New synthesis and reactions of ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole- 3-carboxylate

Article abstract of DOI:10.1002/jhet.1691

Synthesis of ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o-chloroaldehyde 1. Reaction of o-aminocarbonitrile 5 with concentrated H₂SO₄ furnished expected o-amino

Full text of DOI:10.1002/jhet.1691

Month 2014
New Synthesis and Reactions of Ethyl 5-amino-4-cyano-1-phenyl-1H-
pyrazole-3-carboxylate
*
Sachin A. Gangurde, Shrikant B. Kanawade, Prashant S. Nikam, Dinesh C. Bhavsar, and Raghunath B. Toche
Organic Chemistry Research Center, Department of Chemistry, K.R.T. Arts, B.H. Commerce and A. M. Science College,
University of Pune, Gangapur Road, Nashik 422002, Maharashtra, India
*
E-mail: raghunath_toche@rediffmail.com
Received November 2, 2011
DOI 10.1002/jhet.1691
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
N
O
N
O
N
CN
Cl
CHO
Cl
EtO
EtO
CN
EtO
N
X
N
N
N
Ph
3
Ph
1
Ph
13a,b
O
N
O
O
CN
NH2
EtO
EtO
NH2
NH2
N
N
N
Ph
5
Ph
6
Synthesis of ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate 5 has been achieved via
abnormal Beckmann rearrangement of o-chloroaldehyde 1. Reaction of o-aminocarbonitrile 5 with concentrated
H2SO4 furnished expected o-aminocarboxamide pyrazole 6. Key intermediates o-aminocarbonitrile 5 and
o-aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The
replacement of Cl in o-chlorocarbonitrile 3 with secondary amine furnished new synthon 13, which was
further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized
by IR, 1H and 13C NMR, and mass spectra.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
yield, tedious workup, and requirement of low temperature
below À5ꢀC for the latter method. In continuation of our
recent work aiming at the synthesis of various new pyrazole
derivatives [10–13], we report a new method for the syn-
thesis of ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole-3-
carboxylate 5 and novel pyrazolopyrimidine, N-alkylated
pyrazolo[3,4-d]pyridazin-7-one, and 3-(hydrazinylcarbonyl)
pyrazole-4-carboxamide derivatives, which have been tested
for their antimicrobial activity.
In recent years, pyrazolopyrimidines and related fused
heterocycles have been identified as bioactive molecules,
were known to function as central nervous system depres-
sants, neuroleptic agents, and as tuberculostatic [1–3].
Pyrazolo[3,4-d]pyrimidines were identified as a general class
of adenosine receptors [4]. Several conformational analo-
gous of pyrazole-3-carboxamide derivatives have been
recently described as cannabinoid receptor-1 antagonists
[5]. Pyrazole and pyrimidine derivatives incorporating
benzothiazole moiety showed very good antimicrobial activ-
ity [6]. The remarkable applications of these compounds
have not only prompted many chemists to synthesize these
derivatives but also become an active research area of
continuing interest.
In literature, the synthesis of ethyl 5-amino-4-cyano-1-
phenyl-1H-pyrazole-3-carboxylate 5 by the reaction of
potassium salt of 2-cyano-4-ethoxy-4-oxobut-2-en-2-olate
with phenylhydrazine in ethanol is relatively expensive [7].
The same compound has also been synthesized by treating
aryldiazonium salt with ethyl-2-chloroacetoacetate to furnish
ethyl 2-chloro-2-phenylhydrazonoacetate that was further
condensed with malononitrile [7–9]. However, both estab-
lished methods were suffered from disadvantages of low
RESULTS AND DISCUSSION
The required o-chloroaldeyde 1 was prepared according
to reported method in 78% yield [13], which was further
treated with hydroxylamine hydrochloride in pyridine to
furnish oxime 2. The abnormal Beckmann rearrangement
is a convenient method for the conversion of oxime to
carbonitrile, hence used for the synthesis of ethyl 5-chloro-
4-cyano-1-phenyl-1H-pyrazole-3-carboxylate 3 (Scheme 1).
Accordingly, oxime 2 was treated with thionyl chloride
in dry benzene to yield carbonitrile 3 in 85% yield. The
nucleophilic C5-Cl substitution by azide furnished azido
derivative 4 in 76% yield. The nucleophilic substitution on
aromatic pyrazole ring was made possible because of strong
© 2013 HeteroCorporation

S. A. Gangurde, S. B. Kanawade, P. S. Nikam, D. C. Bhavsar, and R. B. Toche
Vol 000
Scheme 1
OH
O
N
O
N
O
N
N
CN
Cl
CHO
Cl
EtO
EtO
EtO
H
SOCl2
benzene
reflux, 4h
NH2OH.HCl
pyridine
70 °C, 5h
Cl
N
N
N
Ph
3
Ph
1
Ph
2
82%
85%
DMF,
rt, 6h
NaN3
O
O
N
O
O
CN
NH2
CN
N3
EtO
NH2
EtO
EtO
Na2S2O4
ethanol
reflux, 3h
Conc. H2SO4
rt, 15 h
N
N
NH2
N
N
N
Ph
Ph
Ph
6
5
4
85%
78%
76%
electron-withdrawing nitrile at C4 position. Compound 4 on
reduction with sodium dithionite gave target molecule ethyl
5-amino-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate 5 in
78% yield, higher than in earlier reported procedures [7–9]
and also economical as this process does not require expen-
sive 18-crown-6 or 2-chloroacetoacetate.
The carbonitrile on reaction with acid yielded carboxylic
acid or carboxamide depending upon the reaction conditions
[14]. Reaction of carbonitrile 5 with concentrated (conc.)
H2SO4 at room temperature afforded carboxamide 6, which
is our vital precursor. It was observed that during the course
of reaction, the ester group is not hydrolyzed to carboxylic acid.
The active o-aminocarbonitrile 5 and o-aminocarboxamide
6 moieties have found wide applications in the synthesis of
annulated heterocyclic ring systems [14–16] and hence were
successfully utilized for synthesis of pyrazolopyrimidine
derivatives in good yields.
