Three-component one-pot synthesis of 3-(2-Furanyl)indoles from acetylenedicarboxylate, isocyanide, and 3-formylindole

Article abstract of DOI:10.1055/s-0029-1218824

The zwitterions derived from isocyanide and dimethyl acetylenedicarboxylate undergo smooth condensation with 3-formylindoles in benzene at room temperature to give the corresponding 3-(2-furanyl)indoles in good yields. This method provides a simple and convenient route to produce a wide range of 3-heteroarylindoles in a one-pot operation. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1218824

PAPER
2571
Three-Component One-Pot Synthesis of 3-(2-Furanyl)indoles from
Acetylenedicarboxylate, Isocyanide, and 3-Formylindole
One-Pot Synthes
.
V
anyl)indole
s
. Subba Reddy,*a A. Mallikarjun Reddy,a D. Somashekar,a J. S. Yadav,a B. Sridharb
a
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Centre for X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad 500 007, India
E-mail: basireddy@iict.res.in
b
Received 29 March 2010; revised 9 April 2010
often enhances the biological activity significantly. Until
now, only two approaches have been reported for the syn-
thesis of 3-furanylindoles.9 However, the synthesis of pyr-
rolyl- and furanylindoles could not be achieved by the
Abstract: The zwitterions derived from isocyanide and dimethyl
acetylenedicarboxylate undergo smooth condensation with 3-
formylindoles in benzene at room temperature to give the corre-
sponding 3-(2-furanyl)indoles in good yields. This method provides
a simple and convenient route to produce a wide range of 3-het- well-known Fischer indole synthesis.10 Furthermore,
eroarylindoles in a one-pot operation.
there have been no reports on the synthesis of 3-(2-furan-
yl)indoles via zwitterionic intermediates.
Key words: 3-formylindoles, isocyanides, DMAD, zwitterions, 3-
furanylindoles
Recently, we have reported the coupling of indoles with
zwitterions derived from quinolines/isoquinolines and
dimethyl acetylenedicarboxylate to furnish indol-3-yl-
quinolines/isoquinolines.11 In addition to this, the conden-
sation of alkynes with activated quinolines and isoquino-
lines has also been reported using gold(III) chloride to
generate alkynylated aza-aromatic systems.12 This result
provided an inspiration to study the annulation of zwitter-
ions, derived from DMAD and isocyanides with 3-
formylindoles. Thus, treatment of 3-formylindole with
cyclohexyl isocyanide and dimethyl acetylenedicarboxy-
late in benzene at room temperature gave the correspond-
ing dimethyl 2-(1-tert-butoxycarbonyl)-1H-indol-3-yl)-5-
(cyclohexylamino)furan-3,4-dicarboxylate (4a) in 89%
yield (Scheme 1).
The multi-component reactions (MCRs) are highly im-
portant because of their wide range of applications in
pharmaceutical chemistry for production of the diverse
structural scaffolds and combinatorial libraries for drug
discovery.1 They are extremely convergent, producing a
remarkably high increase of molecular complexity in just
one step.2 The cycloaddition of 1,4-dipoles with various
electrophiles such as aldehydes, imines, quinones, activat-
ed alkenes, and aza-aromatic systems is one of the most
versatile methods to generate a wide range of heterocycles
including aminofurans, pyrroles, and novel spirolac-
tones.3,4 Furthermore, the cycloaddition of zwitterions
derived from isocyanide and dimethyl acetylenedicarbox-
ylate (DMAD) with phenyl isocyanate, diethyl mesox-
alate, and dimethyl azodicarboxylate has also been
reported to produce six-membered heterocycles.5,6 Be-
sides isocyanides, other nucleophiles such as triphe-
nylphosphine, tertiary amines, and N-heterocyclic
carbenes have also been utilized to generate zwitterions
from dimethyl acetylenedicarboxylate (DMAD). Subse-
quently, these highly reactive zwitterions have been
trapped with different electrophiles.
