Synthesis of indolo[2,3-c]quinolines from 3-arylindole-2-ketoximes

Article abstract of DOI:10.1016/j.tet.2007.04.087

Treatment of the 2,4-dinitrophenyl ethers of some 3-arylindole-2-ketoximes with base results in a cyclisation reaction to yield indolo[2,3-c]quinolines.

Full text of DOI:10.1016/j.tet.2007.04.087

Tetrahedron 63 (2007) 6713–6719
Synthesis of indolo[2,3-c]quinolines from 3-arylindole-2-ketoximes
*
Tutik Dwi Wahyuningsih, Naresh Kumar and David StC Black
School of Chemistry, University of New South Wales, UNSW Sydney NSW 2052, Australia
Received 28 January 2007; revised 12 April 2007; accepted 26 April 2007
Available online 3 May 2007
Abstract—Treatment of the 2,4-dinitrophenyl ethers of some 3-arylindole-2-ketoximes with base results in a cyclisation reaction to yield
indolo[2,3-c]quinolines.
Ó 2007 Elsevier Ltd. All rights reserved.
X
X
1. Introduction
We have previously reported that treatment of 2,4-dinitro-
phenyl ethers of a range of indole-7-ketoximes with base
provides an effective method for the synthesis of the novel
pyrrolo[3,2,1-hi]indazoles.1 In view of this result, we de-
cided to investigate the situation where the oxime ether
was attached in a vicinal relationship to a benzene ring,
and such a possibility arises in the case of the oxime ethers
of 3-arylindole-2-ketoximes. Compounds of this type are
available through the reaction of 3-aryl-4,6-dimethoxy-
indoles with oxalyl chloride, followed by quenching with
alcohols or amines to give both 2- and 7-glyoxylic esters
and amides, which can be readily separated and purified.2
MeO
MeO
1. ClCOCOCl
2. RH
O
N
H
N
H
R
MeO
MeO
O
R
X
X
___
Cl
__________
1
2
OEt
3
4
Cl
Br
Br
NMe2
NH2OH.HCl
base
X
X
+
51-95%
MeO
MeO
NOH
R
N
MeO
N
H
MeO
O
H
O
R
2. Results and discussion
X
O
__________
OEt
NMe2
7
8
Cl
Br
R
R
X
__________
2.1. Formation of indole-2-ketoximes and ketoxime
ethers
OEt
NMe2
5
6
Cl
Br
NaOEt
fluoro-2,4-
49-100%
X
dinitrobenzene
The two activated indoles 1 and 2 were converted to the cor-
responding 2-glyoxylic ester 3 and 2-glyoxylic amide 4, re-
spectively, by acylation with oxalyl chloride followed by
addition of either ethanol or dimethylamine (Scheme 1).
The isomeric 7-gloxylic ester 5 and the 7-glyoxylic amide
6 were also isolated as minor products. It has already been
reported that the bromophenyl indole 2, when treated with
oxalyl chloride in diethyl ether followed by dimethylamine,
gave a predominance of the 2-glyoxylamide 4 over the 7-
glyoxylamide 6.2
X
NO2
MeO
MeO
NaH or
Et3N
N
O
N
O
NO2
N
R
R
N
H
MeO
10-69%
MeO
H
O
R
X
R
__________
X
__________
OEt
11
12
Cl
Br
OEt
NMe2
9
Cl
Br
NMe2
10
Scheme 1.
Reaction of the glyoxylic ester 3 with hydroxylamine hydro-
chloride in absolute ethanol containing sodium acetate
yielded the indole-2-ketoxime 7 in 82%. The related glyoxyl-
amide 4 required different conditions, namely heating in
Keywords: Indoles; Indoloquinolines; Oxime ethers; Cyclisation reactions.
* Corresponding author. Tel.: +61 2 9385 4657; fax: +61 2 9385 6141;
e-mail: d.black@unsw.edu.au
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.04.087

6714
T. D. Wahyuningsih et al. / Tetrahedron 63 (2007) 6713–6719
X
ethanol containing pyridine, to give the oxime 8 in 90% yield
(Scheme 1). The observed spectroscopic data for the oximes
7 and 8 showed mixtures of anti and syn isomers in ratios of
10:1 and 1.2:1, respectively.
X
NO2
MeO
MeO
H
NO2
N
O
N
O
NO2
R
N
H
N
H
Treatment of the indole-2-ketoximes 7 and 8 with fluoro-2,4-
dinitrobenzene in the presence of sodium ethoxide at 0 ꢀC
for 2 h yielded the respective oxime ethers 9 and 10. Both
compounds were characterised fully, with the exception of
13C NMR spectra because of relative insolubility. Again
mixtures of anti and syn isomers were observed, with the
expectedly more stable anti isomer predominating.
R
MeO
MeO
NO2
R = CO2Et, CONMe2
X = Cl, Br
X
MeO
N
2.2. Formation of indolo[3,2-c]quinolines
R
N
H
MeO
On treatment with triethylamine in tetrahydrofuran, the
oxime ethers 9 and 10 gave light yellow solid products.
The H NMR spectra of the products displayed an absence
Scheme 2.
1
with fluoro-2,4-dinitrobenzene and sodium ethoxide gave
the crude oxime ether 16 in 97% yield, as a single isomer;
the absence of any significant hydrogen bonding of the in-
dole NH proton suggests the assignment of the anti configu-
ration (Scheme 3). Base treatment of the oxime ether 16 was
carried out by heating it with triethylamine in dry tetrahydro-
furan. The starting material remained intact after 12 h, a
result that further supports the electrocyclic mechanism.
of the typical 1,4-disubstituted benzene pattern, with two
doublets at d 8.33 and 9.33 ppm and one doublet of doublets
at 7.69 ppm, in total corresponding to three protons. This in-
dicates the loss of one proton from the 3-aryl group, presum-
ably resulting from linkage to the oxime nitrogen atom. The
resulting structures 11 and 12, which are indolo[3,2-c]quin-
olines are supported by all the spectroscopic and analytical
evidence (Scheme 1).
MeO
MeO
Me
Compounds 11 and 12 are benzo analogues of b-carboline,
which is an important structural feature of alkaloids of the
harman group.3,4 Benzo-b-carbolines can be prepared by
a variety of specialised methods involving indole formation
via pyrolysis of a 3-azido-4-arylquinoline derivative,4 intra-
molecular coupling of a 2-arylaminomethylindole,5 or the
application of a stepwise Bischler indole synthesis.6
Me
1. ClCOCOCl
2. EtOH
O
N
N
OEt
69%
MeO
MeO
H
H
O
13
14
NH2OH.HCl
pyridine
63%
Me
The cyclisation reactions leading to compounds 11 and 12
could possibly proceed via several different mechanisms.
