Convenient synthesis of a library of lactam-fused β-carbolines via the Ugi reaction

Article abstract of DOI:10.1055/s-0030-1258374

We present a convenient synthesis of a chemical library of lactam-fused β-carbolines via a Ugi four-center three-component reaction employing [1-formyl-3-(methoxycarbonyl)-9H-pyrido[3,4-b]indol-9-yl]acetic acid or (1-formyl-9H-pyrido[3,4-b]indol-9-yl)acet

Full text of DOI:10.1055/s-0030-1258374

PAPER
419
Convenient Synthesis of a Library of Lactam-Fused b-Carbolines via the Ugi
Reaction1
Samiran Hutait, Maloy Nayak, Ashok Penta,2 Sanjay Batra*
Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), PO Box 173, Lucknow 226 001, India
Fax +91(522)2623405; fax +91(522)2623938; E-mail: batra_san@yahoo.co.uk
Received 2 November 2010
Dedicated to Dr. Vijay Nair on the occasion of his 70th birthday
corporating an aldehyde and an acid group for the syn-
Abstract: We present a convenient synthesis of a chemical library
thesis of a variety of lactams via this route.6 Ivachtchenko
of lactam-fused b-carbolines via a Ugi four-center three-component
and co-workers elegantly exploited this protocol for the
reaction employing [1-formyl-3-(methoxycarbonyl)-9H-pyri-
synthesis of an array of annulated systems.7 More
do[3,4-b]indol-9-yl]acetic acid or (1-formyl-9H-pyrido[3,4-b]in-
dol-9-yl)acetic acid, amines and isonitriles.
recently, adopting a similar approach, Ghandi and co-
workers reported the synthesis of 3-oxo-1,2,3,4-tetrahy-
dropyrazino[1,2-a]benzimidazole-1-carboxamides.8 Tak-
ing a cue from these reports, we decided to investigate the
potential of a b-carboline-based bifunctional substrate for
the Ugi reaction. In principle, installing an acetic acid sub-
unit at N-9 of 1-formyl-9H-b-carboline would offer a sub-
strate which could serve as a reactant in the Ugi reaction
to produce new annulated b-carbolines. Such lactam-
fused b-carbolines have not been previously reported in
the literature.
Key words: Ugi reaction, multicomponent reactions, b-carbolines
The b-carboline scaffold represents a core unit of several
alkaloids and pharmaceutical agents. In particular, the an-
nulated b-carboline-containing compounds and natural
products are of high medicinal importance as these ana-
logues are known to display a number of bioactivities
such as antimicrobial, antifungal, antiparasitic and anti-
cancer activity.3 In our project related to the development
of general protocols for accessing annulated b-carbolines
from 1-formyl-9H-b-carboline, we have reported the syn-
thesis of canthines, canthin-6-ones, homofascaplysin,
harmicine mimics and several b-carboline-fused hetero-
cycles using Morita–Baylis–Hillman (MBH), cycloaddi-
tion, carbonyl–ene or RCM-based approaches.4 In a
continuation of our studies under the program, we now re-
port the synthesis of new lactam-fused b-carbolines via an
isonitrile-based multicomponent reaction (IMCR) em-
ploying [1-formyl-3-(methoxycarbonyl)-9H-pyrido[3,4-
b]indol-9-yl]acetic acid and (1-formyl-9H-pyrido[3,4-
b]indol-9-yl)acetic acid as the bifunctional starting mate-
rials.
The synthesis of the key bifunctional b-carbolines 5 and 8
was accomplished from 1 and 2, respectively, as outlined
in Scheme 1. Initially, the aldehyde 3 that was obtained
from the acetal 1 was subjected to a substitution reaction
with tert-butyl bromoacetate to furnish 4. Trifluoroacetic
acid promoted chemoselective hydrolysis of the tert-butyl
ester group in 4 afforded the required starting material 5.
At this stage, it occurred to us to first carry out the substi-
tution reaction of 1 with tert-butyl bromoacetate and then
perform the acid hydrolysis to generate 5 as this would re-
duce the number of steps involved for the synthesis of 5.
Accordingly, acetal 1 was treated with tert-butyl bro-
moacetate in the presence of cesium carbonate to give di-
ester 6 in more than 95% yield. Trifluoroacetic acid
promoted hydrolysis of the tert-butyl ester coupled with
unmasking of the acetal in 6 afforded the required alde-
hyde–acid substrate 5 in 84% yield. Likewise, treatment
of acetal 2 with tert-butyl bromoacetate gave ester 7
which on treatment with trifluoroacetic acid afforded the
required material 8 in 81% yield.
Over the last several years, multicomponent reactions
(MCRs) including IMCRs have become increasingly im-
portant in organic and medicinal chemistry because they
allow the synthesis of highly sophisticated polyfunctional
molecules with a wide structural and functional diversity
combined with excellent combinatorial efficacy.5 Among
IMCRs, the modified Ugi four-center three-component
reaction (U-4C-3CR) based on the use of bifunctional
components has been a popular strategy for obtaining six-
and seven-membered fused heterocycles. Amidst such bi-
functional substrates, prototypes incorporating an acid
and an aldehyde or keto group are reported to be highly
successful. Zhang and co-workers demonstrated the utili-
ty of several commercially available starting materials in-
The optimization study for determining the reaction con-
ditions for the Ugi reaction was initiated with 5. Com-
pound 5 was treated with commercially available 4-
tolylsulfonylmethyl isocyanide (TosMIC) and aniline in
methanol at room temperature (Scheme 2; R2 = Ph,
R3 = 4-Ts). It was satisfying to observe that the reaction
was complete in 12 hours and was typically characterized
by the separation of a solid product in the reaction mix-
ture. Isolation and spectroscopic characterization of the
separated solid indicated it to be the desired lactam-annu-
lated carboline 5Ja. This result provoked us to investigate
SYNTHESIS 2011, No. 3, pp 0419–0430
x
x
.
x
x
.2
0
1
1
Advanced online publication: 20.12.2010
DOI: 10.1055/s-0030-1258374; Art ID: P16410SS
© Georg Thieme Verlag Stuttgart · New York

420
S. Hutait et al.
PAPER
R
R
N
R
N
N
i
ii
83%
87%
N
H
N
N
CHO
OMe
CHO
H
MeO
3 R = CO2Me
t-BuO2C
1 R = CO2Me
2 R = H
4 R = CO2Me
iii 71%
ii 93–95%
R
R
N
N
iv
81–84%
N
N
OMe
CHO
MeO
t-BuO2C
HO2C
6 R = CO2Me
7 R = H
5 R = CO2Me
8 R = H
Scheme 1 Reagents and conditions: (i) AcOH–H2O (2:3, v/v), 100 °C, 45 min; (ii) BrCH2CO2t-Bu, Cs2CO3, anhyd DMF, r.t., 45 min; (iii)
TFA–H2O (100:1, v/v), r.t., 12 h; (iv) TFA–H2O (100:1, v/v), 90 °C, 1.5 h.
this strategy for the synthesis of a chemical library of lac-
tam-fused carbolines. Aiming at this objective, we per-
formed reactions of 5 and 8 with TosMIC and several
amines (Figure 1) in parallel fashion. Gratifyingly, in all
(1-formyl-9H-pyrido[3,4-b]indol-9-yl)acetic acids
CO2Me
reactions solids separated out, which were collected by
N
N
filtration and washed with cold methanol to afford the an-
alytically pure products 5Aa–5La, 8Aa, 8Ea and 8La in
moderate to good yields. Product which was dissolved in
the methanol during filtration was easily retrieved via pro-
cessing of the filtrate followed by purification via short-
column chromatography. In general, it was observed that
75–80% of the isolated yield of each product was obtained
via filtration, while the remaining 20–25% of the product
was recovered from the filtrate. It was found that the best
yields of the products were isolated when anilines or ben-
zylamine was employed as the amine component. Methyl
glycinate (HCl salt neutralized with Et3N before addition)
and 3-aminopropanol gave the products in moderate
yields only, whereas yields of products from other amines
ranged between the two limits.
N
N
O
O
HO
HO
O
O
5
8
amines
NH2
NH2
NH2
NH2
A
B
C
D
NH2 HO
NH2
NH2
MeO2C
NH2
O
NH2
E
G
F
H
I
NH2
Cl
NH2
MeO
NH2
Next, to expand the structural diversity accessible via the
developed approach, reactions with alternative isonitriles
were investigated. One of the isonitriles was generated
from a glycine ester, whereas the other isonitriles were ob-
tained from the allylamines synthesized from the MBH
adducts, as reported earlier9 (Figure 1). The double bond
stereochemistry of the isonitriles c and d was Z, whereas
J
L
K
isonitriles
NC
O
S
O
CN
EtO2C
NC
NC
R1
R1
b
c
R2 NH2
+
N
N
i
a
+
HN
O
N
Cl
55–78%
R3
N
R3
NC
NC
CN
O
N
NC
HO
R2
CO2Me
O
O
Cl
5 R1 = CO2Me
e
d
8 R1 = H
Figure 1 Diversity elements
Scheme 2 Reagents and conditions: (i) MeOH, r.t., 3–12 h.
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

PAPER
Synthesis of a Library of Lactam-Fused b-Carbolines
421
that of e was E. Accordingly, 5 and 8 were treated with three to four hours to yield the required products as solids,
several amines and these alternative isonitriles in parallel which were isolated by simple filtration. Similar to earlier
format. It was pleasing to discover that, in contrast to observations, here, too, the anilines and benzylamine gave
TosMIC, reactions with these isonitriles were complete in the products in best yields. The various products generat-
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
N
N
N
N
N
HN
O
HN
O
HN
O
HN
O
HN
O
N
O
N
O
N
N
O
S
O
N
S
S
S
S
O
O
O
O
O
O
N
N
N
N
N
O
O
O
O
Ph
O
Ph
O
5Aa (57%)
CO2Me
5Ba (64%)
CO2Me
5Ca (75%)
5Da (75%)
CO2Me
5Ea (72%)
CO2Me
CO2Me
N
N
N
N
N
H
N
N
HN
O
HN
HN
O
HN
O
N
N
N
O
N
O
O
O
S
S
O
S
S
S
O
O
O
O
N
O
O
N
N
O
N
N
Ph
O
O
O
O
O
5Ha (55%)
MeO2C
OH
5Fa (63%)
5Ga (68%)
5Ia (56%)
5Ja (70%)
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
N
N
N
N
N
N
N
HN
CO2Et
H
N
H
N
HN
HN
N
N
CO2Et
CO2Et
O
O
O
N
N
N
S
S
O
O
N
N
O
O
O
O
N
O
O
O
O
O
Ph
5Ka (62%)
5La (76%)
5Ab (65%)
5Bb (76%)
5Cb (78%)
Cl
OMe
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
N
N
N
N
N
N
HN
Ph
HN
HN
HN
CO2Et
HN
CO2Et
CO2Et
CO2Et
CO2Et
N
N
N
N
O
N
O
O
O
O
N
N
N
N
O
O
O
O
O
CO2Me
O
5Db (77%)
5Eb (76%)
5Fb (67%)
5Gb (73%)
5Ib (61%)
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
N
N
N
N
N
N
N
HN
HN
HN
O
HN
O
CO2Et
CO2Et
CO2Et
N
N
N
N
N
Ph
O
O
O
N
H
NC
N
N
N
Ph
Ph
NC
O
5Cc (75%)
O
5Jb (75%)
O
O
O
Cl
OMe
Ph
5Kb (64%)
5Lb (76%)
5Bc (78%)
CO2Me
CO2Me
CO2Me
CO2Me
N
N
N
N
O
N
O
O
O
N
Ph
N
N
N
Cl
N
H
N
H
N
H
Ph
HN
N
N
N
CN
CN
Cl
Cl
NC
O
O
O
O
Ph
NC
Cl
5Dc (78%)
5Lc (77%)
OMe
5Ad (72%)
5Bd (74%)
CO2Me
CO2Me
N
N
N
N
N
HN
HN
O
H
O
N
N
O
O
N
N
O
S
S
N
Ph
O
O
O
O
N
N
N
S
N
N
O
O
HN
N
H
N
O
O
O
Cl
MeO2C
O
O
NC
O
OMe
5Fd (71%)
5Be (77%)
8Aa (61%)
8Ea (69%)
8La (74%)
Cl
N
N
N
N
HN
Ph
HN
HN
CO2Et
HN
CO2Et
CO2Et
CO2Et
N
N
N
O
N
O
O
O
N
N
N
N
O
O
O
O
8Bb (72%)
8Cb (73%)
8Db (78%)
8Lb (76%)
Ph
OMe
Figure 2 Structures of the isolated products (% yields)
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

422
S. Hutait et al.
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13C NMR (50 MHz, CDCl3): d = 27.9, 49.3, 52.9, 82.7, 110.2,
120.7, 121.1, 121.6, 122.1, 130.0, 133.2, 136.9, 137.3, 143.0, 165.5,
167.3, 193.8.
ed during the present study along with the isolated yields
are illustrated in Figure 2. These results show that this ap-
proach is general and works well with a wide range of sub-
strates.
