Efficient and novel one-pot synthesis of antifungal active 1-substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2, 4]triazepines using solid support

Article abstract of DOI:10.1016/j.ejmech.2010.11.043

A simple, efficient and environment-friendly procedure is developed for the synthesis of 1-substitued-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4] triazolo[4,3-b][1,2,4]triazepines in the presence of N,N-dimethylformamide as an energy transfer medium, p-

Full text of DOI:10.1016/j.ejmech.2010.11.043

European Journal of Medicinal Chemistry 46 (2011) 631e635
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Efficient and novel one-pot synthesis of antifungal active 1-substituted-8-aryl-
3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines using solid
support
*
Monika Gupta , Satya Paul, Rajive Gupta
Department of Chemistry, University of Jammu, Jammu-180006, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 June 2010
Received in revised form
24 November 2010
Accepted 28 November 2010
Available online 8 December 2010
A simple, efficient and environment-friendly procedure is developed for the synthesis of 1-substitued-8-
aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in the presence of N,N-dime-
thylformamide as an energy transfer medium, p-TsOH as catalyst and basic alumina as solid support
under microwave irradiation. The products are obtained in moderate to good yields and are in a state of
high purity. Moreover, title compounds have been screened for antifungal activity.
Ó 2010 Elsevier Masson SAS. All rights reserved.
Keywords:
Pyazolotriazolo triazepines
Microwave irradiation
Antifungal
Basic alumina
N,N-Dimethylformamide
p-TsOH
1. Introduction
novel one-pot synthesis of 1-substituted-8-aryl-3-alkyl/aryl-4H-
pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines by irradiating
Heterocyclic compounds, whether natural or synthetic show
interesting biological activities and are often key components in
various biological processes. Nitrogen containing heterocycles have
attracted considerable attention due to their wide range of phar-
macological activities. For instance, a number triazole derivatives
are known to possess antifungal [1,2], antibacterial [3], antiin-
flammatory [4], antimicrobial [5,6], tuberculo-therapeutic [7] and
antiasthmatic [8] activities. Benzotriazepine derivatives [9], were
also reported to possess antibacterial, antiviral and psychotropic
activities [10,11]. Some of these derivatives were used in the
manufacture of plant protecting agents [12]. The malaria therapy,
acaricidal, herbicidal and insecticidal properties [13] of benzo-
triazepine analogues have also been documented. A variety of
pyrazole derivatives are associated with wide range of biological
activities [14] such as antifungal, antibacterial activities etc. by
virtue of incorporating toxophoric C]N linkage. In order to study
the additive effect of three heterocyclic moieties in a single frame
a mixture of 5-aryl-3,4-diamino-1,2,4-triazoles and (1-substituted
-3-alkyl/aryl-5-chloropyrazol-4-yl)formaldehydes in the presence
of N,N-dimethylformamide as an energy transfer medium, p-TsOH
as catalyst and basic alumina as solid support under microwave
irradiation as well as stirring in an oil-bath at 80 ꢀC.
2. Results and discussion
In our earlier communication, we reported the synthesis of 1-
suibstitued-3,7-dialkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[3,4-
b][1,3,4]thiadiazepines [15]. Here, we report the modification of
our previously reported tricyclic heterocyclic core pyrazolo tri-
azolotriazepines to generate 1-substituted-8-aryl-3-alkyl/aryl-4H-
pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines as potential
antifungal agents. The required precursor, 5-aryl-3,4-diamino-
1,2,4-triazoles (1) and (1-substituted-3-alkyl/aryl-5-chloropyrazol-
4-yl)formaldehydes (2) were condensed to afford title compounds
(3aej) in N,N-dimethylformamide as an energy transfer medium,
p-TsOH as catalyst and basic alumina as solid support under
microwave irradiation (Scheme 1). Physical data of these comp-
ounds is summarized in Table 1.
work, there is
a continued interest in the synthesis of 1-
substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo
[4,3-b][1,2,4]triazepines (3aej). This paper reports an efficient and
In order to optimize the reaction conditions, (3-methyl-5-
chloropyrazol-4-yl)formaldehyde (2a) and 5-phenyl-3,4-diamino-
* Corresponding author.
E-mail address: monika.gupta77@indiatimes.com (M. Gupta).