CO2Me
MeO2C
CO2Me
CHO
anhyd benzene
25 °C, 4 h
N
H
O
+
N
N
CO2Me
NC
Boc
Boc
1
3
4a: 89%
2
Scheme 1 Reaction of cyclohexyl isocyanide, DMAD, and 3-
formylindole
Indole nucleus is frequently found in medicinal chemistry
and is considered as a ‘privileged scaffold’.7 Substituted
indoles are capable of binding to many receptors with
high affinity. Therefore, there is a continuing interest in
the development of improved methods for the synthesis of
3-substituted indoles.8 Given this proven utility, it seems
likely that the synthesis of a novel series of 3-furanylin-
doles would provide additional lead molecules for use in
drug discovery. It is known that the introduction of two or
more different heterocyclic moieties in a single molecule
Encouraged by the results obtained with 3-formylindole,
we turned our attention to other substituted 3-formylin-
doles. Interestingly, various 3-formylindoles such as 5-
bromo-, and 5-methoxy derivatives underwent smooth
condensation with in situ formed zwitterions from isocy-
anide and DMAD (Table 1). Simple indole-3-carboxalde-
hyde failed to give the desired product under similar
conditions. It is noteworthy to mention that reaction was
successful only with N-Boc-3-formylindoles. Other iso-
cyanides such as tert-butyl isocyanide and 1,1,3,3-tetra-
methylbutyl isocyanide also participated well in this
reaction (Table 1).
SYNTHESIS 2010, No. 15, pp 2571–2576
x
x.
x
x
.
2
0
1
0
Advanced online publication: 18.06.2010
DOI: 10.1055/s-0029-1218824; Art ID: Z08010SS
© Georg Thieme Verlag Stuttgart · New York

2572
B. V. S. Reddy et al.
PAPER
Table 1 Three-Component One-Pot Synthesis of 3-Furanylindoles
Entry
Isocyanide
Enal/DMAD/DEADa
Product 4b
Time (h)
4.0
Yield (%)c
89
MeO2C
CO2Me
CHO
NC
N
H
a
O
O
N
R
N
R
CO2Me
MeO2C
CHO
N
H
b
c
4.0
4.0
87
90
NC
N
R
N
R
CO2Me
MeO2C
CHO
N
H
O
NC
N
R
N
R
CO2Et
EtO2C
CHO
NC
d
4.0
92
N
H
O
N
R
N
R
CO2Et
EtO2C
CHO
e
f
4.0
4.0
4.0
4.0
4.0
4.0
94
91
92
89
85
88
N
H
NC
O
N
R
N
R
CO2Et
EtO2C
CHO
N
H
O
NC
N
R
N
R
CO2Me
MeO2C
CHO
NC
Br
Br
Br
Br
g
h
i
N
H
O
O
N
R
N
R
CO2Me
MeO2C
CHO
Br
N
H
NC
N
R
N
R
CO2Me
MeO2C
CHO
Br
N
H
O
NC
N
R
N
R
CO2Et
EtO2C
CHO
NC
Br
Br
j
N
H
O
N
R
N
R
Synthesis 2010, No. 15, 2571–2576 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of 3-(2-Furanyl)indoles
2573
Table 1 Three-Component One-Pot Synthesis of 3-Furanylindoles (continued)
Entry
Isocyanide
Enal/DMAD/DEADa
Product 4b
Time (h)
Yield (%)c
CO2Et
EtO2C
CHO
Br
Br
k
4.0
87
89
75
76
N
NC
O
H
N
R
N
R
CO2Et
EtO2C
CHO
Br
Br
l
4.0
6.0
6.0
N
H
O
NC
N
R
N
R
CO2Me
MeO2C
CHO
MeO
MeO
NC
m
n
N
H
O
N
R
N
R
CO2Me
MeO2C
CHO
MeO
MeO
N
H
NC
O
N
R
N
R
a DMAD was used for the preparation of 4a–c,g–i,m,n and DEAD was used for the preparation of 4d–f,j–l.
b All the products were characterized by NMR, IR, and mass spectrometry; R = Boc.
c Yield refers to pure products after chromatography.
Diethyl acetylenedicarboxylate (DEAD) was also equally
effective for this conversion (Table 1, entries d–f and j–l).
The structure of 4a–n was established using 1H, 13C NMR,
IR, and HRMS. The scope and generality of this process
is illustrated with respect to various 3-formylindoles and
isocyanides and the results are presented in Table 1. This
method offers several advantages such as high yields of
products, mild reaction conditions, greater regioselectivi-
ty, cleaner reaction profiles, and operational simplicity.
