Silver-and gold-mediated domino transformation: A strategy for synthesizing benzo[ e ]indolo[1,2-a ]pyrrolo/pyrido[2,1-c ][1,4]diazepine-3,9-diones

Article abstract of DOI:10.1021/jo101727r

We reported a strategy for the synthesis of fused heterocyclic compounds benzo[e]indolo[1,2-a]pyrrolo/pyrido[2,1-c][1,4]diazepine-3,9-diones via an AgSbF₆/gold-complex catalyzed one-pot cascade transformation. The strategy is tolerant of a broad range of substrates and affords a series of intriguing fused diazepinedione heterocycles.(Figure Presented)

Full text of DOI:10.1021/jo101727r

pubs.acs.org/joc
Silver- and Gold-Mediated Domino Transformation: A Strategy
for Synthesizing Benzo[e]indolo[1,2-a]pyrrolo/pyrido[2,1-c][1,4]-
diazepine-3,9-diones
Yu Zhou,† Jian Li,† Xun Ji,†,‡ Wei Zhou,§ Xu Zhang,† Wangke Qian,†,‡
Hualiang Jiang,†,§ and Hong Liu*,†
†State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of
Sciences, Shanghai 201203, China, ‡School of Pharmaceutical Engineering, Shenyang Pharmaceutical
University, Shenyang 110016, China, and School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China
§
hliu@mail.shcnc.ac.cn
Received September 2, 2010
We reported a strategyfor the synthesis of fusedheterocycliccompoundsbenzo[e]indolo[1,2-a]pyrrolo/
pyrido[2,1-c][1,4]diazepine-3,9-diones via an AgSbF6/gold-complex catalyzed one-pot cascade trans-
formation. The strategy is tolerant of a broad range of substrates and affords a series of intriguing
fused diazepinedione heterocycles.
Introduction
cyclic molecules, which in turn can be used to obtain bioactive
lead compounds. Recently, transition-metal-catalyzed cas-
cade transformations have attracted vast attention owing to
their intriguing selectivity and high atom economy.3 Among
the numerous catalysts available, silver salts and/or gold
complexes are very attractive catalysts. This is because they
are powerful tools for the electrophilic activation of alkynes
toward a variety of nucleophiles under mild conditions.4
The increasing resource consciousness of the chemical
community has led to a search for more efficient and atom-
economical methods for chemical synthesis. One of the most
practical strategies is to develop a cascade reaction in which
multiple bond formation and/or bond cleavage events occur
in one synthetic sequence.1 Heterocyclic scaffolds, especially
some fused heterocyles, have generally played a very impor-
tant role in pharmaceutical and agrochemical fields.2 There-
fore, an increasing number of studies are being carried out to
develop new approaches for the synthesis of these hetero-
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Org. Lett. 2009, 11, 2888. (b) Baskar, B.; Bae, H. J.; An, S. E.; Cheong, J. Y.;
Rhee, Y. H.; Duschek, A.; Kirsch, S. F. Org. Lett. 2008, 10, 2605. (c) Witham,
(2) For selected examples, see: (a) Chernyak, N.; Gevorgyan, V. Angew.
Chem., Int. Ed. 2010, 49, 2743. (b) Lazarski, K. E.; Hu, D. X.; Stern, C. L.;
Thomson, R. J. Org. Lett. 2010, 12, 3010. (c) Tan, C. J.; Di, Y. T.; Wang,
Y. H.; Zhang, Y.; Si, Y. K.; Zhang, Q.; Gao, S.; Hu, X. J.; Fang, X.; Li, S. F.;
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DOI: 10.1021/jo101727r
r
Published on Web 02/03/2011
J. Org. Chem. 2011, 76, 1239–1249 1239
2011 American Chemical Society

Zhou et al.
JOCArticle
SCHEME 1. Synthesis of Benzo[e]indolo[1,2-a]pyrrolo/pyrido[2,1-c][1,4]diazepine-3,9-diones
TABLE 1. Optimization of the Reaction Conditionsa
Although significant improvements have been made to domino
sequences, most of the reported reactions employ intramo-
lecular ring-closing reaction of a single starting material.5 It
is still a synthetic challenge for the one-pot synthesis of fused
heterocycles through an intermolecular reaction of multiple
simple starting materials.
Recently, we carried out gold and/or silver catalysts-
catalyzed cascade transformations for the efficient synthesis
of pyrrolo[1,2-a]quinolin-1(2H)-ones,6a pyrrolo/pyrido[2,1-
b]benzo[d][1,3]oxazin-1-ones,6b pyrrolo/pyrido [2,1-a][1,3]-
benzoxazinones, and pyrrolo/pyrido[2,1-a]quinazolinones.6c
As part of our ongoing efforts to develop new convenient and
efficient protocols for the synthesis of potential bioactive
fused heterocyles using transition-metal catalysts,7 we report
our recent findings for the synthesis of benzo[e]indolo[1,2-a]-
pyrrolo[2,1-c][1,4]diazepine-3,9-diones via a silver-/gold-mediated
one-pot domino process (Scheme 1); analogues of these
diazepinediones are distributed in various biologically inter-
esting natural products and synthetic molecules.8 However,
to the best of our knowledge, there is no published report on
the synthesis of these intriguing molecular scaffolds referred
to here. The advantage of this chemical transformation is the
formation of one new C-C bond and two new C-N bonds
to construct polycyclic heterocycles in one-pot cascade reac-
tion using two simple starting materials.
entry
catalyst system (mol %)b
solvent
toluene
yield (%)
1
2
3
4
5
6
7
8
AuCl(PPh3) (5)
Au catalyst A (5)
Au catalyst B (5)
AgSbF6 (5)
AgOTf (5)
AgBF4 (5)
TFA (5)
<5
20
23
50
49
45
0
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
Cl CH2CH2Cl
dioxane
CH3OH
H2O
-
0
9
AgSbF6 (5)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (30)/Au catalyst B (5)
AgSbF6 (20)
66
92
90
84
85
87
83
80
10
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
AgSbF6 (20)/TfOH (5)
AgOTf (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
AgSbF6 (20)/Au catalyst B (5)
0
0
THF
toluene
toluene
toluene
toluene
88c
78d
87e
91f
b
Results and Discussion
To identify the optimal reaction conditions for one-pot
synthesis of benzo[e]indolo[1,2-a]pyrrolo[2,1-c][1,4]diazepine-
3,9-diones, we carried out the experiments using (2-amino-
phenyl)(4-methyl-1H-indol-1-yl)methanone (1A) and 4-pen-
tynoic acid (2a) as model substrates (as shown in Table 1). In
a1A (0.1 mmol), 2a (0.15 mmol), Au catalyst, 120 °C for 12 h. Au
catalyst A = [Au{1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene}]Cl;
Au catalyst B = [Au{P(t-Bu)2(o-biphenyl)}{CH3CN}]SbF6. cThe reac-
tion time was prolonged to 24 h. dThe reaction temperature was below
100 °C. eThe reaction temperature was 140 °C. Reaction performed
f
under Ar protection.
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our previous studies, we found that some gold-complexes
and/or silver salts are highly efficient catalysts for cascade
reactions between less reactive aromatic amines and alkynoic
acids.6 Therefore, in the present study, different gold cata-
lysts and silver salts, such as AuCl(PPh3), [Au{1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene}]Cl (Au catalyst A),
[Au{P(t-Bu)2(o-biphenyl)}{CH3CN}]SbF6 (Au catalyst B),
AgSbF6, AgOTf, and AgBF4 were first investigated at 120 °C
for 12 h in a sealed tube using dry toluene as the solvent.
However, an excellent yield was not obtained, and only a
moderate yield product was formed under the presence of
AgSbF6 or AgOTf catalyst (Table 1, entries 1-6). Protonic
acid (TFA) was also explored, but no product was detected
(Table 1, entry 7). In addition, the desired product was not
formed in the absence of catalyst and only the starting mate-
rials were recovered (Table 1, entry 8). In our past studies, we
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found that some silver salts and gold catalysts can be used as
cocatalysts for certain organic transformations.6a,7a,b There-
fore, AgSbF6 and Au catalyst B was first selected as a
cocatalyst for this tandem transformation. Treatment of
the model substrates with AgSbF6 (5 mol %) in the presence
of 5 mol % of Au catalyst B resulted in a slight improvement
of the product yield (Table 1, entry 9). Further investigations
revealed that the yield could be improved to 92% by increas-
ing the amount of AgSbF6 to 20 mol % (Table 1, entry 10).
However, the product yield did not further increase when the
amount of AgSbF6 was increased beyond 20 mol % (Table 1,
entry 11). 84% yield was obtained by using only 20 mol %
AgSbF6 as a catalyst (Table 1, entry 12). In addition, TfOH
was added as a cocatalyst, 85% yield was detected (Table 1,
entry 13). AgOTf (20 mol %) was also investigated under the
presence of 5 mol % of Au catalyst B, but an improved result
was not obtained (Table 1, entry 14). Subsequently, we screened
different solvents with the use of an AgSbF6 (20 mol %)/ Au
catalyst B (5 mol %) as a catalyst system. Among the solvents
tested, nonpolar solvents such as CH2Cl2 and ClCH2CH2Cl
gave relatively better results (Table 1, entries 15-16). How-
ever, when toluene was replaced with dioxane, CH3OH, H2O
or THF, the product yield became poor (Table 1, entries
17-20). Therefore, toluene appeared to be the most effective
solvent for this transformation (Table 1, entry 10). We also
attempted to increase the product yields by prolonging the
reaction time to 24 h, but the yield did not improve (Table 1,
entry 21). In addition, we found that the reaction tempera-
ture played an important role in this domino transformation,
the product yield decreased drastically when the reaction
temperature was decreased to 100 °C (Table 1, entry 22). When
the reaction temperature was elevated to 140 °C, the yield
also showed a slight decrease (Table 1, entry 23). Although
this tandem transformation was also performed under argon
gas protection, no further improvement of the yield of 3Aa
was afforded (Table 1, entry 24). Therefore, the optimal yield
was obtained when (2-aminophenyl)(4-methyl-1H-indol-1-
yl)methanone (1A, 0.1 mmol) reacted with 4-pentynoic acid
(2a, 0.15 mmol) in dry toluene in the presence 20 mol %
of AgSbF6 and 5 mol % of Au catalyst B in a sealed tube at
120 °C for 12 h.
