Microwave-assisted one-pot synthesis of pyrazolo[3,4- b]indoles and new isoxazolo[5,4- b]indoles via copper-catalyzed intramolecular C-N/C-O bond formation

Article abstract of DOI:10.1055/s-0031-1289572

A facile one-pot, two-step synthesis of highly substituted pyrazolo[3,4-b]indoles and isoxazolo[5,4-b]indoles was developed via microwave-assisted, copper-catalyzed intramolecular heterocyclization (involving C-N/C-O bond formation) from 3-acetyl-2-chloroindoles in good to excellent yields. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0031-1289572

3878
PAPER
Microwave-Assisted One-Pot Synthesis of Pyrazolo[3,4-b]indoles and New
Isoxazolo[5,4-b]indoles via Copper-Catalyzed Intramolecular C–N/C–O Bond
Formation
S
ynthesis of Pyraz
r
olo[3,4-
b
e
]indolesan
p
dIsoxazolo[
a
5,4-
b
]indol
l
es li Sateesh Kumar, P. V. Amulya Rao, Rajagopal Nagarajan*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Fax +91(40)23012460; E-mail: rnsc@uohyd.ernet.in
Received 1 August 2011; revised 19 September 2011
A survey of the literature disclosed that the pyrazolo[3,4-
b]indole skeleton (Figure 1) has been found to display an-
tiviral activity against HCMV (human cytomegalovi-
rus)15c and the reported synthetic methods were poorly
accomplished without further details involving applicabil-
ity and scope.15 Recently, Ila and co-workers reported16
the synthesis of pyrazolo[3,4-b]indoles through a palladi-
um-catalyzed intramolecular cyclization. To the best of
our knowledge, however, this is the first report on the syn-
thesis of highly substituted, new isoxazolo[5,4-b]indoles
and pyrazolo[3,4-b]indoles via microwave-assisted one-
pot, two-step, copper-catalyzed intramolecular O-het-
eroarylation and N-heteroarylation.
Abstract: A facile one-pot, two-step synthesis of highly substituted
pyrazolo[3,4-b]indoles and isoxazolo[5,4-b]indoles was developed
via microwave-assisted, copper-catalyzed intramolecular heterocy-
clization (involving C–N/C–O bond formation) from 3-acetyl-2-
chloroindoles in good to excellent yields.
Key words: copper catalysis, 3-acyl-2-chloroindoles, pyrazo-
lo[3,4-b]indoles, isoxazolo[5,4-b]indoles, intramolecular hetero-
arylation
Nitrogen- and oxygen-containing heterocycles are being
given great attention due to their role in the pharmaceuti-
cal industry and their occurrence in natural, biologically
active1 organic compounds, as well as in drugs such as
Celebrex2 and Viagra.3 Moreover, pyrazole and
H2N
Cl
Cl
isoxazole4 nuclei are prominent structural motifs found in
several natural products and synthetic compounds with vi-
tal medicinal value, and also the indole system is found in
numerous natural products as well as in therapeutics.5 The
synthesis of fused indoles has therefore become an impor-
tant research field and several synthetic methods have
been developed.6 The core structure of a fused indole is
N
N
N
Cl
HO
NH
Cl
HO
N
Me
N
O
O
OH
HO
OH
HO
Figure 1 (2R,3S,4R,5R)-2-(5,6-Dichloropyrazolo[3,4-b]indol-8(1H)-
present in numerous biologically active indole deriva- yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol nucleosides having
tives, such as mitomycin and vincamine.7 We were inter-
antiviral and cytotoxic activity
ested in developing an efficient synthetic method for
biologically important indoles fused with pyrazole and
To obtain the best optimized reaction conditions for the
isoxazole frameworks through copper-catalyzed intramo-
synthesis of pyrazolo[3,4-b]indoles and isoxazolo[5,4-
lecular C–N and C–O bond formation.
b]indoles, we initiated our investigation with convention-
During the past century, cross-coupling reactions have
emerged as a powerful tool in organic synthesis,8 in par-
ticular the copper-mediated Ullmann reaction9 (N-aryla-
tion of amine) and the Goldberg reaction10 (N-arylation of
amide); however, these reactions have limitations, such as
high reaction temperatures and the necessity to use sto-
ichiometric amounts of copper, and several modifications
have been introduced to overcome these shortcomings for
the construction of carbon–carbon, carbon–nitrogen and
carbon–oxygen bonds.11–14 The success of these results
prompted us to examine copper-catalyzed N-heteroaryla-
tion and O-heteroarylation in the synthesis of pyrazo-
lo[3,4-b]indoles and isoxazolo[5,4-b]indoles, especially
for 3-acyl-2-chloroindoles as starting materials.
al heating, as shown in Tables 1 and 2, respectively.
These data show the effect of various parameters, such as
different copper sources (CuI, CuBr, CuCl, Cu2O),
ligands (see Figure 2), bases (Cs2CO3, K2CO3, K3PO4,
Et3N, t-BuOK) and solvents (DMSO, DMF, NMP,
MeOH, toluene, MeCN) at various temperatures, on the
efficiency of the reaction.
Gratifyingly, in our initial experiments we noticed that
good yields could be achieved in the presence of a cop-
per(I) iodide/trans-1,2-diaminocyclohexane catalyst sys-
tem with potassium carbonate as base and N-methyl-2-
pyrrolidinone (NMP) as solvent at 160 °C for the forma-
tion of 8-ethyl-3-methyl-1-phenyl-1,8-dihydropyrazo-
lo[3,4-b]indole in 62% yield (Table 1, entry 9) and 8-
ethyl-3-methyl-8H-isoxazolo[5,4-b]indole in 66% yield
(Table 2, entry 5) by conventional heating.
SYNTHESIS 2011, No. 23, pp 3878–3886
x
x.
x
x
.