The effect of various solvents such as water, THF, aceto-
nitrile, and benzene was studied for this conversion. As
solvent, benzene appeared to give the best results. No de-
sired product was formed in water. The proposed structure
of 4h was established by X-ray crystallography
(Figure 1).
Figure 1 X-ray crystal structure of 4h
Mechanistically, isocyanide may initially react with di-
methyl acetylenedicarboxylate to generate the 1,4-dipole.
The highly reactive zwitterion undergoes subsequent an-
nulation with 3-formylindole to give the desired fura-
nylindole (Scheme 2).
Melting points were recorded on Büchi R-535 apparatus and are un-
corrected. IR spectra were recorded on a PerkinElmer FT-IR spec-
1
trophotometer using KBr optics. H NMR and 13C spectra were
recorded on Varian Gemini 200 and Bruker 300 spectrometer in
CDCl3 using TMS as internal standard. Mass spectra were recorded
on a Finnigan MAT 1020 mass spectrometer operating at 70 eV.
In conclusion, we have developed a novel three-compo-
nent reaction to accomplish the synthesis of 3-furanylin-
doles in a single step operation. The zwitterion generated
by the addition of isocyanide to dimethyl acetylenedicar-
boxylate has been trapped by N-Boc-3-formylindoles to
produce N-Boc-3-furanylindoles in good yields. We be-
lieve that this method may be useful in generating a wide
range of 3-furanylindoles for drug discovery program.
Dimethyl 2-[1-(tert-Butoxycarbonyl)-1H-indol-3-yl]-5-(cyclo-
hexylamino)furan-3,4-dicarboxylate (4a); Typical Procedure
A mixture of cyclohexyl isocyanide (0.044 g, 0.4 mmol) and di-
methyl acetylenedicarboxylate (0.048 g, 0.4 mmol) in anhyd ben-
zene (5 mL) was purged with N2 at r.t. After 5 min, N-Boc-3-
formylindole (0.100 g, 0.4 mmol) was added and then the resulting
Synthesis 2010, No. 15, 2571–2576 © Thieme Stuttgart · New York

2574
B. V. S. Reddy et al.
PAPER
ESIMS: m/z = 527 (M + H).
CO2Me
HRMS-ESI: m/z calcd for C29H39N2O7: 527.2757; found: 527.240.
(+)
N
: O
(-)
N
+
N
C
+
Boc
Diethyl 2-[1-(tert-Butoxycarbonyl)-1H-indol-3-yl]-5-(cyclohex-
ylamino)furan-3,4-dicarboxylate (4d)
Pale yellow liquid.
–
CO2Me
MeO2C
CO2Me
IR (film): 3347, 2979, 2932, 2856, 1733, 1673, 1614, 1545, 1472,
1374, 1340, 1250, 1215, 1155, 1104, 1070, 1037 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.17 (d, J = 7.9 Hz, 1 H), 7.97 (s,
1 H), 7.80 (d, J = 7.3 Hz, 1 H), 7.34–7.22 (m, 2 H), 6.69 (d, J = 8.1
Hz, 1 H), 4.30 (q, J = 7.1 Hz, 2 H), 4.24 (q, J = 6.9 Hz, 2 H), 3.73
(s, 1 H), 2.08–1.80 (m, 3 H), 1.68 (s, 9 H), 1.55–1.43 (m, 5 H), 1.36–
1.33 (m, 6 H), 0.88–0.83 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 164.7, 164.6, 161.4, 149.2, 138.5,
135.1, 128, 124.2, 123.1, 120.7, 115.3, 113.6, 110.0, 86.7, 84.1,
61.2, 59.5, 51.5, 33.6, 28.1, 25.5, 24.4, 14.4, 14.1.
CO2Me
MeO2C
MeO2C
N
CO2Me
N
O
H
O
N
H
N
Boc
Boc
Scheme 2 A plausible reaction mechanism
ESIMS: m/z = 525 (M + H), 547 (M + Na).
HRMS-ESI: m/z calcd for C29H37N2O7: 525.2600; found: 525.2592.
mixture was allowed to stir at r.t. in benzene for 4 h. After comple-
tion of the reaction as monitored by TLC, the solvent was evaporat-
ed in vacuo and the crude product was purified by column
chromatography on silica gel using EtOAc and hexane as eluent to
give the pure 3-furanylindole 4a; yellow solid; mp 126–128 °C.
