Pyridazine derivatives and related compounds part 10. Reactions of 3-diazopyrazolo[3,4-c]pyridazine with reactive methylene compounds and other groups

Article abstract of DOI:10.3987/COM-03-9960

3-Diazopyrazolo[3,4-c]pyridazine was synthesized and its transformations were investigated. With reactive methylene compounds the corresponding hydrazones and condensed 1,2,4-triazines were formed. With aromatic amines and naphthols the diazo compound was converted into arylazo derivatives. The diazo compound underwent cycloaddition, reacting as a 1,4-dipole to yield cycloaddition products.

Full text of DOI:10.3987/COM-03-9960

HETEROCYCLES, Vol. 63, No. 5, 2004, pp. 1143 - 1151
Received, 14th November, 2003, Accepted, 4th March, 2004, Published online, 8th March, 2004
PYRIDAZINE DERIVATIVES AND RELATED COMPOUNDS PART 10.1
REACTIONS OF 3-DIAZOPYRAZOLO[3,4-c]PYRIDAZINE WITH
REACTIVE METHYLENE COMPOUNDS AND OTHER GROUPS
Ali Deeb* and Mahmoud Kotb
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
Abstract – 3-Diazopyrazolo[3,4-c]pyridazine was synthesized and its transforma-
tions were investigated. With reactive methylene compounds the corresponding
hydrazones and condensed 1,2,4-triazines were formed. With aromatic amines and
naphthols the diazo compound was converted into arylazo derivatives. The diazo
compound underwent cycloaddition, reacting as a 1,4-dipole to yield cyclo-
addition products.
Heterocyclic diazo compounds represent an interesting class of reactive substrates and their stability
depends mainly on charge delocalization through the heterocyclic ring. Moreover, several heterocyclic
diazo compounds possess a biological activity.2 In view of these facts and our interest in the synthetic
potential of fused pyridazine systems, we reported the synthesis of naphtho[2,1-c]pyridaz-
ino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine and pyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine deriva-
tives based on coupling reaction of 3-diazo-4,5-diphenylpyrazolo[3,4-c]pyridazine (1) with β−naphthol
and with ethyl acetoacetate respectively.3 In continuation of this work, we report here the results of our
further investigation on the reaction of compound (1) with further active methylene compounds and
cycloaddition reactions.
The reaction of 1 with ethyl cyanoacetate, diethyl malonate, cyclohexane-1,3-dione, dimedone, 1,3-
indandione, 3-methyl-5-pyrazolone, 1-phenyl-3-methyl-5-pyrazolone, thiobarbituric acid, 8-hydroxy-
quinoline, 4-hydroxycarbostyrile and 4-hydroxy-1-phenyl-2-quinolone, formed easily the corresponding
hydrazone compounds (2-12). For all compounds of this type several tautomeric forms can be written.
For example, compounds of the types (2) and (3) can be regarded as azo compounds or as hydrazones,
and the carbonyl part can be written in the keto or enolized form. The end of the reaction was judged by
the disappearance of the diazo compound according to TLC analysis. The reaction time varied from a
few minutes to several hours. The reaction products were isolated in high yield and gave satisfactory
elemental analysis. The spectroscopic properties of the products were in excellent agreement with the
proposed structures.
On the other hand, malononitrile, cyanoacetamide, malonamide and malonyl-α-aminopyridine4 afforded

O
O
O
H
H
Het-NHN
O
N
N
Het-NHN
O
Het-NHN
S
N
R
N
10
9
R = H
11,
12,
R = Ph
･
Ph
Ph
N
N N
N2
N
Ph
Ph
N
X
N
Het-NHN C
N
N
･
N
Y
N
X = CN, Y = COOEt
2,
3,
1
X = Y = COOEt
Me
O
O
O
R
N
N
Het-NHN
Het-NHN
Het-NHN
Het-NHN
R
R
O
O
O
R = H
R = H
7,
8,
4,
5,
6
R = Ph
R = Me
Ph
N
Ph
N
Het =
N
N
H
pyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine derivatives (13-16). The assignment of the cyclic
compounds involves the initial formation of acyclic hydrazones which undergo immediate intramolecular
nucleophilic attack of pyrazole ring 2-nitrogen to the cyano group or amide carbonyl group.
