Design and synthesis of some new pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]triazines, pyrazolo[3,4-d]pyridazines, and isoxazolo[3,4-d] pyridazines containing the pyrazole moiety

Article abstract of DOI:10.1080/00397911.2011.616639

Pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]triazines, [1,2,4]triazolo [4,3-a]pyrimidine, [1,2,4]triazolo[3,4-c][1,2,4]triazine, pyrazolo[3,4-d] pyridazines, and isoxazolo[3,4-d]pyridazines were prypared from 3-(3-(dimethylamino)acryloyl)-1-aryl-5-diphenyl-1H-pyrazole-5-carbonitrile with each of hydrazonoyl halides, hydroximoyl chlorides, heterocyclic amines, and diazotized heterocyclic amines. All the newly synthesized compounds were confirmed by elemental analyses, spectral data, and alternative synthetic routes whenever possible.

Full text of DOI:10.1080/00397911.2011.616639

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Design and Synthesis of Some
New Pyrazolo[1,5-a]pyrimidines,
Pyrazolo[5,1-c]triazines, Pyrazolo[3,4-
d]pyridazines, and Isoxazolo[3,4-
d]pyridazines Containing the Pyrazole
Moiety
Abdou O. Abdelhamid a , Abdelgawad A. Fahmi a & Karema N. M.
Halim a
a Department of Chemistry, Faculty of Science, Cairo University,
Giza, Egypt
Accepted author version posted online: 22 Feb 2012.Version of
record first published: 21 Feb 2013.
To cite this article: Abdou O. Abdelhamid , Abdelgawad A. Fahmi & Karema N. M. Halim (2013):
Design and Synthesis of Some New Pyrazolo[1,5-a]pyrimidines, Pyrazolo[5,1-c]triazines, Pyrazolo[3,4-
d]pyridazines, and Isoxazolo[3,4-d]pyridazines Containing the Pyrazole Moiety, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:8, 1101-1126
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Synthetic Communications1, 43: 1101–1126, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.616639
DESIGN AND SYNTHESIS OF SOME NEW
PYRAZOLO[1,5-a]PYRIMIDINES, PYRAZOLO
[5,1-c]TRIAZINES, PYRAZOLO[3,4-d]PYRIDAZINES,
AND ISOXAZOLO[3,4-d]PYRIDAZINES
CONTAINING THE PYRAZOLE MOIETY
Abdou O. Abdelhamid, Abdelgawad A. Fahmi, and
Karema N. M. Halim
Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
GRAPHICAL ABSTRACT
Abstract
Pyrazolo[1,5-a]pyrimidines,
pyrazolo[5,1-c]triazines,
[1,2,4]triazolo
[4,3-a]pyrimidine, [1,2,4]triazolo[3,4-c][1,2,4]triazine, pyrazolo[3,4-d]pyridazines,
and isoxazolo[3,4-d]pyridazines were prypared from 3-(3-(dimethylamino)acryloyl)-
1-aryl-5-diphenyl-1H-pyrazole-5-carbonitrile with each of hydrazonoyl halides, hydroxi-
moyl chlorides, heterocyclic amines, and diazotized heterocyclic amines. All the newly
synthesized compounds were confirmed by elemental analyses, spectral data, and alternative
synthetic routes whenever possible.
Keywords Isoxazolo[3,4-d]pyridazines; pyrazolo[1,5-a]pyrimidines; pyrazolo[3,4-d]pyri-
dazines; pyrazolo[5,1-c]triazines
INTRODUCTION
Some pyrazole derivatives possess biological and pharmacological activities[1–9]
and also find application in dyes.[10,11] Robins et al. reported that certain 3-substi-
tuted pyrazolo[1,5-a]pyrimidines inhibit the metabolism schistosomiasis in
snails.[12,13] Also, pyrazolopyrimidine systems are reported as inhibitors for the
synthesis of DNA and RNA in the cells of some types of cancer[14] and viruses.[15]
Received June 23, 2011.
Address correspondence to Abdou O. Abdelhamid, Department of Chemistry, Faculty of Science,
Cairo University, Giza 12613, Egypt. E-mail: Abdelhamid45@gmail.com
1101

1102
A. O. ABDELHAMID ET AL.
In addition, a large number of thiazole derivatives have been found to exhibit
pharmacological activity.[16–21] In view of this we become interested in the syn-
thesis of some new pyrazoles, pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]triazines,
pyrazolo[3,4-d]pyridazines, and isoxazolo[3,4-d]pyridazines. This work is an exten-
sion of an ongoing research program devoted to the synthesis and characteriza-
tion of different heterocyclic ring systems endowed with potential biological
activities.[22–28]
RESULTS AND DISCUSSION
Treatment of 3-((E)-3-(dimethylamino)acryloyl)-1,5-diphenyl-1H-pyrazole-
4-carbonitrile 1a with 3-amino-5-phenylpyrazole 2a in acetic acid containing
ammonium acetate by boiling under reflux gave 1,5-diphenyl-3-(2-phenylpyra-
zolo[1,5-a]pyrimidin-7-yl)-1H-pyrazole-4-carbonitrile 4a. The structure 4a was
established by elemental analysis, spectral data, and alternative synthesis [1H
NMR d ¼ 6.55 (s, 1H, pyrazole H-4), 7.26–7.80 (m, 12 H, ArH’s), 8.23 (d, 2H,
J ¼ 6 Hz), 8.34 (d, 2H, J ¼ 6 Hz), 9.29 (d, 1H)]. The formation of compound 4 is
assumed to take place via an initial Michael addition of the exocyclic amino group
in compound 2 to the activated double bond in 1a to give the acyclic nonisolable
intermediate 3, which undergoes cyclization and aromatization via loss of both
dimethylamine and water molecules, producing the final isolable product 4a.
Although the endocyclic imino group in compound 2a is the most nucleophilic
center, nevertheless, it is the most sterically hindered site,[29] as shown in Scheme 1.
Thus, treatment of N,N-dimethyl-N0-(3-phenyl-1H-pyrazol-5-yl)formamidine 6 with
3-acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile 7 in ethanol under reflux gives a
product identical in all aspects (mp, mixed mp, and spectra) with 4a (Scheme 1).
Analogously, 1a and 1b reacted with the appropriate aminopyrazoles 2b and c,
3-aminotraiazole, and 2-aminobenzimidazole to afford pyrazolo[1,5-a]pyrimidines
4b, 4c, 5a–c, [1,2,4]triazolo[4,3-a]pyrimidine 8a and 8b, and benzo[4,5]imidazo[1,2-
a]pyrimidine 9a and 9b, respectively.
On the other hand, treatment of 2 with diazotized 3-amino-5-phenylpyrazole 10a
in an ethanolic sodium acetate solution gave 1,5-diphenyl-3-(8-phenyl-pyrazolo[5,1-
c][1,2,4]triazine-3-carbonyl)-1H-pyrazole-4-carbonitrile 12a (Scheme 2). Structure
12a was elucidated by elemental analysis and spectral data. The formation of 12a
was formed via coupling diazonium chloride 10a to 2 to form the intermediate 11,
which converted to the final product 6 through elimination of dimethylamine.
Analogously, treatment of the appropriate diazonium salt 10a–c, triazole-3-
diazonium nitrate, or benzimidazole-2-diazonium sulfate with each of 2a and 2b in
ethanolic sodium acetate afforded pyrazolo[5,1-c][1,2,4]triazines 12b–g, [1,2,4]tria-
zolo[3,4-c][1,2,4]triazine 13a and b and benzo[4,5]imidazo[2,1-c][1,2,4]triazine 14a
and b, respectively (Scheme 2).
Also, treatment of 2a with benzenediazonium chloride in ethanol containing
a buffer solution yielded 3-[3-oxo-2-(phenyl-hydrazono)-
sodium acetate as
propionyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile 15a. Structure 15a was confirmed
by elemental analysis, spectral data, and chemical transformation. 1H NMR spectrum
of 15a showed signals at d ¼ 6.65–8.27 (m, 15 H, ArH’s), 9.98 (s, 1H, -CHO), and 14.39

DESIGN AND SYNTHESIS OF FUSED AZOLES
1103
Scheme 1. Pyrazolo[1,5-a]pyrimidines, triazolo[4,3-a]pyrimidine, and benzo[4,5]imidazo[1,2-a]pyrimidine
derivatives.
Scheme 2. Pyrazolo[5,1-c]triazine, triazolo[3,4-c]triazine, and benzo[4,5]imidazo[2,1-c]triazine derivatives.

1104
A. O. ABDELHAMID ET AL.
(s, br., 1H, NH). Thus, 15a was reacted with hydrazine hydrate in boiling ethanol
under reflux to give 1,5-diphenyl-40-(phenyl-hydrazono)-1H,40H-[3,30]bipyrazolyl-
4-carbonitrile 16a (Scheme 3). Also, 2a reacted with hydrazine hydrate to give
1,5-diphenyl-3-(1H-pyrazol-3-yl)-1H-pyrazole-4-carbonitrile 17a. Compound 17a
was reacted with benzenediazonium chloride in ethanolic sodium acetate solution to
afford a product identical in all respects (mp, mixed mp, and spectra) with 17a.
Treatment of C-ethoxycarbonyl-N-phenylhydrazonoyl chloride (18a) with 2a
and triethylamine in boiling benzene under reflux afforded ethyl 4-(4-cyano-
1,5-diphenyl-1H-pyrazole-3-carbonyl)-1-phenyl-1H-pyrazole-3-carboxylate
(22a)
1
(Scheme 4). H NMR spectrum of 22a showed signals at d ¼ 1.13 (t, 3H, J ¼ 7 Hz,
CH2CH3), 4.18 (q, 2H, J ¼ 7 Hz, CH2CH3), 7.44–7.88 (m, 15H, ArHs), and 8.44
(s, 1H, pyrazole H-5). Similarly, the appropriate hydrazonoyl halides 18a–e reacted
with each of 2a and 2b to give pyrazole derivatives 22b–e and 23a–e.
Compound 22a with hydrazine hydrate in boiling ethanol afforded one isolable
product according to thin-layer chromatography (TLC), formulated as 3-(7-oxo-
2-phenyl-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-4-yl)-1,5-diphenyl-1H- pyrazole-4-
carbonitrile (24a). Structure of 24a was elucidated by elemental analysis, spectral data,
1
and alternative synthesis. H NMR spectrum of 24a showed signals at d ¼ 7.23–8.41
(m, 15 H, ArHs), 8.52 (s, 1H, pyrazole H-5), and 12.12 (s, br., 1H, NH). Thus, treat-
ment of either 22a (or 22b) and 23a (or 23g) with boiling hydrazine hydrate in ethanol
gave a product identical in all aspects (mp, mixed mp, and spectra) with 24a and
25a, respectively.
Also, pyrazolo[3,4-d]pyridazines 24b,c,e and 25a–d were obtained from the
appropriate pyrazoles 22b,c,e and 23a–c,e with hydrazine hydrate (Scheme 4).
Treatment of the appropriate hydroximoyl chlorides 26a–e with each of 2a and
2b in toluene at room temperature in the presence of triethylamine (or boiling
without triethylamine) gave 4,5-diacylisoxazoles 27a–e and 28a–e, respectively.
Compounds 27a–e and 28a–e were converted to isoxazolo[3,4-d] pyridazines 29a–e
and 30a–e, respectively (Scheme 4).
Scheme 3. Pyrazoles 16 and 17.

DESIGN AND SYNTHESIS OF FUSED AZOLES
1105
Scheme 4. Pyrazolo[3,4-d]pyridazines and isoxazolo[3,4-d]pyrimidines.
EXPERIMENTAL
All melting points were determined on an electrothermal apparatus and are
uncorrected. Infrared (IR) spectra were recorded (KBr discs) on a Shimadzu Fourier
1
Transform (FT)–IR 8201 PC spectrophotometer. H NMR and 13C NMR spectra
were recorded in CDCl3 and (CD3)2SO solutions on a Varian Gemini 300-MHz spec-
trometer and chemical shifts are expressed in d units using tetramethylsilane (TMS)
as an internal reference. Elemental analyses were carried out at the Microanalytical
Center of the Cairo University.

1106
A. O. ABDELHAMID ET AL.
3-(3-(Dimethylamino)acryloyl)-1,5-diphenyl-1H-Pyrazole-4-
carbonitrile (1a) and 3-(3-(Dimethylamino)acryloyl)-5-phenyl-
1-p-Tolyl-1H-Pyrazole-4-carbonitrile (1b)
Equimolar amounts of each 3-acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile
and 3-acetyl-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile and dimethylformamide-
dimethylacetal (50 mmol each) were refluxed in dry xylene (40 mL) for 4 h. The hot
solution was evaporated to its half volume and then cooled. The resulting solid was
collected and crystallized to give 1a and 1b.
3-((E)-3-(Dimethylamino)acryloyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile
(1a). Pale brown crystals from EtOH, yield (81%), mp: 236–238 ꢀC; IR (KBr): 3059,
1
2952 (CH), 2228 (CN), 1641 (CO, conjugated), 1563 (C C); H NMR (CDCl3):
=
=
d ¼ 2.97 (s, 3H, CH3), 3.18 (s, 3H, CH3), 6.15 (d, 1H, J ¼ 12 Hz, CH CH),
7.27–7.42 (m, 10H, ArH’s), and 7.94 (d, 1H, J ¼ 12 Hz, CH CH); 13C NMR
=
(CDCl3): d ¼ 41.2 (NCH3), 88.1, 93.5, 117.6 (CN), 129.3, 129.5, 129.7, 129.8,
130.2, 130.3, 143.5, 143.6, 152.2, 159.4, 184.2; MS: m=z ¼ 344 (M þ 1, 1.9%), 343
(Mþ, 10.14%), 342 (M ꢁ 1, 34.88%), 326 (27.88%), 325 (100%), 300 (10.64%), 272
(21.53%), 103 (6.09), 94 (10.08%). Anal. calcd. for C21H18N4O (342.39): C, 73.67;
H, 5.30; N, 16.36. Found: C, 73.82; H, 5.15; N, 16.57%.
3-((E)-3-(Dimethylamino)acryloyl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-
carbonitrile (1b). Pale brown crystals from EtOH, yield (82%), mp: 224–226 ꢀC; IR
=
(KBr): 3060, 2952 (CH), 2225 (CN), 1639 (CO, conjugated), 1562 (C C), 1350
1
(CH3); H NMR [(CD3)2SO]: d ¼ 2.37 (s, 3H, CH3), 2.88 (s, 3H, CH3), 3. 17 (s,
=
3H, CH3), 5.80–5.84 (d, 1H, J ¼ 12 Hz, CH CH), 7.24–7.46 (m, 9H, ArH’s) and
7.81–7.85 (d, 1H, J ¼ 12 Hz, CH CH); 13C NMR [(CD3)2SO]: d ¼ 20.6 (CH3),
=
41.3 (NCH3), 88.3, 93.7, 117.2 (CN), 125.3, 129.2, 130.7, 132.3, 136.6, 137.5,
143.6, 152.2, 159.4, 184.4; MS: m=z ¼ 356 (Mþ, 100%), 314 (4.49%), 287 (32.91%),
257 (13.53%), 242 (7.68%), 230 (7.64), 178 (12.27%), 167 (4.29%), 163 (12.87%),
154 (21.45%), 141 (10.99%), 127 (13.00%), 114 (9.53%), 104 (10.46%), 98 (75.99%),
84 (21.27%), 76 (16.06%), 69 (49.94%), 65 (23.88%), 54 (50.74%). Anal. calcd. for
C22H20N4O (356.42): C, 74.14; H, 5.66; N, 15.72. Found: C, 74.25; H, 5.75; N,
15.92%.
Pyrazolo[1,5-a]pyrimidine 4a–c, 5a–c, 1,2,4-triazolo[4,3-a]pyrimidine
8a and b, and 4a-hydropyrimidino[1,2-a]benzimidazoles 9a and 9b
A mixture of the appropriate 3-amino-5-phenylpyrazole, 3-amino-4-phenylpyr-
azole, 3-amino-4-cyanopyrazole, 3-aminotriazole, or 2-aminobenzimidazole (5 mmol);
3-(3-(dimethylamino)acryloyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1a) or 3-(3-
(dimethylamino)acryloyl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile (1b) (5 mmol);
and ammonium acetate (0.37 g, 5 mmol) in acetic acid (20 mL) was refluxed for
4 h. The resulting solid that formed was collected and recrystallized from the
proper solvent to give 4a–c, 5a–c, 8a, 8b, 9a, and 9b, respectively.
1,5-Diphenyl-3-(2-phenylpyrazolo[1,5-a]pyrimidin-7-yl)-1H-pyrazole-4-
carbonitrile (4a). Pale yellow crystals from diluted AcOH, yield (87%), mp:
ꢀ
=
187–189 C; IR (KBr): 3043 (CH, aromatic), 2229 (CN), 1612 (C N), and 1585

