Synthesis of imidazo[1′,5′:1,2]pyrido [3,4-b]indole derivatives

Article abstract of DOI:10.1007/s007060200114

The reactions of 1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid and its ethyl ester with alkyl and aryl isothiocyanates under mild conditions resulted in the corresponding thiohydantoin-fused tetrahydro-β-carbolines. Treatment of the ethyl ester with isocyanates furnished ethyl 2-alkyl- or arylcarbamoyl-1,2,3,4-tetrahydro-β-carboline-1-carboxylates which were transformed to hydantoinfused tetrahydro-β-carbolines. The structures of the thiohydantoin compounds, involving two conformers and the presence of keto-enol tautomerism, were determined by NMR spectroscopy.

Full text of DOI:10.1007/s007060200114

Monatshefte fur Chemie 133, 1423±1430 ꢀ2002)
Synthesis of Imidazo[10,50:1,2]pyrido
[3,4-b]indole Derivatives
Ã
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Magdolna Solymar, Marta Palko, Tamas Martinek, and Ferenc FuÈlop
Institute of Pharmaceutical Chemistry, University of Szeged, H-6701 Szeged, Hungary
Summary. The reactions of 1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylic acid and its ethyl ester with
alkyl and aryl isothiocyanates under mild conditions resulted in the corresponding thiohydantoin-fused
tetrahydro-ꢀ-carbolines. Treatment of the ethyl ester with isocyanates furnished ethyl 2-alkyl- or
arylcarbamoyl-1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylates which were transformed to hydantoin-
fused tetrahydro-ꢀ-carbolines. The structures of the thiohydantoin compounds, involving two confor-
mers and the presence of keto-enol tautomerism, were determined by NMR spectroscopy.
Keywords. ꢀ-Carbolines; Hydantoins; Thiohydantoins; Keto-enol tautomerism.
Introduction
The ꢀ-carboline structure is present in important natural compounds, and its deriv-
atives exert various pharmacological effects on the benzodiazepine receptors in the
mammalian nervous system [1±4]. It is also found as a structural element of
compounds exerting anticancer potential, analgesic activity, or oxytocin antago-
nism [5]. In 1994, in a programme with the goal of developing new drugs affecting
the central nervous system, Lopez-Rodriguez et al. have studied the ring-closure
possibilities of the 1,2,3,4-tetrahydro-ꢀ-carboline skeleton through the reaction of
1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylic acid ꢀ1) with alkyl and aryl isocya-
nates under vigorous conditions ꢀre¯uxing for 40 h in acetone or DMSO). In their
case the corresponding hydantoin analogues have been formed [6]. Some further
derivatives of the 4-ring hydantoins exert pharmacological effects on ꢁ1-adreno-
receptors [7]. However, the synthesis of thiohydantoin derivatives remained un-
solved under the circumstances applied: in the reactions of 1 and isothiocyanates,
decarboxylation took place, and open-chain thiourea derivatives have been isolated
instead of the desired thiohydantoins [6].
Our present aim is to attempt the synthesis of thiohydantoin-fused imidazo
[10,50:1,2]pyrido[3,4-b]indole derivatives under mild conditions based on the
results of similar ring closures [8±13], starting from ethyl 1,2,3,4-tetrahydro-ꢀ-
carboline-1-carboxylate ꢀ2).
Ã
Corresponding author. E-mail: fulop@pharma.szote.u-szeged.hu

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M. Solymar et al.
1424
Results and Discussion
1,2,3,4-Tetrahydro-ꢀ-carboline-1-carboxylic acid ꢀ1) was obtained from trypt-
amine hydrochloride and glyoxylic acid [14]. Racemic 1 was esteri®ed by two
methods ꢀScheme 1): re¯uxing in ethanol with thionyl chloride ꢀmethod A) or
reaction with dry hydrogen chloride gas in ethanol ꢀmethod B) [14]. Both methods
resulted besides 2 in a by-product, the hydrochloride of 1,2,3,4-tetrahydronorhar-
mane ꢀ3) as a consequence of decarboxylation. This side-product could be ®ltered
off from the hot ethanolic solutions. Method A gave 2 in a somewhat higher yield
ꢀA: 76%, B: 57%).