To explore the application scopes of this cascade reaction,
we tried to survey the diversity of the substrates by probing
the changes in both the substituted (2-aminophenyl)(1H-
indol-1-yl)methanones and the alkynoic acids. As demon-
strated in Table 2, different substituted 2-aminophenyl(1H-
indol-1-yl)methanones could furnished the corresponding
benzodiazepinones products 3Aa-3Gb in good to excellent
yields (70%-92%). However, we found that the type of
substituent and its site on the 2-aminophenyl(1H-indol-1-yl)-
methanones (1B) were important such that the yield of
products was influenced (Table 2, entries 1-17). When the
4-position of the indole-ring of 1B was substituted by a
methyl group, we obtained high yields (Table 2, entry 1).
No substituent or introduction of the methyl function at the
5- or 6-position of the indole ring of 2-aminophenyl(1H-
indol-1-yl)methanones resulted in a decrease in the yield of
the target products (Table 2, entries 2-4). Replacement of
the 5-methyl group in the indole-ring of 1C with a methoxyl
group also led to a slight decrease in the yield (Table 2, entry 5).
Introduction of a strong electron-withdrawing group (-CN)
at the 5-position of the indole-ring in 1B resulted in a drastic
reduction in the yield of the product, presumably because of
the influence of the electronic effects (Table 2, entry 6). A
good yield of the product was obtained when the 50-fluoro-
substituted substrate 1F was treated with 4-pentynoic acid
(2a) under the optimized reaction conditions (Table 2, entry 7).
Subsequently, we obtained substrates 1I-R by introducing
methyl, chloro, and fluoro groups in the benzene ring of 1B.
Results of further investigations demonstrated that all the
tested substrates were tolerated in this cascade transforma-
tion (Table 2, entries 8-17). Furthermore, substitution of an
alkyl group (n-hexyl group) into the alkynoic acid chain was
also tolerated, and excellent yields were obtained (Table 2,
entries 18-19). The target product 3Ba was crystallized from
dichloromethane and characterized by X-ray crystallography.9
Subsequently, we have investigated whether this protocol
can be used to prepare benzo[e]indolo[1,2-a] pyrido[2,1-c]-
[1,4]diazepine-3,9-diones (3Ac-3Rc) by the treatment of sub-
stituted (2-aminophenyl)(1H-indol-1-yl)methanones (1A-1R)
and 5-hexynoic acid (2c) under the optimized reaction con-
ditions. Although we have observed good yields in the above-
mentioned experimental examples under the optimal condi-
tions, a relatively longer time (18 h) was needed to complete
the substrate conversion fully when 5-hexynoic acid (2c) was
used as one of substrates. As shown in Table 3, substituted
2-aminophenyl(1H-indol-1-yl)methanones having substitu-
ents with steric and electronic properties were tolerated in
these cascade reactions (Table 3, entries 1-17). However,
introduction of a strong electron-withdrawing group (-CN)
at the 5-position of the indole ring in 1B led to a dramatic
decrease in the yield of the target product. Even if the
reaction time was prolonged to 24 h, we have still detected
a small amount of keto-amide intermediate10 that did not
fully convert into the end product, probably owing to the
strong electronic effects (Table 3, entry 6). In addition, we
also used 2-(prop-2-ynyloxy)acetic acid (2d) as a substrate to
investigate the scope of this domino transformation. Treat-
ment of 1B, 1G, and 1I with 2-(prop-2-ynyloxy)acetic acid
(2d) in toluene at 120 °C for 18 h afforded the expected
products, 3Bd, 3Gd, and 3Id, respectively, in good yields
(Table 3, entries 18-20). In view of these findings, we feel
that this synthetic strategy will be an effective approach for
the synthesis of intriguing polycyclic molecular architectures.
Scheme 2 depicts a plausible mechanism for the present
domino transformation. We presumed that the catalyst would
induce the cyclization of the alkynoic acid 2 to generate the
activated enol-lactone intermediate A,11 and then the amino
group of aromatic primary amine 1 attacked this intermedi-
ate to afford the ketoamide B,10 which was further converted
to N-acyl iminium ion C via nucleophilic addition and
(9) CCDC 779689 contains the supplementary crystallographic data for
3Ba. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(10) In fact, when we treated 1-(2-aminobenzoyl)-1H-indole-5-carboni-
trile (1F) with 5-hexynoic acid (2c) under the optimal reaction conditions, the
keto-amide intermediate N-(2-(5-cyano-1H-indole-1-carbonyl)phenyl)-5-oxo-
hexanamide (3Fc-M) was isolated. Characteristic data for 3Fc-M: 1H NMR
(CDCl3, 300MHz) δ 9.2 (br, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.35 (d, J = 8.7 Hz,
1H), 7.96 (s, 1H), 7.62-7.67 (m, 2H), 7.49 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 3.9
Hz, 1H), 7.22 (t, 1H), 6.71 (d, J = 3.3 Hz, 1H), 2.54 (t, 2H), 2.41 (t, 2H), 2.11 (s,
3H), 1.92-1.98 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 208.2, 171.2, 168.5,
138.7, 137.8, 133.7, 130.9, 130.4, 129.9, 128.1, 125.9, 123.3, 123.1, 121.6, 119.þ4,
117.1, 108.3, 107.5, 42.2, 36.5, 29.9, 19.1. LRMSþ(ESI) m/z 396 [M þ Na] ;
HRMS (ESI) m/z calcd C22H19N3O3Na [M þ Na] 396.1324, found 396.1327.
^
(11) Genin, E.; Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genet, J.-P.;
Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112.
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TABLE 2. Silver- and Gold-Mediated One-Pot Domino Synthesis of 3a
a1 (0.1 mmol), 2 (0.15 mmol), Aucatalyst B (5 mol %), AgSbF6 (20 mol %), toluene (2-3 mL), 120 °C for 12 h. bThe reaction time was prolonged to24 h.
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TABLE 3. Scopes of Silver-/Gold-Catalyzed Domino Transformationa
a1 (0.1 mmol), 2 (0.15 mmol), Aucatalyst B (5 mol %), AgSbF6 (20 mol %), toluene (2-3 mL), 120 °C for 18 h. bThe reaction timewas prolonged to24 h.
J. Org. Chem. Vol. 76, No. 5, 2011 1243

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SCHEME 2. A Plausible Mechanism
subsequent dehydration (cascade process). Finally, nucleo-
philic addition of C to the alkene moiety in the indole ring of
the substrate yielded the ring-closure product 3. In order to
further support the proposed mechanism, we treated one
intermediate (A, R-angelica lactone) with a starting material
1B under the optimized conditions, and the desired product
3Ba was obtained in 90% yield.12
evaporated under reduced pressure. The residue was quickly
dissolved in CH2Cl2 (15 mL), then was dropped slowly into a
solution of 4-methylindole (0.47 g), DMAP (37 mg), and Et3N
(1.3 mL) in CH2Cl2 (15 mL) under an argon atmosphere
protection. The resulting mixture was stirred at room temperature
for overnight until the starting materials were fully consumed.
Then, the mixture was concentrated and purified by flash column
chromatography (petroleum ether (PE)/ethyl acetate (EA) =
4/1, v/v, as an eluent) to afford 0.68 g of the intermediate.
To a mixture of 0.5 g of the above intermediate and 0.4 g of
Sn in 25 mL of C2H5OH was added 1.5 mL of concentrated
hydrochloric acid, and further stirred at 70 °C for 2 h. The
reaction was monitored by TLC. After cooling, the mixture was
added H2O (40 mL) and neutralized with saturated NaHCO3.
Then, the solution was extracted with ethyl acetate (3 ꢀ 20 mL).
The combined organic layers were washed with water and dried
by anhydrous Na2SO4. After removal of the solvent, the crude
product was purified by column chromatography (PE/EA =
5/1, v/v, as an eluent) to give the desirable substrate 1A. 1H NMR
(CDCl3, 300 MHz) δ 8.13 (d, J = 8.7 Hz, 1H), 7.24-7.38 (m,
4H), 7.11 (d, J = 7.5 Hz, 1H), 6.71-6.81 (m, 2H), 6.65 (d, J =
3.9 Hz, 1H), 4.78 (br, 2H), 2,58 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 169.3, 148.9, 135.7, 133.2, 131.4, 130.4, 130.3, 127.4,
124.6, 124.0, 117.0, 116.6, 116.1, 113.6, 106.3, 18.5; LRMS (EI)
m/z 250 (Mþ); HRMS (EI) m/z calcd C16H14N2O (Mþ) 250.1106,
found 250.1107.
Conclusion
In summary, a strategy for the one-pot synthesis of intri-
guing polycyclic heterocycles benzo[e]indolo[1,2-a]pyrrolo/
pyrido[2,1-c][1,4]diazepine-3,9-diones was reported via a silver-
and gold-mediated domino transformation from simple starting
materials. Multiple carbon-carbon and carbon-nitrogen bonds
were formed from two simple starting materials through a
one-pot reaction operation. In view of a large assortment of
biological activities of benzodiazepinones, we believe that
this new strategy will open the door to prepare new members
of benzodiazepinone derivatives family, and have potential
applications in drug discovery.