These broadly include the involvement of a nitrenium cation
or nitrene, a base catalysed displacement, or an electrocyclic
process. Nitrenes have been postulated in some photochem-
ical and thermal transformations of O-acyl oximes.7,8 On the
other hand, cyclisation reactions of oximes to form the pyr-
idine ring moiety of harman-like structures appear to involve
electrocyclisation of an intermediate azatriene.9,10 Com-
pound 11 was formed in 25 and 55% yields by heating the
oxime ether 9 in tetrahydrofuran and xylene, respectively,
for 24 h, results were consistent with an electrocyclic mech-
anism (Scheme 2). Further studies will be carried out in
order to attempt to clarify the mechanism of this interesting
cyclisation reaction. The extent to which the reaction is
affected by the stereochemistry of the oxime ether is also
unclear, as pure isomers have not been obtainable.
NO2
NaOEt
MeO
MeO
Me
fluoro-2,4-
NOH
dinitrobenzene
N
O
NO2
97%
MeO
N
OEt
N
OEt
MeO
H
H
O
O
15
16
Scheme 3.
Furthermore, similar reaction of the 3-unsubstituted oxime
ether 19 was investigated. The 2-benzoyl indole 1712 was
converted to the oxime 18 (as a mixture of syn and anti iso-
mers) in 92% yield by reaction with hydroxylamine hydro-
chloride and pyridine. Treatment of the oxime 18 with
fluoro-2,4-dinitrobenzene gave the oxime ether 19 (as the
single anti isomer) in 91% yield. Once again, no reaction
was observed when this compound was heated with triethyl-
amine at reflux in tetrahydrofuran for 12 h (Scheme 4).
As the 3-aryl group is essential for the observed cyclisation
reaction, it was of interest to investigate the effect of replac-
ing it with a 3-methyl group. The 3-methylindole-2-gly-
oxylic ester 14 was prepared11 in 69% yield by reaction of
4,6-dimethoxy-3-methylindole 13 with oxalyl chloride in di-
ethyl ether, followed by the addition of ethanol (Scheme 3).
Reaction of the glyoxylic ester 14 with hydroxylamine hy-
drochloride in the presence of pyridine gave the indole ox-
ime 15 in 63% yield, as a mixture of syn and anti isomers
in a ratio of 1:0.6. Subsequent treatment of the oxime 15
It was also of interest to investigate the possible cyclisation
of an indole-2-oxime ether on to a substituent on the nitrogen
atom. In this context, cyclisation on to an N-benzyl or N-ben-
zoyl group would be synthetically useful, as benzodiazepine
derivatives would be formed. Such benzodiazepine deriva-
tives are generally biologically active,13 and in particular,
the indolobenzodiazepines 20 show antihistamine and sero-
tonin activities, as well as an ability to inhibit mediator

T. D. Wahyuningsih et al. / Tetrahedron 63 (2007) 6713–6719
6715
MeO
MeO
minor products. All attempts to prepare the related oxime
yielded only the 2-benzoyl oxime 18 as a result of hydrolysis
of the N-benzoyl group. Alternativeattempts to N-benzoylate
the oxime ether 19 were unsuccessful, so the critical starting
material for the potential cyclisation was unavailable.
NH2OH.HCl
pyridine
O
NOH
Ph
N
R
Ph
N
R
MeO
MeO
81-92%
R
R
______
H
______
H
17
21
26
18
22
CH2Ph
CH2Ph
COPh
3. Conclusion
91%
The treatment of 2,4-dinitrophenyl ethers of a range of in-
dole 7-ketoximes with base provides an effective method
for the synthesis of the novel pyrazolo[4,5,1-hi]indoles.
Further work aims to explore the scope and mechanism of
the cyclisation reaction.
NaOEt
fluoro-2,4-
NO2
NO2
dinitrobenzene
MeO
N
O
N
R
Ph
MeO
R
4. Experimental
4.1. General
______
H
19
23
CH2Ph
Scheme 4.
Melting points were measured using a Mel-Temp melting
point apparatus, and are uncorrected. Microanalyses were
performed on a Carlo Erba Elemental Analyser EA 1108
at the Campbell Microanalytical Laboratory, University of
release and thus have potential for treatment of allergic
reactions.14
1
Otago, New Zealand. H and 13C NMR spectra were ob-
tained on a Bruker DPX300 (300 MHz) spectrometer.
Mass spectra were recorded on either Bruker FT-ICR MS
(EI) or Micromass ZQ2000 (ESI) at UNSW, or Shimadzu
LCMS QP 8000 (ESI) at the University of Otago, New
Zealand. Infrared spectra were recorded with a Thermo
Nicolet 370 FTIR Spectrometer using KBr discs. Ultravio-
let–visible spectra were recorded using a Varian Cary 100
Scan Spectrometer. Column chromatography was carried
out using Merck 230–400 mesh ASTM silica gel, whilst pre-
parative thin layer chromatography was performed using
The 2-benzoyl indole 17 was benzylated using benzyl bro-
mide and potassium hydroxide in dry dimethyl sulfoxide to
give the N-benzyl indole 21 in 76% yield. Treatment of this
compound with hydroxylamine hydrochloride and pyridine
gave the oxime 22 in 90% yield, as a mixture of syn and
anti isomers. In this case, it is not possible to identify the in-
dividual isomers because there is no possibility of hydrogen
bondingto distinguish between them. Treatment of the oxime
22 with fluoro-2,4-dinitrobenzene and sodium ethoxide gave
the oxime ether 23 as a mixture of isomers (Scheme 4).
Merck silica gel 7730 60GF254
.
Cyclisation of oxime ether 23 was attempted by treatment
under a variety of basic conditions. Heating the oxime ether
23 and triethylamine in tetrahydrofuran gave only unreacted
starting material. In contrast, heating the mixture of oxime
ether 23 and sodium hydride in dioxan gave a complex prod-
uct mixture. However, stirring compound 23 with sodium
hydride in dioxan at room temperature for 24 h gave an
orange solid, which was indicated to be the cyclic product
24, on the basis of NMR spectra, although the compound
could not be obtained fully pure.
