4, 124.1, 125.8, 126.8
(q), 127.6, 131.1 (q), 134.3 (q), 135.5 (q), 143.7 (q), 169.6
(C]O), 171.8 (C]O); EI HRMS calcd MC for
C20H15N3O2 329.1164, found 329.1177 (100), MCK
(CO)2NH 285 (13%).
4.2.5. 3-(Indol-3-yl)-4-[(4-methoxyphenyl)thio]male-
imide (16e). Compound 16e was obtained from 14e
(300 mg, 1.5 mmol) and 15 (305 mg, 1.5 mmol). The
residue after solvent evaporation was chromatographed
(CHCl3) and left to crystallize. 22e crystallized from CHCl3
as orange crystals as a solvate with CHCl3 (178 mg,
0.38 mmol, 25%); mp 185–186 8C (CHCl3); [Found: C,
51.43; H, 3.21; N, 6.06. C20H15Cl3N2O3S requires C, 51.13;
4.2.2. 3-(Indol-3-yl)-4-(N-ethylanilino)maleimide (16b).
Compound 16b was obtained from 14b (200 mg,
1.12 mmol) and 15 (230 mg, 1.12 mmol) as dark red
crystals (300 mg, 0.78 mmol, 70%); mp 248–250 8C
(EtOH); [Found: C, 72.80; H, 5.39; N, 12.72. C20H17N3O2
requires C, 72.49; H, 5.17; N, 12.68%]; Rf 0.29 (CHCl3–
MeOH 25:1); nmax: 1223, 1239, 1262, 1311, 1340, 1398,
1435, 1499, 1509, 1594, 1615, 1625, 1694, 1756, 3040,
3223, 3377 cmK1; dH (d6-DMSO) 1.05 (3H, m, ethyl CH3),
3.55 (2H, m, ethyl CH2), 6.87 (1H, t, JZ7.2 Hz, Ph), 6.91
(1H, t, JZ7.9 Hz, Ph), 6.99 (2H, d, JZ7.9 Hz, Ph, C2–H
and C6–H), 7.09 (1H, t, JZ7.6 Hz, indole), 7.17–7.20 (2H, t
and t, indole and Ph C4–H), 7.28 (1H, d, JZ8.0 Hz, indole),
7.42 (1H, d, JZ8.0 Hz, indole), 7.96 (1H, d, JZ2.8 Hz,
indole C2–H), 10.74 (1H, s, imide NH), 11.70 (1H, d, JZ
H, 3.22; N, 5.96%]; Rf 0.46 (CHCl3–MeOH 10:1); nmax
:
1231, 1292, 1303, 1338, 1425, 1489, 1579, 1701, 1762,
3251, 3374, 3539, 3635 cmK1; dH (d6-DMSO) 3.7 (3H, s),
6.81 (2H, d, JZ8.8 Hz), 7.11 (1H, dt, 4JZ1.1, 7.9 Hz), 7.18
4
(1H, dt, JZ1.1, 8.2 Hz), 7.21 (CHCl3), 7.26 (2H, d, JZ
8.8 Hz), 7.46 (1H, d, JZ8.1 Hz), 7.85 (1H, d, JZ2.9 Hz,
indole C2–H), 7.88 (1H, d, JZ8.0 Hz), 11.09 (1H, s), 11.97
(1H, br d, JZ2.9 Hz); dC (d6-DMSO) 55.2 (OCH3), 79.2
(CHCl3), 104.8 (q), 112.0, 114.6 (2C), 120.1, 122.1, 122.3,
122.8 (q), 125.0 (q), 126.0 (q), 131.1, 131.6 (2C), 136.4 (q),
137.9 (q), 158.7 (q), 169.2 (C]O), 170.4 (C]O); m/z
(EI-MS) MC350 (100), MCKC(O)NHC(O) 279 (10%).

S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
8247
4.2.6. 3-(Indol-1-yl)-4-(indol-3-yl)maleimide (16f). (A) To
the solution of 16a (100 mg, 0.3 mmol) in toluene (50 mL)
was added the solution of DDQ (76 mg, 0.33 mmol) in
toluene (3 mL). The reaction mixture was refluxed for 3 h.