Experimental Section
Typical Procedure for Synthesis of the Substrates (1A as an
Example). To a solution of 2-nitrobenzoic acid (0.5 g) in dry
CH2Cl2 (15 mL) was added 2 mL of thionylchloride. The resulting
mixture was heated to reflux for 3 h, and then the solvent was
(2-Aminophenyl)(1H-indol-1-yl)methanone (1B): 1H NMR
(CDCl3, 300 MHz) δ 8.31 (d, J = 7.8 Hz, 1H), 7.61 (d, J =
7.2 Hz, 1H), 7.35 (7.28-7.40, 5H), 6.72-6.81 (m, 2H), 6.61 (d,
J = 3.9 Hz, 1H), 5.03 (br, 2H); 13C NMR (CDCl3, 100 MHz) δ
169.2, 149.0, 136.0, 133.2, 131.4, 130.8, 128.0, 124.6, 123.6,
120.9, 117.0, 116.6, 116.1, 116.0, 107.9; LRMS (EI) m/z 236
(Mþ); HRMS (EI) m/z calcd C15H14N2O (Mþ) 236.0950, found
236.0951.
(12) To further explore the proposed mechanism, we treated 1B with the
tautomer of intermediate A (R-angelica lactone, as shown below) under the
optimized reaction conditions. Operational procedure: To a solution of
R-angelica lactone (1.5 mmol) in dry toluene (3 mL) were added Au catalyst
B (5 mol %) and AgSbF6 (20 mol%). After stirring at room temperature for
10 min, 1B (1 mmol) were added. Subsequently, the reaction vial was sealed,
the mixture was heated to 120 °C for 12 h, and then, the cold mixture was
concentrated under reduced pressure. The resulting residue was purified by
flash column chromatography to afford 3Ba in 90% yield.
(2-Aminophenyl)(5-methyl-1H-indol-1-yl)methanone (1C): 1H
NMR (CDCl3, 300 MHz) δ 8.18 (d, J = 8.4 Hz, 1H), 7.28-7.39
(m, 4H), 7.19 (d, J = 8.7 Hz, 1H), 6.71-6.80 (m, 2H), 6.54 (d,
J = 3.6 Hz, 1H), 4.67 (br, 2H), 2.48 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ 169.0, 148.8, 134.2, 133.2, 133.1, 131.3, 131.0, 128.0,
125.9, 120.8, 117.0, 116.6, 116.2, 115.7, 107.8, 21.4; LRMS (EI)
m/z 250 (Mþ); HRMS (EI) m/z calcd C16H14N2O (Mþ) 250.1106,
found 250.1103.
(2-Aminophenyl)(6-methyl-1H-indol-1-yl)methanone (1D): 1H
NMR (CDCl3, 300 MHz) δ 8.18 (s, 1H), 7.48 (d, J = 8.1 Hz,
1244 J. Org. Chem. Vol. 76, No. 5, 2011

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JOCArticle
1H), 7.24-7.38 (m, 3H), 7.14 (d, J = 8.1 Hz, 1H), 6.67-6.80 (m,
2H), 6.55 (d, J = 3.6 Hz, 1H), 5.04 (br, 2H), 2.51 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 169.3, 148.9, 136.4, 134.7, 133.1,
131.3, 128.5, 127.5, 125.1, 120.4, 117.0, 116.6, 116.3, 107.8, 21.9;
LRMS (EI) m/z 250 (Mþ); HRMS (EI) m/z calcd C16H14N2O
(Mþ) 250.1106, found 250.1115.
J = 7.2 Hz, 1H), 7.25-7.38 (m, 5H), 6.73 (d, J = 9.0 Hz, 1H),
6.65 (d, J = 4.2 Hz, 1H), 5.02 (br, 2H); 13C NMR (CDCl3, 100
MHz) δ 167.8, 147.3, 135.9, 133.1, 130.8, 130.3, 127.5, 124.8,
123.9, 121.3, 121.0, 118.3, 117.1, 116.1, 108.7; LRMS (EI) m/z
270 (Mþ); HRMS (EI) m/z calcd C15H11ClN2O (Mþ) 270.0560,
found 270.0559.
(2-Aminophenyl)(5-methoxy-1H-indol-1-yl)methanone (1E):
1H NMR (CDCl3, 300 MHz) δ 8.23 (d, J = 9.0 Hz, 1H),
7.28-7.38 (m, 3H), 7.07 (d, J = 2.7 Hz, 1H), 6.98 (dd, J =
9.0 Hz, 2.7 Hz, 1H), 6.76 (q, 2H), 6.53 (d, J = 3.6 Hz, 1H), 5.03
(br, 2H), 3.88 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 168.8,
156.5, 148.8, 133.0, 131.8, 131.2, 130.7, 128.6, 117.0, 116.9,
116.6, 116.1, 113.1, 107.9, 103.5, 55.6; LRMS (EI) m/z 266
(Mþ); HRMS (EI) m/z calcd C16H14N2O2 (Mþ) 266.1055, found
266.1054.
(2-Amino-5-chlorophenyl)(5-methyl-1H-indol-1-yl)methanone
(1N): 1H NMR (CDCl3, 300 MHz) δ 8.18 (d, J = 8.4 Hz, 1H),
7.39 (s, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.24-7.29 (m, 2H), 7.19
(d, J = 8.4 Hz, 1H), 6.73 (d, J = 8.7 Hz, 1H), 6.57 (d, J = 3.9 Hz,
1H), 4.97 (br, 2H), 2.47 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
167.6, 147.1, 134.1, 133.6, 132.9, 131.1, 130.3, 127.5, 126.2,
121.3, 120.9, 118.3, 117.3, 115.7, 108.5, 21.4; LRMS (EI) m/z
284 (Mþ); HRMS (EI) m/z calcd C16H13ClN2O (Mþ) 284.0716,
found 284.0723.
(2-Amino-5-chlorophenyl)(5-fluoro-1H-indol-1-yl)methanone
(1O): 1H NMR (CDCl3, 300 MHz) δ 8.27 (q, 1H), 7.33-7.37 (m,
2H), 7.24-7.29 (m, 2H), 7.10 (td, 1H), 6.74 (d, J = 9.0 Hz, 1H),
6.61 (d, J = 3.6 Hz, 1H), 4.96 (br, 2H); 13C NMR (CDCl3, 100
MHz) δ 167.6, 159.8 (d, J = 239.2 Hz), 147.4, 133.2, 132.3, 131.8
(d, J = 10.1 Hz), 130.3, 129.1, 121.4, 118.4, 117.1 (d, J = 9.1
Hz), 116.7, 112.6 (d, J = 25.1 Hz), 108.4, 106.5 (d, J = 23.7 Hz);
LRMS (EI) m/z 288 (Mþ); HRMS (EI) m/z calcd C15H10-
ClFN2O (Mþ) 288.0466, found 288.0471.
1
1-(2-Aminobenzoyl)-1H-indole-5-carbonitrile (1F): H NMR
(CDCl3, 300 MHz) δ 8.31 (d, J = 8.4 Hz, 1H), 7.95 (s, 1H), 7.59
(dd, J = 8.4 Hz, 1.5 Hz, 1H) 7.51 (d, J = 3.9 Hz, 1H), 7.34-7.39
(m, 2H), 6.82 (d, J = 9.0 Hz, 1H), 6.75 (t, 1H), 6.67 (d, J = 3.6
Hz, 1H), 5.30 (br, 2H); 13C NMR (CDCl3, 100 MHz) δ 169.1,
149.7, 137.9, 134.2, 131.5, 130.6, 130.2, 127.5, 125.8, 119.7,
117.4, 116.8, 116.7, 114.4, 107.2, 106.8; LRMS (EI) m/z 261
(Mþ); HRMS (EI) m/z calcd C16H11N3O (Mþ) 261.0902, found
261.0894.
1
(2-Aminophenyl)(5-fluoro-1H-indol-1-yl)methanone (1G): H
(2-Amino-5-chlorophenyl)(5-chloro-1H-indol-1-yl)methanone
(1P): 1H NMR (CDCl3, 300 MHz) δ 8.22 (d, J = 9.0 Hz, 1H),
7.59 (d, J = 4.5 Hz, 1H), 7.25-7.40 (m, 4H), 6.74 (d, J = 8.7 Hz,
1H), 6.59 (d, J = 3.3 Hz, 1H), 4.98 (br, 2H); 13C NMR (CDCl3,
100 MHz) δ 167.7, 147.6, 134.3, 133.4, 132.0, 130.3, 129.4, 128.8,
125.0, 121.4, 120.6, 118.5, 117.1, 116.4, 107.9; LRMS (EI) m/z
304 (Mþ); HRMS (EI) m/z calcd C15H10Cl2N2O (Mþ) 304.0170,
found 304.0178.
NMR (CDCl3, 300 MHz) δ 8.28 (q, 1H), 7.23-7.41 (m, 4H),
7.09 (td, 1H), 6.72-6.81 (m, 2H), 6.57 (d, J = 3.9 Hz, 1H), 5.00
(br, 2H); 13C NMR (CDCl3, 100 MHz) δ 168.9, 159.6 (d, J =
238.7 Hz), 149.0, 133.4, 132.3, 131.7 (d, J = 10.0 Hz), 131.2,
129.5, 117.1, 117.0 (d, J = 8.6 Hz), 116.6, 115.6, 112.3 (d, J =
24.6 Hz), 107.5, 106.3 (d, J = 23.6 Hz); LRMS (EI) m/z 254
(Mþ); HRMS (EI) m/z calcd C15H11FN2O (Mþ) 254.0855,
found 254.0860.