When the ester base 2 was combined with alkyl and aryl isothiocyanates at
room temperature in methanol, the corresponding target thiohydantoins 4 could be
®ltered off from the reaction mixtures after stirring overnight ꢀScheme 2). Gener-
ally, the yields were fair to good ꢀ41±74%), except in the case of 4d where it
was only 16%. No decarboxylation was observed during the reactions, and no
Scheme 1
Scheme 2

Imidazo[10,50:1,2]pyrido[3,4-b]indole Derivatives
1425
intermediates or by-products could be isolated from the residues. From the reac-
tions of 1 and isothiocyanates under the same conditions, but with sodium methyl-
ate as the catalyst, the thiohydantoins 4 were obtained in rather low yields.
In the reactions of 2 and ethyl and phenyl isocyanates under similarly mild
conditions, the corresponding urea derivatives 5 were formed as crystalline prod-
ucts. These were cyclized by re¯uxing in ethanol for one day under hydrochloric
acid catalysis. Hydantoin compounds 6a and 6b were formed in 56 and 37% yield;
and no other products could be isolated.
The low solubility and susceptibility to degradation of 4a±h made the proof of
the thiohydantoin structure by NMR spectroscopy dif®cult. Hydantoin derivatives
can undergo keto-enol tautomerism [6]. In addition, the saturated nitrogen contain-
ing heterocycles tend to populate more than one low-energy conformation in solu-
tion due to the relative ease of nitrogen inversion [15]. Bearing in mind the above
possible processes, the observed line broadening in pyridine-d5 at 300 K was not
surprising. In order to slow down the chemical exchange we decreased the tem-
perature to 243 K. At this temperature two exchanging species were observed. The
1
results of H and 13C resonance assignment by means of COSY, HSQC, and
HMBC for 4b as an example demonstrated that the two species have the same
spin connectivity and similar chemical shifts. Concerning the constitution, the
missing H-11b signal and the chemical shift values for C-11b ꢀ71.25 and
67.96 ppm) pointed to the predominance of the enol form for both species; how-
ever, the presence of the keto form cannot be excluded. In addition to the argu-
ments described above, the 13C chemical shifts relating to C-1 ꢀ170.06 and
169.03 ppm) are between the values for the possible enol ꢀca. 90 ppm) and keto
ꢀca. 220 ppm) forms. The chemical shifts of C-11b ꢀ71.25 and 67.96 ppm) are also
Table 1. 1H and 13C NMR data of the conformers 4bA and 4bB dissolved in pyridine-d5
4bA ꢂ=ppm
4bB ꢂ=ppm
1H
13C
1H
13C
1
±
170.06
182.8
40.46
20.21
112.45
125.85
138.24
112.23
123.36
119.18
118.92
±
±
169.03
184.74
42.62
19.94
111.65
126.21
138.30
120.17
119.64
112.8
123.48
±
3
±
±
5
2.52, 4.98
3.88, 5.44
6
2.44, 2.84
2.76, 2.93
6a
6b
6c
7
±
±
±
±
±
±
6.96
7.05
7.17
7.51
12.4
±
7.35
7.74
7.43
7.33
13.41
±
8
9
10
11
11a
11b
121.94
71.25a
122.75
67.96a
b
b
±
±
a
ꢂ values between those for the enol ꢀ80 ppm) and keto ꢀ56 ppm) forms ꢀC-11b) [5]; b the methine
proton at C-11b is missing because of the suggested keto-enol tautomerism and HD exchange

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M. Solymar et al.
1426
average values in both species between the chemical shifts found in the literature
[6] for the enol ꢀ80 ppm) and keto ꢀ56 ppm) forms. These observations, together
with the missing H-11b, suggest a rapid acid-catalyzed equilibrium between the
two tautomeric forms in both conformers. From these data we may conclude that
the NMR signals belong to two exchanging conformational isomers which are
predominantly the enol forms of the thiohydantoin derivatives. The two conformers
are designated by 4bA and 4bB; the chemical shifts given in Table 1.
In CDCl3 solutions of 4, broadened signals were obtained which would also
suggest the possibility of a conformational equilibrium. The compounds 4 were
satisfactorily soluble in DMSO-d6, where characteristic but still slightly broadened
signals appeared. The geometry of the two conformations could not be estab-
lished, but the conformational equilibrium is obviously due to nitrogen inversion
[15].
