Synthesis of new multi-functionalised 1,1'-carbonylbispyrazole derivatives

Article abstract of DOI:10.3184/174751915X14271377629065

A new series of multi-functionalised 1,1'-carbonylbispyrazole derivatives were synthesised through cyclisation of pyrazole carbohydrazides with some substituted methylene malononitriles in very good yields. The structures of all synthesised compounds were established on the basis of NMR, IR, MS and elemental analysis.

Full text of DOI:10.3184/174751915X14271377629065

220 RESEARCH PAPER
VOL. 39 APRIL, 220–222
JOURNAL OF CHEMICAL RESEARCH 2015
Synthesis of new multi-functionalised 1,1’-carbonylbispyrazole derivatives
Manijeh Mohadeszadeh, Hossein Eshghi*, Sattar Saberi and Mostafa Gholizadeh
Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, PO Box 91775-1436, Mashhad, Iran
A new series of multi-functionalised 1,1’-carbonylbispyrazole derivatives were synthesised through cyclisation of pyrazole carbohydrazides
with some substituted methylene malononitriles in very good yields. The structures of all synthesised compounds were established on the
basis of NMR, IR, MS and elemental analysis.
Keywords: pyrazole carbohydrazide, hetero-cyclisation, substituted methylene malononitrile, secondary amines, Michael addition, multi-
functionalised 1,1’-carbonylbispyrazoles
Recent research into the synthesis of bis-heterocyclic
compounds, which have various practical applications, have
attracted the attention of scientists. Bis-pyrazole derivatives
formation of compound 8a–c was confirmed by the presence
–1
of the C=O band around 1771 cm in the IR spectrum. The
1
1
H NMR spectrum of 8c showed a triplet signal at δ = 1.53
have been used as excellent inhibitors of corrosion for many
and a quartet signal at δ = 4.53 ppm corresponding to an
ethoxy group, a singlet signal at δ = 2.58 corresponding to the
thiomethyl group and a broad singlet at δ = 6.18 corresponding
2
-5
metals and alloys (1, Fig. 1). They are also used as efficient
ligands in palladium-catalysed C–O and C–N cross-coupling
6
-9
reactions. The bispyrazole derivatives have coordination
to an NH group.
2
10
properties to metals and are useful as catalysts, for example,
Nucleophilic displacement of the ethoxy group with hydrazine
hydrate, a bis-nucleophile instead of a simple amine, was carried
out using absolute ethanol as the solvent to afford 5-amino-4-
cyano-1H-pyrazole-1-carbohydrazide (9a), 5-amino-4-cyano-
3-methyl-1H-pyrazole-1-carbohydrazide (9b) and 5-amino-4-
cyano-3-(methylthio)-1H-pyrazole-1-carbohydrazide (9c). The
IR spectrum of 9c showed absorption bands at 3400–3245, 3010,
heteroscorpionate[RR’C(pz) ]ligandsderivedfrombis(pyrazol-
2
11
1-yl)methane (2, Fig. 1). The high fluorescence quantum yield
of pyrazoline rings add to their wide application in selective
12
recognition of metal ions (3, Fig. 1). Bis-pyrazoles have been
used in the treatment of Alzheimer’s disease, brain ischaemia,
heart diseases, gastrointestinal diseases, cancer, ageing and
1
3-16
-1
inflammation.
These compounds are also antibacterial
2770, 2210, 1718 and 1634 cm indicating the presence of NH
and NH, cyano and C=O groups, respectively. The H NMR
2
17
1
and antifungal agents (4, Fig. 1). In addition, palladium and
platinum complexes of 5,5’-dimethyl-3,3’-bipyrazole and some
poly substituted 1,1’-carbonylbispyrazoles have been reported
as potential anti-tumour agents (5, Fig. 1).
