Synthesis of new pyrido[3,4-c]carbazole derivatives

Article abstract of DOI:10.1007/s11172-006-0470-1

Previously unknown 2-[6-hydroxy-9-(4-methoxyphenyl)-1,2,3,9-tetrahydro-4H- carbazol-4-ylidene]malononitrile was synthesized by the Nenitzescu reaction and was used for the construction of new tetracyclic compounds, viz., pyrido[3,4-c]carbazoles.

Full text of DOI:10.1007/s11172-006-0470-1

Russian Chemical Bulletin, International Edition, Vol. 55, No. 9, pp. 1659—1663, September, 2006
1659
Synthesis of new pyrido[3,4ꢀc]carbazole derivatives
V. M. Lyubchanskaya, L. M. Alekseeva, and V. G. Granikꢀ
State Scientific Center of Antibiotics,
3a ul. Nagatinskaya, 117105 Moscow, Russian Federation.
Eꢀmail: vggranik@mail.ru
Previously unknown 2ꢀ[6ꢀhydroxyꢀ9ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3,9ꢀtetrahydroꢀ4Hꢀcarbazolꢀ
4ꢀylidene]malononitrile was synthesized by the Nenitzescu reaction and was used for the
construction of new tetracyclic compounds, viz., pyrido[3,4ꢀc]carbazoles.
Key words: Nenitzescu reaction, 6ꢀhydroxyꢀ4ꢀdicyanomethylidenecarbazole, pyriꢀ
do[3,4ꢀc]carbazole.
The development of new approaches to the synthesis
of new fused heterocycles is a topical problem of organic
chemistry. Many compounds of the carbazole series fused
to other heterocycles exhibit biological activity or are used
as drugs.1,2 1ꢀOxotetrahydrocarbazole derivatives were
used for annelation at positions 1, 9а, and 9,1,2 as well as
at positions 1 and 2.3 The use of isomeric 4ꢀoxo derivaꢀ
tives for the construction of heterocycles annulated at
positions 3 and 4 of carbazole presents difficulties. Reꢀ
cently, it has been demonstrated4 that 4ꢀoxocarbazoles
are less reactive than their 1ꢀoxo analogs. The 4ꢀoxo group
provides the required level of CHꢀacidity of the adjacent
methylene group to a much lesser degree, due to which,
for example, DMF acetal cannot be fused at this methylꢀ
ene unit.4 Hence, tetrahydrocarbazolꢀ4ꢀones are not very
attractive as components for the construction of new
tetracyclic systems by annulation at the 3,4 bond.
We succeeded in synthesizing tetrahydrocarbazole
containing the dicyanomethylene group at position 4. We
expected that the presence of this substituent containing
two electronꢀwithdrawing cyano groups would provide
better activation of the adjacent 3ꢀCH2 group toward the
nucleophilic attack than the carbonyl group.
To synthesize this carbazole by the Nenitzescu reacꢀ
tion, we used for the first time new enamine, viz.,
[3ꢀ(4ꢀmethoxyanilino)ꢀ2ꢀcyclohexenylidene]malonoꢀ
nitrile (1), which was prepared from (3ꢀoxocyclohexylꢀ1ꢀ
idene)malononitrile5 and pꢀanisidine. Condensation of
pꢀbenzoquinone with enamine 1 in acetone in the presꢀ
ence of TsOH leads to indole cyclization giving rise to
2ꢀ[6ꢀhydroxyꢀ9ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3,9ꢀtetrahydroꢀ
4Hꢀcarbazolꢀ4ꢀylidene]malononitrile (2) in a yield (40%)
satisfactory for the Nenitzescu reaction (Scheme 1).
To prevent side reactions associated, for example, with
bromination of the benzene ring activated by the hydroxy
group or alkylation of the phenol group in compound 1
typical of amide acetals,6 we prepared Oꢀacetyl derivaꢀ
tive 3. It appeared that bromination of acetoxycarbazole 3
occurs unusually to give 7ꢀbromo derivative 4 (rather than
the expected 3ꢀbromo derivative) regardless of the nature
of the brominating agent (bromine or Nꢀbromosuccinꢀ
imide) and the solvent (AcOH, CCl4, or CH2Cl2). The
following two unusual facts should be noted: the methylꢀ
ene group at position 3 of carbazole is inert toward bromiꢀ
nation, and the reaction proceeds at the benzene ring
although it is known that, in the presence of the Oꢀacetoxy
group in indole or benzofuran, the side chain is generꢀ
ally subjected to bromination.7,8 The reactions of carbꢀ
azoles 3 and 4 with DMF diethyl acetal produce the corꢀ
responding 3ꢀdimethylaminomethylidene derivatives 5
and 6 that serve as the key compounds for further heteroꢀ
cyclizations.