Conclusions
It was proven that 2-substituted 5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]
pyrido[3,4-b]indole-3-thiones 4 can be prepared under mild conditions from
1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylic acid ꢀ1) and its ethyl ester 2. The struc-
tures of the thiohydantoin compounds, involving two conformers and the presence
of keto-enol tautomerism, were determined by NMR spectroscopy.
Experimental
Melting points were determined with a Ko¯er apparatus at a heating rate of 4ꢀC=min; the values are
not corrected. 1H NMR spectra were recorded in 5 mm tubes in the appropriate solvents on a Bruker
DRX 400 instrument at 400 MHz. IR spectra were measured in KBr disks on a Perkin Elmer Paragon
1000PC FT-IR spectrometer. Analytical data were obtained by a Heraeus apparatus; they were in
favourable agreement with the calculated values. The cyanates and isothiocyanates used were com-
mercial products ꢀAldrich, Fluka). Yields in parentheses refer to reactions starting from 1.
Ethyl 1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylate ꢀ2)
Method A: Absolute EtOH ꢀ18 cm3) was cooled below À 10ꢀC. SOCl2 ꢀ1.59 cm3, 21.8mmol) was
added dropwise, the temperature being kept below À 10ꢀC. Then, 1 ꢀ4.3g, 19.8 mmol) was added to
the mixture, which was ®rst stirred for 0.5 h at 0ꢀC and then for 3 h at room temperature, and ®nally
re¯uxed for 1 h.
Method B [14]: A suspension of 7.33 g dried and well-powdered 1 ꢀ33.8 mmol) in 150 cm3 absolute
EtOH was saturated with dry HCl gas under stirring, and the mixture was then re¯uxed for 2 h.
The crystalline product was ®ltered off from the hot solution in both cases and was identi®ed as
1,2,3,4-tetrahydronorharmane ꢀ3; A: 1.28 g, 6.1mmol, 18%; B: 2.45 g, 11.7mmol, 35%). EtOH was
evaporated under reduced pressure, and diethyl ether was added to promote crystallization. From the
hydrochloride, the free base was obtained by treatment with aqueous NaOH and extraction with CHCl3
followed by drying ꢀNa2SO4) and evaporation. The product was puri®ed by column chromatography
on silica gel with a mixture of toluene: MeOHˆ 4:1 as the eluent. Method A resulted in a yield of 76%
2, whereas method B gave a yield of 57%.
Yellowish needles; m.p.: 107±110ꢀC ꢀEt2O; Ref. [14]: m.p.: 110±111ꢀC); IR ꢀKBr): ꢃꢀˆ 3363,
1715, 1252 cmÀ 1
;
1H NMR ꢀDMSO-d6): ꢂ ˆ 1.25 ꢀt, J ˆ 7.05Hz, CH3), 2.54±2.63 ꢀm, H-6a,b),

Imidazo[10,50:1,2]pyrido[3,4-b]indole Derivatives
1427
2.95±3.05 ꢀm, H-5a), 3.06±3.16 ꢀm, H-5b), 4.08±4.23 ꢀm, CH2), 4.67 ꢀs, H-11b), 6.95 ꢀt, J ˆ 7.30 Hz,
H-8), 7.04 ꢀt, J ˆ 7.30Hz, H-9), 7.33 ꢀd, J ˆ 7.8 Hz, H-7), 7.39 ꢀd, J ˆ 7.8 Hz, H-10), 10.64 ꢀs, H-11)
ppm.
2-Substituted 5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-3-
thiones ꢀ4a±4h); general procedure
The appropriate isothiocyanate ꢀ0.8mmol) was added to 195 mg ꢀ0.8mmol) 2 dissolved in 40cm3
MeOH. The mixture was stirred overnight, and the crystalline product was ®ltered off and recrystal-
lized. The synthesis was repeated from the acid 1 in every case, the same method being used with the
application of 1.6 mmol sodium methylate as catalyst. The analytical data were identical.
2-Methyl-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-
3-thione ꢀ4a; C14H13N3OS)
Light-pink crystals; m.p.: 195±200ꢀC ꢀEtOH=CHCl3); yield: 66% ꢀ16%); IR ꢀKBr): ꢃꢀˆ 3447, 3399,
3373, 1742, 1728, 1311cmÀ 1; 1H NMR ꢀDMSO-d6): ꢂ ˆ 2.68±2.88 ꢀm, H-6a,b), 2.95 ꢀbs, H-5a), 3.21
ꢀs, CH3), 4.92 ꢀm, H-5b), 7.02 ꢀt, J ˆ 7.55Hz, H-8), 7.15 ꢀt, J ˆ 7.55Hz, H-9), 7.46 ꢀd, J ˆ 7.55 Hz,
H-7), 7.5 ꢀd, J ˆ 7.55 Hz, H-10), 10.52 ꢀs, H-11) ppm.