DESIGN AND SYNTHESIS OF FUSED AZOLES
1107
1
(C C); H NMR (CDCl3): d ¼ 7.09–8.52 (m, 17H, ArH’s) and 9.11 (s, 1H, ArH); 13C
NMR (CDCl3): d ¼ 96.8 (pyrazole C-4), 102.2, 111.1, 121.6 (CN), 124.1, 127.5,
128.1, 128.6, 129.4, 129.5, 130.3, 130.4, 131.2, 131.3, 131.5, 133.6, 133.7, 141.2,
151.4, 152.6, 153.1, 155.6; MS: m=z ¼ 439 (M þ 1, 13.2%), 438 (Mþ, 19.5%), 307
(5.7%), 229 (9.2%), 219 (4.6%), 195 (5.7%), 165 (10.9), 151 (5.7%), 118 (5.2%), 104
(8%), 103 (6.9%), 102 (8.6%), 11 (9.8%), 91 (7.5%), 90 (6.9%), 89 (10.3%), 77
(100%), 63 (11.5%), and 51 (57.5%). Anal. calcd. for C28H18N6 (438.48): C, 79.76;
H, 4.18; N, 11.63. Found: C, 79.72; H, 4.22; N, 11.65%.
=
1,5-Diphenyl-3-(3-phenylpyrazolo[1,5-a]pyrimidin-7-yl)-1H-pyrazole-4-
carbonitrile (4b). Pale brown crystals from AcOH, yield (87%), mp: 202–204 ꢀC;
IR (KBr): 3043 (CH, aromatic), 2228 (CN), 1610 (C N) and 1587 (C C); 1H
NMR (CDCl3): d ¼ 7.09–8.41 (m, 17H, ArH’s) and 9.10 (s, 1H, ArH);13C NMR
(CDCl3): d ¼ 108.2, 108.1, 110.6, 122.1 (CN), 124.3, 126.1, 126.4, 128.2, 129.3,
129.4, 129.6, 130.2, 130.4, 131.3, 131.5, 133.5, 141.2, 148.4, 151.2, 153.3, 154.8 (pyra-
zole C-3); MS: m=z ¼ 439 (M þ 1, 13.2%), 438 (Mþ, 19.5%), 307 (5.7%), 229 (9.2%),
219 (4.6%), 195 (5.7%), 165 (10.9), 151 (5.7%), 118 (5.2%), 104 (8%), 103 (6.9%), 102
(8.6%), 11 (9.8%), 91 (7.5%), 90 (6.9%), 89 (10.3%), 77 (100%), 63 (11.5%), and 51
(57.5%). Anal. calcd. for C28H18N6 (438.48): C, 79.76; H, 4.18; N, 11.63. Found:
C, 79.72; H, 4.22; N, 11.65%.
=
=
7-(4-Cyano-1,5-diphenyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-
carbonitrile (4c). Pale cream crystals from EtOH, yield (86%), mp: 208–210 ꢀC; IR
1
=
=
(KBr): 3062 (CH, aromatic), 2227 (CN), 1613 (C N) and 1565 (C C); H NMR
(CDCl3): d ¼ 7.27–8.05 (m, 7H, ArH’s), 8.32 (m, 4H, ArH’s), 8.42 (s, 1H, pyrazole
H-5), 9.04 (s, 1H, pyrimidine H-4); 13C NMR (CDCl3): d ¼ 81.2, 102.1, 110.7,
112.1, 120.0 (CN), 122.2 (CN), 1233.8, 127.8, 129.2, 129.3, 130.2, 130.3, 131.1,
131.3, 131.4, 141.2, 151.4, 153.4, 156.4, 158.7 (pyrazole C-3); MS: m=z ¼ 389
(M þ 2, 5.3%), 388 (M þ 1, 16%), 387 (55%), 396 (M ꢁ 1, 100%), 385 (54%), 325
(5.3%), 213 (7.4%), 197 (6.4%), 178 (8.5%), 167 (10.6%), 150 (11.7%), 143 (10.6%),
142 (16%), 127 (9.6%), 124 (10.6%), 97 (10.6%), 77 (75.5%), 64 (12.8%). Anal. calcd.
for C23H13N7 (387.4): C, 71.31; H, 3.38; N, 25.31. Found: C, 71.12; H, 4.11; N,
25.55%.
5-Phenyl-3-(2-phenylpyrazolo[1,5-a]pyrimidin-7-yl)-1-p-tolyl-1H-pyrazole-
4-carbonitrile (4d). Pale cream crystals from diluted AcOH, yield (87.7%), mp:
ꢀ
=
194–196 C; IR (KBr): 3043 (CH, aromatic), 2226 (CN), 1622 (C N), and 1600
=
(C C); 1H NMR (CDCl3): d ¼ 2.36 (s, 3H, CH3), 6.41 (s, 1H, pyrazole H-4),
7.21–8.02 (m, 13H, ArH’s), 8.31 (d, 2H, J ¼ 8 Hz, ArH’s) and 9.11 (s, 1H, ArH);
13C NMR (CDCl3): d ¼ 19.8 (CH3), 97.2 (pyrazole c-4), 102.1, 110.8, 122.2 (CN),
124.2, 127.3, 128.2, 128.5, 130.3, 131.1, 131.2, 131.3, 131.4, 133.2, 136.3, 141.2,
151.2, 152.3, 153.1, 155.4; MS: m=z ¼ 454 (M þ 2, 5.9%), 452 (Mþ, 100%), 425
(34.1%), 218 (25.3%), 203 (15.9%), 193 (34.1%), (13%), 177 (13%), 166 (28.7%),
151 (7.5%), 142 (19.8%), 140 (23.9%), 127 (16.7%), 115 (46.7%), 103 (33%), 914
(50%), 89 (33.2%), 77 (35.1%), 65 (34%). Anal. calcd. for C29H20N6 (452.51): C,
76.97; H, 4.45; N, 18.57. Found: C, 77.10; H, 4.32; N, 18.65%.
5-Phenyl-3-(3-phenylpyrazolo[1,5-a]pyrimidin-7-yl)-1-p-tolyl-1H-pyrazole-
4-carbonitrile (4e). Dark yellow crystals from AcOH, yield (87%), mp: 202–204 ꢀC;

1108
A. O. ABDELHAMID ET AL.
1
=
=
IR (KBr): 3045 (CH, aromatic), 2225 (CN), 1625 (C N), and 1600 (C C); H
NMR (CDCl3): d ¼ 2.34 (s, 3H, CH3), 6.93 (d, 2H, J ¼ 8 Hz, ArH), 7.23–8.22 (m,
14H, ArH’s), and 9.11 (s, 1H, ArH); 13C NMR (CDCl3): d ¼ 20.1 (CH3), 102.1,
108.4, 110.7, 122.1 (CN), 124.4, 126.3, 126.4, 128.2, 129.5, 130.4, 131.2, 131.3,
131.4, 133.3, 136.5, 141.3, 148.2, 151.2, 153.6, 154.4 (pyrazolo C-3). Anal. calcd.
for C29H20N6 (452.51): C, 76.97; H, 4.45; N, 18.57. Found: C, 76.80; H, 4.12; N,
18.85%.
7-(4-Cyano-5-phenyl-1-p-tolyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-
3-carbonitrile (4f). Pale yellow crystals from EtOH, yield (86%), mp 238–240 ꢀC;
=
=
IR (KBr): 3136 (CH, aromatic), 2230 (CN), 1616 (C N), 1562 (C C) and 1323
1
(CH3); H NMR [(CD3)2SO]: d ¼ 2.36 (s, 3H, CH3), 7.23–8.42 (m, 11H, ArH’s),
and 9.51 (s, 1H, ArH); 13C NMR [(CD3)2SO]: d ¼ 20.4 (CH3), 81.5, 102.4, 111.1,
112.4 (CN), 122.2 (CN), 124.5, 128.3, 129.5, 130.3, 1311.2, 131.4, 131.8, 136.3,
141.2, 151, 153.1, 156.3, 158.5 (pyrazole C-3); MS: m=z ¼ 401 (Mþ, 100%), 373
(2.5%), 228 (4.5%), 202 (9.6%), 192 (13.6%), 139 (4.6%), 104 (4.4%), 101 (7.1%),
90 (37.4), 77 (15.1%), 64 (33.4). Anal. calcd. for C24H15N7 (401.42): C, 71.81; H,
3.77; N, 24.42. Found: C, 71.85; H, 3.52; N, 24.65%.
3-([1,2,4]Triazolo[1,5-a]pyrimidin-7-yl)-1,5-diphenyl-1H-pyrazole-4-
carbonitrile (8a). Yellow crystals from diluted AcOH, yield (85%), mp:
ꢀ
=
295–297 C; IR (KBr): 3062 (CH, aromatic), 2225 (CN), 1623 (C N) and 1586
1
=
(C C); H NMR [(CD3)2SO]: d ¼ 7.27–8.02 (m, 7H, ArH’s), 8.29 (s, 1H, triazole
H-3), 9.72 (d, 1H, J ¼ 4 Hz, pyrimidine H-4); 13C NMR [(CD3)2SO]: d ¼ 102.1 (pyra-
zole C-4), 110.2, 117.8 (CN), 124.4, 128.5, 129.8, 129.9, 130.2, 130.7, 131.2, 134.4,
136.8, 141.1, 145.2 (triazole C-5), 149.3, 151.2, 157.8; MS: m=z ¼ 389 (M þ 2,
5.3%), 388 (M þ 1, 16%), 387 (55%), 396 (M ꢁ 1, 100%), 385 (54%), 325 (5.3%),
213 (7.4%), 197 (6.4%), 178 (8.5%), 167 (10.6%), 150 (11.7%), 143 (10.6%), 142
(16%), 127 (9.6%), 124 (10.6%), 97 (10.6%), 77 (75.5%), 64 (12.8%). Anal. calcd.
for C21H13N7(387.4): C, 69.41; H, 3.61; N, 26.98. Found: C, 69.42; H, 3.72; N,
26.75%.
3-([1,2,4]Triazolo[4,3-a]pyrimidin-5-yl)-5-phenyl-1-p-tolyl-1H-pyrazole-
4-carbonitrile (8b). Colorless crystals from diluted AcOH, yield (85%), mp
ꢀ
=
264–266 C; IR (KBr): 3085 (CH, aromatic), 2233 (CN), 1658 (C N) and 1589
1
=
(C C); H NMR [(CD3)2SO]: d ¼ 2.28 (s, 3H, CH3), 7.27–7.30 (m, 3H, ArH’s),
7.67–7.73 (m, 3H, ArH’s), 7.87 (d, 2H, J ¼ 8 Hz, ArH,s), 8.312 (d, 2H, J ¼ 8 Hz),
9.39 (s, 1H, ArH), 9.72 (s, 1H, ArH); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3),
101.2, 111.1, 117.8 (CN), 124.4, 128.4, 128.4, 129.5, 130.2, 131.3, 131.9, 143.5,
136.9, 141.2, 145.4 (triazole C-5), 149.2, 151.5, 158.2; MS: m=z ¼ 387 (M þ 1,
12.2%), 377 (Mþ, 100%), 301 (12.7%), 287 (14.30%), 257 (4.9%), 165 (7%), 149
(11.9), 146 (11.5%), 127 (7.2%), 114 (12.5%), 92 (17.5%), 79 (10.4%), 78 (9.1%), 77
(76.5%), 68 (19.8%), 65 (100%). Anal. calcd. for C22H15N7(377.4): C, 70.01; H,
4.01; N, 25.98. Found: C, 69.85; H, 3.92; N, 26.10%.
3-Benzo[4,5]imidazo[1,2-a]pyrimidin-4-yl-1,5-diphenyl-1H-pyrazole-4-
carbonitrile (9a). Yellow crystals from dioxane, yield (86.9%), mp >300 ꢀC; IR
1
(KBr): 3085 (CH, aromatic), 2230 (CN), 1658 (C N) and 1589 (C C); H NMR
=
=
[(CD3)2SO]: d ¼ 7.27–7.50 (m, 6H, ArH’s), 7.67 (d, 2H, J ¼ 8 Hz, ArH’s), 7.87–8.12