MS (ES+): m/z = 369.1 [M+ + 1].
Anal. Calcd for C20H20N2O5 (368.1372): C, 65.21; H, 5.47; N, 7.60.
Found: C, 65.05; H, 5.32; N, 7.76.
In conclusion, a small library of lactam-fused b-carbo-
lines was prepared by using a b-carboline-based bifunc-
tional scaffold, which can be readily produced from 1-
formyl-9H-b-carboline. The simplicity of the synthetic
protocol and ready availability of diverse starting materi-
als make this an attractive strategy for obtaining new b-
carboline-fused prototypes via combinatorial techniques.
tert-Butyl [1-(Dimethoxymethyl)-b-carbolin-9-yl]acetate (7)
White solid; yield: 5.72 g (93%); mp 130–131 °C; Rf = 0.36 (hex-
anes–EtOAc, 75:25).
IR (KBr): 1756 (CO2t-Bu) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.43 (s, 9 H, 3 × CH3), 3.47 (s, 6
H, 2 × OCH3), 5.48 (s, 2 H, NCH2), 5.61 (s, 1 H, CH), 7.28–7.34 (m,
2 H, ArH), 7.60 (t, J = 8.1 Hz, 1 H, ArH), 8.01 (d, J = 5.2 Hz, 1 H,
ArH), 8.13 (d, J = 7.8 Hz, 1 H, ArH), 8.39 (d, J = 5.1 Hz, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 28.1, 48.3, 53.5, 55.7, 81.6, 109.8,
110.1, 115.6, 120.4, 121.4, 128.9, 131.6, 134.5, 137.0, 140.7, 142.7,
168.4.
Melting points were determined in capillary tubes on a Precision
hot-stage apparatus containing silicon oil and are uncorrected. IR
spectra were recorded using a Perkin Elmer RX 1 FTIR spectropho-
tometer. 1H and 13C NMR spectra were recorded on either a Bruker
300-MHz or a Bruker 200-MHz FT spectrometer, using TMS as an
internal standard (chemical shifts in d values, J in Hz). Mass spectra
were recorded as ES-MS or DART on Micromass Quattro-II or
JEOL-AccuTOF JMS-T100LC mass spectrometers, respectively.
The HRMS spectra were recorded as EI-HRMS on a JEOL system
or as DART-HRMS (recorded as ES+) on a JEOL-AccuTOF JMS-
T100LC mass spectrometer equipped with a DART (Direct Analy-
sis in Real Time) source. Elemental analyses were performed on a
Carlo Erba 1108 microanalyzer or an Elementar Vario EL III mi-
croanalyzer. Hexanes refers to the fraction with bp 65–70 °C. Due
to the poor solubility of compounds 5Ja, 5Ib and 8Lb, the corre-
sponding 13C NMR spectra could not be recorded.
MS (ES+): m/z = 357.1 [M+ + 1].
Anal. Calcd for C20H24N2O4 (356.1736): C, 67.40; H, 6.79; N, 7.86.
Found: C, 67.36; H, 6.74; N, 7.59.
[1-Formyl-3-(methoxycarbonyl)-9H-b-carbolin-9-yl]acetic
Acid (5); Typical Procedure
A mixture of acetal 6 (6.70 g, 16.2 mmol), TFA (75 mL) and H2O
(0.7 mL) was heated at 90 °C for 1.5 h. After completion of the re-
action, as monitored by TLC, the contents were poured into H2O
(300 mL) under stirring and left for 7 h. The separated solid was col-
lected by filtration and dried over P2O5 under reduced pressure to
afford 5 as a brown solid; yield: 4.25 g (84%).
Methyl 9-(tert-Butoxycarbonylmethyl)-1-(dimethoxymethyl)-
9H-b-carboline-3-carboxylate (6); Typical Procedure
Mp 143–145 °C; Rf = 0.12 (CHCl3–MeOH, 90:10).
To a stirred soln of acetal 1 (5.60 g, 18.6 mmol) in anhyd DMF (80
mL), Cs2CO3 (8.49 g, 26.1 mmol) was added at r.t. After 15 min,
tert-butyl bromoacetate (3.63 mL, 22.3 mmol) in anhyd DMF (10
mL) was added dropwise and the reaction was allowed to continue
for an additional 45 min at r.t. On completion of the reaction, as
monitored by TLC, the contents were poured into H2O (250 mL) un-
der stirring with a glass rod. The resulting solid was collected by fil-
tration and dried over P2O5 in a dessicator under reduced pressure
to obtain 6 as a yellowish white solid; yield: 7.35 g (95%).
IR (KBr): 1710 (CHO and CO2CH3), 3460 (CO2H) cm–1.
1H NMR (300 MHz, DMSO-d6): d = 3.99 (s, 3 H, OCH3), 5.63 (s, 2
H, NCH2), 7.47 (t, J = 7.3 Hz, 1 H, ArH), 7.68–7.84 (m, 2 H, ArH),
8.54 (d, J = 7.5 Hz, 1 H, ArH), 9.22 (s, 1 H, ArH), 10.14 (s, 1 H,
CHO).
13C NMR (50 MHz, DMSO-d6): d = 48.5, 52.6, 111.2, 120.5, 120.9,
122.1, 130.2, 132.6, 136.1, 136.8, 137.1, 142.9, 165.0, 170.2, 193.5.
MS (ES+): m/z = 313.2 [M+ + 1].
Mp 141–143 °C; Rf = 0.48 (hexanes–EtOAc, 75:25).
IR (KBr): 1713 (CO2CH3), 1750 (CO2t-Bu) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.42 (s, 9 H, 3 × CH3), 3.48 (s, 6
H, 2 × OCH3), 4.05 (s, 3 H, OCH3), 5.55 (s, 2 H, NCH2), 5.70 (s, 1
H, CH), 7.35–7.40 (m, 2 H, ArH), 7.64 (t, J = 7.2 Hz, 1 H, ArH),
8.20 (d, J = 7.8 Hz, 1 H, ArH), 8.91 (s, 1 H, ArH).
Anal. Calcd for C16H12N2O5 (312.0746): C, 61.54; H, 3.87; N, 8.97.
Found: C, 61.35; H, 3.96; N, 8.67.
(1-Formyl-9H-b-carbolin-9-yl)acetic Acid (8)
Brown solid; yield: 2.30 g (81%); mp 157–158 °C; Rf = 0.27
(CHCl3–MeOH, 90:10).
13C NMR (50 MHz, CDCl3): d = 28.2, 48.6, 52.8, 55.9, 81.8, 110.2,
110.4, 118.5, 121.2, 121.5, 121.7, 129.3, 131.6, 136.0, 141.1, 143.1,
166.5, 168.0.
IR (KBr): 1708 (CHO), 3071 (CO2H) cm–1.
1H NMR (300 MHz, DMSO-d6): d = 5.61 (s, 2 H, NCH2), 7.40 (t,
J = 7.2 Hz, 1 H, ArH), 7.66–7.77 (m, 2 H, ArH), 8.37 (d, J = 7.8 Hz,
1 H, ArH), 8.54 (d, J = 4.9 Hz, 1 H, ArH), 8.66 (d, J = 4.8 Hz, 1 H,
ArH), 10.13 (s, 1 H, CHO).
13C NMR (50 MHz, DMSO-d6): d = 48.2, 110.9, 119.4, 120.3,
121.2, 121.8, 129.6, 132.0, 135.2, 137.7, 138.8, 142.6, 170.3, 194.2.
MS (ES+): m/z = 415.0 [M+ + 1].
Anal. Calcd for C22H26N2O6 (414.1791): C, 63.76; H, 6.32; N, 6.76.
Found: C, 63.57; H, 6.42; N, 6.93.
Methyl 9-(tert-Butoxycarbonylmethyl)-1-formyl-9H-b-carbo-
line-3-carboxylate (4)
MS (ES+): m/z = 255 [M+ + 1].
Light yellow solid; yield: 0.40 g (87% from 3); mp 204–205 °C;
Rf = 0.47 (hexanes–EtOAc, 70:30).
Anal. Calcd for C14H10N2O3 (254.0691): C, 66.14; H, 3.96; N,
11.02. Found: C, 66.35; H, 4.02; N, 11.21.
IR (KBr): 1701 (CHO), 1748 (CO2CH3 and CO2t-Bu) cm–1.
[1-Formyl-3-(methoxycarbonyl)-9H-b-carbolin-9-yl]acetic
Acid (5) from Ester 4
A mixture of tert-butyl ester 4 (0.37 g, 1 mmol), TFA (14 mL) and
1H NMR (200 MHz, CDCl3): d = 1.43 (s, 9 H, 3 × CH3), 4.11 (s, 3
H, OCH3), 5.58 (s, 2 H, NCH2), 7.41–7.50 (m, 2 H, ArH), 7.71 (dt,
J = 1.1, 12.3 Hz, 1 H, ArH), 8.24 (d, J = 7.7 Hz, 1 H, ArH), 9.05 (s,
1 H, ArH), 10.32 (s, 1 H, CHO).
H2O (0.014 mL) was stirred at r.t. for 12 h. After completion of the
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

PAPER
Synthesis of a Library of Lactam-Fused b-Carbolines
423
reaction, as monitored by TLC, the contents were poured into H2O
(30 mL) under stirring and left for 1 h. The separated solid was col-
lected by filtration and dried over P2O5 under reduced pressure to
afford 5 as a brown solid; yield: 0.23 g (71%); mp 143–145 °C;
Rf = 0.12 (CHCl3–MeOH, 90:10).
Methyl 6-Oxo-5-(2-phenylethyl)-4-[(4-tolylsulfonylmethyl)car-
bamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluo-
rene-2-carboxylate (5Ca)
White solid; yield: 0.36 g (75%); mp 230–232 °C; Rf = 0.75 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1656 (CONH), 1690 (CON), 1736 (CO2CH3), 3468 (NH)
cm–1.