2-Ethyl-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-
3-thione ꢀ4b; C15H15N3OS)
White crystals; m.p.: 203±211ꢀC ꢀEtOH=CHCl3); yield: 62% ꢀ27%); IR ꢀKBr): ꢃꢀˆ 3460, 3389, 1742,
1
1727, 1271 cmÀ 1; H NMR ꢀDMSO-d6): ꢂ ˆ 1.19 ꢀt, J ˆ 7.30Hz, CH3), 2.68±2.85 ꢀm, H-6a,b), 2.91
ꢀbs, H-5a), 3.72±3.91 ꢀm, CH2), 4.91 ꢀm, H-5b), 7.03 ꢀt, J ˆ 7.3 Hz, H-8), 7.16 ꢀt, J ˆ 7.30 Hz, H-9),
7.47 ꢀd, J ˆ 7.8Hz, H-7), 7.52 ꢀd, J ˆ 7.8 Hz, H-10), 10.49 ꢀs, H-11).
2-Propyl-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-
3-thione ꢀ4c; C16H17N3OS)
White crystals; m.p.: 188±190ꢀC ꢀEtOH=CHCl3); yield: 41% ꢀ19%); IR ꢀKBr): ꢃꢀˆ 3451, 3389, 1743,
1
1727 cmÀ 1; H NMR ꢀDMSO-d6): ꢂ ˆ 0.87 ꢀt, J ˆ 7.55Hz, CH3), 1.66 ꢀm, CH2), 2.63±2.88 ꢀm, H-
6a,b), 2.96 ꢀbs, H-5a), 3.61±3.83 ꢀm, CH2), 4.92 ꢀm, H-5b), 7.48 ꢀd, J ˆ 8.3 Hz, H-7), 7.02 ꢀt,
J ˆ 7.3 Hz, H-8), 7.15 ꢀt, J ˆ 7.8, H-9), 7.51 ꢀd, J ˆ 7.8, H-10), 8.31 ꢀbs, H-11) ppm.
2-Butyl-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-
3-thione ꢀ4d; C17H19N3OS)
White crystals; m.p.: 186±188ꢀC ꢀEtOH=CHCl3); yield: 16% ꢀ5%); IR ꢀKBr): ꢃꢀˆ 3456, 3387, 1743,
1724 cmÀ 1; 1H NMR ꢀDMSO-d6): ꢂ ˆ 0.90 ꢀt, J ˆ 7.30Hz, CH3), 1.23±1.35 ꢀm, CH2), 1.55±1.69 ꢀm,
CH2), 2.63±2.87 ꢀm, H-6a,b), 2.96 ꢀbs, H-5a), 3.66±3.87 ꢀm, CH2), 4.91 ꢀm, H-5b), 7.03 ꢀt,
J ˆ 7.55Hz, H-8), 7.15 ꢀt, J ˆ 7.55, H-9), 7.46 ꢀd, J ˆ 8.06 Hz, H-7), 7.52 ꢀd, J ˆ 8.06Hz, H-10),
10.44 ꢀs, H-11) ppm.
2-Phenyl-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo [10,50:1,2]pyrido[3,4-b]indole-3-
thione ꢀ4e; C19H15N3OS)
Light-pink crystals; m.p.: 208±214ꢀC ꢀEtOH=CHCl3); yield: 57% ꢀ31%); IR ꢀKBr): ꢃꢀˆ 3423, 3371,
3250, 1754, 1744, 1285 cmÀ 1; 1H NMR ꢀDMSO-d6): ꢂ ˆ 2.77±2.90 ꢀm, H-6a), 2.90±3.02 ꢀm, H-6b),

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M. Solymar et al.
1428
3.12 ꢀbs, H-5a), 5.12 ꢀbs, H-5b), 7.06 ꢀt, J ˆ 7.81, H-8), 7.17 ꢀt, J ˆ 7.81, H-9), 7.30±7.37 ꢀm, H-7 and
H-10), 7.46±7.58 ꢀm, phenyl), 10.54 ꢀs, H-11) ppm.
