Novel and convenient one-pot strategy for regioselective synthesis of new 5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives

Article abstract of DOI:10.1007/s11164-016-2848-5

Abstract: We describe a novel and simple regioselective synthesis of 5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives via one-pot three-component reaction of arylglyoxalmonohydrates, 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and hydrazine hydrate in presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as base-organocatalyst at room temperature in acetonitrile. This one-pot method has the advantages of simple methodology, high atom economy, cost-effectiveness, high regioselectivity, and easy workup. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-016-2848-5

Res Chem Intermed
DOI 10.1007/s11164-016-2848-5
Novel and convenient one-pot strategy for regioselective
synthesis of new 5-aryl-3-methyl-1-phenyl-1,2-dihydro-
7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives
Mehdi Rimaz1 Hossein Mousavi1 Laya Nikpey1
Behzad Khalili2
•
•
•
Received: 21 November 2016 / Accepted: 21 December 2016
Ó Springer Science+Business Media Dordrecht 2017
Abstract We describe a novel and simple regioselective synthesis of 5-aryl-3-methyl-1-
phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives via one-pot three-
component reaction of arylglyoxalmonohydrates, 5-methyl-2-phenyl-2,4-dihydro-3H-
pyrazol-3-one, and hydrazine hydrate in presence of 1,4-diazabicyclo[2.2.2]octane
(DABCO) as base-organocatalyst at room temperature in acetonitrile. This one-pot method
has the advantages of simple methodology, high atom economy, cost-effectiveness, high
regioselectivity, and easy workup.
Graphical Abstract
&
Mehdi Rimaz
rimaz.mehdi@gmail.com
1
2
Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
Department of Chemistry, Faculty of Sciences, University of Guilan, PO Box 41335-1914,
Rasht, Iran
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M. Rimaz et al.
Keywords Pyrazolo[3,4-c]pyridazine Á Arylglyoxalmonohydrate Á DABCO Á One-
pot synthesis
Introduction
One-pot, multicomponent reactions (MCRs) constitute a unique and extraordinary
synthetic strategy, offering benefits such as speed, synthetic efficiency, avoidance of
purification steps, facile and convenient operation, and diversity [1–6].
1,2-Dicarbonyl compounds, especially arylglyoxals (AGs), are very important
precursors used to synthesize diverse organic compounds [7–11]. Synthesis of
nitrogen-containing heterocyclic scaffolds has always represented an important and
attractive area of chemical research, as these moieties have found extensive
application in fields such as materials science [12, 13], catalysis [14–17], color
chemistry [18–20], and most importantly drug chemistry [21–24]. Among nitrogen-
containing heterocyclic compounds, pyrazole and its derivatives serve as building
blocks for different pharmaceutically important heterocyclic systems and possess a
wide range of biological activities [25, 26]; Some examples are shown in Fig. 1.
Recently, fused-pyrazole heterocyclic scaffolds have been applied to obtain useful
organic compounds that display unique biological activities [27–31]. In particular,
pyrazolopyridazines show potential activities such as antifungal [32], anti-herpes
simplex virus (HSV)-1 [33], antiinflammatory [34–37], and antimicrobial actions
[38, 39], and also as inhibitors of cyclin-dependent kinase 1 (CDK1) [40], as shown
Fig. 1 Example pyrazole-based drugs
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Novel and convenient one-pot strategy for…
Fig. 2 Selected biologically active pyrazolo[3,4-c]pyridazine derivatives
in Fig. 2. Recently, some pyrazolopyrimidopyridazinone derivatives and pyra-
zolo[3,4-b]pyridazines have been reported as potent and selective phosphodi-
esterase 5 (PDE5) [41, 42] and glycogen synthase kinase 3 (GSK-3) [43] inhibitors,
respectively. Also, some 3-amino-5,6-diaryl-1H-pyrazolo[3,4-c]pyridazines show
insecticidal activity [44].
