Synthesis of 4-(1-phenyl-1H-pyrazol-3-yl)-[1,2,4]triazolo[4,3-a] quinoxalines and their 4-halogenopyrazolyl analogs

Article abstract of DOI:10.1002/jhet.694

Synthesis of {3-[1-(ethoxycarbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]- 1-phenyl-1H-pyrazol-5-yl}methyl ethyl oxalate (2), ethyl 4-[5-(acetoxymethyl)-1- phenyl-1H-pyrazol-3-yl]-[1,2,4]triazolo[4,3-a]quioxaline-1-carboxylate (4), [4-halo-1-phenyl-3-(1-

Full text of DOI:10.1002/jhet.694

1216
Synthesis of 4-(1-Phenyl-1H-pyrazol-3-yl)-[1,2,4]triazolo[4,3-
a]quinoxalines and Their 4-Halogenopyrazolyl Analogs
Vol 48
Kamal F. M. Atta and El Sayed H. El Ashry*
Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21321, Egypt
*E-mail: eelashry60@hotmail.com
Received June 14, 2010
DOI 10.1002/jhet.694
Published online 27 May 2011 in Wiley Online Library (wileyonlinelibrary.com).
Synthesis of {3-[1-(ethoxycarbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]-1-phenyl-1H-pyrazol-5-
yl}methyl ethyl oxalate (2), ethyl 4-[5-(acetoxymethyl)-1-phenyl-1H-pyrazol-3-yl]-[1,2,4]triazolo[4,3-
a]quioxaline-1-carboxylate (4), [4-halo-1-phenyl-3-(1-phenyl-[1,2,4]triazolo[4,3-a]quioxalin-4-yl)-1H-
pyrazol-5-yl]methyl acetate (11), {4-halo-3-[1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]-1-phenyl-
1H-pyraz-ol-5-yl}methyl acetate (13), and [3-([1,2,4]triazolo-[4,3-a]quinoxalin-4-yl)-4-halo-1-phenyl-
1H-pyrazol-5-yl] methyl formate (15) was accomplished. The structural investigation of the new com-
pounds is based on chemical and spectroscopic evidences.
J. Heterocyclic Chem., 48, 1216 (2011)
INTRODUCTION
benzodiazepine-binding site of GABAA receptors [11]
as well as potential antagonist ligands for imaging the
A2A adenosine receptor by position emission tomogra-
phy [12]. The bis-triazoloquinoxalines showed antifun-
gal activity [13,14].
The concept of molecular simplification as a drug
design strategy of tricyclic compounds has led to the
discovery of a series of 1,2,4-triazolo[4,3-a]quinoxalines
I as high affinity and selective human A3 adenosine re-
ceptor (hA3AR) antagonists [1–4]. A receptor-based
SAR analysis provided anchoring this ring I as versatile
scaffold for selective hA3AR antagonists [5]. A class of
such ring I as small molecules has inhibited the TNF-a-
induced survival and death pathway [6]. A triazoloqui-
noxalinone moiety has been investigated for an antago-
nist receptor modeling study [7]. Moreover, derivatives
of 1,2,4-triazolo[4,3-a]quinoxalines have been reported
as anti-inflammatory drugs, allergy inhibitors [8], fungi-
cides [9], for treating glycogen synthase kinase 3-medi-
ated conditions [10], and submicromolar affinity for the
QSAR of adenosine receptor antagonists suggested the
precursors of five possible interaction sites for 1,2,4-tria-
zolo[4,3-a]quinoxaline derivatives [15]. Thus, the pyrazo-
lyl-triazoloquinoxalines II have been patented as A1,
A2a, A2b, and A3 adenosine receptor ligands as well as
cardiovascular, antiarrhythmic, and antianginal agents
[16] (Fig. 1). The quinoxaline ring can be generally con-
structed from o-phenylene diamine by reaction with a-
dicarbonyl compounds [17,18]. The anelation of the
triazole ring to the quinoxaline has been performed by the
cyclization of 2-hydrazinoquinoxalines III, prepared from
IV, with one-carbon cyclizing agents [19] or by the 1,3-
C
V
2011 HeteroCorporation

September 2011
Synthesis of 4-(1-Phenyl-1H-pyrazol-3-yl)-[1,2,
4]triazolo[4,3-a]quinoxalines and Their 4-Halogenopyrazolyl Analogs
1217
drazine residue requires higher temperature than the boiling
point of the solvent dioxane, which otherwise achieve by
the boiling of diethyl oxalate or acetic anhydride.
The structures of 2–4 were deduced from their spec-
tral analysis. The IR spectrum of 2 showed two absorp-
tion bands at 1772 and 1728 cmꢀ1 for the ester groups,
whereas 3 showed one ester band only at 1725 cmꢀ1 in
addition to an amide band at 1643 cmꢀ1, which disap-
pear in 4 that showed only two ester bands, in accord-
1
ance with the structures. Their H-NMR spectra revealed
signals leading to the deduction of the structures. The
methylene group linked to pyrazole ring appeared as a
singlet at d 5.36 ppm in 2 that shifted to a higher mag-
netic field (d 4.62 ppm) in 3 that shifted to lower mag-
netic field (d 5.22 ppm) in 4 agreeing with the struc-
tures. Signals for two and one ethyl groups were present
in the spectra of 2 and 3, respectively, whereas that of 4
showed one ethyl group in addition to a one acetyl
group. Furthermore, their mass spectra showed molecu-
lar ion peaks and fragment at ion pattern agreeing with
the structures (cf. Experimental). Combination of the
results of mass spectra with that of elemental analysis
led to the conclusion of the molecular formulae.
Figure 1. Construction of triazoloquinoxaline ring.
dipolar cycloaddition of aryl nitrilimines to quinoxalines
[19]. The first strategy for anelation of the triazole ring
was used in this investigation. Thus, continuing our work
on the synthesis of functionalized quinoxalines [17–26], it
becomes interesting to prepare a library of pyrazolyl- and
4-halogenopyrazolyl-triazoloquinoxalines.