DESIGN AND SYNTHESIS OF FUSED AZOLES
1109
(m, 5H, ArH’s), 8.31 (d, 2H, J ¼ 8 Hz, ArH’s), 9.39 (s, 1H, ArH); 13C NMR
[(CD3)2SO]: d ¼ 101.8, 110.9, 115.2, 117.2 (CN), 119.5, 122.2, 124.3, 124.5, 128.6,
129.2, 129.5, 130.3, 130.5, 137.1, 137.4, 141.2, 147.4, 149.3, 155.8, 158.2; MS: m=
z ¼ 413 (M þ 1, 2.2%), 412 (Mþ, 0.9%), 319 (2.5%), 244 (11.45%), 180 (24.99%),
141 (10.40%), 114 (11.06), 103 (11.7%), 91 (10.5%), 90 (18.65%), 77 (100%), 65
(8.9%), 64 (11.28%). Anal. calcd. for C26H16N6(412.45): C, 75.71; H, 3.91; N,
20.38. Found: C, 75.85; H, 3.90; N, 20.10%.
3-Benzo[4,5]imidazo[1,2-a]pyrimidin-4-yl-5-phenyl-1-p-tolyl-1H-pyrazole-
4-carbonitrile (9b). Pale yellow crystals from diluted dimethylformamide (DMF),
yield (87%), mp 276–278 ꢀC; IR (KBr): 3085 (CH, aromatic), 2230 (CN), 1658
1
=
=
(C N) and 1589 (C C); H NMR [(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 7.21–7.32
(m, 5H, ArH’s), 7.67–7.83 (m, 6H, ArH’s), 8.10 (d, 1H, J ¼ 8 Hz, ArH,s), 8.31 (d,
2H, J ¼ 8 Hz), 9.35 (s, 1H, ArH); 13C NMR [(CD3)2SO]: d ¼ 20.8 (CH3), 101.9,
110.3, 115.2, 117.6 (CN), 119.1, 122.4, 124.6, 124.7, 128.4, 129.4, 132.5, 137.4,
141.3, 147.2, 149.4, 155.2, 157.8; MS: m=z ¼ 427 (M þ 1, 1.31%), 301 (26.56%), 286
(34.66%), 244 (6.91%), 194 (19.5%), 165 (8.53%), 140 (10.6), 127 (10.35%), 114
(15.09%), 104 (25.53%), 103 (32.85%), 91 (100%), 89 (49.53%), 77 (96.06%), 65
(83.80%), 63 (40.89%). Anal. calcd. for C27H18N6(426.47): C, 76.04; H, 4.25; N,
19.71. Found: C, 76.15; H, 3.95; N, 19.55%.
(Pyrazolo[5,1-c][1,2,4]triazin-3-yl)methanone 12a–e,
([1,2,4]Triazolo[3,4-c][1,2,4]triazin-6-yl)(1H-pyrazol-3-yl)methanone
13a and b, Benzo[4,5]imidazo[2,1-c][1,2,4]triazin-3-yl-(1H-pyrazol-
3-yl)-methanone 14a and b, 1H-Pyrazol-3-yl)-4H-pyrazol-4-
ylidene)hydrazine 16, and 3-(1H-Pyrazol-3-yl)-1H-pyrazole 17
A solution of the appropriate diazonium salt of heterocyclic amines
[(3-amino-5-phenylpyrazole (3a), 3-amino-4-phenylpyrazole (3b), 3-amino-4-cyano-
pyrazole (3c), 3-amino-1,2,4-triazole (3d), and 2-amino-benzimidazole (3e)] (5 mmol)
was added to a mixture of sodium salt of 5-hydroxy-1-naphtho[2,1-b]furan-2-
ylpropenone (2) (5 mmol), sodium acetate (0.65 g, 5 mmol) in ethanol (30 mL) at
0–5 ꢀC while stirring. The resulting solid that formed after 3 h was collected, washed
with water, and recrystallized to give 12a–c, 13a–c, 14a, 14b, 16, and 17, respectively
1,5-Diphenyl-3-(7-phenyl-pyrazolo[5,1-c][1,2,4]triazine-4-carbonyl)-1H-
pyrazole-4-carbonitrile (12a). Brown crystals from EtOH, yield (93%), mp:
ꢀ
=
214–216 C; IR (KBr): 3057 (CH, aromatic), 2227 (CN), 1642 (C O) and 1567
(C C); 1H NMR (CDCl3): d ¼ 6.67 (s, 1H, pyrazole H-4), 7.27–8.05 (m, 13H,
=
ArH’s), 8.42 (d, 2H, J ¼ 8 Hz, ArH’s), 9.72 (d, 1H, J ¼ 8 Hz, ArH); 13C NMR
(CDCl3): d ¼ 88.1, 103.2, 117.6 (CN), 125.6, 126.8, 129.1, 129.2, 129.4, 131.3,
131.7, 133.4, 138.8, 143.2, 145.2, 151.7, 152.4, 153.2, 153.5, 181.2 (CO); MS:
m=z ¼ 467 (Mþ, 5.3%), 439 (6.0%), 296 (4.27%), 272 (27.45.3%), 244 (5.4%), 216
(16.4%), 180 (15.5%), 141 (70.6%), 101 (19.7%), 88 (28.6%), 76 (56%). Anal. calcd.
for C28H17N7O (467.48): 71.94; H, 3.67; N, 20.97. Found: C, 72.12; H, 3.78; N,
20.85%.

1110
A. O. ABDELHAMID ET AL.
1,5-Diphenyl-3-(8-phenyl-pyrazolo[5,1-c][1,2,4]triazine-4-carbonyl)-1H-
pyrazole-4-carbonitrile (12b). Dark brown from EtOH, yield (93%), mp:
ꢀ
=
242–244 C; IR (KBr): 3058 (CH, aromatic), 2233 (CN), 1654 (C O) and 1596
1
=
(C C); H NMR (CDCl3): 7.27–8.05 (m, 13H, ArH’s), 8.42 (d, 3H, J ¼ 8 Hz, ArH’s),
9.72 (d, 1H, J ¼ 8 Hz, ArH); 13C NMR (CDCl3): d ¼ 103.0, 118.1 (CN), 128.1, 128.3,
129.2, 129.4, 129. 6, 131.6, 134.3, 139.2, 143.2, 145.4, 151.2, 152.3, 153.4, 154.6, 181.2
(CO); MS: m=z ¼ 467 (Mþ, 100%), 439 (5.99%), 272 (27.54%), 269 (15.27%), 244
(5.26%), 223 (10.69%), 216 (16.05%), 190 (15.65%), 177 (5.26%), 152 (10.16%), 141
(70.53%), 127 (8.87%), 104 (7.10%), 101 (19.66%), 88 (29.90%). Anal. calcd. for
C28H17N7O (467.48): C, 71.94; H, 3.67; N, 20.97. Found: C, 72.12; H, 3.78; N,
20.85%.
4-(4-Cyano-1,5-diphenyl-1H-pyrazole-3-carbonyl)-pyrazolo[5,1-c][1,2,4]
triazine-8-carbonitrile (12c). Yellowish green crystals from diluted AcOH, yield
ꢀ
=
(95%), mp: 218–220 C; IR (KBr): 3070 (CH, aromatic), 2237 (CN), 1664 (C O)
and 1596 (C C); 1H NMR (CDCl3): 7.27–8.05 (m, 7H, ArH’s), 8.22 (d, 2H,
=
J ¼ 8 Hz, ArH’s), 8.42 (d, 2H, J ¼ 8 Hz, ArH’s), 9.72 (d, 1H, J ¼ 8 Hz, ArH); 13C
NMR (CDCl3): d ¼ 88.2, 98.2, 117.3 (CN), 122.1 (CN), 129.1, 129.2, 129.5, 129.7,
129.9, 131.2, 131.6, 136.2, 143.1, 145.3, 151.2, 151.4, 152.3, 180.9 (CO); MS: m=
z ¼ 400 (0.86%), 325 (19.85%), 315 (4.73%), 287 (7.33%), 272 (12.09%), 245
(11.33%), 180 (11.35%), 167 (14.75%), 149 (32.74%), 141 (5.92%), 114 (6.96%), 98
(33.98%), 78 (10.88%), 77 (100%), 70 (69.51%), 65 (21.48%). Anal. calcd. for
C23H12N8O (416.39): C, 66.34; H, 2.90; N, 26.91. Found: C, 66.12; H, 2.78; N,
26.65%.
5-Phenyl-3-(7-phenyl-pyrazolo[5,1-c][1,2,4]triazine-4-carbonyl)-1-p-tolyl-
1H-pyraꢀzole-4-carbonitrile (12d). Brown crystals from EtOH, yield (93%), mp:
=
198–200 C; IR (KBr): 3055 (CH, aromatic), 2233 (CN), 1684 (C O) and 1595
1
(C C), 1350 (CH3); H NMR [(CD3)2SO]: 2.37 (s, 3H, CH3), 7.17–7.81 (m, 10H,
=
ArH’s), 8.16 (d, 2H, J ¼ 8 Hz, ArH’s), 8.42 (d, 2H, J ¼ 8 Hz, ArH’s), 9.02 (s, 1H,
ArH), 9.85 (s, 1H, ArH); 13C NMR (CDCl3): d ¼ 20.1 (CH3), 87.9, 103.2, 117.6
(CN), 125.2, 125.4, 126.2, 129.4, 129.7, 130.9, 131.6, 132.3, 133.8, 136.7, 137.5,
139.4, 145.4, 151.2, 152.4, 153.1, 153.4 (pyrazole C-4), 181.2 (CO). Anal. calcd. for
C29H19N7O (481.51): C, 72.34; H, 3.98; N, 20.36. Found: C, 72.12; H, 3.78; N,
20.55%.
5-Phenyl-3-(7-phenyl-pyrazolo[5,1-c][1,2,4]triazine-3-carbonyl)-1-p-tolyl-
1H-pyrazole-4-carbonitrile (12e). Pale brown crystals from EtOH, yield (93%),
mp 262–264 ꢀC; IR (KBr): 3055 (CH, aromatic), 2237 (CN), 1658 (CO), 1608
1
=
=
(C N) and 1595 (C C), 1350 (CH3); H NMR [(CD3)2SO]: 2.36 (s, 3H, CH3),
7.12–7.79 (m, 10H, ArH’s), 8.16 (d, 2H, J ¼ 8 Hz, ArH’s), 8.42 (d, 2H, J ¼ 8 Hz,
ArH’s), 9.02 (s, 1H, ArH), 9.85 (s, 1H, ArH); 13C NMR (CDCl3): d ¼ 20.0 (CH3),
88.2, 101.2 (pyrszole C-3), 117.6 (CN), 125.3, 128.4, 129.3, 129.6, 130.4, 131.2,
132.5, 134.5, 136.6, 137.82, 139.4, 145.5, 151.2, 152.4, 153.3, 154.6, 181.1 (CO);
MS: m=z ¼ 482 (M þ 1, 30.7%), 481 (100%), 480 (M ꢁ 1, 87.2%), 286 (28.4%), 285
(17.6%), 223 (16.8%), 194 (11.2%), 155 (13.9%), 142 (12.2%), 140 (13.0%), 128
(12.6%), 115 (18.7%), 114 (12.5%), 102 (20.2%), 91 (30.0%), 89 (14.8%), 77

DESIGN AND SYNTHESIS OF FUSED AZOLES
1111
(24.6%), 65 (33.2%). Anal. calcd. for C29H19N7O (481.51): C, 72.34; H, 3.98; N,
20.36. Found: C, 72.25; H, 3.74; N, 20.47%.
4-(4-Cyano-5-phenyl-1-p-tolyl-1H-pyrazole-3-carbonyl)-pyrazolo[5,1-c]
[1,2,4]-triazine-8-carbonitrile (12f). Yellow crystals from EtOH, yield (95%), mp
ꢀ
=
204–206 C; IR (KBr): 3070 (CH, aromatic), 2237 (CN), 1664 (C O) and 1596
1
(C C); H NMR (CDCl3): 2.41 (s, 3H, CH3), 7.27–7.34 (m, 3H, ArH’s), 7.70–7.82
=
(m, 2H, ArH’s), 8.22–8.45 (m, 2H, ArH’s), 8.72 (s, 1H, ArH), 8.85 (d, 2H, J ¼ 8 Hz,
Hz, ArH), 10.82 (s, 1H, ArH); 13C NMR: 20.2 (CH3), 88.1, 97.9 (pyrazole C-3),
117.6 (CN), 120.4 (CN), 125.4, 129.4, 129.6, 132.2, 137.1, 137.4, 145.2, 151.4,
151.5, 152.2, 181.2 (CO); MS: m=z ¼ 343 (100%), 328 (3.59%), 310 (11.35%), 272
(49.42%), 243 (12.66%), 230 (6.17%), 179 (24.96%), 171 (8.66%), 156 (32.74%), 141
(18.54%), 127 (6.43%), 114 (11.13%), 97 (61.14%), 84 (13.72%), 77 (45.49%), 64
(32.52%), 54 (37.17%), 51 (17.77). Anal. calcd. for C24H14N8O (430.42): C, 66.97;
H, 3.28; N, 26.03. Found: C, 67.12; H, 3.18; N, 26.25%.
1,5-Diphenyl-3-([1,2,4]triazolo[3,4-c][1,2,4]triazine-5-carbonyl)-1H-
pyrazole-4-carbonitrile (13a). Yellowish green crystals from diluted AcOH, yield
ꢀ
=
(92%), mp: 192–194 C; IR (KBr): 3062 (CH, aromatic), 2233 (CN), 1659 (C O),
1
and 1593 (C C); H NMR [(CD3)2SO]: 7.27–7.7.64 (m, 6H, ArH’s), 7.95 (d, 2H,
=
J ¼ 8 Hz, ArH’s), 8.45 (s, 1H, ArH), 8.65 (d, 2H, J ¼ 8 Hz, ArH), 9.82 (s, 1H,
ArH); 13C NMR: 87.9, 117.6 (CN), 129.2, 129.3, 129.6, 129.9, 13.2, 131.5, 139.5 (tria-
zole C-5), 143.4, 144.5, 145.5, 150.8, 152.2, 156.3, 178.4 (CO); MS: m=z ¼ 365 (M-N2,
1.91%), 287 (4.19%), 272 (13.07%), 259 (6.15%), 245 (27.15%), 149 (10.50%), 104
(28.20%), 104 (40.23%), 91 (37.09%), 77 (100%), 65 48.24%), 50 (79.19%). Anal.
calcd. for C21H12N8O (392.11): C, 64.28; H, 3.08; N, 28.56. Found: C, 64.15; H,
3.28; N, 28.69%.
5-Phenyl-1-p-tolyl-3-([1,2,4]triazolo[3,4-c][1,2,4]triazine-5-carbonyl)-1H-
pyrazole-4-carbonitrile (13b). Yellowish green crystals from diluted AcOH, yield
ꢀ
=
(92.5%), mp 250–252 C; IR (KBr): 3062 (CH, aromatic), 2237 (CN), 1660 (C O),
1
1635 (C N), and 1380 (CH3); H NMR [(CD3)2SO]: 2.41 (s, 3H, CH3), 7.27–7.34
=
(m, 3H, ArH’s), 7.70–7.79 (m, 2H, ArH’s), 8.20–8.28 (m, 2H, ArH’s), 8.45 (s, 1H,
ArH), 8.65 (d, 2H, J ¼ 8 Hz, ArH), 9.82 (s, 1H, ArH); 13C NMR: 20.1 (CH3),
87.9, 117.6 (CN), 125.4, 129.4, 129.6, 130.4, 132.3, 136.7, 137.6, 139.4 (triazole
C-5), 144.4, 145.6, 156.4, 178.4 (CO); MS: m=z ¼ 407 (M þ 1, 2.03%), 406 (Mþ,
10.86%), 258 (12.49%), 243 (10.71%), 230 (4.33%), 215 (4.65%), 180 (8.12%), 147
(28.20%), 119 (39.48%), 103 (47.27%), 92 (12.73%), 91 (50.10%), 97 (4.32%), 74
(12.80%), 67 (10.61%), 64 (100%), 54 (7.65%), 54 (13.95), 53 (60.06%), 50
(62.87%). Anal. calcd. for C22H14N8O (406.4): C, 65.02; H, 3.47; N, 27.57.03. Found:
C, 65.12; H, 3.68; N, 27.75%.
3-(Benzo[4,5]imidazo[2,1-c][1,2,4]triazine-4-carbonyl)-1,5-diphenyl-1H-
pyrazole-4-carbonitrile (14a). Pale cream crystals from diluted AcOH, yield
ꢀ
=
(92.8%), mp >300 C; IR (KBr): 3062 (CH, aromatic), 2233 (CN), 1654 (C O), and
1
1593 (C C); H NMR [(CD3)2SO]: 7.27–7.85 (m, 8H, ArH’s), 8.15–8.35 (m, 2H,
=
ArH’s), 8.42–8.65 (m, 2H, ArH’s), 8.65 (d, 1H, J ¼ 8 Hz, ArH), 8.65 (d, 1H, J ¼ 8 Hz,
Hz, ArH), 9.27 (s, 1H, ArH); 13C NMR: 87.9, 113.2, 117.5 (CN), 118.5, 124.4, 124.5,
129.3, 129.6, 129.7, 129.9, 130.7, 131.3, 131.6, 143.3, 144.2, 144.4, 146.3, 148.2, 152.3,