In continuation of our work, an intermediate 5 was
condensed with N,N-dimethylformamide dimethylacetal
in p-xylene at reflux temperature to yield amidine 7, which
was further utilized for the synthesis of pyrazolo[3,4-d]
pyrimidines 8–10. The chemoselective reaction of 7 with hy-
drazine hydrate at room temperature in dry benzene furn-
ished pyrazolo[3,4-d]pyrimidine-3-carboxylate 8 whereas
at reflux temperature furnished hydrazine derivative 9 in 62
and 68% yields, respectively. Compound 7 with ammonium
hydroxide solution in ethanol led the formation of ethyl
4-amino-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylate
10 at reflux temperature (Scheme 2). The structures of 8–10
were established on the basis of spectral data and by elemental
analysis. For instance, IR spectrum of 8 and 10 showed
absorption band at 1710 and 1715 cmÀ1, respectively, for
ester carbonyl group. However, in IR spectrum of 9,
absorption band was observed at 1610 cmÀ1 for amide
group. In the 1H NMR spectrum of 8 in DMSO-d6, two broad
singlets were observed at 4.88 and 10.51 d corresponding to
1
two NH2 and one NH protons, respectively. However, H
NMR spectrum of 9 in DMSO-d6 showed two broad singlets
at 4.78 and 4.91 d corresponding to four NH2 protons
and another two singlets at 9.40 and 10.11 d corresponding
to two NH protons. The 1H NMR spectrum of 10 in
DMSO-d6 showed triplet and quartet at 1.42 and 4.46 d,
respectively, for ethoxy protons and one broad singlet at
5.60 d corresponding to two NH2 protons. Furthermore,
13C NMR and elemental analysis data of these compounds
were in agreement with the proposed structure.
The regioselective reaction of aldehydes with o-amino-
carboxamide 6 in acetonitrile and slight excess of iodine
furnished pyrazolo[3,4-d]pyrimidines 11a–c in 60–68%
yield, whereas the same reaction in n-butanol and catalytic
amount of piperidine afforded tetrahydropyrimidines
12a–c in 58–62% yield (Scheme 3). It was clearly observed
that mild Lewis acid and oxidant [17], that is, iodine play
important role in C═N bond formation in pyrazolo[3,4-d]
pyrimidines 11a–c.
The novel intermediate ethyl 5-chloro-4-cyano-1-phenyl-
1H-pyrazole-3-carboxylate 3 was used for the synthesis of
new pyrazolo[3,4-d]pyridazin-7-one and pyrazole-4-carbox-
amide derivatives 13–17 (Scheme 4). The nucleophilic
substitution reactions were performed on o-chlorocarbonitrile
3 using cyclic secondary amines as nucleophiles. Thus,
reaction of 3 with secondary amines at reflux temperature
furnished pyrazole derivatives 13a,b in quantitative yield.
Compounds 13a,b were treated with conc. H2SO4 at room
temperature and afforded carboxamide derivatives 14a,b.
However, the reaction of 14a,b with hydrazine hydrate
proved to be difficult at low temperature, which might be
because C4-carboxamide of pyrazole blocks the attack of
Journal of Heterocyclic Chemistry
DOI 10.1002./jhet

Month 2014
New Synthesis and Reactions of Ethyl 5-amino-4-cyano-1-phenyl-1H-
pyrazole-3-carboxylate
Scheme 2
O
N
HN
NH2
EtO
N
.
NH2NH2 H2O
dry benzene
24h, rt
N
N
Ph
8
62%
O
N
O
N
HN
O
N
NH2
CN
CN
NH2
H2NHN
EtO
DMF-DMA
xylene, reflux
5h
EtO
N
.
CH3
NH2NH2 H2O
N
N
N
dry benzene
reflux, 3h
N
N
N
CH3
Ph
9
68%
Ph
7
Ph
5
90%
O
H2N
EtO
N
NH4OH
N
N
ethanol, reflux
14h
N
Ph
10
60%
weakly nucleophilic hydrazine hydrate on ester functionality
due to hydrogen bonding. Hence, we perform this reaction
in high-boiling solvent n-butanol at reflux temperature to
yield 3-(hydrazinylcarbonyl)-pyrazole-4-carboxamide 15a,b
in 65–68% yield.
Compounds 13a,b containing nitrile and ester functional-
ity at ortho position were utilized for the synthesis of novel
pyrazolo[3,4-d]pyridazin-7-one 16a,b. The reaction of 13a,
b with hydrazine hydrate in ethanol at reflux temperature
yielded pyrazolo[3,4-d]pyridazin-7-one 16a,b in 82–85%
yield. N-alkylation of compounds 16a,b with ethyl bromoa-
cetate in DMF at 20–25ꢀC with stoichiometric amount of
potassium carbonate selectively occurred at secondary amide
NH instead of amine NH2 and gave 17a,b in 72–75% yield
without any O-substituted and/or O,N-disubstituted
products. It might be due to amide–enaminol tautomerism.
1
IR, H NMR, MS, and elemental analysis were used to
deduce the structures of 16 and 17. For example, 1H NMR
spectrum of 16a in DMSO-d6 contained broad singlets at
5.38 and 11.17 d corresponding to two NH2 and one NH
Scheme 3
O
O
H
EtO
N
ArCHO, I2
11a: Ar = 3,4-MeOC6H3
11b: Ar = 3-MeOC6H4
11c: Ar = 4-ClC6H4
Ar
N
N
CH3CN, reflux
5h
N
Ph
11a-c
60-68%
O
N
O
EtO
NH2
NH2
N
Ph
6
O
O
H
EtO
N
ArCHO
12a: Ar = 3,4-MeOC6H3
12b: Ar = 3-MeOC6H4
12c: Ar = 4-ClC6H4
Ar
N
N
H
n-butanol,
piperidine,
reflux, 12h
N
Ph
12a-c
58-62%
Journal of Heterocyclic Chemistry
DOI 10.1002./jhet

S. A. Gangurde, S. B. Kanawade, P. S. Nikam, D. C. Bhavsar, and R. B. Toche
Vol 000
Scheme 4
H
O
N
N
O
N
O
NH2
CN
Cl
CN
EtO
EtO
HN
reflux, 3h
NH2NH2.H2O
ethanol, reflux,
X
N
N
X
N
X
N
N
N
4h
Ph
3
Ph
16a,b
82-85%
Ph
13a,b
88-90%
13a-17a: X=O
13b-17b: X=CH2
DMF, K CO ,
BrCH2CO2Et
Conc. H2SO4
rt, 14h
3
rt, 152h
EtO2C
O
O
O
O
O
N
EtO
NH2NH2 H2O
NH2
NH2
H2NHN
NH2
.