It should be noted that condensation at the active
methylene unit of tricyclic compound 2 requires the use
of triethylamine as the catalyst, which is, as a rule, not
necessary in the reactions of amide acetals with active
methylene compounds. In our opinion, this is due to the
aboveꢀmentioned relatively low CHꢀacidity of the methꢀ
ylene unit at position 3 of the tetrahydrocarbazole molꢀ
ecule. Even in the presence of the dicyanomethylidene
fragment, the reaction of the fused indole ring adversely
affects the possibility of generating the 3ꢀCH anion due to
resonance, which leads to a substantial weakening of the
electronegative effect of the cyano groups (Scheme 2).
It should be noted that the presence of even a rather
weak electronꢀwithdrawing group, such as the bromine
atom, at position 7 of the carbazole molecule makes it
possible to perform the reaction of compound 6 with DMF
acetal without the use of triethylamine as the catalyst.
It is known6,9 that high reactivity of amide acetals is
based on the fact that in solution these compounds exist
in equilibrium with alkoxy anions and immonium catꢀ
ions, the equilibrium being, however, strongly shifted to
the left10 (Scheme 3).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1600—1604, September, 2006.
1066ꢀ5285/06/5509ꢀ1659 © 2006 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
Lyubchanskaya et al.
Scheme 1
R = H (5), Br (6)
Reagents and conditions: i. pꢀanisidine, TsOH, benzene, refluxing, 7 h; ii. pꢀbenzoquinone, TsOH, acetone, 20 °C, 8 h;
iii. Ac2O, H2SO4; iv. Br2, CH2Cl2, refluxing, 5.5 h; v. DMF diethyl acetal, toluene, triethylamine, refluxing, 15 min.
review.6 In some cases, such cyclizations led to the conꢀ
Scheme 2
struction of the pyridine and pyrimidine rings.6 In the
present study, we used this approach for the synthesis of
new tetracyclic compounds 7—10 and pentacyclic comꢀ
pound 11. Treatment of enamines 5 and 6 with ammoꢀ
nium acetate gives rise to transamination accompanied by
pyridine cyclization and Oꢀdeacetylation to form pyriꢀ
do[3,4ꢀc]carbazole derivatives 7 and 8. The reaction of
carbazole 7 with DMF diethyl acetal proceeds smoothly
to give amidine 9 (Scheme 4).
We expected that treatment of enamine 5 with hydrꢀ
azine hydrate would afford the 1,2ꢀdiazepinocarbazole
derivative. However, this attempt also led to pyridine cyꢀ
clization giving rise to Nꢀaminopyridine derivative 10.
Due to the presence of two adjacent functional groups in
compound 9, we subjected the latter compound to yet
another cyclization. The reaction of amidine 9 with amꢀ
monium acetate produced pentacyclic pyrimidopyridoꢀ
carbazole derivative 11 in 24% yield. The low yield is due
to the fact that pyridocarbazole 7 was isolated as the maꢀ
jor reaction product.
Scheme 3
The formation of compound 7 along with pentacyclic
compound 11 is attributed to the fact that intermediate 12
in this transformation is consumed for both cyclization to
form compound 11 and fragmentation yielding N,Nꢀdiꢀ
methylformamidine and pyridocarbazole 7.
The structures of the resulting compounds were estabꢀ
lished by mass spectrometry and NMR spectroscopy.
Based on the 1H NMR spectrum of compound 10, it was
impossible to unambiguously decide whether this comꢀ
As a result, in the case of low CHꢀacidity of the active
methylene group, it is necessary to add an additional basic
catalyst facilitating proton abstraction from the CH2 group.
Compounds 5 and 6 contain functional substituents
(the nitrile group and the enamine fragment) in the adjaꢀ
cent positions, which allows annulation of another ring.