Treatment of 2 or 4 with hydrazine hydrate in etha-
nolic solutions caused hydrazinolysis of the ethoxycar-
bonyl moiety on position 1 in addition to the deacyla-
tion of the ester groups on the 4-hydroxymethyl group
on pyrazole ring to afford the same target hydrazide, 4-
[5-(hydroxymethyl)-1-phenyl-1H-pyrazol-3-yl]-[1,2,4]tri-
azolo[4,3-a]quinoxaline-1-carbohydrazide (5). The struc-
ture of 5 was based on the absence of ester absorption
band and the presence of a band at 1658 cmꢀ1 due to
RESULTS AND DISCUSSION
The first target group is the pyrazolyl-triazoloquinoxa-
lines whose starting material [3-(3-hydrazinylquinoxalin-
2-yl)-1-phenyl-1H-pyrazol-5-yl]methanol (1) [19] was
prepared via five steps sequence from L-ascorbic acid
whose carbon skeleton became the carbon backbone of
the pyrazolyl quinoxaline ring 1. Heating of 1 with
diethyl oxalate under reflux afforded {3-[1-(ethoxycar-
bonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl]-1-phenyl-
1H-pyrazol-5-yl}methyl ethyl oxalate (2) in high yield.
Its formation can be explained to be a consequence of
the role of ethyl oxalate that acted as oxaloylating agent
for both the hydrazine and the hydroxymethyl groups,
and then the oxaloylhydrazine residue underwent dehy-
drative cyclization to form the triazole ring in 2. On the
other hand, when the reaction of 1 with diethyl oxalate
was carried out in dioxan under reflux, the product was
found to be ethyl 2-{2-[3-(hydroxymethyl)-1-phenyl-1H-
pyrazol-3-yl]quinoxalin-2-yl}hydrazinyl-2-oxoacetate (3)
whose oxalylhydrazine moiety can be cyclized to the tri-
azole ring with concomitant acetylation of the hydroxyl
group with boiling acetic anhydride to give ethyl 4-[5-(ace-
toxymethyl)-1-phenyl-1H-pyrazol-3-yl]-[1,2,4]triazolo[4,3-
a]quioxaline-1-carboxylate (4) in a good yield. These
results may lead to the conclusion that oxaloylation of the
hydrazine moiety and then the hydroxyl group, to give the
bis-oxaloylated intermediate, has preceded the cyclization
step to give 2. Moreover, the cyclization of the oxaloylhy-
1
CON group. Its H-NMR spectrum revealed signals at d
4.63 ppm (s, 2H, CH2), a similar magnetic field to that
of the methylene group in 3, confirming the absence of
ester groups on it. Moreover, its mass spectrum showed
the molecular ion peak at m/z 400 agreeing with the
assigned molecular formula. Acetylation of 5 by boiling
acetic anhydride or by acetic anhydride in pyridine
afforded {3-[1-(2,2-diacetylhydrazinecarbonyl)-[1,2,4]tria-
zolo[4,3-a]quinoxalin-4-yl]-1-phenyl-1H-pyrazol-5-yl}methyl
acetate (6) and {3-[1-(1,2-diacetylhydrazinecarbonyl)-
[1,2,4]-triazolo[4,3-a]quioxalin-4-yl]-1-phenyl-1H-pyrazol-
5-yl}methyl acetate (7), respectively, Scheme 1. Their IR
spectra showed the presence of an ester band at 1726–
1735 cmꢀ1 because of the acetoxymethyl group, in addi-
tion to an amide absorption bands at 1700 and 1649 cmꢀ1
for 6 and a one band at 1618 cmꢀ1 for 7. In addition, the
1H-NMR spectra of 6 showed two singlets at d 2.52 and
2.54 ppm for the two N-acetyl groups, whereas that of 7
showed a one singlet at d 2.50 ppm for the two acetyl
groups. These data indicated the presence of two N-acetyl
groups in each compound, and these two acetyls are
equivalent in case of 7. The mass spectra and elemental
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K. F. M. Atta and E. S. H. El Ashry
Vol 48
Scheme 1. Synthesis of pyrazolyl-triazoloquinoxalines.
analysis confirmed the presence of the three acetyl
groups.
atoms were introduced at the 4-position of the pyrazole
ring by the electrophilic substitution reactions on [3-(3-
chloroquinoxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methyl
acetate (8) [19]. Thus, the reaction of 8 with equimolar
The second target group of compounds was triazolo-
quinoxalines linked to halogeno-pyrazoles. The halogen
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Synthesis of 4-(1-Phenyl-1H-pyrazol-3-yl)-[1,2,
4]triazolo[4,3-a]quinoxalines and Their 4-Halogenopyrazolyl Analogs
1219
amounts of Br2/AcOH or ICl/AcOH afforded [4-bromo-
3-(3-chloroquioxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methyl
acetate (9a) and [3-(3-chloroquioxalin-2-yl)-4-iodo-1-phe-
nyl-1H-pyrazol-5-yl]methyl acetate (9b), respectively, via
the electrophilic attack of the active 4-position of the pyraz-
ole ring. The reaction of 9a and 9b with benzoylhydrazine
gave {3-[3-(2-benzoylhydrazinyl)quinoxalin-2-yl]-4-halo-1-
phenyl-1H-pyrazol-5-yl}methyl acetate 10a and 10b, which
underwent dehydrative cyclization on boiling with acetic an-
hydride to yield [4-halo-1-phenyl-3-(1-phenyl-[1,2,4]tria-
zolo[4,3-a]quioxalin-4-yl)-1H-pyrazol-5-yl]methyl acetate
(11). The structures of 10 and 11 were confirmed from their
spectral analysis. Their IR spectrum showed two absorption
bands at 1736–1741 cmꢀ1 for the ester group, in addition to
an amide absorption band at 1660–1675 cmꢀ1 for 10 and
only one band at 1728 cmꢀ1 due to ester group for 11.
Moreover, the 1H-NMR spectrum of 10 showed two
exchangeable singlets at d 11.79–11.80 and 12.17 ppm for
two NH protons, in addition to a singlet at d 2.00 ppm due
to the acetyl group, whereas that of 11 showed the absence
of the two singlets for the two NH protons and showed the
acetyl group as a singlet at d 2.06–02.08 ppm. Also, the
structures 10 and 11 were confirmed by mass spectrometry.
Nucleophilic substitution of the chlorine atom on the
quinoxaline ring in 9 with hydrazine hydrate afforded
the key starting material, [4-halo-3-(3-hydrazinyl-qui-
and a methyl group at d 3.21–3.24 ppm, whereas that
for 15a and 15b also showed the absence of exchange-
able singlet beside the presence of a singlet at d 8.27–
8.28 ppm due to formate proton and a singlet at d 10.19
ppm for the triazole-H. Deacetylation of compounds 13
with methanolic ammonia yielded the corresponding
deacetylated products [4-halo-3-(1-methyl-[1,2,4]tria-
zolo[4,3-a]quinoxalin-4-yl)-1-phenyl-1H-pyrazol-5-
yl]methanol 14a and 14b, Scheme 2. The structures of
all prepared compounds were confirmed by elemental
analysis and spectral data (cf. Experimental).