Recently, we have investigated a new versatile route for
spectrum of 9c showed a signal at δ = 2.47 ppm corresponding
to the thiomethyl group. Moreover, the disappearance of the
characteristic pattern of the ethoxy group in addition to the
18,19
presence of two singlets corresponding to two NH and NH
2
2
0
the synthesis of 1,1’-carbonylbispyrazole derivatives . In an
extension of this work, we are undertaking related studies
employing bispyrazole derivatives derived from pyrazole
carbohydrazides. We now consider the nature of some
nucleophiles and the properties of substituted methylene
malonitriles which react through Michael addition–cyclisation
with the subsequent construction of bis-heterocyclic compounds.
protons at δ = 5.90 and δ = 11.85 ppm confirmed the structure
of the product. Compounds 7d–f have been prepared from the
substitution of one thiomethyl group of 2-(bis(methylthio)
methylene)malononitrile 7c with secondary amines in
absolute ethanol at room temperature. The mass spectrum of
2-((methylthio)(pyrrolidin-1-yl)methylene)malononitrile (7d)
+
showed a molecular ion signal at m/z 209 [M ] corresponding
to the molecular formula C H N OS. Compound 9a reacted
9
11
3
Results and discussion
with 7d under different reaction conditions. The excellent
conversion of this compound (9a) into the product 10a was
achieved within 8 h in refluxing pyridine. Under the optimised
conditions, the cyclo-condensation of a range of pyrazole
carbohydrazides carrying substituents on their aromatic rings,
with 7d–f, proceeded smoothly and gave the corresponding
multi-substituted 1,1’-carbonylbispyrazole derivatives (10a–i)
in very good yields (Scheme 1).
Ethyl hydrazinecarboxylate
methylene malonitriles 7a–c in absolute ethanol to give ethyl
6
reacted with substituted
5
5
-amino-4-cyano-1H-pyrazole-1-carboxylate 8a and ethyl
-amino-4-cyano-3-methyl-1H-pyrazole-1-carboxylate 8b
2
0
which have been reported previously, and ethyl 5-amino-
4
-cyano-3-(methylthio)-1H-pyrazole-1-carboxylate 8c. They
were prepared in 80–85% yield, respectively (Scheme 1). The
CH3
N
F3C
H C
N
O
3
R2
N
R'
HO
N
N
N
N
R
B
M
O
O
R
N
N
N
N
N
N
N
N
N N
N
N
N
N
N
H C
N
N
R1
3
CH3
Cl
1
2
3
4
5
Fig. 1 Scaffold 1–5.
*
Correspondent. E-mail: heshghi@um.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2015 221
O
R1
R2
CN
CN
abs. EtOH
reflux
H N
+
2
N
O
H
7
7
7
a: R =H, R =OEt
1 2
6
b: R =CH , R =OEt
1
3
2
c: R =SCH , R =SCH
3
1
3
2
N
N
NH2
N
NH2
O
N H .H O
2
4
2
O
N
R1
N
EtOH
reflux
N
NH
R1
H N
O
2
8
8
8
a: R =H
H N
O
NH2
R3
1
9a: R =H
2
1
1
b: R =CH3
9b: R =CH3
1
N
N
N
N
N
N
c:
R =SCH3
Pyridine
1
9c: R =SCH3
1
reflux, 8-10h
R1
1
0a-i
CH3
CH3
N
N
CH3
N
N
S
S
amine
S
10a: R1
R3=
:
, R
3=
N
: R =SCH R3=
N
cyclic secondary
=H,
N
10d R
1
=CH
3
10g
1
3
,
abs. EtOH
stirr at r.t.
