Fused quinoline heterocycles. II. First synthesis of 1,2,3,4,5,6-hexaazaaceanthrylenes and 5,7,8,10a,11-pentaazabenzo[a]-fluorenes

Article abstract of DOI:10.1081/SCC-100104413

The new tetracyclic ring systems 5-alkyl-1,5-dihydro-1,2,3,4,5,6-hexaazaaceanthrylenes 5a-d were synthesized by diazotization of 4-alkylamino-3-amino-1H-pyrazolo[4,3-c]quinolines 4a-d. The 4-arylamino-3-diazo-1H-pyrazolo-[4,3-c]quinolines 6e-h, which were prepared by diazotisation of the corresponding amines 4e-h, readily formed the novel tetracyclic ring system ethyl 6-arylamino-10-methyl-5,7,8,10a,11-pentaazabenzo[a]fluorene-9-carboxylates 8e-h, when treated with ethyl acetoacetate.

Full text of DOI:10.1081/SCC-100104413

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FUSED QUINOLINE HETEROCYCLES.
II. FIRST SYNTHESIS OF 1,2,3,4,5,6-
HEXAAZAACEANTHRYLENES AND 5,7,8,10a,11-
PENTAAZABENZO[a]-FLUORENES
Ramadan Ahmed Mekheimer a
a Chemistry Department, Faculty of Science , El-Minia University , El-Minia, 61519, AR,
Egypt
Published online: 09 Nov 2006.
To cite this article: Ramadan Ahmed Mekheimer (2001) FUSED QUINOLINE HETEROCYCLES. II. FIRST SYNTHESIS OF
1,2,3,4,5,6-HEXAAZAACEANTHRYLENES AND 5,7,8,10a,11-PENTAAZABENZO[a]-FLUORENES, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:13, 1971-1982, DOI: 10.1081/
SCC-100104413
To link to this article: http://dx.doi.org/10.1081/SCC-100104413
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SYNTHETIC COMMUNICATIONS, 31(13), 1971–1982 (2001)
FUSED QUINOLINE HETEROCYCLES.
II. FIRST SYNTHESIS OF 1,2,3,4,5,6-
HEXAAZAACEANTHRYLENES AND
5,7,8,10a,11-PENTAAZABENZO[a]-
FLUORENES
Ramadan Ahmed Mekheimer*
Chemistry Department, Faculty of Science,
El-Minia University, El-Minia 61519, AR, Egypt
ABSTRACT
The new tetracyclic ring systems 5-alkyl-1,5-dihydro-
1,2,3,4,5,6-hexaazaaceanthrylenes 5a–d were synthesized by
diazotization of 4-alkylamino-3-amino-1H-pyrazolo[4,3-c]qui-
nolines 4a–d. The 4-arylamino-3-diazo-1H-pyrazolo-[4,3-c]-
quinolines 6e–h, which were prepared by diazotisation of the
corresponding amines 4e–h, readily formed the novel tetra-
cyclic ring system ethyl 6-arylamino-10-methyl-5,7,8,10a,11-
pentaazabenzo[a]fluorene-9-carboxylates 8e–h, when treated
with ethyl acetoacetate.
Recent years have witnessed a significant interest in the synthesis
of new heterocyclic rings stimulated by reports that a wide range of
polyheterocyclic compounds isolated from marine organisms show anti-
tumor activity.1–4 Tetracyclic ring systems, such as 2-dimethylamino[1]
*Corresponding author.
1971
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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1972
MEKHEIMER
benzothiopyrano[4,3,2-de]-quinoline,5 1-amino-6-methyl[1]benzothiopyrano-
[4,3,2-de]quinoline-2(3H)-one6 and pyrido [3ꢀ, 2ꢀ: 6,5]thiopyrano[4,3,2-de]-
quinoline7 have already been synthesized and reported to have promising
antitumor activity or analgesic and psychopharmacological properties.