Ph
Ph
Ph
H
N
H
N
Ph
N
Z
Ph
N
Ph
N
N
N
1
N
N
N
N
N
N
N
Y
N
N
Y
N
N
CONH2
X
O
13,
14,
15
X = NH2, Y = CN
X = NH , Y = CONH
2
2
O
N
X + Y =
16,
N
The o-aminonitrile (13) was converted into compound (17) in boiling formamide.5
The reaction of the o-aminonitrile (13) with phenyl isocyanate yielded the thiourea derivative (18). With
view of studying some of the reactions of the hydrazone (2), that was allowed to react with hydrazine

Ph
N
Ph
N
Ph
N
N
Ph
N
N
N
N
N
NH2
N
N
N
N
CN
N
NH
C
S
NHPh
18
17
hydrate produced aminopyrazolone derivative (19), and the hydrazone (2) was also readily cyclized in
concentrated sulfuric acid at 70° to give the ester (20), whose reaction with alcoholic ammonia afforded
the amide (14).
NH2
N
Ph
NHN
N
Ph
H
N
O
N
N
N
H
2
19
Ph
Ph
N
NH3
N
14
N
N
N
N
COOEt
NH2
20
Thermal cyclization of compound (3) was unsuccessful, but its refluxing in glacial acetic acid provided
the ester (21), whose reaction with alcoholic ammonia afforded the amide (15).
Ph
H
N
Ph
N
NH3
3
15
N
N
N
N
COOEt
O
21
Azo coupling of 1 also took place with N,N-dimethylaniline, β-naphthylamine, naphthol-AS and with
naphthol-AS-LC to give the C-azo products (22-25).
H2N
Ph
Ph
N
NMe2
N
N
N
N
Ph
Ph
N
N
N
N
N
N
N
H
H
22
23

HO
CONHAr
Ar = Ph
24,
25,
Ph
N
N
N
MeO
Ph
N
Ar =
Cl
OMe
N
N
H
Compound (1), because of charge polarization and potential bifunctional reactivity, reacts with
dipolarophiles to give cycloaddition products. Compound (1) reacts with phenyl isothiocyanate as well
as ethoxycarbonylisothiocyanate in boiling dichloromethane to give cyclic tetrazine derivatives (26) and
(27). These reactions were regarded as a [4+2] cycloaddition of the diazo derivative to isothiocyanates.
The cycloaddition reaction of diazo compound (1) with dimethyl acetylenedicarboxylate at room
temperature afforded dimethyl 9,10-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3,4-di-
carboxylate (28).
Ph
Ph
Ph
N
Ph
N
N
N
N
N
N
N
N
N
N
COOMe
COOMe
N
N
R
S
28
26,
27,
R = Ph
R = COOEt
EXPERIMENTAL
All the melting points are uncorrected. The IR spectra of the compounds were recorded on a Perkin
1
Elmer spectrophotometer model 1310, H-NMR spectra on a Perkin Elmer R12B spectrometer and
chemical shifts (δ) are in ppm relative to internal tetramethylsilane and mass spectra were recorded on a
Shimadzu GCMS-GB 1000 PX (70 eV).
Compound (1) was prepared in 96% yield as yellow crystals (mp 110°C) by diazotization of 3-amino-4,5-
diphenyl-1H-pyrazolo[3,4-c]pyridazine with sodium nitrite in glacial acetic acid at rt.3 Its IR spectrum
revealed an absorption band at 2119 cm-1 typical for diazo compounds,6 MS spectrum: m/z: 298 (M+,
8.5%), 271 (51.4%), 242 (100%), 214 (66.3%).
General Procedure for the Preparation of Coupling Products from 3-Diazo-4,5-diphenylpyrazolo-
[3,4-c]pyridazine (1) and Active Methylene Compounds.
A solution of compound (1) (0.6 g, 2 mmol) in ethanol or in glacial acetic acid (20 mL) was treated with
the corresponding active methylene compound (2 mmol). The reaction mixture was refluxed for few
minutes to several hours. The separated product was filtered off and recrystallized. In this manner the
following compounds were prepared.
Ethyl 2-cyano-2-(4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono) acetate (2).