R3
10b: R =H, R =O
N
N
10e: R =CH , R =O
N
10h: R
=SCH , R =O
N
1
3
1
3
3
1
3
3
7c
7d: R3
e: R3
f: R3
=pyrrolidine
=morpholine
=piperidine
7
7
10c: R =H, R =
10f: R =CH , R =
N
10i: R =SCH , R =
N
1
3
1
3
3
1
3
3
Scheme 1
The structure assignment of compounds 10a–i was based on
spectroscopic and microanalytical data. For example, the IR
spectrum of 10f revealed the presence of an additional cyano
band at 2220 cm . The H NMR spectrum of 10f showed the
presence of a singlet signal at δ = 2.45 ppm corresponding
to a methyl group, the multiplet signals in the range of δ =
Experimental
All reagents were purchased from Merck Company and used
without further purification. The melting points were recorded on an
Electrothermal type 9100 melting point apparatus. The IR spectra were
obtained on an Avatar 370 FT-IR Thermo Nicolet and only noteworthy
absorptions are listed. The H NMR (400 MHz) and the C NMR (100
MHz) spectra were recorded on a Bruker Avance, using DMSO-d6
-1
1
1
13
1
.79–1.89 ppm and a triplet signal at 3.89 ppm correspond to
1
or CDCl as solvents. Chemical shifts are reported in ppm downfield
the piperidinyl protons. Whereas H NMR spectrum of 9b in
3
from TMS as internal standard; coupling constants J are given in
Hertz. The mass spectra were scanned on a Varian Mat CH-7 at 70 eV.
Elemental analyses were performed on a Thermo Finnigan Flash EA
microanalyser.
CDCl showed the signals corresponding to NH and NH at δ
3
2
=
6.82 and δ =12.09 ppm, respectively, which disappeared on
1
addition of D O, the H NMR spectrum of the cyclised product
2
10f did not show these resonances. Instead, an exchangeable
broad singlet at δ = 5.99 ppm in CDCl confirmed that
3
13
heterocyclisation had occurred. The C NMR spectrum of
0f revealed the appearance of two signals at δ = 113.9 and δ
115.9 ppm, attributed to the two cyano groups confirming
Synthesis of pyrazoles (8a–c); general procedure
1
=
A 50 mL round-bottomed flask was charged with a mixture of
hydrazinecarboxylic acid ethyl ester (6, 2.13 g, 20.5 mmol) and 7a–c
(20 mmol) in absolute EtOH (30 mL) and the reaction mixture was
refluxed for 4 h. After this time, the mixture was cooled to room
temperature and stayed in the refrigerator overnight; the precipitate
that heterocyclisation with 2-[(methylthio)(piperidin-1-yl)
methylene]malononitrile (7f) had occurred. The carbonyl
carbon interfacing the two pyrazole rings of 10f appeared as a
resonance at δ = 156.33 ppm. Moreover, the chemical shift of the
methyl group and the piperidinyl carbons in 10f were reported
at δ 13.7 ppm and δ 23.7, 26.2 and 52.5 ppm respectively. The
was filtered and washed with cold Et O to afford 8 as colourless
2
needles. Ethyl 5-amino-4-cyano-1H-pyrazole-1-carboxylate (8a) and
ethyl 5-amino-4-cyano-3-methyl-1H-pyrazole-1-carboxylate (8b) are
2
0
well known.
mass spectrum of 10f showed a molecular ion signal at m/z
Ethyl 5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-carboxylate
+
3
39 [M ] corresponding to the molecular formula C H N O.
15
17
9
-1
(
3
8c): Yield 85%; m.p. 194°C; IR (KBr, υ /cm ): 3481, 3275, 3210,
110, 2207, 1772, 1634. H NMR (400 MHz, CDCl ) δ 1.53 (t, J=7.6
max
Moreover, this compound gave satisfactory elemental analysis.
1
3
Hz, 3H, CH CH ), 2.58 (s, 3H, SCH ), 4.53 (q, J=7.6 Hz, 2H, CH CH ),
2
3
3
2
3
6
2
.48 (br.s, 2H, NH ). Anal calcd for C H N O S: C, 42.47, H, 4.46, N,
4.76, S, 14.17; found: C, 42.27, H, 4.13, N, 24.12, S, 14.61%.