1
(2-Amino-5-fluorophenyl)(1H-indol-1-yl)methanone (1Q): H
1
(2-Aminophenyl)(5-chloro-1H-indol-1-yl)methanone (1H): H
NMR (CDCl3, 300 MHz) δ 8.31 (d, J = 8.1 Hz, 1H), 7.62 (d, J =
7.5 Hz, 1H), 7.29-7.41 (m, 3H), 7.05-7.11 (m, 2H), 6.73-6.78
(m, 1H), 6.64 (d, J = 3.9 Hz, 1H), 4.84 (br, 2H); 13C NMR
(CDCl3, 100 MHz) δ 168.0, 154.1 (d, J = 236.0 Hz), 145.1,
135.9, 130.8, 127.5, 124.8, 123.9, 121.0, 120.6 (d, J = 22.8 Hz),
118.3 (d, J = 7.3 Hz), 116.7 (d, J = 23.7 Hz), 116.1, 108.6;
LRMS (EI) m/z 254 (Mþ); HRMS (EI) m/z calcd C15H11FN2O
(Mþ) 254.0855, found 254.0861.
NMR (CDCl3, 300 MHz) δ 8.22 (d, J = 8.7 Hz, 1H), 7.57 (s,
1H), 7.26-7.40 (m, 4H), 6.72-6.81 (m, 2H), 6.54 (d, J = 3.3 Hz,
1H), 5.10 (br, 2H); 13C NMR (CDCl3, 100 MHz) δ 169.0, 149.2,
134.3, 133.5, 131.9, 131.3, 129.3, 129.1, 124.7, 120.4, 117.1,
117.0, 116.6, 115.3, 107.1; LRMS (EI) m/z 270 (Mþ); HRMS
(EI) m/z calcd C15H11ClN2O (Mþ) 270.0560, found 270.0565.
(2-Amino-5-methylphenyl)(1H-indol-1-yl)methanone (1I): 1H
NMR (CDCl3, 300 MHz) δ 8.31 (d, J = 7.8 Hz, 1H), 7.61 (d, J =
6.9 Hz, 1H), 7.30-7.37 (m, 3H), 7.13-7.17 (m, 2H), 6.72 (d, J =
8.4 Hz, 1H), 6.61 (d, J = 3.9 Hz, 1H), 4.86 (br, 2H), 2.45 (s, 3H);
13C NMR (CDCl3, 100 MHz) δ 169.3, 146.5, 136.0, 134.1, 131.1,
130.8, 128.1, 126.0, 124.5, 123.6, 120.8, 117.2, 116.3, 116.1,
107.8, 20.3; LRMS (EI) m/z 250 (Mþ); HRMS (EI) m/z calcd
C16H14N2O (Mþ) 250.1106, found 250.1108.
(2-Amino-5-methylphenyl)(5-methyl-1H-indol-1-yl)methanone
(1J): 1H NMR (CDCl3, 300 MHz) δ 8.18 (d, J = 8.4 Hz, 1H),
7.40 (s, 1H), 7.32 (d, J = 3.9 Hz, 1H), 7.12-7.20 (m, 3H), 6.71
(d, J = 8.1 Hz, 1H), 6.54 (d, J = 3.9 Hz, 1H), 4.80 (br, 2H), 2.48
(s, 3H), 2.25 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 169.1, 146.3,
134.1, 133.9, 133.2, 131.0, 128.1, 126.0, 125.9, 120.7, 117.2, 116.6,
115.7, 107.7, 21.4, 20.3; LRMS (EI) m/z 264 (Mþ); HRMS (EI)
m/z calcd C17H16N2O (Mþ) 264.1263, found 264.1259.
(2-Amino-5-fluorophenyl)(5-chloro-1H-indol-1-yl)methanone
(1R): 1H NMR (CDCl3, 300 MHz) δ 8.23 (d, J = 8.7 Hz, 1H),
7.58 (d, J = 1.8 Hz, 1H), 7.30-7.38 (m, 2H), 7.06-7.13 (m, 2H),
6.73-6.79 (m, 1H), 6.58 (d, J = 3.9 Hz, 1H), 4.81 (br, 2H); 13
C
NMR (CDCl3, 100 MHz) δ 167.8, 154.1 (d, J = 236.4 Hz),
145.3, 134.3, 132.0, 129.4, 128.8, 125.0, 121.1 (d, J = 22.8 Hz),
120.6, 118.4 (d, J = 7.3 Hz), 117.1, 116.6 (d, J = 23.7 Hz), 107.8;
LRMS (EI) m/z 288 (Mþ); HRMS (EI) m/z calcd C15H10-
ClFN2O (Mþ) 288.0466, found 288.0465.
General Procedure for Synthesis of Benzo[e]indolo[1,2-a]pyrrolo/
pyrido[2,1-c][1,4]diazepine-3,9-diones (3Aa as an Example). To a
solution of 4-pentynoic acids (2a, 1.5 mmol) in dry toluene (3 mL)
were added Au catalyst B (5 mol %) and AgSbF6 (20 mol %).
After stirring for 10 min at room temperature, (2-aminophenyl)-
(4-methyl-1H-indol-1-yl)methanone (1A, 1 mmol) was added.
Subsequently, the reaction vial was sealed, and the mixture
was heated to 120 °C for 12 h, and then, the cold mixture was
concentrated under reduced pressure. The resulting reside was
purified by flash column chromatography (PE/EA = 4/1, v/v,
as an eluent) to afford the desired product 3Aa in 92% yield. 1H
NMR (CDCl3, 300 MHz) δ 8.61 (d, J = 8.7 Hz, 1H), 8.41 (d,
J = 8.4 Hz, 1H), 7.62-7.68 (m, 2H), 7.42-7.48 (m, 1H), 7.24-
7.29 (m, 1H), 7.11 (d, J = 7.5 Hz 1H), 6.62 (s, 1H), 2.96-3.0 (m,
1H), 2.65-2.73 (m, 2H), 2.54 (s, 3H), 2.29-2.36 (m, 1H), 1.51 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 172.3, 164.0, 139.9, 138.7,
134.5, 134.1, 133.7, 129.9, 128.3, 127.3, 126.7, 125.5, 124.9,
115.6, 103.2, 62.4, 34.4, 30.5, 27.7, 18.4; LRMS (EI) m/z 330
(2-Amino-5-methylphenyl)(5-fluoro-1H-indol-1-yl)methanone
(1K): 1H NMR (CDCl3, 300 MHz) δ 8.27 (q, 1H), 7.40 (d, J =
3.6 Hz, 1H), 7.223-7.30 (m, 1H), 7.7.05-7.16 (m, 3H), 6.72 (d,
J = 6.6 Hz, 1H), 6.56 (d, J = 3.9 Hz, 1H), 4.84 (br, 2H), 2.25 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 169.0, 159.6 (d, J = 238.3
Hz), 146.6, 134.3, 132.4, 131.7 (d, J = 10.1 Hz), 131.0, 129.6,
126.0, 117.3, 117.1 (d, J = 9.1 Hz), 115.9, 112.3 (d, J = 24.6 Hz),
107.5, 106.3 (d, J = 23.7 Hz), 20.3; LRMS (EI) m/z 268 (Mþ);
HRMS (EI) m/z calcd C16H13FN2O (Mþ) 268.1012, found
268.1007.
(2-Amino-5-chlorophenyl)(1H-indol-1-yl)methanone (1M): 1H
NMR (CDCl3, 300 MHz) δ 8.31 (d, J = 8.4 Hz, 1H), 7.62 (d,
J. Org. Chem. Vol. 76, No. 5, 2011 1245

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JOCArticle
(Mþ); HRMS (EI) m/z calcd C21H18N2O2 (Mþ) 330.1368, found
330.1376.
62.2, 34.4, 30.4, 27.6, 21.0; LRMS (EI) m/z 330 (Mþ); HRMS
(EI) m/z calcd C21H18N2O2 (Mþ) 330.1368, found 330.1359.
7,13,15b-Trimethyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c][1,4]-
diazepine-3,9(2H,15bH)-dione (3Ja): 1H NMR (CDCl3, 300 MHz)
δ 8.45 (d, J = 8.7 Hz, 1H), 8.37 (s, 1H), 7.49 (s, 2H), 7.31 (s, 1H),
7.18 (d, J = 8.7 Hz, 1H), 6.51 (s, 1H), 2.89-2.97 (m, 1H),
2.62-2.69 (m, 2H), 2.47 (s, 3H), 2.45 (s, 3H), 2.22-2.34 (m, 1H),
1.48 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 172.3, 164.0, 140.6,
137.0, 136.7, 135.0, 134.0, 133.7, 132.0, 129.1, 127.2, 126.6,
126.5, 120.4, 117.8, 104.8, 62.3, 34.5, 30.4, 27.7, 21.3, 21.0;
LRMS (EI) m/z 344 (Mþ); HRMS (EI) m/z calcd C22H20N2O2
(Mþ) 344.1525, found 344.1528.
7,15b-Dimethyl-13-fluoro-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Ka): 1H NMR (CDCl3,
300 MHz) δ 8.51-8.56 (m, 1H), 8.36 (s, 1H), 7.50 (s, 2H), 7.15-
7.20 (m, 1H), 7.03-7.11 (m, 1H), 6.55 (s, 1H), 2.89-2.93 (m,
1H), 2.62-2.69 (m, 2H), 2.47 (s, 3H), 2.27-2.36 (m, 1H), 1.49 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 172.3, 164.0, 159.8 (d, J =
239.6 Hz), 142.2, 136.8, 135.2, 135.1, 133.7, 132.0, 129.9 (d, J =
10.0 Hz), 127.2, 126.2, 119.4 (d, J = 8.6 Hz), 112.8 (d, J = 24.1
Hz), 106.0 (d, J = 23.7 Hz), 104.4, 62.2, 34.4, 30.3, 27.6, 21.0;
LRMS (EI) m/z 348 (Mþ); HRMS (EI) m/z calcd C21H17FN2O2
(Mþ) 348.1274, found 348.1276.