N
N
N
n-butanol,
reflux, 4h
N
X
N
X
N
X
N
N
N
Ph
Ph
Ph
15a,b
17a,b
72-75%
14a,b
65-68%
85-87%
1
relative to TMS, and multiplicities are given as s (singlet), bs
(broad singlet), d (doublet), t (triplet), q (quartet), or m (multiplet).
Infrared spectra were recorded as KBr pellets on a Shimadzu
FTIR-408 spectrophotometer (Nashik, India). Mass spectra were
recorded on a Shimadzu LC-MS: EI QP 2010A mass spectrometer
(Mumbai, India) with an ionization potential of 70 eV. Elemental
analyses were performed on ThermoQuest Flash 1112 Series
EA analyzer (Mumbai, India). Reactions were monitored by TLC,
carried out on 0.2-mm silica gel 60 F254 (Merck, Mumbai, India)
plates using UV light (254 and 366 nm) for detection, and
compounds were purified by column chromatography by using
silica gel of 5–20 mm (Merck, 60–120 mesh). Column dimension is
39 Â 2cm, and elution volume used is about 200–400 mL for each
product where necessary. Common reagent-grade chemicals are
either commercially available and were used without further
purification or were prepared by standard literature procedures.
Ethyl 5-chloro-4-formyl-1-phenyl-1H-pyrazole-3-carboxylate
(1). White solid, yield 78%, mp 135–136ꢀC (lit. mp 135ꢀC [12]).
Ethyl 5-chloro-4-[(E)-(hydroxyimino) methyl]-1-phenyl-
1H-pyrazole-3-carboxylate (2). A mixture of ethyl 5-chloro-
protons. However, H NMR of 17a in DMSO-d6 showed
triplet and quartet at 1.20 and 4.14 d, respectively, for ethoxy
protons and one broad singlet at 5.60 d corresponding to two
NH2 protons, but singlet corresponding to amide NH
disappeared. Furthermore, elemental analysis data of these
compounds was in agreement with the proposed structure.
Antimicrobial activity. The antibacterial activities of the
synthesized compounds 8, 9, 10, 11a–c, 12a–c, 15a,b, and
17a,b were determined by the well-diffusion method [18]. In
this work, Escherichia coli (ATCC-25922), Pseudomonas
aeruginosa (ATCC 27853), and Staphylococcus aureus
(ATCC 25923) were used to investigate the antibacterial
activities by using gentamycin and nystatin as standards.
The investigation of antibacterial screening data revealed
that these compounds did not show significant bacterial
inhibition even at higher concentration, that is, 1 mg mlÀ1
.
CONCLUSION
4-formyl-pyrazole-3-carboxylate 1 (0.27 g, 1.0 mmol) and
hydroxyl amine hydrochloride (0.69 g, 1.0 mmol) dissolved in
pyridine (5 mL) was heated with stirring at 70–75ꢀC for 5 h
(TLC check, chloroform : methanol, 9:1). The solution was
cooled, poured into cold water, and neutralized with dilute
hydrochloric acid. The solid obtained was isolated by filtration
under vacuum, and using column chromatography eluting with
chloroform : methanol (9:1) gave 2 as pale yellow solid, yield
82%, 0.23 g, mp 125–126ꢀC; IR (KBr) vmax 1625 (C═N), 1735
A simple and convenient method for the synthesis of
ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole-3-carboxyl-
ate 5 with improved yield was developed. A new class
of pyrazolo[3,4-d]pyrimidines, tetrahydropyrimidines,
pyrazolo[3,4-d]pyridazin-7-one, and 3-(hydrazinylcarbonyl)-
pyrazole-4-carboxamide was obtained in good yield from
o-aminopyrazolecarbonitrile 5 and o-aminopyrazolecarbonitrile
6 with simple workup and clean products.
1
(C═O), 2940 (C-H aliph.), 3560 (OH) cmÀ1; H NMR (CDCl3)
d 1.43 (t, J = 6.9 Hz, 3H), 4.46 (q, J = 6.9 Hz, 2H, OCH2), 7.54
(m, 5H, Ar-H), 7.51 (s, 1H, CH), 8.72 (s, 1H, OH); 13C NMR
(CDCl3) d 14.2, 61.7, 114.0, 125.7, 127.3, 129.1, 129.4, 129.6,
137.0, 141.8, 161.3; MS m/z (%): 293 (M+, 100%), 295 (M + 2,
33%); Anal. Calcd. for C13H12ClN3O3: C, 53.16; H, 4.12; N,
14.31. Found: C, 53.30; H, 4.20; N, 14.38.
EXPERIMENTAL
General remarks.
Melting points were determined on a
Gallenkamp melting point apparatus (Nashik, India) in an open
capillary tube and are uncorrected. The 1H (300 MHz) and 13C
(75 MHz) NMR spectra were recorded on a Varian XL-300
spectrometer (Pune, India). Chemical shifts were reported in ppm
Ethyl 5-chloro-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate
(3).
A solution of oxime 2 (0.29g, 1.0 mmol) and thionyl
chloride (0.15 mL, 2.0 mmol) in dry benzene (20 mL) was reflux
Journal of Heterocyclic Chemistry
DOI 10.1002./jhet

Month 2014
New Synthesis and Reactions of Ethyl 5-amino-4-cyano-1-phenyl-1H-
pyrazole-3-carboxylate
for 4 h (TLC check, chloroform : methanol, 9:1). The excess solvent
was removed under reduced pressure. The solid obtained was
filtered, washed with cold methanol and recrystallized from
ethanol to afford compound 3 as white solid, yield 85%, 0.23 g,
mp 125–126ꢀC; IR (KBr) vmax 1602 (C═C), 1732 (C═O), 2239
dried. The crude product was recrystallized from toluene to
give 7 as white solid, yield 90%, 0.27 g, mp 137–138ꢀC; IR
(KBr) vmax 1600 (C═C, arom.), 1622 (C═N), 1722 (C═O),
2228 (CꢁN), 2929 (C-H), 2932 cmÀ1
;
1H NMR (CDCl3): d
1.42 (t, J = 7.2 Hz, 3H, CH3), 3.01 (s, 3H, NCH3), 3.13 (s, 3H,
NCH3), 4.46 (q, J = 7.2 Hz, 2H, CH2), 7.34–7.74 (m, 5H,
Ar-H), 8.35 (s, 1H, N═C-H); 13C NMR (CDCl3) d 13.6, 61.8,
40.6, 79.5, 114.9, 124.3, 127.6, 128.3, 138.0, 138.5, 142.9,
155.6, 160.7; MS m/z (%): 312 (M + 1, 100%); Anal. Calcd for
C16H17N5O2: C, 61.72; H, 5.50; N, 22.49. Found: C, 61.66; H,
5.47; N, 22.54.