1112
A. O. ABDELHAMID ET AL.
155.4, 178.8 (CO); MS: m=z ¼ 413 (M-N2, 0.67%), 342 (3.75%), 326 (12.87%), 259
(5.15%), 167 (8.25%), 149 (32.21%), 141 (5.69%), 114 (4.76%), 98 (67.07%), 81
(42.17%), 79 (23.02%), 77 (97.19%), 69 (48.95%). Anal. calcd. for C26H15N7O
(441.44): C, 70.74; H, 3.42; N, 22.21. Found: C, C, 70.87 H, 3.25; N, 22.00%.
3-(Benzo[4,5]imidazo[2,1-c][1,2,4]triazine-4-carbonyl)-5-phenyl-1-p-tolyl-
1H-pyrazole-4-carbonitrile (14b). Pale cream crystals from diluted AcOH, yield
ꢀ
=
(93%), mp 194–196 C; IR (KBr): 3047 (CH, aromatic), 2233 (CN), 1654 (C O),
=
1624 (C N), and 1380 (CH3); 1H NMR [(CD3)2SO]: d ¼ 2.38 (s, 3H, CH3),
7.27–7.75 (m, 7H, ArH’s), 8.10–7.14 (m, 2H, ArH’s), 8.20–8.23 (m, 2H, ArH’s),
8.65 (d, 1H, J ¼ 8 Hz, ArH), 8.72 (d, 1H, J ¼ 8 Hz, ArH), 9.18 (s, 1H, ArH); 13C
NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 88.1, 113.2, 117.5 (CN), 118.2, 124.3, 124.5,
129.2, 129.4, 129.8, 130.7, 132.2, 136.7, 137.6, 144.6, 144.7, 145.9, 148.4, 152.2,
179.1 (CO); MS: m=z ¼ 456 (Mþ, 011%), 356 (16.17%), 340 (60.78%), 301
(12.09%), 286 (20.97%), 273 (12.06%), 258 (28.36%), 243 (15.36%), 231 (6.74%),
215 (8.34%), 194 (21.76%), 165 (7.91%), 152 (14.87%), 140 (18.92%), 127 (31.24%),
114 (26.17%), 100 (13.79%), 98 (88.09%), 91 (73.86%), 88 (31.33%), 76 (72.94%),
69 (49.98%), 54 (100%), 50 (40.1%). Anal. calcd. for C27H17N7O (455.47): C,
71.20; H, 3.76; N, 21.53. Found: C, 71.00; H, 3.57; N, 21.35%.
3-[3-Oxo-2-(phenylhydrazono)propanoyl]-1,5-diphenyl-1H-pyrazole-4-
carbonitrile (15a). Yellow crystals from diluted AcOH, yield (96%), mp
210–212 ꢀC; IR (KBr): 3047 (CH), 2870, 2785 (CH, Fermi resonance), 2229 (CN),
1640 (CO), 1562 (C C), and 1380 (CH3); 1H NMR [(CD3)2SO]: 6.89–8.51 (m,
=
15H, ArH’s), 9.75 (s, 1H, CHO), 14.89 (s, br., 1H, NH); MS: m=z ¼ 420 (M þ 1,
0.1%), 343 (20.36%), 326 (56.41%), 259 (6.68%), 152 (6.50%), 140 (8.22%), 103
(6.69%), 98 (67.48%), 81 (18.55%), 77 (54.37%), 70 (33.26%), 68 (18.02%), 54
(100%). Anal. calcd. for C25H17N5O2 (419.43): C, 71.59; H, 4.09; N, 16.70. Found:
C, 71.65; H, 4.18; N, 16.85%.
3-[3-Oxo-2-(p-tolylhydrazono)propanoyl]-1,5-diphenyl-1H-pyrazole-4-
carbonitrile (15b). Brown crystals from EtOH, yield (96%), mp 220–222 ꢀC; IR
(KBr): 3047 (CH), 2816, 2765 (CH, Fermi resonance), 2229 (CN), 1640 (CO),
1562 (C C), and 1353 (CH3); 1H NMR [(CD3)2SO]: 2.32 (s, 3H, CH3C6H4),
=
7.26–8.34 (m, 14H, ArH’s), 9.75 (s, 1H, CHO), 14.89 (s, br., 1H, NH); MS:
m=z ¼ 433 (Mþ, 0.07%), 343 (28.50%), 329 (12.17%), 325 (75.95%), 272 (10.49%),
259 (13.02%), 141 (13.77%), 98 (48.05%), 77 (54.48%), 69 (49.42%), 54 (100%). Anal.
calcd. for C26H19N5O2 (433.46): C, 72.04; H, 4.42; N, 16.16. Found: C, 72.13; H,
4.57; N, 16.34%.
3-[3-Oxo-2-(phenylhydrazono)propanoyl]-1-p-tolyl-5-phenyl-1H-pyrazole-
4-carbonitrile (15c). Brown crystals from EtOH, yield (96%), mp: 212–214 ꢀC; IR
(KBr): 3047 (CH), 2804, 2754 (CH, Fermi resonance), 2225 (CN), 1640 (CO), 1566
1
=
(C C), and 1350 (CH3); H NMR [(CD3)2SO]: 2.38 (s, 3H, CH3C6H4), 7.26–8.34 (m,
14H, ArH’s), 9.75 (s, 1H, CHO), 14.89 (s, br., 1H, NH); MS: m=z ¼ 433 (Mþ,
0.19%), 357 (37.80%), 340 (100%), 287 (11.33%), 98 (32.91%), 91 (12.94%), 77
(5.99%), 69 (24.96%), 65 (12.46%), 55 (31.15%). Anal. calcd. for C26H19N5O2
(433.46): C, 72.04; H, 4.42; N, 16.16. Found: C, 72.08; H, 4.48; N, 16.38%.

DESIGN AND SYNTHESIS OF FUSED AZOLES
1113
3-[3-Oxo-2-(p-tolylhydrazono)propanoyl]-1-p-tolyl-5-phenyl-1H-pyrazole-
4-carbonitrile (15d). Red crystals from EtOH, yield (96%), mp: 202–204 ꢀC; IR
(KBr): 3047 (CH), 2804, 2754 (CH, Fermi resonance), 2230 (CN), 1640 (CO),
1
1566 (C C), and 1353 (CH3); H NMR [(CD3)2SO]: 2.38 (s, 3H, CH3C6H4), 2.40
=
(s, 3H, CH3C6H4), 7.26–8.34 (m, 13H, ArH’s), 9.75 (s, 1H, CHO), 14.89 (s, br.,
1H, NH); MS: m=z ¼ 447 (Mþ, 0.19%), 357 (37.55%), 340 (100%), 287 (10.04%),
273(9.52%), 98 (43.41%), 91 (14.61%), 84 (9.05%), 81 (9.44%), 76 (7.85%), 69
(32.50%), 65 (13.71%), 54 (45.10%). Anal. calcd. for C27H21N5O2 (447.49): C,
72.47; H, 4.73; N, 15.65. Found: C, 72.52; H, 4.94; N, 15.72%.
Synthesis of Pyrazoles 17a and b
A mixture of the appropriate 1a and 1b (5 mmol) and hydrazine hydrate
(0.5 mL, 10 mmol) in ethanol (15 mL) was refluxed for 2 h. The resulting solid was
collected and recrystallized from ethanol to give 17a and 17b.
1,5-Diphenyl-3-(4H-pyrazol-3-yl)-1H-pyrazole-4-carbonitrile
(17a). Brown crystals from EtOH, yield (81%), mp 236–238 ꢀC; IR (KBr): 3047
1
(CH), 2230 (CN), 1640 (CO), 1566 (C C), and 1353 (CH3); H NMR [(CD3)2SO]:
=
6.45 (s, 1H, pyrazple H-4), 7.26–8.33 (m, 11H, ArH’s and pyrazole H-5), 11.89 (s,
br., 1H, NH). Anal. calcd. for C19H13N5 (311.34): C, 73.30; H, 4.21; N, 22.49.
Found: C, 73.45; H, 4.33; N, 22.4962%.
5-Phenyl-3-(4H-pyrazol-3-yl)-1-p-tolyl-1H-pyrazole-4-carbonitrile
(17b). Colorless crystals from EtOH, yield (80%), mp 278–280 ꢀC; IR (KBr): 3047
=
(CH), 2804, 2754 (CH, Fermi resonance), 2230 (CN), 1640 (CO), 1566 (C C), and
1
1353 (CH3); H NMR [(CD3)2SO]: 2.38 (s, 3H, CH3C6H4), 6.44 (s, 1H, pyrazple
H-4), 7.21–8.25 (m, 10H, ArH’s and pyrazole H-5), 11.89 (s, br., 1H, NH). Anal.
calcd. for C20H15N5 (325.37): C, 73.83; H, 4.65; N, 21.52. Found: C, 73.75; H,
4.54; N, 21.74%.
Synthesis of Pyrazoles 16a–d
A mixture of the appropriate 15a–d and hydrazine hydrate (5 mmol), (0.5 g,
0.5 mL, 10 mmol) in ethanol (15 mL) was refluxed for 2 h. The resulting solid was
collected and recrystallized to give 16a–d, respectively.
Alternative method. A solution of the appropriate arendiazonium chloride
(5 mmol) was added to a mixture of the appropriate 15a and b (5 mmol) and sodium
acetate (0.65 g, 5 mmol) in ethanol (30 mL) at 0–5 ꢀC while stirring. The resulting
solid that formed after 3 h was collected, washed with water, and recrystallized from
the proper solvent to give a product identical in all aspects (mp, mixed mp, and spec-
tra) with the corresponding 16a–d.
4,5-Dimethyl-1-phenyl-1H,4’h-3,3’-bipyrazol-4’-one phenylhydrazone
(16a). Dark red crystals from EtOH, yield (88%), mp 256–258 ꢀC; IR (KBr): 3282
1
(NH), 3070 (CH), 2218 (CN), 1589 (C C); H NMR [(CD3)2SO]: 7.18–8.01 (m,
=
15H, ArH’s), 8.54 (s, 1H, pyrazole H-5), 10.89 (s, br., 1H, NH); MS: m=z ¼ 414
(M ꢁ 1, 0.01%), 311 (100%), 282 (10.34%), 77 (19.76%), 51 (17.12%). Anal. calcd.

1114
A. O. ABDELHAMID ET AL.
for C25H17N7 (415.45): C, 72.28; H, 4.12; N, 23.60. Found: C, 72.35; H, 4.31; N,
23.72%.
4,5-Dimethyl-1-phenyl-1H,4’H-3,3’-bipyrazol-4’-one(4-methylphenyl)
hydrazone (16b). Light pink crystals from diluted AcOH, yield (89%), mp
1
260–226 C; IR (KBr): 3283 (NH), 3066 (CH), 2218 (CN), 1589 (C C); H NMR
ꢀ
=
[(CD3)2SO]: 2.38 (s, 3H, CH3C6H4), 7.26–8.34 (m, 14H, ArH’s), 8.75 (s, 1H, pyrazole
H-5), 10.89 (s, br., 1H, NH); MS: m=z ¼ 429 (M ꢁ 1, 0.05%), 311 (100%), 282
(18.18%), 255 (13.00), 228 (6.09%), 216 (7.27%), 190 (8.72%), 178 (10.91%), 151
(12.8%), 126 (13.39%), 134 (7.77%), 100 (9.63%), 94 (6.63%), 88 (6.45%), 76
(70.93%), 66 (11.31%), 63 (15.84%), 51 (70.65%). Anal. calcd. for C26H19N7
(429.48): C, 72.71; H, 4.46; N, 22.83. Found: C, 72.92; H, 4.64; N, 22.77%.
4,5-Dimethyl-1-(4-methylphenyl)-1H,4’H-3,3’-bipyrazol-4’-one phenyl-
hydrazone (16c). Yellow crystals from EtOH, yield (88%), mp 262–264 ꢀC; IR
(KBr): 3294 (NH), 3043 (CH), 2221 (CN), 1577 (C C), 1H NMR [(CD3)2SO]:
=
2.38 (s, 3H, CH3C6H4), 7.15–8.22 (m, 14H, ArH’s), 8.55 (s, 1H, pyrazole H-5),
10.89 (s, br., 1H, NH); MS: m=z ¼ 430 (M þ 1, 0.06%), 326 (67.28%), 281 (6.79%),
255 (7.14), 228 (10.30%), 215 (10.38%), 204 (9.15%), 189 (8.85%), 177 (13.25%),
167 (12.46%), 151 (28.88%), 126 (24.97%), 103 (17.33%), 100 (21.29%), 93
(17.60%), 91 (43.56%), 88 (38.91%), 78 (70.65%), 66 (23.52%), 65 (100%), 53
(9.307%), 52 (20.30%), 50 (62.87%). Anal. calcd. for C26H19N7 (429.48): C, 72.71;
H, 4.46; N, 22.83. Found: C, 72.94; H, 4.58; N, 22.98%.
4,5-Dimethyl-1-phenyl-1H,4’H-3,3’-bipyrazol-4’-one (4-methylphenyl)-
hydrazone (16d). Brown crystals from EtOH, yield (89%), mp 264–266 ꢀC; IR
(KBr): 3290 (NH), 3143 (CH), 2221 (CN), 1577 (C C), 1H NMR [(CD3)2SO]:
=
2.38 (s, 3H, CH3C6H4), 2.40 (s, 3H, 4-CH3C6H4), 7.27–8.15 (m, 13H, ArH’s), 8.47
(s, 1H, pyrazole H-5), 10.75 (s, br., 1H, NH). Anal. calcd. for C27H21N7 (443.5):
C, 73.12; H, 4.77; N, 22.11. Found: C, 73.27; H, 4.85; N, 22.46%.
5-Phenyl-3-(1-phenyl-1H-pyrazole-4-carbonyl)-1-p-tolyl-1H-pyrazole-4-
carbonitrile 22 and 23
Equimolar amounts of each of 3-(3-(dimethylamino)acryloyl)-1,5-diphenyl-1H-
pyrazole-4-carbonitrile (1a) or 3-(3-(dimethylamino)acryloyl)-5-phenyl-1-p-tolyl-1H-
pyrazole-4-carbonitrile (1b) and the appropriate hydrazonoyl halides 18a–e (5 mmol)
were refluxed in dry toluene (20 mL) containing triethylamine (0.75 mL) for 3 h. The
hot solution was filtered off, and the filtrate was evaporated and triturated with
petroleum ether (40–60 ꢀC). The resulting solid was collected and recrystallized from
ethanol to give 22a–e and 23a–e.
Ethyl 4-(4-cyano-1,5-diphenyl-1H-pyrazole-3-carbonyl)-1-phenyl-1H-
pyrazole-3-carboxylate (22a). Pale yellow crystals from EtOH, yield (85%), mp
ꢀ
=
190–192 C; IR (KBr): 3060, 2981 (CH), 2232 (CN), 1731 (C O), 1649 (C N),
=
1
=
1591 (C C), 1437 (CH2) and 138 (CH3); H NMR [(CD3)2SO]: d ¼ 1.10 (t, 3H,
J ¼ 7.5 Hz, CH2CH3), 4.15 (q, 2H, J ¼ 7.5 Hz, CH2CH3), 7.37–7.75 (m, 13H, ArH’s),
7.82–7.96 (m, 2H, ArH’s), 9.31 (s, 1H, pyrazole C-5); 13C NMR [(CD3)2SO]: d ¼ 14.5
(CH3), 60.6 (CH2), 94.8, 117.6 (CN), 120.1, 123.1, 127.3, 129.2, 129.3, 129.4, 129.8,