2-0p-Tolyl)-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-3-
thione ꢀ4f; C20H17N3OS)
Light-brown crystals; m.p.: 187±189ꢀC ꢀEtOH=CHCl3); yield: 67% ꢀ36%); IR ꢀKBr): ꢃꢀˆ 3442, 3408,
1752, 1736, 1284 cmÀ 1; 1H NMR ꢀDMSO-d6): ꢂ ˆ 2.35 ꢀs, CH3), 2.78±2.88 ꢀm, H-6a), 2.89±3.00 ꢀm,
H-6b), 3.10 ꢀs, H-5a), 5.11 ꢀbs, H-5b), 7.05 ꢀt, J ˆ 7.55, H-8), 7.12±7.23 ꢀm, H-9, H-7 and H-10), 7.31
ꢀd, J ˆ 8.06 Hz, phenyl), 7.52 ꢀd, J ˆ 7.81 Hz, phenyl), 10.51 ꢀs, H-11) ppm.
2-0p-Chlorophenyl)-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido
[3,4-b]indole-3-thione ꢀ4g; C19H14ClN3OS)
Light-pink crystals; m.p.: 202±209ꢀC ꢀEtOH=CHCl3); yield: 59% ꢀ28%); IR ꢀKBr): ꢃꢀˆ 3419, 3396,
1745, 1730, 1281, 1253 cmÀ 1; 1H NMR ꢀDMSO-d6): ꢂ ˆ 2.76±3.01 ꢀm, H-6a,b), 3.08 ꢀbs, H-5a) 5.09
ꢀbs, H-5b), 7.06 ꢀt, J ˆ 7.55 Hz, H-8), 7.17 ꢀt, J ˆ 7.55Hz, H-9), 7.39 ꢀd, J ˆ 8.56Hz, phenyl),
7.49±7.56 ꢀm, H-7 and H-10), 7.62 ꢀd, J ˆ 8.56Hz, phenyl), 10.56 ꢀs, H-11) ppm.
2-0p-Methoxyphenyl)-5,6,11,11b-tetrahydro-1-oxo-1H-imidazo[10,50:1,2]pyrido
[3,4-b]indole-3-thione ꢀ4h; C20H17N3O2S)
Light-brown crystals; m.p.: 183±185ꢀC ꢀEtOH=CHCl3); yield: 74% ꢀ21%); IR ꢀKBr): ꢃꢀˆ 3363, 1715,
1
1252, 1246, 1236 cmÀ 1; H NMR ꢀDMSO-d6): ꢂ ˆ 2.73±3.01 ꢀm, H-6a,b), 3.10 ꢀbs, H-5a), 3.32 ꢀs,
OCH3), 5.10 ꢀbs, H-5b), 6.95±7.09 ꢀm, H-8, H-7 and H-10), 7.16 ꢀt, J ˆ 7.55 Hz, H-9), 7.24 ꢀd,
J ˆ 7.81Hz, phenyl), 7.53 ꢀd, J ˆ 7.81 Hz, phenyl), 10.51 ꢀs, H-11) ppm.
2-Substituted ethyl carbamoyl-1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylates
ꢀ5a,b); general procedure
The appropriate isocyanate ꢀ0.8mmol) was added to 195 mg ꢀ0.8mmol) 2 dissolved in 40cm3 MeOH.
The mixture was stirred overnight, and the crystalline product was ®ltered off and recrystallized from
EtOH and diethyl ether.
Ethyl 2-ethylcarbamoyl-1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylate ꢀ5a; C17H21N3O3)
Pale-yellow crystals; m.p.: 167±170ꢀC ꢀEtOH=Et2O); yield: 66%; IR ꢀKBr): ꢃꢀˆ 3338, 3290, 1726,
1606 cmÀ 1
;
1H NMR ꢀCDCl3): ꢂ ˆ 1.19 ꢀt, J ˆ 7.3 Hz, CH3), 1.30 ꢀt, J ˆ 7.3 Hz, CH3, ester),
2.76±2.94 ꢀm, H-6a,b), 3.30±3.39 ꢀm, CH2), 3.53 ꢀddd, J ˆ 4.53, 11.33, 13.6Hz, H-5a), 3.92 ꢀddd,
J ˆ 1.51, 5.04, 13.6 Hz, H-5b), 4.18±4.31 ꢀm, CH2, ester), 4.65 ꢀt, J ˆ 4.5Hz, H-11b), 5.93 ꢀs, NH),
7.11 ꢀt, J ˆ 7.8Hz, H-8), 7.2 ꢀt, J ˆ 7.81Hz, H-9), 7.36 ꢀd, J ˆ 7.8Hz, H-7), 7.49 ꢀd, J ˆ 7.8 Hz, H-10),
8.28 ꢀs, H-11) ppm.