4.1.1. Ethyl 2-[3-(4-chlorophenyl)-4,6-dimethoxyindol-2-
yl]glyoxylate (3) and ethyl 2-[3-(4-chlorophenyl)-4,6-di-
methoxyindol-7-yl]glyoxylate (5). This was prepared as
described2 for glyoxylamide 4 from indole 1 (1.00 g,
3.5 mmol) in anhydrous diethyl ether (30 mL) with oxalyl
chloride (0.40 mL, 4.2 mmol) and the resulting red solid
glyoxyloyl chloride was stirred at room temperature in abso-
lute ethanol (15 mL) for 2 h. The precipitate was filtered off,
washed until neutral and dried to give compound 3 (0.56 g,
42%) as an orange solid, mp 188 ꢀC. Found: C, 61.9; H,
4.8; N, 3.7. C20H18ClNO5 requires C, 61.9; H, 4.7; N,
3.6%. nmax: 3323, 1741, 1600, 1571, 1236, 1206, 1132,
MeO
Ph
816 cmÀ1
. lmax:
228 nm (3 18,350 cmÀ1 MÀ1), 264
NR2
N
Me
O
Ph
N
(20,350), 334 (13,850). 1H NMR spectrum (300 MHz,
CDCl3): d 1.14 (3H, t, J 7.2 Hz, Me), 3.63, 3.86 (6H, 2s,
OMe), 3.79 (2H, q, J 7.2 Hz, OCH2), 6.11 (1H, d, J 1.9 Hz,
H5), 6.41 (1H, d, J 1.9 Hz, H7), 7.34 (4H, m, ArH), 9.44
(1H, br s, NH). 13C NMR spectrum (75 MHz, CDCl3):
d 13.5 (CH3), 55.1, 55.6 (OCH3), 62.0 (OCH2), 85.6 (C5),
93.8 (C7), 127.1, 132.2 (ArCH), 113.3, 127.1, 128.6, 131.9,
133.6, 139.8, 156.9, 162.4 (ArC), 163.9, 176.8 (C]O).
Mass spectrum (EI): m/z 389 (M+2, 37Cl, 20%), 387 (M,
35Cl, 62), 316 (27), 314 (83), 279 (100), 264 (21).
N
NH
N
N
MeO
O
25
24
20
The indolobenzodiazepinedione 25 and related structures
have been shown to behave as antibacterial agents against
Escherichia coli and Staphylococcus aureus.15 This infor-
mation prompted an attempt to synthesise similar com-
pounds by the oxime ether route. Thus, the 2-benzoyl
indole 17 was benzoylated on nitrogen to give 1,2-dibenzoyl
indole 26 in only a modest yield together with a range of
Absolute ethanol (10 mL) was added to the filtrate and the
mixture was refluxed for 2 h. Water was then added and

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T. D. Wahyuningsih et al. / Tetrahedron 63 (2007) 6713–6719
the mixture was extracted with dichloromethane. The
organic layer was washed until neutral, dried and the solvent
was removed under reduced pressure to give compound 5
(0.33 g, 24%) as a yellow solid, mp 188–189 ꢀC. Found:
C, 61.7; H, 4.5; N, 3.7. C20H18ClNO5 requires C, 61.9; H,
4.7; N, 3.6%. nmax: 3426, 1728, 1584, 1309, 1218, 1170,
1058 cmÀ1. lmax: 232 nm (3 21,600 cmÀ1 MÀ1), 256
(20,900), 336 (12,100). 1H NMR spectrum (300 MHz,
CDCl3): d 1.41 (3H, t, J 7.2 Hz, Me), 3.92, 3.94 (6H, 2s,
OMe), 4.43 (2H, q, J 7.2 Hz, OCH2), 6.18 (1H, s, H5),
7.09 (1H, d, J 2.2 Hz, H2), 7.31–7.48 (4H, m, ArH), 10.56
(1H, br s, NH). 13C NMR spectrum (75 MHz, CDCl3):
d 14.1 (Me), 55.4, 56.9 (OMe), 61.4 (OCH2), 87.4 (C5),
121.9 (C7), 127.7, 130.6 (ArCH), 100.8, 110.7, 118.0,
131.9, 133.6, 138.4, 162.0, 162.1 (ArC), 165.9, 185.1
(C]O). Mass spectrum (EI): m/z 389 (M+2, 37Cl, 16%),
387 (M, 35Cl, 47), 316 (58), 314 (100).
11.34, 11.99 (1H, s, syn and anti OH). 13C NMR spectrum
(75 MHz, d6-DMSO): d 31.0, 32.8, 36.6, 38.3 (Me), 55.4,
55.6 (OMe), 87.2, 87.5 (C5), 92.3, 92.5 (C7), 129.4, 133.2,
133.4 (ArCH), 112.6, 117.1, 120.1, 122.1, 124.2, 134.1,
134.4, 138.3, 147.1, 154.9 (ArC), 158.5 (C]N), 162.8
(C]O). Mass spectrum (EI): m/z 448 (M+2, 81Br, 22%),
447 (86), 446 (M, 79Br, 19), 445 (93), 428 (24), 372 (23),
356 (39), 333 (57), 331 (59), 292 (33), 291 (100), 263 (33).
4.1.4. Ethyl 2-[3-(4-chlorophenyl)-4,6-dimethoxyindol-2-
yl]-2-(O-2,4-dinitrophenyloxyimino)acetate (9). This was
prepared from indole oxime 7 (0.27 g, 0.66 mmol), absolute
ethanol (25 mL), sodium (22 mg, 0.96 mmol) and fluoro-
2,4-dinitrobenzene (0.12 mL, 0.66 mmol) in an ice bath.
After filtration and washing, the product was dried to
yield the oxime ether 9 (0.34 g, 89%) as an orange solid,
mp 214–216 ꢀC. Found: C, 54.3; H, 3.7; N, 9.5.
C26H21ClN4O9$0.3H2O requires C, 54.4; H, 3.8; N, 9.8%.
nmax: 3383, 1736, 1605, 1565, 1536, 1340, 1251, 1137,
1089 cmÀ1. lmax: 231 nm (3 34,950 cmÀ1 MÀ1), 327
4.1.2. Ethyl 2-[3-(4-chlorophenyl)-4,6-dimethoxyindol-2-
yl]-2-(hydroxyimino)acetate (7). This was prepared from
indole glyoxylic ester 5 (0.40 g, 1.0 mmol), hydroxylamine
hydrochloride (0.36 g, 5.2 mmol) and sodium acetate
(0.4 g, 2.9 mmol) in absolute ethanol (40 mL) under reflux
for 7 h. After extraction and concentration the residue was
chromatographed with dichloromethane/ethyl acetate
(95:5) as an eluent to give the oxime 7 (0.34 g, 82%) as a light
brown solid, mp 183–184 ꢀC. Found: C, 59.6; H, 4.8; N, 7.0.