Methyl 6-Oxo-5-propyl-4-[(4-tolylsulfonylmethyl)carbamoyl]-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Aa); Typical Procedure for the Intramolecular Ugi
Reaction
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, CH3), 2.64–2.71 (m,
1 H, NCH2CHH), 2.79–2.88 (m, 1 H, NCH2CHH), 3.62–3.69 (m, 1
H, NCHHCH2), 3.81–3.88 (m, 1 H, NCHHCH2), 4.12 (s, 3 H,
OCH3), 4.22 (dd, J = 3.8, 14.2 Hz, 1 H, NCHH), 4.34 (d, J = 15.2
Hz, 1 H, NCHH), 4.85 (d, J = 14.9 Hz, 1 H, NHCHH), 5.08 (dd,
J = 9.4, 14.3 Hz, 1 H, NHCHH), 5.36 (s, 1 H, CH), 6.43 (d, J = 7.9
Hz, 2 H, ArH), 6.98–7.05 (m, 7 H, ArH), 7.49 (t, J = 7.8 Hz, 1 H,
ArH), 7.57 (d, J = 8.1 Hz, 1 H, ArH), 7.77 (t, J = 8.1 Hz, 1 H, ArH),
8.06 (br s, 1 H, NH), 8.30 (d, J = 7.8 Hz, 1 H, ArH), 8.92 (s, 1 H,
ArH).
13C NMR (50 MHz, CDCl3): d = 21.1, 34.0, 49.9, 53.0, 53.4, 60.0,
68.4, 110.2, 118.1, 121.0, 121.9, 122.4, 126.4, 128.3, 128.4, 128.8,
129.1, 130.0, 133.2, 135.2, 136.7, 138.0, 138.5, 141.4, 144.7, 165.9,
167.5, 167.9.
To a soln of acid 5 (0.25 g, 0.80 mmol) in MeOH (2 mL), n-PrNH2
(0.066 mL, 0.80 mmol) was added and the mixture was stirred for 5
min. Then, TosMIC (0.16 g, 0.80 mmol) was added and stirring was
continued for 12 h at r.t. After completion of the reaction, as moni-
tored by TLC, the separated solid was collected by filtration and
washed with cold MeOH (3 × 1 mL) and Et2O (2 × 1 mL). The
white solid (0.21 g) so obtained was the required product and was
analytically pure. Further product was recovered from the filtrate by
concentration under reduced pressure to furnish an oily residue
which was treated with H2O (20 mL) and extracted with EtOAc (30
mL). The separated organic layer was dried (Na2SO4) and concen-
trated to yield an oily residue. Purification of this residue via short
silica gel (60–120 mesh) column chromatography (hexanes–
EtOAc, 70:30) afforded 5Aa as a white solid (0.04 g); total yield:
0.25 g (57%).
MS (ES+): m/z = 611.1 [M+ + 1].
HRMS (ESI+): m/z calcd for C33H31N4O6S: 611.1964; found:
611.2008.
Mp 218–220 °C; Rf = 0.66 (hexanes–EtOAc, 40:60).
IR (KBr): 1660 (CONH), 1711 (CO2CH3), 3451 (NH) cm–1.
Methyl 5-Benzyl-6-oxo-4-[(4-tolylsulfonylmethyl)carbamoyl]-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Da)
White solid; yield: 0.36 g (75%); mp 209–211 °C; Rf = 0.77 (hex-
anes–EtOAc, 40:60).
1H NMR (300 MHz, CDCl3): d = 0.80 (t, J = 7.3 Hz, 3 H,
NCH2CH2CH3), 1.33–1.59 (m, 2 H, NCH2CH2CH3), 1.94 (s, 3 H,
CH3), 3.35–3.44 (m, 1 H, NCHHCH2CH3), 3.48–3.60 (m, 1 H,
NCHHCH2CH3), 4.12 (s, 3 H, OCH3), 4.23–4.35 (m, 2 H, NCH2),
4.86 (d, J = 15.0 Hz, 1 H, NHCHH), 5.14 (dd, J = 9.3, 14.1 Hz, 1 H,
NHCHH), 5.50 (s, 1 H, CH), 6.46 (d, J = 8.0 Hz, 2 H, ArH), 7.01
(d, J = 8.0 Hz, 2 H, ArH), 7.48 (t, J = 7.5 Hz, 1 H, ArH), 7.57 (d,
J = 8.5 Hz, 1 H, ArH), 7.77 (t, J = 7.6 Hz, 1 H, ArH), 8.19 (br s, 1
H, NH), 8.29 (d, J = 7.8 Hz, 1 H, ArH), 8.95 (s, 1 H, ArH).
IR (KBr): 1660 (CONH), 1711 (CON and CO2CH3), 3463 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.85 (s, 3 H, CH3), 4.08 (s, 4 H,
OCH3 and NCHH), 4.46–4.62 (m, 2 H, NCH2), 4.83–5.05 (m, 3 H,
NCHH and NHCH2), 5.50 (s, 1 H, CH), 6.38 (d, J = 7.5 Hz, 2 H,
ArH), 6.93 (d, J = 7.7 Hz, 2 H, ArH), 7.22–7.26 (m, 5 H, ArH), 7.49
(t, J = 6.9 Hz, 1 H, ArH), 7.60 (d, J = 8.2 Hz, 1 H, ArH), 7.77 (d,
J = 7.0 Hz, 1 H, ArH), 8.30 (d, J = 7.5 Hz, 2 H, ArH and NH), 8.92
(s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 11.2, 21.0, 21.3, 50.1, 52.7, 53.1,
60.1, 67.6, 110.4, 118.3, 121.2, 122.0, 122.5, 128.5, 129.3, 130.1,
133.4, 135.4, 137.0, 138.9, 141.6, 144.8, 166.1, 167.5, 168.1.
MS (ES+): m/z = 549.1 [M+ + 1].
13C NMR (50 MHz, CDCl3): d = 21.1, 50.1, 53.0, 53.5, 59.9, 66.7,
110.3, 118.2, 121.2, 122.0, 122.5, 128.0, 128.4, 128.5, 128.7, 129.1,
130.1, 130.2, 133.3, 135.4, 135.5, 136.9, 138.5, 141.5, 144.6, 165.9,
167.7, 168.1.
HRMS (ESI+): m/z calcd for C28H29N4O6S: 549.1808; found:
549.1809.
Methyl 5-Allyl-6-oxo-4-[(4-tolylsulfonylmethyl)carbamoyl]-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Ba)
White solid; yield: 0.28 g (64%); mp 214–216 °C; Rf = 0.66 (hex-
anes–EtOAc, 40:60).
MS (ES+): m/z = 597.2 [M+ + 1].
Anal. Calcd for C32H28N4O6S (596.1730): C, 64.42; H, 4.73; N,
9.39. Found: C, 64.72; H, 4.54; N, 9.03.
IR (KBr): 1653 (CONH), 1702 (CON), 1727 (CO2CH3), 3433 (NH)
cm–1.
Methyl 5-(Furan-2-ylmethyl)-6-oxo-4-[(4-tolylsulfonylmeth-
yl)carbamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Ea)
White solid; yield: 0.34 g (72%); mp 208–210 °C; Rf = 0.47 (hex-
anes–EtOAc, 50:50).
1H NMR (200 MHz, CDCl3): d = 1.89 (s, 3 H, CH3), 3.92–4.07 (m,
1 H, NCHH), 4.12 (s, 3 H, OCH3), 4.18–4.39 (m, 3 H, NCHH and
=CH2), 4.91 (d, J = 15.2 Hz, 1 H, NHCHH), 5.11–5.24 (m, 3 H,
NHCHH and NCH2), 5.48 (s, 1 H, CH), 5.61–5.80 (m, 1 H, =CH),
6.42 (d, J = 8.0 Hz, 2 H, ArH), 6.98 (d, J = 8.2 Hz, 2 H, ArH), 7.46–
7.60 (m, 2 H, ArH), 7.73–7.81 (m, 1 H, ArH), 8.30 (d, J = 8.0 Hz, 1
H, ArH), 8.50 (br s, 1 H, NH), 8.95 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.1, 49.9, 52.7, 52.9, 60.0, 66.4,
110.2, 118.1, 119.4, 121.0, 121.9, 122.4, 128.4, 129.1, 130.0, 130.1,
131.9, 133.3, 135.3, 136.9, 138.5, 141.4, 144.6, 165.9, 167.7, 167.9.
IR (KBr): 1632 (CONH), 1716 (CON and CO2CH3), 3451 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.85 (s, 3 H, CH3), 4.11 (s, 3 H,
OCH3), 4.19 (dd, J = 4.2, 14.2 Hz, 1 H, NCHH), 4.37 (d, J = 15.8
Hz, 1 H, NCHH), 4.50 (d, J = 15.4 Hz, 1 H, NCHH), 4.87–4.94 (m,
2 H, NCHH and NHCHH), 5.08 (dd, J = 9.3, 14.1 Hz, 1 H, NH-
CHH), 5.70 (s, 1 H, CH), 6.28 (s, 2 H, ArH), 6.39 (d, J = 7.9 Hz, 2
H, ArH), 6.96 (d, J = 8.1 Hz, 2 H, ArH), 7.26 (s, 1 H, ArH), 7.48 (t,
J = 7.4 Hz, 1 H, ArH), 7.57 (d, J = 8.8 Hz, 1 H, ArH), 7.76 (t,
J = 7.5 Hz, 1 H, ArH), 8.29 (d, J = 7.9 Hz, 1 H, ArH), 8.40 (br s, 1
H, NH), 8.93 (s, 1 H, ArH).
MS (ES+): m/z = 547.1 [M+ + 1].
HRMS (ESI+): m/z calcd for C28H27N4O6S: 547.1651; found:
547.1665.
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

424
S. Hutait et al.
PAPER
13C NMR (50 MHz, CDCl3): d = 21.2, 46.0, 49.9, 53.1, 60.0, 66.9,
109.8, 110.3, 110.7, 118.2, 121.2, 122.0, 122.5, 128.5, 129.2, 130.0,
130.2, 133.4, 135.4, 137.0, 138.4, 141.6, 142.9, 144.7, 149.3, 166.0,
167.6, 167.8.
MS (ES+): m/z = 587.3 [M+ + 1].
HRMS (ESI+): m/z calcd for C30H27N4O7S: 587.1600; found:
NCHHCH2CH2OH), 3.85–3.92 (m, 1 H, NCHHCH2CH2), 4.08 (s,
3 H, OCH3), 4.31 (dd, J = 4.4, 14.2 Hz, 1 H, NCHH), 4.54 (d,
J = 15.1 Hz, 1 H, NCHH), 4.91 (d, J = 15.2 Hz, 1 H, NHCHH), 5.07
(dd, J = 8.5, 14.0 Hz, 1 H, NHCHH), 5.61 (s, 1 H, CH), 6.52 (d,
J = 7.9 Hz, 2 H, ArH), 7.06 (d, J = 8.1 Hz, 2 H, ArH), 7.49 (t,
J = 7.5 Hz, 1 H, ArH), 7.57 (d, J = 8.2 Hz, 1 H, ArH), 7.77 (t,
J = 7.6 Hz, 1 H, ArH), 8.30 (d, J = 7.9 Hz, 1 H, ArH), 8.66 (br s, 1
H, NH), 8.94 (d, J = 6.6 Hz, 1 H, ArH).
587.1568.
13C NMR (50 MHz, DMSO-d6): d = 20.7, 45.0, 49.0, 60.1, 66.1,
109.0, 110.4, 115.3, 120.3, 120.6, 122.4, 128.1, 129.0, 129.2, 133.4,
133.7, 138.4, 138.9, 140.6, 142.9, 144.3, 149.9, 167.5, 168.3.
Methyl 5-Cyclopropyl-6-oxo-4-[(4-tolylsulfonylmethyl)car-
bamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluo-
rene-2-carboxylate (5Fa)
White solid; yield: 0.27 g (63%); mp 218–220 °C; Rf = 0.57 (hex-
MS (ES+): m/z = 565.2 [M+ + 1].
anes–EtOAc, 40:60).
Anal. Calcd for C28H28N4O7S (564.1679): C, 59.56; H, 5.00; N,
9.92. Found: C, 59.62; H, 5.24; N, 9.85.
IR (KBr): 1670 (CONH), 1687 (CON), 1740 (CO2CH3), 3350 (NH)
cm–1.