0223-5234/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2010.11.043

632
M. Gupta et al. / European Journal of Medicinal Chemistry 46 (2011) 631e635
N
N
N
R
N
R'
CHO
Cl
N
N
B.Al2O3/DMF
MW
CH
HN
+
NH2
N
N
R
N
p-TsOH
N
R'
NH2
N
R"
R"
1
2
3
Scheme 1. Synthesis of 1-Substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines using basic alumina, p-TsOH and N,N-dimethylformamide under
microwave irradiation (Power ¼ 640 W). 3a: R ¼ C6H5, R0 ¼ CH3, R00 ¼ H. 3b: R ¼ 4-ClC6H4, R0 ¼ CH3, R00 ¼ H. 3c: R ¼ C6H5, R0 ¼ C6H5, R00 ¼ C6H5. 3d: R ¼ CH2C6H5, R0 ¼ 4-BrC6H4,
R00 ¼ C6H5. 3e: R ¼ 4-ClC6H4, R0 ¼ 4-BrC6H4, R00 ¼ C6H5. 3f: R ¼ (4-NO2)C6H4, R0 ¼ 4-BrC6H4, R00 ¼ C6H5. 3g: R ¼ C6H5, R0 ¼ 4-BrC6H4, R00 ¼ C6H5. 3h: R ¼ C6H5, R0 ¼ (4-NO2)C6H4,
R00 ¼ C6H5. 3i: R ¼ CH2C6H5, R0 ¼ (4-NO2)C6H4, R00 ¼ C6H5. 3j:R ¼ (4-NO2)C6H4, R0 ¼ (4-NO2)C6H4, R00 ¼ C6H5.
1,2,4-triazole (1a) were selected as test substrates in an open vessel.
It was found that for 5 mmol of each of 5-phenyl-3,4-diamino-
1,2,4-triazole (1a), (3-methyl-5-chloropyrazol-4-yl)formaldehyde
(2a), 2.5 mmol of N,N-dimethylformamide, 200 mg of p-TsOH and
basic alumina was required to get maximum yield under mild
reaction conditions. The test reaction was carried out at different
power levels from 80 to 900 W and it was found that 640 W was
the optimum power level as far as yield and reaction times are
concerned.
In order to determine the possibility of a specific microwave
effect accelerating the reaction with respect to conventional
heating, a pre-heated oil-bath was used as a source of heat in
comparative experiments. The lower yields were obtained with
conventional heating under the same conditions of time, indicate
that the effect of microwave is not purely thermal. The reaction is
faster in the microwave experiment than under conventional
heating at the same time and same temperature because this is
the characteristic feature of microwave irradiations that reactions
with polar substrates carry out at a fast rate. Moreover, the heating
starts from interior than exterior as in case of conventional
heating.
4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines to be per-
formed in 4e25 min.
The important findings while carrying out the reaction was that
the heterocyclic core pyrazolo triazolotriazepine was composed of
three heterocyclic moieties and each were associated with broad
spectrum of activities while in condensed system, the title
compounds were known for antifungal activity. Moreover, reac-
tions were fast and yields were more as compared to conventional
heating. The reason was that these contained polar groups that
made the molecule polar and the polar molecules were microwave
active. Also, the reaction was carried out in high boiling point polar
solvent i.e. high dielectric constant that made the reaction highly
microwave active. This is what the reaction yields were more under
microwave irradiation.
3. Antifungal activity
Fungal infections have been reported to have dramatically
increased in the past decade, and these often occur as systemic
infections or as coinfections with other diseases, such as AIDS or
cancer, or in patients who are immunocompromised. In fact,
candidiasis has become the most common infection in AIDS and
cancer patients. Unfortunately, in addition to the limited number of
antifungal drugs currently available, fungal infections tend to
rapidly develop resistance to these drugs. For these reasons, fungal
infections now show much higher mortality rates than bacterial
infections.
The rapid increase in fungal infections and the growing number
of new antifungal agents indicate an increasing need for rapid
and accurate methods for antifungal screening and susceptibility
testing. The National Committee for Clinical Laboratory Standards
(NCCLS) recently approved a standardized method for antifungal
susceptibility testing, and proposed a method for testing of fila-
mentous fungi, based on a broth macrodilution method (BMM).