These valuable properties prompted us to prepare new tetracyclic systems
containing a quinoline nucleus with potential biological activity in our
search for novel heterocyclic compounds of pharmacological interest.
In a previous paper,8 we have shown that the reaction of 4-arylamino-
2-chloroquinoline-3-carbonitriles A with hydrazine hydrate gave 3-amino-
4-arylamino-1H-pyrazolo[3,4-b]quinolines which by diazotization yielded
1-aryl-1,5-dihydro-1,2,3,4,5,6-hexaazaacephenanthrylenes B, as new tetra-
cyclic ring systems. Interestingly, when 4-alkylamino-2-chloroquinoline-
3-carbonitriles underwent the same sequence of reactions, the reaction
took a different course. In all cases, the unexpected 2,4-diazidoquinoline-
3-carbonitrile was the isolated product instead of the tetracyclic system (B).8
In order to obtain better understanding of this kind of reaction and to
extend the scope of this reaction to other heterocyclic systems, we examined
this reaction sequence in 3-amino-4-chloro-1H-pyrazolo[4,3-c]quinoline 2,
as another model system for pyrazoloquinolines. In this paper and as a
further extension of our previous work,8–14 aimed to prepare new hetero-
cyclic systems containing the quinoline moiety. We would like to report on a
novel and convenient procedure for new 5-alkyl-1,5-dihydro-1,2,3,4,5,6-hex-
aazaaceanthrylenes 5a–d and 5,7,8,10a,11-pentaazabenzo[a]fluorenes 8e–h,
containing both the pyrazole and triazine moieties condensed with a quino-
line nucleus, otherwise accessible only with difficulty, commencing with
3-amino-4-chloro-1H-pyrazolo-[4,3-c]quinoline (2). In a search of the litera-
ture it is surprising that these ring systems have been largely ignored.
The key 3-amino-4-chloro-1H-pyrazolo[4,3-c]quinoline 2 was easily
prepared by reacting 2,4-dichloroquinoline-3-carbonitrile (1)9 with hydrazine
hydrate in DMF at room temperature. Replacement of the chlorine atom at
position 4 was achieved when compound 2 was heated in an excess of the
alkylamines 3a–d at reflux temperature, giving the corresponding 4-alkyl-
amino-3-amino-1H-pyrazolo[4,3-c]quinolines 4a–d, in yields higher than
80%. Analytical and spectroscopic data fully support the structural

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FUSED QUINOLINE HETEROCYCLES. II
1973
assignment for compounds 4a–d. The 1H NMR spectra showed the presence
of signals corresponding to the protons of the amino groups at C-3, C-4 and a
singlet in the region d 12.63–12.68 ppm due to the pyrazole NH as well
as aliphatic protons in their expected positions. Reaction of compounds
4a–d with sodium nitrite in a 70% solution of H2SO4 at ꢀ5ꢁC gave the
previously unreported 5-alkyl-1,5-dihydro-1,2,3,4,5,6-hexaazaaceanthrylenes
5a–d (Scheme 1), in good yield. The other possible structure 6 was readily
ruled out for the reaction product on the basis of spectral data. The absence
of a diazo absorption at 2160 cmꢀ1 15 in IR spectrum of the reaction product
confirmed the assigned structure 5 and allowed us to discard the other poss-
ible structure 6. Furthermore, the structures of 5a–d were established from
their 1H NMR spectra, correct elemental analyses as well as mass spectra. The
data used to characterize these prepared compounds are given in the
Experimental.
Scheme 1.