Consequently, design and development of simple, efficient, and affordable
methodologies for preparation of pyrazolopyridazine derivatives is one of the most
attractive areas of organic synthesis and medicinal chemistry. A recent literature
survey revealed only two reports on synthesis of pyrazolopyridazines via one-pot
multicomponent reaction [45, 46].
In continuation of our work on synthesis of novel heterocyclic compounds
[47–50], especially new pyridazine derivatives [51–55] using one-pot multicompo-
nent strategies, we report herein an investigation of three-component condensation
of arylglyoxalmonohydrates, 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and
hydrazine hydrate under different conditions to determine whether pyrazolo[3,4-
c]pyridazine derivatives could be prepared by such a one-pot protocol (Scheme 1).
Results and discussion
Development of convenient protocols for biologically active pyrazolopyridazine
scaffolds from simple raw materials is a key research area in heterocyclic chemistry
and especially drug discovery programs. Therefore, the main goal of this work is to
introduce a simple one-pot strategy for synthesis of new pyrazolo[3,4-c]pyridazines
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M. Rimaz et al.
Scheme 1 One-pot synthesis of new pyrazolo[3,4-c]pyridazine derivatives
using inexpensive and available materials. To approach this goal, we first chose the
reaction of phenylglyoxalmonohydrate (1a), 5-methyl-2-phenyl-2,4-dihydro-3H-
pyrazol-3-one (2), and hydrazine (hydrazine hydrate or hydrazinium dihydrochlo-
ride) as model reaction. We optimized the reaction conditions using various solvents
such as water, ethanol, H2O–EtOH (1:1), acetonitrile (CH3CN), chloroform
(CHCl3), dioxane, and dimethylformamide (DMF) in presence of different molar
ratios of some basic organocatalysts such as 1,4-diazabicyclo[2.2.2]octane
(DABCO), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]un-
dec-7-ene (DBU), and pyridine. Use of zirconium(IV) oxydichloride octahydrate
(ZrOCl2Á8H2O) as green Lewis acid catalyst under different temperature conditions
was also examined. The reaction in pyridine as basic solvent was also carried out
without catalyst (Table 1, entries 27, 28). The results for these reactions indicated
that the solvent and catalyst had a significant effect on the synthesis of 3a. The best
results were obtained when the reaction of 1a, 2, and hydrazine hydrate was
performed in acetonitrile as polar organic solvent in presence of DABCO
(50 mol%) as catalyst. Note that, when the reaction was attempted without catalyst
in the aforementioned solvents (except pyridine), no product was obtained. This
shows that the catalyst (DABCO) plays a very important and effective role in this
transformation. Using the optimized conditions, the generality and effectiveness of
the present protocol was examined with a variety of arylglyoxalmonohydrates. It
was observed that arylglyoxalmonohydrates having electron-withdrawing or
electron-donating groups participated in the reaction without any significant
deviation in yield. However, some substituents (p-F and p-OCH3) required longer
reaction time (Table 2, entries 4, 5). The arylglyoxalmonohydrates were prepared
by oxidation of corresponding aryl methyl ketones according to standard literature
procedure (Scheme 2) [56].
The operational procedure for synthesis of 5-aryl-3-methyl-1-phenyl-1,2-dihy-
dro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives was found to be very simple.
After reaction completion, the solid product was filtered and washed with cool
acetonitrile and then hot methanol to afford pure product.