Subsequently, several modifications of these methods were pro-
posed. Most of these methods were developed for the determina-
tion of MICs of agents against yeasts.
To sum up, the microwave irradiation provides an excellent
methodology for the synthesis of 1-substituted-8-aryl-3-alkyl/aryl-
Table 1
Physical data of synthesized compounds 1-
Substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f]
[1,2,4]triazolo[4,3-b][1,2,4]triazepines using basic
alumina, p-TsOH and N,N-dimethylformamide under
microwave irradiation (Power ¼ 640 W).
Producta
Timeb (min)
3ac
3bc
3cc
3dd
3ec
3fd
3gc
3hc
3ic
11
4
20
23
17
14
25
8
Heterocyclic compounds exhibit a broad spectrum of biological
activities. Keeping in view the biological importance of condensed
heterocyclic compounds, the title compounds were evaluated for
the antifungal activity against Aspergillus flavus, Aspergillus niger,
Rhizopus species and Penicillium species by paper disc technique
13
22
3jc
a
Products were characterized by 1H NMR, IR and
mass spectral data.
b
against the concentration 500
mg and 1000 mg. The zone of inhi-
Time was measured by immersing the glass
bition after 24 h of incubation at 28 ꢁ 2 ꢀC was compared with
that of standard fluconazole. The screening data indicated that the
compounds 3a, 3b, 3c, 3e, 3h and 3j showed moderate activity
against Penicillium species and Rhizopus species, while low activity
was observed against A. niger and A. flavus. Some of the synthe-
sized compounds were screened for antifungal activity against A.
thermometer in reaction mixture by giving a short
pulse of 5 s followed by 5 s cooling time.
c
Products were purified by crystallization from
ethyl acetate.
d
Products were purified by passing through
a column of alumina and elution with ethyl acetate
and petroleum ether in the ration of (2:8).

M. Gupta et al. / European Journal of Medicinal Chemistry 46 (2011) 631e635
633
flavus, A. niger, Rhizopus species and Penicillium species by paper
disc technique against two concentrations 500 g/mL and
the medium to 40 ꢀC and then adding spore suspension to seeded
medium. The spores were obtained from ten days culture of A. niger,
A. flavus, Penicillium species and Rhizopus species. Before the solid-
ification of agar, the plate was tilted to ensure that coverage should
be even. These petridishes were then put into the refrigerator
upside down to prevent condensation of moisture. Two concen-
m
1000
mg/mL. The zone of inhibition after 24 h of incubation at
28 ꢁ 2 ꢀC was compared with that of identical concentrations of
standard fluconazole. The screening data indicated that the
compounds 3d, 3f, 3g and 3i showed excellent activity against A.
niger and Penicillium species at 500
mg as well as 1000
mg
trations viz. 500 and 1000 mg/mL of the synthesized compounds
concentrations whereas, these compounds showed good to
moderate activity against A. flavus and Rhizopus species at both the
concentrations as shown in Table 2.
The medium used for evaluation of antifungal activity was
Potato dextrose agar -agar medium.
were prepared by dissolving the required quantity of compounds in
DMF. Sterilized Whatman filter paper number 541 discs were
prepared by cutting 6 mm diameter with a cork borer and were
spread individually with a needle and planted upon the chilled
seeded medium. The plates were then incubated for 24e72 h at
28 ꢀCꢁ2 ꢀC and inhibition of zone around each disc was measured
from the centre of the discs. The percentage zone of inhibition was
calculated by the formula
3.1. Experimental
3.1.1. Preparation of the medium
I% ¼ C ꢂ T=C ꢃ 100
Potato dextrose agar -agar medium [16] was prepared as below:
Where, I ¼ inhibition
Potato ¼ 250 g; Dextrose ¼ 10 g; Agar-agar ¼ 20 g; Distilled
water ¼ 100 mL
C ¼ diameter of zone of micro- organisms in check
T ¼ diameter of the disc
The zone of inhibition was measured after 24 h, fluconazole
Sliced potatoes were taken with 500 mL of distilled water in
a pan and boiled for half an hour till a spoon when placed on a slice
can pierce into it. Filter it while in hot and broth was again taken in
a pan with rest of the distilled water. Dextrose dissolved in distilled
water and weighed agar-agar was added to the broth and heated it
to boil. The medium thus obtained was sterillized in pressure
cooker for 30 min and few drops of streptomycin were added to
prevent it from any bacterial contamination. The zone of inhibition
(500 mg/mL and 1000 mg/mL) was used as control standard.