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1974
MEKHEIMER
Our interest to synthesize the interesting novel heterocyclic pyrazolo-
triazino-quinoline ring system 5, led us to investigate the reaction of 2 with
arylamines 3e–h, which gave pyrazoloquinolines 4e–h, a good precursor for
the synthesis of 5. When compound 2 was reacted with 3e–h in DMF at
reflux for 3 hours the corresponding 4-arylamino-pyrazoloquinolines 4e–h
were isolated. Structural elucidation of compounds 4e–h was accomplished
from their elemental analyses and spectroscopic data. The 1H NMR spectra
were in accord with the proposed structures which revealed the presence of
signals at d 5.62–5.72 and d 8.16–8.44 ppm assignable to amino group at
C-3, C-4, respectively, and there was a pyrazole NH at d 12.88–12.99 ppm,
besides signals due to aromatic protons in their expected positions. We
expected that the reaction of 4e–h with sodium nitrite in a solution of
H2SO4 (70%) at ꢀ5ꢁC would lead to the formation of the hitherto unknown
tetracyclic system 5, since a similar reaction had readily been achieved with
Scheme 2.

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FUSED QUINOLINE HETEROCYCLES. II
1975
the analogous compound, 3-amino-4-arylamino-1H-pyrazolo[3,4-b]quino-
lines.8 Surprisingly, we found that the new 4-arylamino-3-diazo-1H-pyra-
zolo-[4,3-c]quinolines 6e–h were obtained by diazotisation of the amines
4e–h under ordinary condition, when it separated from the reaction mixture,
in high yields, without the need for basification. The structural constitutions
of compounds 6 were inferred from their elemental analyses and spectral
data. The IR spectra exhibited absorption bands at 3350 and 2150 cmꢀ1 due
1
to the NH and (diazo) groups, respectively. The H NMR spectra gave
strong evidence for the formation of the diazo compound 6, which revealed
the presence of an absorption band at about d ꢂ 8.70 ppm, assigned for NH
group at quinoline C-2 and the absence of pyrazole NH (ca. 14.34 ppm).
In view of the work already described we aimed first to prepare the
new tetracyclic ring system of type 5. We treated the 3-diazo compound 6e–h
with ethyl acetoacetate in the expectation that the respective hydrazones 7
would be formed,16 and that they could subsequently be cyclised. In prac-
tice, the hydrazones 7 cyclised spontaneously, to afford directly the target
tetracyclic ring system 8 for which the alternative isomeric structure 9 is
theoretically possible. The latter structure could be eliminated on account of
the 1H NMR spectra, which revealed the presence of NH group at quinoline
C-2; and the absence of pyrazole NH in their expected positions. It should
be noted that compound 8 had been formed by intramolecular cyclisation,
via elimination of water, involving the acetyl group of the hydrazone 7,
rather than the ethoxycarbonyl group, this is perhaps surprising since cycli-
sation via the latter would have preserved the aromaticity of quinoline ring.
We conclude that this second-generation version of our annulation
strategy shows for the first time a new general route to 5-alkyl-1,5-dihy-
dro-1,2,3,4,5,6-hexaazaaceanthrylenes 5a–d and ethyl 6-arylamino-
10-methyl-5,7,8,10a,11-pentaazabenzo[a]fluorene-9-carboxylates 8e–h bear-
ring various substituents at the triazine ring. This synthetic approach, for
the preparation of 5a–d and 8e–h, may be useful in view of the pharmaco-
logical interest in this compound class. Further studies are under way in our
laboratory aimed at the application of this methodology to the preparation
of new tetracyclic systems starting from pyrrolo[3,2-c]quinolines.
EXPERIMENTAL
M.P.’s were measured on a Gallenkamp melting point apparatus and
are uncorrected. IR spectra were recorded on a Shimadzu 470 spectro-
1
photometer (KBr pellets). H NMR spectra were recorded on a Bruker
AC270 or a Bruker AM400 spectrometer at 270 or 400 MHz, respectively,
in (DMSO-d6) using TMS as internal standard and Chemical shifts are

ORDER
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1976
MEKHEIMER
expressed as d values (ppm). Microanalyses were performed by the micro-
analytical Data Unit at Cairo University. Mass spectra were recorded on
GCMS-QP 1000EX spectrometer (ionization energy 70 eV). Analytical TLC
was performed with silica gel plates using silica gel 60 PF254 (Merck).