2 8 10 4 2
Conclusion
In summary,
a
new series of multi-functionalised
1
,1’-carbonylbispyrazole derivatives (10a–i) has been
Synthesis of 1H-pyrazole-1-carbohydrazides (9a–c); general
procedure
successfully synthesised in good yields through cyclisation
of pyrazole carbohydrazides (9a–c) with different methylene
malonitriles (7d–f), through a related procedure which has
been reported. Moreover, the presence of functionalities such
as NH , CH , SCH , CN and cyclic amines like pyrrolidinyl,
morpholinyl and piperidinyl on the pyrazole rings are expected
to be of interest because of their potential relevance to biological
activity and drug research.
A mixture of 8a–c (15 mmol) and hydrazine monohydrate (3 mL,
62 mmol) in absolute ethanol (10 mL) was refluxed for 3 h. After
2
0
completion of the reaction (TLC), the excess of solvent was distilled
off, and the crude product obtained was poured into ice water, then
the products were removed from water. The product obtained is
sufficiently pure for further reaction. 5-Amino-4-cyano-1H-pyrazole-
2
3
3
1-carbohydrazide (9a) and 5-amino-4-cyano-3-methyl-1H-pyrazole-

222 JOURNAL OF CHEMICAL RESEARCH 2015
2
0
+
1
-carbohydrazide (9b) are well known. Compound 9c is a known
113.95, 115.9, 152.5, 154.1, 156.8, 159.3. m/z calcd for C H N O [M] :
15 17 9
21
compound but we have synthesised it in a new pathway.
-Amino-4-cyano-3-(methylthio)-1H-pyrazole-1-carbohydrazide (9c):
Yield 87%; m.p. 230 °C (lit. not reported) IR (KBr, υ /cm ): 3429,
403, 3344, 3245, 3010, 2770, 2210, 1718, 1634; H NMR (100 MHz,
CD COCD ): 2.47 (s, 3H, SCH ), 5.90 (br. s, 4H, 2NH ), 11.85 (br. s, 1H,
339.16, found: 337.0. Anal. calcd for C H N O: C, 53.09; H, 5.05; N, 37.15;
15 17 9
5
found: C, 53.49; H, 5.20; N, 37.40%.
21
-1
5-Amino-1-(5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-
carbonyl)-3-(pyrrolidin-1-yl)-1H-pyrazole-4-carbonitrile (10g): Yield
63%; white solid; m.p. 270 °C (dec.), H NMR (400 MHz, DMSO-d ): δ
1.94 (t, J=6.4 Hz, 4H, 2CH ), 2.56 (s, 3H, SCH ), 4.15 (t, J=6.4 Hz, 4H,
2CH ), 7.35 (br.s, 4H, 2NH , D O exchangeable). C NMR (100 MHz,
max
1
3
1
3
3
3
2
6
NH). Anal calcd for C H N OS: C, 33.96, H, 3.80, N, 39.60; found: C,
6
8
6
2
3
13
33.58, H, 4.03, N, 39.78%.
2
2
2
DMSO-d ): δ 13.3, 25.8, 25.8, 54.4, 54.4, 64.7, 75.1, 114.1, 117.7, 124.5,
6
Synthesis of 1,1’-carbonyl-bispyrazole derivatives (10a–i); general
procedure
+
1
48.7, 155.1, 155.4, 161.1. m/z calcd for C H N OS [M] : 357.11, found:
14
15
9
3
57.0. Anal. calcd for C H N OS: C, 47.05; H, 4.23; N, 35.27; found: C,
14 15 9
A mixture of compound 9 (5 mmol) and compound 7d–f (5 mmol) was
stirred under reflux in dry pyridine (25 mL) for 8–10 h. The mixture was
47.35; H, 4.35; N, 35.48%.
5
-Amino-1-(5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-
cooled to room temperature, then H O (5mL) was added, and the mixture
2
carbonyl)-3-morpholino-1H-pyrazole-4-carbonitrile (10h): Yield 60%,
was neutralised by HCl. The collected solid was purified by preparative
-1
pale yellow solid; m.p. 243 °C; IR (KBr, υ /cm ): 3477, 3452, 3315, 3204,
max
1
TLC (1:15 MeOH:CHCl ). The crude product was rinsed in MeOH and the
3
2974, 2929, 2872, 2212, 1646, 1614, 1552; H NMR (400 MHz, DMSO-d ):
6
organic layer phase was filtered and evaporated under reduced pressure to
give the pure product.