4. Experimental
General. Melting points were determined on a Tempo melting
point apparatus and are uncorrected.1H NMR spectra were recorded
on
a Bruker DPX-200 NMR spectrometer (200 MHz) in
was measured after 24 h, fluconazole (500 mg/mL and 1000 mg/mL)
was used as control standard.
CDCl3 þ DMSO-d6 using tetramethylsilane as an internal standard
and IR spectra were recorded using KBr disc on a Perkin Elmer FTIR
spectrometer. The mass spectral data was obtained on a JEOL JMS-D
300 spectrometer. C, H, N and S were studied by Leco Analyzer (932).
The reactions were carried out in domestic microwave oven LG
Smart Chef MS-255R with maximum output power of 900 W having
voltage 240 V to 50 Hz. Final temperature is measured by immersing
glass thermometer in reaction mixture at the end of exposure to
microwave irradiation and its approximate temperature range.
3.2. Procedure
Potato dextrose medium was prepared and sterilized in pressure
cooker for 30 min. Sterillized medium (15 mL) each was pipetted
out into flat petridishes. When it solidified 15 mL of warm seeded
medium was applied over it. The seeded agar was made by cooling
Table 2
Antifungal activity of title compounds 1-substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines under microwave irradiation at 640 W.
S.No.
Product No.
Zone of inhibition in mm (%)
Aspergillus niger
Aspergilus Flavus
Rhizopus species
Pencillium species
500
22
m
g
1000
32
m
g
500
20
m
g
1000
24
mg
500
32
m
g
1000
40
m
g
500
06
m
g
1000
08
mg
1
3a
(36.66)
23
(53.33)
32
(33.33)
22
(40.00)
24
(53.33)
31
(60.66)
40
(10.00)
08
(13.33)
09
2
3b
(38.33)
20
(53.33)
31
(36.66)
21
(40.00)
21
(51.66)
36
(60.66)
39
(13.33)
05
(15.00)
02
3
3c
(33.33)
02
(51.66)
14
(35.36)
20
(35.36)
08
(66.66)
28
(65.00)
24
(8.33)
05
(3.33)
e
4
3d
(3.33)
32
(23.33)
21
(33.33)
22
(13.33)
24
(46.66)
40
(40.00)
32
(8.33)
09
5
3e
08
(53.33)
14
(35.36)
02
(36.66)
18
(40.00)
08
(60.66)
24
(53.33)
21
(15.00)
02
(13.33)
05
6
3f
(23.33)
02
(3.33)
12
(31. 33)
18
(13.33)
06
(40.00)
26
(35.36)
22
(3.33)
05
(8.33)
08
7
3g
(3.33)
31
(21.33)
20
(31.33)
24
(11.33)
22
(42.66)
39
(38.00)
36
(8.33)
07
(13.33)
09
8
3h
(51.66)
02
(33.33)
14
(40.00)
20
(36.66)
08
(65.00)
28
(66.66)
24
(12.98)
e
(15.00)
e
9
3i
(3.33)
08
(13.33)
42
(23.33)
15
(25.00)
48
(33.33)
03
(5.00)
35
(13.33)
09
(15.00)
42
(46.66)
18
(30.00)
38
(40.00)
23
(38.33)
42
10
11
3j
e
e
Standard Fluconazole
52
54
(70.00)
(80.00)
(58.33)
(70.00)
(63.33)
(70.00)
(86.66)
(90.00)

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M. Gupta et al. / European Journal of Medicinal Chemistry 46 (2011) 631e635
5. General procedure for the synthesis of novel antifungal
active 1-substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5-f]
[1,2,4]triazolo[4,3-b][1,2,4]triazepines (3aej)
NMR: d
158 (C-3, 7, 5a and 10a), 135(C-400), 130 (C-40, 4000), 129 (C-10,
100, 10000), 128 (C-30,300,30000 500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77
(C-3a), 41 (CH2), 28(CH3); IR (nmax in cmꢂ1, KBr): 3112, 3010, 1622,
1429, 562. Anal. Calcd. for C25H18N7Br: C, 61.00; H, 3.66; N, 19.14; Br,
14.25. Found; C, 60.99; H, 3.64; N,19.12; Br,14.24. m/z(%) ¼ 491(Mþ)
A mixture of 5-aryl-3,4-diamino-1,2,4-triazole 1 (5 mmol), (1-
substituted-3-alkyl/aryl-5-chloropyrazol-4-yl)formaldehyde
2
(5 mmol), N,N-dimethylformamide (2.5 mmol), p-TsOH (200 mg)
and basic alumina (1 g) was mixed thoroughly in a borosil beaker
(50 mL) with the help of a glass rod. The mixture was exposed to
microwave irradiation for the appropriate time (monitored by TLC,
shown in Table 1) at 640 W. After the completion of reaction, the
mixture was extracted with hot N,N-dimethylformamide
(3 ꢃ 15 mL). The solid obtained after pouring of the N,N-dime-
thylformamide extract onto the crushed ice, was collected, washed
with water and dried. The crude product was purified either by
crystallization from ethyl acetate or passing through a column of
alumina and elution with ethyl acetate and petroleum ether (2:8).