C20H19ClN2O5 requires C, 59.6; H, 4.8; N, 6.9%. nmax: 3373,
1
(17,150). H NMR spectrum (300 MHz, CDCl3): d 1.12–
1.18 (6H, m, syn and anti Me), 3.59–3.92 (16H, m, syn
and anti OCH2 and OMe), 6.14 (2H, s, syn and anti H5),
6.47, 6.61 (2H, 2d, J 1.5 Hz, syn and anti H7), 7.33 (8H, s,
syn and anti ArH), 7.89 (1H, d, J 9.4 Hz, ArH), 8.23 (1H,
d, J 9.4, ArH), 8.43–8.56 (2H, m, ArH), 8.88, 9.09 (2H,
2d, ArH), 8.68, 10.77 (2H, 2s, syn and anti NH). The sample
was not soluble enough for 13C NMR measurement. Mass
spectrum (EI): m/z 386 (23%), 384 (59), 314 (32), 312
(100), 295 (27), 269 (19).
1719, 1624, 1584, 1212, 1151, 1131, 998, 818 cmÀ1. lmax
:
228 nm (3 23,750 cmÀ1 MÀ1), 255 (19,850), 337 (7,200).
1H NMR spectrum (300 MHz, d6-DMSO): d 0.97 (6H, m,
syn and anti Me), 3.51–3.76 (16H, m, syn and anti OCH2
and OMe), 6.09, 6.17 (2H, 2s, syn and anti H5), 6.52, 6.56
(2H, 2d, J 1.5 Hz, syn and anti H7), 7.19, 7.32 (8H, 2d,
J 8.3 Hz, syn and anti ArH), 11.17, 11.28 (2H, 2s, syn and
anti NH), 11.64, 12.60 (2H, 2s, syn and anti OH). 13C
NMR spectrum (75 MHz, d6-DMSO): d 13.7, 13.9 (Me),
55.3, 55.4, 55.6, 55.6 (OMe), 61.1, 61.2 (OCH2), 87.2,
87.3 (C5), 92.4 (C7), 126.9, 127.3, 132.2, 133.4 (ArCH),
110.2, 112.4, 117.3, 117.6, 121.7, 123.4, 131.1, 131.8,
134.5, 138.3, 138.4, 143.4, 144.7, 154.9, 155.0 (ArC),
158.2, 158.7 (C]N), 162.2, 163.2. (C]O). Mass spectrum
(EI): m/z 404 (M+2, 37Cl, 31%), 402 (M, 35Cl, 100), 385
(35), 313 (34), 312 (81), 291 (61), 262 (46).
4.1.5. N,N-Dimethyl 2-[3-(4-bromophenyl)-4,6-dime-
thoxyindol-2-yl]-2-(O-2,4-dinitrophenyloxyimino) acet-
amide (10). This was prepared from indole oxime 8
(0.15 g, 0.33 mmol), absolute ethanol (15 mL), sodium
(20 mg, 0.87 mmol) and fluoro-2,4-dinitrobenzene
(0.06 mL, 0.33 mmol) in an ice bath. After filtration and
washing, the product was dried to yield the oxime ether 10
(0.20 g, 100%) as an orange solid, mp 182 ꢀC. Found: C,
50.1; H, 3.5; N, 11.0. C26H22BrN5O8$0.5 H2O requires C,
50.3; H, 3.7; N, 11.3%. nmax: 3277, 1648, 1606, 1534,
1475, 1343, 1300, 1205, 1133, 1068, 928 cmÀ1. lmax
:
229 nm (3 26,900 cmÀ1 MÀ1), 262 (19,800), 348 (15,100),
378 (15,350). 1H NMR spectrum (300 MHz, CDCl3):
d 2.40, 2.67, 2.74, 2.80 (6H, 4s, syn and anti Me), 3.50,
3.57, 3.83, 3.92 (6H, 4s, syn and anti OMe), 6.01, 6.11
(1H, d, J 1.9 Hz, syn and anti H5), 6.36, 6.61 (1H, d, J
1.9 Hz, syn and anti H7), 7.22, 7.50 (4H, d, J 8.3 Hz, syn
and anti ArH), 7.83, 8.20 (1H, d, J 9.4 Hz, ArH), 8.32, 8.50
(1H, dd, J 9.4, 2.6 Hz, syn and anti ArH), 8.73, 9.10 (1H, d,
J 2.6 Hz, syn and anti ArH), 9.43, 11.04 (2H, 2s, syn and
anti NH). The sample was not soluble enough for 13C
NMR measurement. Mass spectrum (EI): m/z 614 (M+2,
4%), 428 (27), 355 (100).
4.1.3. N,N-Dimethyl 2-[3-(4-bromophenyl)-4,6-dime-
thoxyindol-2-yl]-2-(hydroxyimino) acetamide (8). This
was prepared from indole glyoxylamide 6 (0.15 g, 0.3
mmol), hydroxylamine hydrochloride (0.08 g, 5.2 mmol),
and pyridine (2 mL) in absolute ethanol (2 mL) under reflux
overnight. After extraction and concentration, the residue
was chromatographed with dichloromethane/methanol
(95:5) as an eluent to give the oxime 8 (0.14 g, 90%) as a light
brown solid, mp 134 ꢀC (dec). Found: C, 53.1; H, 4.6; N, 9.3.