DESIGN AND SYNTHESIS OF FUSED AZOLES
1115
130.8, 131.2, 132.8, 140.7, 142.6, 144.6, 147.8, 152.4, 160.4 (CO), 178.7 (CO); MS: m=
z ¼ 489 (M þ 2, 1.8%), 488 (M þ 1,16.7.5%), 487 (Mþ, 24.1%), 442 (29.8%), 272
(12.4%), 215 (19.9%), 180 (15.8%), 141 (16.3%), 104 (48.2%), 77 (100%), 65
(4.1%). Anal. calcd. for C29H21N5O3 (487.51): C, 71.45; H, 4.34; N, 14.37. Found:
C, 71.20; H, 4.57; N, 14.35%.
3-(3-Acetyl-1-phenyl-1H-pyrazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-
4-carbonitrile (22b). Pale cream crystals from diluted AcOH, yield (84%), mp
ꢀ
=
198–200 C; IR (KBr): 3062, 2914 (CH), 2229 (CN), 1700, 1656 (2 C O), 1594
1
=
(C C), and 1350 (CH3); H NMR [(CD3)2SO]: d ¼ 2.61 (s, 3H, CH3), 7.35–7.63
(m, 13H, ArH’s), 7.95–7.99 (d, 2H, J ¼ 8 Hz), ArH’s), 9.25 (s, 1H, pyrazole C-5);
13C NMR [(CD3)2SO]: d ¼ 27.1 (CH3), 94.5, 117.6 (CN), 119.8, 127.1, 127.3,
128.7, 129.4, 129.5, 129.9, 131.2, 132.6, 142.3, 144.5, 146.3, 149.6, 150.4, 152.6,
180.1 (CO), 194.8 (CO); MS: m=z ¼ 459 (M þ 2, 5.2%), 458 (M þ 1, 11.0%), 457
(Mþ, 23.5)%, 456 (M ꢁ 1, 13.5%), 442 (36.5%), 325 (12.9%), 272 (13.9%), 213
(14.8%), 171 (40.0%), 141 (14.2%), 104 (20.0%), 77 (100%), 51 (29.0%). Anal. calcd.
for C28H19N5O2 (457.48): C, 73.51; H, 4.19; N, 15.31. Found: C, 73.35; H, 4.31; N,
15.48%.
3-(3-Benzoyl-1-phenyl-1H-pyrazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-
4-carbonitrile (22c). Brown crystals from AcOH, yield (80%), mp 219–221 ꢀC; IR
1
=
=
(KBr): 3061 (CH), 2230 (CN), 1654 (C O), 1592 (C C); H NMR [(CD3)2SO]:
d ¼ 7.16–7.60 (m, 18H, ArH’s), 7.96–7.98 (d, 2H,, J ¼ 8 Hz), ArH’s), 9.44 (s, 1H,
pyrazole C-5); 13C NMR [(CD3)2SO]: d ¼ 94.5, 117.6 (CN), 119.8, 125.2, 127.6,
127.9, 129.2, 129.3, 129.6, 130.2, 130.6, 131.2, 132.4, 138.2, 141.5, 144.7, 145.4,
150.2, 152.1, 153.4, 178.6 (CO), 187.3 (CO); MS: m=z ¼ 521(M þ 2, 2.3%), 520
(M þ 1, 13.2%), 519 (Mþ, 29)%, 490 (4.7%), 442 (12.4%), 275 (112.9%), 275
(11.9%), 180 (7.9%), 106 (6.2%), 105 (82.7%), 104 (10.0%), 77 (100%), 51 (23.2%).
Anal. calcd. for C28 C33H21N5O2 (519.55): C, 76.29; H, 4.07; N, 13.48. Found: C,
76.08; H, 4.12; N, 13.61%.
4-(4-Cyano-1,5-diphenyl-1H-pyrazole-3-carbonyl)-3-carbamoyl-1-phenyl-
1H-pyrazole (22d). Brown crystals from AcOH, yield (86%), mp: 198–200 ꢀC; IR
=
=
=
(KBr): 3260 (NH), 3025 (CH), 2230 (CN), 1679 (C O), 1639 (C N), 16.1 (C C);
1H NMR [(CD3)2SO]: d ¼ 7.12–7.72 (m, 18H, ArH’s), 9.35 (s, 1H, pyrazole C-5),
10.72 (s, br., 1H, NH); 13C NMR [(CD3)2SO]: d ¼ 94.5, 117.6 (CN), 119.8, 120.7,
124.4, 127.5, 129.3, 129.4, 129.6, 129.9, 130.2, 131.4, 132.7, 140.4, 140.8, 143.2,
134.5, 145.6, 148.3, 152.4, 157.7 (CO), 178.2 (CO). Anal. calcd. for C28
C33H22N6O2 (534.57): C, 74.14; H, 4.15; N, 15.72. Found: C, 74.00; H, 3.95; N,
15.57%.
3-(f4-[(4-Cyano-1,5-diphenylpyrazol-3-yl)carbonyl]1-phenylpyrazole-3-
ylg-carbonylg-1-(4-methylphenyl)-5-phenylpyrazole-4-carbonitrile
(22e). Pale cream crystals from diluted AcOH, yield (84.7%), mp 250–252 ꢀC; IR
=
(KBr): 3061, 2919 (CH), 2234 (CN), 1681 (C O), 1646 (C N), 1596 (C C), 1379
=
=
1
(CH3); H NMR [(CD3)2SO]: d ¼ 2.27 (s, 3H, CH3), 7.09–8.03 (m, 24H, ArH’s),
9.74 (s, 1H, pyrazole C-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 91.6, 94.5, 117.6
(CN), 119.8, 124.2, 125.3, 127.6, 128.4, 129.2, 129.4, 129.8, 130.2, 131.4, 132.2,
132.7, 136.6, 137.5, 142.5, 144.6, 144.8, 148.2, 150.3, 152.1, 154.3, 174.5 (CO),

1116
A. O. ABDELHAMID ET AL.
178.6 (CO); MS: m=z ¼ 700 (Mþ, 0.59%), 676 0.69%), 580 (0.71%), 325 (4.38%), 286
(6.61%), 180 (3.77%), 167 (14.13%), 149 (40.14%), 111 (10.79%), 92 (11.64%), 84
(18.16%), 77 (37.98%), 77 (100%), 57 (52.79%), 50 (18.33%). Anal. calcd. for
C44H28N8O2 (700.75): C, 75.42; H, 4.03; N, 15.99. Found: C, 75.21; H, 3.83; N,
16.19%.
Ethyl 4-(4-cyano-5-phenyl-1-p-tolyl-1H-pyrazole-3-carbonyl)-1-phenyl-
1H-pyrazole-3-carboxylate (23a). Yellow crystals from diluted AcOH, yield
ꢀ
=
(85%), mp 210–212 C; IR (KBr): 3039, 2920 (CH), 2233 (CN), 1708 (C O), 1658
1
(CO, conjugated), 1596 (C C), 1413 (CH2), 1379 (CH3); H NMR [(CD3)2SO]:
=
1.16 (t, 3H, J ¼ 7.5 Hz, CH2CH3), 2.34 (s, 3H, CH3), 4.14 (q, 2H, J ¼ 7.5 Hz,
CH2CH3), 7.28–8.41 (m, 12H, ArH’s), 8.52 (d, 1H, J ¼ 8 Hz, ArH’s), 8.48 (s, 1H,
pyrazole H-5); 13C NMR [(CD3)2SO]: d ¼ 14.4 (CH3), 20.1 (CH3), 60.4 (CH2),
94.5, 117.6 (CN), 119.8, 123.1, 125.4, 127.3, 129.4, 129.5, 130.3, 132.1, 132.7,
136.6, 138.7, 140.6, 142.8, 147.7, 152.5, 160.4 (CO), 180.1 (CO); MS: m=z ¼ 504
(M þ 2, 1.18)%, 503 (M þ 1, 4.34%), 202 (Mþ, 14.56%), 429 (4.31%), 301 (5.47%),
257 (5.35%), 244 (7.15%), 243 (10.65%), 215 (15.45%), 149 (17.19%), 142 (11.05%),
103 (62.03%), 91 (42.21%), 77 (100%), 65 (24.65%), 57 (21.75%). Anal. calcd. for
C30H23N5O3 (501.54): C, 71.84; H, 4.62; N, 13.96. Found: C, 72.00; H, 4.81; N,
14.15%.
3-(3-Acetyl-1-phenyl-1H-pyrazole-4-carbonyl)-5-phenyl-1-p-tolyl-1H-
pyrazole-4-carbonitrile (23b). Pale gray crystals from diluted AcOH, yield (85%),
ꢀ
=
=
mp 188–190 C; IR (KBr): 3052, 2920 (CH), 2233 (CN), 1708 (C O), 1658 (C N),
1
=
1596 (C C), 1379 (CH3); H NMR [(CD3)2SO]: d ¼ 2.36 (s, 3H, CH3), 2.62 (s, 3H,
CH3), 7.28–8.41 (m, 12H, ArH’s), 8.52 (d, 1H, J ¼ 8 Hz, ArH’s), 8.49 (s, 1H, pyrazole
H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 27.5 (CH3), 94.5, 117.6 (CN), 119.8,
125.5, 127.3, 128.8, 129.2, 129.4, 130.7, 132.2, 123.4, 136.6, 138.5, 142.5, 146.7,
149.4, 150.7, 152.2, 180.3 (CO), 194.8 (CO); MS: m=z ¼ 472 (Mþ, 100%), 457
(96.57%), 443 (35.03%), 428 (11.85%), 418 (8.36%), 401 (25.55%), 367 (6.39%), 356
(13.88%), 339 (43.25%), 301 (17.23%), 286 (19.61%), 273 (9.68%), 258 (22.56%),
243 (16.99%), 230 (13.47%), 213 (32.80%), 171 (61.22%), 155 (15.76%), 141
(13.50%), 114 (16.06%), 103 (40.68%), 90 (52.98%), 76 (53.70%), 64 (30.69%). Anal.
calcd. for C29H21N5O2 (471.51): C, 73.87; H, 4.49; N, 14.85 Found: C, 73.68; H,
4.54; N, 15.11%.
3-(3-Benzoyl-1-phenyl-1H-pyrazole-4-carbonyl)-5-phenyl-1-p-tolyl-1H-
pyrazole-4-carbonitrile (23c). Pale cream crystals from diluted AcOH, yield
ꢀ
1
=
(80%), mp 185–187 C; IR (KBr): 3058 (CH), 2233 (CN), 1658 (C O), 1600
=
(C C), 1384 (CH3); H NMR [(CD3)2SO]: d ¼ 2.36 (s, 3H, CH3), 7.28–8.41 (m,
19H, ArH’s), 8.49 (s, 1H, pyrazole H-5); 13C NMR [(CD3)2SO]: (¼20.0 (CH3),
94.5, 117.6 (CN), 119.8, 125.3, 127.7, 129.3, 129.6, 130.2, 132.3, 132.7, 136.4,
138.2, 138.6, 141.6, 145.7, 150.4, 152.7, 153.6, 178.2 (CO), 187.4 (CO); MS: m=
z ¼ 534 (M þ 1, 28.29%), 472 (44.46%), 457 (65.55%), 443 (18.66%), 415 (11.00%),
400 (4.95%), 214 (43.43%), 178 (10.27%), 154 (33.79%), 141 (17.37%), 115
(18.76%), 104 (87.95%), 90 (64.43%), 77 (100%), 65 (26.02%). Anal. calcd. for
C34H23N5O2 (533.58): C, 76.53; H, 4.34; N, 13.13. Found: C, 76.35; H, 4.45; N,
13.27%.