3-Amino-4-cyclohexylamino-1H-pyrazolo[4,3-c]quinoline (4d) was prepared
according to the procedure described in reference 9.
General Procedure for the Synthesis of 3-Amino-4-amino-substituted-
1H-pyrazolo[4,3-c]quinolines 4a–h
For 4a–d: Asolution of 2 (0.5g, 2.29mmol) in excess of alkylamines 3a–c
(15 mL) was heated at reflux. After 96 hours all the starting 2 was consumed
(tlc). After cooling, the mixture was evaporated to dryness in vacuo. Crushed
ice was added to the remaining oil residue with stirring. The solution was
neutralized with conc. HCl, the precipitated solid product was collected by
filtration, dried and recrystallized from methanol. For 4e–h, the appropriate
aromatic amine (4.58 mmol) was added to a solution of 2 (0.5 g, 2.29 mmol) in
DMF (10 mL). The reaction mixture was heated at reflux for 3 hours. The
mixture was then evaporated to dryness under reduced pressure. The residue
was triturated with cold water and the resulting solid product was collected,
dried and recrystallized from methanol.
3-Amino-4-propylamino-1H-pyrazolo[4,3-c]quinoline, 4a
Colorless prisms, Yield 82%, mp 247–248ꢁC; H NMR (DMSO-d6):
1
d 0.97 (t, 3H), 1.68 (m, 2H), 3.50 (q, 2H), 5.49 (s br, 2H), 6.42 (t, 1H), 7.13
(t, 1H), 7.40 (t, 1H), 7.50 (d, 1H), 7.95 (dd, 1H) and 12.64 (s, 1H) ppm;
Infrared (KBr): 3400, 3300, 3200 (NH, NH2), 2950, 2900 (aliph CH) and
1625 (C ¼ N) cmꢀ1; Anal. Calcd. for C13H15N5: C, 64.71; H, 6.26; N, 29.02.
Found: C, 64.89; H, 6.37; N, 29.07.
3-Amino-4-isobutylamino-1H-pyrazolo[4,3-c]quinoline, 4b
Colorless prisms, Yield 86%, mp 307–308ꢁC; H NMR (DMSO-d6):
1
d 0.97 (d, 6H), 2.08 (m, 1H), 3.56 (t, 2H), 5.54 (s br, 2H), 6.35 (t, 1H), 7.14
(t, 1H), 7.46 (t, 1H), 7.58 (d, 1H), 8.00 (d, 1H) and 12.68 (s, 1H) ppm;
Infrared (KBr): 3400, 3150 (NH, NH2), 2950, 2900 (aliph CH) and 1620
(C ¼ N) cmꢀ1; Mass Spectrum (m/z): 255 (15) (Mþ); Anal. Calcd. for
C14H17N5: C, 65.86; H, 6.71; N, 27.43. Found: C, 65.70; H, 6.85; N, 27.50.

ORDER
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FUSED QUINOLINE HETEROCYCLES. II
1977
3-Amino-4-butylamino-1H-pyrazolo[4,3-c]quinoline, 4c
Colorless crystals, Yield 83%, mp 224–225ꢁC; H NMR (DMSO-d6):
d 0.95 (t, 3H), 1.42 (m, 2H), 1.65 (m, 2H), 3.54 (q, 2H), 5.47 (s br, 2H), 6.38
(t, 1H), 7.13 (t, 1H), 7.40 (t, 1H), 7.52 (d, 1H), 7.95 (d, 1H) and 12.63 (s,
1H) ppm; Infrared (KBr): 3400, 3150 (NH, NH2), 2950, 2900, 2850 (aliph
CH) and 1625 (C ¼ N) cmꢀ1; Anal. Calcd. for C14H17N5: C, 65.86; H, 6.71;
N, 27.43. Found: C, 65.96; H, 6.77; N, 27.41.