C20H20BrN3O4$0.3H2O requires C, 53.2; H, 4.6; N, 9.3%.
nmax: 3263, 1629, 1585, 1513, 1285, 1205, 1151, 1131,
1074, 996 cmÀ1. lmax: 229 nm (3 25,000 cmÀ1 MÀ1), 262
4.1.6. Ethyl 3-chloro-9,11-dimethoxyindolo[3,2-c]quino-
line-6-carboxylate (11). This was prepared from indole
oxime ether 9 (0.33 g, 0.59 mmol), and triethylamine
(1 mL) in dry tetrahydrofuran (25 mL) under reflux over-
night. After extraction and concentration, the residue was
chromatographed with dichloromethane/methanol (95:5)
as an eluent to give the product 11 (98 mg, 43%) as a pale
yellow solid, mp 197–198 ꢀC. Found: C, 55.4; H, 4.0; N,
1
(20,400), 327 (18,100). H NMR spectrum (300 MHz, d6-
DMSO): d 2.06, 2.30, 2.62, 2.73 (6H, s, syn and anti Me),
3.49, 3.53, 3.74 (6H, 2s, syn and anti OMe), 6.07, 6.10
(1H, d, J 1.9 Hz, syn and anti H5), 6.54, 6.71 (1H, d,
J 1.9 Hz, syn and anti H7), 7.10, 7.43 (4H, 2d, J 8.3 Hz,
syn and anti ArH), 11.06, 11.30 (1H, br, syn and anti NH),

T. D. Wahyuningsih et al. / Tetrahedron 63 (2007) 6713–6719
6717
6.1. C20H17ClN2O4$0.75CH2Cl2 requires C, 55.6; H, 4.2; N,
6.2%. nmax: 3431, 1702, 1621, 1345, 1247, 1190, 1152,
hydrochloride (1.4 g, 20.6 mmol) and pyridine (6 mL) in ab-
solute ethanol (6 mL) under reflux for 17 h. After extraction
and concentration, the residue was chromatographed with
dichloromethane/ethyl acetate (95:5) to give the oxime 15
(0.40 g, 63%) as a pale brown oil. Found: C, 57.8; H, 5.9;
N, 9.0. C15H18N2O5$0.3H2O requires C, 57.8; H, 6.0; N,
9.0%. nmax: 3407, 1731, 1627, 1588, 1464, 1211, 1155,
1031, 807 cmÀ1. lmax: 229 nm (3 18,850 cmÀ1 MÀ1), 319
1
1101 cmÀ1. H NMR spectrum (300 MHz, CDCl3): d 1.58
(3H, t, J 7.1 Hz, Me), 3.95, 4.12 (6H, 2s, OMe), 4.66 (2H,
q, J 7.1 Hz, OCH2), 6.42 (1H, d, J 1.9 Hz, H5), 6.67 (1H,
d, J 1.9 Hz, H7), 7.61 (1H, dd, J 7.2, 2.3 Hz, ArH), 8.36
(1H, d, J 2.3 Hz, ArH), 9.46 (1H, d, J 9.4 Hz, ArH), 10.36
(H, br, NH). 13C NMR spectrum (75 MHz, CDCl3): d 14.3
(Me), 55.4, 55.6 (OMe), 62.4 (OCH2), 86.9 (C5), 92.9
(C7), 128.1, 128.5, 129.7 (ArCH), 106.6, 123.7, 125.6,
129.7, 131.9, 132.6, 142.6, 143.2, 155.9, 162.1 (ArC),
166.7 (C]O).
1
(7,900). H NMR spectrum (300 MHz, d6-DMSO): d 1.25
(3H, m, syn and anti OCH2Me), 2.18, 2.30 (3H, s, syn and
anti Me), 3.72–3.78 (6H, m, syn and anti OMe), 4.20–3.32
(2H, m, syn and anti OCH2), 6.07, 6.08 (1H, s, syn and
anti H5), 6.42, 6.46 (1H, d, J 1.9, 1.9 Hz, syn and anti
H7), 10.72, 10.75 (1H, s, syn and anti NH), 11.49, 12.46
(1H, s, syn and anti OH). 13C NMR spectrum (75 MHz,
d6-DMSO): d 10.8, 12.3, 14.2, 14.4 (Me), 55.5 (OMe),
61.7, 61.8 (OCH2), 87.0 (C5), 91.5, 91.8 (C7), 112.1,
113.0, 113.1, 120.7, 122.2, 138.3, 138.8, 143.1, 145.2,
155.7, 155.8, 158.0 (ArC), 158.5, 164.0 (C]N), 164.2,
170.7 (C]O). Mass spectrum (EI): m/z 306 (M, 100%),
289 (29), 243 (31), 230 (27), 217 (59), 215 (63), 200 (36),
173 (31), 158 (43).
4.1.7. N,N-Dimethyl 3-bromo-9,11-dimethoxy indolo[3,2-
c]quinoline-6-carboxamide (12). This was prepared from
indole oxime ether 10 (0.15 g, 0.24 mmol) and triethylamine
(1 mL) in dry tetrahydrofuran (15 mL) under reflux over-
night. After extraction and concentration, the residue was
chromatographed with dichloromethane/methanol (95:5)
as an eluent to give the product 12 (57 mg, 54%) as a
yellow solid, mp 233–235 ꢀC. Found: C, 56.1; H, 4.2; N,
9.8. C20H18BrN3O3 requires C, 56.1; H, 4.2; N, 9.8%.
nmax: 3423, 1610, 1491, 1347, 1329, 1148, 1115, 1077,
811 cmÀ1
.
lmax
:
230 nm (3 24,250 cmÀ1 MÀ1), 281
4.1.10. Ethyl 2-(4,6-dimethoxy-3-methylindol-2-yl)-2-(O-
2,4-dinitrophenyloxyimino)acetate (16). This was pre-
pared from indole oxime 15 (0.17 g, 0.6 mmol), absolute
ethanol (15 mL), sodium (24 mg, 1.0 mmol) and fluoro-
2,4-dinitrobenzene (0.1 mL, 0.6 mmol) to yield the oxime
ether 16 (0.25 g, 97%) as an orange solid, which could not
be obtained analytically pure, mp 166–168 ꢀC. nmax: 3392,
1743, 1605, 1570, 1522, 1469, 1340, 1248, 1231, 1149,
(34,450), 386 (17,000). 1H NMR spectrum (300 MHz,
CDCl3): d 3.29, 3.50 (6H, 2s, Me), 3.82, 4.07 (6H, 2s,
OMe), 6.31 (1H, s, H5), 6.49 (1H, s, H7), 7.69 (1H, dd, J
7.2, 1.9 Hz, ArH), 8.33 (1H, d, J 1.9 Hz, ArH), 9.33 (1H,
d, J 9.0 Hz, ArH), 10.35 (H, br, NH). 13C NMR spectrum
(75 MHz, CDCl3): d 36.7, 39.7 (Me), 55.4, 55.5 (OMe),
86.9 (C5), 92.7 (C7), 128.8, 129.7, 132.0 (ArCH), 106.9,
119.2, 123.1, 124.7, 131.3, 138.4, 142.5, 142.6, 155.7,
161.6 (ArC), 167.6 (C]O). Mass spectrum (EI): m/z 430
(M+2, 81Br, 4%), 429 (18), 428 (M, 79Br, 4), 372 (25), 370
(28), 358 (94), 356 (100), 313 (21).