DESIGN AND SYNTHESIS OF FUSED AZOLES
1117
4-(4-Cyano-5-phenyl-1-p-tolyl-1H-pyrazole-3-carbonyl)-3-carbamoyl-1-
phenyl-1H-pyrazole (23d). Brown crystals from diluted AcOH, yield (87%), mp
ꢀ
=
132–134 C; IR (KBr): 3475 (NH), 3042 (CH), 2231 (CN), 1676 (C O), 1624
(C N), 1601 (C C), 1368 (CH3); 1H NMR (CD3Cl): d ¼ 2.39 (s, 3H, CH3),
7.14–7.92 (m, 19H, ArH’s), 9.27 (s, 1H, pyrazole H-5), 11.58 (s, br., 1H, NH); 13C
NMR [(CD3)2SO]: (¼20.1 (CH3), 94.5, 117.6 (CN), 119.8, 120.8, 124.5, 125.7,
127.6, 129.4, 129.7, 130.4, 130.5, 132.4, 132.8, 136.7, 138.5, 140.3, 140.6, 143.5,
145.6, 148.2, 152.1, 157.7 (CO), 177.9 (CO); MS: m=z ¼ 549 (M þ 1, 5%), 548
(Mþ, 18.5%), 274 (17.4%), 193 (13.5%), 104 (12.4%), 89 (7.9%), 77 (26%), 76
(14%), 65 (22.5%). Anal. calcd. for C34H24N6O2 (548.59): C, 74.44; H, 4.41; N,
15.32. Found: C, 74.65; H, 4.31; N, 15.48%.
=
=
3-[(4-f[4-Cyano-1-(4-methylphenyl)-5-phenylpyrazol-3-yl]carbonylg-1-
phenyl-pyrazol-3-yl)carbonyl]-1-(4-methylphenyl)-5-phenylpyrazole-4-
carbonitrile (23e). Pale brown crystals from AcOH, yield (85%), mp 256–258 ꢀC;
=
=
IR (KBr): 3055 (CH), 2233 (CN), 1678 (C O), 1639 (C N), 1600 (C C), 1380
=
1
(CH3); H NMR [(CD3)2SO]: d ¼ 2.39 (s, 3H, CH3), 2.40 (s, 3H, CH3), 7.14–7.92
(m, 23H, ArH’s), 9.27 (s, 1H, pyrazole H-5); 13C NMR [(CD3)2SO]: (¼20.1 (CH3),
91.7, 94.5, 117.6 (CN), 120.1, 124.2, 125.4, 127.4, 128.2, 129.4, 130.7, 132.3, 132.8,
136.6, 138.7, 142.4, 144.6, 148.3, 150.2, 152.2, 154.8, 174.5 (CO), 178.1 (CO); MS:
m=z ¼ 715 (M þ 1, 0.81%), 714 (Mþ, 0.80%), 456 (4.60%), 286 (11.07%), 258
(11.22%), 243 (15.13%), 231 (8.52%), 195 (7.09%), 171 (4.52%), 155 (14.24%), 104
(36.75%), 91 (58.81%), 77 (100%), 65 (36.95%). Anal. calcd. for C45H30N8O2
(714.77): C, 75.62; H, 4.23; N, 15.68. Found: C, 75.80; H, 4.35; N, 15.87%.
3-(Isoxazole-4-carbonyl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile
27 and 28
Method A. Triethylamine (0.5 g, (0.75 ml, 5 mmol) was added dropwise to an
equimolar amount of 1a (or 1b) and the appropriate hydroximoyl chloride 26a–d
(5 mmol, each) in dry toluene (20 ml) while stirring. The reaction mixture was stirred
for 6 h, the solvent was evaporated and then it was triturated with petroleum ether
(40–60 ꢀC). The resulting solid was collected and crystallized to give 27a–e and
28a–d respectively.
Method B. Equimolar amount of 1a (or 1b) and the appropriate hydroximoyl
chloride 26a–d (5 mmol, each) in dry toluene (20 ml) were heated under reflux for
18 h. The reaction mixture was filtered off, the solvent was evaporated, and the
filtrate was triturated with petroleum ether (40–60 ꢀC). The resulting solid was
collected and crystallized to give products identical in all aspects (mp, mixed mp,
and spectra) with 27a–e and 28a–d, respectively.
3-(3-Benzoyl-isoxazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-4-carbonit
rile (27a). Brown crystals from diluted AcOH, yield (84%), mp 178–180 ꢀC; IR
1
=
=
=
(KBr): 3062, 2918 (CH), 2233 (CN), 1681 (C O), 1658 (C N), 1593 (C C); H
NMR [(CD3)2SO]: d ¼ 7.14–7.71 (m, 9H, ArH’s), 8.26 (d, 2H, J ¼ 8 Hz), 8.52 (d,
4H, J ¼ 8 Hz), 8.95 (s, 1H, isoxazole H-5); 13C NMR [(CD3)2SO]: (¼ 94.5, 117.6
(CN), 118.8, 128.5, 129.4, 129.6, 130.2, 130.5, 132.9, 137.2, 142.4, 144.6, 152.2,

1118
A. O. ABDELHAMID ET AL.
162.2, 179.6 (CO), 187.4 (CO), 191.8 isoxazole C-5); MS: m=z ¼ 445 (M þ 1, 0.44%),
444 (Mþ,1.63%), 339 (0.75%), 311 (2.94%), 287 (0.96%), 272 (4.41%), 180 (2.03%),
105 (100%), 77 (51.36%), 51 (19.27%). Anal. calcd. for C27H16N4O3 (444.44): C,
72.97; H, 3.63; N, 12.61. Found: C, 73.12; H, 3.75; N, 12.45%.
3-[3-(Furan-2-carbonyl)-isoxazole-4-carbonyl]-1,5-diphenyl-1H-pyrazole-
4-carbonitrile (27b). Gray crystals from AcOH, yield (84%), mp 178–180 ꢀC; IR
(KBr): 3015, 2923 (CH), 2237 (CN), 1658 (C O), 1558 (C C); 1H NMR
[(CD3)2SO]: d ¼ 6.63 (d, 1H, J ¼ 6 Hz, furan H-4), 7.14–7.28 (m, 7H, ArH’s), 8.01
(d, 1H, J ¼ 6 Hz, furan H-5), 8.26 (d, 2H, J ¼ 8 Hz), 8.52 (d, 2H, J ¼ 8 Hz), 8.95 (s,
1H, isoxazole H-5); 13C NMR [(CD3)2SO]: (¼94.5, 109.8, 114.5, 117.6 (CN),
129.3, 129.5, 129.7, 129.9, 130.7, 131.3, 132.7, 137.5, 144.8, 145.7, 151.2, 151.4,
152.4, 160.2 (CO), 180.0 (CO), 183.8 (isoxazole C-5); MS: m=z ¼ 435 (M þ 2,
0.44%), 434 (M þ 1, 2.02%), 405 (Mþ, 5.13%), 272 (1.49%), 244 (0.52%), 180
(0.59%), 95 (100%), 77 (13.74%), 51 (7.29%). Anal. calcd. for C25H14N4O4 (434.4):
C, 69.12; H, 3.25; N, 12.90. Found: C, 69.00; H, 3.41; N, 13.15%.
=
=
1,5-Diphenyl-3-[3-(thienyl-2-carbonyl)-isoxazole-4-carbonyl]-1H-pyrazole-
4-carbonitrile (27c). Beige crystals from diluted AcOH, yield (84%), mp:
1
ꢀ
=
=
156–158 C; IR (KBr): 3097, 2923 (CH), 2233 (CN), 1658 (C O), 1596 (C C); H
NMR [(CD3)2SO]: d ¼ 7.14–7.98 (m, 11H, ArH’s), 8.24 (d, 2H, J ¼ 8 Hz), 8.94 (s,
1H, isoxazole H-5); 13C NMR [(CD3)2SO]: (¼ 94.5, 114.5, 117.6 (CN), 125.3,
129.3, 129.5, 130.8, 131.3, 132.2, 132.7, 142.1, 144.7, 147.8, 151.5, 152.4, 166.9,
179.7 (CO), 179.9 (CO), 183.7 (isoxazole C-5); MS: m=z ¼ 452 (M þ 2, 0.47%), 451
(M þ 1, 1.58%), 450 (Mþ, 5.30%), 339 (0.57%), 272 (1.41%), 141 (1.65%), 111
(100%), 77 (16.47%), 51 (7.85%). Anal. calcd. for C25H14N4O3S (450.47): C, 66.66;
H, 3.13; N, 12.44; S, 7.12. Found: C, 66.84; H, 3.00; N, 12.60; S, 7.32%.
3-[3-(Naphthalene-2-carbonyl)-isoxazole-4-carbonyl]-1,5-diphenyl-1H-
pyrazole-4-carbonitrile (27d). Brown crystals from AcOH, yield (85%), mp
1
ꢀ
=
=
208–210 C; IR (KBr): 3068, 2916 (CH), 2233 (CN), 1639 (C O), 1562 (C C); H
NMR [(CD3)2SO]: d ¼ 7.14–8.12 (m, 13H, ArH’s), 8.42 (d, 2H, J ¼ 8 Hz), 8.57 (d,
1H, J ¼ 8 Hz), 8.94 (s, 1H, isoxazole H-5); 13C NMR [(CD3)2SO]: (¼94.5, 117.6
(CN), 119.1, 126.4, 127.8, 128.3, 128.7, 129.3, 129.5, 129.7, 129.8, 129.9, 130.7,
131.2, 131.3, 132.6, 133.2, 133.1, 133.3, 142.2, 144.7, 152.2, 161.9, 179.5 (CO),
187.3 (CO), 191.8 (isoxazole C-5); MS: m=z ¼ 496 (M þ 2, 0.02%), 495 (M þ 1,
0.07%), 494 (Mþ, 0.17%), 325 (100%), 272 (9.74%), 180 (5.20%), 98 (16.10%), 77
(6.58%), 55 (10.74%). Anal. calcd. for C31H18N4O3 (494.5): C, 75.29; H, 3.67; N,
11.33. Found: C, 75.31; H, 3.75; N, 11.46%.
5-[(3-f[4-Cyano-1-(4-methylphenyl)-5-phenylpyrazol-3-yl]carbonylg
isoxazol-4-yl)carbonyl]- 2,3-diphenyl-5-hydropyrazole-4-carbonitrile (27e).
Pale cream crystals from diluted AcOH, yield (88%), mp 168–170 ꢀC; IR (KBr):
=
=
=
3060, 2922 (CH), 2235 (CN), 1697 (C O), 1557 (C N), 1540 (C C), 1385 (CH3);
1H NMR [(CD3)2SO]: d ¼ 2.41 (s, 3H, CH3), 7.14–7.79 (m, 11H, ArH’s), 8.142 (d,
2H, J ¼ 8 Hz), 8.40 (d, 2H, J ¼ 8 Hz), 8.51 (d, 4H, J ¼ 8 Hz), 8.94 (s, 1H, isoxazole
H-5); 13C NMR [(CD3)2SO]: (¼20.1 (CH3), 91.6, 94.5, 117.6 (CN), 117.9 (CN),
125.6, 129.3, 129.5,129.9, 130.9, 132.4, 132.6, 137.5, 144.7, 147.2, 151.5, 152.2,
159.7, 174.6 (CO), 179.8 (CO), 193.2 (isoxazole C-5); MS: m=z ¼ 624 (M ꢁ 1,

DESIGN AND SYNTHESIS OF FUSED AZOLES
1119
0.02%), 337 (73.087%), 329 (30.12%), 303 (49.82%), 286 (7.77%), 273 (100%), 260
(31.43%), 246 (10.67%), 189 (14.63%), 154 (34.85%), 141 (43.12%), 104 (37.66.%),
90 (44.28%), 76 (64.80%), 50 (33.48%). Anal. calcd. for C38H23N7O3(625.63): C,
72.95; H, 3.71; N, 15.67. Found: C, 73.15; H, 3.50; N, 15.79%.
3-(3-Benzoyl-isoxazole-4-carbonyl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-
carbonitrile (28a). Yellow crystals from diluted AcOH, yield (84%), mp
ꢀ
=
=
210–212 C; IR (KBr): 3056, 2918 (CH), 2233 (CN), 1659 (C O), 1565 (C C),
1385; 1H NMR [(CD3)2SO]: d ¼ 2.33 (s, 3H, CH3), 7.21–7.93 (m, 14H, ArH’s),
9.48 (s, 1H, isoxazole H-5); 13C NMR [(CD3)2SO]: (¼20.1 (CH3), 94.5, 117.6
(CN), 118.5, 125.6, 128.5, 129.3, 129.7, 131.1, 132.2, 132.8, 136.7, 138.8, 142.4,
152.5, 161.7, 179.5 (CO), 187.3 (CO), 192.0 (isoxazole C-5); MS: m=z ¼ 459
(M þ 1, 1.39%), 458 (Mþ, 4.15%), 339 (12.74%), 300 (17.78%), 286 (15.63%), 273
(4.45%), 194 (4.75%), 105 (100%), 91 (14.56%), 77 (45.32%), 51 (17.77%). Anal.
calcd. for C28H18N4O3(458.47): C, 73.35; H, 3.96; N, 12.22. Found: C, 73.53; H,
4.15; N, 12.35%.
3-f[3-(2-Furoyl)isoxazol-4-yl]carbonylg-1-(4-methylphenyl)-5-phenyl-1H-
pyrazole-4-carbonitrile (28b). Yellow crystals from diluted DMF, yield (84%),
ꢀ
=
=
mp 188–190 C; IR (KBr): 2925 (CH), 2230 (CN), 1670 (C O), 1562 (C C), 1385;
1H NMR [(CD3)2SO]: d ¼ 2.33 (s, 3H, CH3), 6.32 (s, 1H, furan H-3), 7.21–7.93
(m, 12H, ArH’s), 9.23(s, 1H, isoxazole H-5); 13C NMR [(CD3)2SO]: (¼20.1 (CH3),
94.5, 109.8, 114.5, 117.6 (CN), 125.4, 129.3, 129.5, 130.7, 132.1, 132.7, 136.5,
137.4, 138.8, 146.1, 151.2, 152.1, 160.2, 179 (CO), 180 (CO), 183.3 (isoxazole C-5);
MS: m=z ¼ 448 (Mþ, 4.2%), 447 (4.2%), 325 (7.9%), 301 (7.4%), 286 (11.6%), 121
(10.6%), 112 (21.7%), 95 (100%), 84 (25.9%), 93 (12.7%), 91 (12.2%), (77 (6.9%),
65 (18.0%). Anal. calcd. for C26H16N4O4 (448.43): C, 69.64; H, 3.60; N, 12.49.
Found: C, 69.45; H, 3.72; N, 12.57%.
5-Phenyl-3-[3-(thienyl-2-carbonyl)-isoxazole-4-carbonyl]-1-p-tolyl-1H-
pyrazole-4-carbonitrile (28c). Pale cream crystals from diluted AcOH, yield (85%),
ꢀ
=
mp 174–176 C; IR (KBr): 3058, 2920 (CH), 2237 (CN), 1705 (C O), 1658 (C N),
=
1
=
1516 (C C), 1384 (CH3); H NMR [(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 7.14–7.18
(m, 10H, ArH’s), 8.26 (d, 2H, J ¼ 8 Hz), 8.52 (d, 2H, J ¼ 8 Hz), 8.95 (s, 1H, isoxazole
H-5); 13C NMR [(CD3)2SO]: (¼20.1 (CH3), 94.5, 109.8, 114.5, 117.6 (CN), 125.0,
125.5, 129.4, 129.7, 130.1, 132.0, 132.4, 132.8, 136.4, 138.7, 142.2, 147.8, 151.6,
152.2, 166.9, 179.8 (CO), 180.0 (CO), 183.2 (isoxazole C-5); MS: m=z ¼ 456 (M þ 2,
0.66%), 465 (M þ 1, 1.52%), 464 (Mþ, 5.36%), 354 (0.71%), 325 (2.71%), 301
(4.37%), 286 (10.02%), 272 (0.69%), 258 (1.41%) 243 (1.48%), 180 (2.48%), 111
(100%), 91 (9.46%), 77 (8.36%), 51 (5.11%). Anal. calcd. for C26H16N4O3S (464.09):
C, 67.23; H, 3.47; N, 12.06; S, 6.90. Found: C, 67.10; H, 3.62; N, 11.89; S, 7.15%.
3-[3-(Naphthalene-2-carbonyl)-isoxazole-4-carbonyl]-5-phenyl-1-p-tolyl-
1H-pyrazole-4-carbonitrile (28d). Pale cream crystals from diluted AcOH, yield
ꢀ
=
(86%), mp 204–206 C; IR (KBr): 3055, 2920 (CH), 2233 (CN), 1666 (C O), 1627
(C N), 1566 (C C), 1353 (CH3); 1H NMR [(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3),
7.14–7.29 (m, 14H, ArH’s), 8.52 (d, 2H, J ¼ 8 Hz), 8.95 (s, 1H, isoxazole H-5); 13C
NMR [(CD3)2SO]: (¼20.1 (CH3), 94.5, 109.8, 114.5, 117.6 (CN), 125.5, 126.4, 127.8,
129.4, 129.7, 130.2, 131.4, 131.6, 132.4, 133.2, 134.2, 142.2, 152.4, 162.0, 179.0,
=
=