(CꢁN) 2916 (C═H) cmÀ1
;
1H NMR (CDCl3) d 1.45 (t,
J = 6.9 Hz, 3H, CH3), 4.52 (q, J = 6.9 Hz, 2H, CH2), 7.56 (m, 5H,
Ar-H); 13C NMR (CDCl3) d 13.6, 61.9, 95.5, 109.9, 124.9, 129.1,
129.9, 134.8, 135.9, 144.1, 158.4; MS m/z (%): 275 (M+, 100%),
277 (M+ 2, 33%); Anal. Calcd. for C13H10ClN3O2: C, 56.64; H,
3.66; N, 15.24. Found: C, 56.79; H, 3.61; N, 15.41.
Ethyl 5-azido-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate
(4). To the vigorously stirred solution of compound 3 (0.27 g,
1.0 mmol) dissolved in DMF (5 mL), sodium azide (0.078g,
1.2 mmol) was slowly added for 10min. The reaction mixture
was stirred at room temperature for 6 h (TLC check,
chloroform: methanol, 9:1). The solution was then poured into
cold water; the solid obtained was filtered off and recrystallized
from ethanol to give compound 4 as pale green solid, yield 76%,
0.21 g, mp 70ꢀC; IR (KBr) vmax 1593 (C═C), 1740 (C═O), 2133
Ethyl 5-amino-4-imino-1-phenyl-4,5-dihydro-1H-pyrazolo
[3,4-d]pyrimidine-3-carboxylate (8). A mixture of 7 (0.31 g,
1.0 mmol) and hydrazine hydrate (0.05 mL, 1.0 mmol) in dry
benzene (15 mL) was stirred at room temperature for 24 h (TLC
check, chloroform : methanol, 8:2). The obtained solid was
collected by filtration under vacuum, washed with hexane, dried,
and recrystallized from ethanol-DMF (7:3) to give compound 9 as
white solid, yield 62%, 0.18g, mp 299–300ꢀC; IR (KBr) vmax
1600 (C═C), 1710 (C═O), 2925 (CH aliph.), 3306, 3420 (NH2),
3470 (NH) cmÀ1; 1H NMR (DMSO-d6): d 1.42 (t, J = 6.9 Hz, 3H,
CH3), 4.46 (q, J = 6.9 Hz, 2H, CH2), 4.88 (s, 2H, NH2), 7.39–7.5
(m, 5H, Ar-H), 8.39 (s, 1H, Ar-H), 10.51 (brs, 1H, NH); 13C
NMR (DMSO-d6) d 13.9, 61.4, 118.2, 124.3, 127.6, 128.3, 138.0,
140.9, 145.1, 158.9, 163.2, 163.9; MS m/z (%): 298 (M+, 100%);
Anal. Calcd for C14H14N6O2: C, 56.37; H, 4.73; N, 28.17. Found:
C, 56.45; H, 4.82; N, 28.11.
1
(N3), 2227 (CꢁN), 2929 (C-H aliph.) cmÀ1; H NMR (CDCl3)
d 1.44 (t, J = 6.6 Hz, 3H, CH3), 4.52 (q, J = 6.6 Hz, 2H, CH2),
7.51 (m, 5H, Ar-H); 13C NMR (CDCl3) d 13.9, 62.2, 85.7, 110.2,
124.2, 125.1, 129.3, 136.2, 142.0, 144.0, 159.1; MS m/z (%): 305
(M+ Na, 100%); Anal. Calcd. for C13H10N6O2: C, 55.32; H, 3.57;
N, 29.77. Found: C, 55.25; H, 3.60; N, 29.74.
Ethyl 5-amino-4-cyano-1-phenyl-1H-pyrazole-3-carboxylate
(5). A solution of 4 (0.28g, 1.0 mmol) and sodium dithionite
(0.2 g, 1.2 mmol) in ethanol (10 mL) was refluxed for 3 h (TLC
check, chloroform : methanol, 9:1). The reaction mixture was
concentrated and cooled, and residue was poured into cold
water. The solid obtained was filtered off and recrystallized
from ethanol to give compound 5 as white solid, yield 78%,
0.19 g, mp 158–159ꢀC (Lit. mp 157–161ꢀC [7,8]); IR (KBr)
5-Amino-4-imino-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]
pyrimidine-3-carbohydrazide (9).
A mixture of 7 (0.31 g,
1.0 mmol) and hydrazine hydrate (0.05 mL, 1.0 mmol) in dry
benzene (15 mL) was refluxed for 3 h (TLC check,
chloroform : methanol, 8:2). The reaction mixture was cooled to
room temperature, and obtained solid was collected by filtration
under vacuum, washed with hexane, dried, and recrystallized from
ethanol-DMF (6:4) to give compound 9 as white solid, yield 68%,
0.19g, mp 314–315ꢀC; IR (KBr) vmax 1604 (C═C, arom.), 1610
vmax 1706 (C═O), 2217 (CꢁN), 3222, 3306 (NH2) cmÀ1
;
1H
NMR (CDCl3) d 1.41 (t, J = 7.2 Hz, 3H, CH3), 4.43 (q,
J = 7.2 Hz, 2H, CH2), 4.96 (s, 2H, NH2), 7.49 (m, 5H, Ar-H);
MS m/z (%): 257 (M + 1, 30%), 279 (M + 23, 100%); Anal.
Calcd for C13H12N4O2: C, 60.93; H, 4.72; N, 21.86. Found: C,
61.01; H, 4.66; N, 21.72.
(C═O, amide), 3278, 3335, 3465 (NH2/NH) cmÀ1 1H NMR
;
(DMSO-d6): d 4.78 (s, 2H, NH2), 4.91 (s, 2H, NH2), 7.40–7.57
(m, 5H, Ar-H), 8.42 (s, 1H, Ar-H), 9.40 (s, 1H, NH), 10.11
(brs, 1H, NH); 13C NMR (DMSO-d6) d 112.1, 124.3, 127.6,
128.3, 138.0, 141.8, 142.7, 145.1, 161.2, 163.1, 163.9; MS m/z
(%): 285 (M+ 1, 100%); Anal. Calcd for C12H12N8O: C, 50.70;
H, 4.25; N, 39.42 Found: C, 50.48; H, 4.32; N, 39.29.