906 cmÀ1
. lmax:
228 nm (3 23,050 cmÀ1 MÀ1), 256
(22,350), 334 (18,100). 1H NMR spectrum (300 MHz,
CDCl3): d 1.45 (3H, t, J 7.1 Hz, OCH2Me), 2.51 (3H, s,
Me), 3.88, 3.89 (6H, 2s, OMe), 4.49 (2H, q, J 7.1 Hz,
OCH2), 6.11 (1H, d, J 1.5 Hz, H5), 6.50 (1H, d, J 1.9 Hz,
H7), 8.22 (1H, d, J 9.4 Hz, ArH), 8.51 (1H, dd, J 9.4,
2.6 Hz, ArH), 9.06 (1H, d, J 2.6 Hz, ArH), 10.58 (1H, br,
NH). The sample was not soluble enough for 13C NMR mea-
surement. Mass spectrum (EI): m/z 472 (M, 14%), 290 (100),
217 (50).
4.1.8. Ethyl 2-(4,6-dimethoxy-3-methylindol-2-yl)glyoxy-
late (14). This was prepared from 3-methyl-4,6-dimethoxy-
indole 13 (2.0 g, 10.5 mmol) in anhydrous diethyl ether
(75 mL) with oxalyl chloride (1.15 mL, 11.5 mmol) and
the resulting red solid was stirred at room temperature in ab-
solute ethanol (50 mL) for 1 h. Water was then added and the
mixture was extracted with dichloromethane. The organic
layer was washed with water, dried and concentrated. The
residue was chromatographed with dichloromethane as an
eluent to give the indole 14 (2.32 g, 69%) as an orange solid,
mp 96–97 ꢀC. Found: C, 62.1; H, 6.0; N, 4.9. C15H17NO5
requires C, 61.9; H, 5.9; N, 4.8%. nmax: 3384, 1736, 1712,
1627, 1597, 1508, 1448, 1299, 1209, 1155, 1075,
1019 cmÀ1. lmax: 227 nm (3 10.000 cmÀ1 MÀ1), 262
(13,100), 342 (12,550). 1H NMR spectrum (300 MHz,
CDCl3): d 1.43 (3H, t, J 7.2 Hz, OCH2Me), 2.76 (3H, s,
Me), 3.84, 3.88 (6H, 2s, OMe), 4.42 (2H, q, J 7.2 Hz,
OCH2), 6.07 (1H, d, J 1.9 Hz, H5), 6.30 (1H, d, J 1.9 Hz,
H7), 9.68 (1H, br, NH). 13C NMR spectrum (75 MHz,
CDCl3): d 12.6, 13.9 (Me), 55.2, 55.5 (OMe), 62.4
(OCH2), 85.5 (C5), 92.9 (C7), 114.3, 127.5, 139.9 (ArC),
157.8, 162.2 (C]O). Mass spectrum (EI): m/z 291 (M,
26%), 218 (100), 145 (20).
4.1.11. (4,6-Dimethoxyindol-2-yl)-phenylmethanone
oxime (18). This was prepared from indole 17 (0.15 g,
0.4 mmol),
hydroxylamine
hydrochloride
(0.30 g,
4.3 mmol) and pyridine (1.5 mL) in absolute ethanol
(1.5 mL) under reflux for 2 h. After extraction and concen-
tration, the residue was chromatographed with dichloro-
methane/ethyl acetate (95:5) to give the oxime 18 (0.11 g,
92%) as a brown solid, mp 90–92 ꢀC. Found: C, 68.7; H,
5.7; N, 9.3. C17H16N2O3 requires C, 68.9; H, 5.4; N, 9.4%.
nmax: 3426, 3386, 1627, 1592, 1514, 1455, 1376, 1294,
1149 cmÀ1. lmax: 229 nm (3 19,550 cmÀ1 MÀ1), 251
1
(18,800), 317 (13,100). H NMR spectrum (300 MHz, d6-
DMSO): d 3.73–3.76 (6H, m, syn and anti OMe), 5.88,
6.13 (1H, d, J 1.9 Hz, syn and anti H5), 6.09, 6.27 (1H, d,
J 1.9 Hz, syn and anti H7), 6.52, 6.69 (1H, s, syn and anti
H3), 7.37–7.52 (5H, m, syn and anti ArH), 11.11, 11.30
(1H, s, syn and anti NH), 10.99, 11.85 (1H, s, syn and anti
OH). 13C NMR spectrum (75 MHz, d6-DMSO): d 55.3,
55.3, 55.5 (Me), 87.4, 87.7 (C5), 91.6, 91.9 (C7), 102.7,
105.2 (C3), 128.2, 128.5, 128.8, 129.1, 129.2, 129.4
(ArCH), 112.1, 113.1, 127.7, 132.3, 133.2, 136.9, 138.6,
4.1.9. Ethyl 2-(4,6-dimethoxy-3-methylindol-2-yl)-2-(hy-
droxyimino)acetate (15). This was prepared from indole
glyoxylic ester 14 (0.60 g, 2.1 mmol), hydroxylamine

6718
T. D. Wahyuningsih et al. / Tetrahedron 63 (2007) 6713–6719
139.1, 148.6, 149.8, 153.5, 153.8 (ArC), 158.2, 158.5
(C]N). Mass spectrum (EI): m/z 296 (M, 92%), 278 (25),
263 (37), 235 (48), 220 (29), 201 (23), 149 (26), 77 (100).
d 48.3 (CH2), 55.4, 55.5, 55.8 (OMe), 86.8, 87.1, (C5),
92.0, 92.1 (C7), 101.4, 105.7 (C3), 126.8, 127.1, 127.2,
127.2, 127.4, 128.2, 128.6, 128.5, 128.8, 129.2, 129.4
(ArCH), 112.3, 112.8, 129.2, 133.2, 134.4, 136.5, 138.4,
138.7, 139.2, 140.7, 149.2, 151.0, 153.6, 153.7 (ArC),
157.9, 158.7 (C]N). Mass spectrum (EI): m/z 386 (M,
38), 369 (44), 266 (40), 91 (100).