Methyl 5-(Methoxycarbonylmethyl)-6-oxo-4-[(4-tolylsulfonyl-
methyl)carbamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Ia)
White solid; yield: 0.26 g (56%); mp 164–165 °C; Rf = 0.24 (hex-
anes–EtOAc, 40:60).
1H NMR (200 MHz, CDCl3): d = 0.52–0.65 (m, 2 H, CH2), 0.74–
0.95 (m, 2 H, CH2), 1.90 (s, 3 H, CH3), 2.75–2.84 (m, 1 H, NCH),
4.12 (s, 3 H, OCH3), 4.21–4.31 (m, 2 H, NCH2), 4.87 (d, J = 15.5
Hz, 1 H, NHCHH), 5.18 (dd, J = 9.2, 14.1 Hz, 1 H, NHCHH), 5.72
(s, 1 H, CH), 6.42 (d, J = 8.1 Hz, 2 H, ArH), 6.99 (d, J = 8.2 Hz, 2
H, ArH), 7.45–7.58 (m, 2 H, ArH), 7.77 (t, J = 8.3 Hz, 1 H, ArH),
8.29 (d, J = 7.8 Hz, 1 H, ArH), 8.50 (br s, 1 H, NH), 8.94 (s, 1 H,
ArH).
13C NMR (50 MHz, CDCl3): d = 7.8, 9.9, 21.2, 34.4, 50.3, 53.1,
60.1, 69.4, 110.3, 118.2, 121.2, 122.0, 122.5, 128.6, 129.2, 130.1,
130.2, 133.3, 135.3, 137.0, 138.8, 141.6, 144.7, 166.1, 168.3, 170.0.
MS (ES+): m/z = 547.1 [M+ + 1].
HRMS (ESI+): m/z calcd for C28H27N4O6S: 547.1651; found:
IR (KBr): 1660 (CONH), 1702 (CON and CO2CH3), 3456 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 2.15 (s, 3 H, CH3), 3.71 (s, 3 H,
OCH3), 4.02 (s, 3 H, OCH3), 4.24 (d, J = 17.8 Hz, 1 H, NCHH),
4.47 (d, J = 17.7 Hz, 1 H, NCHH), 4.68–4.90 (m, 3 H, NCHH and
NHCH2), 5.04 (d, J = 15.4 Hz, 1 H, NCHH), 5.52 (s, 1 H, CH), 6.90
(d, J = 8.0 Hz, 2 H, ArH), 7.38–7.47 (m, 3 H, ArH), 7.54 (d, J = 8.4
Hz, 1 H, ArH), 7.72 (t, J = 7.5 Hz, 1 H, ArH), 8.25 (d, J = 7.9 Hz, 1
H, ArH), 8.92 (s, 1 H, ArH), 9.21 (t, J = 6.1 Hz, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = 21.4, 49.3, 51.2, 52.8, 52.9, 60.5,
68.3, 110.0, 118.5, 121.3, 121.8, 122.4, 128.7, 129.7, 129.8, 129.9,
133.9, 135.5, 136.9, 138.3, 141.4, 145.0, 166.1, 167.6, 168.2, 170.7.
547.1699.
Methyl 5-Cyclohexyl-6-oxo-4-[(4-tolylsulfonylmethyl)carbam-
oyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-
carboxylate (5Ga)
MS (ES+): m/z = 579.3 [M+ + 1].
White solid; yield: 0.32 g (68%); mp 185–186 °C; Rf = 0.84 (hex-
anes–EtOAc, 40:60).
HRMS (ESI+): m/z calcd for C28H27N4O8S: 579.1550; found:
579.1614.
IR (KBr): 1656 (CONH), 1708 (CON and CO2CH3), 3347 (NH)
cm–1.
Methyl 6-Oxo-5-phenyl-4-[(4-tolylsulfonylmethyl)carbamoyl]-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Ja)
White solid; yield: 0.33 g (70%); mp 187–189 °C; Rf = 0.73 (hex-
anes–EtOAc, 40:60).
1H NMR (300 MHz, CDCl3): d = 1.08–1.15 (m, 2 H, CH2), 1.32 (br
s, 4 H, 2 × CH2), 1.62–1.77 (m, 4 H, 2 × CH2), 1.96 (s, 3 H, CH3),
4.11 (s, 3 H, OCH3), 4.28 (t, J = 11.8 Hz, 2 H, NCH2), 4.60 (br s, 1
H, NCH), 4.86 (d, J = 15.1 Hz, 1 H, NHCHH), 5.13 (dd, J = 8.0,
11.7 Hz, 1 H, NHCHH), 5.60 (s, 1 H, CH), 6.48 (d, J = 7.2 Hz, 2 H,
ArH), 7.01 (d, J = 7.6 Hz, 2 H, ArH), 7.49 (d, J = 7.5 Hz, 1 H, ArH),
7.58 (d, J = 7.6 Hz, 1 H, ArH), 7.75 (d, J = 6.2 Hz, 1 H, ArH), 8.11
(br s, 1 H, NH), 8.28 (d, J = 7.4 Hz, 1 H, ArH), 8.93 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.3, 25.3, 25.6, 29.6, 30.7, 50.3,
53.0, 55.2, 60.1, 61.8, 110.3, 118.3, 121.2, 121.9, 122.5, 128.5,
129.3, 130.0, 133.4, 135.5, 137.2, 139.3, 141.6, 144.8, 166.0, 167.4,
168.6.
IR (KBr): 1668 (CONH), 1714 (CON and CO2CH3), 3387 (NH)
cm–1.
1H NMR (200 MHz, CDCl3): d = 1.97 (s, 3 H, CH3), 4.10 (s, 3 H,
OCH3), 4.30 (dd, J = 4.4, 14.2 Hz, 1 H, NCHH), 4.51 (d, J = 15.2
Hz, 1 H, NCHH), 5.02 (d, J = 15.2 Hz, 1 H, NHCHH), 5.12–5.30
(m, 1 H, NHCHH), 5.80 (s, 1 H, CH), 6.50 (d, J = 8.0 Hz, 2 H, ArH),
7.05 (d, J = 7.9 Hz, 4 H, ArH), 7.26–7.35 (m, 3 H, ArH), 7.52 (t,
J = 7.6 Hz, 1 H, ArH), 7.62 (d, J = 8.5 Hz, 1 H, ArH), 7.80 (t,
J = 8.0 Hz, 1 H, ArH), 8.34 (d, J = 7.7 Hz, 1 H, ArH), 8.45–8.49 (m,
1 H, NH), 8.99 (s, 1 H, ArH).
MS (ES+): m/z = 589.2 [M+ + 1].
Anal. Calcd for C31H32N4O6S (588.2043): C, 63.25; H, 5.48; N,
9.52. Found: C, 63.08; H, 5.39; N, 9.68.
MS (ES+): m/z = 583.1 [M+ + 1].
HRMS (ESI+): m/z calcd for C31H27N4O6S: 583.1651; found:
Methyl 5-(3-Hydroxypropyl)-6-oxo-4-[(4-tolylsulfonylmeth-
yl)carbamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Ha)
White solid; yield: 0.25 g (55%); mp 198–200 °C; Rf = 0.35 (hex-
anes–EtOAc, 25:75).
583.1606.
Methyl 5-(4-Chlorophenyl)-6-oxo-4-[(4-tolylsulfonylmeth-
yl)carbamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Ka)
White solid; yield: 0.30 g (62%); mp 238–240 °C; Rf = 0.77 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1657 (CONH), 1712 (CON and CO2CH3), 3414 (NH)
cm–1.
IR (KBr): 1657 (CONH), 1686 (CON), 1741 (CO2CH3), 3449 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.69–1.71 (m,
2 H,
NCH2CH2CH2), 1.94 (s, 3 H, CH3), 3.51–3.54 (m, 4 H,
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

PAPER
Synthesis of a Library of Lactam-Fused b-Carbolines
425
1H NMR (200 MHz, CDCl3): d = 2.00 (s, 3 H, CH3), 4.06 (s, 3 H,
OCH3), 4.23–4.50 (m, 2 H, NCH2), 4.98–5.20 (m, 2 H, NHCH2),
5.78 (s, 1 H, CH), 6.52 (d, J = 7.7 Hz, 2 H, ArH), 7.05–7.06 (m, 4
H, ArH), 7.29 (d, J = 8.3 Hz, 2 H, ArH), 7.46–7.63 (m, 2 H, ArH),
7.78 (t, J = 7.42 Hz, 1 H, ArH), 8.15 (br s, 1 H, NH), 8.32 (d,
J = 11.6 Hz, 1 H, ArH), 8.98 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.3, 50.1, 53.0, 60.0, 70.3, 110.3,
118.4, 121.2, 122.1, 122.6, 128.3, 128.5, 129.3, 129.8, 130.2, 130.5,
133.4, 133.9, 135.3, 137.4, 138.1, 141.6, 142.3, 144.8, 165.8, 167.6,
168.0.
Methyl 5-Allyl-4-[(ethoxycarbonylmethyl)carbamoyl]-6-oxo-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Bb)
White solid; yield: 0.28 g (76%); mp 219–220 °C; Rf = 0.37 (hex-
anes–EtOAc, 30:70).
IR (KBr): 1675 (CON and CONH), 1711 (CO2CH3), 1740
(CO2C2H5), 3356 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.34 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.86–4.29 (m, 9 H, OCH3, OCH2CH3, NCH2 and
=CH2), 4.41 (dd, J = 5.5, 15.2 Hz, 1 H, NCHH), 5.15–5.34 (m, 3 H,
NHCH2 and NCHH), 5.64 (s, 1 H, CH), 5.80–5.89 (m, 1 H, =CH),
7.08 (br s, 1 H, NH), 7.41 (t, J = 7.4 Hz, 1 H, ArH), 7.59 (d, J = 8.5
Hz, 1 H, ArH), 7.69 (t, J = 7.3 Hz, 1 H, ArH), 8.19 (d, J = 8.0 Hz, 1
H, ArH), 8.85 (s, 1 H, ArH).
MS (ES+): m/z = 617.1 [M+ + 1].
HRMS (ESI+): m/z calcd for C31H26ClN4O6S: 617.1262; found:
617.1259.
Methyl 5-(4-Methoxyphenyl)-6-oxo-4-[(4-tolylsulfonylmeth-
yl)carbamoyl]-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5La)
13C NMR (50 MHz, CDCl3): d = 14.1, 42.0, 50.2, 52.8, 61.6, 66.6,
110.3, 118.4, 119.3, 121.2, 121.6, 122.2, 129.8, 129.9, 132.4, 135.5,
136.9, 139.1, 141.6, 166.0, 167.7, 168.6, 169.0.
White solid; yield: 0.37 g (76%); mp 164–166 °C; Rf = 0.62 (hex-
anes–EtOAc, 40:60).
MS (ES+): m/z = 465.3 [M+ + 1].
HRMS (ESI+): m/z calcd for C24H25N4O6: 465.1774; found:
IR (KBr): 1673 (CONH), 1713 (CON and CO2CH3), 3416 (NH)
cm–1.
465.1795.
1H NMR (300 MHz, CDCl3): d = 1.96 (s, 3 H, CH3), 3.49 (s, 3 H,
OCH3), 3.78 (s, 3 H, OCH3), 4.28 (dd, J = 4.1, 14.2 Hz, 1 H,
NCHH), 4.47 (d, J = 15.2 Hz, 1 H, NCHH), 5.00 (d, J = 15.1 Hz, 1
H, NHCHH), 5.17 (dd, J = 9.2, 14.0 Hz, 1 H, NHCHH), 5.77 (s, 1
H, CH), 6.48 (d, J = 7.9 Hz, 2 H, ArH), 6.84 (d, J = 8.8 Hz, 2 H,
ArH), 6.96–7.05 (m, 4 H, ArH), 7.51 (t, J = 7.5 Hz, 1 H, ArH), 7.62
(d, J = 8.4 Hz, 1 H, ArH), 7.79 (t, J = 7.7 Hz, 1 H, ArH), 8.33 (d,
J = 7.9 Hz, 1 H, ArH), 8.41 (d, J = 4.1 Hz, 1 H, NH), 8.98 (s, 1 H,
ArH).