After cooling to rt it was diluted with EtOAc (50 mL),
washed with saturated aq NaHSO3 (30 mL), aq NaHCO3
(2!30 mL), water (30 mL), brine (30 mL), dried and
evaporated. The product was isolated by flash chromato-
graphy (CHCl3) as a red solid (78 mg, 0.24 mmol, 80%); mp
160–161 8C (EtOH–CHCl3); [Found: C, 73.45; H, 4.10; N,
12.96. C20H13N3O2 requires C, 73.38; H, 4.00; N, 12.84%];
EI HRMS, found MC327.1016 (100), MCK (CO)2NH 256
(30%). C20H13N3O2 requires 327.1008; Rf 0.5 (CHCl3–
MeOH 10:1); nmax: 1207, 1238, 1329, 1420, 1457, 1513,
1616, 1712, 1761, 2925, 3342 cmK1; dH (d6-DMSO) 6.05
(1H, d, JZ8.2 Hz), 6.49 (1H, t, JZ7.6 Hz), 6.76 (1H, d, JZ
3.3 Hz), 6.86 (1H, t, JZ8.2 Hz), 6.93 (1H, t, JZ8.1 Hz),
6.95–7.00 (2H, t and d), 7.34 (1H, d, JZ8.2 Hz), 7.56 (1H,
d, JZ3.3 Hz), 7.57 (1H, d, JZ7.7 Hz), 8.06 (1H, d, JZ
3.0 Hz), 11.23 (1H, s), 11.97 (1H, br s); dC (d6-DMSO) 103.8
(q), 105.1, 111.8, 112.0, 119.7, 120.3, 120.6, 120.7, 122.1,
122.2, 125.3 (q), 126.0 (q), 126.4 (q), 128.1 (q), 128.4, 131.1,
136.6 (q), 136.1 (q), 169.3 (C]O), 171.0 (C]O).
pyrrolo[3,4-b][1]benzazepine-5,7(6H,8H)-dione (17b).
The extract was evaporated and the residue was chromato-
graphed (CHCl3) to give 17b as a yellow crystals (140 mg,
0.42 mmol, 70%, from 16b, 200 mg, 0.6 mmol); mp 209–
210 8C (CHCl3); [Found: C, 72.42; H, 5.31; N, 12.40.
C20H17N3O2 requires C, 72.49; H, 5.17; N, 12.68%]; Rf 0.27
(CHCl3); nmax: 1249, 1279, 1348, 1409, 1481, 1492, 1598,
1650, 1701, 1755, 2924, 2972, 3350, 3380 cmK1; lmax
:
240 nm (3 19,332 cmK1 MK1), 276 (8254), 404 (4934); dH
(d6-DMSO) 1.10 (3H, m, CH2CH3), 4.03 (2H, m, CH2CH3),
4.25 (1H, d, JZ7.1 Hz C4b–H), 4.94 (1H, dd, J12b–4b
7.3 Hz, J12b–13Z2.6 Hz, C12b–H), 6.12 (1H, d, J13–12b
Z
Z
2.6 Hz, N13–H), 6.54 (1H, dt, JZ7.5, 1.0 Hz, C3–H), 6.57
(1H, d, JZ6.8 Hz, C1–H), 6.95 (1H, dt, JZ7.6, 1.3 Hz, C2–
H), 7.08–7.12 (1H, m), 7.19 (1H, d, JZ7.3 Hz, C4–H),
7.31–7.39 (3H, m), 10.5 (1H, s, N6–H); dC (d6-DMSO) 14.3
(CH2CH3), 41.6 (C4b), 44.7 (N–CH2–), 64.9 (C12b), 108.6,
113.1 (q), 116.8, 122.4, 123.5, 124.4, 127.4, 130.5 (q), 131.4
(q), 131.5, 141.1 (q), 145.6 (q), 150.9 (q), 169.0 (C]O),
171.4 (C]O); m/z (EI-MS) MC331 (100) MCKC(O)NH
288 (15), MCKC(O)NHC(O) 260 (20%).