Diethyl 2-[1-(tert-Butoxycarbonyl)-1H-indol-3-yl]-5-(tert-butyl-
amino)furan-3,4-dicarboxylate (4e)
Pale yellow liquid.
IR (film): 3332, 2979, 2934, 1737, 1673, 1607, 1547, 1453, 1371,
1297, 1267, 1209, 1155, 1088, 1051 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.18 (d, J = 8.1 Hz, 1 H), 7.95 (s,
1 H), 7.82 (d, J = 7.3 Hz, 1 H), 7.36–7.24 (m, 2 H), 6.95 (s, 1 H),
4.31 (q, J = 7.1 Hz, 2 H), 4.24 (q, J = 6.9 Hz, 2 H), 1.68 (s, 9 H),
1.50 (s, 9 H), 1.33–1.36 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 164.8, 164.7, 161.9, 149.2, 138.3,
135.1, 127.9, 124.8, 124.6, 123.1, 120.4, 115.3, 113.6, 110.0, 87.8,
84.1, 61.2, 59.5, 52.6, 30.0, 28.0, 14.3, 14.1.
IR (KBr): 3358, 2925, 2853, 1737, 1676, 1614, 1457, 1370, 1234,
1154, 1106, 1073 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.19 (d, J = 8.1 Hz, 1 H), 7.99 (s,
1 H), 7.82 (d, J = 7.3 Hz, 1 H), 7.38–7.26 (m, 2 H), 6.66 (d, J = 8.1
Hz, 1 H), 3.86 (s, 3 H), 3.79 (s, 4 H), 2.08–1.79 (m, 6 H), 1.68 (s, 9
H), 1.44–1.33 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 164.7, 164.6, 161.4, 149.4, 138.5,
135.1, 128, 124.8, 124.2, 123.1, 120.7, 115.3, 113.6, 110.0, 86.7,
84.1, 61.0, 59.5, 51.5, 33.6, 28.1, 25.4, 24.4.
ESIMS: m/z = 499 (M + H).
ESIMS: m/z = 497 (M + H).
HRMS-ESI: m/z calcd for C27H35N2O7: 499.2444; found: 499.2450.
HRMS-ESI: m/z calcd for C27H33N2O7: 497.2287; found: 497.2295.
Diethyl 2-[1-(tert-Butoxycarbonyl)-1H-indol-3-yl]-5-(2,4,4-tri-
methylpentan-2-ylamino)furan-3,4-dicarboxylate (4f)
Pale yellow liquid.
Dimethyl 2-[1-(tert-Butoxycarbonyl)-1H-indol-3-yl]-5-(tert-bu-
tylamino)furan-3,4-dicarboxylate (4b)
Yellow solid; mp 117–120 °C.
IR (film): 3332, 2974, 1737, 1671, 1607, 1547, 1454, 1371, 1213,
1154, 1086, 1051 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.18 (d, J = 8.3 Hz, 1 H), 7.94 (s,
1 H), 7.84 (d, J = 7.5 Hz, 1 H), 7.36–7.23 (m, 2 H), 7.07 (s, 1 H),
4.35–4.20 (m, 4 H), 1.82 (s, 2 H), 1.68 (s, 9 H), 1.54 (s, 6 H), 1.36–
1.33 (m, 6 H), 1.05 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.8, 164.7, 161.7, 149.2, 138,
135.1, 127.9, 124.7, 124.5, 123.0, 120.5, 115.3, 113.7, 110.0, 87.5,
84.0, 61.2, 59.5, 56.32, 53.4, 31.6, 31.4, 30.3, 28.0, 14.3, 14.1.
IR (KBr): 3500, 2922, 2852, 1714, 1512, 1461, 1376, 1258, 1140,
1036 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.19 (d, J = 8.1 Hz, 1 H), 7.96 (s,
1 H), 7.82 (d, J = 7.3 Hz, 1 H), 7.39–7.26 (m, 2 H), 6.94 (s, 1 H),
3.85 (s, 3 H), 3.79 (s, 3 H), 1.68 (s, 9 H), 1.49 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.8, 164.7, 161.9, 149.2, 138.3,
135.1, 127.9, 124.8, 124.6, 123.1, 120.4, 115.3, 113.6, 110.0, 87.8,
84.1, 61.2, 59.5, 52.6, 30.0, 28.0.