In conclusion, a library of functionalized pyrazolyl-
quinoxalines and their halogeno-pyrazolyl analogs has
been successfully achieved. The strategy for construct-
ing the target compounds started by [3-(3-hydrazinylqui-
noxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methanol
(1),
where the hydrazine moiety can be readily heterocycl-
ized with one-carbon inserting agent to give the triazole
ring fused to the quinoxaline skeleton.
EXPERIMENTAL
Melting points were determined on a Kofler Block and are
uncorrected. TLC was done on Merck Kiesel gel 60-f 254 pre-
coated plastic plates. Infrared spectra were measured with Fou-
rier transform infrared 8400 spectrophotometer for potassium
bromide pellets. The 1H-NMR spectra were recorded on a
JEOL JNM ECA 500 MHz with tetramethylsilane as an inter-
nal standard. Mass spectra were recorded at 70 eV with
GCMS-QP 1000 EX and Shimadzu Gc Qp 5050 A. Microanal-
yses were performed by the microanalytical unit, Cairo univer-
sity, Cairo.
noxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methanol
12a
1
and 12b. The H-NMR spectrum of 12a showed three
exchangeable singlets at d 3.60 ppm for OH group, d
8.85 ppm for NH2 group, and d 10.08 ppm for NH
group, whereas that for 12b showed four exchangeable
singlets at d 3.71 ppm due to OH group, d 8.87, 09.25,
and d 10.18 ppm for three NH protons. A selective sub-
stitution of the chlorine at position 3 of the quinoxaline
ring rather than the halogen on the pyrazole ring has
been found, with no sign of substitution of the latter hal-
ogen. This selectivity can be attributed to the preference
of the nucleophilic attack on the more positive carbon-3
because of the withdrawal of electrons from that carbon
toward the nitrogen. Subsequent loss of the chlorine
atom gave the product. The synthetic potential of com-
pound 12 for constructing fused [1,2,4]triazolo[4,3-
a]quinoxalines was investigated by its boiling with ace-
tic or formic acids, whereby [4-halo-3-(1-methyl-
[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-1-phenyl-1H-pyra-
zol-5-yl]methyl acetate 13a and 13b or [3-([1,2,4]tria-
zolo[4,3-a]quinoxalin-4-yl)-4-halo-1-phenyl-1H-pyrazol-
5-yl]methyl formate 15a and 15b, respectively, were
formed. The structures 13 and 15 were confirmed
through spectral data. The IR spectrum showed an ester
absorption band at 1718–1739 cmꢀ1. The 1H-NMR
spectra of 13a and 13b showed the absence of
exchangeable singlets as the former but showed the
presence of acetyl group as singlet at d 2.08–2.09 ppm
{3-[1-(Ethoxycarbonyl)-[1,2,4]triazolo[4,3-a]quinoxalin-4-
yl]-1-phenyl-1H-pyrazol-5-yl}methyl ethyl oxalate (2). A
mixture of [3-(3-hydrazinylquinoxalin-2-yl)-1-phenyl-1H-pyra-
zol-5-yl] methanol (1, 1.0 g, 0.003 mol) and diethyl oxalate
(20 mL) was heated under reflux for 3 h. The mixture was
evaporated under reduced pressure, and the residue was tritu-
rated with water, filtered, washed with ether, and crystallized
from ethanol to give the title compound 2 as colorless needles
(75%); m.p. 191–192ꢁC; IR: 1772 (COO), 1728 (COO), and
1
1596 cmꢀ1 (C¼¼N); H-NMR (CDCl3): d ¼ 1.37 (t, 3H, CH3),
1.56 (t, 3H, CH3), 4.35 (q, 2H, CH2), 4.67 (q, 2H, CH2), 5.36
(s, 2H, OCH2), 7.48–7.55 (m, 3H, Ar-H), 7.65 (dd,2H, Ar-H),
7.69–7.74 (m, 2H, Ar-H), 8.17 (s, 1H, pyrazole-H), 8.32–8.35
(m, 1H, Ar-H), and 8.87–8.91 (m, 1H, Ar-H); MS (m/z, %):
514 (77, Mþ), 486 (31, Mþ-CO), and 413 (100, Mþ-
COCOOEt); Anal. Calcd for C26H22N6O6 (514.49): C, 60.70;
H, 4.31; N, 16.33%. Found: C, 60.59; H, 4.23; N, 16.17%.
Ethyl
2-{2-[3-(hydroxymethyl)-1-phenyl-1H-pyrazol-3-
yl]quinoxalin-2-yl}hydra-zinyl-2-oxoacetate (3). A solution
of [3-(3-hydrazinylquinoxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]
methanol (1, 1.0 g, 0.003 mol) in dioxin (50 mL) was treated
with diethyl oxalate (20 mL), and the mixture was heated
under reflux for 8 h. The reaction mixture was allowed to
attain ambient temperature, and the product that separated out
was filtered off, washed with ether, and crystallized from
dioxan to give the title compound as orange needles (80%),
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K. F. M. Atta and E. S. H. El Ashry
Vol 48
Scheme 2. Synthesis of 4-halogen-pyrazolyl-triazoloquinoxalines.
m.p. 325–326ꢁC; IR: 3437 (OH), 3125 (NH), 1725 (COO),
7.95 (s, 1H, pyrazole-H), 10.33 (s, 1H, NH, exchangeable),
and 12.22 (s, 1H, NH, exchangeable); MS (m/z, %): 359 (7,
Mþ-COOEt), 341 (12, Mþ-COOEt-OH), 301 (11, Mþ-
NHNHCOCOOEt), and 76 (100, C6Hþ4 ); Anal. Calcd for
1
1634 (CON), and 1598 cmꢀ1 (C¼¼N); H-NMR (DMSO-d6): d
¼ 1.29 (t, 3H, CH3), 4.29 (q, 2H, CH2), 4.62 (s, 2H, CH2O),
5.69 (s, 1H, OH, exchangeable), 7.32–7.93 (m, 9H, Ar-H),
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Synthesis of 4-(1-Phenyl-1H-pyrazol-3-yl)-[1,2,
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1221
C22H20N6O4 (432.43): C, 61.10; H, 4.66; N, 19.43%. Found:
C, 61.07; H, 4.51; N, 19.18%.