Ethyl 2-phenylcarbamoyl-1,2,3,4-tetrahydro-ꢀ-carboline-1-carboxylate ꢀ5b; C21H21N3O3)
Pale-yellow crystals; m.p.: 145±150ꢀC ꢀEtOH=Et2O); yield: 61%; IR ꢀKBr): ꢃꢀ ˆ 3386, 3289, 1723,
1630, 1622 cmÀ 1; 1H NMR ꢀCDCl3): ꢂ ˆ 1.31 ꢀt, J ˆ 7.3 Hz, CH3), 2.84±3.03 ꢀm, H-6a,b), 3.67 ꢀddd,
J ˆ 4.28, 11.83, 13.6 Hz, H-5a), 4.13 ꢀddd, J ˆ 1.02, 5.04, 13.6Hz, H-5b), 4.23±4.32 ꢀm, CH2), 5.99
ꢀbs, H-11b), 6.62 ꢀs, NH), 7.06 ꢀt, J ˆ 7.55Hz, phenyl), 7.13 ꢀt, J ˆ 7.3Hz, H-8), 7.21 ꢀt, J ˆ 8.06 Hz,
H-9), 7.31 ꢀt, J ˆ 7.3 Hz, phenyl), 7.36±7.41 ꢀm, phenyl and H-7), 7.51 ꢀd, J ˆ 8.06Hz, H-10), 8.31
ꢀs, H-11) ppm.

Imidazo[10,50:1,2]pyrido[3,4-b]indole Derivatives
1429
2-Substituted 5,6,11,11b-tetrahydro-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-
1,302H)-diones ꢀ6a,b); general procedure
The appropriate carbamoyl compounds 5a or 5b ꢀ50 mg) were re¯uxed in 25cm3 EtOH containing 4%
dry HCl for one day. The reaction mixture was evaporated, diethyl ether was added, and the crystalline
product was ®ltered off and recrystallized.
2-Ethyl-5,6,11,11b-tetrahydro-1H-imidazo[10,50:1,2]pyrido[3,4-b]
indole-1,302H)-dione ꢀ6a)
Pale-yellow crystals; m.p.: 182±184ꢀC ꢀEtOH=H2O; Ref. [6]: m.p.: 184ꢀC); yield: 56%.
2-Phenyl-5,6,11,11b-tetrahydro-1H-imidazo[10,50:1,2]pyrido[3,4-b]indole-1,302H)-dione
ꢀ6b; C19H15N3O2)
Pale-yellow crystals; m.p.: 239±241ꢀC ꢀEtOH=H2O; Ref. [6]: m.p.: 241ꢀC); yield: 37%; IR ꢀKBr):
ꢃꢀ ˆ 3412, 1772, 1704 cmÀ 1
;
1H NMR ꢀCDCl3): ꢂ ˆ 2.89 ꢀddd, J ˆ 1.26, 4.53, 15.86 Hz, H-6a),
2.99±3.12 ꢀm, H-6b), 3.33 ꢀddd, J ˆ 5.04, 11.58, 13.6Hz, H-5a), 4.64 ꢀdd, J ˆ 6.04, 13.6 Hz, H-5b),
5.39 ꢀt, J ˆ 1.76Hz, H-11b), 7.16 ꢀt, J ˆ 7.55 Hz, H-8), 7.25 ꢀt, J ˆ 7.81 Hz, H-9), 7.33±7.48 ꢀm, phenyl
and H-7), 7.53 ꢀd, J ˆ 7.8Hz, H-10), 8.51 ꢀs, H-11) ppm.
Acknowledgement
The authors' thanks are due to OTKA ꢀgrants No. T030452 and T034901) for ®nancial support.
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Received February 2, 2002. Accepted 0revised) March 4, 2002