4.3.3. 9-Methyl-6,7,11,15b-tetrahydro-5H-indolo[20,30:4,
5]pyrrolo[30,40:6,7]azepino[3,2,1-ij]quinoline-1,3(2H,
10bH)-dione (17c). Compound 17c was obtained from 16c
(200 mg, 0.56 mmol) as described for 17b as a yellow solid
(120 mg, 0.42 mmol, 60%,); EI HRMS, found MC357.1489
(100%). C22H19N3O2 requires 357.1477; Rf 0.27 (CHCl3);
nmax: 1263, 1337, 1405, 1437, 1454, 1477, 1606, 1637,
1706, 1753, 2729, 2926, 3424 cmK1; lmax: 245 nm (3
13,059 cmK1 MK1), 294 (4515), 408 (3253); dH (d6-
DMSO) 1.93 (1H, m, C6–H), 2.08 (1H, m, C6–H), 2.26
(3H, s, PhCH3), 2.81–2.89 (2H, m, C7–H), 3.32–3.40 (1H,
m, C5–H), 4.48 (1H, dt, JZ13.0, 4.0 Hz, C5–H), 4.85 (1H,
d, JZ7.3 Hz, C10b–H), 6.01 (1H, br s, N11–H), 6.52–6.57
(2H, t and d, C14–H and C12–H), 6.93 (1H, d, JZ1.9 Hz,
C8–H or C10–H), 6.95 (1H, dt, J13–15Z1.4, 7.7 Hz, C13–
H), 7.19 (1H, d, JZ7.22 Hz, C15–H), 10.45 (1H, s, N2–H);
dC (d6-DMSO) 20.1 (CH3), 22.7, 26.5, 42.0 (C15b), 46.8
(C5), 65.8 (C10b), 109.4, 110.8 (q), 117.4, 124.9, 127.8,
129.8, 129.9 (q), 130.3 (q), 130.4, 131.7 (q), 132.3 (q), 140.5
(q), 141.5 (q), 151.2 (q), 168.7 (C]O), 171.8 (C]O); m/z
(EI-MS) MC357 (100), MCKC(O)NHC(O) 286 (23%).
(B) Bisindolylmaleimide 16f was also obtained by
condensation of (indol-1-yl)acetamide 14f and 15 by the
action of KOBut in 60% yield after column chromatography
(CHCl3). It was identical to 16f obtained by method A
according to TLC and NMR data.
4.3. Transformation of 4-substituted 3-(indol-3-yl)male-
imides 16 upon the action of CH3SO3H
To the solution of 16 (200–300 mg) in TFA (5 mL) was
added CH3SO3H (1 mL) and the reaction mixture was
stirred for 3 h at rt and then was poured into aq NaHCO3/
EtOAc (1:1, 100 mL), NaHCO3 was added up to neutral pH.
The organic layer was separated, washed with water
(50 mL), dried, and worked up as indicated below.
4.3.1. 5,6,10,14b-Tetrahydro[10,70:1,2,3]pyrrolo[30,40:6,
7]azepino[4,5-b]indol-1,3(2H,9bH)-dione (17a). The solu-
tion was concentrated and left to crystallize at 0 8C. The
precipitate was filtered, washed with EtOAc (2!5 mL) and
dried to give 23a as a dark yellow solid (130 mg, 0.4 mmol,
65%, from 22a 200 mg, 0.61 mmol); mp 254–255 8C
(EtOAc, decomp.); EI HRMS, found 329.1173 (100),
MCKCO 301 (13), MCK(CO)2NH 258 (40%).
C20H15N3O2 requires MC329.1164; Rf 0.7 (CHCl3–MeOH
10:1); nmax: 1245, 1303, 1334, 1355, 1415, 1462, 1586,
4.3.4. Indolo[10,70:1,2,3]pyrrolo[30,40:6,7]azepino[4,5-b]
indol-1,3(2H,10H)-dione (20a) and its dimer (22). The
solution of 17a (200 mg, 0.61 mmol) in THF (100 mL) was
treated with DDQ (300 mg, 1.3 mmol) in THF (2 mL). The
reaction mixture was stirred at 60 8C for 3 h, concentrated to
the volume 5 mL, and the residue was dissolved in EtOAc
(150 mL). The solution was washed with aq NaHSO3 (2!
30 mL), aq NaHCO3 (2!30 mL), water (50 mL), dried and
evaporated. The residue was chromatographed (PhCH3–
acetone 20:1) to give 20a as a dark blue solid (40 mg,
0.12 mmol, 20%); mp 248–250 8C (EtOH); EI HRMS,
found MC325.0857 (100), MCK(CO)2NH 254 (16%).