2
0
1
1
Advanced online publication: 21.10.2011
DOI: 10.1055/s-0031-1289572; Art ID: Z75511SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Pyrazolo[3,4-b]indoles and Isoxazolo[5,4-b]indoles
3879
NH2
MeHN
NHMe
N
N
N
N
NH2
N1,N2-dimethylethane-1,2-diamine
1,10-phenanthroline
trans-1,2-diaminocyclohexane
2,2'-bipyridine
L1
L2
L3
L4
N
N
OH
HO
OH
OH
COOH
N
H
L-proline
ethane-1,2-diol
1,1'-binaphthyl-2,2'-diol
DABCO
L5
L6
L7
L8
Figure 2 Selected ligands used in copper-catalyzed intramolecular heterocyclization
Table 1 Optimization of the Copper-Catalyzed Synthesis of 8-Ethyl-3-methyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole (2c)
O
NHNH2
1) solvent
N
Cu source (5 mol%)
+
N
Cl
N
N
2) ligand (10 mol%)
base, temp, time
2c
1b
Microwave heating
Conventional heating
Temp (°C) Time (min) Yield (%) Temp (°C) Time (h) Yield (%)
Entry
1
Catalyst
–
Ligand
–
Base
Solvent
DMSO
DMSO
DMSO
DMSO
DMF
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
60
60
60
60
60
60
60
60
20
30
30
30
30
30
30
30
30
30
30
30
30
–
150
150
150
150
150
110
100
100
160
160
160
160
160
160
110
160
160
160
160
150
150
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
–
2
CuO
Cu2O
CuI
L1
L1
L1
L2
L3
L4
L5
L3
L3
L3
L3
L3
L3
L6
L7
L8
L3
–
–
–
3
20
38
–
17
–
4
5
CuI
–
6
CuI
Cs2CO3
t-BuOK
K2CO3
K2CO3
Cs2CO3
K3PO4
t-BuOK
K2CO3
K2CO3
Et3N
DMSO
MeOH
MeCN
NMP
NMP
45
–
–
7
CuI
–
8
CuCl
CuI
CuI
25
92
86
71
52
36
10
–
–
9
62
65
52
47
30
–
10
11
12
13
14
15
16
17
18
19
20
21
CuI
NMP
CuI
NMP
CuBr
CuCl
CuI
NMP
NMP
toluene
DMF
–
CuI
Cs2CO3
Et3N
–
–
CuI
DMF
–
–
Cu2O
CuI
Et3N
DMF
–
–
K2CO3
K2CO3
K2CO3
NMP
20
–
12
–
–
L3
L2
NMP
CuI
NMP
83
67
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

3880
A. S. Kumar et al.
PAPER
Having an interest in the application of microwave irradi- b]indoles 3 in good to excellent yields, as shown in
ation technology,17 we used microwave heating to speed Tables 3 and 4, respectively.
up the optimized reaction, at first conducting the synthesis
With our successfully developed method for the synthesis
of the pyrazolo[3,4-b]indoles and isoxazolo[5,4-b]indoles
of pyrazolo[3,4-b]indoles and isoxazolo[5,4-b]indoles,
in a single step in one pot. After several experiments, we
we concluded that an electron-withdrawing group present
in position 1 of the 3-acetyl-2-chloroindoles 1 produced
excellent yields, as shown for the formation of 2d (95%)
and 2p (93%) in Table 3, and 3c (96%) and 3h (94%) in
concluded that better yields could be achieved by stepwise
cyclization. Thus, the one-pot, two-step, copper-catalyzed
intramolecular N-heteroarylation and O-heteroarylation
procedure was developed. We found that the reaction was
completed in the second step within 10–15 minutes and
the isolated yields were 92% for 2c (Table 1, entry 9) and
90% for 3b (Table 2, entry 5). Finally, we found that the
best reaction conditions for the formation of pyrazolo[3,4-
Table 4, relative to electron-releasing groups. The struc-
ture of compound 2a was also determined by X-ray crys-
tallography.18 The ORTEP diagram of 2a is shown in
Figure 3.
In conclusion, we have described a rapid, convenient and
high-yielding method for the synthesis of an array of pyra-
zolo[3,4-b]indoles and isoxazolo[5,4-b]indoles via micro-
wave-assisted one-pot, two-step, copper-catalyzed
b]indoles and isoxazolo[5,4-b]indoles in the second step
involves 5 mol% of copper(I) iodide, 10 mol% of trans-
1,2-diaminocyclohexane, 2.0 equivalents of potassium
carbonate as base and NMP as solvent. By employing the
intramolecular heteroarylation involving C–N/C–O bond
optimal reaction conditions in the second step, we synthe-
formation.