Mþ-CONAcNHAc-CH2CO); Anal. Calcd for C26H22N8O5
(526.50): C, 59.31; H, 4.21; N, 21.28%. Found: C, 59.38; H,
4.32; N, 21.18%.
Ethyl
4-[5-(acetoxymethyl)-1-phenyl-1H-pyrazol-3-yl]-
[1,2,4]triazolo[4,3-a]quinoxaline-1-carboxylate (4). A suspen-
sion of ethyl 2-{2-[3-(hydroxymethyl)-1-phenyl-1H-pyrazol-3-
yl]quinoxalin-2-yl}hydrazinyl-2-oxoacetate (3, 1.0 g, 0.0023
mol) in acetic anhydride (10 mL) was heated under reflux for 1
h, and the mixture was cooled and poured onto crushed ice. The
solid that separated out was filtered off, washed with water, and
then dried. It was recrystallized from ethanol to give the title
compound as colorless needles (82%). m.p. 211–212ꢁC; IR:
1734 (COO), 1718 (COO), and 1635 cmꢀ1 C¼¼N); 1H-NMR
(DMSO-d6): d ¼ 1.42 (t, 3H, CH3), 2.00 (s, 3H, OAc), 4.58 (q,
2H, CH2), 5.22 (s, 2H, OCH2), 7.53–7.78 (m, 7H, Ar-H), 7.82
(s, 1H, pyrazole-H), 8.14–8.16 (m, 1H, Ar-H), and 8.66–8.68
(m, 1H, Ar-H); MS (m/z, %): 456 (35, Mþ), 414 (100, Mþ-
CH2CO), and 341 (40, Mþ-CH2CO-COOEt). Anal. Calcd for
C24H20N6O4 (456.45): C, 63.15; H, 4.42; N, 18.41%. Found: C,
63.05; H, 4.29; N, 18.22%.
{3-[1-(1,2-Diacetylhydrazinecarbonyl)-[1,2,4]triazolo[4,3-
a]quioxalin-4-yl]-1-phenyl-1H-pyrazol-5-yl}methyl acetate
(7). A solution of 4-[5-(hydroxymethyl)-1-phenyl-1H-pyrazol-
3-yl]-[1,2,4]tri-azolo[4,3-a]quinoxaline-1-carbohydrazide
(5,
0.5 g, 0.0013 mol) in dry pyridine (2 mL) was treated with
acetic anhydride (5 mL), and the mixture was kept overnight
at room temperature. The reaction mixture was poured onto
crushed ice, and the solid that separated out was filtered off,
washed repeatedly with water, and dried. The product was
recrystallized from ethanol to give the title compound as color-
less needles (90%); m.p. 167–168ꢁC; IR: 3193 (NH), 1726
1
(COO), and 1618 cmꢀ1 (CON); H-NMR (CDCl3): d 2.09 (s,
3H, OAc), 2.50 (s, 6H, 2 NAc), 5.14 (s, 2H, CH2), 7.42–7.68
(m, 7H, Ar-H), 7.94 (s, 1H, pyrazole-H), 8.27 (m, 1H, Ar-H),
9.29 (m, 1H, Ar-H), and 10.28 (s, 1H, NH, exchangeable); MS
(m/z, %): 484 (11, Mþ-CH2CO), 424 (42, Mþ-OAc-Ac), 384
(24, Mþ-CONHNAc2), 341 (73, Mþ-CONHNAc2-Ac), and 76
(100, C6Hþ5 ). Anal. Calcd for C26H22N8O5 (526.50): C, 59.31;
H, 4.21; N, 21.28%. Found: C, 59.07; H, 4.01; N, 21.16%.
[4-Bromo-3-(3-chloroquioxalin-2-yl)-1-phenyl-1H-pyrazol-
5-yl]methyl acetate (9a). A solution of bromine (0.06 mL;
0.0012 mol) in acetic acid (10 mL) was gradually added to a sus-
pension of [3-(3-chloroquinoxalin-2-yl)-1-phenyl-1H-pyrazol-5-
yl]methyl acetate (8, 0.4 g, 0.001 mol) in acetic acid (10 mL) with
stirring for 24 h at room temperature. The precipitated [4-bromo-3-
(3-chloroquioxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methyl acetate
(9a) was filtered off, washed with water, dried, and crystallized
from ethanol as colorless needles (75%); m.p. 127–128ꢁC; IR:
1743 (COO), 1656 (C¼¼N), and 1595 cmꢀ1 (C¼¼C); 1H-NMR
(CDCl3): d ¼ 2.09 (s, 3H, OAc), 5.19 (s, 2H, CH2), 7.45–7.62 (m,
5H, Ar-H), 7.75–7.87 (m, 2H, Ar-H), 8.01–8.10 (m, 1H, Ar-H),
and 8.16–8.20 (m, 1H, Ar-H); MS (m/z, %): 458 (49, Mþ), 399
(11, Mþ-OAc), 378 (60, Mþ-Br), and 335 (100, Mþ-Ac-Br); Anal.
Calcd for C20H14BrClN4O2 (457.70): C, 52.48; H, 3.08; N,
12.24%. Found: C, 52.25; H, 2.95; N, 12.00%.
[3-(3-Chloroquioxalin-2-yl)-4-iodo-1-phenyl-1H-pyrazol-5-
yl]methyl acetate (9b). A solution of iodine monochloride (0.2
g, 0.0012 mol) in acetic acid (10 mL) was gradually added to a
suspension of[3-(3-chloroquinoxalin-2-yl)-1-phenyl-1H-pyrazol-5-
yl]methyl acetate (8, 0.4g, 0.001 mol) in acetic acid (10 mL)
with stirring for 24 h at ambient temperature. The reaction mix-
ture was then poured onto crushed ice, and the solid that sepa-
rated out was filtered off, washed with water, and dried. It was
recrystallized from ethanol to give the title compound (9b) as
colorless needles (80%), m.p. 117–118ꢁC; IR: 1741 (COO),
1660 (C¼¼N), and 1595 cmꢀ1 (C¼¼C); 1H-NMR (CDCl3): d ¼
2.09 (s, 3H, OAc), 5.19 (s, 2H, CH2), 7.45–7.62 (m, 5H, Ar-H),
7.75–7.87 (m, 2H, Ar-H), 8.01–8.10 (m, 1H, Ar-H), and 8.16–
8.21 (m, 1H, Ar-H); MS (m/z, %): 504 (96, Mþ), 445 (10, Mþ-
OAc), 378 (30, Mþ-I), and 335 (100, Mþ-Ac-I); Anal. Calcd for
C20H14IClN4O2 (504.70): C, 47.59; H, 2.80; N, 11.10%. Found:
C, 47.35; H, 2.56; N, 10.91%.