C20H11N3O2 requires 325.0851; Rf 0.57 (CHCl3–MeOH
10:1); nmax: 1208, 1232, 1283, 1359, 1419, 1449, 1523,
1623, 1679, 1757, 2877, 3044, 3249, 3359 cmK1; lmax
:
243 nm (3 13,337 cmK1 MK1), 293 (4225), 413 (8464); dH
(d6-DMSO) 3.09–3.13 (2H, m, C6–H), 4.42–4.49 (3H, m),
4.66 (1H, d, JZ6.6 Hz, C14b–H), 6.48 (1H, br s, N10–H),
6.52 (1H, t, JZ7.5 Hz), 6.55 (1H, d, JZ7.3 Hz), 6.91 (1H, t,
JZ7.6 Hz), 6.98 (1H, t, JZ7.6 Hz), 7.00 (1H, d, JZ
7.1 Hz), 7.17 (1H, d, JZ7.1 Hz), 7.42 (1H, d, JZ7.8 Hz,
C14–H), 10.63 (1H, s, N2–H); dC (d6-DMSO) 27.5, 42.5,
49.6, 62.6, 103.1 (q), 108.9, 117.2, 122.8, 124.1, 124.2,
127.4, 129.6, 131.6 (q), 133.0 (q), 138.1 (q), 142.1 (q), 149.5
(q), 168.3 (C]O), 171.9 (C]O).
1587, 1649, 1704, 1757, 2974, 3057, 3165, 3414 cmK1
;
lmax: 245 nm (3 27,191 cmK1 MK1), 350 (23,491), 586
(1933); dH (d6-DMSO) 6.5 (1H, d, JZ3.6 Hz, C6–H), 6.91
(1H, t, JZ7.7 Hz, C8–H), 6.99 (1H, t, JZ7.1 Hz), 7.07 (1H,
t, JZ7.1 Hz), 7.11 (1H, d, JZ7.5 Hz), 7.15 (1H, d, JZ
4.3.2.
8-Ethyl-12b,13-dihydro-4bH-indolo[3,2-d]

8248
S. A. Lakatosh et al. / Tetrahedron 61 (2005) 8241–8248
8.1 Hz), 8.01 (1H, d, JZ8.1 Hz), 8.12 (1H, d, JZ3.6 Hz,
C5–H); dC (d6-DMSO) 104.3 (q), 106.2, 118.1, 118.8 (q),
121.09, 121.14 (q), 121.4, 123.0, 123.5, 123.8, 125.8, 126.0
(q), 130.5 (q), 132.7 (q), 137.2 (q), 138.2 (q), 141.8 (q),
166.8 (C]O), 169.6 (C]O); and 22 as a green solid
(80 mg, 0.12 mmol, 20%); mpO330 8C (PhCH3/acetone);
EI HRMS, found MC648.1555 (100%). C40H20N6O4
or C8–H), 6.94 (1H, d, JZ1.3 Hz, C10–H or C8–H), 6.99
(1H, dt, JZ1.0, 8.1 Hz, C14–H), 7.10 (1H, dt, JZ1.0,
8.0 Hz, C13–H), 7.34 (1H, d, JZ8.2 Hz, C12–H), 7.84 (1H,
d, JZ8.1 Hz, C15–H), 10.62 (1H, s, N2–H), 11.65 (1H, s,
N11–H); dC (d6-DMSO) 20.0, 49.5, 51.2, 45.3, 106.1 (q),
111.5, 120.2, 122.1, 122.5 (q), 122.6, 125.1 (q), 126.7 (q),
127.0, 129.8 (q), 132.0, 133.2 (q), 137.3 (q), 139.7 (q), 145.0
(q), 146.6 (q), 166.9 (C]O), 1701.0 (C]O); m/z (EI-MS)
MC355(100), MCKCH3 340(20),MC284–(CO)2NH(21%).