Ethyl 5-amino-4-carbamoyl-1-phenyl-1H-pyrazole-3-
carboxylate (6). Compound 5 (0.25g, 1.0mmol) was stirred in
conc. H2SO4 (8mL) at room temperature for 15h (TLC check,
chloroform: methanol, 9:1). The reaction mass was then added to
crushed ice (150mL) and neutralized with saturated NaHCO3
(20 mL). The crude solid separated was filtered, washed with
water, dried, and recrystallized from ethanol to give compound 6
as white solid, yield 85%, 0.23 g, mp 170–171ꢀC; IR (KBr) vmax
1613 (C═C arom.), 1670 (C═O, amide), 1725 (C═O, ester),
Ethyl 4-amino-1-phenyl-1H-pyrazolo [3, 4-d] pyrimidine-3-
carboxylate (10). A solution of compound 7 (0.31 g, 1.0 mmol)
and ammonium hydroxide (8 mL, excess) in ethanol (15 mL) was
refluxed for 14 h (TLC check, chloroform : methanol, 8:2). The
solution was cooled to room temperature, and obtained solid
was collected by filtration under vacuum, washed with ethanol,
and dried to afford analytically pure compound 8 as white
crystalline solid, yield 60%, 0.17 g, mp 250ꢀC; IR (KBr) vmax
1604 (C═C, arom.), 1715 (C═O), 2920, 3430, 3370 (NH2)
1
3310, 3440, 3210 cmÀ1; H NMR (CDCl3) d 1.43 (t, J = 6.7 Hz,
3H, CH3), 4.49 (q, J = 6.7 Hz, 2H, CH2), 7.58 (m, 5H, Ar-H); 13
C
NMR (CDCl3) d 14.1, 62.2, 96.4, 124.7, 128.9, 129.6, 136.6,
139.2, 151.6, 164.2, 166.1; MS m/z (%): 275 (M+ 1, 100%);
Anal. Calcd for C13H14N4O3: C, 56.93; H, 5.14; N, 20.43. Found:
C, 56.88; H, 5.10; N, 20.48.
cmÀ1 1H NMR (DMSO-d6): d 1.42 (t, J = 6.9 Hz, 3H, CH3),
;
4.46 (q, J = 6.9 Hz, 2H, CH2), 5.60 (s, 2H, NH2), 7.46–7.65 (m,
5H, Ar-H), 8.42 (s, 1H, CH); 13C NMR (DMSO-d6) d 13.6,
61.9, 104.3, 124.9, 129.1, 129.9, 135.8, 142.9, 148.1, 154.9,
155.5, 161.1; MS m/z (%): 284 (M + 1, 100%); Anal. Calcd for
C14H13N5O2: C, 59.36; H, 4.63; N, 24.72. Found: C, 59.42; H,
4.55; N, 24.71.
Ethyl 4-cyano-5-((E)-formamido)-1-phenyl-1H-pyrazole-3-
carboxylate (7).
Compound 5 (0.25 g, 1.0 mmol) and DMF-
DMA (0.13mL, 1.0 mmol) in dry p-xylene (10 mL) was refluxed
for 5 h (TLC check, chloroform: methanol, 9:1). The excess
solvent was removed under reduced pressure. The solid
obtained was stirred in hexane (20 mL) for 1 h. The solid
that formed was filtered, washed with cold methanol, and
General procedure for the synthesis of compounds
11a–c.
To a mixture of compound 6 (0.27 g, 1.0 mmol) and
aromatic aldehydes (1.0 mmol), namely, 3,4-dimethoxybenzaldehyde,
Journal of Heterocyclic Chemistry
DOI 10.1002./jhet

S. A. Gangurde, S. B. Kanawade, P. S. Nikam, D. C. Bhavsar, and R. B. Toche
Vol 000
3-methoxybenzaldehyde, and 4-chlorobenzaldehyde in dry
acetonitrile (15 mL), iodine (0.27 g, 1.1 mmol) was added. The
mixture was refluxed for 5–6 h (TLC check, chloroform : methanol,
8:2). The reaction mixture was cooled to room temperature. An
aqueous solution of sodium thiosulphate (5%, 15 mL) was added,
and resulted solid was filtered off, washed with water, and dried.
The crude product was recrystallized from ethanol : DMF (8:2) to
give 11a–c.
Ethyl-4,5,6,7-tetrahydro-6-(3-methoxyphenyl)-4-oxo-1-phenyl-
1H-pyrazolo[3,4-d]pyrimidi-ne-3-carboxylate (12b). White
solid, yield 60%, 0.23 g, mp 336–337ꢀC; IR (KBr) vmax 1600
(C═C, arom.), 1675 (C═O), 2934 (C-H), 3455, 3472 (N-H)
1
cmÀ1; H NMR (DMSO-d6) d 1.44 (t, J = 7.2Hz, 3H, CH3), 4.46
(q, J = 7.2 Hz, 2H, OCH2), 5.85 (s, 1H, CH), 7.15–7.70 (m, 5H,
Ar-H), 7.73–7.86 (m, 4H, Ar-H), 8.50 (bs, 1H, NH), 10.21
(bs, 1H, NH); Mass m/z: 392 (M+, 100%); Anal. Calcd for
C21H20N4O4: C, 64.28; H, 5.14; N, 14.28. Found: C, 64.15; H,
5.23; N, 14.30.
Ethyl 4, 5-dihydro-6-(3,4-dimethoxyphenyl)-4-oxo-1-phenyl-
1H-pyrazolo[3,4-d]pyrimidine-3-carboxylate (11a).
White solid,
yield 68%, 0.29 g, mp 280–281ꢀC; IR (KBr) vmax 1612 (C═C
arom.), 1666 (C═O), 1718 (C═O), 2925 (C-H, aliph.), 3480, 3460
Ethyl 6-(4-chlorophenyl)-4,5,6,7-tetrahydro-4-oxo-1-phenyl-
1H-pyrazolo[3,4-d]pyrimidine-3-carboxylate (12c).