4-[5-(Hydroxymethyl)-1-phenyl-1H-pyrazol-3-yl]-[1,2,4]tria-
zolo[4,3-a]quinoxaline-1-carbohydrazide (5).
Method A. A solution of {3-[1-(ethoxycarbonyl)-[1,2,4]tria-
zolo[4,3-a]quinoxalin-4-yl]-1-phenyl-1H-pyrazol-5-yl}methyl ethyl
oxalate (2, 1.0 g, 0.002 mol) and hydrazine hydrate (99%, 1 mL)
in ethanol (50 mL) was heated under reflux for 10 h. The reac-
tion mixture on cooling gave a solid mass, which was filtered off,
washed with ethanol, and crystallized from N,N-dimethylforma-
mide to give the title compound as colorless needles (85%); m.p.
259–260ꢁC; IR: 3326,3282 (NH2), 3103 (NH), 1658 (CON), and
1
1593 cmꢀ1 (C¼¼N); H-NMR (DMSO-d6): d 4.63 (s, 2H, CH2),
5.04 (broad, 1H, OH, exchangeable), 5.67 (s, 1H, NH, exchange-
able), 7.49–7.63 (m, 3H, Ar-H), 7.75–7.80 (m, 5H, Ar-H), 8.18
(s, 1H, pyrazole-H), 8.48–8.51 (m, 1H, Ar-H), and 9.93 (s, 2H,
NH2, exchangeable); MS (m/z, %): 400 (40, Mþ), 369 (7, Mþ-
CH2OH), 343 (14, Mþ-CH2OH, NH2), and 77 (100, C6Hþ5 ).
Anal. Calcd for C20H16N8O2 (400.93): C, 59.99; H, 4.03; N,
27.99%. Found: C, 59.93; H, 3.94; N, 27.86%.
Method B. A solution of ethyl 4-[5-(acetoxymethyl)-1-phenyl-
1H-pyrazol-3-yl]-[1,2,4]triazolo[4,3-a]quioxaline-1-carboxylate (4,
1.0 g, 0.0022 mol) and hydrazine hydrate (99%, 1 mL) in ethanol
(50 mL) was heated at reflux for 10 h. The solid that separated
out on cooling was filtered off, washed with ethanol, and crystal-
lized from N,N-dimethylformamide to give the title compound as
colorless needles (90%); m.p. and mixed m.p. with that prepared
1
according to method A. 259–260ꢁC; The IR and H-NMR spectra
of 5 obtained according to methods A and B were identical.
{3-[1-(2,2-Diacetylhydrazinecarbonyl)-[1,2,4]triazolo[4,3-
a]quinoxalin-4-yl]-1-phenyl-1H-pyrazol-5-yl}methyl
acetate
(6). A suspension of 4-[5-(hydroxymethyl)-1-phenyl-1H-pyrazol-
3-yl]-[1,2,4]tri-azolo[4,3-a]quinoxaline-1-carbohydrazide (5, 0.5
g, 0.0013 mol) in acetic anhydride (5 mL) was heated under
reflux for 1 h, and the mixture was cooled and poured onto
crushed ice. The product that separated out was filtered off,
washed with water, and then dried. It was crystallized from etha-
nol to give the title compound as colorless needles (85%); m.p.
191–192ꢁC; IR: 3201 (NH), 1735 (COO), 1700 (CON), 1649
(CON), and 1604 cmꢀ1 (C¼¼N); 1H-NMR (CDCl3): d 2.09
(s,3H, OAc), 2.52 (s, 3H, NAc), 2.54 (s, 3H, NAc), 5.19 (s, 2H,
CH2), 7.45–7.72 (m, 7H, Ar-H), 7.97 (s, 1H, pyrazole-H), 9.37–
9.39 (m, 1H, Ar-H), and 10.05 (s, 1H, NH, exchangeable); MS
(m/z, %): 527 (1, Mþþ1), 484 (22, Mþ-CH2CO), and 341 (100,
General procedure for the preparation of {3-[3-(2-ben-
zoylhydrazinyl)quinoxalin-2-yl]-4-halo-1-phenyl-1H-pyrazol-5-
yl}methyl acetate (10). A solution of [4-halo-3-(3-chloroquiox-
alin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methyl acetate (9, 0.002
mol) and benzoylhydrazine (0.75 g, 0.004 mol) in butanol (20
mL) was heated under reflux for 8 h. The reaction mixture
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1222
K. F. M. Atta and E. S. H. El Ashry
Vol 48
was concentrated, and the desired product that separated out
was filtered off, washed well with ethanol, and recrystallized
from ethanol to give the title compound as orange needles.
{3-[3-(2-Benzoylhydrazinyl)quinoxalin-2-yl]-4-bromo-1-phe-
nyl-1H-pyrazol-5-yl}methyl acetate (10a). Yield (80%); m.p.
285–286ꢁC; IR: 1741 (COO), 1660 (CON), and 1587 cmꢀ1
cmꢀ1 (C¼¼C); 1H-NMR (CDCl3): d ¼ 3.60 (s, 1H, OH,
exchangeable), 4.72 (s, 2H, CH2), 7.35–7.99 (m, 7H, Ar-H),
8.07 (m, 1H, Ar-H), 8.18 (m, 1H, Ar-H), 8.85 (s, 2H, NH2,
exchangeable), and 10.08 (s, 1H, NH, exchangeable); MS (m/z,
%): 412 (16, Mþþ2), 410 (1þ2, Mþ), 384 (31, Mþþ2-CO), 382
(37, Mþ-CO), 303 (51, M -Br-CO), and 76 (100, C6Hþ4 );
Anal. Calcd for C18H15BrN6O (411.26): C, 52.57; H, 3.68; N,
20.44%. Found: C, 52.36; H, 3.52; N, 20.26%.
[3-(3-Hydrazinylquinoxalin-2-yl)-4-iodo-1-phenyl-1H-pyr-
azol-5-yl]methanol (12b). Yield (92%); m.p. 233–234ꢁC; IR:
3315 (OH), 3110–3055 (NH and NH2), 1625 (C¼¼N), and
1590 cmꢀ1 (C¼¼C); 1H-NMR (CDCl3): d ¼ 3.71 (s, 1H, OH,
exchangeable), 4.78 (s, 2H, CH2), 7.35–8.04 (m, 7H, Ar-H),
8.09–8.12 (m, 1H, Ar-H), 8.18–8.22 (m, 1H, Ar-H), 8.87 (s,
1H, NH, exchangeable), 9.25 (s, 1H, NH, exchangeable), and
10.18 (s, 1H, NH, exchangeableþ); MS (m/z, %): 458 (26, Mþ),
430 (33, Mþ-CO), 303 (93, M -I-CO), and 76 (100, C6Hþ4 );
Anal. Calcd for C18H15IN6O (458.26): C, 47.18; H, 3.30; N,
18.34%. Found: C, 47.06; H, 3.33; N, 18.27%.