Light brown crystals, 72% yield, mp 247-248°C (ethanol); MS: m/z 411 (M+, 100%), 338 (52%), 284
(66.6%), 214 (42.1%), 127 (34%), 77 (84.3%). IR: 3218-3160 (NH), 2225 (CN), 1720 (C=O), 1620
(C=N) and 1550 cm-1 (C=C); 1H-NMR (DMSO-d6): 14.5 (s, 1H, NH), 12.4 (s, 1H, NH), 7.8-7.2 (m, 10H,
2Ph), 4.6-4.4 (q, J = 6.4 Hz, 2H, CH2CH3) and 1.3 (t, J = 6.4 Hz, 3H, CH2CH3). Anal. Calcd for
C22H17N7O2 : C, 64.22; H, 4.17; N, 23.83. Found: C, 64.20; H, 4.10; N, 23.70.
Diethyl 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazonomalonate (3).
White crystals, 60% yield, mp 144-145oC (ethanol); IR: 3420, 3300 (NH), 1700 (C=O), 1655 (C=N) and
1515 cm-1 (C=C), 1H-NMR (DMSO-d6): 14.3 (s, 1H, NH), 12.4 (s, 1H, NH), 7.6-7.3 (m, 10H, 2Ph), 4.6-
4.0 (m, 4H, 2 CH2CH3) and 1.5-1.3 (m, 6H, 2 CH2CH3). MS: m/z 458 (M+, 14.79%), 385 (100%), 330
(13.83%), 271 (48.34%). Anal. Calcd for C24H22N6O4: C, 62,87; H, 4.84; N, 18.33. Found: C, 62.70; H,
4.70; N, 18.20
2-(4,5-Diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-1,3-cyclohexanedione (4).
Brown crystals, 54% yield, mp > 300oC (ethanol); IR: 3500, 3470 (NH), 1695 (C=O), 1625 (C=N) and
1550 cm-1 (C=C); 1H-NMR (DMSO-d6): 7.6-7.2 (m, 10H, 2Ph), 3.9-3.6 (m, 2H, 4`-CH2), 3.1-2.8 (m, 2H,
5`-CH2) and 2.6-2.2 (m, 2H, 6`-CH2). Anal. Calcd for C23H18N6O2: C, 67,30; H, 4.42; N, 20.48. Found:
C, 67.20; H, 4.30; N, 20.30.
5,5-Dimethyl-2-(4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-1,3-cyclohexanedione (5).
Yellow crystals, 28% yield, mp 187-188oC (ethanol); IR: 3550, 3470 (NH), 1710, 1700 (C=O), 1650
(C=N) and 1530 cm-1 (C=C); 1H-NMR (CDCl3): 7.6-7.2 (m, 10H, 2Ph), 3.65 (s, 2H, 4`-CH2), 2.85 (s, 2H,
6`-CH2) and 1.25 (s, 6H, 2CH3). Anal. Calcd for C25H22N6O2: C, 68.47; H, 5.06; N, 19.17. Found: C,
68.40; H, 4.90; N, 19.00.
2-(4,5-Diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-1,3-indanedione (6).
Orange crystals, 64% yield, mp 267-268oC (ethanol); IR: 3300 (NH), 1695, 1667 (C=O), 1655 (C=N) and
1515 cm-1 (C=C), 1H-NMR (CDCl3): 13.9 (s, 1H, NH), 12.8 (br s, 1H, NH) and 7.8-7.2 (m, 14H,
aromatic protons). Anal. Calcd for C26H16N6O2: C, 70,26; H, 3.63; N, 18.91. Found: C, 70.10; H, 3.50;
N, 18.80.
3-Methyl-4-(4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-2-pyrazolin-5-one (7).
Yellow crystals, 75% yield, mp > 300oC (ethanol); IR: 3170 (NH), 1670 (C=O), 1625 (C=N) and 1530
cm-1 (C=C); 1H-NMR (DMSO-d6): 9.9 (d, J=5.3 Hz, 1H, NH hydrazone), 8.6 (br, 1H, NH pyrazolo), 8.2
(br, 1H, NH pyrazolone), 7.8-7.6 (m, 10H, 2Ph) and 2.8 (s, 3H, CH3). Anal. Calcd for C21H16N8O: C,
63,62; H, 4.07; N, 28.27. Found: C, 63.50; H, 3.90; N, 28.10.