ESIMS: m/z = 471 (M + H), 493 (M + Na).
ESIMS: m/z = 555 (M + H), 577 (M + Na).
HRMS-ESI: m/z calcd for C25H31N2O7: 471.2131; found: 471.2135.
HRMS-ESI: m/z calcd for C31H43N2O7: 555.3070; found: 555.3056.
Dimethyl 2-[1-(tert-Butoxycarbonyl)-1H-indol-3-yl]-5-(2,4,4-
trimethylpentan-2-ylamino)furan-3,4-dicarboxylate (4c)
Pale yellow liquid.
Dimethyl 2-[5-Bromo-1-(tert-butoxycarbonyl)-1H-indol-3-yl]-
5-cyclohexylamino)furan-3,4-dicarboxylate (4g)
Pale orange solid; mp 185–187 °C.
IR (film): 3337, 2952, 1738, 1675, 1608, 1455, 1371, 1216, 1154,
1087 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.19 (d, J = 8.3 Hz, 1 H), 7.95 (s,
1 H), 7.83 (d, J = 7.7 Hz, 1 H), 7.39–7.26 (m, 2 H), 7.05 (s, 1 H),
3.85 (s, 3 H), 3.79 (s, 3 H), 1.81 (s, 2 H), 1.68 (s, 9 H), 1.54 (s, 6 H),
1.04 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.2, 165.1, 161.8, 149.2, 138.6,
135.1, 127.8, 124.8, 123.0, 120.4, 115.3, 113.3, 109.9, 87.2, 84.1,
56.3, 53.4, 52.1, 51.0, 31.4, 30.3, 29.6, 28.0.
IR (KBr): 3356, 2931, 2854, 1738, 1675, 1616, 1541, 1451, 1368,
1268, 1231, 1153, 1107, 1073 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.06–8.01 (m, 3 H), 7.42–7.39 (d,
J = 1.9 Hz, 1 H), 6.66 (d, J = 7.9 Hz, 1 H), 3.84 (s, 3 H), 3.78 (s, 4
H), 2.17–2.14 (m, 2 H), 1.87–1.83 (m, 2 H), 1.68 (s, 9 H), 1.54–1.41
(m, 5 H), 1.33–1.28 (m, 1 H).
Synthesis 2010, No. 15, 2571–2576 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of 3-(2-Furanyl)indoles
2575
13C NMR (75 MHz, CDCl3): d = 164.9, 164.7, 161.3, 148.8, 138.6,
133.7, 129.4, 127.5, 124.9, 123.8, 116.6, 116.5, 113.1, 109.2, 86.3,
84.6, 52.1, 51.9, 51.0, 33.7, 28.0, 25.3, 24.7.
IR (KBr): 3351, 3160, 2979, 2933, 1739, 1672, 1608, 1542, 1451,
1369, 1270, 1209, 1155, 1088, 1052 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.07–8.02 (m, 2 H), 7.90 (s, 1 H),
7.42 (d, J = 1.8 Hz, 1 H), 6.96 (s, 1 H), 4.30 (q, J = 7.1 Hz, 2 H),
4.24 (q, J = 7.1 Hz, 2 H), 1.67 (s, 9 H), 1.52 (s, 9 H), 1.35 (t, J = 7.1
Hz, 3 H), 1.32 (t, J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.7, 164.6, 161.8, 148.9, 137.7,
133.8, 129.5, 127.6, 125.2, 123.4, 116.7, 116.5, 113.9, 109.4, 87.8,
84.6, 61.3, 59.6, 52.7, 30.0, 28.0, 14.3, 14.1.
ESIMS: m/z = 575 (M + H).
HRMS-ESI: m/z calcd for C27H32BrN2O7: 575.1392; found:
575.1400.
Dimethyl 2-[5-Bromo-1-(tert-butoxycarbonyl)-1H-indol-3-yl]-
5-(tert-butylamino)furan-3,4-dicarboxylate (4h)
White crystalline solid; mp 183–185 °C.
ESIMS: m/z = 577 (M + H).