4.1.12. (4,6-Dimethoxyindol-2-yl)-phenylmethanone
O-2,4-dinitrophenyloxime (19). This was prepared from
indole oxime 18 (0.20 g, 0.7 mmol), absolute ethanol
(20 mL), sodium (30 mg, 1.3 mmol) and fluoro-2,4-dinitro-
benzene (0.08 mL, 0.4 mmol) to yield the oxime ether 19
(0.28 g, 91%) as an orange solid, mp 198–200 ꢀC. Found:
C, 59.8; H, 3.7; N, 11.9. C23H18N4O7 requires C, 59.7; H,
3.9; N, 12.1%. nmax: 3390, 1606, 1530, 1341, 1251,
1148 cmÀ1. lmax: 229 nm (3 28,200 cmÀ1 MÀ1), 255
(32,250), 325 (23,300). 1H NMR spectrum (300 MHz,
CDCl3): d 3.87, 3.92 (6H, 2s, OMe), 6.17 (1H, d, J 1.5 Hz,
H5), 6.64 (1H, s, H3), 6.69 (1H, d, J 2.2 Hz, H7), 7.51–
7.68 (5H, m, ArH), 8.30 (1H, d, J 9.4 Hz, ArH), 8.50 (1H,
dd, J 9.4, 2.6 Hz, ArH), 9.11 (1H, d, J 2.6 Hz, ArH), 11.11
(1H, br, NH). The sample was not soluble enough for 13C
NMR measurement. Mass spectrum (EI): m/z 463 (M+1,
22%), 297 (80), 281 (100).
4.1.15. (1-Benzyl-4,6-dimethoxyindol-2-yl)-phenylme-
thanone O-2,4-dinitrophenyloxime (23). This was pre-
pared from indole oxime 22 (0.50 g, 1.3 mmol), absolute
ethanol (50 mL), sodium (40 mg, 1.7 mmol) and fluoro-
2,4-dinitrobenzene (0.23 mL, 1.3 mmol) to yield the oxime
ether 23 (0.65 g, 91%) as a yellow solid, mp 115 ꢀC. Found:
C, 65.3; H, 4.6; N, 9.7. C30H24N4O7 requires C, 65.2; H, 4.4;
N, 10.1%. nmax: 1604, 1535, 1510, 1470, 1337, 1287, 1248,
1
1204 cmÀ1. lmax: 231 nm (3 36,200 cmÀ1 MÀ1). H NMR
spectrum (300 MHz, CDCl3): d 3.79, 3.81, 3.87, 3.92 (6H,
s, syn and anti OMe), 5.15, 5.81 (2H, s, syn and anti CH2),
6.22, 6.26 (1H, d, J 1.9 Hz, syn and anti H5), 6.31, 6.42
(1H, d, J 1.1 Hz, syn and anti H7), 6.63, 6.84 (1H, d, J
0.75 Hz, syn and anti H3), 6.86–6.93, 7.08–7.14, 7.33–
7.40, 7.46–7.55 (10H, m, syn and anti ArH), 7.98, 8.42
(1H, dd, J 9.4, 2.6 Hz, syn and anti ArH), 8.01 (1H, d, J
9.4 Hz, syn and anti ArH), 8.70, 8.84 (1H, d, J 2.6 Hz, syn
and anti ArH). 13C NMR spectrum (75 MHz, CDCl3):
d 48.9, 49.6 (OCH2), 55.3, 55.5, 55.6 (OMe), 85.0, 85.9
(C5), 92.5, 92.6 (C7), 106.5 (C3), 112.1, 116.8, 117.6,
121.6, 121.9, 125.6, 126.4, 127.2, 127.3, 127.9, 128.4,
128.5, 128.8, 128.9, 128.9, 129.1, 129.9, 131.4 (ArCH),
113.0, 113.1, 126.5, 129.7, 131.7, 133.8, 136.2, 137.3,
138.2, 140.2, 140.9, 142.4, 154.4, 154.5, 156.9, 157.2,
158.2, 158.9, 159.2, 160.5, 172.3 (ArC). Mass spectrum
(EI): m/z 553 (M+1, 7%), 369 (100).
4.1.13. 2-Benzoyl-1-benzyl-4,6-dimethoxyindole (21).
The mixture of 2-benzoyl-4,6-dimethoxyindole 17 (0.40 g,
1.4 mmol) and potassium hydroxide (0.32 g, 5.7 mmol) in
dry dimethyl sulfoxide (8 mL) was stirred at room tempera-
ture for 1 h. Benzyl bromide (0.4 mL, 3.4 mmol) was added
dropwise and the mixture was stirred for another 2 h. Water
was added and the reaction mixture was extracted with di-
chloromethane. The organic layer was washed with water,
dried and concentrated. The residue was chromatographed
with dichloromethane/light petroleum (7:3) to give the
indole 21 (0.40 g, 76%) as a yellow solid, mp 128–130 ꢀC.
Found: C, 77.8; H, 5.8; N, 3.7. C24H21NO3 requires
C, 77.6; H, 5.7; N, 3.8%. nmax: 1613, 1586, 1484, 1268,
1250, 1203, 1156, 1096, 1044 cmÀ1. lmax: 228 nm (3
22,650 cmÀ1 MÀ1), 263 (22,400), 324 (14,200), 364
4.1.16. 7,9-Dimethoxy-12-phenylindolo[2,1-c][1,4]benzo-
diazepine (24). This was prepared from indole oxime ether
23 (0.42 g, 0.76 mmol) and sodium hydride (0.11 g, 80%
dispersion in oil, 3.80 mmol) in dioxane at room temperature
for 24 h. After extraction and concentration, the residue was
chromatographed with dichloromethane as an eluent to yield
the product 24 (91 mg, 32%) as a yellow solid, but which
could not be obtained analytically pure. 1H NMR spectrum
(300 MHz, CDCl3): d 3.76, 3.84 (6H, 2s, OMe), 5.75 (2H,
s, CH2), 6.17 (1H, d, J 1.9 Hz, H5), 6.31 (1H, d, J 1.9 Hz,
H7), 6.33 (1H, s, H3), 7.0–7.5 (9H, m, ArH). 13C NMR spec-
trum (75 MHz, CDCl3): d 49.0 (CH2), 55.2, 55.5 (OMe),
85.8 (C5), 91.9 (C7), 107.4 (C3), 126.2, 126.7, 126.8,
127.9 (ArCH) (ArC). Mass spectrum (EI): m/z 369 (M+1,
100%), 282 (91).