1
3-Amino-4-anilino-1H-pyrazolo[4,3-c]quinoline, 4e
Colorless crystals, Yield 87%, mp 258–259ꢁC; H NMR (DMSO-d6):
1
d 5.64 (s, 2H), 7.00–7.64 (m, 5H), 7.96–8.07 (m, 4H), 8.24 (s, 1H) and 12.92
(s, 1H) ppm; Infrared (KBr): 3350, 3200 (NH, NH2), 3050 (ArCH) and 1625
(C ¼ N) cmꢀ1; Mass Spectrum (m/z): 275 (86) (Mþ); Anal. Calcd. for
C16H13N5: C, 69.80; H, 4.76; N, 25.44. Found: C, 69.68; H, 4.57; N, 25.30.
3-Amino-4-(3-fluorophenylamino)-1H-pyrazolo[4,3-c]quinoline, 4f
Buff crystals; Yield 84%, mp 235–237ꢁC; 1H NMR (DMSO-d6): d 5.70
(s, 2H), 7.33–7.71 (m, 5H), 8.08–8.21 (m, 3H), 8.44 (s, 1H) and 12.99 (s,
1H) ppm; Infrared (KBr): 3350, 3200 (NH, NH2), 3050 (ArCH) and 1620
(C ¼ N) cmꢀ1; Mass Spectrum (m/z): 293 (98) (Mþ); Anal. Calcd. for
C16H12FN5: C, 65.52; H, 4.13; N, 23.88. Found: C, 65.67; H, 3.95; N, 24.02.
3-Amino-4-(4-methylphenylamino)-1H-pyrazolo[4,3-c]quinoline, 4g
Colorless crystals, Yield 88%, mp 296–298ꢁC; H NMR (DMSO-d6):
1
d 2.32 (s, 3H), 5.62 (s, 2H), 7.03–7.42 (m, 4H), 7.64–8.05 (m, 4H), 8.20
(s, 1H) and 12.89 (s, 1H) ppm; Infrared (KBr): 3350, 3300, 3200 (NH,
NH2) and 1640 (C ¼ N) cmꢀ1; Anal. Calcd. for C17H15N5: C, 70.57; H,
5.23; N, 24.20. Found: C, 70.39; H, 5.26; N, 24.11.
3-Amino-4-(4-methoxyphenylamino)-1H-pyrazolo[4,3-c]quinoline, 4h
Colorless crystals, Yield 80%, mp 235–237ꢁC; H NMR (DMSO-d6):
1
d 3.77 (s, 3H), 5.72 (s, 2H), 6.95 (d, 2H), 7.26 (t, 1H), 7.47 (t, 1H), 7.58
(d, 1H), 7.81 (d, 2H), 8.04 (d, 1H), 8.16 (s, 1H) and 12.88 (s, 1H) ppm;

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1978
MEKHEIMER
Infrared (KBr): 3350, 3200 (NH, NH2) and 1630 (C ¼ N) cmꢀ1; Anal. Calcd.
for C17H15N5O: C, 66.87; H, 4.95; N, 22.94. Found: C, 66.95; H, 4.97;
N, 22.88.
General Procedure for the Synthesis of 5-Alkyl-1,5-dihydro-
1,2,3,4,5,6-hexaazaaceanthrylenes 5a–d and 4-Arylamino-
3-diazo-1H-pyrazolo[4,3-c]quinolines 6e–h
Asolution of NaNO (4.5 mmol) in H2O (2 mL) was added dropwise
2
to a solution of 4a–h (1.5 mmol) in H2SO4 (5 mL, 70%) cooled to ꢀ10ꢁC,
whilst maintaining the temperature at (ꢀ10ꢁC) to (ꢀ5ꢁC). The reaction
mixture was kept at ꢀ5ꢁC for 1 hour and then poured into ice water. The
resulting solid product was filtered, washed well with water, dried and
recrystallized from methanol to give 5a–d and 6e–h.