3-Methyl-1-phenyl-4-(4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-2-pyrazolin-5-one
(8).
Orange crystals, 88% yield, mp 298-299oC (ethanol); IR: 3175 (NH), 1675 (C=O), 1630 (C=N) and
1525 cm-1 (C=C); 1H-NMR (DMSO-d6): 9.9 (d, J=5.2 Hz,1H, NH hydrazone), 8.6 (br, 1H, NH pyrazolo),
7.8-7.6 (m, 15H, 3Ph) and 2.8 (s, 3H, CH3). Anal. Calcd for C27H20N8O: C, 68,63; H, 4.27; N, 23.72.
Found: C, 68.50; H, 4.10; N, 23.60.

5-(4,5-Diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-2-thioxohexahydropyrimidine-4,6-
dione (9).
Yellow crystals, 90% yield, mp 290-291oC (ethanol); IR: 3310 (NH), 1695, 1690 (C=O), 1650 (C=N) and
1535 cm-1 (C=C); 1H-NMR (DMSO-d6): 14.5 (s, 1H, NH), 13.5 (s, 1H, NH) and 7.6 - 7.0 (m, 10H, 2Ph).
Anal. Calcd for C21H14N8O2S: C, 57,00; H, 3.19; N, 25.33. Found: C, 56.90; H, 3.00; N, 25.20.
5-(4,5-Diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)quinolin-8(5H)-one (10).
White crystals, 80% yield, mp 177-178oC (ethanol), IR: 3310 (NH), 1695 (C=O), 1655 (C=N) and 1510
cm-1 (C=C), 1H-NMR (CDCl3): 7.8-7.2 (m, 15H, 2Ph and quinoline protons). Anal. Calcd for C26H17N7O:
C, 70,42; H, 3.86; N, 22.11. Found: C, 70.30; H, 3.70; N, 22.00.
3-(4,5-Diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)quinoline-2,4-(1H,3H)-dione (11).
Orange crystals, 63% yield, mp 289-290oC (ethanol); IR: 3340 (NH), 1670 (C=O), 1656 (C=N) and 1530
1
cm-1 (C=C); H-NMR (DMSO-d6): 14.8 (br, 1H, NH) and 8.1-7.0 (m, 14H, aromatic phenyl groups).
Anal. Calcd for C26H17N7O2: C, 67,96; H, 3.73; N, 21.34. Found: C, 67.80; H, 3.60; N, 21.20.
3-(4,5-Diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-1-phenylquinoline-2,4-(1H,3H)-dione
(12).
Orange crystals, 55% yield, mp 284-285oC (ethanol); IR: 3400 (NH), 1690 (C=O), 1650 (C=N) and 1530
1
cm-1 (C=C); H-NMR (DMSO-d6): 8.2 - 6.9 (m, 15H, 3Ph) and 6.6 - 6.2 (m, 4H, aromatic ring). Anal.
Calcd for C32H21N7O2: C, 71,76; H, 3.95; N, 18.31. Found: C, 71.60; H, 3.80; N, 18.20.
4-Amino-9,10-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3-carbonitrile (13).
Red crystals, 81% yield, mp > 300oC (1-butanol); IR: 3320, 3300 (NH2), 2220 (CN), 1660 (C=N) and
1
1530 cm-1 (C=C), H-NMR (DMSO-d6): 7.6-7.1 (m, 10H, 2Ph) and 5.95 (s, 2H, NH2 disappeared by
addition of D2O). Anal. Calcd for C20H12N8: C, 65,92; H, 3.32; N, 30.75. Found: C, 65.80; H, 3.20; N,
30.60.
4-Amino-9,10-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3-carboxamide (14).
Yellow crystals, 52% yield, mp > 300oC (ethanol); IR: 3400, 3300, 3200 (NH2), 1680 (C=O), 1590
(C=N) and 1510 cm-1 (C=C); 1H-NMR (DMSO-d6): 7.5 - 7.3 (m, 10H, 2 Ph) and 3.6 (s, 4H, 4NH). Anal.
Calcd for C20H14N8O: C, 62,82; H, 3.69; N, 29.30. Found: C, 62.70; H, 3.60; N, 29.20.
9,10-Diphenyl-1,4-dihydro-4-oxopyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3-carboxamide
(15).