sized various pyrazolo[3,4-b]indoles 2 and isoxazolo[5,4-
Table 2 Optimization of the Copper-Catalyzed Synthesis of 8-Ethyl-3-methyl-8H-isoxazolo[5,4-b]indole (3b)
O
1) solvent
Cu source (5 mol%)
N
+
O
NH2OH⋅HCl
Cl
N
N
2) ligand (10 mol%)
base, temp, time
1b
3b
Microwave heating
Conventional heating
Temp (°C) Time (min) Yield (%) Temp (°C) Time (h) Yield (%)
Entry
1
Catalyst
CuI
Ligand
Base
Solvent
L8
L7
L6
L4
L3
L5
L1
L2
L3
L3
L3
L3
L3
L3
L5
L7
L8
L3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
t-BuOK
K2CO3
Cs2CO3
Cs2CO3
K3PO4
t-BuOK
K2CO3
K2CO3
Et3N
DMSO
DMSO
DMSO
DMSO
NMP
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
60
60
60
60
20
60
60
60
20
30
30
30
30
30
30
30
30
30
15
–
150
150
160
160
160
110
70
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
7
2
Cu2O
Cu2O
CuI
–
3
15
38
90
45
–
17
5
4
5
CuI
CuI
66
–
6
dioxane
MeOH
MeCN
DMF
7
CuI
–
8
CuCl
CuI
25
55
87
83
49
10
17
–
70
–
9
160
110
160
160
110
110
110
160
160
160
32
65
52
47
30
–
10
11
12
13
14
15
16
17
18
CuI
NMP
CuI
NMP
CuI
DMF
CuBr
CuCl
CuI
toluene
NMP
NMP
–
CuI
Cs2CO3
Et3N
DMF
–
–
CuI
DMF
–
–
CuCl
Et3N
DMSO
–
–
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

PAPER
Synthesis of Pyrazolo[3,4-b]indoles and Isoxazolo[5,4-b]indoles
Table 4 Synthesis of Isoxazolo[5,4-b]indolesa
3881
Table 3 Synthesis of Pyrazolo[3,4-b]indolesa
O
O
R2
R2
1) R3NHNH2, NMP
MW, 120 °C, 10 min
1) NH2OH⋅HCl, NMP
R2
R2
MW, 120 °C, 10 min
N
N
O
Cl
Cl
N
N
R1
N
R1
2) CuI, K2CO3
trans-1,2-diaminocyclohexane
MW, 120 °C, 10–15 min
2) CuI, K2CO3
trans-1,2-diaminocyclohexane
MW, 120 °C, 10–20 min
N
R1
N
R1
R3
1
3
1
2
Product
R1
R2
Me
Me
Me
Me
Me
H
Time (min) Yieldb (%)
Product R1
R2
R3
Time (min) Yieldb (%)
3a
3b
3c
3d
3e
3f
H
20
15
10
10
10
15
13
13
10
15
86
90
96
93
89
82
86
94
86
88
2a
2b
2c
2d
2e
2f
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
Ph
10
10
10
10
10
10
15
15
10
10
10
15
15
13
10
10
89
92
94
95
93
89
86
83
89
87
86
88
82
86
86
93
Et
Et
Et
Bn
Bu
H
Bn
Bu
n-Hex
H
Ph
Ph
Ph
n-Hex
Bu
Ph
3g
3h
3i
Et
H
2g
2h
2i
3-O2NC6H4
3-O2NC6H4
4-ClC6H4
4-NCC6H4
3-Tol
Bn
Bu
n-Hex
H
n-Hex
Bu
H
3j
H
2j
Bu
a Reaction conditions: (1) 3-acyl-2-chloroindole 1 (0.5 mmol, 1.0
equiv), NH2OH·HCl (0.5 mmol, 1.0 equiv), NMP (0.5 mL), MW,
120 °C; (2) CuI (5 mol%), trans-1,2-diaminocyclohexane (10 mol%),
K2CO3 (2.0 equiv), MW, 120 °C.
2k
2l
Bu
n-Hex
H
Ph
b Yield refers to the column-purified product.
2m
2n
2o
2p
H
Ph
Et
H
Ph
Bu
H
Ph
The procedure does not require an inert atmosphere. All the prod-
ucts obtained were purified by column chromatography using silica
gel (100–200 mesh) with EtOAc–hexane as the eluent. 1H NMR and
13C NMR spectra were recorded in CDCl3 with TMS at 400 MHz
and 100 MHz, respectively, on a Bruker DRX 400 instrument. The
chemical shifts are reported in ppm downfield to TMS (d = 0 ppm)
for 1H NMR and relative to the central CDCl3 resonance (d = 77.0
ppm) for 13C NMR spectra. The coupling constants, J, are given in
Hz. IR spectra were recorded on a Jasco FT/IR-5300 spectropho-
tometer. The X-ray diffraction measurements were carried out at
298 K on a Bruker Smart Apex CCD automated diffractometer us-
ing graphite monochromated Mo Ka (l = 0.71073 Å) radiation
with CAD4 software, or the X-ray intensity data were measured at
298 K on a Bruker Smart Apex CCD diffractometer equipped with
a graphite monochromator and a Mo Ka fine-focus sealed tube
(l = 0.71073 Å). Elemental analyses were recorded on a Thermo
Finnigan Flash EA 1112 analyzer at the School of Chemistry, Uni-
versity of Hyderabad. Mass spectra were recorded on a Shimadzu
LCMS-2010A mass spectrometer. Melting points were measured in
open capillary tubes and are uncorrected. Microwave reactions were
performed with an LG (MG 607APR)TM 900 W domestic micro-
wave oven.
Bn
H
Ph
a Reaction conditions: (1) 3-acyl-2-chloroindole 1 (0.5 mmol, 1.0
equiv), R3NHNH2 (0.5 mmol, 1.0 equiv), NMP (0.5 mL), MW,
120 °C; (2) CuI (5 mol%), trans-1,2-diaminocyclohexane (10 mol%),
K2CO3 (2.0 equiv), MW, 120 °C.
b Yield refers to the column-purified product.
8-Ethyl-3-methyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole
(2c); Typical Procedure
A domestic microwave oven was charged with 3-acetyl-2-chloro-1-
ethyl-1H-indole (100 mg, 0.5 mmol, 1.0 equiv), PhNHNH2 (48 mg,
0.5 mmol, 1.0 equiv) and NMP (0.5 mL) in an open vessel. The ves-
sel was heated at 120 °C for 10 min (fixed hold time) in the micro-
wave oven. Then, to the preformed hydrazone solution, K2CO3 (124
Figure 3 ORTEP diagram of 2a
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

3882
A. S. Kumar et al.
PAPER
mg, 1.0 mmol, 2.0 equiv), CuI (4 mg, 0.025 mmol, 0.05 equiv) and
trans-1,2-diaminocyclohexane (5 mg, 0.05 mmol, 0.1 equiv) were
added. The reaction vessel was again heated at 120 °C for 10 min
(fixed hold time) in the microwave oven. The reaction mixture was
filtered through Celite® and purified by column chromatography
(EtOAc–hexane) to give 2c as a colorless viscous liquid; yield: 117
mg (94%).
Anal. Calcd for C23H19N3: C, 81.87; H, 5.68; N, 12.45. Found: C,
81.65; H, 5.75; N, 12.32.
8-Butyl-3-methyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole
(2e)
Yield: 112 mg (93%); pale brown, viscous liquid.