The physical data of the synthesized compounds is given in Table 1.
The structures of the synthesized products were confirmed by 1H
NMR and mass spectral data.
6.5. N-(4000Bromophenyl)-8-(40-chlorophenyl)-3-phenyl-4H-
pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepine (3e)
Brown coloured solid, Yield (64%), M.p. 210e212 ꢀC. 1H NMR
(CDCl3þDMSO-d6):
d
7.23e7.45 (m, 9H, Harom), 7.50e7.58 (m, 4H,
158 (C-3, 7,
Harom), 7.70 (s, 1H, C-4H), 8.53 (bs, 1H, NH); 13C NMR:
d
5a and 10a), 142 (C-4000), 137(C-400), 130 (C-40), 129 (C-10, 100, 10000), 128
(C-30,300,30000 500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77 (C-3a), 41
(CH2), 28(CH3); IR (nmax in cmꢂ1, KBr): 3110, 3030, 1404, 742, 592.
Anal. Calcd. for C24H15ClBrN7: C, 56.30; H, 2.97; Cl, 7.05; Br, 15.69; N,
19.46. Found: C, 56.25; H, 2.95; Cl, 7.04; Br, 15.69; N, 19.42. m/z
(%) ¼ 511.5 (Mþ)
6.6. N-(4000-Bromophenyl)-8-(40-nitrophenyl)-3-phenyl-4H-
pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepine (3f)
6. Spectral data of the synthesized compounds (3aej)
Brown coloured solid, Yield (68%), M.p. 178e180 ꢀC. 1H NMR
6.1. 8-Phenyl-3-methyl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b]
[1,2,4]triazepines (3a)
(CDCl3þDMSO-d6):
7.38e7.52 (m, 2H, Harom), 7.68 (s, 1H buried C-4H), 8.20 (bs, 1H, NH),
8.55 (bs, 1H, NH); 13C NMR: 158 (C-3, 7, 5a and 10a),134 (C-4000),
d 2.32 (s, 3H, CH3), 7.22e7.32 (m, 2H, Harom),
d
Light brown coloured solid, Yield (62%), M.p. 204e206 ꢀC 1H
142 (C-40000), 137(C-400), 130 (C-40), 129 (C-10, 100, 10000), 128 (C-30,300,30000
500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77 (C-3a), 41 (CH2), 28(CH3);
IR (nmax in cmꢂ1, KBr): 3110, 3040, 2810, 1612, 1410, 718. Anal. Calcd.