1120
A. O. ABDELHAMID ET AL.
(CO), 187 (CO), 191.8 (isoxazole C-5); MS: m=z ¼ 510 (M þ 2, 0.63%), 509 (M þ 1,
2.63%), 508 (Mþ, 7.29%), 325 (10.94%), 172 (28.87%), 155 (100%), 128 (13.25%),
127 (95.07%), 115 (3.88%), 101 (7.19%), 89 (3.20%), 77 (15.19%), 65 (10.60%). Anal.
calcd. for C32H20N4O3 (508.53): C, 75.58; H, 3.96; N, 11.02. Found: C, 75.77; H, 4.11;
N, 11.15%.
5-[(3-f[4-Cyano-1-(4-methylphenyl)-5-phenylpyrazol-3-yl]carbonylg
isoxazol-4-yl)carbonyl]-2-(4-methylphenyl)-3-phenyl-5-hydropyrazole-4-
carbonitrile (28e). Pale cream crystals from diluted AcOH, yield (88%), mp
174–176 ꢀC; IR (KBr): 3053, 2921 (CH), 2235 (CN), 1385 (CH3); 1H NMR
[(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 2.37 (s, 3H, CH3), 7.14–7.95 (m, 14H, ArH’s),
8.12 (d, 4H, J ¼ 8 Hz), 8.45(d, 4H, J ¼ 8 Hz), 8.78 (s, 1H, isoxazole H-5); 13C NMR
[(CD3)2SO]: (¼20.1 (CH3), 94.5, 109.8, 114.5, 117.2 (CN), 117.8 (CN), 125.5, 129.4,
129.7, 130.7, 132.2, 132.7, 136.8, 137.2, 138.2, 147.4, 151.4, 152.2, 159.8, 174.5 (CO),
179.7 (CO), 183.4 (isoxazole C-5); MS: m=z ¼ 638 (M ꢁ 1, 1.25%), 601 (1.27%), 584
(1.1%), 286 (3.04%), 284 (5.2%), 243 (2.05%), 202 (3.55%), 167 (5.73%), 160
(5.05%), 149 (22.23%), 125 (19.45%), 103 (10.53%), 91 (39.33%), 81 (10.2%), 78
(17.00%), 77 (100%), 65 (52.98%). Anal. calcd. for C39H25N7O3 (639.66): C, 73.23;
H, 3.94; N, 15.33. Found: C, 73.31; H, 4.12; N, 15.51%.
3-(2-P-Tolyl-2h-pyrazolo[3,4-d]pyridazin-4-yl)-1H-pyrazole-
4-carbonitrile 24, 25 and 3-(7-Phenyl-isoxazolo[3,4-d]pyridazin-4-
yl)-1-p-tolyl-1H-pyrazole-4-carbonitrile 29, 30
Equimolar amounts of each of the appropriate pyrazoles (22a–e, and 23a–e),
isoxazoles (27a–e and 28a–e), 5 mmol), and hydrazine hydrate (1 ml, 99%) in ethanol
(20 ml) were boiled under reflux for 2 h. The resulting solid was collected and crystal-
lized to give pyrazolo[3,4-d]pyridazines (24a–e and 25a–e) and isoxazolo[3,4-d]pyri-
dazines (29a–e and 30a–e), respectively.
3-(6,7-Dihydro-7-oxo-2-phenyl-2h-pyrazolo[3,4-d]pyridazin-4-yl)-1-
phenyl-1H-pyrazole-4-carbonitrile (24a). Cololess crystals from AcOH, yield
(84%), mp 322–324 ꢀC; IR (KBr): 3381 (NH), 3059, (CH), 2230 (CN), 1684 (CO),
1
=
1591 (C C); H NMR [(CD3)2SO]: d ¼ 7.48–8.08 (m, 14H, ArH’s), 9.21 (s, 1H, pyra-
zole H-5), 12.93 (s, br., 1H, NH); 13C NMR [(CD3)2SO]: (¼104.5, 117.6 (CN), 120.5,
124.2 (pyrazole C-5), 125.6, 127.2, 128.4, 129.5, 129.9, 131.4, 131.6, 138.6, 139.6, 146.4,
148.2, 149.7, 154.2, 155.0 (CO); MS: m=z ¼ 454 (M ꢁ 1, 4.3%), 453 (61.7%), 452
(95.7%), 425 (12.8%), 285 (10.8%), 227 (23.7%), 207 (12.8%), 138 (8.5%), 137
(12.8%), 138 (10.6%), 127 (12.8%), 104 (38.3%), 103 (17%), 102 (19.1%), 93 (10.6^),
92 (10.6%), 90 (8.5%), 89 (27.7%), 77 (100%), 65 (25.5%). Anal. calcd. for
C27H17N7O (455.15): C, 71.20; H, 3.76; N, 21.53. Found: C, 71.35; H, 3.57; N, 21.72%.
3-(7-Methyl-2-phenyl-2h-pyrazolo[3,4-d]pyridazin-4-yl)-1,5-diphenyl-
1H-pyrazole-4-carbonitrile (24b). Pale cream crystals from AcOH, yield (89%),
1
mp 288–290 C; IR (KBr): 3061, 2989 (CH), 2223 (CN), 1590 (C C); H NMR
ꢀ
=
[(CD3)2SO]: d ¼ 2.93 (s, 3H, CH3), 7.48–8.18 (m, 15H, ArH’s), 9.41 (s, 1H, pyrazole
H-5); 13C NMR [(CD3)2SO]: (¼17.2 (CH3), 104.5, 117.6 (CN), 122.5 (pyrazole C-5),
124.2, 126.6, 128.2, 129.7, 129.8, 131.2, 131.3, 139.3, 139.8, 143.2, 149.7, 151.6, 156.8,

DESIGN AND SYNTHESIS OF FUSED AZOLES
1121
168.1; MS: m=z ¼ 455 (M þ 2, 4.5%), 454 (M þ 2, 15.9%), 453 (Mþ, 54.9%), 452
(M ꢁ 1, 87.3%), 321 (2.6%), 226 (4.9%), 190 (5.2%), 180 (6.4%), 115 (5.2%), 104
(7.9%), 77 (100%), 76 (20.6%), 64 (6.9%). Anal. calcd. for C28H19N7 (453.5): C,
74.16; H, 4.22; N, 21.62. Found: C, 74.34; H, 4.40; N, 21.81%.
1,5-Diphenyl-3-(2,7-diphenyl-2H-pyrazolo[3,4-d]pyridazin-4-yl)-1H-
pyrazole-4-carbonitrile (24c). Pale yellow crystals from AcOH, yield (90%), mp
300–302 C; IR (KBr): 3057 (CH), 2225 (CN), 1635 (C N), 1595 (C C); 1H
NMR [(CD3)2SO]: d ¼ 7.52–8.82 (m, 15H, ArH’s), 9.53 (s, 1H, pyrazole H-5); 13C
NMR [(CD3)2SO]: (¼104.5, 117.6 (CN), 120.5, 123.9, 124.0 (pyrazole C-5), 126.2,
127.2, 128.3, 129.1, 129.8, 131.0, 131.2, 131.4, 131.7, 136.2, 139.6, 139.7, 140.4,
149.8, 151.8, 156.0, 157.9; MS: m=z ¼ 517 (M þ 2, 3.12%), 5.16 (M þ 2, 8.77%),
515 (Mþ, 22.02%), 300 (6.3%), 284 (30.87%), 257 (6.44%), 243 (10.82%), 184
(16.60%), 167 (7.67%), 140 (7.84%), 104 (38.53%), 77 (100%), 76 (20.6%), 65
(30.00%). Anal. calcd. for C33H21N7 (515.57): C, 76.88; H, 4.11; N, 19.02. Found:
C, 77.00; H, 4.25; N, 19.23%.
ꢀ
=
=
3-(4-(4-Cyano-1,5-diphenyl-1H-pyrazol-3-yl)-2-phenyl-2H-pyrazolo[3,4-d]
pyridazin-7-yl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile
(24d). Yellow
crystals from AcOH, yield (92%), mp >340 ꢀC; IR (KBr): 3054 (CH), 2227 (CN),
1590 (C C); 1H NMR [(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 7.26–8.15 (m, 24H,
=
ArH’s), 9.55 (s, 1H, pyrazole H-5); 13C NMR [(CD3)2SO]: (¼21 (CH3), 96.5,
104.5, 117.6 (CN), 120.1, 122.2, 124.1, 127.2, 127.7 (CN), 128.3, 130.8, 131.2,
131.6, 133.2, 136.8, 139.4, 140.7, 141.6, 146.2, 147.1, 149.7, 151.7, 166.1, 166.6;
MS: m=z ¼ 696 (Mþ, 1.23%), 630 (1.53%), 572 (4.10%), 534 (3.19%), 439 (1.72%),
270 (7.62%), 167 (7.53%), 149 (21.87%), 135 (13.46%), 111 (7.06%), 97 (25.74%),
77 (100%), 69 (51.09%). Anal. calcd. for C44H28N10 (696.76): C, 75.85; H, 4.05; N,
20.10. Found: C, 76.00; H, 3.85; N, 20.32%.
3-(6,7-Dihydro-7-oxo-2-p-tolyl-2h-pyrazolo[3,4-d]pyridazin-4-yl)-1,5-
diphenyl-1H-pyrazole-4-carbonitrile (25a). Colorless crystals from dioxane,
yield (85%), mp 272–274 ꢀC; IR (KBr): 3425 (OH), 3062 (CH), 2233 (CN), 1728
(CO), 1658 (C N), 1600 (C C); 1H NMR [(CD3)2SO]: d ¼ 2.32 (s, 3H, CH3),
7.26–8.09 (m, 14H, ArH’s), 8.95 (s, 1H, pyrazole H-5), 12.21 (s, br., 1H, NH);13C
NMR [(CD3)2SO]: d ¼ 20.2 (CH3), 104.2, 117.6 (CN), 120.4, 124.1, 125.7 (pyrazole
C-5), 127.2, 128.4, 129.1, 129.5, 129.8, 131.3, 131.6, 139.0, 139.8, 146.3, 148.1,
149.4, 145.2 (CO), 154.8; MS: m=z ¼ 471 (M þ 2, 2.04%), 470 (M þ 1, 2.07%), 469
(Mþ, 16.58%), 380 (3.13%), 270 (3.25%), 243 (2.04%), 218 (2.17%), 165 (3.45%),
154 (2.49%), 127 (4.04%), 104 (14.86%), 92 (19.18%), 91 (19.79%), 78 (10.59%), 77
(100%), 65 (17.76%). Anal. calcd. for C28H19 N7O (469.5): C, 71.63; H, 4.08; N,
20.88. Found: C, 71.75; H, 3.89; N, 21.00%.
=
=
3-(7-Methyl-2-p-tolyl-2H-pyrazolo[3,4-d]pyridazin-4-yl)-1,5-diphenyl-1H-
pyrazole-4-carbonitrile (25b). Pale cream crystals from diluted AcOH, yield
ꢀ
=
=
(89%), mp 218–220 C; IR (KBr): 3043 (CH), 2235 (CN), 1643 (C N), 1593 (C C);
1H NMR [(CD3)2SO]: d ¼ 2.32 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.24–8.14 (m, 14H,
ArH’s), 8.92 (s, 1H, pyrazole H-5); 13C NMR [(CD3)2SO]: d ¼ 17.1 (CH3), 20.2
(CH3), 104.2, 117.6 (CN), 121.1, 122.8 (pyrazole C-5), 123.7, 126.8, 128.4, 129.4, 129.8,
131.2, 131.4, 131.7, 139.4, 139.7, 143.2, 149.6, 151.7, 156.8, 168.1; MS: m=z¼ 467