1
(11,100). H NMR spectrum (300 MHz, CDCl3): d 3.80,
3.89 (6H, 2s, OMe), 5.84 (2H, s, CH2), 6.19 (1H, s, H5),
6.35 (1H, s, H7), 7.12–7.86 (11H, m, H3 and ArH). 13C
NMR spectrum (75 MHz, CDCl3): d 48.3 (CH2), 55.3,
55.5 (OMe), 85.0, (C5), 92.8 (C7), 114.6 (C3), 126.4,
127.0, 127.9, 128.5, 129.4, 131.5 (ArCH), 112.5, 132.7,
138.3, 139.7, 142.3, 155.4, 161.1 (ArC), 187.4 (C]O).
Mass spectrum (EI): m/z 371 (M, 19%), 105 (22), 91 (100).
4.1.14. (1-Benzyl-4,6-dimethoxyindol-2-yl)-phenylme-
thanone oxime (22). This was prepared from indole 21
(0.23 g, 0.6 mmol), hydroxylamine hydrochloride (0.44 g,
6.4 mmol) and pyridine (2 mL) in absolute ethanol (3 mL)
under reflux for 19 h. After extraction and concentration,
the residue was chromatographed with dichloromethane/eth-
yl acetate (95:5) to give the oxime 22 (0.20 g, 81%) as a pale
yellow solid, mp 180–182 ꢀC. Found: C, 74.8; H, 5.9; N, 7.4.
C24H22N2O3 requires C, 74.6; H, 5.7; N, 7.3%. nmax: 3243,
1627, 1580, 1503, 1455, 1361, 1249, 1203, 1155,
4.1.17. 1,2-Dibenzoyl-4,6-dimethoxyindole (26). A mix-
ture of 2-benzoyl-4,6-dimethoxyindole 17 (0.38 g, 1.3
mmol), sodium hydroxide (0.20 g, 5.0 mmol) and tetrabutyl
ammonium hydrogen sulfate (30 mg) in dichloromethane
(50 mL) was stirred at room temperature for 15 min. Benzo-
yl chloride (0.16 mL, 1.3 mmol) was added dropwise and
the mixture was stirred for another 30 min. The mixture
was filtered and the filtrate was evaporated under reduced
pressure. The residue was chromatographed with dichloro-
methane as an eluent to give the indole 26 (0.21 g, 41%)
as a pale yellow solid, mp 174–176 ꢀC. Found: C, 74.5; H,
4.9; N, 3.5. C24H19NO4 requires C, 74.8; H, 5.0; N, 3.6%.
1
1094 cmÀ1. lmax: 231 nm (3 34,800 cmÀ1 MÀ1). H NMR
spectrum (300 MHz, d6-DMSO): d 3.69–3.82 (6H, m, syn
and anti OMe), 5.17, 5.79 (2H, s, syn and anti CH2), 6.18,
6.23 (1H, d, J 1.9 and 1.9 Hz, syn and anti H5), 5.98, 6.33
(1H, s, syn and anti H7), 6.53, 6.60 (1H, s, H3), 6.93–7.42
(10H, m, syn and anti ArH), 11.15, 11.84 (1H, s, syn and
anti OH). 13C NMR spectrum (75 MHz, d6-DMSO):

T. D. Wahyuningsih et al. / Tetrahedron 63 (2007) 6713–6719
6719
nmax: 1687, 1640, 1615, 1597, 1496, 1290, 1214, 1151 cmÀ1
.
3. Ishida, J.; Wang, H. K.; Oyama, M.; Cosentino, M. L.;
Hu, C. Q.; Lee, H. H. J. Nat. Prod. 2001, 64, 958–
960.
4. Fryer, R. L.; Ning, R. Y. F; Sternbach, L. H.; Walser, A. U.S.
Patent 4,014,883, 1977.
5. Jeevanandam, A.; Srinivasan, P. C. Synth. Commun. 1995, 25,
3427–3434.
6. Jones, A. W. Ph.D. Thesis, UNSW, 2000.
7. Armesto, D.; Gallego, M. G.; Horspool, W. M. J. Chem. Soc.,
Perkin Trans. 1 1989, 1623–1626.
lmax: 229 nm (3 23,850 cmÀ1 MÀ1), 251 (29,400), 348
(17,850), 361 (19,450). 1H NMR spectrum (300 MHz,
CDCl3): d 3.84, 3.91 (6H, 2s, OMe), 6.34 (1H, d, J 1.9 Hz,
H5), 7.02 (1H, d, J 1.9 Hz, H7), 7.22 (1H, s, H3), 7.33–
7.82 (10H, m, ArH). 13C NMR spectrum (75 MHz,
CDCl3): d 55.5, 55.7 (OMe), 88.7, (C5), 95.2 (C7), 116.9
(C3), 128.3, 128.5, 128.8, 129.1, 132.4, 132.8 (ArCH),
112.8, 135.8, 137.4, 141.7, 155.0, 162.3 (ArC), 169.9,
184.8 (C]O). Mass spectrum (EI): m/z 385 (M, 18%),
105 (100), 77 (55).
8. Wenkert, E.; Barnett, B. F. J. Am. Chem. Soc. 1960, 82, 4671–
4675.
9. Kusurkar, R. S.; Goswami, S. K.; Vyas, S. M. Tetrahedron Lett.
2003, 44, 4761–4763.
Acknowledgements
10. Hibino, S.; Kano, S.; Mochizuki, N.; Sugino, E. J. Org. Chem.
1984, 49, 5006–5008.
11. Black, D. S.; Bowyer, M. C.; Ivory, A. J.; Jolliffe, K. A.;
Kumar, N. Tetrahedron 1996, 52, 4687–4696.
12. Black, D. S.; Wong, L. C. H. J. Chem. Soc., Chem. Commun.
1980, 200.
Financial support from the Australian Research Council is
gratefully acknowledged. T.D.W. acknowledges receipt of
an Indonesian Government Quality of Undergraduate Edu-
cation (QUE) Scholarship.
References and notes
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1. Wahyuningsih, T. D.; Pchalek, K.; Kumar, N.; Black, D. S.
Tetrahedron 2006, 62, 6343–6348.
14. Ho, C. Y.; Hageman, W. E.; Persico, F. J. J. Med. Chem. 1986,
29, 1118–1121.
2. Black, D. S.; Kumar, N.; McConnell, D. B. Tetrahedron 1996,
52, 8925–8936.
15. Hiremath, S. P.; Bajji, A. C.; Biradar, J. S. Indian J. Chem.
1988, 27B, 756–757.