IR (KBr): 2926, 2858, 1686, 1554, 1448, 1161, 1107, 1018, 744
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.54–7.50 (d, J = 8.0 Hz, 1 H),
7.45–7.41 (m, 2 H), 7.29–7.28 (m, 2 H), 7.26–7.24 (m, 1 H), 7.23–
7.21 (m, 3 H), 4.01–3.97 (m, 2 H), 2.76 (s, 3 H), 1.04–1.00 (m, 2 H),
0.90–0.87 (m, 2 H), 0.68 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 146.7, 142.7, 141.6, 139.0, 132.3,
129.2, 128.0, 125.3, 121.9, 120.2, 119.8, 119.0, 109.8, 108.4, 43.6,
31.0, 19.7, 14.1, 13.6, 13.4.
IR (KBr): 3051, 2928, 2854, 1595, 1564, 1520, 1494, 1454, 1375,
1321, 1261, 1165, 1103, 1020, 742 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.2 Hz, 1 H), 7.62–
7.61 (m, 2 H), 7.56–7.52 (m, 2 H), 7.46–7.44 (m, 1 H), 7.31–7.24
(m, 3 H), 4.08 (q, J = 7.2 Hz, 2 H), 2.68 (s, 3 H), 1.13 (t, J = 4.2 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 146.4, 142.5, 141.7, 139.3, 129.2,
127.8, 124.9, 121.9, 119.0, 110.0, 109.7, 38.6, 29.7, 22.7.
LC-MS (positive mode): m/z = 276 [M + H]+.
LC-MS (positive mode): m/z = 304 [M + H]+.
Anal. Calcd for C18H17N3: C, 78.52; H, 6.22; N, 15.26. Found: C,
78.65; H, 6.25; N, 15.07.
Anal. Calcd for C20H21N3: C, 79.17; H, 6.98; N, 13.85. Found: C,
79.26; H, 6.89; N, 13.68.
3-Methyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole (2a)
Yield: 113 mg (89%); colorless solid; mp 161–163 °C.
8-Hexyl-3-methyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole
(2f)
Yield: 106 mg (89%); colorless viscous liquid.
IR (KBr): 3223, 3063, 2928, 2878, 1682, 1670, 1593, 1560, 1502,
1450, 1404, 1302, 1263, 1224, 1113, 1076, 1026, 1003, 754, 692
cm–1.
IR (KBr): 3362, 2926, 2854, 1599, 1558, 1523, 1493, 1454, 1157,
1028, 740, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.48 (s, 1 H), 7.72–7.67 (m, 3 H),
7.45 (t, J = 7.2 Hz, 2 H), 7.38–7.26 (m, 1 H), 7.25–7.20 (m, 3 H),
2.68 (s, 3 H).
1H NMR (400 MHz, CDCl3): d = 8.40–8.39 (m, 1 H), 7.32–7.28 (m,
8 H), 4.27–4.23 (m, 2 H), 2.71 (s, 3 H), 1.83–1.39 (m, 2 H), 1.37–
1.23 (m, 4 H), 0.93–0.91 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 144.7, 142.1, 141.6, 139.1, 129.1,
125.4, 122.5, 121.9, 121.3, 120.3, 119.0, 118.4, 117.5, 112.0, 111.2,
31.8.
13C NMR (100 MHz, CDCl3): d = 142.7, 141.6, 139.2, 129.5, 129.2,
128.3, 127.9, 126.9, 125.6, 125.3, 121.8, 120.1, 119.8, 119.0, 115.3,
109.8, 43.8, 31.0, 28.9, 26.1, 22.3, 13.8.
LC-MS (positive mode): m/z = 248 [M + H]+.
LC-MS (positive mode): m/z = 332 [M + H]+.
Anal. Calcd for C16H13N3: C, 77.71; H, 5.30; N, 16.99. Found: C,
77.65; H, 5.36; N, 16.85.
Anal. Calcd for C22H25N3: C, 79.72; H, 7.60; N, 12.68. Found: C,
79.63; H, 7.55; N, 12.59.
8-Ethyl-3-methyl-1,8-dihydropyrazolo[3,4-b]indole (2b)
Yield: 92 mg (92%); brown viscous liquid.
8-Butyl-3-methyl-1-(3-nitrophenyl)-1,8-dihydropyrazolo[3,4-
b]indole (2g)
Yield: 119 mg (86%); pale yellow solid; mp 225–227 °C.
IR (KBr): 2924, 2860, 1633, 1599, 1452, 1375, 1338, 1269, 1269,
1091, 1018, 740 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.70 (d, J = 8.0 Hz, 1 H), 7.32–
7.24 (m, 2 H), 7.11 (t, J = 8.0 Hz, 1 H), 4.18 (q, J = 8.0 Hz, 2 H),
2.63 (s, 3 H), 1.45 (t, J = 4.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 157.8, 144.3, 130.9, 123.4, 120.2,
119.5, 118.6, 108.6, 107.3, 38.1, 13.7, 11.5.
IR (KBr): 2959, 2930, 2866, 1614, 1554, 1523, 1475, 1442, 1352,
1165, 1107, 1026, 879, 798, 752 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.46 (t, J = 4.0 Hz, 1 H), 8.27–
8.25 (m, 1 H), 8.01–8.00 (m, 1 H), 7.99–7.77 (m, 2 H), 7.75–7.25
(m, 3 H), 4.10 (t, J = 6.0 Hz, 2 H), 2.66 (s, 3 H), 1.56–1.53 (m, 2 H),
1.08–1.04 (m, 2 H), 0.73 (t, J = 9.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 148.5, 146.4, 143.4, 142.9, 140.5,
130.2, 129.9, 122.4, 122.1, 121.7, 120.7, 119.7, 118.6, 113.1, 110.2,
44.2, 31.0, 19.7, 13.6, 13.4.
LC-MS (positive mode): m/z = 200 [M + H]+.
Anal. Calcd for C12H13N3: C, 72.33; H, 6.58; N, 21.09. Found: C,
72.21; H, 6.52; N, 21.18.