13C NMR (50 MHz, CDCl3): d = 21.3, 50.2, 53.1, 60.0, 70.4, 110.4,
118.5, 121.2, 122.1, 122.6, 126.7, 128.2, 128.5, 129.3, 129.7, 130.2,
130.5, 133.4, 135.3, 137.3, 138.3, 141.7, 143.9, 144.8, 166.0, 167.7,
168.1.
Methyl 4-[(Ethoxycarbonylmethyl)carbamoyl]-6-oxo-5-(2-phe-
nylethyl)-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluo-
rene-2-carboxylate (5Cb)
White solid; yield: 0.33 g (78%); mp 128–130 °C; Rf = 0.37 (hex-
anes–EtOAc, 30:70).
IR (KBr): 1647 (CONH), 1671 (CON), 1690 (CO2CH3), 1734
(CO2C2H5), 3350 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.14 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 2.78–3.02 (m, 2 H, NCH2CH2), 3.72–3.86 (m, 1 H,
NCHHCH2), 3.90–4.10 (m, 8 H, NCHHCH2, OCH2CH3, OCH3 and
NCH2), 5.13 (d, J = 15.2 Hz, 1 H, NHCHH), 5.26 (d, J = 15.2 Hz, 1
H, NHCHH), 5.56 (s, 1 H, CH), 6.86 (br s, 1 H, NH), 7.04–7.07 (m,
5 H, ArH), 7.40 (t, J = 7.6 Hz, 1 H, ArH), 7.59 (d, J = 8.3 Hz, 1 H,
ArH), 7.69 (t, J = 7.4 Hz, 1 H, ArH), 8.19 (d, J = 7.8 Hz, 1 H, ArH),
8.83 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 14.1, 34.1, 42.0, 50.2, 52.8, 53.5,
61.6, 68.6, 110.3, 118.4, 121.1, 121.6, 122.2, 126.3, 128.3, 128.8,
129.7, 129.8, 135.4, 136.8, 138.3, 139.1, 141.5, 166.0, 167.4, 168.7,
169.0.
MS (ES+): m/z = 613.1 [M+ + 1].
Anal. Calcd for C32H28N4O7S (612.1679): C, 62.73; H, 4.61; N,
9.14. Found: C, 62.83; H, 4.58; N, 9.09.
Methyl 4-[(Ethoxycarbonylmethyl)carbamoyl]-6-oxo-5-propyl-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Ab)
White solid; yield: 0.24 g (65%); mp 218–220 °C; Rf = 0.32 (hex-
anes–EtOAc, 30:70).
MS (ES+): m/z = 529.3 [M+ + 1].
HRMS (ESI+): m/z calcd for C29H28N4NaO6: 551.1907; found:
551.1958.
IR (KBr): 1671 (CON and CONH), 1708 (CO2CH3), 1743
(CO2C2H5), 3321 (NH) cm–1.
Methyl 5-Benzyl-4-[(ethoxycarbonylmethyl)carbamoyl]-6-oxo-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Db)
White solid; yield: 0.32 g (77%); mp 215–216 °C; Rf = 0.37 (hex-
anes–EtOAc, 30:70).
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.4 Hz, 3 H,
NCH2CH2CH3), 1.14 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.48–1.59 (m,
2 H, NCH2CH2CH3), 3.61 (br s, 2 H, NCH2CH2CH3), 3.94–4.11 (m,
7 H, OCH3, OCH2CH3 and NCH2), 5.14 (d, J = 15.2 Hz, 1 H, NH-
CHH), 5.27 (d, J = 15.1 Hz, 1 H, NHCHH), 5.65 (s, 1 H, CH), 6.87
(br s, 1 H, NH), 7.40 (t, J = 7.4 Hz, 1 H, ArH), 7.60 (d, J = 8.4 Hz,
1 H, ArH), 7.69 (t, J = 7.6 Hz, 1 H, ArH), 8.19 (d, J = 7.7 Hz, 1 H,
ArH), 8.87 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 11.2, 14.1, 21.2, 42.0, 50.3, 52.6,
52.8, 61.6, 67.8, 110.3, 118.5, 121.2, 121.6, 122.3, 129.8, 129.9,
135.4, 137.0, 139.3, 141.6, 166.1, 167.3, 168.8, 169.0.
MS (ES+): m/z = 467.3 [M+ + 1].
HRMS (ESI+): m/z calcd for C24H27N4O6: 467.1930; found:
IR (KBr): 1668 (CON and CONH), 1704 (CO2CH3), 1728
(CO2C2H5), 3331 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.12 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.72–3.88 (m, 2 H, NCH2), 3.98–4.16 (m, 5 H, OCH3
and OCH2CH3), 4.82 (d, J = 15.1 Hz, 1 H, NCHH), 4.95 (d, J = 15.1
Hz, 1 H, NCHH), 5.24 (d, J = 15.2 Hz, 1 H, NHCHH), 5.41 (d,
J = 15.2 Hz, 1 H, NHCHH), 5.63 (s, 1 H, CH), 6.86 (s, 1 H, NH),
7.26 (m, 5 H, ArH), 7.40 (t, J = 7.6 Hz, 1 H, ArH), 7.61 (d, J = 8.2
Hz, 1 H, ArH), 7.70 (t, J = 7.7 Hz, 1 H, ArH), 8.19 (d, J = 7.8 Hz, 1
H, ArH), 8.83 (s, 1 H, ArH).
467.1924.
13C NMR (50 MHz, CDCl3): d = 14.1, 41.7, 50.2, 52.6, 53.5, 61.5,
66.9, 110.3, 118.4, 121.2, 121.6, 122.3, 127.9, 128.3, 128.8, 129.8,
129.9, 135.6, 136.1, 136.8, 139.1, 141.6, 165.8, 168.1, 168.4, 168.9.
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

426
S. Hutait et al.
PAPER
MS (ES+): m/z = 515.2 [M+ + 1].
HRMS (ESI+): m/z calcd for C28H26N4NaO6: 537.1750; found:
13C NMR (75 MHz, CDCl3): d = 14.1, 25.3, 25.6, 25.7, 29.9, 31.0,
42.1, 50.5, 52.8, 55.2, 61.6, 62.0, 110.3, 118.5, 121.2, 121.5, 122.3,
129.7, 135.5, 137.1, 140.0, 141.5, 166.1, 167.2, 169.0, 169.3.
537.1801.
MS (ES+): m/z = 507.3 [M+ + 1].
Methyl 4-[(Ethoxycarbonylmethyl)carbamoyl]-5-(furan-2-yl-
methyl)-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Eb)
Anal. Calcd for C27H30N4O6 (506.2165): C, 64.02; H, 5.97; N,
11.06. Found: C, 64.19; H, 5.78; N, 11.01.
White solid; yield: 0.31 g (76%); mp 143–145 °C; Rf = 0.38 (hex-
anes–EtOAc, 55:45).
Methyl 4-[(Ethoxycarbonylmethyl)carbamoyl]-5-(methoxy-
carbonylmethyl)-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclo-
hepta[jk]fluorene-2-carboxylate (5Ib)
White solid; yield: 0.24 g (61%); mp >250 °C; Rf = 0.35 (hexanes–
EtOAc, 20:80).
IR (KBr): 1681 (CON and CONH), 1701 (CO2CH3), 1732
(CO2C2H5), 3331 (NH) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.15 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.91 (d, J = 5.6 Hz, 2 H, NCH2), 4.01–4.13 (m, 5 H,
OCH3 and OCH2CH3), 4.69 (d, J = 15.4 Hz, 1 H, NCHH), 5.20 (d,
J = 15.4 Hz, 1 H, NCHH), 5.16–5.42 (m, 2 H, NHCH2), 5.82 (s, 1
H, CH), 6.29–6.38 (m, 2 H, ArH), 7.08 (t, J = 5.3 Hz, 1 H, NH),
7.27–7.43 (m, 2 H, ArH), 7.57–7.72 (m, 2 H, ArH), 8.18 (d, J = 7.9
Hz, 1 H, ArH), 8.84 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 14.1, 42.0, 46.0, 50.1, 52.7, 61.5,
66.9, 109.8, 110.3, 110.7, 118.4, 121.2, 121.6, 122.2, 129.7, 129.8,
135.5, 136.8, 139.0, 141.5, 142.9, 149.7, 166.0, 167.6, 168.5, 169.2.
IR (KBr): 1652 (CONH), 1674 (CON), 1703 (CO2CH3), 1746
(CO2C2H5), 3334 (NH) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.25 (t, J = 7.0 Hz, 3 H,
OCH2CH3), 3.83 (s, 3 H, OCH3), 3.94–4.33 (m, 8 H, OCH2CH3,
NCH2, OCH3, and NCHH), 4.78 (d, J = 17.9 Hz, 1 H, NCHH), 5.22
(d, J = 15.4 Hz, 1 H, NHCHH), 5.54 (d, J = 16.0 Hz, 2 H, NHCHH
and CH), 7.38 (d, J = 15.3 Hz, 1 H, ArH), 7.53–7.70 (m, 2 H, ArH),
8.19 (d, J = 8.0 Hz, 1 H, ArH), 8.88 (s, 1 H, ArH), 9.03 (br s, 1 H,
NH).
MS (ES+): m/z = 505.4 [M+ + 1].
MS (ES+): m/z = 497.2 [M+ + 1].
HRMS (ESI+): m/z calcd for C26H25N4O7: 505.1723; found:
505.1701.
Anal. Calcd for C24H24N4O8 (496.1594): C, 58.06; H, 4.87; N,
11.29. Found: C, 58.13; H, 4.96; N, 11.06.
Methyl 5-Cyclopropyl-4-[(ethoxycarbonylmethyl)carbamoyl]-
6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-
carboxylate (5Fb)
White solid; yield: 0.25 g (67%); mp 237–238 °C; Rf = 0.32 (hex-
anes–EtOAc, 30:70).
Methyl 4-[(Ethoxycarbonylmethyl)carbamoyl]-6-oxo-5-phenyl-
4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-car-
boxylate (5Jb)
White solid; yield: 0.30 g (75%); mp 193–195 °C; Rf = 0.42 (hex-
anes–EtOAc, 30:70).
IR (KBr): 1671 (CON and CONH), 1706 (CO2CH3), 1737
(CO2C2H5), 3346 (NH) cm–1.
IR (KBr): 1657 (CONH), 1669 (CON), 1707 (CO2CH3), 1738
(CO2C2H5), 3303 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.72–0.76 (m, 2 H, CH2), 0.89–
0.97 (m, 2 H, CH2), 1.14 (t, J = 7.1 Hz, 3 H, OCH2CH3), 3.01–3.03
(m, 1 H, CH), 3.86–4.11 (m, 7 H, OCH3, OCH2CH3 and NCH2),
5.01–5.21 (m, 2 H, NHCH2), 5.88 (s, 1 H, CH), 7.02 (br s, 1 H, NH),
7.39 (t, J = 7.5 Hz, 1 H, ArH), 7.58 (d, J = 8.3 Hz, 1 H, ArH), 7.68
(t, J = 7.5 Hz, 1 H, ArH), 8.18 (d, J = 7.8 Hz, 1 H, ArH), 8.85 (s, 1
H, ArH).
13C NMR (50 MHz, CDCl3): d = 8.1, 9.5, 14.1, 34.5, 42.0, 50.5,
52.7, 61.6, 69.5, 110.3, 118.4, 121.1, 121.6, 122.2, 129.8, 129.9,
135.3, 136.9, 139.3, 141.6, 166.0, 169.0, 169.1, 169.6.