7,15b-Dimethyl-13-chloro-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3La): 1H NMR (CDCl3, 300
MHz) δ 8.49 (d, J = 9.0 Hz, 1H), 8.36 (s, 1H), 7.48-7.50 (m,
3H), 7.31 (d, J = 9.6, 1H), 6.52 (s, 1H), 2.88-2.91 (m, 1H),
2.62-2.68 (m, 2H), 2.47 (s, 3H), 2.27-2.36 (m, 1H), 1.49 (s, 3H);
13C NMR (CDCl3, 100 MHz) δ 172.3, 164.0, 142.0, 137.1, 136.9,
135.3, 133.7, 132.0, 130.1, 129.7, 127.2, 126.0, 125.3, 120.0,
119.2, 104.0, 62.2, 34.4, 30.3, 27.5, 21.0; LRMS (EI) m/z 364
(Mþ); HRMS (EI) m/z calcd C21H17ClN2O2 (Mþ) 364.0979,
found 364.0971.
7-Chloro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Ma): 1H NMR (CDCl3,
300 MHz) δ 8.59 (s, 1H), 8.53 (d, J = 8.1 Hz, 1H), 7.62 (s, 2H),
7.54 (d, J = 7.5, 1H), 7.28-7.40 (m, 2H), 6.60 (s, 1H), 2.93-2.99
(m, 1H), 2.64-2.71 (m, 2H), 2.26-2.35 (m, 1H), 1.51 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 172.3, 162.6, 140.0, 138.8, 134.1,
133.2, 133.1, 132.5, 128.8, 128.6, 127.7, 125.6, 124.7, 120.7,
118.0, 105.2, 62.2, 34.2, 30.3, 27.6; LRMS (EI) m/z 350 (Mþ);
HRMS (EI) m/z calcd C20H15ClN2O2 (Mþ) 350.0822, found
350.0828.
7-Chloro-13,15b-dimethyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Na): 1H NMR (CDCl3,
300 MHz) δ 8.58 (s, 1H), 8.41 (d, J = 8.7 Hz, 1H), 7.60 (s,
2H), 7.32 (s, 1H), 7.19 (d, J = 8.7 Hz, 1H), 6.53 (s, 1H), 2.91-
2.98 (m, 1H), 2.63-2.70 (m, 2H), 2.45 (s, 3H), 2.25-2.34 (m,
1H), 1.49 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 172.3, 162.4,
140.0, 136.9, 134.4, 134.0, 133.2, 133.0, 132.5, 129.0, 128.6,
127.9, 126.9, 120.6, 117.7, 105.2, 62.2, 34.2, 30.3, 27.6, 21.3;
LRMS (EI) m/z 364 (Mþ); HRMS (EI) m/z calcd C21H17ClN2O2
(Mþ) 364.0979, found 364.0982.
7-Chloro-13-fluoro-15b-methyl-1H-benzo[e]indolo[1,2-a]-
pyrrolo[2,1-c][1,4]diazepine-3,9(2H,15bH)-dione (3Oa): 1H NMR
(CDCl3, 300 MHz) δ 8.56 (s, 1H), 8.47-8.52 (m, 1H), 7.61 (s,
2H), 7.15-7.19 (m, 1H), 7.05-7.11 (m, 1H), 6.56 (s, 1H), 2.90-
2.93 (m, 1H), 2.63-2.69 (m, 2H), 2.28-2.33 (m, 1H), 1.50 (s, 3H);
13C NMR (CDCl3, 100 MHz) δ 172.3, 162.4, 141.6, 135.0, 134.2,
133.2, 133.0, 132.6, 129.9, 128.7, 127.6, 119.3 (d, J = 8.6 Hz),
113.1 (d, J = 24.1 Hz), 106.2 (d, J = 23.7 Hz), 104.8, 62.2, 34.2,
30.3, 27.6; LRMS (EI) m/z 368 (Mþ); HRMS (EI) m/z calcd
C20H14ClFN2O2 (Mþ) 368.0728, found 368.0720.
15b-Methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c][1,4]diazepine-
3,9(2H,15bH)-dione (3Ba): 1H NMR (CDCl3, 400 MHz) δ 8.59
(t, 2H), 7.61-7.69 (m, 2H), 7.54 (d, J = 7.6 Hz, 1H), 7.46 (t, 1H),
7.37 (t, 1H), 7.31 (t, 1H), 6.60 (s, 1H), 2.93-2.96 (m, 1H),
2.65-2.71 (m, 2H), 2.28-2.35 (m, 1H), 1.51 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 172.4, 163.9, 140.4, 138.8, 134.5, 134.1,
133.7, 128.8, 127.3, 126.7, 126.6, 125.4, 124.4, 120.5, 118.1,
104.9, 62.3, 34.4, 30.4, 27.6; LRMS (EI) m/z 316 (Mþ); HRMS
(EI) m/z calcd C20H16N2O2 (Mþ) 316.1212, found 316.1212.
13,15b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c][1,4]-
diazepine-3,9(2H,15bH)-dione (3Ca): 1H NMR (CDCl3, 300 MHz)
δ 8.58 (d, J = 8.1 Hz, 1H), 8.45 (d, J = 8.4 Hz, 1H), 7.60-7.67
(m, 2H), 7.46 (t, 1H), 7.31 (s, 1H), 7.18 (d, J = 8.4 Hz, 1H), 6.52
(s, 1H), 2.9-2.96 (m, 1H), 2.63-2.70 (m, 2H), 2.44 (s, 3H),
2.27-2.35 (m, 1H), 1.49 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
172.4, 163.8, 140.4, 137.0, 134.5, 134.1, 134.0, 133.7, 129.0,
127.3, 126.8, 126.7, 120.5, 117.8, 104.8, 62.3, 34.4, 30.4, 27.7, 21.3;
LRMS (EI) m/z 330 (Mþ); HRMS (EI) m/z calcd C21H18N2O2
(Mþ) 330.1368, found 330.1367.
12,15b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c][1,4]-
diazepine-3,9(2H,15bH)-dione (3 Da): 1HNMR(CDCl3,300MHz)
δ 8.59 (d, J = 7.8 Hz, 1H), 8.42 (s, 1H), 7.64 (m, 2H), 7.46 (d, J =
7.2 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H),
6.54 (s, 1H), 2.90-2.95 (m, 1H), 2.52-2.72 (m, 2H), 2.50 (s, 3H),
2.25-2.34 (m, 1H), 1.49 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
172.4, 164.0, 139.8, 139.2, 135.5, 134.5, 134.0, 133.6, 127.2,
126.7, 126.5, 125.7, 120.0, 118.3, 104.8, 62.3, 34.3, 30.4, 27.6,
22.0; LRMS (EI) m/z 330 (Mþ); HRMS (EI) m/z calcd
C21H18N2O2 (Mþ) 330.1368, found 330.1359.
13-Methoxyl-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Ea): 1H NMR (CDCl3, 300
MHz) δ 8.58 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 9.3 Hz, 1H),
7.59-7.68 (m, 2H), 7.45 (t, 1H), 6.94-7.00 (m, 2H), 6.53 (s, 1H),
3.87 (s, 3H), 2.90-2.96 (m, 1H), 2.63-2.70 (m, 2H), 2.28-2.35
(m, 1H), 1.48 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 172.3,
163.5, 156.8, 141.1, 134.4, 134.0, 133.6, 133.4, 129.8, 127.3,
126.8, 119.1, 113.3, 104.9, 103.4, 62.3, 55.6, 34.5, 30.4, 27.7;
LRMS (EI) m/z 346 (Mþ); HRMS (EI) m/z calcd C21H18N2O3
(Mþ) 346.1317, found 346.1318.
13-Cyano-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Fa): 1H NMR (CDCl3, 300
MHz) δ 8.56-8.64 (m, 2H), 7.87 (s, 1H), 7.59-7.72 (m, 3H),
7.48 (t, 1H), 6.64 (s, 1H), 2.93-2.99 (m, 1H), 2.65-2.71 (m, 2H),
2.33-2.41 (m, 1H), 1.54 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
172.2, 164.1, 143.0, 140.7, 134.8, 133.8, 129.0, 128.3, 127.4,
126.9, 125.7, 125.2, 119.3, 118.8, 107.6, 103.8, 62.1, 34.2, 30.3,
27.4; LRMS (EI) m/z 341 (Mþ); HRMS (EI) m/z calcd
C21H15N3O2 (Mþ) 341.1164, found 341.1166.
13-Fluoro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Ga): 1H NMR (CDCl3,
300 MHz) δ 8.50-8.59 (m, 2H), 7.61-7.69 (m, 2H), 7.47 (t,
1H), 7.16-7.20 (m, 1H), 7.07-7.12 (m, 1H), 6.56 (s, 1H), 2.90-
2.92 (m, 1H), 2.64-2.71 (m, 2H), 2.30-2.34 (m, 1H), 1.50 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 172.4, 163.7, 159.9 (d, J =
239.6 Hz), 142.0, 135.1, 134.5, 134.3, 133.7, 129.9, 127.3, 126.9,
126.5, 119.3 (d, J = 8.7 Hz), 112.9 (d, J = 24.1 Hz), 105.1 (d, J =
23.7 Hz), 104.5, 62.3, 34.4, 30.3, 27.6; LRMS (EI) m/z 334 (Mþ);
HRMS (EI) m/z calcd C20H15FN2O2 (Mþ) 334.1118, found
334.1114.