White
1
(NH) cmÀ1; H NMR (DMSO-d6) d 1.35 (t, J= 6 Hz, 3H, CH3),
solid, yield 62%, 0.24 g, mp 345–346ꢀC; IR (KBr) vmax 1600
(C═C arom.), 1673 (C═O), 2932 (C-H), 3455, 3472 (N-H)
3.83 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 4.48 (q, J= 6 Hz, 2H,
CH2), 7.11 (d, J= 9 Hz, 1H, Ar-H), 7.46 (t, J= 9 Hz, 1H, Ar-H).
7.61 (m, 2H, Ar-H), 7.80 (s, 1H, Ar-H), 7.85 (m, 1H, Ar-H), 8.09
(d, J= 9 Hz, 2H, Ar-H), 12.54 (s, 1H, NH); 13C NMR (DMSO-d6) d
13.6, 55.6, 61.7, 112.4, 112.9, 115.5, 118.3, 120.2, 121.4, 124.9,
129.1, 129.9, 134.8, 142.1, 144.0, 148.1, 148.6, 160.1, 160.9, 161.2;
MS m/z (%): 421 (M + 1, 100%); Anal. Calcd for C22H20N4O5: C,
62.85; H, 4.79; N, 13.33. Found: C, 62.91; H, 4.66; N, 13.44.
Ethyl 4,5-dihydro-6-(3-methoxyphenyl)-4-oxo-1-phenyl-1H-
1
cmÀ1; H NMR (DMSO-d6) d 1.44 (t, J = 7.2Hz, 3H, CH3), 4.46
(q, J = 7.2 Hz, 2H, OCH2), 5.86 (s, 1H, CH), 7.15–7.62 (m, 5H,
Ar-H), 7.63–7.80 (m, 3H, Ar-H), 8.50 (bs, 1H, NH), 10.53
(bs, 1H, NH); 13C NMR (DMSO-d6) d 14.1, 62.2, 70.3, 109.3,
124.7, 128.9, 129.0, 129.6, 131.2, 133.1, 136.6, 139.1, 142.9,
149.4, 158.6, 162.5; MS m/z (%): 397 (M+, 100%), 399
(M+ 2, 33%); Anal. Calcd for C20H17ClN4O3: C, 60.53; H, 4.32;
N, 14.12. Found: C, 60.47; H, 4.41; N, 14.08.
pyrazolo[3,4-d]pyrimidine-3-carboxylate (11b).
White solid,
General procedure for the synthesis of compounds 13a,b.
A
yield 65%, 0.25 g, mp 265–266ꢀC; IR (KBr) vmax 1612 (C═C
arom.), 1665 (C═O), 1718 (C═O), 2925 (C-H, aliph.), 3480, 3460
solution of compound 3 (0.27g, 1.0 mmol) and secondary amines
(10 mL), namely, morpholine and piperidine was refluxed for 3 h
(TLC check, chloroform : methanol, 9:1). The reaction mixture
after cooling was poured into cold water, and precipitate that
separated was filtered off and recrystallized from ethanol to give
13a,b.
1
(NH) cmÀ1; H NMR (DMSO-d6) d 1.43 (t, J= 6.9 Hz, 3H), 3.85
(s, 3H, OCH3), 4.46 (q, J= 6.9 Hz, 2H, OCH2), 7.19 (d, J=7.8Hz,
1H, Ar-H), 7.51 (t, J= 7.8 Hz, 2H, Ar-H), 7.63 (t, J=7.8Hz, 2H,
Ar-H), 7.77 (t, J= 8.1 Hz, 2H, Ar-H), 7.11 (d, J= 8.1 Hz, 2H,
Ar-H), 13.20 (s, 1H, NH). MS m/z (%): 391 (M + 1, 100%); Anal.
Calcd for C21H18N4O4: C, 64.61; H, 4.65; N, 14.35. Found: C,
64.44; H, 4.70; N, 14.28.
Ethyl 4-cyano-5-morpholino-1-phenyl-1H-pyrazole-3-
carboxylate (13a).
White solid, yield 88%, 0.28 g, mp
143–144ꢀC; IR (KBr) vmax 1719 (C═O), 2223 (CꢁN), 2920, 2930
Ethyl 6-(4-chlorophenyl)-4,5-dihydro-4-oxo-1-phenyl-1H-
cmÀ1 1H NMR (CDCl3): d 1.45 (t, J= 7.2 Hz, 3H, CH3), 3.13
;
pyrazolo[3,4-d]pyrimidine-3-carboxylate (11c).
White solid,
(m, 4H, 2 Â CH2), 3.54 (m, 4H, 2 Â CH2), 4.52 (q, J= 7.2 Hz, 2H,
CH2), 7.56–7.71 (m, 5H, Ar-H). 13C NMR (CDCl3) d 13.9, 61.8,
49.9, 66.6, 83.2, 113.4, 123.8, 129.9, 129.5, 138.1, 147.8, 153.7,
159.7; MS m/z (%): 326 (M+, 100%); Anal. Calcd for C17H18N4O3:
C, 62.57; H, 5.56; N, 17.17. Found: C, 62.63; H, 5.48; N, 17.20.
yield 68%, 0.26 g, mp 301–302ꢀC; IR (KBr) vmax 1612
(C═C arom.), 1668 (C═O), 1720 (C═O), 2926 (C-H, aliph.),
3480, 3460 (N-H) cmÀ1 1H NMR (DMSO-d6) d 1.44 (t,
;
J = 6.9 Hz, 3H), 4.46 (q, J = 6.9 Hz, 2H, OCH2), 7.32–7.62
(m, 5H, Ar-H), 7.63–7.65 (m, 4H, Ar-H), 12.89 (s, 1H,
NH); MS m/z (%): 395 (M+, 100%), 397 (M + 2, 33%);
Anal. Calcd for C22H22N4O5: C, 60.84; H, 3.83; N, 14.19.
Found: C, 62.48; H, 3.77; N, 13.98.
General procedure for the synthesis of compounds 12a–c. To
a mixture of compound 6 (0.27 g, 1.0mmol) and aromatic
aldehydes (1.0mmol), namely, 3,4-dimethoxybenzaldehyde, 3-
methoxybenzaldehyde, and 4-chlorobenzaldehyde in n-butanol
(10 mL) with catalytic amount of piperidine was refluxed in oil
bath with stirring for 10–12h (TLC check, chloroform : methanol,
8:2). The reaction mixture was cooled and poured into crushed
ice (30 mL). The residue obtained was filtered, washed with
cold ethanol, and recrystallized from ethanol-DMF (8:2) to
give 12a–c.