LC-MS (positive mode): m/z = 349 [M + H]+.
8-Benzyl-3-methyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole
(2d)
Anal. Calcd for C20H20N4O2: C, 68.95; H, 5.79; N, 16.08. Found: C,
68.85; H, 5.71; N, 16.21.
Yield: 112 mg (95%); pale brown solid; mp 271–273 °C.
8-Hexyl-3-methyl-1-(3-nitrophenyl)-1,8-dihydropyrazolo[3,4-
b]indole (2h)
Yield: 132 mg (83%); red viscous liquid.
IR (KBr): 3061, 2926, 1718, 1593, 1562, 1494, 1454, 1323, 1157,
1113, 1022, 1005, 740, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.76–7.75 (m, 1 H), 7.37–7.34 (m,
2 H), 7.33–7.32 (m, 3 H), 7.25–7.24 (m, 1 H), 7.19–7.18 (m, 6 H),
6.84–6.83 (m, 1 H), 5.21 (s, 2 H), 2.66 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 171.1, 146.5, 143.2, 141.7, 138.9,
136.4, 129.7, 129.1, 128.7, 127.7, 127.4, 126.0, 125.3, 124.8, 122.4,
122.2, 120.6, 119.9, 119.0, 118.4, 110.2, 47.4, 13.8.
IR (KBr): 2926, 2854, 1622, 1529, 1462, 1350, 1150, 1022, 966,
875, 740 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.45 (t, J = 4.0 Hz, 1 H), 8.26–
8.01 (m, 1 H), 7.99–7.77 (m, 1 H), 7.75–7.72 (m, 2 H), 7.61–7.50
(m, 2 H), 7.34–6.95 (m, 1 H), 4.11–4.08 (m, 2 H), 2.66 (s, 3 H),
1.59–1.53 (m, 2 H), 0.91–0.90 (m, 5 H), 0.88–0.76 (m, 4 H).
LC-MS (positive mode): m/z = 338 [M + H]+.
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

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Synthesis of Pyrazolo[3,4-b]indoles and Isoxazolo[5,4-b]indoles
3883
13C NMR (100 MHz, CDCl3): d = 143.5, 143.0, 140.5, 130.2, 129.1,
129.0, 122.4, 121.7, 120.7, 120.5, 119.1, 118.7, 113.2, 110.2, 109.0,
44.4, 31.9, 31.0, 29.3, 22.6, 14.0, 13.7.
13C NMR (100 MHz, CDCl3): d = 146.7, 142.7, 141.6, 139.2, 129.2,
128.9, 128.3, 127.9, 125.3, 121.8, 120.1, 119.8, 119.0, 109.8, 109.7,
43.8, 31.0, 28.9, 26.1, 22.3, 13.7.
LC-MS (positive mode): m/z = 377 [M + H]+.
LC-MS (positive mode): m/z = 318 [M + H]+.
Anal. Calcd for C22H24N4O2: C, 70.19; H, 6.43; N, 14.88. Found: C,
70.25; H, 6.38; N, 14.75.
Anal. Calcd for C21H23N3: C, 79.46; H, 7.30; N, 13.24. Found: C,
79.35; H, 7.33; N, 13.16.
8-Butyl-1-(4-chlorophenyl)-3-methyl-1,8-dihydropyrazolo[3,4-
b]indole (2i)
1-Phenyl-1,8-dihydropyrazolo[3,4-b]indole (2m)
Yield: 106 mg (82%); colorless solid; mp 167–169 °C.
Yield: 120 mg (89%); pale green, viscous liquid.
IR (KBr): 3425, 3246, 3057, 2939, 2876, 2546, 1668, 1599, 1502,
1462, 1404, 1302, 1263, 1113, 1026, 985, 927, 754, 696, 657 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.32 (s, 1 H), 7.97 (s, 1 H), 7.76–
7.52 (m, 3 H), 7.40–7.38 (m, 2 H), 7.30–7.25 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 144.9, 142.2, 141.9, 139.1, 129.5,
125.3, 122.4, 120.8, 120.2, 119.0, 118.4, 112.0, 111.1.
LC-MS (negative mode): m/z = 232 [M – H]+.
IR (KBr): 3248, 3051, 2932, 2860, 1672, 1612, 1493, 1466, 1402,
1300, 1091, 1028, 831, 744 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.80–7.74 (m, 2 H), 7.72–7.70 (m,
3 H), 7.32–7.24 (m, 3 H), 4.11–4.08 (m, 2 H), 2.65 (s, 3 H), 1.49–
1.45 (m, 2 H), 1.04–1.01 (m, 2 H), 0.71 (t, J = 8.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 146.3, 143.7, 143.0, 142.8, 133.3,
124.0, 122.4, 120.0, 119.8, 119.1, 118.3, 112.3, 111.3, 111.2, 110.4,
44.2, 31.8, 29.3, 19.7, 13.7.
Anal. Calcd for C15H11N3: C, 77.23; H, 4.75; N, 18.01. Found: C,
77.32; H, 4.68; N, 17.95.
LC-MS (positive mode): m/z = 338/340 [M + H]+.
Anal. Calcd for C20H20ClN3: C, 71.10; H, 5.97; N, 12.44. Found: C,
71.25; H, 5.88; N, 12.35.
8-Ethyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole (2n)
Yield: 108 mg (86%); colorless viscous liquid.
IR (KBr): 3040, 2930, 2852, 1702, 1590, 1552, 1520, 1490, 1450,
1370, 1150, 1109, 1012, 742, 689 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.75–7.63 (m, 1 H), 7.63–7.61 (m,
2 H), 7.56–7.52 (m, 2 H), 7.45 (d, J = 8.0 Hz, 1 H), 7.31–7.24 (m, 4
H), 4.08 (q, J = 8.0 Hz, 2 H), 1.14 (t, J = 4.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 146.4, 143.2, 141.7, 138.9, 136.4,
129.7, 128.7, 127.7, 126.0, 125.3, 124.8, 122.4, 121.0, 119.9, 118.4,
47.3, 21.0.