1,5-Dihydro-5-propyl-1,2,3,4,5,6-hexaazaaceanthrylene, 5a
Yellow crystals, Yield 68%, mp 216–218ꢁC (decp.); 1H NMR (DMSO-
d6): d 0.99 (t, 3H), 1.93 (m, 2H), 4.37 (t, 2H), 7.42 (t, 1H), 7.59 (t, 1H), 7.80
(d, 1H), 7.99 (d, 1H) and 14.33 (s, 1H) ppm; Infrared (KBr): 3350 (NH),
3050 (ArCH), 2950, 2900, 2800 (aliph CH), 1685 (N ¼ N) and 1630
(C ¼ N) cmꢀ1; Mass Spectrum (m/z): 252 (8) (Mþ); Anal. Calcd. for
C13H12N6: C, 61.89; H, 4.80; N, 33.31. Found: C, 61.98; H, 4.77; N, 33.38.
1,5-Dihydro-5-isobutyl-1,2,3,4,5,6-hexaazaaceanthrylene, 5b
Yellow crystals, Yield 70%, mp 240ꢁC (decp.); 1H NMR (DMSO-d6):
d 0.99 (d, 6H), 2.10 (m, 1H), 4.24 (d, 2H), 7.44 (t, 1H), 7.59 (t, 1H),
7.81 (d, 1H), 8.00 (d, 1H) and 14.35 (s, 1H) ppm; Infrared (KBr): 3350
(NH), 3050 (ArCH), 2950, 2900 (aliph CH), 1685 (N ¼ N) and 1630
(C ¼ N) cmꢀ1; Mass Spectrum (m/z): 266 (12) (Mþ); Anal. Calcd. for
C14H14N6: C, 63.14; H, 5.30; N, 31.56. Found: C, 62.95; H, 5.26; N, 31.42.
5-Butyl-1,5-dihydro-1,2,3,4,5,6-hexaazaaceanthrylene, 5c
Yellow crystals, Yield 66%, mp 202–204ꢁC; 1H NMR (DMSO-d6): d 0.96
(t, 3H), 1.43 (m, 2H), 1.89 (m, 2H), 4.40 (t, 2H), 7.42 (t, 1H), 7.59 (t, 1H),

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FUSED QUINOLINE HETEROCYCLES. II
1979
7.80 (d, 1H), 7.99 (d, 1H) and 14.34 (s, 1H) ppm; Infrared (KBr): 3400 (NH),
3050 (ArCH), 2950, 2900, 2850 (aliph CH), 1685 (N ¼ N) and 1630
(C ¼ N) cmꢀ1; Anal. Calcd. for C14H14N6: C, 63.14; H, 5.30; N, 31.56.
Found: C, 63.21; H, 5.36; N, 31.69.
5-Cyclohexyl-1,5-dihydro-1,2,3,4,5,6-hexaazaaceanthrylene, 5d
Orange crystals, Yield 87%, mp 220–222ꢁC (decp.); 1H NMR
(DMSO-d6): d 1.32–2.05 (m, 10H), 4.87 (m, 1H), 7.43 (t, 1H), 7.60
(t, 1H), 7.83 (d, 1H), 8.01 (d, 1H) and 14.34 (s, 1H) ppm; Infrared (KBr):
3350 (NH), 3050 (ArCH), 2950, 2850 (aliph CH), 1685 (N ¼ N) and
1630 (C ¼ N) cmꢀ1; Mass Spectrum (m/z): 292 (18) (Mþ); Anal. Calcd.
for C16H16N6: C, 65.73; H, 5.52; N, 28.75. Found: C, 65.54; H, 5.57;
N, 28.58.
4-Anilino-3-diazo-1H-pyrazolo[4,3-c]quinoline, 6e
Off-brown crystals, Yield 85%, mp 315–316ꢁC (decp.); 1H NMR
(DMSO-d6): d 7.28–8.06 (m, 9H) and 8.74 (s, 1H) ppm; Infrared (KBr):
3350 (NH), 3050 (ArCH), 2150 (diazo) and 1620 (C ¼ N) cmꢀ1; Mass
Spectrum (m/z): 286 (5) (Mþ); Anal. Calcd. for C16H10N6: C, 67.12; H,
3.52; N, 29.36. Found: C, 67.23; H, 3.48; N, 29.31.