7,15b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c][1,4]-
diazepine-3,9(2H,15bH)-dione (3Ia):1H NMR (CDCl3, 300 MHz)
δ 8.57 (d, J = 8.4 Hz, 1H), 8.39 (s, 1H), 7.49.7.55 (m, 3H),
7.27-7.39 (m, 2H), 6.59 (s, 1H), 2.91-2.96 (m, 1H), 2.62-2.70
(m, 2H), 2.47 (s, 3H), 2.26-2.35 (m, 1H), 1.50 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 172.3, 164.2, 140.6, 138.8, 136.7, 135.1,
133.7, 132.0, 128.9, 127.2, 126.3, 125.3, 124.3, 120.5, 118.1, 104.8,
7,13-Dichloro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo-
[2,1-c][1,4]diazepine-3,9(2H,15bH)-dione (3 Pa): 1H NMR (CDCl3,
300 MHz) δ 8.56 (s, 1H), 8.45 (d, J = 9.0 Hz, 1H), 7.62 (s, 2H), 7.49
(s, 1H), 7.30-7.34 (m, 1H), 6.54 (s, 1H), 2.90-2.97 (m, 1H), 2.63-
2.69 (m, 2H), 2.27-2.36 (m, 1H), 1.51 (s, 3H); 13C NMR (CDCl3,
1246 J. Org. Chem. Vol. 76, No. 5, 2011

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100 MHz) δ 172.3, 162.5, 141.4, 137.1, 134.3, 133.2, 133.1, 132.6,
130.0, 128.7, 127.4, 125.7, 120.2, 119.1, 104.3, 62.1, 34.1, 30.2, 27.5;
LRMS (EI) m/z 384 (Mþ); HRMS (EI) m/z calcd C20H14Cl2N2O2
(Mþ) 384.0432, found 384.0427.
127.1, 119.7 (d, J = 9.0 Hz), 112.8 (d, J = 23.8 Hz), 106.3, 105.9 (d,
J = 23.8 Hz), 62.4, 42.0, 40.5, 31.5, 30.7, 28.8, 28.7, 27.6, 22.5, 14.0;
LRMS (EI) m/z 418 (Mþ); HRMS (EI) m/z calcd C26H27FN2O2
(Mþ) 418.2057, found 418.2058.
7-Fluoro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Qa): 1H NMR (CDCl3,
300 MHz) δ 8.55 (d, J = 8.1 Hz, 1H), 8.29 (dd, J = 10.2 Hz,
3.0 Hz, 1H), 7.60-7.65 (m, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.29-
7.42 (m, 3H), 6.61 (s, 1H), 2.93-2.96 (m, 1H), 2.64-2.71 (m, 2H),
2.29-2.34 (m, 1H), 1.51 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
172.3, 162.7, 160.6 (d, J = 245.5 Hz), 140.2, 138.8, 130.6, 129.2
(d, J = 7.8 Hz), 128.8, 128.4, 125.6, 124.6, 121.5 (d, J = 22.8
Hz), 120.6, 119.6 (d, J = 25.1 Hz), 118.1, 105.3, 62.2, 34.3, 30.3,
27.6; LRMS (EI) m/z 334 (Mþ); HRMS (EI) m/z calcd
C20H15FN2O2 (Mþ) 334.1118, found 334.1123.
7-Fluoro-13-chloro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo-
[2,1-c][1,4]diazepine-3,9(2H,15bH)-dione (3Ra): 1H NMR (CDCl3,
300 MHz) δ 8.47 (d, J = 9.0 Hz, 1H), 8.25 (dd, J = 10.2 Hz, 3.3
Hz, 1H), 7.59-7.65 (q, 1H), 7.49 (s, 1H), 7.36-7.43 (m, 1H), 7.31
(dd, J = 9.0 Hz, 2.4 Hz, 1H), 6.54 (s, 1H), 2.90-2.97 (m, 1H),
2.63-2.69 (m, 2H), 2.29-2.36 (m, 1H), 1.50 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 172.3, 162.5, 160.6 (d, J = 245.5 Hz), 141.6,
137.1, 130.6, 130.1, 130.0, 129.3 (d, J = 8.2 Hz), 128.1 (d, J = 6.9
Hz), 125.6, 121.8 (d, J = 22.8 Hz), 120.2, 119.6 (d, J = 25.1 Hz),
119.1, 104.4, 62.1, 34.3, 30.2, 27.5; LRMS (EI) m/z 368 (Mþ);
HRMS (EI) m/z calcd C20H14ClFN2O2 (Mþ) 368.0728, found
368.0730.
15,16b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c][1,4]-
diazepine-4,10(2H,16bH)-dione (3Ac):1HNMR(CDCl3, 300MHz)
δ 8.57 (d, J = 8.7 Hz, 1H), 8.19 (d, J = 7.8 Hz, 1H), 7.60 (t, 1H),
7.46 (t, 1H), 7.28-7.32 (m, 2H), 7.12 (d, J = 7.2 Hz, 1H), 6.52 (s,
1H), 2.76-2.81(m, 1H), 2.55-2.64 (m, 2H), 2.52 (s, 3H), 2.10-2.28
(m, 2H), 1.91-1.96 (m, 1H), 1.35 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 169.9, 165.3, 142.6, 138.1, 137.1, 132.9, 132.4, 131.5, 129.9,
129.6, 128.5, 127.8, 125.5, 125.0, 116.3, 105.1, 60.9, 37.7, 31.8, 31.7,
18.3, 17.1; LRMS (EI) m/z 344 (Mþ); HRMS (EI) m/z calcd
C22H20N2O2 (Mþ) 344.1525, found 344.1527.
16b-Methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c][1,4]diazepine-
4,10(2H,16bH)-dione (3Bc): 1H NMR (CDCl3, 300 MHz) δ 8.75
(d, J = 8.7 Hz, 1H), 8.23 (d, J = 8.1 Hz, 1H), 7.62 (t, 1H),
7.45-7.55 (m, 2H), 7.31-7.42 (m, 3H), 6.52 (s, 1H), 2.75-2.80
(m, 1H), 2.57-2.66 (m, 2H), 2.19-2.29 (m, 1H), 2.11-2.14 (m,
1H), 1.92-1.97 (m, 1H), 1.36 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 169.9, 165.3, 143.1, 138.3, 137.1, 133.0, 132.5, 131.3,
130.0, 129.1, 127.8, 125.5, 124.5, 120.3, 118.8, 106.8, 60.8, 37.6,
31.9, 31.6, 17.0; LRMS (EI) m/z 330 (Mþ); HRMS (EI) m/z
calcd C21H18N2O2 (Mþ) 330.1368, found 330.1369.
14,16b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c][1,4]-
diazepine-4,10(2H,16bH)-dione (3Cc):1HNMR(CDCl3, 300MHz)
δ 8.60 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 8.1 Hz, 1H), 7.60 (t, 1H),
7.46 (t, 1H), 7.29-7.31 (m, 2H), 7.18 (d, J = 9.0 Hz, 1H), 6.42 (s,
1H), 2.71-2.76(m, 1H), 2.54-2.63 (m, 2H), 2.45 (s, 3H), 2.16-2.25
(m, 1H), 1.91-2.11 (s, 2H), 1.33 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 169.9, 165.0, 143.1, 137.1, 136.5, 134.2, 132.9, 132.5, 131.4,
130.0, 129.3, 127.8, 126.7, 120.2, 118.5, 106.7, 60.8, 37.6, 31.8, 31.5,
21.3, 17.0; LRMS (EI) m/z 344 (Mþ); HRMS (EI) m/z calcd
C22H20N2O2 (Mþ) 344.1525, found 344.1521.
13,16b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c][1,4]-
diazepine-4,10(2H,16bH)-dione (3Dc):1HNMR(CDCl3,300MHz)
δ 8.60 (s, 1H), 8.20 (d, J = 7.8 Hz, 1H), 7.60 (t, 1H), 7.47 (t, 1H),
7.39 (d, J = 7.5, 1H), 7.29 (d, J = 7.8, 1H), 7.15 (d, J = 8.1, 1H),
6.45 (s, 1H), 2.54-2.75 (m, 3H), 2.52(s, 3H), 2.15-2.26 (m, 1H),
2.08-2.11 (m, 1H), 1.89-1.94 (m, 1H), 1.33 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 169.9, 165.3, 142.4, 138.7, 137.1, 135.5, 132.9,
132.4, 131.4, 129.9, 127.8, 126.7, 125.8, 119.8, 119.1, 106.8, 60.8, 37.6,
31.8, 31.6, 22.1, 17.0; LRMS (EI) m/z 344 (Mþ); HRMS (EI) m/z
calcd C22H20N2O2 (Mþ) 344.1525, found 344.1529.
14-Methoxyl-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Ec): 1H NMR (CDCl3,
300 MHz) δ 8.64 (d, J = 8.1 Hz, 1H), 8.21 (d, J = 7.8 Hz,
1H), 7.60 (t, 1H), 7.46 (t, 1H), 7.29 (d, J = 7.8 Hz, 1H), 6.95-
6.99 (m, 2H), 6.43 (s, 1H), 3.87 (s, 3H), 2.56-2.76 (m, 3H),
1.91-2.26 (m, 3H), 1.33 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
169.9, 156.9, 143.7, 137.1, 132.9, 132.5, 131.3, 130.1, 130.0,
127.8, 119.7, 113.2, 106.7, 103.4, 60.7, 55.6, 37.5, 31.8, 31.5,
17.0; LRMS (EI) m/z 360 (Mþ); HRMS (EI) m/z calcd C22H20-
N2O3 (Mþ) 360.1474, found 360.1478.
14-Cyano-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Fc): 1H NMR (CDCl3,
300 MHz) δ 8.84 (d, J = 9.0 Hz, 1H), 8.19 (d, J = 8.1 Hz,
1H), 7.85 (s, 1H), 7.64 (d, J = 9.3 Hz, 2H), 7.51 (t, 1H), 7.32 (d,
J = 8.1 Hz, 1H), 6.55 (s, 1H), 2.74-2.76 (m, 1H), 2.57-2.66 (m,
2H), 2.20-2.24 (m, 1H), 1.96-2.00 (m, 2H), 1.31 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 169.8, 165.4, 145.7, 140.2, 137.3,
133.6, 132.7, 130.7, 130.2, 129.2, 128.5, 128.1, 124.8, 119.6,
119.4, 107.8, 105.9, 60.7, 37.5, 31.8, 31.4, 17.0; LRMS (EI)
m/z 355 (Mþ); HRMS (EI) m/z calcd C22H17N3O2 (Mþ) 355.1321,
found 355.1316.