1H NMR (300 MHz, CDCl3): d = 1.14 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.88–4.11 (m, 7 H, OCH2CH3, OCH3 and NCH2), 5.29
(d, J = 15.2 Hz, 1 H, NHCHH), 5.47 (d, J = 15.2 Hz, 1 H, NHCHH),
5.97 (s, 1 H, CH), 7.13 (br s, 1 H, NH), 7.24–7.45 (m, 6 H, ArH),
7.63–7.74 (m, 2 H, ArH), 8.22 (d, J = 7.8 Hz, 1 H, ArH), 8.89 (s, 1
H, ArH).
13C NMR (50 MHz, CDCl3): d = 14.1, 42.1, 50.6, 52.8, 61.6, 70.6,
110.4, 118.6, 121.3, 121.8, 122.3, 126.9, 128.0, 129.7, 129.9, 130.2,
135.5, 137.0, 139.0, 141.7, 144.1, 166.0, 167.6, 168.8, 169.0.
MS (ES+): m/z = 501.2 [M+ + 1].
HRMS (ESI+): m/z calcd for C27H24N4NaO6: 523.1594; found:
MS (ES+): m/z = 465.2 [M+ + 1].
HRMS (ESI+): m/z calcd for C24H25N4O6: 465.1774; found:
523.1654.
465.1781.
Methyl 5-(4-Chlorophenyl)-4-[(ethoxycarbonylmethyl)carbam-
oyl]-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluo-
rene-2-carboxylate (5Kb)
White solid; yield: 0.27 g (64%); mp 213–214 °C; Rf = 0.46 (hex-
anes–EtOAc, 40:60).
Methyl 5-Cyclohexyl-4-[(ethoxycarbonylmethyl)carbamoyl]-6-
oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-
carboxylate (5Gb)
White solid; yield: 0.29 g (73%); mp 214–216 °C; Rf = 0.51 (hex-
anes–EtOAc, 60:40).
IR (KBr): 1665 (CON and CONH), 1702 (CO2CH3), 1742
(CO2C2H5), 3284 (NH) cm–1.
IR (KBr): 1658 (CONH), 1675 (CON), 1704 (CO2CH3), 1724
(CO2C2H5), 3379 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.15 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.93–4.13 (m, 7 H, OCH2CH3, OCH3 and NCH2), 5.28
(d, J = 15.4 Hz, 1 H, NHCHH), 5.43 (d, J = 15.3 Hz, 1 H, NHCHH),
5.92 (s, 1 H, CH), 7.11 (t, J = 5.6 Hz, 1 H, NH), 7.20–7.45 (m, 5 H,
ArH), 7.62–7.74 (m, 2 H, ArH), 8.22 (d, J = 7.9 Hz, 1 H, ArH), 8.89
(s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 14.1, 42.1, 50.5, 52.8, 61.7, 70.5,
110.4, 118.6, 121.3, 121.9, 122.4, 128.5, 129.8, 130.0, 130.3, 133.8,
135.4, 137.1, 138.7, 141.7, 142.5, 166.0, 167.7, 168.7, 168.9.
1H NMR (300 MHz, CDCl3): d = 1.34 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.26–1.47 (m, 6 H, 3 × CH2), 1.63–1.72 (m, 2 H, CH2),
1.85 (br s, 1 H, CHH), 2.02 (br s, 1 H, CHH), 3.86–4.11 (m, 7 H,
OCH2CH3, OCH3 and NCH2), 4.70 (br s, 1 H, NCH), 5.14 (d,
J = 15.2 Hz, 1 H, NHCHH), 5.26 (d, J = 15.2 Hz, 1 H, NHCHH),
5.73 (s, 1 H, CH), 6.82 (t, J = 5.4 Hz, 1 H, NH), 7.38 (t, J = 6.6 Hz,
1 H, ArH), 7.59 (d, J = 8.2 Hz, 1 H, ArH), 7.68 (t, J = 7.6 Hz, 1 H,
ArH), 8.18 (d, J = 7.7 Hz, 1 H, ArH), 8.84 (s, 1 H, ArH).
MS (ES+): m/z = 535.2 [M+ + 1].
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

PAPER
Synthesis of a Library of Lactam-Fused b-Carbolines
427
Anal. Calcd for C27H23ClN4O6 (534.1306): C, 60.62; H, 4.33; N,
10.47. Found: C, 60.45; H, 4.42; N, 10.59.
13C NMR (50 MHz, CDCl3): d = 43.8, 50.4, 52.9, 53.5, 68.8, 107.5,
110.3, 118.3, 121.1, 121.6, 122.3, 126.4, 128.4, 128.9, 129.8, 130.8,
132.7, 135.4, 136.8, 138.2, 138.9, 141.6, 144.9, 166.1, 167.6, 168.7.
Methyl 4-[(Ethoxycarbonylmethyl)carbamoyl]-5-(4-methoxy-
phenyl)-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Lb)
White solid; yield: 0.32 g (76%); mp 226–228 °C; Rf = 0.35 (hex-
anes–EtOAc, 30:70).
MS (ES+): m/z = 584.3 [M+ + 1].
Anal. Calcd for C35H29N5O4 (583.2220): C, 72.03; H, 5.01; N,
12.00. Found: C, 72.15; H, 5.23; N, 12.09.
(Z)-Methyl 5-Benzyl-4-[(2-cyano-3-phenylallyl)carbamoyl]-6-
oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-
carboxylate (5Dc)
IR (KBr): 1661 (CONH), 1675 (CON), 1703 (CO2CH3), 1728
(CO2C2H5), 3316 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.14 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.79 (s, 3 H, OCH3), 3.88–4.11 (m, 7 H, OCH2CH3,
OCH3 and NCH2), 5.28 (d, J = 15.5 Hz, 1 H, NHCHH), 5.42 (d,
J = 15.5 Hz, 1 H, NHCHH), 5.94 (s, 1 H, CH), 6.88 (d, J = 8.4 Hz,
2 H, ArH), 6.98 (s, 1 H, NH), 7.18 (d, J = 8.6 Hz, 2 H, ArH), 7.42
(t, J = 7.7 Hz, 1 H, ArH), 7.63–7.74 (m, 2 H, ArH), 8.23 (d, J = 7.9
Hz, 1 H, ArH), 8.90 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 14.1, 42.0, 50.5, 52.7, 55.6, 61.6,
70.9, 110.4, 114.8, 118.6, 121.2, 121.7, 122.3, 128.0, 129.9, 130.1,
135.4, 137.0, 137.1, 139.0, 141.7, 159.0, 166.0, 167.8, 168.8, 169.0.
White solid; yield: 0.36 g (78%); mp 235–236 °C; Rf = 0.53 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1655 (CONH), 1692 (CON and CO2CH3), 3377 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.96 (t, J = 5.4 Hz, 2 H, NCH2),
4.01 (s, 3 H, OCH3), 4.61 (d, J = 14.9 Hz, 1 H, NCHH), 5.15 (d,
J = 14.9 Hz, 1 H, NCHH), 5.26 (d, J = 15.5 Hz, 1 H, NHCHH), 5.49
(d, J = 15.8 Hz, 1 H, NHCHH), 5.65 (s, 1 H, CH), 6.80 (s, 1 H,
ArH), 7.13–7.43 (m, 9 H, ArH and =CH), 7.54–7.72 (m, 4 H, ArH),
8.19 (d, J = 7.6 Hz, 1 H, ArH), 8.84 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 43.6, 50.6, 52.8, 53.6, 67.1, 107.3,
110.4, 117.5, 118.3, 121.2, 121.6, 122.2, 128.1, 128.6, 128.9, 129.8,
130.0, 130.7, 132.8, 135.6, 135.9, 136.7, 138.9, 141.7, 144.8, 166.1,
168.2, 168.4.
MS (ES+): m/z = 531.3 [M+ + 1].
Anal. Calcd for C28H26N4O7 (530.1801): C, 63.39; H, 4.94; N,
10.56. Found: C, 63.71; H, 4.56; N, 10.25.
(Z)-Methyl 5-Allyl-4-[(2-cyano-3-phenylallyl)carbamoyl]-6-
oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-2-
carboxylate (5Bc)
MS (ES+): m/z = 570.2 [M+ + 1].
Anal. Calcd for C34H27N5O4 (569.2063): C, 71.69; H, 4.78; N,
12.30. Found: C, 71.85; H, 4.93; N, 12.12.
White solid; yield: 0.33 g (78%); mp 226–228 °C; Rf = 0.24 (hex-
anes–EtOAc, 40:60).
(Z)-Methyl 4-[(2-Cyano-3-phenylallyl)carbamoyl]-5-(4-meth-
oxyphenyl)-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Lc)
IR (KBr): 1660 (CONH), 1681 (CON), 1695 (CO2CH3), 3374 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 4.05–4.18 (m, 6 H, OCH3, =CH2
and NCHH), 4.46–4.52 (m, 1 H, NCHH), 5.18–5.30 (m, 3 H, NCH2
and NHCHH), 5.40 (d, J = 15.3 Hz, 1 H, NHCHH), 5.64 (s, 1 H,
CH), 5.78–5.91 (m, 1 H, =CH), 6.93 (s, 1 H, ArH), 7.26–7.42 (m, 4
H, ArH and =CH), 7.55–7.60 (m, 3 H, ArH), 7.69 (t, J = 8.4 Hz, 1
H, ArH), 8.19 (d, J = 8.2 Hz, 1 H, ArH), 8.56 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 43.8, 50.6, 52.9, 53.0, 66.9, 107.6,
110.3, 117.4, 118.3, 119.4, 121.2, 121.6, 122.3, 128.9, 129.8, 130.1,
130.7, 132.4, 132.8, 135.5, 136.8, 139.0, 141.7, 144.7, 166.2, 168.0,
168.7.
White solid; yield: 0.36 g (77%); mp 153–155 °C; Rf = 0.18 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1669 (CONH), 1686 (CON), 1708 (CO2CH3), 3388 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.79 (s, 3 H, OCH3), 4.03–4.09
(m, 4 H, OCH3 and NCHH), 4.29 (dd, J = 6.1, 14.9 Hz, 1 H,
NCHH), 5.30 (t, J = 7.8 Hz, 1 H, NHCHH), 5.46–5.53 (m, 1 H, NH-
CHH), 5.94 (d, J = 7.3 Hz, 1 H, CH), 6.89 (t, J = 9.7 Hz, 2 H, ArH),
7.15–7.42 (m, 8 H, ArH and =CH), 7.55 (d, J = 6.2 Hz, 1 H, ArH),
7.63 (d, J = 8.6 Hz, 1 H, ArH), 7.71 (t, J = 8.2 Hz, 1 H, ArH), 8.22
(d, J = 8.0 Hz, 1 H, ArH), 8.89 (d, J = 4.2 Hz, 1 H, ArH).
MS (ES+): m/z = 520.2 [M+ + 1].
Anal. Calcd for C30H25N5O4 (519.1907): C, 69.35; H, 4.85; N,
13.48. Found: C, 69.59; H, 4.72; N, 13.43.
13C NMR (50 MHz, CDCl3): d = 43.8, 50.8, 52.9, 55.6, 71.1, 107.6,
110.5, 114.9, 118.5, 121.2, 121.8, 122.3, 128.0, 128.9, 129.4, 130.0,
130.4, 130.8, 132.7, 136.9, 137.2, 138.9, 141.8, 144.7, 145.6, 159.0,
166.2, 168.1, 168.8.
(Z)-Methyl 4-[(2-Cyano-3-phenylallyl)carbamoyl]-6-oxo-5-(2-
phenylethyl)-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Cc)
White solid; yield: 0.35 g (75%); mp 158–160 °C; Rf = 0.66 (hex-
anes–EtOAc, 40:60).
MS (ES+): m/z = 586.1 [M+ + 1].