Orange crystals, 62% yield, mp 201-202oC (1-butanol); IR: 3200 (NH2), 1686 (C=O), 1630 (C=N) and
1520 cm-1 (C=C), 1H-NMR (DMSO-d6): 11.88 (br s, 1H, NH), 7.6-7.0 (m, 10H, 2Ph) and 6.9 (br s, 2H,
NH2). Anal. Calcd for C20H13N7O2: C, 62,66; H, 3.42; N, 25.58. Found: C, 62.50; H, 3.30; N, 25.40.
10,11-Diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]pyrido[1`,2`:1,2]pyrimido[4,5-e]-1,2,4-triazin-14-
one (16).
Orange crystals, 60% yield, mp > 300oC (acetic acid); IR: 1665 (C=O), 1655 (C=N) and 1560 cm-1

(C=C); 1H-NMR (CF3COOD): 8.8 - 8.6 (m, 4H, aromatic H) and 8.2 - 7.4 (m, 10H, 2Ph). Anal. Calcd for
C25H14N8O: C, 67.86; H, 3.19; N, 25.33. Found : C, 67.70; H, 3.00; N, 25.20.
12-Amino-8,9-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]pyrimido[4,5-e]-1,2,4-triazine (17).
The aminonitrile (13) (1.0 g, 2.7 mmol) was boiled in formamide (10 mL) for 1 h and the mixture was
diluted with water to precipitate crystals. The solid product was collected and recrystallized from
dimethylformamide, (0.6 g, 56%), mp > 300oC; IR: 3340, 3325 (NH2), 1655 (C=N) and 1530 cm-1 (C=C),
1H-NMR (DMSO-d6): 8.13 (s, 2H, NH2 exchangeable with D2O), 7.61-7.20 (m, 10H, 2Ph) and 6.8 (s, 1H,
H-2). Anal. Calcd for C21H13N9: C, 64.44; H, 3.35; N, 32.21. Found: C, 64.20; H, 3.20; N, 32.10.
9,10-Diphenyl-4-(N-phenylthiocarbamoylamino)pyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-
3-carbonitrile (18).
A mixture of the o-aminonitrile (13) (0.73 g, 2 mmol) and phenylisothiocyanate (0.27 g, 2 mmol) in
1-butanol (20 mL) was refluxed for 5 h. The yellow solid separated on cooling was filtered and
recrystallized from 1-butanol, (0.88 g, 88%), mp 242-243oC; IR: 3450, 3150 (NH), 1680 (C=S) and 1525
1
cm-1 (C=C); H-NMR (DMSO-d6): 13.0 (s, 1H, NH), 12.7 (s, 1H, NH) and 7.5-7.3 (m, 15H, 3Ph). Anal.
Calcd for C27H17N9S : C, 64.91; H, 3.43; N, 25.23. Found: C, 69.90; H, 3.40; N, 25.20.
3-Amino-4-(4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-ylhydrazono)-2-pyrazolin-5-one ( (19).
To a solution of acyclic hydrazone (2) (0.82 g, 2 mmol) in ethanol (20 mL), hydrazine hydrate (85%, 1
mL, 20 mmol) was added. The reaction mixture was refluxed for 3 h. Upon cooling a brown precipitate
product was filtered and recrystallized from ethanol, (0.7 g, 80%), mp > 300oC; IR: 3355, 3280, 3210,
1
3140 (NH), 1680 (C=O), 1620 (C=N) and 1570 cm-1 (C=C); H-NMR (DMSO-d6): 7.8 - 7.2 (m, 10H,
2Ph) and 3.4 (br s, 2H, NH2). Anal. Calcd for C20H15N9O: C, 60.44; H, 3.80; N, 31.72. Found: C, 60.30;
H, 3.70; N, 31.60.
Ethyl 4-amino-9,10-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3-carboxylate (20).