requires 648.1546; Rf 0.25 (CHCl3–MeOH 10:1); nmax
:
1214, 1231, 1313, 1360, 1431, 1578, 1618, 1646, 1707,
2870, 2956, 3386, 3641 cmK1; lmax: 246 nm (3 23,257 cmK1
MK1), 301–368 (24,561–23,307), 602 (1950); dH (d6-DMSO)
5.93 (1H, d, JZ8.1 Hz), 6.65 (1H, t, JZ7.9 Hz), 6.92 (1H, td,
JZ7.7, 1.1 Hz), 6.92 (1H, d, JZ3.8 Hz), 6.97 (1H, d, JZ
7.5 Hz), 7.01(1H, td, JZ7.0,1.0 Hz), 7.21(1H, d, JZ7.8 Hz),
7.24 (1H, td, JZ7.5, 0.9 Hz), 7.33 (1H, t, JZ7.7 Hz), 7.70
(1H, d, JZ7.3 Hz), 7.76 (1H, d, JZ7.1 Hz), 7.79 (1H, d, JZ
7.1 Hz), 7.95(2H, two doublets, JZ7.7 Hz), 8.06(1H, s), 8.41
(1H, d, JZ3.7 Hz); dC (d6-DMSO) 104.1 (q), 109.0, 109.2 (q),
111.6, 114.3 (q), 117.9, 118.4, 119.2 (q), 119.3 (q), 120.4,
121.1, 121.4 (q), 123.1, 123.3, 123.4, 124.0, 124.6, 124.8,
124.9, 125.0, 125.6 (q), 125.8 (q), 128.0, 129.0, 129.2, 130.1
(q), 131.0 (q), 131.6 (q), 136.6 (q), 136.7 (q), 138.1 (q), 142.8
(q), 154.9 (q), 166.1 (C]O), 166.4 (C]O), 168.9 (C]O),
169.3 (C]O); m/z (EI-MS) MC648 (100), MCK(CO)2NH
577 (10), MCK((CO)2NH)2 508 (10), MC/2 324 (20%).
4.3.7. 8b,9-Dihydroindolo[40,30:3,4,5]pyrrolo[30,40:6,7]
azepino[1,2-a]indole-1,3(2H,5H)-dione (23). The solution
of 16f (100 mg, 0.31 mmol) in CHCl3 (5 mL) was treated
with CH3SO3H (0.2 mL) and TFA (1 mL). The reaction
mixture was left with stirring for 2 h and then poured into
the mixture of saturated aq NaHCO3/EtOAc (1:1, 150 mL).
The organic layer was separated, washed with water (2!
50 mL), dried and evaporated. The residue was chromato-
graphed (toluene–acetone 15:1), the fractions containing 23
were pooled and left for crystallization at rt for 24 h. The
dark violet crystals were filtered off, washed with toluene
and dried in vacuo to give pure 23 (56 mg, 0.17 mmol,
56%); mpO330 8C; [Found: C, 73.44; H, 3.84; N, 12.28.
C20H13N3O2 requires C 73.38; H, 4.00; N, 12.84%]; Rf 0.41
(PhCH3–acetone 5:2); nmax: 1249, 1264, 1350, 1412, 1480,
1518, 1603, 1613, 1639, 1694, 1752, 2922, 3051, 3165,
3300 cmK1; lmax: 246 nm (3 17,157 cmK1 MK1), 337
4.3.5. 8-Ethyl-8,13-dihydro-5H-indolo[3,2-d]pyrrolo[3,4-
b][1]benzazepine-5,7(6H)-dione (20b). To the solution of
17b (200 mg, 0.6 mmol) in EtOAc (50 mL) was added DDQ
(140 mg (0.62 mmol) and the reaction mixture was left with
stirring at rt for 3 h. The reaction mixture was diluted with
EtOAc (50 mL), washed with aq NaHSO3 (30 mL), aq
NaHCO3 (2!30 mL), water (50 mL), dried and evaporated.
The residue was chromatographed (CHCl3–MeOH 50:1) to
give 20b as dark blue crystals (160 mg, 0.48 mmol, 80%);
mpO330 8C (iPrOH); [Found: C, 72.91; H, 4.77; N, 12.72.
C20H15N3O2 requires C, 72.94; H, 4.59; N, 12.76%]; Rf 0.58
(CHCl3–MeOH 20:1); nmax: 1201, 1227, 1241, 1313, 1347,
(5417), 502 (6693); dH (d6-DMSO) 3.66 (1H, dd, Jgem
Z
16.3 Hz, J9–8bZ10.0 Hz), 3.94 (1H, dd, JgemZ16.3 Hz,
J9–8bZ2.8 Hz), 5.12 (1H, dd, J8b–9Z10.3, 2.5 Hz), 6.79–
6.81 (2H, triplet and doublet), 7.00 (1H, t, JZ7.8 Hz), 7.17–
7.21 (2H, m), 7.28 (1H, d, JZ7.5 Hz), 7.46 (1H, d, JZ
7.7 Hz), 7.99 (1H, d, JZ2.8 Hz, C4–H), 10.52 (1H, s), 11.85
(1H, br d, JZ2.0 Hz, NindH); dC (d6-DMSO) 30.2 (C9), 64.5
(C8b), 106.9 (q), 111.9, 112.0, 115.8, 117.5 (q), 120.2,
122.1, 124.0, 124.5 (q), 125.0, 126.8 (q), 128.4, 133.3 (q),
133.4 (q), 136.3 (q), 144.2 (q), 176.3 (C]O), 170.9 (C]O).