Ethyl
4-cyano-1-phenyl-5-(piperidin-1-yl)-1H-pyrazole-3-
carboxylate (13b). White solid, yield 90%, 0.29 g, mp 132ꢀC;
IR (KBr) vmax 1722 (C═O), 2221 (CꢁN), 2920, 2932 cmÀ1; H
1
NMR (CDCl3): d 1.18–1.39 (m, 6H, 3 Â CH2), 1.46 (t, J = 6.9 Hz,
3H, CH3), 3.05 (m, 4H, 2 Â NCH2), 4.52 (q, J = 6.9 Hz, 2H,
CH2), 7.56–7.66 (m, 5H, Ar-H); MS m/z (%): 324 (M+, 100%);
Anal. Calcd for C18H20N4O2: C, 66.65; H, 6.21; N, 17.27. Found:
C, 66.58; H, 6.31; N, 17.12.
General procedure for the synthesis of compounds 14a,b.
Compound 13a,b (1.0 mmol) was stirred in conc. H2SO4
(10 mL) at room temperature for 14h (TLC check, chloroform:
methanol, 9:1). The reaction mass was then added to crushed ice
(150 mL) and neutralized with saturated NaHCO3 (40 mL). The
crude product separated was filtered, washed with water, and
Ethyl 4,5,6,7-tetrahydro-6-(3,4-dimethoxyphenyl)-4-oxo-
1-phenyl-1H-pyrazolo[3,4-d] pyrimidine-3-carboxylate (12a).
White solid, yield 58%, 0.24 g, mp 319–320ꢀC; IR (KBr) vmax
1600 (C═C, arom.), 1672 (C═O), 2930 (C-H), 3455, 3472
recrystallized from acetonitrile to give 14a,b.
Ethyl 4-carbamoyl-5-(morpholin-4-yl)-1-phenyl-1H-pyrazole-
3-carboxylate (14a).
White solid, yield 85%, 0.29 g, mp
(N-H) cmÀ1 1H NMR (DMSO-d6) d 1.44 (t, J = 7.2 Hz, 3H,
;
220ꢀC; IR (KBr) vmax 1665 (C═O, amide), 1735 (C═O, ester),
2942 (C-H), 3338, 3468 (NH2); 1H NMR (CDCl3): d 1.46
(t, J = 6.9 Hz, 3H, CH3), 3.14 (m, 4H, 2 Â CH2), 3.55 (m, 4H,
2 Â CH2), 4.52 (q, J = 6.9 Hz, 2H, CH2), 7.1 (brs, 2H, NH2),
7.48–7.68 (m, 5H, Ar-H); 13C NMR (CDCl3) d 13.9, 61.8,
49.9, 66.5, 83.2, 123.8, 129.9, 129.5, 138.1, 147.8, 149.9,
CH3), 4.46 (q, J= 7.2 Hz, 2H, OCH2), 5.82 (s, 1H, CH), 7.15–7.70
(m, 5H, Ar-H), 7.73–7.86 (m, 3H, Ar-H), 8.4 (bs, 1H, NH), 9.78
(bs, 1H, NH); MS m/z (%): 422 (M+, 100%); Anal. Calcd for
C22H22N4O5: C, 62.55; H, 5.25; N, 13.26. Found: C, 62.61; H,
5.23; N, 13.32.
Journal of Heterocyclic Chemistry
DOI 10.1002./jhet

Month 2014
New Synthesis and Reactions of Ethyl 5-amino-4-cyano-1-phenyl-1H-
pyrazole-3-carboxylate
160.9, 166.2; MS m/z (%): 344 (M+, 100%); Anal. Calcd for
C17H20N4O4: C, 59.29; H, 5.85; N, 16.27. Found: C, 59.33; H,
5.82; N, 16.40.
General procedure for the synthesis of compounds
17a,b.
A solution of compound 16a,b (1.0 mmol) and
ethyl 2-bromoacetate (1.0 mmol) in 9 mL DMF containing
K2CO3 (0.13 g, 1.0 mmol) was stirred at room temperature
for 15–16 h (TLC check, chloroform : methanol, 9:1).
Resulting reaction mixture was poured into cold water and
neutralized with dil. HCl. The separated solid was filtered,
washed with cold water, dried under vacuum, and
recrystallized from ethanol-DMF (85:15) and afforded white
amorphous solid compound 17a,b.
Ethyl 4-carbamoyl-1-phenyl-5-(piperidin-1-yl)-1H-pyrazole-
3-carboxylate (14b).
White solid, yield 87%, 0.29g, mp
225ꢀC; IR (KBr) vmax 1662 (C═O, amide), 1736 (C═O, ester),
2942, 3335, 3463 (NH2) cmÀ1; H NMR (CDCl3): d 1.17–1.39
1
(m, 6H, 3 Â CH2), 1.46 (t, J = 6.9 Hz, 3H, CH3), 3.05 (m, 4H,
2 Â NCH2), 4.52 (q, J = 6.9 Hz, 2H, CH2), 6.89 (brs, 2H, NH2),
7.56–7.66 (m, 5H, Ar-H); MS m/z (%): 342 (M+, 100%); Anal.
Calcd for C18H22N4O3: C, 63.14; H, 6.48; N, 16.36. Found:
C, 63.17; H, 6.50; N, 16.28.
Ethyl 2-(4-amino-3-morpholino-7-oxo-2-phenyl-2H-pyrazolo
[3,4-d]pyridazin-6(7H)-yl) acetate (17a).
White solid, yield
72%, 0.28g, mp 321–323ꢀC; IR (KBr) vmax 1220 (C-O), 1662
(C═O amide), 1695 (C═O, ester), 2932 (C-H), 3320, 3410 (NH2)
General procedure for the synthesis of compounds 15a,b. An
equimolar mixture of compound 14a,b (1.0 mmol) and hydrazine hy-
drate (1.0 mmol) in n-butanol (10 mL) was heated under reflux for 4 h
(TLC check, chloroform : methanol, 8:2). The mixture was then
cooled to room temperature, and the obtained crude solid was
collected by filtration under vacuum, washed with ethanol (25 mL),
and recrystallized from ethanol-DMF (8:2) to give compounds 15a,b.