4-(8-Butyl-3-methylpyrazolo[3,4-b]indol-1(8H)-yl)benzonitrile
(2j)
Yield: 114 mg (87%); brown viscous liquid.
IR (KBr): 3251, 2926, 2854, 1590, 1564, 1520, 1494, 1454, 1375,
1325, 1280, 1166, 1110, 1020, 742 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.80–7.74 (m, 2 H), 7.72–7.70 (m,
3 H), 7.31–7.24 (m, 3 H), 4.10–4.08 (q, J = 7.2 Hz, 2 H), 2.63 (s, 3
H), 1.50–1.42 (m, 2 H), 1.04–0.95 (m, 2 H), 0.72 (t, J = 4.2 Hz, 3
H).
LC-MS (positive mode): m/z = 262 [M + H]+.
13C NMR (100 MHz, CDCl3): d = 146.3, 143.7, 143.0, 142.8, 133.3,
124.0, 120.7, 119.8, 119.1, 118.3, 112.2, 111.2, 110.4, 44.2, 30.9,
29.3, 19.7, 13.7, 13.4.
Anal. Calcd for C17H15N3: C, 78.13; H, 5.79; N, 16.08. Found: C,
78.25; H, 5.72; N, 16.18.
8-Butyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole (2o)
Yield: 99 mg (86%); light brown, viscous liquid.
LC-MS (positive mode): m/z = 329 [M + H]+.
Anal. Calcd for C21H20N4: C, 76.80; H, 6.14; N, 17.06. Found: C,
76.89; H, 6.08; N, 17.18.
IR (KBr): 3031, 2948, 2854, 1580, 1564, 1529, 1494, 1434, 1355,
1310, 1261, 1145, 1130, 1010, 742 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.75–7.73 (m, 1 H), 7.59–7.58 (m,
2 H), 7.54–7.50 (m, 2 H), 7.45–7.41 (m, 1 H), 7.29–7.21 (m, 4 H),
4.01–3.99 (m, 2 H), 1.04–1.00 (m, 2 H), 0.90–0.87 (m, 2 H), 0.69–
0.65 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 146.7, 142.8, 141.5, 138.7, 134.5,
129.3, 128.2, 125.4, 122.1, 120.3, 119.7, 119.1, 109.9, 109.7, 43.5,
31.0, 22.7, 19.7, 14.1.
8-Butyl-3-methyl-1-m-tolyl-1,8-dihydropyrazolo[3,4-b]indole
(2k)
Yield: 109 mg (86%); pale yellow, viscous liquid.
IR (KBr): 3051, 2957, 2930, 2868, 1676, 1645, 1610, 1520, 1464,
1390, 1197, 1159, 1107, 1008, 744 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.74–7.72 (m, 1 H), 7.41–7.20 (m,
7 H), 4.02–3.98 (m, 2 H), 2.64 (s, 3 H), 2.44 (s, 3 H), 1.50–1.46 (m,
2 H), 1.06–1.01 (m, 2 H), 0.71 (t, J = 4.2 Hz, 3 H).
LC-MS (positive mode): m/z = 290 [M + H]+.
13C NMR (100 MHz, CDCl3): d = 146.7, 142.7, 141.8, 139.3, 139.1,
128.8, 128.6, 125.8, 122.1, 121.7, 120.1, 119.8, 118.9, 109.8, 43.6,
31.0, 29.7, 21.3, 19.7, 13.7, 13.4.
Anal. Calcd for C19H19N3: C, 78.86; H, 6.62; N, 15.26. Found: C,
78.51; H, 6.57; N, 14.41.
8-Benzyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole (2p)
Yield: 111 mg (93%); brown solid; mp 257–259 °C.
LC-MS (positive mode): m/z = 318 [M + H]+.
Anal. Calcd for C21H23N3: C, 79.46; H, 7.30; N, 13.24. Found: C,
79.35; H, 7.26; N, 13.36.
IR (KBr): 2932, 2150, 1682, 1504, 1404, 1300, 1172, 1114, 1026,
985, 927, 850, 752, 700, 657 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.75–7.74 (m, 1 H), 7.41–7.40 (m,
6 H), 7.39–7.36 (m, 2 H), 7.35–7.34 (m, 3 H), 7.28–7.19 (m, 3 H),
5.23 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 146.5, 143.3, 141.7, 138.9, 136.4,
129.7, 129.1, 128.7, 128.1, 127.6, 127.4, 126.1, 125.4, 124.9, 122.4,
122.2, 121.0, 120.5, 120.0, 119.1, 118.4, 47.5.
8-Hexyl-1-phenyl-1,8-dihydropyrazolo[3,4-b]indole (2l)
Yield: 100 mg (88%); brown viscous liquid.
IR (KBr): 3059, 2928, 2856, 1711, 1599, 1566, 1523, 1493, 1456,
1375, 1159, 1109, 1018, 740, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.01–7.99 (m, 1 H), 7.76–7.74 (m,
4 H), 7.60–7.44 (m, 1 H), 7.29–7.22 (m, 4 H), 4.03–3.99 (m, 2 H),
1.51–1.44 (m, 2 H), 1.14–1.10 (m, 6 H), 1.00–0.76 (m, 3 H).
LC-MS (positive mode): m/z = 324 [M + H]+.
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

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A. S. Kumar et al.
PAPER
Anal. Calcd for C22H17N3: C, 81.71; H, 5.30; N, 12.99. Found: C,
81.62; H, 5.35; N, 12.81.
13C NMR (100 MHz, CDCl3): d = 135.0, 128.1, 126.0, 123.4, 122.8,
122.2, 121.2, 113.3, 109.3, 43.8, 34.0, 31.4, 20.0, 13.7.
LC-MS (negative mode): m/z = 227 [M – H]+.
8-Ethyl-3-methyl-8H-isoxazolo[5,4-b]indole (3b); Typical Pro-
cedure
Anal. Calcd for C14H16N2O: C, 73.66; H, 7.06; N, 12.27. Found: C,
73.56; H, 7.12; N, 12.36.