1439, 1504, 1633, 1696, 1753, 2975, 3056, 3252 cmK1; lmax
:
244 nm (3 25,465 cmK1 MK1), 331 (15,850), 500 (2163); dH
(d6-DMSO) 1.12 (3H, m, CH2CH3), 3.86 (2H, m, CH2CH3),
7.07 (1H, d, JZ7.9 Hz), 7.09 (1H, t, JZ7.9 Hz, C3–H), 7.16
(1H, t, JZ7.4 Hz), 7.20 (1H, t, JZ7.3 Hz, C2–H), 7.39 (1H, t,
JZ7.5 Hz), 7.44(2H, dCd, JZ7.6 Hz, C1–H andPh-H), 7.97
(1H, d, C4–H), 10.75 (1H, s, N6–H), 11.96 (1H, s, N13–H); dC
(d6-DMSO) 14.4, 44.3, 106.2 (q), 111.6, 120.3, 121.6, 122.1,
123.0, 124.5, 124.9 (q), 126.1 (q), 127.9 (q), 128.6, 130.8,
137.0 (q), 140.0 (q), 142.6 (q), 150.4 (q), 167.6 (C]O), 170.0
(C]O); m/z (EI-MS) MC329 (78), MCKCH2CH3 300 (100),
MCKCH2CH3–(CO)2NH 229 (27%).
Acknowledgements
This work was supported by Russian Foundation for Basic
Research grant No 03-03-32090-a, S.A. Lakatosh was also
supported by Regional Social Fund for Support of Russian
Medical Science.
References and notes
1. Pindur, U.; Kim, Y.-S. F.; Meharbani, F. Curr. Med. Chem.
1999, 6, 29–68.
4.3.6. 9-Methyl-6,7-dihydro-5H-indolo[20,30:4,5]pyr-
rolo[30,40:6,7]azepino[3,2,1-ij]quinoline-1,3(2H,11H)-
dione (20c). Compound 20c was obtained from 17c
(250 mg, 0.7 mmol) as described for 20b as dark blue
crystals (186 mg, 0.53 mmol, 75%); mpO330 8C (iPrOH);
[Found: C, 74.33; H, 4.78; N, 11.71. C22H17N3O2 requires
C, 74.35; H, 4.82; N, 11.82]; Rf 0.67 (CHCl3–MeOH 20:1);
nmax: 1207, 1240, 1318, 1335, 1362, 1435, 1497, 1538,
2. Steglich, W. Pure Appl. Chem. 1989, 61, 281–288.
3. Bergman, J.; Pelcman, B. Tetrahedron Lett. 1987, 28,
4411–4444.
4. Lakatosh, S. A.; Luzhikov, Y. N.; Preobrazhenskaya, M. N.
Org. Biomol. Chem. 2003, 1, 826–833.
5. Lakatosh, S. A.; Luzhikov, Y. N.; Preobrazhenskaya, M. N.
Tetrahedron 2005, 61, 2017–2020.
1638, 1690, 1745, 2878, 2915, 3054, 3234, 3303, 3344 cmK1
;
6. Brenner, M.; Rexhausen, H.; Steffan, B.; Steglich, W.
Tetrahedron 1988, 44, 2887–2892.
lmax: 245 nm (3 21,199 cmK1 MK1), 340 (15,347); dH (d6-
DMSO) 2.01 (2H, m, C6–H2), 2.69 (2H, t, JZ2.0 Hz, C7–
H2), 3.55 (2H, m, C5–H2), 6.83 (1H, d, JZ1.3 Hz, C10–H
7. Faul, M. M.; Winneroski, L. L.; Krumrich, C. A. J. Org. Chem.
1998, 63, 6053–6058.