IR (KBr): 3327, 3148, 2974, 1747, 1669, 1617, 1541, 1450, 1369,
1272, 1216, 1154, 1084, 1051 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.08–7.99 (m, 3 H), 7.44 (d,
J = 1.8 Hz, 1 H), 6.96 (s, 1 H), 3.88 (s, 3 H), 3.80 (s, 3 H), 1.68 (s,
9 H), 1.52 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.1, 164.8, 161.8, 148.8, 138.2,
133.7, 129.4, 127.6, 125.5, 123.4, 116.6, 116.4, 113.4, 109.2, 87.6,
84.6, 52.7, 52.1, 51.0, 29.9, 28.0.
HRMS-ESI: m/z calcd for C27H34BrN2O7: 577.1549; found:
577.1553.
Dethyl 2-[5-Bromo-1-(tert-butoxycarbonyl)-1H-indol-3-yl]-5-
(2,4,4-trimethylpentan-2-ylamino)furan-3,4-dicarboxylate (4l)
Yellow liquid.
IR (film): 3332, 2975, 1739, 1671, 1607, 1542, 1451, 1368, 1267,
1214, 1154, 1086, 1052 cm–1.
ESIMS: m/z = 549 (M + H).
1H NMR (300 MHz, CDCl3): d = 8.06 (d, J = 8.4 Hz, 1 H), 8.01 (s,
1 H), 7.93 (s, 1 H), 7.43 (d, J = 8.4 Hz, 1 H), 7.08 (s, 1 H), 4.31 (q,
J = 6.7 Hz, 2 H), 4.24 (q, J = 6.7 Hz, 2 H), 1.83 (s, 2 H), 1.67 (s, 9
H), 1.56 (s, 6 H), 1.35 (t, J = 6.7, 7.5 Hz, 3 H), 1.32 (t, J = 6.7 Hz,
3 H), 1.06 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.8, 164.7, 161.7, 148.9, 137.3,
133.9, 129.5, 127.6, 125.2, 123.3, 116.7, 116.5, 114.1, 109.4, 87.5,
84.6, 61.4, 59.6, 56.4, 53.5, 31.5, 30.3, 29.6, 28.0, 14.3, 14.1.
HRMS-ESI: m/z calcd for C25H30BrN2O7: 549.1236; found:
549.1228.
Dimethyl 2-[5-Bromo-1-(tert-butoxycarbonyl)-1H-indol-3-yl]-
5-(2,4,4-trimethylpentan-2-ylamino)furan-3,4-dicarboxylate
(4i)
Yellow liquid.
IR (film): 3418, 2952, 1740, 1674, 1608, 1540, 1451, 1367, 1268,
1220, 1153, 1087, 1052 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.05 (d, J = 8.6 Hz, 1 H), 8.01 (d,
J = 2.0 Hz, 1 H), 7.96 (s, 1 H), 7.42 (d, J = 2.0 Hz, 1 H), 7.09 (s, 1
H), 3.84 (s, 3 H), 3.78 (s, 3 H), 1.83 (s, 2 H), 1.68 (s, 9 H), 1.56 (s,
6 H), 1.06 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.1, 165, 161.7, 148.9, 137.9,
133.8, 129.4, 127.6, 125.5, 123.3, 116.7, 116.5, 113.6, 109.3, 87.2,
84.6, 56.4, 53.5, 52.2, 51.0, 31.4, 30.3, 29.6, 28.0.
ESIMS: m/z = 633 (M + H).
HRMS-ESI: m/z calcd for C31H42BrN2O7: 633.2175; found:
633.2177.
Dimethyl 2-[1-(tert-Butoxycarbonyl)-5-methoxy-1H-indol-3-
yl]-5-(cyclohexylamino)furan-3,4-dicarboxylate (4m)
Brown liquid.
IR (film): 3348, 2928, 2854, 1734, 1675, 1617, 1471, 1372, 1248,
1155, 1105, 1072, 1034 cm–1.
ESIMS: m/z = 605 (M + H).