All of the new pyrazolo[3,4-c]pyridazine structures were confirmed by infrared
(IR), 1H and 13C nuclear magnetic resonance (NMR), and microanalysis; For
example, the 1H NMR spectrum of 3f revealed sets of eight aromatic proton signals
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Novel and convenient one-pot strategy for…
Table 1 Optimization of reaction conditions
Entry Solvent
Hydrazine
Catalyst (mol%)
Temp. (°C) Time (h) Yield (%)
1
H2O
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
DABCO (20)
DABCO (20)
rt
24
24
24
24
24
24
24
24
48
48
24
24
24
24
24
24
24
24
24
24
48
24
72
48
24
24
24
NR
NR
NR
NR
NR
NR
NR
30
2
H2O
50
3
H2O
ZrOCl2Á8H2O (20) rt
DABCO (20)
4
EtOH
EtOH
EtOH
rt
5
DABCO (20)
rt
6
Dihydrochloride ZrOCl2Á8H2O (20) Reflux
7
H2O–EtOH (1:1) Hydrate
DABCO (20)
DABCO (20)
DABCO (20)
DABCO (20)
50
8
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CHCl3
Hydrate
Hydrate
Hydrate
rt
9
0
10
10
11
12
13
15
16
17
18
19
20
21
22
23
24
25
26
27
28
45
rt
NR
NR
NR
NR
5
Dihydrochloride DABCO (20)
Hydrate
ZrOCl2Á8H2O (20) rt
Dihydrochloride ZrOCl2Á8H2O (20) rt
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
Hydrate
DBN (20)
DBU (20)
Pyridine (50)
DABCO (10)
DABCO (30)
DABCO (50)
DABCO (100)
–
rt
rt
NR
NR
5
rt
rt
rt
33
rt
45
rt
45
rt
NR
NR
27
DABCO (20)
DABCO (20)
DABCO (20)
DABCO (20)
–
rt
Dioxane
DMF
rt
rt
3
DMF
Reflux
rt
28
Pyridine
Pyridine
NR
25
–
Reflux
in the region d = 7.42–6.79 ppm, in addition to a sharp singlet signal at
d = 7.98 ppm due to CH protons of pyridazine ring, close to previous reports
1
[51–55, 57–61] of pyridazine hydrogen protons at d = 8 ppm. Furthermore, the H
NMR spectrum of 3f showed a singlet at d = 3.79 ppm for six methoxy protons,
and also a singlet signal at d = 2.28 ppm for the three protons of the methyl group.
It should be mentioned that the two peaks at d = 9.56 ppm and d = 13.10 ppm in
123

M. Rimaz et al.
the 1H NMR spectrum of compound 3f are related to OH and NH protons,
respectively. The observation of these peaks (OH and NH) shows that, in the one-
pot synthesis of these new pyrazolo[3,4-c]pyridazines, the aromatization process
Table 2 One-pot synthesis of 5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-
ol derivatives
Entry
1
Arylglyoxalmonohydrate
Product
Time (h)
24
Yield (%)
45
2
3
4
24
24
36
45
48
46
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Novel and convenient one-pot strategy for…
Table 2 continued
Entry
5
Arylglyoxalmonohydrate
Product
Time (h)
36
Yield (%)
46
6
24
52
7
24
57
8
24
53
Scheme 2 Synthesis of arylglyoxalmonohydrates
123

M. Rimaz et al.
was not completed. The 13C NMR spectrum of 3f showed two peaks at
d = 57.0 ppm and d = 56.6 ppm due to the two methoxy groups, and also a
signal at d = 14.3 ppm for the methyl group. It should be noted that, due to the low
solubility of these new 5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-
c]pyridazin-7a-ol derivatives, even in dimethyl sulfoxide (DMSO), attempts to
prepare single crystal suitable for X-ray analysis failed.
Based on literature reports [62–65] and the experimental results described above,
a plausible catalytic cycle for the presented one-pot regioselective synthesis of
5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol deriva-
tives is outlined in Scheme 3. The base-induced intermediate 6 undergoes
regioselective Knoevenagel condensation with the formyl group of arylglyoxal
(5a–h) (path A), leading to formation of the a‘b-unsaturated-1,4-dicarbonyl
compounds 7a–h with elimination of water. Intermolecular heterocyclization with
hydrazine hydrate (8) then affords the final product 3a–h.
Experimental
Materials and techniques
Melting points were determined on an Electrothermal 9200 apparatus. 1H
(300 MHz) and 13C (75.5 MHz) NMR spectra were recorded on a Bruker DRX-
300 AVANCE spectrometer in DMSO-d6 with tetramethylsilane as internal
standard. Infrared spectra were recorded on a PerkinElmer Spectrum Two FT-
infrared spectrophotometer, measured as KBr disks. Microanalyses were performed
on a Leco Analyzer 932. All chemical and reagents were purchased from Fluka,
Acros, and Merck and used without further purification.