1122
A. O. ABDELHAMID ET AL.
(Mþ, 100%), 325 (13.14%), 333 (4.25%), 242 (8.46%), 230 (7.82%), 226 (5.74%), 219
(10.17%), 178 (10.09%), 151 (10.19%), 140 (11.75%), 127 (10.81%), 105 (9.97%), 90
(41.27%), 91 (19.79%), 78 (10.59%), 77 (49.45%), 65 (25.39%). Anal. calcd. for
C29H21N7 (467.52): C, 74.50; H, 4.53; N, 20.97. Found: C, 74.34; H, 4.35; N, 21.15%.
1,5-Diphenyl-3-(7-phenyl-2-p-tolyl-2H-pyrazolo[3,4-d]pyridazin-4-yl)-
1H-pyrazole-4-carbonitrile (25c). Yellow crystals from diluted AcOH, yield
1
(90%), mp 252–254 C; IR (KBr): 3058 (CH), 2229 (CN), 1593 (C C); H NMR
ꢀ
=
[(CD3)2SO]: d ¼ 2.32 (s, 3H, CH3), 7.24–8.24 (m, 20H, ArH’s), 8.95 (s, 1H, pyrazole
H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 104.2, 117.6 (CN), 123.8, 123.9 (pyra-
zole C-5), 127.6, 128.2, 128.8, 129.3, 129.9, 131.0, 131.2, 131.3, 131.6, 136.2, 139.5,
139.8, 140.5, 149.8, 151.5, 156.7, 157.8; MS: m=z ¼ 529 (Mþ, 0.34%), 310
(65.23%), 296 (84.69%), 284 (9.82%), 269 (45.46%), 254 (32.53%), 241 (17.80%),
231 (11.79%), 228 (18.44%), 221 (17.75%), 196 (7.12%), 177 (32.30%), 165
(14.05%), 162 (52.45%), 155 (58.13%), 148 (28.88%), 90 (100%), 76 (39.48%), 65
(51.97%). Anal. calcd. for C34H23N7 (529.59): C, 77.11; H, 4.38; N, 18.51. Found:
C, 77.25; H, 4.42; N, 18.35%.
3-(4-(4-Cyano-5-phenyl-1-p-tolyl-1H-pyrazol-3-yl)-2-p-tolyl-2h-pyrazolo
[3,4-d]pyridazin-7-yl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (25d). Yellow
crystals from diluted AcOH, yield (92%), mp >330 ꢀC; IR (KBr): 3033 (CH), 2229
1
=
(CN), 1598 (C C); H NMR [(CD3)2SO]: d ¼ 2.32 (s, 6H, 2CH3), 7.24–8.31 (m,
23H, ArH’s), 8.85 (s, 1H, pyrazole H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3),
95.3, 104.2, 117.6 (CN), 119.1 (pyrazole), 122.2, 124.8, 126.1, 126.7, 127.1, 127.7
(CN), 128.3, 129.4, 130.9, 131.4, 131.6, 133.2, 136.7, 139.9, 140.7, 141.4, 146.2,
147.1, 149.6, 151.7, 166.2, 166.8; MS: m=z ¼ 711 (Mþ, 2.37%), 570 (6.14%), 300
(5.81%), 285 (4.25%), 259 (13.68%), 241 (5.54%), 219 (4.88%), 194 (4.22%), 180
(10.05%), 191 (4.39%), 177 (3.58%), 166 (6.30%), 154 (3.01%), 150 (4.10%), 147
(10.21%), 127 (8.46%), 114 (9.46%), 104 (25.98%), 91 (43.81%), 77 (100%), 65
(43.62%). Anal. calcd. for C45H30N10(710.79): C, 76.04; H, 4.25; N, 19.71. Found:
C, 75.85; H, 4.12; N, 19.94%.
1,5-Diphenyl-3-(7-phenylisoxazolo[4,3-d]pyridazin-4-yl)-1H-pyrazole-4-
carbonitrile (29a). Colorless crystals from EtOH, yield (89%), mp 248–250 ꢀC; IR
1
=
(KBr): 3058 (CH), 2233 (CN), 1596 (C C); H NMR [(CD3)2SO]: d ¼ 7.24–8.31 (m,
15H, ArH’s), 8.65 (s, 1H, oxazole H-5); 13C NMR [(CD3)2SO]: d ¼ 104.2, 113.6,
119.0 (CN), 123.8, 128.2, 128.7, 129.3, 129.8, 131.2, 131.3, 131.5, 131.7, 136.3,
141.7, 148.2, 149.6, 150.4 (oxazole C-5), 153.2, 156.2, 158.6; MS: m=z ¼ 442
(M þ 1, 11.36%), 441 (Mþ, 32.29%), 338 (10.01%), 310 (5.99%), 272 (11.69%), 180
(19.40%), 172 (30.21%), 155 (22.20%), 141 (13.80%), 127 (37.98%), 115 (22.05%),
105 (18.37%), 77 (100%), 65 (11.24%). Anal. calcd. for C27H16N6O (440.46): C,
73.63; H, 3.66; N, 19.08. Found: C, 73.82; H, 3.45; N, 19.12%.
3-(7-(Furan-2-yl)isoxazolo[4,3-d]pyridazin-4-yl)-1,5-diphenyl-1H-pyrazole-
4-carbonitrile (29b). Brown crystals from diluted AcOH yield (89%), mp
1
280–282 C; IR (KBr): 3028 (CH), 2229 (CN), 1593 (C C); H NMR [(CD3)2SO]:
ꢀ
=
d ¼ 6.68 (d, 1H, J ¼ 8 Hz, furan H-3), 7.24–8.31 (m, 12H, ArH’s), 8.65 (s, 1H,
oxazole H-5); 13C NMR [(CD3)2SO]: d ¼ 104.2, 112.2, 113.4, 116.5, 118.6 (CN),
123.9, 128.6, 129.6, 129.9, 131.2, 131.6, 131.8, 141.3, 148.4, 149.2 (oxazole C-5),

DESIGN AND SYNTHESIS OF FUSED AZOLES
1123
149.7, 150.6, 153.4, 153.8, 157.6, 158.5; MS: m=z ¼ 432 (M þ 2, 1.66%), 431 (M þ 1,
6.01%), 430 (Mþ, 30.93%), 338 (3.74%), 310 (3.01%), 272 (7.53%), 244 (3.73%), 180
(25.30%), 141 (9.46%), 123 (4.12%), 104 (14.03%), 77 (100%), 65 (4.54%). Anal.
calcd. for C25H14N6O2(430.42): C, 69.76; H, 3.28; N, 19.53. Found: C, 69.65; H,
3.18; N, 19.75%.
1,5-Diphenyl-3-(7-(thien-2-yl)isoxazolo[4,3-d]pyridazin-4-yl)-1H-pyrazole-
4-carbonitrile (29c). Yellow crystals from diluted AcOH yield (89%), mp
1
ꢀ
=
284–286 C; IR (KBr): 3066 (CH), 2233 (CN), 1600 (C C); H NMR [(CD3)2SO]:
d ¼ 7.24–8.41 (m, 13H, ArH’s), 8.85 (s, 1H, isoxazole H-5); 13C NMR [(CD3)2SO]:
d ¼ 104.2, 111.6, 116.1, 118.7 (CN), 125.8, 129.7, 129.9. 131.2, 131.4, 131.7, 140.4,
141.6, 147.7 (oxazole C-5), 149.7, 149.9, 150.8, 154.5, 154.7, 156.5. 167.2; MS: m=
z ¼ 448 (M þ 1, 4.10%), 446 (Mþ, 38.72%), 338 (3.74%), 391 (5.84%), 310 (5.84%),
272 (8.75%), 180 (27.59%), 141 (13.43%), 123 (15.19%), 110 (10.19%), 104 (9.89%),
77 (100%), 65 (5.99%). Anal. calcd. for C25H14N6OS (446.48): C, 67.25; H, 3.16;
N, 18.82; S, 7.18. Found: C, 67.37; H, 3.04; N, 18.98; S, 7.33%.
3-(7-(Naphthalen-2-yl)isoxazolo[4,3-d]pyridazin-4-yl)-1,5-diphenyl-1H-
pyrazole-4-carbonitrile (29d). Pale yellow crystals from diluted AcOH yield
1
(90%), mp 258–260 C; IR (KBr): 3058 (CH), 2225 (CN), 1593 (C C); H NMR
ꢀ
=
[(CD3)2SO]: d ¼ 7.28–8.33 (m, 16H, ArH’s), 8.83 (s, 1H, ArH), 8.85 (s, 1H, isoxazole
H-5); 13C NMR [(CD3)2SO]: d ¼ 104.2, 118.6 (CN), 123.1, 125.4, 125.7, 126.4, 126.6,
127.4, 128.7, 129.7, 129.9, 131.1, 131.2, 131.3, 131.4, 131.45, 140.0, 141.4, 149.2,
149.7, 153.1, 154.5, 157.8, 163.0; MS: m=z ¼ 490 (Mþ, 1.10%), 489 (M ꢁ 1, 1.0%),
311 (3.74%), 255 (5.84%), 77 (45.36%). Anal. calcd. for C31H18N6O (490.51): C,
75.91; H, 3.70; N, 17.13. Found: C, 76.11; H, 3.85; N, 17.26%.
3-(4-(4-Cyano-1,5-diphenyl-1H-pyrazol-3-yl)isoxazolo[4,3-d]pyridazin-7-
yl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile (29e). Pale cream crystals
from diluted AcOH yield (92%), mp 242–244 ꢀC; IR (KBr): 3060 (CH), 2235
(CN), 1597 (C C); 1H NMR [(CD3)2SO]: d ¼ 2.32 (s, 3H, CH3), 7.24–8.33 (m,
=
19H, ArH’s), 8.85 (s, 1H, isoxazole H-5);13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3),
95.4, 104.2, 110.7, 118.6 (CN), 123.7, 127.8, 128.3, 129.8, 130.8, 131.4, 131.8,
133.2, 136.8, 141.4, 142.8, 146.3 (isoxazole C-5, 147.5, 149.3, 154.6, 1.65.7, 167.8.
Anal. calcd. for C38H23N9O (621.65): C, 73.42; H, 3.73; N, 20.28. Found: C,
73.24; H, 3.85; N, 20.42%.
5-Phenyl-3-(7-phenylisoxazolo[4,3-d]pyridazin-4-yl)-1-p-tolyl-1H-
pyrazole-4-carbonitrile (30a). Colorless crystals from diluted AcOH yield (89%),
1
ꢀ
=
=
mp 270–272 C; IR (KBr): 3044 (CH), 2225 (CN), 1617 (C N), 1576 (C C); H
NMR [(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 7.19–8.14 (m, 14H, ArH’s), 8.84 (s, 1H, iso-
xazole H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 104.2, 113.4, 118.6 (CN), 124.5,
128.3, 128.4, 129.9, 131.1, 131.6, 133.6, 136.2, 136.4, 142.5, 148.4, 149.3, 150.5 (iso-
xazole C-5), 152.9, 156.8, 158.5. Anal. calcd. for C28H18N6O (454.48): C, 74.00; H,
3.99; N, 18.49. Found: C, 74.15; H, 4.18; N, 18.67%.
3-[7-(2-Furyl)isoxazolo[3,4-d]pyridazin-4-yl]-1-(4-methylphenyl)-5-phenyl-
1H-pyrazole-4-carbonitrile (30b). Deep brown from diluted AcOH yield (89%),
mp 242–244 C; IR (KBr): 3066 (CH), 2233 (CN), 1600 (C C); 1H NMR
ꢀ
=

1124
A. O. ABDELHAMID ET AL.
[(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3C6H4), 6.92–8.23 (m, 12H, ArH’s), 8.93 (s, 1H, iso-
xazole H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 104.2, 112.1, 113.4, 116.8, 117.8
(CN), 124.2, 128.6, 129.8, 131.4, 131.5, 133.0, 136.7, 142.1, 148.2, 149.8 (isoxazole
C-5), 150.4, 153.5, 153.8, 156.8, 158.2; MS: m=z ¼ 446 (0.44%), 310 (79.38%), 296
(100%), 284 (11.96%), 291 (53.33%), 268 (52.26%), 255 (34.69%), 228 (20.76%),
215 (18.35%), 203 (25.10%), 193 (31.06%), 189 (16.10%), 194 (11.84%), 177
(35.26%), 167 (18.29%), 165 (14.52%), 151 (25.14%), 140 (44.05%), 134 (19.04%),
114 (33.09%), 131 (15.78%), 100 (30.71%), 91 (72.61%), 88 (31.98%), 76 (48.90%),
65 (59.48%). Anal. calcd. for C26H16N6O2 (444.44): C, 70.26; H, 3.63; N, 18.91.
Found: C, 70.45; H, 3.72; N, 19.07%.
5-Phenyl-3-(7-(thien-2-yl)isoxazolo[4,3-d]pyridazin-4-yl)-1-p-tolyl-1H-
pyrazole-4-carbonitrile (30c). Brown crystals from EtOH yield (89%), mp
1
ꢀ
=
238–240 C; IR (KBr): 3066 (CH), 2233 (CN), 1600 (C C); H NMR [(CD3)2SO]:
d ¼ 2.34 (s, 3H, CH3), 7.24–8.41 (m, 12H, ArH’s), 8.85 (s, 1H, isoxazole H-5); 13C
NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 113.4, 118.8 (CN), 124.2, 127.4, 128.3, 129.8,
131.6, 131.7, 132.5, 123.7, 133.2, 136.1, 139.4, 142.2, 148.3, 149.2 (isoxazole C-5),
149.9, 158.5, 160.4, 162.8; MS: m=z ¼ 462 (M þ 2, 16.39%), 461 (M þ 1, 8.88%),
460 (Mþ, 16.39%), 448 (20.45%), 477 (5.63%), 405 (7.25%), 390 (5.09%), 352
(12.13%), 315 (17.84%), 286 (15.91%), 231 (11.31%), 194 (37.18%), 155 (10.95%),
128 (15.81%), 123 (26.57%), 121 (30.89%), 111 (23.92%), 110 (17.92%), 104
(22.91%), 96 (23.00%), 91 (100%), 77 (56.98%), 65 (77.35%). Anal. calcd. for
C26H16N6OS (460.11): C, 67.81; H, 3.50; N, 18.25; S, 6.96. Found: C, 67.71; H,
3.68; N, 18.12; S, 7.15%.
3-(7-(Naphthalen-2-yl)isoxazolo[4,3-d]pyridazin-4-yl)-5-phenyl-1-p-tolyl-
1H-pyrazole-4-carbonitrile (30d). Colorless crystals from diluted AcOH yield
1
(87%), mp: 278–280 C; IR (KBr): 3047 (CH), 2225 (CN), 1577 (C C); H NMR
ꢀ
=
[(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 7.24–8.41 (m, 16H, ArH’s), 8.85 (s, 1H, isoxazole
H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (CH3), 113.4, 118.8 (CN), 123.2, 124.4, 125.3,
127.2, 127.4, 128.2, 129.8, 130.5, 131.4, 131.6, 131.7, 133.4, 136.6, 142.4, 148.0, 149.5,
150.6 (isoxazole C-5), 152.9, 156.6, 158.4. Anal. calcd. for C32H20N6O (504.54): C,
76.18; H, 4.00; N, 16.66. Found: C, 76.24; H, 4.11; N, 16.82%.
3-(4-(4-Cyano-5-phenyl-1-p-tolyl-1H-pyrazol-3-yl)isoxazolo[4,3-d]pyrida
zin-7-yl)-5-phenyl-1-p-tolyl-1H-pyrazole-4-carbonitrile (30e). Pale cream crys-
tals from diluted AcOH yield (92%), mp 258–260 ꢀC; IR (KBr): 3047 (CH), 2226
1
=
(CN), 1625 (1577 (C C); H NMR [(CD3)2SO]: d ¼ 2.34 (s, 3H, CH3), 7.24–8.41
(m, 16H, ArH’s), 8.85 (s, 1H, oxazole H-5); 13C NMR [(CD3)2SO]: d ¼ 20.1 (2
CH3), 95.6, 104.3, 110.6, 113.4, 118.8 (CN), 124.2, 127.4, 128.3, 129.6, 130.8,
131.6, 133.2, 136.4, 141.2, 142.4, 142.8, 146.6 (isoxazole C-5), 147.2, 148.7, 149.7,
154.3, 165.2, 167.5. Anal. calcd. for C39H25N9O (635.68): C, 73.69; H, 3.96; N,
19.83. Found: C, 73.69; H, 3.96; N, 19.83%.
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