General procedure for the preparation of [4-halo-3-(1-
methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-1-phenyl-1H-pyr-
azol-5-yl]methyl acetate (13). A solution of [4-halo-3-(3-
hydrazinylquinoxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]methanol
(12, 0.002 mol) in acetic anhydride (3 mL) was refluxed for 1
h. The mixture was allowed to cool to ambient temperature
and was then poured onto crushed ice. The product was col-
lected by filtration, washed well with water, and dried. It was
recrystallized from ethanol to give the title compound as color-
less needles.
1
(C¼¼C); H-NMR (CDCl3): d ¼ 2.00 (s, 3H, OAc), 5.25 (s, 2H,
CH2), 7.43–7.88 (m, 14H, Ar-H), 11.79 (s, 1H, NH, exchange-
able), and 12.17 (s, 1H, NH, exchangeable); MS (m/z, %): 439
(21, Mþ-NHCOC6H5), 359 (68, Mþ-NHCOC6H5-Br), and 77
(100, C6Hþ5 ); Anal. Calcd for C27H21BrN6O3 (557.39): C, 58.18;
H, 3.80; N, 15.08%. Found: C, 58.07; H, 3.65; N, 14.91%.
{3-[3-(2-Benzoylhydrazinyl)quinoxalin-2-yl]-4-iodo-1-phe-
nyl-1H-pyrazol-5-yl}methyl acetate (10b). Yield (82%); m.p.
251–252ꢁC; IR: 1736 (COO), 1675 (CON), and 1589 cmꢀ1
1
(C¼¼C); H-NMR (DMSO-d6): d ¼ 2.00 (s, 3H, OAc), 5.25 (s,
2H, CH2), 6.78–7.98 (m, 14H, Ar-H), 11.80 (s, 1H, NH,
exchangeable), and 12.17 (s, 1H, NH, exchangeable); MS (m/z,
%): 485 (20, Mþ-NHCOC6H5), 427 (7, Mþ-NHCOC6H5-
OCOCH3), 359 (60, Mþ-NHCOC6H5-I), and 77 (100, C6Hþ5 );
Anal. Calcd for C27H21IN6O3 (604.40): C, 53.65; H, 3.50; N,
13.90%. Found: C, 53.51; H, 3.32; N, 13.66%.
General procedure for the preparation of [4-halo-1-phe-
nyl-3-(1-phenyl-[1,2,4]-triazolo[4,3-a]quioxalin-4-yl)-1H-pyr-
azol-5-yl]methyl acetate (11). A solution [3-(3-(2-benzoylhy-
drazinyl)quinoxalin-2-yl)-4-halo-1-phenyl-1H-pyrazol-5-
yl]methyl acetate (10, 0.001 mol) in acetic anhydride (3 mL)
was heated under reflux for 1 h. The mixture was then cooled
and poured onto crushed ice. The product was filtered off,
washed successfully with water, dried, and recrystallized from
ethanol to give the title compound as orange needles.
[4-Bromo-3-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-
1-phenyl-1H-pyrazol-5-yl]methyl acetate (13a). Yield (90%);
m.p. 183–184ꢁC; IR: 1739 (OAc), 1625 (C¼¼N), and 1595
[4-Bromo-1-phenyl-3-(1-phenyl-[1,2,4]triazolo[4,3-a]quioxa-
lin-4-yl)-1H-pyra-zol-5-yl]methyl acetate (11a). Yield (95%);
m.p. 141–142ꢁC; IR: 1728 (OAc), 1620 (C¼¼N), and 1596 cmꢀ1
1
cmꢀ1 (C¼¼C); H-NMR (CDCl3): d ¼ 2.08 (s, 3H, OAc), 3.24
(s, 3H, CH3), 5.19 (s, 2H, CH2), 7.45–7.51 (m, 3H, Ar-H),
7.58–7.75 (m, 4H, Ar-H), and 8.20–8.27 (m,2H, Ar-H); MS
(m/z, %): 478 (33, Mþþ2), 476 (30, Mþ), 435 (85, Mþþ2-
COCH3), 433 (73, Mþ-COCH3), and 355 (100, Mþ-Br-
CH2CO); Anal. Calcd for C22H17BrN6O2 (477.31): C, 55.36;
H, 3.59; N, 17.61%. Found: C, 55.37; H, 3.52; N, 17.51%.
[4-Iodo-3-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-1-
phenyl-1H-pyrazol-5-yl]methyl acetate (13b). Yield (85%);
m.p. 205–206ꢁC; IR: 1735 (OAc), 1630 (C¼¼N), and 1595
1
(C¼¼C); H-NMR (CDCl3): d ¼ 2.06 (s, 3H, OAc), 5.21 (s, 2H,
CH2), 7.40 (t, 1H, Ar-H), 7.43–7.52 (m, 3H, Ar-H), 7.55–7.68
(m, 6H, Ar-H), 7.72–7.73 (m, 2H, Ar-H), 7.84 (d, 1H, Ar-H),
anþd 8.23 (d, 1H, Ar-H); MS (m/z, %): 540 (41, Mþþ2), 497 (92,
M þ2-CH3CO), 417 (29, Mþ-Br-CH3CO), and 76 (100, C6Hþ4 );
Anal. Calcd for C27H19BrN6O2 (539.38): C, 60.12; H, 3.55; N,
15.58%. Found: C, 60.31; H, 3.75; N, 15.55%.
[4-Iodo-1-phenyl-3-(1-phenyl-[1,2,4]triazolo[4,3-a]quioxalin-
4-yl)-1H-pyrazol-5-yl]methyl acetate (11b). Yield (96%); m.p.
271–272ꢁC; IR: 1728 (OAc), 1620 (C¼¼N), and 1593 cmꢀ1
(C¼¼C); 1H-NMR (CDCl3): d ¼ 2.08 (s, 3H, OAc), 5.24 (s,
2H, CH2), 7.34–7.73 (m, 12H, Ar-H), 7.85 (d, 1H, Ar-H), and
8.24 (d, 1H, Ar-H); MS (m/z, %): 588 (8, Mþþ2), 587 (43,
Mþþ1), 460 (13, Mþ-I), and 417 (46, Mþ-I-CH3CO); Anal.