General procedure for the regioselective synthesis of 5-aryl-3-methyl-1-phenyl-1,2-
dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives (3a–h) A mixture of
arylglyoxalmonohydrates (1 mmol) and 5-methyl-2-phenyl-2,4-dihydro-3H-pyra-
zol-3-one (1 mmol) and hydrazine hydrate (4 mmol) in the presence of DABCO
(50 mol%) as base-organocatalyst was stirred at room temperature in acetonitrile
(7 mL). After the reaction was completed, the solid products obtained were filtered
and washed with cool acetonitrile (5 mL) and then washed with hot methanol
(10 mL) to afford the pure products.
Physical and spectral data for compounds 3a–h: 5-Phenyl-3-methyl-1-phenyl-1,2-
dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol (3a) Yellow powder; m.p. 226 °C
(dec.). 1H NMR (300 MHz, DMSO-d6): 10.93 (s, 1H, OH), 8.12 (s, 1H, Ar), 7.85 (d,
J = 7.2 Hz, 2H, Ar), 7.75 (s, 1H, Ar), 7.50 (d, J = 7.2 Hz, 2H, Ar), 7.35–7.18 (m,
4H, Ar), 6.95 (t, J = 7.8 Hz, 1H, Ar), 2.43 (s, 3H, CH3); 13C NMR (75 MHz,
DMSO-d6): 160.6, 143.7, 139.1, 138.0, 130.3, 130.0, 129.6, 128.4, 127.8, 127.6,
126.7, 125.8, 125.3, 125.0, 114.4, 113.3, 112.5, 13.2 (CH3); IR (KBr) m: 3359, 3120,
3020, 2950, 2875, 1651, 1600, 1591, 1577, 1529, 1507, 1490, 1462, 1245, 1170,
123

Novel and convenient one-pot strategy for…
Scheme 3 Plausible mechanism for DABCO-promoted synthesis of 5-aryl-3-methyl-1-phenyl-1,2-
dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives
747, 716, 688, 604 cm-1. Anal. calcd. for C18H16N4O: C, 71.04; H, 5.30; N, 18.41.
Found: C, 71.06; H, 5.32; N, 18.60.
5-(4-Bromophenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-
1
7a-ol (3b) Yellow powder; m.p. 214 °C (dec.). H NMR (300 MHz, DMSO-d6):
123

M. Rimaz et al.
11.96 (bs, 1H, NH), 9.59 (s, 1H, OH), 7.99 (s, 1H, Ar), 7.84 (d, J = 8.4 Hz, 2H, Ar),
7.67 (d, J = 8.4 Hz, 2H, Ar), 7.25–7.18 (m, 4H, Ar), 6.80 (t, J = 6.3 Hz, 1H, Ar),
2.28 (s, 3H, CH3); 13C NMR (75 MHz, DMSO-d6): 160.3, 145.6, 143.8, 140.4,
139.6, 138.7, 133.3, 133.2, 131.3, 130.3, 129.3, 128.4, 127.3, 127.2, 126.6, 114.7,