2-Hexyl-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Ab-1): H NMR (CDCl3,
1
300 MHz) δ 8.59 (t, 2H), 7.60-7.67 (m, 2H), 7.54 (d, J = 6.6 Hz,
1H), 7.42-7.48 (m, 1H), 7.27-7.39 (m, 1H), 6.58 (s, 1H), 3.10
(q, 1H), 2.67-2.70 (m, 2H), 2.05-2.07 (m, 1H), 1.94 (t, 1H),
1.25-1.55 (m, 12H), 0.92 (t, 3H); 13C NMR (CDCl3, 100 MHz)
δ 174.1, 164.0, 140.7, 138.8, 134.8, 134.0, 133.7, 128.9, 127.3,
126.6, 126.5, 125.3, 124.4, 120.5, 118.1, 104.8, 60.1, 41.2, 40.8,
31.7, 30.3, 29.3, 27.7, 27.2, 22.6, 14.1; LRMS (EI) m/z 400 (Mþ);
HRMS (EI) m/z calcd C26H28N2O2 (Mþ) 400.2151, found
400.2143.
2-Hexyl-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo[2,1-c]-
[1,4]diazepine-3,9(2H,15bH)-dione (3Ab-2): H NMR (CDCl3,
1
300 MHz) δ 8.67 (d, J = 8.4 Hz, 1H), 8.41 (d, J = 7.8 Hz, 1H),
7.64-7.67 (m, 2H), 7.54 (d, J = 7.5 Hz, 1H), 7.42-7.48 (m, 1H),
7.32-7.40 (m, 2H), 6.61 (s, 1H), 2.73-2.78 (m, 2H), 2.53-2.59
(m, 1H), 1.72-1.76 (m, 1H), 1.51 (s, 3H), 1.39-1.45 (m, 3H),
1.24-1.30 (m, 6H), 0.86 (t, 3H); 13C NMR (CDCl3, 100 MHz) δ
175.7, 164.7, 143.7, 138.4, 134.3, 133.7, 133.2, 128.9, 128.3,
127.2, 127.0, 125.3, 124.4, 120.3, 118.4, 106.7, 62.4, 42.0, 40.4,
31.5, 30.6, 28.8, 28.7, 27.6, 22.5, 14.0; LRMS (EI) m/z 400 (Mþ);
HRMS (EI) m/z calcd C26H28N2O2 (Mþ) 400.2151, found
400.2143.
2-Hexyl-13-fluoro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo-
[2,1-c][1,4]diazepine-3,9(2H,15bH)-dione (3Gb-1):1HNMR(CDCl3,
300 MHz) δ 8.51-8.60 (m, 2H), 7.60-7.68 (m, 2H), 7.45 (t, 1H),
7.18 (dd, J = 8.4, 2.4 Hz, 1H), 7.04-7.17 (m, 1H), 6.55 (s, 1H),
3.05-3.12 (q, 1H), 2.68-2.70 (m, 1H), 1.89-2.26 (m, 2H), 1.48 (s,
3H), 1.25-1.44 (m, 9H), 0.86-0.93 (m, 3H);13CNMR (CDCl3, 100
MHz) δ 174.1, 163.8, 159.9 (d, J = 240.3 Hz), 148.9, 142.3, 135.0,
134.8, 134.2, 133.7, 130.0, 127.4, 126.7, 126.3, 119.4 (d, J = 9.0 Hz),
112.8 (d, J = 24.5 Hz), 106.0 (d, J = 23.8 Hz), 104.4, 60.1, 41.2, 40.8,
31.7, 30.3, 29.3, 27.7, 27.2, 22.6; LRMS (EI) m/z 418 (Mþ); HRMS
(EI) m/z calcd C26H27FN2O2 (Mþ) 418.2057, found 418.2058.
2-Hexyl-13-fluoro-15b-methyl-1H-benzo[e]indolo[1,2-a]pyrrolo-
[2,1-c][1,4]diazepine-3,9(2H,15bH)-dione (3Gb-2):1HNMR(CDCl3,
300 MHz) δ8.59-8.61 (m, 1H), 8.39 (d, J = 7.5 Hz, 1H), 7.63-7.67
(m, 2H), 7.45 (t, 1H), 7.07-7.19 (m, 2H), 6.56 (s, 1H), 2.69-2.75(m,
2H), 2.52-2.58 (m, 1H), 1.69 (m, 1H), 1.49 (s, 3H), 1.21-1.45 (m,
9H), 0.81-0.88 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ 175.7,
164.5, 160.0, 145.4, 134.7, 134.4, 133.9, 133.3, 130.0, 128.1, 127.3,
14-Fluoro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Gc): 1H NMR (CDCl3,
300 MHz) δ 8.68-8.73 (q, 1H), 8.20 (d, J = 7.8 Hz, 1H), 7.62
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(t, 1H), 7.47 (t, 1H), 7.30 (d, J = 7.5 Hz, 1H), 7.05-7.18 (m, 2H),
6.46 (s, 1H), 2.56-2.76 (m, 3H), 2.17-2.27 (m, 1H), 2.04-2.09
(m, 1H), 1.92-1.97 (m, 1H), 1.34 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 169.8, 165.0, 160.0, 144.7, 137.1, 134.6, 133.1, 132.5,
131.0, 130.2, 130.0, 127.9, 120.0 (d, J = 8.2 Hz), 112.8 (d, J =
24.2 Hz), 106.3, 105.8 (d, J = 23.7 Hz), 60.7, 37.5, 31.8, 31.4,
17.0; LRMS (EI) m/z 348 (Mþ); HRMS (EI) m/z calcd
C21H17FN2O2 (Mþ) 348.12741, found 348.1279.
14-Chloro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Hc): 1H NMR (CDCl3,
300 MHz) δ 8.67 (d, J = 9.0 Hz, 1H), 8.19 (d, J = 8.1 Hz, 1H),
7.60 (t, 1H), 7.47 (t, 2H), 7.29-7.35 (m, 2H), 6.44 (s, 1H),
2.56-2.76 (m, 3H), 2.17-2.24 (m, 1H), 1.95-2.04 (m, 2H), 1.34
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ 169.8, 165.1, 144.5,
137.1, 136.6, 133.2, 132.5, 131.0, 130.3, 130.0, 129.9, 127.9,
125.4, 119.8, 105.9, 60.7, 37.5, 31.8, 31.4, 17.0; LRMS (EI)
m/z 364 (Mþ); HRMS (EI) m/z calcd C21H17ClN2O2 (Mþ)
364.0979, found 364.0977.
8,16b-Dimethyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c][1,4]dia-
zepine-4,10(2H,16bH)-dione (3Ic): 1H NMR (CDCl3, 300 MHz)
δ 8.73 (d, J = 8.1 Hz, 1H), 8.00 (s, 1H), 7.52 (d, J = 7.8 Hz 1H),
7.28-7.42 (m, 3H), 7.19 (d, J = 8.1 Hz 1H), 6.49 (s, 1H), 2.72-
2.77 (m, 1H), 2.54-2.62 (m, 2H), 2.44 (s, 3H), 2.16-2.25 (m,
1H), 2.05-2.10 (m, 1H), 1.89-1.94 (m, 1H), 1.35 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 170.0, 165.5, 143.2, 138.3, 137.8,
134.5, 134.0, 132.6, 130.9, 129.7, 129.0, 125.4, 124.4, 120.2,
118.8, 106.8, 60.7, 37.6, 31.9, 31.5, 21.0, 17.0; LRMS (EI) m/z
344 (Mþ); HRMS (EI) m/z calcd C22H20N2O2 (Mþ) 344.1525,
found 344.1522.
8,14,16b-Trimethyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Jc): 1H NMR (CDCl3,
300 MHz) δ 8.59 (d, J = 8.4 Hz, 1H), 8.00 (s, 1H), 7.40 (d,
J = 8.1 Hz, 1H), 7.29 (s, 1H), 7.16-7.21 (m, 2H), 6.41 (s, 1H),
2.53-2.75 (m, 3H), 2.45 (s, 3H), 2.44 (s, 3H), 2.15-2.24 (m, 1H),
2.03-2.08 (m, 1H), 1.86-1.92 (m, 1H), 1.34 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 170.0, 165.2, 143.2, 137.8, 136.5, 134.5,
134.1, 133.9, 132.6, 131.0, 129.7, 129.3, 126.6, 120.2, 118.4,
106.6, 60.7, 37.6, 31.9, 31.5, 21.3, 21.0, 17.0; LRMS (EI) m/z
358 (Mþ); HRMS (EI) m/z calcd C23H22N2O2 (Mþ) 358.1681,
found 358.1685.
J = 23.6 Hz), 106.8, 106.1 (d, J = 23.7 Hz), 60.7, 37.3, 31.8, 31.5,
17.0; LRMS (EI) m/z 382 (Mþ); HRMS (EI) m/z calcd C21H16-
ClFN2O2 (Mþ) 382.0884, found 382.0878.
8,14-Dichloro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Pc): 1H NMR (CDCl3,
300 MHz) δ 8.63 (d, J = 8.7 Hz, 1H), 8.20 (d, J = 2.4 Hz,
1H), 7.56 (dd, J = 8.4 Hz, 1.8 Hz, 1H), 7.48 (d, J = 2.1 Hz, 1H),
7.33 (dd, J = 9.3 Hz, 1.8 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 6.45
(s, 1H), 2.57-2.77 (m, 3H), 2.11-2.22 (m, 1H), 1.94-2.02 (m,
2H), 1.37 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 169.9, 163.7,
144.1, 136.6, 135.7, 133.8, 133.3, 132.2, 131.6, 130.3, 130.2, 125.7,
120.0, 119.9, 106.3, 60.7, 37.3, 31.8, 31.5, 29.7, 16.9; LRMS (EI)
m/z 398 (Mþ); HRMS (EI) m/z calcd C21H16Cl2N2O2 (Mþ)
398.0589, found 398.0589.