3-Diazo-4-(3-fluorophenylamino)-1H-pyrazolo[4,3-c]quinoline, 6f
Orange crystals, Yield 92%, mp 302–304ꢁC (decp.); 1H NMR
(DMSO-d6): d 7.18–8.25 (m, 8H) and 8.80 (s, 1H) ppm; Infrared (KBr):
3350 (NH), 3050 (ArCH), 2150 (diazo) and 1620 (C ¼ N) cmꢀ1; Anal.
Calcd. for C16H9FN6: C, 63.15; H, 2.98; N, 27.62. Found: C, 63.09; H,
3.05; N, 27.76.
3-Diazo-4-(4-methylphenylamino)-1H-pyrazolo[4,3-c]quinoline, 6g
Orange crystals, Yield 94%, mp 310–311ꢁC (decp.); 1H NMR
(DMSO-d6): d 2.37 (s, 3H), 7.19–7.52 (m, 3H), 7.62–8.04 (m, 5H) and
8.57 (s, 1H) ppm; Infrared (KBr): 3400 (NH), 3050 (ArCH), 2950 (aliph
CH), 2150 (diazo) and 1620 (C ¼ N) cmꢀ1; Mass Spectrum (m/z): 272 (54)
Mþ -N2); Anal. Calcd. for C17H12N6: C, 67.99; H, 4.03; N, 27.98. Found: C,
67.87; H, 4.01; N, 27.83.

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1980
MEKHEIMER
3-Diazo-4-(4-methoxyphenylamino)-1H-pyrazolo[4,3-c]quinoline, 6h
Off-brown crystals, Yield 82%, mp>360ꢁC (decp.); 1H NMR
(DMSO-d6): d 3.75 (s, 3H), 7.20–7.61 (m, 4H), 7.73–8.05 (m, 4H) and 8.70
(s, 1H) ppm; Infrared (KBr): 3350 (NH), 2800 (aliph CH), 2150 (diazo) and
1620 (C ¼ N) cmꢀ1; Anal. Calcd. for C17H12N6O: 64.55; H, 3.82; N, 26.57.
Found: C, 64.39; H, 3.76; N, 26.46.
General Procedure for the Synthesis of Ethyl
6-Arylamino-10-methyl-5,7,8,10a,11-pentaazabenzo-
[a]fluorene-9-carboxylates 8e-h
Astirred mixture of the 3-diazo compound 6e–h (1 mmol), ethyl aceto-
acetate (0.156 g, 1.2 mmol) and absolute ethanol (10 mL) was kept at room
temperature for 20 h. The resulting pink precipitate was collected, dried and
purified by preparative TLC (toluene:acetone, 10:3), followed by recrystal-
lization from acetone to afford 8e–h.
Ethyl 6-Anilino-10-methyl-5,7,8,10a,11-pentaazabenzo[a]fluorene-
9-carboxylate, 8e
Yellow crystals, Yield 70%, mp 209–210ꢁC (decp.); 1H NMR (DMSO-
d6): d 1.45 (t, 3H), 3.16 (s, 3H), 4.53 (q, 2H) and 7.08–8.71 (m, 10H) ppm;
Infrared (KBr): 3400 (NH), 3050 (ArCH), 2950 (aliph CH), 1730 (ester C ¼ O)
and 1620 (C ¼ N) cmꢀ1; Mass Spectrum (m/z): 398 (89) (Mþ); Anal. Calcd.
for C22H18N6O2: C, 66.32; H, 4.55; N, 21.09. Found: C, 66.43; H, 4.68;
N, 20.99.