112.8, 15.0 (CH3); IR (KBr) m: 3354, 2948, 1658, 1602, 1527, 1492, 1452, 1377,
1246, 1165, 830, 724 cm-1. Anal. calcd. for C18H15BrN4O: C, 56.41; H, 3.95; N,
14.62. Found: C, 56.44; H, 3.96; N, 14.78.
5-(4-Chlorophenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-
1
7a-ol (3c) Yellow powder; m.p. 208 °C (dec.). H NMR (300 MHz, DMSO-d6):
13.27 (s, 1H, NH), 9.59 (s, 1H, OH), 8.00 (s, 1H, Ar), 7.90 (d, J = 8.4 Hz, 2H, Ar),
7.53 (d, J = 8.4 Hz, 2H, Ar), 7.28–7.19 (m, 4H, Ar), 6.80 (t, J = 6.9 Hz, 1H, Ar),
2.29 (s, 3H, CH3); 13C NMR (75 MHz, DMSO-d6): 162.3, 145.6, 143.8, 139.6,
138.7, 134.3, 129.0, 128.4, 128.1, 126.9, 126.7, 124.7, 121.0, 119.3, 114.7, 112.8,
13.6 (CH3); IR (KBr) m: 3351, 3028, 2948, 1655, 1601, 1573, 1543, 1508, 1493,
1451, 1246, 1167, 1091, 886, 831, 734, 689 cm-1. Anal. calcd. for C18H15ClN4O:
C, 63.81; H, 4.46; N, 16.54. Found: C, 63.80; H, 4.42; N, 16.74.
5-(4-Fluorophenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-
1
7a-ol (3d) Yellow powder; m.p. 219 °C (dec.). H NMR (300 MHz, DMSO-d6):
11.85 (bs, 1H, NH), 9.58 (s, 1H, OH), 7.98 (s, 1H, Ar), 7.90 (t, J = 6.9 Hz, 2H, Ar),
7.33–7.21 (m, 6H, Ar), 6.79 (t, J = 6.6 Hz, 1H, Ar), 2.06 (s, 3H, CH3); 13C NMR
(75 MHz, DMSO-d6): 160.2, 145.6, 144.0, 139.6, 138.8, 132.0, 130.3, 129.5, 128.4,
127.5, 126.8, 124.9, 121.0, 119.3, 117.4, 117.1, 115.3, 115.0, 114.7, 112.7, 15.1
(CH3); IR (KBr) m: 3357, 3125, 3015, 2876, 1659, 1600, 1528, 1508, 1490, 1383,
1246, 1236, 1171, 1158, 1101, 838, 751, 692, 599 cm-1. Anal. calcd. for
C18H15FN4O: C, 67.07; H, 4.69; N, 17.38. Found: C, 67.07; H, 4.69; N, 17.38.
5-(4-Methoxyphenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyri-
dazin-7a-ol (3e) Yellow powder; m.p. 199 °C (dec.). 1H NMR (300 MHz,
DMSO-d6): 13.12 (s, 1H, NH), 9.56 (s, 1H, OH), 7.95 (s, 1H, Ar), 7.81 (d,
J = 8.7 Hz, 2H, Ar), 7.23 (d, J = 7.8 Hz, 4H, Ar), 7.03 (d, J = 8.4 Hz, 2H, Ar),
6.79 (t, J = 6.9 Hz, 1H, Ar), 3.80 (s, 3H, OCH3), 2.29 (s, 3H, CH3); 13C NMR
(75 MHz, DMSO-d6): 160.3, 160.2, 145.7, 144.7, 139.5, 139.0, 130.3, 128.3, 127.9,
126.8, 126.6, 124.8, 120.9, 115.8, 114.7, 113.7, 112.7, 54.7 (OCH3), 15.5 (CH3); IR
(KBr) m: 3415, 3018, 2953, 2878, 1655, 1602, 1591, 1540, 1510, 1491, 1455, 1379,
1248, 1177, 887, 832, 748, 696 cm-1. Anal. calcd. for C19H18N4O2: C, 68.25; H,
5.43; N, 16.76. Found: C, 68.27; H, 5.46; N, 16.95.