Anal. Calcd for C34H27N5O5 (585.2012): C, 69.73; H, 4.65; N,
11.96. Found: C, 69.84; H, 4.76; N, 11.89.
IR (KBr): 1659 (CONH), 1692 (CON and CO2CH3), 3321 (NH)
cm–1.
(Z)-Methyl 4-{[2-Cyano-3-(2,4-dichlorophenyl)allyl]carbam-
oyl}-6-oxo-5-propyl-4,5,6,7-tetrahydro-3,5,7a-triazacyclo-
hepta[jk]fluorene-2-carboxylate (5Ad)
White solid; yield: 0.34 g (72%); mp 135–136 °C; Rf = 0.44 (hex-
anes–EtOAc, 40:60).
1H NMR (300 MHz, CDCl3): d = 1.78–2.86 (m, 1 H, NCH2CHH),
2.88–3.00 (m, 1 H, NCH2CHH), 3.72–3.82 (m, 1 H, NCHHCH2),
4.00–4.06 (m, 5 H, OCH3, NCHHCH2 and NCHH), 4.17–4.24 (m,
1 H, NCHH), 5.14 (d, J = 15.1 Hz, 1 H, NHCHH), 5.31 (d, J = 15.2
Hz, 1 H, NHCHH), 5.55 (s, 1 H, CH), 6.91 (s, 1 H, ArH), 7.05 (s, 5
H, ArH), 7.29–7.42 (m, 4 H, ArH and =CH), 7.53–7.60 (m, 3 H,
ArH), 7.69 (t, J = 7.5 Hz, 1 H, ArH), 8.19 (d, J = 7.9 Hz, 1 H, ArH),
8.33 (s, 1 H, ArH).
IR (KBr): 1658 (CONH), 1689 (CON), 1721 (CO2CH3), 3439 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.1 Hz, 3 H,
NCH2CH2CH3), 1.54–1.66 (m, 2 H, NCH2CH2CH3), 3.57–3.66 (m,
2 H, NCH2CH2CH3), 4.06–4.14 (m, 4 H, OCH3 and NCHH), 4.26–
4.33 (m, 1 H, NCHH), 5.16 (d, J = 14.8 Hz, 1 H, NHCHH), 5.37 (d,
J = 14.7 Hz, 1 H, NHCHH), 5.68 (s, 1 H, CH), 7.15 (s, 1 H, NH),
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S. Hutait et al.
PAPER
7.21–7.43 (m, 3 H, =CH and ArH), 7.59 (d, J = 8.5 Hz, 2 H, ArH),
7.67–7.76 (m, 2 H, ArH), 8.19 (d, J = 5.2 Hz, 1 H, ArH), 8.86 (s, 1
H, ArH).
(m, 1 H, =CH), 7.08 (s, 1 H, NH), 7.27–7.44 (m, 6 H, ArH), 7.57–
7.74 (m, 3 H, =CH and ArH), 8.20 (d, J = 7.7 Hz, 1 H, ArH), 8.86
(s, 1 H, ArH).
13C NMR (50 MHz, DMSO-d6): d = 10.8, 20.9, 49.4, 51.2, 52.2,
66.6, 110.6, 113.6, 116.8, 118.2, 120.6, 121.2, 122.7, 127.9, 128.6,
129.4, 130.4, 130.5, 133.9, 134.9, 135.4, 136.6, 139.3, 139.6, 140.9,
165.7, 166.2, 169.2.
13C NMR (50 MHz, CDCl3): d = 37.2, 50.4, 52.2, 52.9, 53.0, 66.9,
110.3, 118.3, 119.4, 121.2, 121.6, 122.3, 127.4, 128.7, 129.4, 129.8,
130.0, 132.4, 134.0, 135.4, 137.1, 139.3, 141.6, 142.9, 166.1, 167.5,
167.6, 167.7.
MS (ES+): m/z = 590.2 [M+ + 1].
MS (ES+): m/z = 553.3 [M+ + 1].
HRMS (ESI+): m/z calcd for C30H26Cl2N5O4: 590.1362; found:
590.1376.
Anal. Calcd for C31H28N4O6 (552.2009): C, 67.38; H, 5.11; N,
10.14. Found: C, 67.52; H, 5.01; N, 10.06.
(Z)-Methyl 5-Allyl-4-{[2-cyano-3-(2,4-dichlorophenyl)allyl]car-
bamoyl}-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Bd)
White solid; yield: 0.35 g (74%); mp 186–188 °C; Rf = 0.47 (hex-
anes–EtOAc, 40:60).
6-Oxo-5-propyl-N-(4-tolylsulfonylmethyl)-4,5,6,7-tetrahydro-
3,5,7a-triazacyclohepta[jk]fluorene-4-carboxamide (8Aa)
White solid; yield: 0.29 g (61%); mp 226–228 °C; Rf = 0.44 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1656 (CONH), 1689 (CON), 3451 (NH) cm–1.
IR (KBr): 1659 (CONH), 1692 (CON and CO2CH3), 3420 (NH)
cm–1.
1H NMR (300 MHz, CDCl3): d = 0.80 (t, J = 6.8 Hz, 3 H,
NCH2CH2CH3), 1.42–1.57 (m, 2 H, NCH2CH2CH3), 1.94 (s, 3 H,
CH3), 3.41–3.53 (m, 2 H, NCH2CH2CH3), 3.99 (d, J = 15.1 Hz, 1 H,
NCHH), 4.24 (d, J = 13.6 Hz, 1 H, NCHH), 4.76 (d, J = 15.2 Hz, 1
H, NHCHH), 5.15 (dd, J = 9.9, 13.0 Hz, 1 H, NHCHH), 5.36 (s, 1
H, CH), 6.39 (d, J = 7.5 Hz, 2 H, ArH), 6.95 (d, J = 7.7 Hz, 2 H,
ArH), 7.41–7.53 (m, 3 H, ArH), 7.70 (d, J = 7.1 Hz, 1 H, ArH), 8.07
(d, J = 5.0 Hz, 1 H, NH), 8.24 (d, J = 7.6 Hz, 1 H, ArH), 8.49 (d,
J = 4.4 Hz, 1 H, ArH).
1H NMR (300 MHz, CDCl3): d = 4.05 (s, 3 H, OCH3), 4.12–4.31
(m, 3 H, NCH2 and NCHH), 4.46–4.51 (m, 1 H, NCHH), 5.18–5.41
(m, 4 H, NHCH2 and =CH2), 5.66 (s, 1 H, CH), 5.83–5.85 (m, 1 H,
=CH), 7.14–7.42 (m, 4 H, NH, =CH and ArH), 7.60–7.98 (m, 4 H,
ArH), 8.18 (d, J = 7.2 Hz, 1 H, ArH), 8.84 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 43.3, 50.5, 52.9, 53.0, 66.9, 110.3,
111.7, 116.5, 118.4, 119.5, 121.2, 121.7, 122.3, 127.7, 129.6, 129.8,
129.9, 130.2, 132.4, 134.9, 135.5, 136.9, 137.0, 139.0, 139.4, 141.7,
166.1, 167.9, 168.7.
13C NMR (50 MHz, CDCl3): d = 11.2, 21.1, 21.3, 49.9, 52.7, 59.7,
67.6, 109.9, 115.6, 121.0, 121.1, 122.5, 128.5, 129.4, 129.7, 130.5,
133.0, 134.2, 138.7, 139.2, 141.4, 144.9, 167.7, 168.5.
MS (ES+): m/z = 588.4 [M+ + 1].
HRMS (ESI+): m/z calcd for C30H23Cl2N5NaO4: 610.1025; found:
MS (ES+): m/z = 491.3 [M+ + 1].
610.1020.
Anal. Calcd for C26H26N4O4S (490.1675): C, 63.66; H, 5.34; N,
11.42. Found: C, 63.34; H, 5.56; N, 11.35.
(Z)-Methyl 4-{[2-Cyano-3-(2,4-dichlorophenyl)allyl]carbam-
oyl}-5-cyclopropyl-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclo-
hepta[jk]fluorene-2-carboxylate (5Fd)
White solid; yield: 0.33 g (71%); mp 228–230 °C; Rf = 0.46 (hex-
anes–EtOAc, 40:60).
5-(Furan-2-ylmethyl)-6-oxo-N-(4-tolylsulfonylmethyl)-4,5,6,7-
tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-4-carboxamide
(8Ea)
White solid; yield: 0.36 g (69%); mp 214–216 °C; Rf = 0.35 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1662 (CONH), 1693 (CON), 3377 (NH) cm–1.
IR (KBr): 1666 (CONH), 1701 (CON and CO2CH3), 3332 (NH)
cm–1.
1H NMR (200 MHz, CDCl3): d = 0.70–0.79 (m, 2 H, CH2), 0.85–
1.01 (m, 2 H, CH2), 2.98–3.06 (m, 1 H, NCH), 4.06–4.18 (m, 4 H,
OCH3 and NCHH), 4.29–4.41 (m, 1 H, NCHH), 5.19 (dd, J = 15.4,
18.2 Hz, 2 H, NHCH2), 5.92 (s, 1 H, CH), 7.14–7.44 (m, 5 H, =CH
and ArH), 7.55–7.77 (m, 2 H, ArH), 8.18 (d, J = 7.7 Hz, 1 H, ArH),
8.84 (s, 1 H, ArH).
13C NMR (50 MHz, DMSO-d6): d = 7.7, 9.0, 33.9, 42.5, 52.2, 68.8,
75.3, 76.1, 110.7, 113.6, 116.8, 118.3, 120.6, 121.3, 122.6, 127.9,
128.8, 129.4, 130.4, 130.5, 133.9, 134.7, 135.4, 136.7, 139.1, 141.0,
165.7, 168.3, 169.1.
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, CH3), 3.95 (d,
J = 15.0 Hz, 1 H, NCHH), 4.15 (dd, J = 3.4, 14.2 Hz, 1 H, NCHH),
4.70 (d, J = 3.4 Hz, 2 H, NCH2), 4.80 (d, J = 22.4 Hz, 1 H, NH-
CHH), 5.13 (dd, J = 10.1, 14.2 Hz, 1 H, NHCHH), 5.56 (s, 1 H,
CH), 6.25–6.26 (m, 2 H, ArH), 6.33 (d, J = 8.0 Hz, 2 H, ArH), 6.90
(d, J = 8.1 Hz, 2 H, ArH), 7.41 (t, J = 7.5 Hz, 2 H, ArH), 7.52 (d,
J = 8.5 Hz, 1 H, ArH), 7.72 (t, J = 8.2 Hz, 1 H, ArH), 8.06 (d,
J = 5.2 Hz, 1 H, ArH), 8.23 (d, J = 7.9 Hz, 1 H, ArH), 8.49 (d,
J = 5.2 Hz, 1 H, ArH).
13C NMR (50 MHz, DMSO-d6): d = 20.9, 30.8, 52.3, 58.3, 66.5,
110.7, 118.3, 120.6, 121.4, 122.8, 128.2, 128.8, 129.4, 129.6, 134.2,
134.9, 136.6, 139.0, 141.0, 144.6, 165.6, 166.5, 168.8.
MS (ES+): m/z = 588.4 [M+ + 1].
HRMS (ESI+): m/z calcd for C30H23Cl2N5NaO4: 610.1025; found:
MS (ES+): m/z = 529.2 [M+ + 1].
610.1047.
Anal. Calcd for C28H24N4O5S (528.1467): C, 63.62; H, 4.58; N,
10.60. Found: C, 63.34; H, 4.86; N, 10.25.
(E)-Methyl 5-Allyl-4-{[2-(methoxycarbonyl)-3-phenylallyl]car-
bamoyl}-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluorene-2-carboxylate (5Be)
White solid; yield: 0.34 g (77%); mp 203–204 °C; Rf = 0.47 (hex-
anes–EtOAc, 40:60).