Heating acyclic hydrazone (2) (1 g, 2.44 mmol) in conc. sulfuric acid (5 mL) at 70o for 10 min. The
reaction mixture after cooling was poured onto water (100 mL). The solid precipitated filtered,
recrystallized from ethanol, (0.7 g, 78%), mp > 300oC; IR: 3340, 3210 (NH2), 1670 (C=O), 1625 (C=N)
1
and 1510 cm-1 (C=C); H-NMR (DMSO-d6): 9.8 (s, 2H, NH2), 7.7-7.2 (m, 10H, 2Ph), 4.6-4.4 (q, J=6.5
Hz, 2H, CH2CH3) and 1.3 (t, J=6.5 Hz, 3H, CH2CH3). Anal. Calcd for C22H17N7O2: C, 64.22; H, 4.17; N,
23.83. Found: C, 64.00; H, 4.00; N, 23.70.
Ethyl 9,10-diphenyl-1,4-dihydro-4-oxopyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3-carbox-
ylate (21).
Compound (3) (1 g, 2.18 mmol) was dissolved in glacial acetic acid (20 mL), and heated under reflux for
3 h. The solvent was evaporated to one-third of its original volume, and after cooling the product
separated was filtered off and recrystallized from ethanol, (0.75 g, 83%), mp 291-292oC; IR: 3200 (NH),
1739, 1690 (C=O), 1620 (C=N), and 1515 cm-1 (C=C), 1H-NMR (DMSO-d6): 11.7 (br s, 1H, NH), 7.67-

7.40 (m, 10H, 2Ph), 4.5-4.3 (q, J=6.0 Hz, 2H, CH2CH3) and 1.3 (t, J=6.0 Hz, 3H, CH2CH3). Anal. Calcd
for C22H16N6O3: C, 64.07; H, 3.91; N, 20.38. Found: C, 63.90; H, 3.70; N, 20.10.
Reaction of o-aminoester (20) and ester (21) with ammonia.
A solution of compound (20) or (21) (0.5 g) in absolute ethanol (50 mL) was saturated at 0° with dry
ammonia gas and left at rt for 24 h. The mixture was filtered to remove insoluble solid and the filtrate
was evaporated to afford the o-aminocarboxamide (14) (0.35 g, 76%) or carboxamide (15) (0.3 g, 65%)
respectively.
4,5-Diphenyl-3-[4-(N,N-dimethylanilin-1-yl)azo]-1H-pyrazolo[3,4-c]pyridazine (22).
To a solution of compound (1) (0.6 g, 2 mmol) in ethanol (20 mL), was added at rt N,N-dimethylaniline
(0.25 g, 2 mmol) in ethanol (20 mL). A brown crystals deposit. The separated product was filtered and
1
recrystallized from ethanol (0.49, 58%), mp 266 – 268°C; IR: 1655 (C=N) and 1535 cm-1 (C=C), H-
NMR (CDCl3):12.1 (br s, 1H, NH), 7.8-7.4 (m, 2H, aryl), 7.6-7.5 (m, 2H, aryl), 7.4-7.0 (m, 10H, 2Ph)
and 3.25 (s, 6H, NMe2). Anal. Calcd for C25H21N7: C, 71.58; H, 5.05; N, 23.37. Found: C, 71.40; H,
4.90; N, 23.20.
4,5-Diphenyl-3-[(2-naphthylamin-1-yl)azo]-1H-pyrazolo[3,4-c]pyridazine (23).
A mixture of compound (1) (0.6 g, 2 mmol) and β-naphthylamine (0.29 g, 2 mmol) in ethanol (30 mL)
containing sodium acetate (0.4 g) was refluxed for 30 min. Brown crystals deposit during the refluxing
time. The separated product was collected and recrystallized from ethanol (0.72 g, 81%), mp 266-267oC;
IR: 3320, 3300 (NH2), 1660 (C=N) and 1530 cm-1 (C=C), 1H-NMR (DMSO-d6): 13.1 (br s, 1H, NH), 8.1
(s, 2H, NH2) and 7.8-7.6 (m, 16H, aromatic protons). Anal. Calcd for C27H19N7: C, 73.45; H, 4.34; N,
22.21. Found: C, 73.30; H, 4.20; N, 22.10.
Reaction of compound (1) with naphthol-AS and naphthol-AS-LC.