Ethyl 6-(3-Fluorophenylamino)-10-methyl-5,7,8,10a,11-pentaazabenzo-
[a]fluorene-9-carboxylate, 8f
Orange crystals, Yield 79%, mp 206–208ꢁC (decp.); 1H NMR
(DMSO-d6): d 1.46 (t, 3H); 3.18 (s, 3H), 4.53 (q, 2H) and 6.88–8.80
(m, 9H) ppm; Infrared (KBr): 3400 (NH), 3050 (ArCH), 2950, 2900
(aliph CH), 1720 (ester C ¼ O) and 1620 (C ¼ N) cmꢀ1; Mass Spectrum
(m/z): 416 (100) (Mþ); Anal. Calcd. for C22H17FN6O2: C, 63.45; H,
4.12; N, 20.18. Found: C, 63.66; H, 4.02; N, 20.36.

ORDER
REPRINTS
FUSED QUINOLINE HETEROCYCLES. II
1981
Ethyl 6-(4-Methylphenylamino)-10-methyl-5,7,8,10a,11-pentaazabenzo-
[a]-fluorene-9-carboxylate, 8g
Orange crystals, Yield 73%, mp 270–271ꢁC (decp.); 1H NMR
(DMSO-d6): d 1.44 (t, 3H); 2.33 (s, 3H), 3.28 (s, 3H), 4.54 (q, 2H),
7.24 (d, 2H), 7.49 (t, 1H), 7.76 (t, 1H), 7.85 (d, 1H), 8.02 (d, 2H), 8.45 (d,
1H) and 8.82 (s, 1H) ppm; Infrared (KBr): 3380 (NH), 2900, 2850 (aliph
CH), 1710 (ester C ¼ O) and 1620 (C ¼ N) cmꢀ1; Mass Spectrum (m/z): 412
(100) (Mþ); Anal. Calcd. for C23H20N6O2: C, 66.97; H, 4.89; N, 20.38.
Found: C, 67.14; H, 4.95; N, 20.29.
Ethyl 6-(4-Methoxyphenylamino)-10-methyl-5,7,8,10a,11-pentaazabenzo-
[a]-fluorene-9-carboxylate, 8h
Orange crystals, Yield 83%, mp 220–221ꢁC (decp.); 1H NMR
(DMSO-d6): d 1.46 (t, 3H), 3.23 (s, 3H), 3.79 (s, 3H), 4.53 (q, 2H), 6.99
(d, 2H), 7.44 (t, 1H), 7.70 (t, 1H), 7.74 (d, 1H), 7.99 (d, 2H), 8.36 (d, 1H) and
8.66 (s, 1H) ppm; Infrared (KBr): 3400 (NH), 2900 (aliph CH), 1710 (ester
C ¼ O) and 1620 (C ¼ N) cmꢀ1; Mass Spectrum (m/z): 428 (100) (Mþ); Anal.
Calcd. for C23H20N6O3: C, 64.47; H, 4.71; N, 19.62. Found: C, 64.28; H,
4.56; N, 19.46.
REFERENCES
1. Molinski, T.F. Chem. Rev. 1993, 93, 1825.
2. Carroll, A.R. and Scheuer, P.J. J. Org. Chem. 1990, 55, 4426;
Charyulu, G.A.; McKee, T.Z. and Ireland, C.M. Tetrahedron Lett.
1989, 30, 4201.
3. Kobayashi, J.; Cheng, J.F.; Walchli, M.R.; Nakamura, H.; Hirata, Y.;
Sasaki, T. and Ohizumi, Y. J. Org. Chem. 1988, 53, 1800; Rudi, A. and
Kashman, Y. J. Org. Chem. 1989, 54, 5331; Carroll, A.R.; Cooray,
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Schmitz, F.J.; DeGuzman, F.S.; Hossain, M.B. and Van der Helm, D.
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ORDER
REPRINTS
1982
MEKHEIMER
7. Fujiwara, H. and Okabayashi, I. Heterocycles 1993, 36, 1105.
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Received in the UK April 14, 2000

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