Calcd for C27H19IN6O2 (586.06): C, 55.30; H, 3.27; N,
14.33%. Found: C, 55.15; H, 3.18; N, 14.25%.
General procedure for the preparation of [4-halo-3-(3-
hydrazinylquinoxalin-2-yl)-1-phenyl-1H-pyrazol-5-yl]metha-
nol (12). A suspension of [4-halo-3-(3-chloroquioxalin-2-yl)-1-
phenyl-1H-pyrazol-5-yl]methyl acetate (9, 0.005 mol) in hy-
drazine hydrate (99%, 5 mL) was heated under reflux for 3 h.
The resulting product was filtered off, washed with methanol,
and dried. It was crystallized from ethanol to give the title
compound as golden yellow needles.
1
cmꢀ1 (C¼¼C); H-NMR (CDCl3): d 2.09 (s, 3H, OAc), 3.21 (s,
3H, CH3), 5.19 (s, 2H, CH2), 7.43–7.56 (m, 3H, Ar-H), 7.59–
7.66 (m, 4H, Ar-H), and 8.18–8.30 (m,2H, Ar-H); MS (m/z,
%): 524 (3, Mþ), 481 (3, Mþ-CH3CO), and 355 (100, Mþ-I-
CH3CO); Anal. Calcd for C22H17IN6O2 (524.31): C, 50.40; H,
3.27; N, 16.03%. Found: C, 50.26 H, 3.18; N, 15.91%.
General procedure for the preparation of [4-halo-3-(1-
methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-1-phenyl-1H-pyrazol-
5-yl]methanol (14). A solution of [4-halo-3-(1-methyl-[1,2,4]tria-
zolo[4,3-a]quinoxalin-4-yl)-1-phenyl-1H-pyrazol-5-yl]methyl ace-
tate (13, 0.002 mol) in methanolic ammonia (20 mL) was stirred
for 24 h at ambient temperature. The reaction mixture was con-
centrated under reduced pressure, and the solid that separated out
was filtered off, washed with ethanol, and crystallized from etha-
nol to give the title compound as colorless needles.
[4-Bromo-3-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-
1-phenyl-1H-pyrazol-5-yl]methanol (14a). Yield (90%); m.p.
241–242ꢁC; IR: 3340 (OH), 1640 (C¼¼N), and 1597 cmꢀ1
[4-Bromo-3-(3-hydrazinylquinoxalin-2-yl)-1-phenyl-1H-pyr-
azol-5-yl]methanol (12a). Yield (90%); m.p. 252–253ꢁC; IR:
3315 (OH), 3103,3051 (NH and NH2), 1633 (C¼¼N), and 1562
1
(C¼¼C); H-NMR (CDCl3): d ¼ 3.20 (s, 3H, CH3), 4.75 (s, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2011
Synthesis of 4-(1-Phenyl-1H-pyrazol-3-yl)-[1,2,
4]triazolo[4,3-a]quinoxalines and Their 4-Halogenopyrazolyl Analogs
1223
[2] Colotta, V.; Catarzi, D.; Varano, F.; Lenzi, O.; Filacchioni,
G.; Martini, C.; Trincavelli, L.; Ciampi, O.; Traini, C.; Pugliese, A. M.;
Pedata, F.; Morizzo, E.; Moro, S. Bioorg Med Chem 2008, 16, 6086.
[3] Lenzi, O.; Colotta, V.; Catarzi, D.; Varano, F.; Filacchioni,
G.; Martini, C.; Trincavelli, L.; Ciampi, O.; Varani, K.; Marighetti, F.;
Morizzo, E.; Moro, S. J Med Chem 2006, 49, 3916.
[4] Moro, S.; Deflorian, F.; Bacilieri, M.; Spalluto, G. Curr
Med Chem 2006, 13, 639.
CH2), 5.36–5.40 (m, 1H, OH, exchangeable), 7. 38–7.45 (m, 3H,
Ar-H), 7.66–7.78 (m, 4H, Ar-H), and 8.21–8.24 (m, 2H, Ar-H);
MS (m/z, %): 436 (41, Mþþ2), 434 (41, Mþ), and 355 (61, Mþ-
Br); Anal. Calcd for C20H15BrN6O (435.28): C, 55.19; H, 3.47;
N, 19.31%. Found: C, 55.12; H, 3.41; N, 19.29%.
[4-Iodo-3-(1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)-
1-phenyl-1H-pyrazol-5-yl]methanol (14b). Yield (89%);
m.p. 213–214ꢁC; IR: 3329 (OH), 1640 (C¼¼N), and 1593
cmꢀ1 (C¼¼C); 1H-NMR (DMSO-d6): d ¼ 3.11 (s, 3H, CH3),
4.59 (s, 2H, CH2), 5.54–5.56 (m, 1H, OH, exchangeable), 7.
47–7.50 (m, 3H, Ar-H), 7.57 (t, 2H, Ar-H), 7.65–7.80 (m, 4H,
Ar-H), 8.09–8.11 (d, þ1H, Ar-H), and 8.33 (d, 1H, Ar-H); MS
(m/z, %): 482 (36, M ), 356 (94, Mþ-I), and 76 (100, C6H4þ);
Anal. Calcd for C20H15IN6O (482.28): C, 49.81; H, 3.13; N,
17.43%. Found: C, 49.82; H, 3.21; N, 17.37%.
General procedure for the preparation of [3-([1,2,4]tria-
zolo[4,3-a]quinoxalin-4-yl)-4-halo-1-phenyl-1H-pyrazol-5-yl]methyl
formate (15). A solution of (4-halo-3-(3-hydrazinylquinoxalin-
2-yl)-1-phenyl-1H-pyrazol-5-yl)methanol (12, 0.002 mol) in
formic acid (10 mL) was heated under reflux for 10 h. The
reaction mixture was evaporated under reduced pressure, and
the residue was filtered off and washed repeatedly with etha-
nol. The product was crystallized from N,N-dimethylforma-
mide to give the title compound as coreless needles.
[5] Catarzi, D.; Colotta, V.; Varano, F.; Lenzi, O.; Filacchioni,
G.; Trincavelli, L.; Martini, C.; Montopoli, C.; Moro, S. J Med Chem
2005, 48, 7932.