This type of cyclizations was described in detail in the

The synthesis of pyrido[3,4ꢀc]carbazole derivatives
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
1661
Scheme 4
R = H (7), Br (8)
Reagents and conditions: i. ammonium acetate, 140 °C, 30 min, silica gel chromatography; ii. DMF diethyl acetal, PriOH, refluxing,
15 min; iii. hydrazine hydrate, MeOH, 20 °C, 12 h.
trap for 7 h and then kept at 20 °C for 12 h. The precipitate was
filtered off, washed with benzene, dried, and recrystallized from
benzene. Compound 1 was obtained in a yield of 11.2 g. 1H NMR
(DMSOꢀd6), δ: 1.84 (br.s, 2 H, H(5); 2.59 (m, 4 H, 2 H(4),
2 H(6)); 3.77 (s, 3 H, OMe); 5.80 (s, 1 H, H(2)); 7.01 (m,
2 H, H(3´), H(5´)); 7.18 (m, 2 H, H(2´), H(6´)); 10.05 (br.s,
1 H, NHC(3)).
pound has the diazepine or pyridine structure, because
the spectroscopic data do not contradict both these strucꢀ
tures. Structure 10 is evidenced by electrospray and elecꢀ
tron impact mass spectra. Both mass spectra of comꢀ
pound 10 show intense peaks at 381 [M – 16]+, which
indicates that the NH2 group is easily eliminated, and this
process is possible only for Nꢀaminopyridine 10.
[6ꢀHydroxyꢀ9ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3,9ꢀtetrahydroꢀ4Hꢀ
carbazolꢀ4ꢀylidene]malononitrile (2). Compound 1 (10.6 g,
40 mmol) and TsOH (6.88 g, 40 mmol) were added with stirring
to a solution of pꢀbenzoquinone (4.32 g, 40 mmol) in acetone
(120 mL) at 20 °C. The reaction mixture was stirred for 8 h, and
the precipitate was filtered off, refluxed in acetone, and again
filtered off. The combined acetone filtrates were concentrated,
the residue was triturated with hot ethanol, and cooled, and the
precipitate was filtered off, washed with ethanol, and dried.
Compound 2 was obtained in a yield of 5.68 g. 1H NMR
(DMSOꢀd6), δ: 2.01 (q, 2 H, 2 H(2), Jo = 6.0 Hz); 2.74 and 2.93
(both t, 2 H each, 2 H(1), 2 H(3), Jo = 6.0 Hz); 3.85 (s, 3 H,
OMe); 6.75 (dd, 1 H, H(7), Jo = 8.8 Hz, Jm = 2.2 Hz); 6.89 (d,
1 H, H(8), Jo = 8.8 Hz); 7.17 (m, 2 H, H(3´), H(5´)); 7.37 (d,
1 H, H(5), Jm = 2.2 Hz); 7.45 (m, 2 H, H(2´), H(6´)); 9.39
(br.s, 1 H, OH).
Experimental
The electrospray mass spectra were recorded on a Waters
ZQꢀ2000 mass spectrometer using a system for injection of the
sample without a chromatographic column and on a Finnigan
SSQꢀ710 mass spectrometer using a direct inlet system. The
1H NMR spectra were measured on a Bruker ACꢀ300 spectromꢀ
eter in DMSOꢀd6 with the use of the standard Bruker software.
The course of the reactions was monitored and the purity of the
compounds was checked on Merck 60 F254 plates. The yields,
elemental analysis data, and physicochemical characteristics are
given in Table 1.
[3ꢀ(4ꢀMethoxyphenylamino)ꢀ2ꢀcyclohexenylidene]malonoꢀ
nitrile (1). A mixture of (3ꢀoxocyclohexylꢀ1ꢀidene)malononitrile5
(7.73 g, 48 mmol), pꢀanisidine (5.94 g, 48 mmol), and TsOH
(0.001 g) in benzene (400 mL) was refluxed with a Dean—Stark
[6ꢀAcetoxyꢀ9ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3,9ꢀtetrahydroꢀ4Hꢀ
carbazolꢀ4ꢀylidene]malononitrile (3). One drop of sulfuric acid
was added to a suspension of compound 2 (7.11 g, 20 mmol) in

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Lyubchanskaya et al.
Table 1. Yields, melting points, elemental analysis data, and mass spectrometric data for compounds 1—11
Comꢀ
pound
Yield
(%)
M.p./°C
(solvent)
Found
Calculated
Molecular
formula
MS
(%)
(electrospray ionization)
С
H
N
1
88
40
135—138
(benzene)
243—245
(EtOH)
183—185
(EtOH)
180—183
(toluene)
252—255
(PriOH)
230—233
(PriOH)
72.87
72.43
74.34
74.35
72.49
72.53
60.36
60.51
71.68
71.66
5.70
5.70
5.30
4.82
4.93
4.82
4.04
3.81
5.38
5.35
15.60
15.84
11.84
11.82
10.50
10.57
8.73
C16H15N3O
266 [M + H]+, 553 [2 M + Na]+,
818 [3 M + Na]+
2
C22H17N3O2
C24H19N3O3
C24H18BrN3O3
C27H24N4O3
C27H23BrN4O3
C23H18N4O2
C23H17BrN4O2
C26H23N5O2
C23H18N5O2
C23H18N5O2
356 [M + H]+, 378 [M + Na]+,
733 [2 M + Na]+
3
84
397 [M + H]+, 420 [M + Na]+,
817 [2 M + Na]+
4
63
500 [M + Na]+, (Br81);
541 [M + Na + MeCN]+, (Br81)
452 [M + H]+, 474 [M + Na]+,
490 [M + K]+, 927 [2 M + Na]+
530 [M + H]+, (Br79);
8.82
5
70.8
48
12.37
12.38
11.00
10.54
14.44
14.65
11.65
12.14
15.52
16.00
17.23
17.62
17.23
17.11
6
533 [M + H]+, (Br81)
7
50
287—290
(dichloroethane)
269—271
(MeCN)
258—262
(PriOH)
275 decomp.
(DMF)
293—295
(DMF)
72.33
72.23
59.35
59.88
70.80
71.38
69.78
69.51
69.94
70.40
4.72
4.74
3.74
3.71
4.74
5.30
4.85
4.82
4.85
4.68
383 [M + H]+, 405 [M + Na]+,
787 [2 M + Na]+
8
27
499 [M + K]+, (Br79);
501 [M + K]+, (Br81)
9
68.4
94.7
24.4
438 [M + H]+, 875 [2 M + H]+,
897 [2 M + Na]+
10
11
398 [M + H]+, 795 [2 M + Na]+
398 [M + H]+, 795 [2 M + Na]+
1
acetic anhydride (65 mL) and the mixture was heated until a
solution was obtained. Then the mixture was cooled and the
precipitate that formed was filtered off, washed with water, and
obtained in a yield of 1.06 g. H NMR (DMSOꢀd6), δ: 2.30 (s,
3 H, OAc); 2.64 (s, 4 H, 2 H(1), 2 H(2)); 3.27 (s, 6 H, NMe2);
3.86 (s, 3 H, OMe); 7.00 (dd, 1 H, H(7), Jo = 8.8 Hz, Jm
2.1 Hz); 7.15 (m, 2 H, H(3´), H(5´)); 7.18 (d, 1 H, H(8), Jo =
8.8 Hz); 7.47 (m, 2 H, H(2´), H(6´)); 7.57 (d, 1 H, Jm = 2.1 Hz,
H(5)); 8.02 (s, 1 H, CHN).
=
1
dried. Compound 3 was obtained in a yield of 6.68 g. H NMR
(DMSOꢀd6), δ: 2.05 (q, 2 H, 2 H(2), Jo = 6.0 Hz); 2.29 (s, 3 H,
OAc); 2.79 and 2.96 (both t, 2 H each, 2 H(1), 2 H(3), Jo =
6.0 Hz); 3.87 (s, 3 H, OMe); 7.05 (dd, 1 H, H(7), Jo = 8.8 Hz,
Jm = 1.9 Hz); 7.11 (d, 1 H, H(8´), Jo = 8.8 Hz); 7.19 (m, 2 H,
H(3´), H(5´)); 7.50 (m, 2 H, H(2´), H(6´)); 7.72 (d, 1 H, H(5),
Jm = 1.9 Hz).
[6ꢀAcetoxyꢀ7ꢀbromoꢀ9ꢀ(4ꢀmethoxyphenyl)ꢀ1,2,3,9ꢀtetraꢀ
hydroꢀ4Hꢀcarbazolꢀ4ꢀylidene]malononitrile (4). A solution of
bromine (1.12 g, 7 mmol) in dichloromethane (50 mL) was
added dropwise with stirring to a boiling solution of compound 3
(2.85 g, 7 mmol) in dichloromethane (35 mL) for 1.5 h. Then
the mixture was refluxed with stirring for 3 h. The solvent was
removed, the residue was triturated with ethanol, and the preꢀ
cipitate was filtered off and recrystallized from toluene. Comꢀ
pound 4 was obtained in a yield of 2.1 g. 1H NMR (DMSOꢀd6),
δ: 2.07 (q, 2 H, 2 H(2), Jo = 6.0 Hz); 2.35 (s, 3 H, OAc); 2.78
and 2.96 (both t, 2 H each, 2 H(1), 2 H(3´), Jo = 6.0 Hz); 3.88
(s, 3 H, OMe); 7.20 (m, 2 H, H(3´), H(5´)); 7.31 (s, 1 H, H(5));
7.51 (m, 2 H, H(2´), H(6´)); 7.89 (s, 1 H, H(8)).
[6ꢀAcetoxyꢀ7ꢀbromoꢀ3ꢀ(dimethylamino)methylideneꢀ9ꢀ
(4ꢀmethoxyphenyl)ꢀ1,2,3,9ꢀtetrahydroꢀ4Hꢀcarbazolꢀ4ꢀylꢀ
idene]malononitrile (6). The synthesis was carried out analoꢀ
gously to that of compound 5 but without triethylamine. Comꢀ
pound 6 was obtained in a yield of 1.0 g from compound 4 (1.9 g,
4 mmol). 1H NMR (DMSOꢀd6), δ: 2.35 (s, 3 H, OAc); 2.63 (s,
4 H, 2 H(1), 2 H(2)); 3.28 (s, 6 H, NMe2); 3.86 (s, 3 H, OMe);
7.18 and 7.50 (both m, 2 H each, C6H4OMe); 7.3 and 7.70
(both s, 1 H each, H(5), H(8)); 8.06 (s, 1 H, H(1)).
2ꢀAminoꢀ10ꢀhydroxyꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ6,7ꢀdihydroꢀ5Hꢀ
pyrido[3,4ꢀc]carbazoleꢀ1ꢀcarbonitrile (7). A mixture of comꢀ
pound 5 (2.05 g, 4.5 mmol) and ammonium acetate (35 g,
45 mmol) was heated at 135—140 °C for 30—35 min. After
cooling, the reaction mixture was diluted with water, and the
precipitate was filtered off, washed with water, dried, suspended
in hot dichloroethane, and chromatographed on a silica gel
column eluted with ethyl acetate. Compound 7 was obtained in
a yield of 0.86 g. 1H NMR (DMSOꢀd6), δ: 2.65 (s, 4 H, 2 H(5),
2 H(6)); 3.85 (s, 3 H, OMe); 6.50 (br.s, 2 H, NH2); 6.70 (dd,
1 H, H (9), Jo = 8.8 Hz, Jm = 2.4 Hz); 6.98 (d, 1 H, H(8), Jo =
8.8 Hz); 7.15 (m, 2 H, H(3), H(5)); 7.42 (m, 3 H, H(2), H (6),
H (11)); 7.99 (s, 1 H, H(4)); 9.09 (br.s, 1 H, OH).
[6ꢀAcetoxyꢀ3ꢀ(dimethylamino)methylideneꢀ9ꢀ(4ꢀmethoxyꢀ
phenyl)ꢀ1,2,3,9ꢀtetrahydroꢀ4Hꢀcarbazolꢀ4ꢀylidene]malononitrile
(5). Dimethylformamide diethyl acetal (5.4 mL, 3.7 mmol) and
triethylamine (1 drop) were added to a suspension of compound 3
(1.47 g, 3.7 mmol) in toluene (35 mL). The reaction mixture
was refluxed for 15 min and then cooled. The precipitate was
filtered off, washed with toluene, and dried. Compound 5 was
2ꢀAminoꢀ11ꢀbromoꢀ10ꢀhydroxyꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ6,7ꢀ
dihydroꢀ5Hꢀpyrido[3,4ꢀc]carbazoleꢀ1ꢀcarbonitrile (8). The synꢀ

The synthesis of pyrido[3,4ꢀc]carbazole derivatives
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 9, September, 2006
1663
thesis was carried out analogously to that of compound 7. Comꢀ
pound 8 was obtained in a yield of 0.1 g from compound 6
(0.43 g, 0.8 mmol). 1H NMR (DMSOꢀd6), δ: 2.66 (s, 4 H,
2 H(5), 2 H(6)); 3.86 (s, 3 H, OMe); 6.54 (br.s, 2 H, NH2); 7.17
(m, 2 H, H(3), H(5)); 7.21 (s, 1 H, H(11)); 7.46 (m, 2 H,
H(2), H(6)); 7.63 (s, 1 H, H(8)); 8.01 (s, 1 H, H(4)); 9.94
(br.s, 1 H, OH).