δ 2.59 (s, 3H, SCH ), 3.82–3.83 (m, 8H, 4CH morpholine), 7.65 (br.s,
3
2
13
4
H, 2NH , D O exchangeable); C NMR (100 MHz, DMSO-d ): δ 13.1,
2
2
6
5
-Amino-1-(5-amino-4-cyano-1H-pyrazole-1-carbonyl)-3-(pyrrolidin-
5
1.3, 51.3, 66.7, 66.7, 69.8, 75.6, 113.9, 116.1, 124.5, 152.2, 155.1, 156.6,
1
>
-yl)-1H-pyrazole-4-carbonitrile (10a): Yield 75%; white solid; m.p.
+
160.4. m/z calcd for C H N O S [M] : 373.11, found: 372.0. Anal. calcd
1
14 15 9 2
300°C (dec.); H NMR (400 MHz, DMSO-d ): δ 1.94 (t, J=6.4 Hz, 4H,
6
for C H N O S: C, 45.03; H, 4.05; N, 33.76; found: C, 45.28; H, 4.14; N,
14
15
9
2
2
CH ), 4.15 (t, J=6 Hz, 4H, 2CH ), 7.35 (br.s, 4H, NH ,D O exchangeable),
2
2
2
2
3
4.07%.
-Amino-1-(5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-
carbonyl)-3-(piperidin-1-yl)-1H-pyrazole-4-carbonitrile (10i): Yield
13
8.23 (s, 1H, CH); C NMR (100 MHz, DMSO-d ): δ 22.8, 22.8, 54.6,
6
5
5
4.6, 65.2, 76.1, 114.9, 117.7, 145.9, 149.7, 154.5, 160.9, 162.9. m/z calcd for
+
C H N O [M] : 311.12, found: 311.0. Anal. calcd for C H N O: C, 50.16;
1
3
13
9
13 13
9
1
55%; white solid; m.p. >300 °C (dec.); H NMR (400 MHz, DMSO-d ):
6
H, 4.21; N, 40.49; found: C, 50.66; H, 4.40; N, 40.61%.
-Amino-1-(5-amino-4-cyano-1H-pyrazole-1-carbonyl)-3-morpholino-
H-pyrazole-4-carbonitrile (10b): Yield 70%; white solid; m.p. 260–261°C
δ 1.72 (m, 6H, 3CH piperidine), 2.61 (s, 3H, SCH ), 3.74 (m, 4H, 2CH
2
2
3
5
13
piperidine), 7.60 (br.s, 4H, 2NH ,D O exchangeable); C NMR(100 MHz,
2
2
1
DMSO-d ): δ 13.1, 23.5, 26.2, 26.2, 52.2, 52.22, 69.4, 75.5, 114.1, 116.3,
-1
6
(
dec.); IR (KBr, υmax /cm ): 3455, 3318, 3100, 2970, 2859, 2214, 1659, 1608.
+
1
52.4, 155.2, 156.4, 160.5. m/z calcd for C H N OS [M] : 371.11, found:
1
15 17
9
H NMR (400 MHz, DMSO-d ): δ 3.78–3.84 (m, 8H, morpholine), 7.65
6
3
71.0. Anal. calcd for C H N OS: C, 48.51; H, 4.61; N, 33.94; found: C,
13
15 17 9
(br.s, 4H, NH ,D O exchangeable), 8.39 (s, 1H, aromatic); C NMR (100
2 2
48.72; H, 4.47; N, 33.76%.
MHz, DMSO-d ): 51.4, 51.4, 66.3, 66.3, 70.9, 76.8, 114.7, 116.1, 147, 153.4,
6
+
1
54.1, 160.3. m/z calcd for C H N O [M] : 327.12, found: 327.0. Anal.