5-(4-Methoxyphenyl)-6-oxo-N-(4-tolylsulfonylmethyl)-4,5,6,7-
tetrahydro-3,5,7a-triazacyclohepta[jk]fluorene-4-carboxamide
(8La)
White solid; yield: 0.40 g (74%); mp 243–245 °C; Rf = 0.38 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1664 (CONH), 1685 (CON), 3483 (NH) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.96 (s, 3 H, CH3), 3.78 (s, 3 H,
OCH3), 4.09 (d, J = 15.0 Hz, 1 H, NCHH), 4.22 (dd, J = 3.7, 14.3
IR (KBr): 1666 (CONH), 1677 (CON), 1725 (CO2CH3), 3406 (NH)
cm–1.
1H NMR (200 MHz, CDCl3): d = 3.61 (s, 3 H, OCH3), 4.06–4.21
(m, 4 H, OCH3 and NCHH), 4.26–4.50 (m, 3 H, NCHH and NCH2),
5.12–5.29 (m, 4 H, NHCH2 and =CH2), 5.54 (s, 1 H, CH), 5.76–5.95
Synthesis 2011, No. 3, 419–430 © Thieme Stuttgart · New York

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Synthesis of a Library of Lactam-Fused b-Carbolines
429
Hz, 1 H, NCHH), 4.89 (d, J = 15.1 Hz, 1 H, NHCHH), 5.19 (dd,
J = 9.8, 14.1 Hz, 1 H, NHCHH), 5.64 (s, 1 H, CH), 6.40 (d, J = 7.8
Hz, 2 H, ArH), 6.85 (d, J = 8.9 Hz, 2 H, ArH), 6.96 (d, J = 8.2 Hz,
2 H, ArH), 7.03 (d, J = 8.9 Hz, 2 H, ArH), 7.44 (t, J = 7.3 Hz, 2 H,
ArH), 7.56 (d, J = 8.2 Hz, 1 H, ArH), 7.74 (t, J = 7.5 Hz, 1 H, ArH),
8.12 (d, J = 5.2 Hz, 1 H, NH), 8.28 (d, J = 7.9 Hz, 1 H, ArH), 8.52
(d, J = 5.2 Hz, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.4, 50.1, 55.6, 59.8, 70.9, 110.1,
114.9, 115.6, 121.2, 122.6, 127.9, 128.6, 129.4, 129.8, 130.7, 133.1,
134.3, 137.3, 138.5, 139.4, 141.5, 144.9, 159.1, 168.1, 168.6.
1H NMR (200 MHz, CDCl3): d = 1.13 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.87 (d, J = 5.5 Hz, 2 H, NCH2), 4.06 (q, J = 7.2 Hz, 2
H, OCH2CH3), 4.70 (d, J = 15.1 Hz, 1 H, NHCHH), 5.09 (d,
J = 15.0 Hz, 1 H, NHCHH), 5.21 (s, 2 H, NCH2), 5.48 (s, 1 H, CH),
6.60 (s, 1 H, NH), 7.22–7.26 (m, 5 H, ArH), 7.33 (t, J = 7.2 Hz, 1
H, ArH), 7.57 (d, J = 8.4 Hz, 1 H, ArH), 7.65 (t, J = 7.1 Hz, 1 H,
ArH), 7.93 (d, J = 5.3 Hz, 1 H, ArH), 8.13 (d, J = 7.9 Hz, 1 H, ArH),
8.31 (d, J = 5.3 Hz, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 14.3, 41.8, 50.2, 53.3, 61.6, 66.9,
109.9, 115.3, 120.6, 121.0, 122.2, 127.9, 128.4, 128.8, 129.3, 130.0,
134.2, 136.1, 138.7, 139.1, 141.2, 168.4, 168.8, 169.0.
MS (ES+): m/z = 555.2 [M+ + 1].
MS (ES+): m/z = 457.4 [M+ + 1].
Anal. Calcd for C30H26N4O5S (554.1624): C, 64.97; H, 4.73; N,
10.10. Found: C, 65.07; H, 4.84; N, 10.02.
Anal. Calcd for C26H24N4O4 (456.1798): C, 68.41; H, 5.30; N,
12.27. Found: C, 68.36; H, 5.16; N, 12.49.
Ethyl [(5-Allyl-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclohep-
ta[jk]fluoren-4-ylcarbonyl)amino]acetate (8Bb)
White solid; yield: 0.32 g (72%); mp 141–143 °C; Rf = 0.38 (hex-
anes–EtOAc, 40:60).
Ethyl {[5-(4-Methoxyphenyl)-6-oxo-4,5,6,7-tetrahydro-3,5,7a-
triazacyclohepta[jk]fluoren-4-ylcarbonyl]amino}acetate (8Lb)
White solid; yield: 0.32 g (76%); mp 243–245 °C; Rf = 0.32 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1662 (CONH), 1691 (CON), 1743 (CO2C2H5), 3378
(NH) cm–1.
IR (KBr): 1668 (CONH), 1691 (CON), 1747 (CO2C2H5), 3309
(NH) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.15 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.96 (d, J = 5.5 Hz, 2 H, NCH2), 4.09 (q, J = 7.1 Hz, 2
H, OCH2CH3), 4.14–4.44 (m, 2 H, NCH2), 5.14–5.51 (m, 4 H, =CH2
and NHCH2), 5.75 (s, 1 H, CH), 5.72–5.92 (m, 1 H, =CH), 6.77 (t,
J = 5.2 Hz, 1 H, NH), 7.28–7.36 (m, 1 H, ArH), 7.52–7.68 (m, 2 H,
ArH), 7.97 (d, J = 5.3 Hz, 1 H, ArH), 8.13 (d, J = 7.9 Hz, 1 H, ArH),
8.41 (d, J = 5.3 Hz, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 14.1, 41.9, 50.1, 52.6, 61.6, 66.5,
109.8, 115.4, 119.3, 120.6, 120.9, 122.2, 129.3, 130.1, 132.6, 134.2,
138.8, 139.1, 141.2, 168.0, 169.0.
1H NMR (300 MHz, CDCl3): d = 1.15 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 3.79 (s, 3 H, OCH3), 3.98–4.01 (m, 2 H, NCH2), 4.09
(q, J = 7.1 Hz, 2 H, OCH2CH3), 5.19–5.30 (m, 2 H, NHCH2), 5.79
(s, 1 H, CH), 6.74 (br s, 1 H, NH), 6.88 (d, J = 8.9 Hz, 2 H, ArH),
7.21 (d, J = 8.9 Hz, 2 H, ArH), 7.35 (t, J = 7.0 Hz, 1 H, ArH), 7.58
(d, J = 8.3 Hz, 1 H, ArH), 7.66 (t, J = 7.3 Hz, 1 H, ArH), 8.00 (d,
J = 5.3 Hz, 1 H, ArH), 8.16 (d, J = 7.8 Hz, 1 H, ArH), 8.42 (d,
J = 5.3 Hz, 1 H, ArH).
MS (ES+): m/z = 473.5 [M+ + 1].
MS (ES+): m/z = 407.4 [M+ + 1].
Anal. Calcd for C26H24N4O5 (472.1747): C, 66.09; H, 5.12; N,
11.86. Found: C, 66.16; H, 5.03; N, 11.96.
Anal. Calcd for C22H22N4O4 (406.1641): C, 65.01; H, 5.46; N,
13.78. Found: C, 65.15; H, 5.59; N, 13.66.
Supporting Information for this article is available online at
Ethyl {[6-Oxo-5-(2-phenylethyl)-4,5,6,7-tetrahydro-3,5,7a-tri-
azacyclohepta[jk]fluoren-4-ylcarbonyl]amino}acetate (8Cb)
White solid; yield: 0.34 g (73%); mp 168–170 °C; Rf = 0.63 (hex-
anes–EtOAc, 40:60).
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
IR (KBr): 1662 (CONH), 1689 (CON), 1742 (CO2C2H5), 3378
(NH) cm–1.
Two of the authors (S.H. and M.N.) acknowledge financial support
from CSIR, New Delhi in the form of fellowships. This work was
carried out under a grant from DST, New Delhi. The authors
acknowledge the SAIF Division of CDRI for providing the spectro-
scopic and analytical data.
1H NMR (300 MHz, CDCl3): d = 1.15 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 2.80–2.86 (m, 1 H, NCH2CHH), 2.92–2.98 (m, 1 H,
NCH2CHH), 3.64–3.73 (m, 1 H, NCHHCH2), 3.94 (d, J = 5.4 Hz, 2
H, NCH2), 4.05–4.16 (m, 3 H, OCH2CH3 and NCHHCH2), 5.09 (s,
2 H, NHCH2), 5.39 (s, 1 H, CH), 6.68 (s, 1 H, NH), 7.05–7.06 (m,
5 H, ArH), 7.32 (t, J = 7.2 Hz, 1 H, ArH), 7.54 (d, J = 8.4 Hz, 1 H,
ArH), 7.64 (t, J = 7.5 Hz, 1 H, ArH), 7.94 (d, J = 5.3 Hz, 1 H, ArH),
8.13 (d, J = 7.9 Hz, 1 H, ArH), 8.34 (d, J = 5.3 Hz, 1 H, ArH).
References
(1) CDRI Communication No. 7998.
(2) Graduate Trainee from the National Institute of
Pharmaceutical Education and Research, Raebareli, India.
(3) Selected references only: (a) Cao, R.; Peng, W.; Wang, Z.;
Xu, A. Curr. Med. Chem. 2007, 14, 479; and references cited
therein. (b) Cao, R.; Guan, X.; Shi, B.; Chen, Z.; Ren, Z.;
Peng, W.; Song, H. Eur. J. Med. Chem. 2010, 45, 2503.
(c) Ma, C.; Cao, R.; Shi, B.; Li, S.; Chen, Z.; Yi, W.; Peng,
W.; Ren, Z.; Song, H. Eur. J. Med. Chem. 2010, 45, 1515.
(d) Chen, Z.; Cao, R.; Shi, B.; Yi, W.; Yu, L.; Song, H.; Ren,
Z.; Peng, W. Bioorg. Med. Chem. Lett. 2010, 20, 3876.
(e) Wu, Q.; Cao, R.; Feng, M.; Guan, X.; Ma, C.; Liu, J.;
Song, H.; Peng, W. Eur. J. Med. Chem. 2009, 44, 533.
(f) Kumar, R.; Gupta, L.; Pal, P.; Khan, S.; Singh, N.;
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K.; Lochab, S.; Trivedi, A. K.; Chauhan, P. M. S. Eur. J.
Med. Chem. 2010, 45, 2265. (g) Wu, J.; Zhao, M.; Qian, K.;
13C NMR (50 MHz, CDCl3): d = 14.1, 34.2, 41.9, 50.1, 53.4, 61.7,
68.8, 109.8, 115.3, 120.6, 120.9, 122.2, 126.3, 128.3, 128.8, 129.3,
130.0, 134.1, 138.4, 138.6, 139.1, 141.2, 167.8, 169.0, 169.1.
MS (ES+): m/z = 471.2 [M+ + 1].
Anal. Calcd for C27H26N4O4 (470.1954): C, 68.92; H, 5.57; N,
11.91. Found: C, 68.86; H, 5.64; N, 11.83.
Ethyl [(5-Benzyl-6-oxo-4,5,6,7-tetrahydro-3,5,7a-triazacyclo-
hepta[jk]fluoren-4-ylcarbonyl)amino]acetate (8Db)
White solid; yield: 0.31 g (78%); mp 148–150 °C; Rf = 0.44 (hex-
anes–EtOAc, 40:60).
IR (KBr): 1655 (CONH), 1692 (CON), 1741 (CO2C2H5), 3391
(NH) cm–1.
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S. Hutait et al.
PAPER
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Lee, K. H.; Morris-Natschke, S.; Peng, S. Eur. J. Med.
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