for C24H15N8O2Br: C,55.17; H, 2.87; N,21.45; O, 6.13. Found: C, 55.15;
H, 2.84; N, 21.42; O, 6.11. m/z(%) ¼ 522 (Mþ)
NMR (CDCl3þDMSO-d6):
Harom), 7.45e7.50 (m, 2H, Harom), 7.68 (s, 1H, C-4H), 8.15 (bs, 1H,
NH); 13C NMR: 158 (C-3, 7, 5a and 10a), 130 (C-40), 129 (C-10), 128
d 2.28 (s, 3H, CH3), 7.20e7.23 (m, 3H,
d
(C-30, 50), 127 (C-20, 60), 77 (C-3a), 41 (CH2), 28(CH3); (IR nmax in
cmꢂ1, KBr): 3600, 3026, 2854, 1625. Anal. Calcd. for C13H11N7: C,
58.86; H, 4.15; N, 36.98. Found: C, 58.82; H, 4.12; N, 36.95. m/z
(%) ¼ 265 (Mþ)
6.7. N-(4000-Bromophenyl)-3,8-diphenyl-4H-pyrazolo[4,5-f][1,2,4]
triazolo[4,3-b][1,2,4]triazepine (3g)
6.2. 8-(40-Chlorophenyl)-3-methyl-4H-pyrazolo[4,5-f][1,2,4]
Yellow coloured solid, Yield (71%), M.p.168e170 ꢀC. 1H NMR
triazolo[4,3-b][1,2,4]triazepines (3b)
(CDCl3þDMSO-d6):
Harom), 7.68 (s,1H, C-4H), 8.55 (bs,1H, NH); 13C NMR:
and 10a),134 (C-4000), 142 (C-4000), 137(C-400), 130 (C-40), 129 (C-10, 100,
d
7.12e7.32 (m, 7H, Harom), 7.35e7.45 (m,7H,
d
158 (C-3, 7, 5a
Pale yellow coloured solid, Yield (72%), M.p. 214e216 ꢀC. 1H NMR
(CDCl3þDMSO-d6):
7.40e7.55 (m, 2H, Harom), 7.70 (s, 1H, C-4H), 8.16 (bs, 1H, NH), 8.50
(bs,1H, NH); 13C NMR: 158 (C-3, 7, 5a and 10a),136 (C-400),130 (C-40,
d
2.35 (s, 3H, CH3), 7.30e7.37 (m, 2H, Harom),
1
0000), 128 (C-30,300,30000 500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77 (C-
3a), 41 (CH2), 28(CH3); IR (nmax in cmꢂ1, KBr): 3080, 3004,1615,1410,
556. Anal. Calcd. for C24H16N7Br: C, 60.37; H, 3.35; N,19.70; Br,16.56.
Found: C, 60.35; H, 3.32; N, 19.68; Br, 16.52. m/z(%) ¼ 477 (Mþ).
d
100),129 (C-10, 300, 500),128 (C-30, 50, 200, 600), 127 (C-20, 60), 77 (C-3a), 41
(CH2), 28(CH3); IR (nmax in cmꢂ1, KBr): 3100, 3020, 2800, 1622, 1415,
728. Anal. Calcd. for C13H10N7Cl: C, 52.08; H, 3.33; N, 32.72; Cl, 11.85.
Found: C, 52.04; H, 3.30; N, 32.70; Cl, 11.83. m/z(%) ¼ 295.5(Mþ).
6.8. N-(4000-Nitrophenyl)-3,8-diphenyl-4H-pyrazolo[4,5-f][1,2,4]
triazolo[4,3-b][1,2,4]triazepine (3h)
6.3. N-Phenyl-3,8-diphenyl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b]
Brown coloured solid, Yield (73%), M.p. 202e204 ꢀC. 1H NMR
[1,2,4]triazepine (3c)
(CDCl3þDMSO-d6):
d 7.15e7.33 (m, 5H, Harom), 7.65e7.72 (m, 5H,
Harom and s,1H buried C-4H), 8.22e8.28 (m, 4H, Harom), 8.52 (bs,1H,
Pale yellow coloured solid, Yield (68%), M.p.192e194 ꢀC. 1H NMR
NH); 13C NMR: 158 (C-3, 7, 5a and 10a),134 (C-4000), 142 (C-4000), 137
d
(CDCl3þDMSO-d6):
Harom), 7.5e7.52 (m, 6H, Harom), 7.67 (s, 1H, C-4H), 8.54 (bs, 1H, NH);
13C NMR: 158 (C-3, 7, 5a and 10a), 130 (C-40, 400, 4000), 129 (C-10, 100,
d
7.08e7.23 (m, 2H, Harom), 7.30e7.38 (m, 7H,
(C-400), 130 (C-40), 129 (C-10, 100, 10000), 128 (C-30,300,30000 500, 50000, 50), 127
(C-20, 60, 200, 2000, 600, 6000), 77 (C-3a), 41 (CH2), 28(CH3); IR (nmax in
d
cmꢂ1
, KBr): 3080, 3032, 1625, 1440, 1404. Anal. Calcd. for
1
0000), 128 (C-30,300,30000 500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77 (C-
C24H16N8O2: C, 64.28; H, 3.57; N, 25.60; O, 7.14. Found: C, 64.24; H,
3a), 41 (CH2), 28(CH3); IR (nmax in cmꢂ1, KBr): 3060, 3010, 2800,
1602, 1415. Anal. Calcd. for C24H17N7: C, 71.46; H, 4.21; N, 24.31.