8-Fluoro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Qc): 1H NMR (CDCl3,
300 MHz) δ 8.71 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H),
7.51 (d, J = 7.2 Hz, 1H), 7.36-7.43 (m, 1H), 7.28-7.36 (m, 3H),
6.51 (s, 1H), 2.73-2.79 (m, 1H), 2.55-2.64 (m, 2H), 2.17-2.27
(m, 1H), 2.07-2.12 (m, 1H), 1.91-1.97 (m, 1H), 1.37 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ 170.0, 163.9, 161.4 (d, J = 246.0
Hz), 142.9, 138.3, 133.2, 133.0, 132.0 (d, J = 8.2 Hz), 129.1,
125.6, 124.8, 120.5 (d, J = 23.7 Hz), 120.4, 118.8, 118.6 (d, J =
24.6 Hz), 107.3, 60.8, 37.5, 31.8, 31.6, 17.0; LRMS (EI) m/z 348
(Mþ); HRMS (EI) m/z calcd C21H17FN2O2 (Mþ) 348.1274,
found 348.1276.
8-Fluoro-14-chloro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido-
[2,1-c][1,4]diazepine-4,10(2H,16bH)-dione (3Rc):1HNMR(CDCl3,
300 MHz) δ 8.63 (d, J = 9.0 Hz, 1H), 7.89 (dd, J = 9.3 Hz, 2.4 Hz,
1H), 7.47 (d, J = 1.8 Hz, 1H), 7.29-7.35 (m, 3H), 6.45 (s, 1H),
2.71-2.77 (m, 1H), 2.55-2.64 (m, 2H), 2.17-2.26 (m, 1H), 2.00-
2.05 (m, 1H), 1.92-1.97 (m, 1H), 1.37 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ 170.0, 163.7, 161.3 (d, J = 246.8 Hz), 144.2, 136.6,
133.2, 132.6 (d, J = 7.7 Hz), 132.0 (d, J = 8.2 Hz), 130.3, 130.1,
125.6, 120.7 (d, J = 22.8 Hz), 120.0, 119.9, 118.6 (d, J = 24.6 Hz),
106.3, 60.7, 37.4, 31.8, 31.4, 16.9; LRMS (EI) m/z 382 (Mþ);
HRMS (EI) m/z calcd C21H16ClFN2O2 (Mþ) 382.0884, found
382.0885.
15,16b-Dimethyl-1H-benzo[e][1,4]oxazino[3,4-c]indolo[1,2-a]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Bd): 1H NMR (CDCl3,
300 MHz) δ 8.55 (d, J = 8.4 Hz, 1H), 8.35 (d, J = 8.1 Hz,
1H), 7.64 (t, 1H), 7.50 (t, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.31 (d,
J = 7.5 Hz, 1H), 7.13 (d, J = 7.5 Hz, 1H), 6.67 (s, 1H), 4.66 (d,
J = 12.0 Hz, 1H), 4.48 (d, J = 16.5 Hz, 1H), 4.35 (d, J = 16.8
8-Chloro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Mc): H NMR (CDCl3,
1
300 MHz) δ 8.70 (d, J = 7.8 Hz, 1H), 8.21 (d, J = 2.4 Hz, 1H),
7.50-7.58 (m, 2H), 7.30-7.43 (m, 2H), 7.27 (d, J = 8.4 Hz, 1H),
6.51 (s, 1H), 2.55-2.78 (m, 3H), 2.16-2.26 (m, 1H), 1.93-2.13
(m, 2H), 1.37 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 169.9,
163.8, 142.7, 138.3, 135.7, 133.7, 133.1, 132.5, 132.2, 131.5,
129.0, 125.7, 124.8, 120.4, 118.8, 107.3, 60.7, 37.4, 31.8, 31.6,
17.0; LRMS (EI) m/z 364 (Mþ); HRMS (EI) m/z calcd
C21H17ClN2O2 (Mþ) 364.0979, found 364.0975.
8-Chloro-14,16b-dimethyl-1H-benzo[e]indolo[1,2-a]pyrido[2,1-c]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Nc): 1H NMR (CDCl3,
300 MHz) δ 8.57 (d, J = 8.7 Hz, 1H), 8.21 (d, J = 1.8 Hz, 1H),
7.54 (dd, J = 8.4 Hz, 2.7 Hz, 1H), 7.28 (d, J = 9.3 Hz, 1H), 7.22
(t, 2H), 6.43 (s, 1H), 2.54-2.77 (m, 3H), 2.45 (s, 3H), 2.15-2.21
(m, 1H), 1.91-2.05 (m, 2H), 1.36 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 169.9, 163.6, 142.6, 136.5, 135.7, 134.5, 133.6, 133.0,
132.6, 132.2, 131.5, 129.2, 126.9, 120.4, 118.5, 107.1, 60.7, 37.4,
31.8, 31.5, 21.3, 16.9; LRMS (EI) m/z 378 (Mþ); HRMS (EI) m/z
calcd C22H19ClN2O2 (Mþ) 378.1135, found 378.1136.
8-Chloro-14-fluoro-16b-methyl-1H-benzo[e]indolo[1,2-a]pyrido-
[2,1-c][1,4]diazepine-4,10(2H, 16bH)-dione (3Oc):1HNMR(CDCl3,
300 MHz) δ 8.67 (q, 1H), 8.20 (d, J = 2.7 Hz, 1H), 7.56 (dd, J = 8.7
Hz, 2.4 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 7.06-7.18 (m, 2H), 6.47 (s,
1H), 2.72-2.77 (m, 1H), 2.57-2.64 (m, 2H), 2.17-2.26 (m, 1H),
1.92-2.06 (m, 2H), 1.37 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
169.9, 163.6, 160.1 (d, J = 241.0 Hz), 144.3, 135.7, 134.6, 133.8,
133.2, 132.3, 132.2, 131.5, 130.1, 120.1 (d, J = 8.7 Hz), 113.1 (d,
Hz, 1H), 4.06 (d, J = 12.3 Hz, 1H), 2.54 (s, 3H), 1.28 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ 165.8, 164.3, 139.4, 138.3, 134.6,
133.2, 133.1, 130.6, 130.0, 129.3, 128.5, 128.1, 125.7, 125.2, 116.1,
105.9, 73.1, 68.0, 59.4, 24.9, 18.4; LRMS (EI) m/z 346 (Mþ);
HRMS (EI) m/zcalcd C21H18N2O3 (Mþ) 346.1317, found 346.1315.
14-Fluoro-16b-methyl-1H-benzo[e][1,4]oxazino[3,4-c]indolo-
[1,2-a][1,4]diazepine-4,10(2H, 16bH)-dione (3Gd): 1H NMR
(CDCl3, 300 MHz) δ 8.67-8.72 (q, 1H), 8.36 (d, J = 6.9 Hz,
1H), 7.64 (t, 1H), 7.52 (t, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.19 (dd,
J = 8.4 Hz, 2.7 Hz, 1H), 7.10 (td, 1H), 6.60 (s, 1H), 4.63 (d, J =
12.3 Hz, 1H), 4.48 (d, J = 17.1 Hz, 1H), 4.36 (d, J = 16.8 Hz,
1H), 4.06 (d, J = 12.6 Hz, 1H), 1.26 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ 165.7, 164.0, 160.0, 141.6, 135.0, 134.6, 133.5, 133.2,
130.1, 129.4, 128.2, 119.9 (d, J = 8.6 Hz), 113.1 (d, J = 24.1 Hz),
107.0, 106.3 (d, J = 24.2 Hz), 73.0, 68.0, 59.3, 24.7; LRMS
(EI) m/z 350 (Mþ); HRMS (EI) m/z calcd C20H15FN2O3 (Mþ)
350.1067, found 350.1067.
8,16b-Dimethyl-1H-benzo[e][1,4]oxazino[3,4-c]indolo[1,2-a]-
[1,4]diazepine-4,10(2H,16bH)-dione (3Id): 1H NMR (CDCl3,
300 MHz) δ 8.72 (d, J = 7.8 Hz, 1H), 8.15 (s, 1H), 7.54 (d, J =
7.8 Hz, 1H), 7.26-7.44 (m, 4H), 6.63 (s, 1H), 4.62 (d, J = 12.6
Hz, 1H), 4.46 (d, J = 17.4 Hz, 1H), 4.33 (d, J = 17.1 Hz, 1H),
4.04 (d, J = 12.6 Hz, 1H), 2.47 (s, 3H), 1.30 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 165.8, 164.5, 140.1, 138.5, 138.3, 134.3,
1248 J. Org. Chem. Vol. 76, No. 5, 2011

Zhou et al.
JOCArticle
S&T Major Projects (2009ZX09301-001, 2009ZX09501-001,
and 2009ZX09501-010).
133.2, 132.0, 130.0, 129.1, 129.0, 125.6, 124.6, 120.7, 118.6, 107.4,
73.1, 68.0, 59.3, 24.8, 21.0; LRMS(EI) m/z 346 (Mþ); HRMS (EI)
m/z calcd C21H18N2O3 (Mþ) 346.1317, found 346.1319.
Supporting Information Available: 1H and 13C NMR spec-
tra for all compounds and crystallographic data for compound
3Ba. This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. We gratefully acknowledge financial
support from the National Natural Science Foundation of
China (Grants 20721003, 20872153, and 81025017), National
J. Org. Chem. Vol. 76, No. 5, 2011 1249