13
13
9
2
Received 17 February 2015; accepted 11 March 2015
Paper 1503211 doi: 10.3184/174751915X14271377629065
Published online: 13 April 2015
calcd for C H N O : C, 47.71; H, 4.00; N, 38.52; found: C, 47.24; H, 4.08;
13
13
9
2
N, 39.08%.
-Amino-1-(5-amino-4-cyano-1H-pyrazole-1-carbonyl)-3-(piperidin-
-yl)-1H-pyrazole-4-carbonitrile (10c): Yield 73%; pale yellow solid; m.p.
5
1
1
234 °C (dec.); H NMR (400 MHz, DMSO-d ): δ 1.7 (br. s, 6H, 3CH ), 3.77
6
2
References
(
1
br. s, 4H, 2CH ), 7.58–7.74 (br.s, 4H, 2NH , D O exchangeable), 8.40 (s,
2
2
2
1
2
B.F. Abdel-Wahaba and K.M. Dawood, Arkivoc, 2012 (i) 491.
M. Bouklah, M. Kaddouri, Y. Toubi, B. Hammouti, S. Radi and E.E. Ebenso,
Int. J. Electrochem. Sci., 2013, 8, 7437.
13
H, aromatic); C NMR (100 MHz, DMSO-d ): δ 23.5, 26.3, 26.3, 52.3,
6
5
2.3, 70.4, 76.7, 114.8, 116.2, 146.8, 146.8, 153.7, 154.2, 160.3. m/z calcd for
+
C H N O [M] : 325.14, found: 325.0. Anal. calcd for C H N O: C, 51.69;
3
4
5
6
7
M. Benabdellah, R. Touzani, A. Aouniti, A. Dafali, S. El Kadiri, B. Hammouti
and M. Benkaddour, Mater. Chem. Phys., 2007, 105, 373.
K. Tebbji, H. Oudda, B. Hammouti, M. Benkaddour, S.S. Al-Deyab, A.
Aouniti, S. Radi and A. Ramdani, Res. Chem. Intermed., 2011, 37, 985.
M. Bouklah, B. Hammouti, M. Benkaddour, A. Attayibat and S. Radi, Pigm.
Resin Tech., 2005, 34, 197.
S. Gowrisankar, A.G. Sergeev, P. Anbarasan, A. Spannenberg, H. Neumann
and M. Beller, J. Am. Chem. Soc., 2010, 132, 11592.
B.J. Kotecki, D.P. Fernando, A.R. Haight and K.A. Lukin, Org. Lett., 2009,
11, 947.
1
4
15
9
14 15
9
H, 4.65; N, 38.75; found: C, 51.36; H, 4.51; N, 38.98%.
-Amino-1-(5-amino-4-cyano-3-(pyrrolidin-1-yl)-1H-pyrazole-1-
carbonyl)-3-methyl-1H-pyrazole-4-carbonitrile (10d): Yield 60%; white
5
-1
solid; m.p. 286-287 °C (dec.); IR (KBr, υmax/cm ): 3462, 3303, 3248, 3164,
1
2
987, 2217, 2196, 1641, 1603; H NMR (400 MHz, DMSO-d ): δ 1.92 (t,
6
J=6.5 Hz, 4H, 2CH ), 2.43 (s, 3H, CH ), 3.85 (t, J=6.5 Hz, 4H, 2CH ), 6.95
2
3
2
13
(
b, 4H, NH , D O exchangeable), 8.23 (s, 1H, CH); C NMR (100 MHz,
2
2
DMSO-d ): δ 12.7, 23.6, 23.6, 53.8, 53.8, 62.9, 75.4, 113.9, 116.6, 145.7,
6
+
8
9
A. Porzelle, M.D. Woodrow and N.C.O. Tomkinson, Org. Lett., 2009, 11, 233.
S. Yu, A. Haight, B. Kotecki, L. Wang, K. Lukin and D.R. Hill, J. Org. Chem.,
1
50.6, 153.7, 161.2, 162.7. m/z calcd for C H N O [M] : 325.14, found:
14
15
9
3
24.0. Anal. calcd for C H N O: C, 51.69; H, 4.65; N, 38.75; found: C,
14 15 9
2009, 74, 9539.