A domestic microwave oven was charged with 3-acetyl-2-chloro-1-
ethyl-1H-indole (100 mg, 0.5 mmol, 1.0 equiv), NH2OH·HCl (31
mg, 0.5 mmol, 1.0 equiv) and NMP (0.5 mL) in an open vessel. The
vessel was heated at 120 °C for 10 min (fixed hold time) in the mi-
crowave oven. Then, to the preformed oxime solution, K2CO3 (124
mg, 1.0 mmol, 2.0 equiv), CuI (4 mg, 0.025 mmol, 0.05 equiv) and
trans-1,2-diaminocyclohexane (5 mg, 0.05 mmol, 0.1 equiv) were
added. The reaction vessel was again heated at 120 °C for 15 min
(fixed hold time) in the microwave oven. The reaction mixture was
filtered through Celite® and purified by column chromatography
(EtOAc–hexane) to give 3b as a pale yellow, viscous liquid; yield:
81 mg (90%).
8-Hexyl-3-methyl-8H-isoxazolo[5,4-b]indole (3e)
Yield: 82 mg (89%); brown viscous liquid.
IR (KBr): 3053, 2930, 2858, 1649, 1493, 1450, 1377, 1336, 1209,
1178, 1099, 933, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.41–8.39 (m, 1 H), 7.32–7.28 (m,
3 H), 4.26–4.22 (m, 2 H), 2.70 (s, 3 H), 1.83–1.80 (m, 2 H), 1.40–
1.27 (m, 5 H), 0.90–0.81 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 134.9, 126.0, 123.4, 122.8, 122.2,
113.2, 109.3, 44.0, 31.3, 30.8, 29.3, 26.4, 22.5, 13.9.
LC-MS (positive mode): m/z = 257 [M + H]+.
IR (KBr): 3035, 2915, 2862, 1702, 1590, 1552, 1520, 1490, 1450,
1370, 1150, 1109, 1012, 742, 689 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.34–8.32 (m, 1 H), 7.58–7.54 (m,
1 H), 7.47–7.45 (m, 1 H), 7.32–7.26 (m, 1 H), 4.49–4.45 (m, 2 H),
2.00 (s, 3 H), 1.47 (t, J = 4.2 Hz, 3 H).
Anal. Calcd for C16H20N2O: C, 74.97; H, 7.86; N, 10.93. Found: C,
75.12; H, 7.81; N, 10.85.
8H-Isoxazolo[5,4-b]indole (3f)
Yield: 72 mg (82%); colorless viscous liquid.
13C NMR (100 MHz, CDCl3): d = 158.1, 144.1, 130.9, 128.3, 123.7,
IR (KBr): 3387, 2943, 2222, 1687, 1651, 1504, 1448, 1302, 1265,
1113, 985, 925, 750 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.98 (s, 1 H), 7.67–7.65 (m, 1 H),
7.39–7.28 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 143.7, 138.5, 133.5, 126.9, 124.5,
122.9, 119.1, 111.3.
120.7, 118.6, 108.7, 107.5, 37.8, 22.5, 13.4.
LC-MS (positive mode): m/z = 201 [M + H]+.
Anal. Calcd for C12H12N2O: C, 71.98; H, 6.04; N, 13.99. Found: C,
72.06; H, 6.11; N, 13.85.
3-Methyl-8H-isoxazolo[5,4-b]indole (3a)
Yield: 76 mg (86%); colorless viscous liquid.
LC-MS (positive mode): m/z = 159 [M + H]+.
IR (KBr): 3342, 2931, 2222, 1691, 1657, 1509, 1455, 1333, 1260,
1111, 992, 915, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.25 (s, 1 H), 8.33–8.32 (m, 1 H),
7.55–7.54 (m, 3 H), 2.03 (s, 3 H).
Anal. Calcd for C9H6N2O: C, 68.53; H, 3.82; N, 17.71. Found: C,
68.21; H, 3.91; N, 17.65.
8-Ethyl-8H-isoxazolo[5,4-b]indole (3g)
Yield: 77 mg (86%); light brown, viscous liquid.
13C NMR (100 MHz, CDCl3): d = 147.6, 144.1, 139.8, 133.8,
IR (KBr): 3061, 2926, 2858, 2222, 1670, 1614, 1516, 1456, 1396,
1350, 1232, 1084, 1028, 742 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 8.0 Hz, 1 H), 7.38–
7.27 (m, 4 H), 4.32 (q, J = 8.0 Hz, 2 H), 1.44 (t, J = 4.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 134.4, 126.9, 125.5, 124.0, 122.7,
119.2, 110.1, 108.2, 105.3, 39.4, 14.6.
128.4, 126.4, 121.2, 120.8, 111.4, 29.6.
LC-MS (negative mode): m/z = 171 [M – H]+.
Anal. Calcd for C10H8N2O: C, 69.76; H, 4.68; N, 16.27. Found: C,
69.85; H, 4.61; N, 16.12.
8-Benzyl-3-methyl-8H-isoxazolo[5,4-b]indole (3c)
Yield: 88 mg (96%); red-brown solid; mp 221–223 °C.
LC-MS (negative mode): m/z = 185 [M – H]+.
IR (KBr): 3408, 3061, 2926, 2854, 1950, 1712, 1651, 1612, 1493,
1467, 1367, 1317, 1170, 1122, 1080, 1030, 752, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.39–7.38 (m, 2 H), 7.36–7.35 (m,
3 H), 7.34–7.26 (m, 1 H), 7.24–7.21 (m, 2 H), 7.21–7.20 (m, 1 H),
5.23 (s, 2 H), 2.68 (s, 3 H).
Anal. Calcd for C11H10N2O: C, 70.95; H, 5.41; N, 15.04. Found: C,
70.85; H, 5.48; N, 15.12.
8-Benzyl-8H-isoxazolo[5,4-b]indole (3h)
Yield: 86 mg (94%); red solid; mp 216–218 °C.