Found: C, 71.44; H, 4.20: N, 24.30. m/z(%) ¼ 403 (Mþ)
3.54; N, 25.59; O, 7.12. m/z(%) ¼ 448 (Mþ)
6.9. N-(4000-Nitrophenyl)-8-benzyl-3-phenyl-4H-pyrazolo[4,5-f]
[1,2,4]triazolo[4,3-b][1,2,4]triazepine (3i)
6.4. N-Phenyl-8-benzyl-3-(400-bromophenyl)-4H-pyrazolo[4,5-f]
[1,2,4]triazolo[4,3-b][1,2,4]triazepine (3d)
Brown coloured solid, Yield (72%), M.p. 200e202 ꢀC .1H NMR
(CDCl3þDMSO-d6):
Harom), 7.58e7.62 (m, 2H, Harom), 7.69 (s, 1H, C-4H), 8.12e8.18 (m,
2H, Harom), 8.58 (bs,1H, NH); 13C NMR:
158 (C-3, 7, 5a and 10a),134
(C-4000), 142 (C-4000), 137(C-400), 130 (C-40), 129 (C-10, 100, 10000), 128 (C-
d 4.05 (s, 12H, Ar-CH2), 7.10e7.32 (m, 10H,
Yellow coloured solid, Yield (74%), M.p. 146e148 ꢀC. 1H NMR
(CDCl3þDMSO-d6):
d
4.00 (s, 2H, Ar-CH2), 7.20e7.28 (m, 6H, Harom),
d
7.38e7.55 (m, 8H, Harom), 7.69 (s, 1H, C-4H), 8.51 (bs, 1H, NH); 13C

M. Gupta et al. / European Journal of Medicinal Chemistry 46 (2011) 631e635
635
30,300,30000 500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77 (C-3a), 41 (CH2),
28(CH3); IR (nmax in cmꢂ1, KBr): 3101, 3030, 2925, 1610, 1475, 1410.
Anal. Calcd. for C25H18N7O2: C, 67.56; H, 4.05; N, 21.17; O, 7.20.
Found: C, 67.54; H, 4.03; N, 21.15; O, 7.18. m/z(%) ¼ 444 (Mþ).
Research Fellowship (SRF) during the period of research. We are
thankful to IIIM Jammu for providing spectral studies.
References
6.10. N-(4000-Nitrophenyl)-8-(40-nitrophenyl)–3-phenyl-4H-
pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepine (3j)
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Brown coloured solid, Yield (76%), M.p. 180e182 ꢀC. 1H NMR
(CDCl3þDMSO-d6):
Harom), 7.62e7.68 9m, 2H, Harom and s, 1H buried C-4H, 8.10e8.20
(m, 4H, Harom), 8.40 (bs, 1H, Harom); 13C NMR:
158 (C-3, 7, 5a and
d 7.18e7.32 (m, 4H, Harom), 7.39e7.50 (m, 3H,
d
10a),134 (C-4000), 142 (C-4000), 137(C-400), 130 (C-40), 129 (C-10, 100, 10000),
128 (C-30,300,30000 500, 50000, 50), 127 (C-20, 60, 200, 2000, 600, 6000), 77 (C-3a), 41
(CH2), 28(CH3); IR (nmax in cmꢂ1, KBr): 3180, 3028, 1622, 1460, 1412.
Anal. Calcd. for C24H15N9O4: C, 58.41; H, 3.04; N, 25.55; O,12.98.
Found: C, 58.39; H, 3.01; N, 25.52; O, 12.95. m/z(%) ¼ 493 (Mþ)
Acknowledgements
The author (MG) is thankful to the Council of Scientific and
Industrial Research (CSIR), New Delhi, for the award of Senior