51.91; H, 4.29; N, 39.09%.
1
11
0
D. Beaudoin and J.D. Wuest, Tetrahedron Lett., 2011, 52, 2221.
A. Otero, J. Fernández-Baeza, A. Antiñolo, J. Tejeda and A. Lara-Sánchez,
Dalton Trans., 2004, 1499.
5
-Amino-1-(5-amino-4-cyano-3-methyl-1H-pyrazole-1-carbonyl)-3-
morpholino-1H-pyrazole-4-carbonitrile (10e): Yield 65%; white solid;
1
m.p. 268 °C (dec.); white solid, H NMR (400 MHz, DMSO-d ): δ 2.32
12 T. Ren, J. Wang, G. Li and Y. Li, J. Fluoresc., 2014, 24, 1149.
6
13
E.M. Kosower and E. Hershkowitz, Isr. Patent ISXXAQIL 94658; Chem.
Abstr., 1994, 122, 214 077.
(
s, 3H, CH ), 3.77–3.82 (m, 4CH , 8H, morpholine), 7.52 (br.s, 4H, NH ,
3
2
2
13
D O exchangeable); C NMR (100 MHz, DMSO-d ): δ 13.8, 46.9, 51.3,
2
6
14
T. Igarashi, K. Sakurai, T. Oi, H. Obara, H. Ohya and H. Kamada, Free Radical
Biol. Med., 1999, 26, 1339.
5
1.3, 66.7, 66.7, 70.3, 77, 114.8, 116.3, 152.8, 154.5, 156.2, 160.2. m/z calcd
+
for C H N O [M] : 341.13, found: 341.0. Anal. calcd for C H N O : C,
1
4
15
9
2
14 15
9
2
15 H. Ohara, T. Igarashi, K. Sakurai and T. Oshii, US 6121305, 2000; Chem.
Abstr., 2000, 133, 232875.
16 H. Ohara, T. Igarashi, K. Sakurai and T. Oshii, JP 10306077, 1998; Chem.
Abstr., 1999, 130, 38378.
17 S. Ujjwal, B. Dhanya, A.K. Seth, A.K. Sen, S. Kumar, Y.C. Yadov, T.C.
Ghelani and R. Chawla, Curr. Pharma Res., 2010, 2, 82.
4
9.26; H, 4.43; N, 36.93; found: C, 49.49; H, 4.56; N, 37.37%.
-Amino-1-(5-amino-4-cyano-3-(piperidin-1-yl)-1H-pyrazole-1-
carbonyl)-3-methyl-1H-pyrazole-4-carbonitrile (10f): Yield 65%; white
5
-1
solid; m.p. 230–231°C, IR (KBr, υmax/cm ): 3463, 3309, 3163, 3115, 2986,
1
2884, 2218, 2220, 1640, 1603, 1561; H NMR (400 MHz, DMSO-d ): δ
6
18 N. Saha and A. Misra, J. Inorg. Biochem. 1995, 59, 234.
1
.79–1.81 (m, 2H, CH ), 1.83–1.89 (m, 4H, 2CH ), 2.45(s, 3H, CH ), 3.89
2
2
3
19 S.A.F. Rostom, Bioorg. Med. Chem., 2010, 18, 2767.
20 S. Saberi, H. Eshghi, M. Rahimizadeh and Kh. Abnous, Synlett, 2014, 889.
21 B. Harald, O. Gisela and P. Klaus, Naturwissenschaftliche Reihe 1984, 33, 67.
13
(t, J=5.6 Hz, 4H, 2CH ), 5.99 (br.s, 4H, NH ,D O exchangeable); C NMR
2
2
2
(
100 MHz, DMSO-d ): δ 13.7, 23.7, 26.2, 26.2, 52.5, 52.5, 69.6, 79, 102,
6

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