1H NMR (300 MHz, CDCl3): d = 8.02 (br d, J = 9.0 Hz, 1 H), 7.94
(s, 1 H), 7.24 (d, J = 2.2 Hz, 1 H), 6.91 (d, J = 2.1 Hz, 1 H), 6.70 (d,
J = 7.5 Hz, 1 H), 3.83 (s, 3 H), 3.82 (s, 3 H), 3.78 (s, 4 H), 2.15–2.04
(m, 2 H), 1.84–1.71 (m, 2 H), 1.69 (s, 9 H), 1.43–1.22 (m, 3 H),
1.21–1.11 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.7, 164.6, 161.4, 156.0, 149.2,
138.6, 129.8, 128.7, 124.7, 115.9, 113.9, 113.5, 109.8, 103.0, 86.6,
83.9, 61.2, 59.5, 55.4, 51.4, 33.6, 25.3, 24.5.
HRMS-ESI: m/z calcd for C29H38BrN2O7: 605.1862; found:
605.1855.
Diethyl 2-[5-Bromo-1-(tert-butoxycarbonyl)-1H-indol-3-yl]-5-
(cyclohexylamino)furan-3,4-dicarboxylate (4j)
Yellow solid; mp 118–120 °C.
IR (KBr): 3459, 3160, 2978, 2930, 2855, 1748, 1669, 1623, 1541,
1452, 1370, 1270, 1230, 1102, 1069 cm–1.
ESIMS: m/z = 527 (M + H), 549 (M + Na).
1H NMR (300 MHz, CDCl3): d = 8.05 (d, J = 8.9 Hz, 1 H), 8.01 (d,
J = 1.6 Hz, 1 H), 7.99 (s, 1 H), 7.41 (d, J = 2.4 Hz, 1 H), 6.67 (d,
J = 7.3 Hz, 1 H), 4.32 (q, J = 6.5 Hz, 2 H), 4.24 (q, J = 7.3 Hz, 2
H), 2.15 (s, 2 H), 1.87–1.79 (m, 2 H), 1.68 (s, 9 H), 1.60–1.41 (m, 5
H), 1.36 (t, J = 6.5 Hz, 3 H), 1.32 (t, J = 7.3 Hz, 3 H).
HRMS-ESI: m/z calcd for C28H35N2O8: 527.2393; found: 527.2412.
Dimethyl 2-[1-(tert-Butoxycarbonyl)-5-methoxy-1H-indol-3-
yl]-5-(tert-butylamino)furan-3,4-dicarboxylate (4n)
Brown liquid.
13C NMR (75 MHz, CDCl3): d = 164.6, 164.5, 161.3, 148.9, 138.0,
133.8, 129.5, 127.6, 124.7, 123.8, 116.7, 116.5, 113.7, 109.4, 86.6,
84.6, 61.3, 59.6, 51.8, 33.7, 28.0, 25.4, 24.7, 14.4, 14.1.
IR (film): 3450, 2929, 1735, 1675, 1609, 1545, 1471, 1373, 1251,
1211, 1156, 1091, 1054 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.01 (d, J = 8.8 Hz, 1 H), 7.92 (s,
1 H), 7.25 (s,1 H), 6.95–6.90 (m, 2 H), 3.82 (s, 3 H), 3.81 (s, 3 H),
3.78 (s, 3 H), 1.68 (s, 9 H), 1.52 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.2, 165.0, 161.9, 156.1, 149.2,
138.9, 129.7, 128.6, 125.3, 116.1, 114.3, 113.0, 109.7, 102.4, 87.7,
84.0, 55.5, 52.7, 52.2, 51.0, 30.0, 28.0.
ESIMS: m/z = 603 (M + H).
HRMS-ESI: m/z calcd for C27H37BrN2O7 + Na: 603.1681; found:
603.1659.
Diethyl 2-[5-Bromo-1-(tert-butoxycarbonyl)-1H-indol-3-yl]-5-
(tert-butylamino)furan-3,4-dicarboxylate (4k)
Orange solid; mp 166–168 °C.
ESIMS: m/z = 501 (M + H), 523 (M + Na).
HRMS-ESI: m/z calcd for C26H33N2O8: 501.2236; found: 501.2239.
Synthesis 2010, No. 15, 2571–2576 © Thieme Stuttgart · New York

2576
B. V. S. Reddy et al.
PAPER
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Acknowledgment
D.S.S. and A.M.R. thank CSIR, New Delhi for the award of fel-
lowships.
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Synthesis 2010, No. 15, 2571–2576 © Thieme Stuttgart · New York