5-(3,4-Dimethoxyphenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyri-
dazin-7a-ol (3f) Yellow powder; m.p. 217 °C (dec.). 1H NMR (300 MHz, DMSO-
d6): 13.10 (s, 1H, NH), 9.56 (s, 1H, OH), 7.98 (s, 1H, Ar), 7.42 (s, 2H, Ar),
7.38–7.18 (m, 4H, Ar), 7.04 (d, J = 8.7 Hz, 1H, Ar), 6.79 (t, J = 6.6 Hz, 1H, Ar),
3.79 (s, 6H, 2 9 OCH3), 2.28 (s, 3H, CH3); 13C NMR (75 MHz, DMSO-d6): 160.3,
145.7, 144.7, 139.5, 139.0, 130.3, 128.4, 128.0, 127.0, 125.0, 120.9, 120.1, 119.3,
118.0, 114.6, 112.7, 111.1, 57.0 (OCH3), 56.6 (OCH3), 14.3 (CH3); IR (KBr) m:
3351, 3132, 3018, 2938, 1660, 1602, 1590, 1583, 1515, 1494, 1270, 1256, 1242,
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Novel and convenient one-pot strategy for…
1165, 1153, 1022, 865, 692 cm-1. Anal. calcd. for C20H20N4O3: C, 65.92; H, 5.53;
N, 15.38. Found: C, 65.94; H, 5.57; N, 15.53.
5-(4-Hydroxy-3-methoxyphenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-
1
c]pyridazin-7a-ol (3g) Yellow powder; m.p. 225 °C (dec.). H NMR (300 MHz,
DMSO-d6): 12.93 (bs, 1H, NH), 9.54 (s, 1H, OH), 7.94 (s, 1H, Ar), 7.39 (s, 1H,
OH), 7.38–7.22 (m, 6H, Ar), 6.88–6.70 (m, 2H, Ar), 3.82 (s, 3H, OCH3), 2.28 (s,
3H, CH3); 13C NMR (75 MHz, DMSO-d6): 160.3, 160.2, 148,3, 145.7, 145.0, 139.5,
139.1, 130.3, 128.4, 127.0, 126.7, 125.0, 120.9, 115.2, 114.6, 112.7, 108.7, 57.1
(OCH3), 15.7 (CH3); IR (KBr) m: 3407, 3121, 3019, 2959, 2925, 2880, 2855, 1655,
1602, 1517, 1464, 1382, 1278, 1254, 1168, 1137, 1062, 1032, 867, 750, 697,
591 cm-1. Anal. calcd. for C19H18N4O3: C, 65.13; H, 5.18; N, 15.99. Found: C,
65.10; H, 5.15; N, 16.20.
5-(3,4-Methylenedioxyphenyl)-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-
1
c]pyridazin-7a-ol (3h) Yellow powder; m.p. 178 °C (dec.). H NMR (300 MHz,
DMSO-d6): 13.13 (s, 1H, NH), 9.55 (s, 1H, OH), 8.47 (s, 1H, Ar), 7.93 (s, 1H, Ar),
7.56 (d, J = 7.5 Hz, 1H, Ar), 7.48–7.21 (m, 4H, Ar), 6.98 (t, J = 8.7 Hz, 1H, Ar),
6.79 (s, 1H, Ar), 6.08 (s, 2H, CH2) 2.81 (s, 3H, CH3); 13C NMR (75 MHz, DMSO-
d6): 160.2, 148,4, 145.7, 139.5, 138.9, 130.3, 129.7, 128.4, 126.9, 120.9, 119.4,
119.3, 114.7, 112.7, 108.4, 105.2, 102.0, 101.8 (OCH2O), 14.6 (CH3); IR (KBr) m:
3371, 3180, 3023, 1645, 1590, 1546, 1502, 1447, 1260, 1247, 1224, 1205, 1168,
1037, 871 cm-1. Anal. calcd. for C19H16N4O3: C, 65.51; H, 4.63; N, 16.08. Found:
C, 65.55; H, 4.65; N, 16.30.
Conclusions
We have developed a novel and convenient method for regioselective synthesis of
new
5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol
derivatives by one-pot, three-component reaction of arylglyoxalmonohydrates,
5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and hydrazine hydrate in pres-
ence of DABCO as base-organocatalyst at room temperature in acetonitrile. This
method has advantages such as simple operation, high regioselectivity, high atom
economy, and easy workup. Furthermore, the NH group adjacent to the N-Ph group
in the pyrazole moiety may be an essential structural requirement for binding of
these new substituted pyrazolopyridazines to a variety of biological receptors.
Acknowledgements Financial support from the Research Council of Payame Noor University is
gratefully acknowledged.
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