4-Carbamoyl-5-morpholino-1-phenyl-1H-pyrazole-3-
1
cmÀ1; H NMR (DMSO-d6) d 1.20 (t, J = 7.2Hz, 3H, CH3), 2.95
(m, 4H, 2 Â CH2), 3.58 (m, 4H, 2 Â CH2), 4.14 (q, J = 7.2 Hz, 2H,
OCH2), 4.65(s, 2H, CH2), 5.60 (s, 2H, NH2), 7.59–7.63 (m, 5H,
Ar-H); MS m/z (%): 399 (M+ 1, 100); Anal. Calcd for
C19H22N6O4: C, 57.28; H, 5.57; N, 21.09. Found: C, 57.68; H,
5.42; N, 21.88.
Ethyl 2-(4-amino-7-oxo-2-phenyl-3-(piperidin-1-yl)-2H-
carbohydrazide (15a).
White solid, yield 68%, 0.22 g, mp
308–309ꢀC; IR (KBr) vmax 1210 (C-O), 1610 (C═O, amide),
1615 (C═C), 1661 (C═O, amide), 3278, 3335, 3450 (NH/
pyrazolo[3,4-d]pyridazin-6(7H)-yl)acetate (17b).
White
solid, yield 75%, 0.29 g, mp 338–339ꢀC; IR (KBr) vmax 1665
(C═O, amide), 1692 (C═O, ester), 2932 (C-H), 3320, 3410
(NH2) cmÀ1; 1H NMR (DMSO-d6) d 1.17–1.39 (m, 9H, 3 Â CH2,
CH3), 3.05 (m, 4H, 2 Â NCH2), 3.58 (m, 4H, 2 Â CH2), 4.14
(q, 2H, OCH2), 4.64(s, 2H, CH2), 5.60 (s, 2H, NH2), 7.59–7.63
(m, 5H, Ar-H); MS m/z (%): 396 (M + 1, 100%); Anal. Calcd for
C20H24N6O3: C, 60.59; H, 6.10; N, 21.20. Found: C, 60.41; H,
5.96; N, 21.32.
1
NH2) cmÀ1; H NMR (DMSO-d6) d 3.14 (m, 4H, 2 Â NCH2),
3.54 (m, 4H, 2 Â CH2), 4.82 (s, 2H, NH2), 6.80 (s, 2H, NH2),
9.62 (brs, 1H, NH), 7.48–7.68 (m, 5H, Ar-H); 13C NMR
(DMSO-d6) d 49.5, 66.0, 110.4, 125.0, 128.3, 129.0, 138.4,
143.6, 149.5, 162.7, 163.5; MS m/z (%): 330 (M+, 100%);
Anal. Calcd for C15H18N6O3: C, 54.54; H, 5.49; N, 25.44.
Found: C, 54.43; H, 5.56; N, 25.51.
4-Carbamoyl-1-phenyl-5-(piperidin-1-yl)-1H-pyrazole-3-
carbohydrazide (15b).
298–300ꢀC; IR (KBr) vmax 1610 (C═O, amide), 1615 (C═C),
1660 (C═O, amide), 3278, 3335, 3450 (NH/NH2) cmÀ1 1H
NMR (DMSO-d6) d 1.17–1.39 (m, 6H, 3 Â CH2), 3.05 (m, 4H,
2 Â NCH2), 5.09 (s, 2H, NH2), 6.92 (s, 2H, NH2), 9.43 (s, 1H,
NH), 7.56–7.66 (m, 5H, Ar-H); MS m/z (%): 328 (M+, 100%);
Anal. Calcd for C16H20N6O2: C, 58.52; H, 6.14; N, 25.59. Found:
C, 58.61; H, 6.09; N, 25.64.
White solid, yield 65%, 0.21 g, mp
Acknowledgments. The authors thank CSIR, New Delhi, India
for financial support to this research project and the principal
of KTHM College, Nashik-422002 for facilities. Authors also
thank Department of Chemistry, University of Pune and IIT
Pawai, Maharashtra, India, for valuable cooperation for
providing spectroscopic data. The award of Research
Internship to one of the authors (Sachin A. Gangurde) from
Council of Scientific and Industrial Research (CSIR) is duly
acknowledged.
;
General procedure for the synthesis of compounds 16a,b.
A
mixture of compound 13 (0.31 g, 1.0 mmol) and hydrazine
hydrate (0.05 mL, 1.0 mmol) in ethanol (10 mL) was refluxed
4 h (TLC check, chloroform : methanol, 8:2). The reaction
mixture after cooling was poured into cold water. The solid
separated was filtered off and recrystallized from ethanol-DMF
REFERENCES AND NOTES
(80:20) to give 16a,b.
4-Amino-3-morpholino-2-phenyl-2H-pyrazolo[3,4-c]pyridin-7
(6H)-one (16a). White solid, yield 75%, 0.23g, mp 325–326ꢀC;
IR (KBr) vmax 1210 (C-O), 1668 (C═O, amide), 3400, 3468, 3312
(NH/NH2) cmÀ1; 1H NMR (DMSO-d6) d 2.92 (m, 4H, 2 Â CH2),
3.57 (m, 4H, 2 Â CH2), 5.38 (s, 2H, NH2), 7.61 (m, 5H, Ar-H),
11.17 (s, 1H, NH); MS m/z (%): 313 (M+ 1, 100%); Anal. Calcd
for C15H16N6O2: C, 57.68; H, 5.16; N, 26.91. Found: C, 57.72;
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4-Amino-2-phenyl-3-(piperidin-1-yl)-2H-pyrazolo [3,4-d]
pyridazin-7(6H)-one (16b). White solid, yield 78%, 0.24 g,
mp 315–317ꢀC; IR (KBr) 1670 (C═O), 3400, 3468, 3312
(NH/NH2) cmÀ1 1H NMR (DMSO-d6) d 1.17–1.39 (m, 6H,
;
3 Â CH2), 3.05 (m, 4H, 2 Â NCH2), 5.37 (s, 2H, NH2), 7.61
(m, 5H, Ar-H), 11.20 (s, 1H, NH); MS m/z (%): 310 (M+,
100%); Anal. Calcd for C16H18N6O: C, 61.92; H, 5.85; N,
27.08. Found: C, 61.88; H, 5.78; N, 27.19.
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Journal of Heterocyclic Chemistry
DOI 10.1002./jhet

S. A. Gangurde, S. B. Kanawade, P. S. Nikam, D. C. Bhavsar, and R. B. Toche
Vol 000
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Journal of Heterocyclic Chemistry
DOI 10.1002./jhet