6.68 (dd, 1 H, H(11), Jo = 8.8 Hz, Jm = 2.2 Hz); 6.79 (d, 1 H,
H(13), Jm = 2.2 Hz); 7.05 (d, 1 H, H(10), Jo = 8.8 Hz); 8.42 (s,
1 H, H(5)); 8.69 (s, 1 H, H(3)); 9.12 (br.s, 1 H, OH).
This study was financially supported by the Federal
Agency for Science and Innovations of the Russian Fedꢀ
eration (Contract No. 1/05).
1ꢀCyanoꢀ2ꢀ(dimethylamino)methylideneaminoꢀ10ꢀhydroxyꢀ
7ꢀ(4ꢀmethoxyphenyl)ꢀ6,7ꢀdihydroꢀ5Hꢀpyrido[3,4ꢀc]carbazole
(9). A suspension of compound 7 (0.17 g, 0.44 mmol) and
dimethylformamide diethyl acetal (0.65 mL, 4.4 mmol) in isoꢀ
propyl alcohol (4 mL) was refluxed for 15 min. The reaction
mixture was cooled, abd the precipitate was filtered, washed
with cold isopropyl alcohol, and dried. Compound 9 was obꢀ
tained in a yield of 0.13 g. 1H NMR (DMSOꢀd6), δ: 2.73 (s, 4 H,
2 H(5), 2 H(6)); 3.09 and 3.15 (both s, 3 H each, NMe2); 3.85
(s, 3 H, OMe); 6.68 (dd, 1 H, H (9), Jo = 8.4 Hz, Jm = 2.1 Hz);
7.00 (d, 1 H, H(8), Jo = 8.4 Hz); 7.15 (m, 2 H, H(3´), H(5´));
7.44 (m, 3 H, H(11), H(2´), H(6´)); 8.15 (s, 1 H, H(4)); 8.63 (s,
1 H, H(1)); 9.07 (br.s, 1 H, N(4)H).
3ꢀAminoꢀ10ꢀhydroxyꢀ2ꢀiminoꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ3,5,6,7ꢀ
tetrahydroꢀ2Hꢀpyrido[3,4ꢀc]carbazoleꢀ1ꢀcarbonitrile (10). A susꢀ
pension of compound 5 (0.45 g, 1 mmol) and hydrazine hydrate
(0.15 mL, 3 mmol) in methanol (25 mL) was stirred at 20 °C for
12 h. The precipitate was filtered off, washed with methanol,
and dried. Compound 10 was obtained in a yield of 0.38 g.
1H NMR (DMSOꢀd6), δ: 2.53 and 2.66 (both t, 2 H each,
2 H(6), 2 H(7), Jo = 6.9 Hz); 3.86 (s, 3 H, OMe); 5.83 (br.s, 2 H,
NH2); 6.71 (dd, 1 H, H(10), Jo = 8.8 Hz, Jm = 2.1 Hz); 6.96
(d, 1 H, H(9), Jo = 8.8 Hz); 7.15 (m, 2 H, H(3), H(5)); 7.40
(m, 3 H, H(12), H(2), H (6)); 7.58 (s, 1 H, H(5)); 9.18
(br.s, 1 H, OH).
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1ꢀAminoꢀ12ꢀhydroxyꢀ9ꢀ(4ꢀmethoxyphenyl)ꢀ8,9ꢀdihydroꢀ7Hꢀ
pyrimido[5´,4´:4,5]pyrido[2,3ꢀc]carbazole (11). A mixture of
compound 9 (0.87 g, 2 mmol) and ammonium acetate (15.4 g,
200 mmol) was heated at 135—140 °C for 1 h, cooled, and
diluted with water. The precipitate was filtered off, washed with
water, dried, suspended in hot dichloroethane, and chromatoꢀ
graphed on a silica gel column. Elution with ethyl acetate afꢀ
forded compound 7 in a yield of 0.44 g (57%), and then elution
1
with methanol gave compound 11 in a yield of 0.2 g. H NMR
(DMSOꢀd6), δ: 2.70 and 2.97 (both m, 1 H each, 2 H(8), 2 H(7);
Received June 26, 2006;
3.86 (s, 3 H, OMe); 6.37 and 7.99 (both br.s, 1 H each, NH2);
in revised form July 21, 2006