To a solution of compound (1) (0.6 g, 2 mmol) in ethanol (30 mL). Was added naphthol AS (0.53 g, 2
mmol) or naphthol-AS-LC (0.72 g, 2 mmol) in water (10 mL) containing sodium hydroxide (0.1 g, 2.5
mmol). The reaction mixture was stirred at rt for 30 min. After acidification with 50% hydrochloric acid,
a red compound was separated, filtered and recrystallized from ethanol, (24, 1.1 g, 97%), mp 190-191oC;
IR: 3400 br (OH), 1660 (C=O), 1650 (C=N) and 1535 cm-1 (C=C), 1H-NMR (DMSO-d6): 12.6 (br s, 1H,
NH), 10.6 (s, 1H, CONH), 10.3 (s, 1H, OH) and 7.8-7.2 (m, 20H, aromatic protons). Anal. Calcd for
C34H23N7O2: C, 72.71; H, 4.13; N, 17.46. Found: C, 72.60; H, 4.00; N, 17.30 and (25, 1.2 g, 90%), mp
119-120oC; IR: 1650 (C=O), 1640 (C=N) and 1530 cm-1 (C=C), 1H-NMR (DMSO-d6): 13.1 (br s, 1H,
NH), 10.6 (s, 1H, CONH), 10.4 (s, 1H, OH), 7.6-7.1 (m, 17H, aromatic protons), 3.61 (s, 3H, OMe-2`)
and 3.4 (s, 3H, OMe-5`). Anal. Calcd for C36H26N7O4Cl: C, 65.90; H, 3.99; N, 14.94. Found: C, 65.70; H,
3.80; N, 14.70 respectively.
3,9,10-Triphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-d]-1,2,3,5-tetrazine-4-thione (26).

Phenyl isothiocyanate (0.27 g, 2 mmol) in dichloroethane (10 mL) was added dropwise to compound (1)
(0.6 g, 2 mmol) in dichloroethane (40 mL) at rt. The reaction mixture was refluxed 2 h. A yellow crystals
deposit on cooling was filtered and recrystallized from dichloroethane, (0.35 g, 40%), mp 152-153oC; IR:
1660 (C=N), 1270 (C=S) and 1550 cm-1 (C=C), 1H-NMR (DMSO-d6): 7.8-7.6 (m, 5H, NPh) and 7.5-7.1
(m, 10H, 2Ph). Anal. Calcd for C24H15N7S: C, 66.49; H, 3.49; N, 22.62. Found: C, 66.40; H, 3.30; N,
22.50.
3-Ethoxycarbonyl-9,10-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-d]-1,2,3,5-tetrazine-4-thione (27).
To a solution of compound (1) (0.6 g, 2 mmol) in dichloroethane (40 mL). Was added ethoxycarbonyl-
isothiocyante (0.27 g, 2 mmol) in dichloroethane (10 mL). The reaction mixture was refluxed for 2 h.
Brown crystals deposit on cooling, filtered and recrystallized from dichloroethane, (0.58 g, 67%), mp 233
- 234oC; IR: 1700 (C=O), 1660 (C=N), 1275 (C=S) and 1540 cm-1 (C=C); 1H-NMR (DMSO-d6): 7.8-7.5
(m, 10H, 2Ph), 4.6-4.4 (q, J=7.2 Hz, 2H, CH2CH3) and 1.3 (t, J=7.2 Hz, 3H, CH2CH3). Anal. Calcd for
C21H15N7O2S: C, 58.73; H, 3.52; N, 22.83. Found: C, 58.60; H, 3.40; N, 22.70.
Dimethyl 9,10-diphenylpyridazino[3`,4`:3,4]pyrazolo[5,1-c]-1,2,4-triazine-3,4-dicarboxylate (28).
A solution of 1 (0.6 g, 2 mmol) in acetonitrile (30 mL) was treated with dimethyl acetylenedicarboxylate
(0.29 g, 2 mmol), and the reaction mixture was stirred at rt for 48 h. The solvent was evaporated to one-
third of its original volume, and after addition of petroleum ether the product separated (0.53, 70%), mp
190-191oC (ethanol-water); IR: 1710, 1705 (C=O), 1630 (C=N), and 1520 cm-1 (C=C), 1H-NMR (DMSO-
d6): 7.54-7.10 (m, 10H, 2Ph), 3.69 (s, 3H, COOMe-3) and 3.6 (s, 3H, COOMe-4). Anal. Calcd for
C23H16N6O4: C, 62.72; H, 3.66; N, 19.08. Found: C, 62.50; H, 3.50; N, 18.80.
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