13C NMR (100 MHz, CDCl3): d = 142.9, 139.2, 135.9, 135.0, 132.9,
130.2, 128.7, 128.4, 127.7, 126.4, 126.2, 124.1, 123.0, 121.7, 108.9,
43.8, 14.2.
IR (KBr): 3447, 2934, 2879, 2156, 1682, 1664, 1504, 1404, 1302,
1114 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.71–7.69 (m, 1 H), 7.35–7.29 (m,
6 H), 7.28 (s, 1 H), 7.12–7.10 (m, 2 H), 5.44 (s, 2 H).
LC-MS (positive mode): m/z = 263 [M + H]+.
13C NMR (100 MHz, CDCl3): d = 143.0, 139.2, 135.0, 132.9, 130.2,
128.7, 128.4, 127.7, 126.4, 126.2, 124.1, 123.0, 121.7, 108.9, 56.4.
Anal. Calcd for C17H14N2O: C, 77.84; H, 5.38; N, 10.68. Found: C,
77.68; H, 5.45; N, 10.56.
LC-MS (negative mode): m/z = 247 [M – H]+.
8-Butyl-3-methyl-8H-isoxazolo[5,4-b]indole (3d)
Yield: 85 mg (93%); colorless solid; mp 168–170 °C.
Anal. Calcd for C16H12N2O: C, 77.40; H, 4.87; N, 11.28. Found: C,
77.31; H, 4.82; N, 11.15.
IR (KBr): 3048, 2925, 1632, 1490, 1444, 1367, 1322, 1210, 1160,
1090, 1017, 930, 772 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.41–8.39 (m, 1 H), 7.32–7.28 (m,
3 H), 4.27–4.24 (m, 2 H), 2.70 (s, 3 H), 1.84–1.78 (m, 2 H), 1.45 (m,
2 H), 0.99 (t, J = 9.2 Hz, 3 H).
8-Butyl-8H-isoxazolo[5,4-b]indole (3i)
Yield: 78 mg (86%); colorless viscous liquid.
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

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Synthesis of Pyrazolo[3,4-b]indoles and Isoxazolo[5,4-b]indoles
3885
IR (KBr): 3051, 2932, 2872, 2222, 1653, 1506, 1458, 1404, 1302,
1263, 1113, 1030, 848, 750 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.70–7.68 (m, 1 H), 7.37–7.28 (m,
4 H), 4.27–4.26 (m, 2 H), 1.83–1.79 (m, 2 H), 1.43–1.38 (q, J = 4.0
Hz, 2 H), 0.99 (t, J = 4.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 134.5, 133.0, 126.4, 123.9, 122.7,
119.1, 114.2, 110.4, 44.0, 31.4, 19.9, 13.6.
(5) (a) Knölker, H.-J.; Reddy, K. R. In The Alkaloids, Vol. 65;
Cordell, G. A., Ed.; Academic Press: Amsterdam, 2008, 1.
(b) Sundberg, R. J. The Chemistry of Indoles; Academic
Press: New York, 1970. (c) Sundberg, R. J. Pyrroles and
Their Benzo Derivatives: Synthesis and Applications, In
Comprehensive Heterocyclic Chemistry, Vol. 4; Katritzky,
A. R.; Rees, C. W., Eds.; Pergamon Press: Oxford, 1984,
313–376. (d) Joule J. A.; Indole and Its Derivatives, In
Science of Synthesis, Houben–Weyl Methods of Molecular
Transformations; Thomas E. J.; George Thieme: Stuttgart,
2000; Vol. 10: 361-652. (e) Gribble, G. W. In
LC-MS (positive mode): m/z = 215 [M + H]+.
Anal. Calcd for C13H14N2O: C, 72.87; H, 6.59; N, 13.07. Found: C,
72.68; H, 6.51; N, 13.21.
Comprehensive Heterocyclic Chemistry II, Vol. 2;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.; Bird, C. W.,
Eds.; Pergamon Press: Oxford, 1996, 207.
8-Hexyl-8H-isoxazolo[5,4-b]indole (3j)
Yield: 80 mg (88%); colorless viscous liquid.
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IR (KBr): 3366, 2924, 2852, 1626, 1452, 1383, 1155, 1030 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.41–8.39 (m, 1 H), 7.32–7.28 (m,
4 H), 4.26–4.22 (m, 2 H), 1.83–1.80 (m, 2 H), 1.35–1.32 (m, 5 H),
0.92–0.89 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 135.0, 131.2, 126.0, 123.5, 122.9,
122.3, 118.7, 113.3, 109.3, 44.2, 31.3, 30.7, 29.4, 26.5, 14.0.
LC-MS (positive mode): m/z = 243 [M + H]+.
Anal. Calcd for C15H18N2O: C, 74.35; H, 7.49; N, 11.56. Found: C,
74.21; H, 7.56; N, 11.65.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Primary Data for this article are available online at
http://www.thieme-connect.com/ejournals/toc/synthesis and can be
cited using the following DOI: 10.4125/pd0020th.
Acknowledgment
We gratefully acknowledge DST for financial assistance (Project
number: SR/S1/OC-70/2008) and for providing the single-crystal
X-ray diffractometer facility in our school. A.S.K. thanks UGC for
a Senior Research Fellowship and P.V.A.R. thanks CSIR for a Ju-
nior Research Fellowship. A.S.K. also thanks Rambabu Bolligarla
and Saikat Sen for helping with the crystal studies.
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Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York

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(18) The crystal data of compound 2a have been deposited with
the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 832662. Copies of the
data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax:
+44 (1223)336033; E-mail: deposit@ccdc.cam.ac.uk] or via
www.ccdc.cam.ac.uk/data_request/cif.
Compound 2a: C16H13N3, M = 247.29; unit cell parameters:
a = 13.2646(12) Å, b = 14.7200(13) Å, c = 15.4448(14) Å,
a = 104.423(2)°, b = 107.550(2)°, g = 112.102(2)°, space
group P1.
Synthesis 2011, No. 23, 3878–3886 © Thieme Stuttgart · New York