[6] Gururaja, T.; Yung, S.; Ding, R.; Huang, J.; Zhou, X.;
McLaughlin, J.; Daniel-Issakani, S.; Singh, R.; Cooper, R. D. G.;
Payan, D. G.; Masuda, E. S.; Kinoshita, T. Chem Biol 2007, 14, 1105.
[7] Colotta, V.; Catarzi, D.; Varano, F.; Calabri, F. R.; Lenzi,
O.; Filacchioni, G.; Martini, C.; Trincavelli, L.; Deflorian, F.; Moro, S.
J Med Chem 2004, 47, 3580.
[8] Hirayama, N.; Kato, T. Jpn. Kokai Tokkyo Koho Heisei
Pat. 09328484 A 19971222 ( 1997). CAN 128:88932.
[9] Ikegami, H. Jpn. Kokai Tokkyo Koho Heisei. Pat.
2005314317 A 20051110 ( 2005).
[10] Benbow, J. W.; Chu-Moyer, M. Y.; Kung, D. W. U.S. Pat.
Appl. 2004192698 A1 20040930 ( 2004). CAN 141:314348.
[11] Matuszczak, B.; Pekala, E.; Mueller, C. E. Arch Pharm
1998, 331, 163.
[3-([1,2,4]Triazolo[4,3-a]quinoxalin-4-yl)-4-bromo-1-phenyl-
1H-pyrazol-5-yl]methyl formate (15a). Yield (75%); m.p.
299–300ꢁC; IR: 1718 (COO), 1640 (C¼¼N), and 1599 cmꢀ1
(C¼¼C); 1H-NMR (DMSO-d6): d ¼ 5.29 (s, 2H, CH2), 7.50–
7.67 (m, 4H, Ar-H), 7.74 (t, 1H, Ar-H), 7.80 (d, 1H, Ar-H), 7.
85 (t, 1H, Ar-H), 8.13 (d, 1H, Ar-H), 8.27 (s, 1H, formate-H),
8.47 (d, 1H, Ar-H), and 10.19 (s, 1H, triazole-H); MS (m/z,
%): 450 (34, Mþþ2), 448 (29, Mþ), 421 (34, Mþþ2-CHO),
419 (29, Mþ-CHO), 369 (33, Mþ-Br), 341 (17, Mþ-Br-CO),
324 (18, Mþ-Br-OOCH), and 76 (100, C6Hþ4 ); Anal. Calcd for
C20H13BrN6O2 (449.26): C, 53.47; H, 2.92; N, 18.71%. Found:
C, 53.39; H, 2.88; N, 18.58%.
[12] Holschbach, M. H.; Bier, D.; Wutz, W.; Sihver, W.; Schuel-
ler, M.; Olsson, R. A. Eur J Med Chem 2005, 40, 421.
[13] Ganapaty, S.; Ramalingam, P.; Babu Rao, C. H. J Pharm
Res 2007, 6, 10.
[14] Ikegami, H. Jpn. Kokai Tokkyo Koho Heisei. Pat. JP
2005314318 A 20051110 ( 2005). CAN 143:434113.
[15] Roy, K. Indian J Chem B 2003, 42, 1485.
[16] Matuszczak, B.; Mueller, C. E. PCT Int. WO Pat. Appl.
2003053973 A1 20030703 ( 2003). CAN 139:85384.
[17] Rashed, N.; Abdel Hamid, H.; El Ashry, E. S. H. Carbo-
hydr Res 1993, 243, 399.
[18] Mousaad, A.; Rashed, N.; Abdel Hamid, H.; El Kilany, Y.;
El Ashry, E. S. H. Carbohydr Res 1992, 225, 59.
[3-([1,2,4]Triazolo[4,3-a]quinoxalin-4-yl)-4-iodo-1-phenyl-
1H-pyrazol-5-yl]methyl formate (15b). Yield (73%); m.p.
279–280ꢁC; IR: 1718 (COO), 1640 (C¼¼N), and 1597 cmꢀ1
(C¼¼C); 1H-NMR (DMSO-d6): d ¼ 5.29 (s, 2H, CH2), 7.53–
7.64 (m, 4H, Ar-H), 7.70–7.80 (m, 2H, Ar-H), 7.84 (t, 1H, Ar-
H), 8.13 (d, 1H, Ar-H), 8.28 (s, 1H, formate-H), 8.47 (d, 1H,
Ar-H), and 10.19 (s, 1H, triazole-H); MS (m/z, %): 496 (81,
Mþ), 467 (27, Mþ-CHO), 370 (40, Mþ-I), 341 (32, Mþ-I-
CHO), 325 (35, Mþ-I-OOCH), and 76 (100, C6Hþ4 ); Anal.
Calcd for C20H13IN6O2 (496.01): C, 48.40; H, 2.64; N,
16.93%. Found: C, 48.28; H, 2.46; N, 16.78%.
[19] Atta, K. F.; El-Massry, A. M.; Abdel Hamid, H.; El Ashry,
E. S. H.; Amer, A. J Heterocycl Chem 1994, 31, 549.
[20] El Ashry, E. S. H.; El Kilany, Y.; Nahas, N. M. In Topics
in Heterocyclic Chemistry; El Ashry, E. S. H., Ed.; Springer: New
York; 2007; Vol. 7, pp 1–30.
[21] El Ashry, E. S. H.; Atta, K. F.; Abu-Elela, S.; Beldi, R. Jor-
dan J Chem 2007, 2, 117.
[22] El Ashry, E. S. H.; Atta, K. F.; Abu-Elela, S.; Beldi. R.
J Carbohydr Chem 2007, 26, 1.
[23] Amer, A.; El Massry, A. M.; Awad, L.; Rashed, N.; El
Ashry, E. S. H.; Ho, D. M. J Chem Soc Perkin I 1990, 2513.
[24] Mousaad, A.; Awad, L.; El Shimy, N.; El Ashry, E. S. H.
J Carbohydr Chem 1989, 8, 773.
REFERENCES AND NOTES
[25] Awad, L.; Mousaad, A.; El Ashry, E. S. H. J Carbohydr
Chem 1989, 8, 765.
[1] Morizzo, E.; Capelli, F.; Lenzi, O.; Catarzi, D.; Varano, F.;
Filacchioni, G.; Vincenzi, F.; Varani, K.; Borea, P. A.; Colotta, V.;
Moro, S. J Med Chem 2007, 50, 6596.
[26] El Kilany, Y.; Rashed, N.; Mansour, M.; Abdel Rahman,
M. M.; El Ashry, E. S. H. J Carbohydr Chem 1988, 7, 199.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet