An efficient microwave-assisted synthesis and antimicrobial activity of novel 2-amino 3-cyano pyridine derivatives using two reusable solid acids as catalysts

Article abstract of DOI:10.1002/jhet.1641

Two solid acids, Fe³⁺ K-10 montmorillonite clay and HY-zeolite, have been employed efficiently for synthesis of 2-amino 3-cyano pyridines 4a-x by multicomponent reaction of 3-acetyl 4-hydroxy coumarin 1a, 1b, 1c, 1,3-diphenyl-1H-pyrazole-4-carb

Full text of DOI:10.1002/jhet.1641

Month 2013 An Efficient Microwave-Assisted Synthesis and Antimicrobial Activity of
Novel 2-Amino 3-Cyano Pyridine Derivatives using Two Reusable Solid
Acids as Catalysts
Shailesh Thakrar, Abhay Bavishi, Ashish Radadiya, Hardevsinh Vala, Shrey Parekh, Dhairya Bhavsar,
*
Ravi Chaniyara, and Anamik Shah
Department of Chemistry, Saurashtra University, Rajkot 360005, India
*
E-mail: anamik_shah@hotmail.com
Received September 9, 2011
DOI 10.1002/jhet.1641
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
Two solid acids, Fe3+ K-10 montmorillonite clay and HY-zeolite, have been employed efficiently for syn-
thesis of 2-amino 3-cyano pyridines 4a–x by multicomponent reaction of 3-acetyl 4-hydroxy coumarin 1a–c,
1,3-diphenyl-1H-pyrazole-4-carbaldehyde 2a–h, malononitrile 3, and ammonium acetate. Both the catalysts
are recoverable and recyclable. The main significant of this procedure is short reaction time, high yields, easy
workup procedure, and being environmentally friendly. The structures of all the compounds have been well
characterized by IR, 1H NMR, 13C NMR, and mass spectral data. All the synthesized compounds were
screened for their antimicrobial and antifungal activities.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
inhibitors, antiparasitic activities [20]. Various routes for the
synthesis of 2-amino-3-cyanopyridine derivatives have been
reported using two-component as well as three-component
reactions [21–25]. Feng Shi and coworkers [21] have reported
a microwave-assisted facile synthesis of 2-amino 3-cyanopyr-
idine derivatives in a one-pot reaction by using aromatic
aldehyde, methyl ketone, malononitrile, and ammonium
acetate. However, the protocols give comparatively lower
yields and longer reaction time. Therefore, the synthesis of
2-amino 3-cyanopyridine derivatives continues to attract
much interest in organic chemistry [26].
Different Lewis acids are used as catalyst for such reac-
tions under microwave condition [27]. However, many of
these Lewis acids are not easily available or expensive, non-
reusable, and afford the unsatisfactory yields. Recently, we
have reported the synthesis of various biologically active
heterocycles by using various methods [28]. These finding
prompted us to synthesize pyrazole and coumarin containing
2-amino 3-cyano pyridine derivatives for biological interest
using cheap, reusable, and easily available catalyst.
Among a wide variety of heterocycles, cyanopyridines [1]
and triazolopyridines [2] have played an important role in me-
dicinal chemistry. They possess a broad spectrum of
biological activity such as potential cardiovascular agents,
antiviral [3,4], CNS depressant [5], bactericidal [6], ulcer
inhibitors [7], and so on. Furthermore, researchers have also
revealed that cyanopyridine derivatives constitute an
important class of compounds possessing diverse type of
biological properties such as antiparasitic [8], antiparkinsonian
[9], anticonvulsant [10], and antihistaminic [11] as well as
antihelmintic [12] properties. Many naturally occurring and
synthetic compounds bearing pyridine scaffold possess inter-
esting biological properties [13]. 2-Amino-3-cyanopyridine
derivatives have been identified as IKK-b inhibitors [14,15].
Coumarin is a biologically active substance, with numerous
metabolites, and is widespread in nature [16]. Coumarin
derivatives constitute an important class of heterocyclic
compounds that has attracted significant attention in recent
years [17]. Moreover, the pyrazole framework containing
compounds are known for its antibacterial, anti-HIV, antican-
cer, anti-inflammatory, analgesic, and hypoglycemic activities
[18]. Pyrazoles are used as insecticides and pesticides because
of their herbicidal and fungicidal activity [19]. Recently,
pyrazoles containing aryl substituted emerged as p38 kinase
RESULT AND DISCUSSION
Initially, 3-acetyl 4-hydroxy coumarin 1a–c and
pyrazole aldehydes 2a–h were synthesized by reported
methods [29,30]. To optimize the reaction condition for
© 2013 HeteroCorporation

S. Thakrar, A. Bavishi, A. Radadiya, H. Vala, S. Parekh, D. Bhavsar, R. Chaniyara, and A. Shah Vol 000
Table 1
Yield optimization for 4a and 4b.
Entry
Condition
Fe+3 K-10a time (min)
HY-zeoliteb time (min)
Yielda (%)
Yieldb (%)
4a
4b
4a
4b
4a
4b
100
100
200
200
400
400
16.0
18.0
9.0
11.0
4.0
17.0
19.0
12.0
14.0
6.0
71
73
82
77
94
92
65
69
79
73
92
90
5.0
7.0
aIsolated yields in Fe+3 K-10 clay after purification
bIsolated yields in HY-zeolite after purification.
Reagents and conditions: 3-acetyl 4-hydroxy coumarin 1a and b (0.01 mol), pyrazole aldehydes 2a and b (0.01 mol), malononitrile 3 (0.01 mol),
ammonium acetate (0.08 mol), HY-zeolite/Fe+3 montmorillonite k-10, MW 400 W.
Scheme 1
Table 2
Physical data.
Substitution
Fe+3 K-10
time (min)
HY-zeoliteb
time (min)
Entry
R1
R
Yielda (%)
Yieldb (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4-Cl
4-CH3
H
4-NO2
2-OH
2-OCH3
3-NO2
4-F
H
4-CH3
4-Cl
4-NO2
2-OH
2-OCH3
3-NO2
4-F
H
4-CH3
4-Cl
4-NO2
2-OH
2-OCH3
3-NO2
4-F
H
H
H
H
H
H
H
H
8-CH3
8-CH3
8-CH3
8-CH3
8-CH3
8-CH3
8-CH3
8-CH3
5,8-di CH3
5,8-di CH3
5,8-di CH3
5,8-di CH3
5,8-di CH3
5,8-di CH3
5,8-di CH3
5,8-di CH3
4.0
5.0
5.0
4.0
5.0
6.0
5.0
6.0
5.0
5.0
7.0
6.0
5.0
6.0
5.0
5.0
5.0
6.0
4.0
4.0
6.0
5.0
6.0
5.0
6.0
7.0
6.0
8.0
6.0
7.0
8.0
7.0
8.0
7.0
9.0
8.0
7.0
8.0
9.0
7.0
9.0
8.0
7.0
6.0
8.0
7.0
9.0
9.0
94
92
91
89
90
91
86
87
88
90
87
91
86
89
89
88
86
89
86
89
87
88
89
94
92
90
88
86
82
89
84
78
79
81
83
87
82
84
79
91
84
79
81
80
82
81
88
92
4t
4u
4v
4w
4x
aIsolated yields in Fe+3 K-10 clay after purification.
bIsolated yields in HY-zeolite after purification.
Reagents and conditions: 3-acetyl 4-hydroxy coumarin 1a-c (0.01 mol), pyrazole aldehydes 2a–h (0.01 mol), malononitrile 3 (0.01 mol), ammonium
acetate (0.08 mol), HY-zeolite/Fe+3 montmorillonite k-10, MW 400 W.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013 An Efficient Microwave-Assisted Synthesis and Antimicrobial Activity of Novel 2-Amino
3-Cyano Pyridine Derivatives using Two Reusable Solid Acids as Catalysts
Table 3
Antimicrobial and antifungal activities of compounds 4a–x.
MIC value (mg/mL)
Compound
S. typhi MTCC-98
V. cholera TCC-3906
S. pyogenus MTCC-442
C. albicans MTCC-227
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
4u
4v
4w
4x
100
250
250
60.5
200
100
58.9
69.4
500
500
250
62.7
250
61.5
200
200
250
250
250
500
500
250
200
500
100
50
100
250
250
200
200
500
250
250
250
200
100
250
250
100
200
250
250
250
500
250
200
200
250
200
100
50
250
1000
250
250
500
250
250
500
500
250
100
500
250
250
200
500
200
250
250
250
500
200
250
500
100
50
1000
1000
250
1000
500
250
500
250
500
250
250
500
250
1000
100
500
1000
1000
1000
500
500
1000
500
100
—
Ampicillin
Chloramphenicol
Nystatin
Greseofulvin
—
100
500
—
—
—
—
—
—
4a and 4b, we undertook a model reaction of 1a and b, 2a
and b, ammonium acetate, and malononitrile 3 with Fe3+
K-10 montmorillonite clay as contrast to HY-zeolite by
using different microwave irradiation powers. It was found
that the reaction gives good yields in short reaction time at
400 wt. The results are shown in Table 1.
Further, the reaction of 1a–c, malononitrile, 2a–h, and
ammonium acetate with Fe3+ K-10 montmorillonite clay/
HY-zeolite under microwave irradiation gives title
Compounds 4c, 4g, 4h, 4m, 4k, and 4o can be optimized
for the broad spectrum of antibacterial activity, whereas
compounds 4a, 4d, 4f, 4h, 4l, and 4n can be optimized
against S. typhi. Herein, electron-withdrawing group
induces the potency (compounds 4a, 4g, 4h, and 4l),
whereas hydrophobic group attached to coumarin ring
lowers the potency. All compounds possess less potency
against C. albicans, although compound 4o can be further
optimized for its potency. Furthermore, we will modify the
compounds with bulkier electron-withdrawing group to
increase the potency against broad-spectrum antibacterial
species including C. albicans.
molecule 4a–x (Scheme 1) in high yield (Table 2).
Antimicrobial and antifungal activities of compounds 4a–x.
The newly synthesized 2-amino 3-cyano compounds 4a–x
have been screened for antimicrobial activity against
Staphylococcus Typhi, S. pyogenus and Vibrio cholera and
antifungal activity against Candida albicans by broth
dilution method [31,32]. Ampicillin, chloramphenicol,
nystatin, and greseofulvin were used as standards for
comparison of antimicrobial and antifungal activities. The
result shows that some of these compounds were active
aligned with all the four organisms. The results of
antimicrobial and antifungal activity are cited in Table 3.
CONCLUSION
We have developed a new method for novel 2-amino
3-cyano derivatives that is rapid and high yielding. During
the reaction procedure, it was observed that the time taken
for reaction at higher temperature is less with high yield as
compared with lower temperature. The antimicrobial and
antifungal activities of these compounds were evaluated
against various bacteria and fungi. Some of the compounds
show good activity, and many of them showed moderate
antimicrobial activity.
Structure–activity relationship.
A
structure–activity
relationship (SAR) study shows that 2-amino 3-cyano
pyridines can be further modified to enhance the potency.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Thakrar, A. Bavishi, A. Radadiya, H. Vala, S. Parekh, D. Bhavsar, R. Chaniyara, and A. Shah Vol 000
C30H18ClN5O3: C, 67.74; H, 3.41; N, 13.17; O, 9.02; found: C,
77.46; H, 3.36; N, 13.08; O, 9.09 (%).
Structure–activity relationship studies give some insights
for enhancing the potency of designed molecules. For
detailed SAR, more diversity of the molecules will be
generated by synthesizing diverse set of 2-amino 3-cyano
pyridines. Thus, our current research is focused for develop-
ment of diverse molecules. Herein, molecules 4a, 4g, 4h, and
4l have the electron-withdrawing groups, so other electron-
withdrawing groups such as –CF3, –CN, and –COOH will
be substituted at various positions to identifying the detailed
SAR. Among the synthesized compounds, 4a, 4d, 4f, 4k, 4l,
4n, and 4o were found to be active against all microorgan-
isms employed both for antimicrobial and antifungal activi-
ties. With this, we are now in a position to investigate the
manifold biological activities of these molecules.
2-Amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-4-(1-phenyl-3-
(p-tolyl)-1H-pyrazol-4-yl)nicotinonitrile (4b). IR (cmÀ1): 3626,
3568, 3421, 3392, 3275, 3189, 3086, 2908, 2891, 2424,
1
2333, 1782, 1668, 1618, 1554, 1379, 1165, 790, 717. H NMR
(DMSO-d6) d ppm: 2.36 (s, 3H), 7.16–7.18 (d, 2H), 7.20 (d, 1H),
7.25–7.27 (t, 1H), 7.34–7.38 (t, 1H), 7.44–7.46 (d, 2H), 7.50–7.52
(d, 2H, J= 8.0 Hz), 7.59–7.77 (t, 1H), 7.86–7.88 (d, 2H,
J = 8.0 Hz), 7.92 (s, 2H), 7.92 (s, 2H), 8.02–8.05 (d, 2H), 8.25
(s, 1H), 8.30 (s, 1H), 8.50 (s, 1H), 18.30 (s, 1H). 13C NMR: 18.58,
32.18, 36.97, 38.18, 39.19, 39.80, 39.88, 40.11, 40.42, 88.18,
97.39, 101.14, 103.55, 113.45, 116.09, 117.07, 119.83, 120.45,
125.73, 126.85, 127.46, 128.91, 130.67, 131.72, 143.32, 144.55,
145.76, 152.68 159.23, 161.25, 166.29. MS: m/z = 511.16; Anal.
Calcd for C31H21N5O3: C, 72.79; H, 4.14; N, 13.69; O, 9.38;
found: C, 72.81; H, 4.10; N, 13.48; O, 9.21 (%).
2-Amino-4-(1,3-diphenyl-1H-pyrazol-4-yl)-6-(4-hydroxy-2-oxo-
2H-chromen-3-yl)nicotinonitrile (4c). IR (cmÀ1): 3635, 3542,
3465, 3401, 3032, 3024, 2984, 2823, 2332, 1778, 1570,
EXPERIMENTAL
1
1428, 1382, 1263, 1158, 793, 716. H NMR (DMSO-d6) d ppm:
All the melting points are uncorrected. Formation of the
compounds was routinely checked by TLC on silica gel-G plates
of 0.5 mm thickness, and spots were located by iodine and UV.
All the reactions were carried out in Q-Pro-M microwave
synthesizer. The IR spectra were recorded on a Shimadzu FTIR-
8400 instrument using KBr pellet method. Mass spectra were
recorded on Shimadzu GC-MS-QP-2010 model using Direct
7.18–7.20 (d, 1H), 7.25–7.28 (t, 1H), 7.36–7.38 (t, 4H), 7.51–7.57
(m, 5H), 7.87–7.89 (d, 2H), 8.02–8.04 (d, 3H), 8.24 (s, 1H), 8.55
(s, 1H), 18.32 (s, 1H). 13C NMR: 32.18, 36.97, 38.18, 38.39,
40.60, 40.81, 98.18, 101.13, 103.45, 113.14, 116.25, 119.55,
120.19, 123.07, 125.63, 127.55, 126.73, 127.75, 129.06, 129.61,
130.67, 131.22, 133.23, 144.05, 146.76, 158.65, 159.51, 161.65.
MS: m/z = 497.50; Anal. Calcd for C30H19N5O3: C, 72.43; H, 3.85;
N, 14.08; O, 9.65; found: C, 72.34; H, 3.75; N, 14.00; O, 9.59 (%).
2-Amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-4-(3-(4-
nitrophenyl)-1-phenyl-1H-pyrazole-4-yl)nicotinonitrile (4d). IR
(cmÀ1): 3552, 3450, 3417, 3062, 3034, 2984, 2901, 2839,
1
Injection Probe technique. H NMR was determined in CDCl3/
DMSO solution on a Bruker Ac 400MHz spectrometer. Elemental
analysis of the all the synthesized compounds were carried out on
Elemental Vario EL III Carlo Erba 1108 model, and the results
are in agreements with the structures assigned.
1
2332, 1767, 1562, 1560, 1439, 1382, 1263, 1160, 794, 717. H
Synthesis of 2-amino 3-cyano pyridine derivatives (3a–c). A
mixture of 3-acetyl 4-hydroxy coumarin 1a–c (0.01 mol), pyrazole
aldehydes 2a–h (0.01 mol), malononitrile (0.01mol), and
ammonium acetate (0.08 mol) HY-zeolite/Fe+3 montmorillonite
k-10 were taken in 100-mL microwave flask. The reaction
mixture was irradiated under microwave irradiation by using
Q-Pro-M microwave synthesizer for the desired time at 400 W.
The progress and the completion of the reaction were checked
at interval of every 1 min by using silica gel-G F254 thin layer
chromatographic plates using hexane:ethyl acetate (2:3) as a
mobile phase. The reaction mixture was allowed to cool at
room temperature and resulting product extracted into CHCl3.
The solid HY-zeolite/Fe+3 montmorillonite k-10 were filtered
off and the solvent removed by rotary evaporator. The solid
clay portion was washed with methanol and dried at 110ꢀC for
4–5 h to be reused in the next reaction. It can be used for more
than three times.
NMR (DMSO-d6) d ppm: 7.23–7.26 (d, 1H), 7.25–7.31 (t, 1H),
7.35–7.37 (d, 2H, J = 8.0 Hz), 7.39–7.42 (d, 1H), 7.52 (d, 1H),
7.57–7.65 (t, 4H), 7.77–7.89 (d, 2H, J = 8.0 Hz), 7.98 (s, 2H),
8.08–8.010 (d, 1H), 8.29 (s, 2H), 8.51 (s, 1H), 18.25 (s, 1H). 13C
NMR: 30.48, 32.87, 38.08, 39.39, 39.62, 40.31, 79.38, 97.68,
101.29, 103.25, 119.14, 119.95, 123.19, 125.87, 126.83, 129.55,
12.93, 131.67, 138.22, 143.02, 145.55, 146.76, 152.23, 159.85,
161.75, 155.65. MS: m/z = 542.50; Anal. Calcd for C30H18N6O5:
C, 66.42; H, 3.34; N, 15.49; O,14.75; found: C, 66.40; H, 3.29;
N, 15.33; O, 14.73 (%).
2-Amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-4-(3-(2-
hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4e). IR
(cmÀ1): 3602, 3451, 3427, 3032, 3014, 2974, 2961, 2838, 2342,
1769, 1572, 1438, 1381, 1262, 1161, 795, 716. 1H NMR
(DMSO-d6) d ppm: 6.84–6.87 (t, 2H), 7.19–7.21 (t, 2H), 7.27
(t, 1H), 7.37–7.41 (q, 2H), 7.52–7.58 (m, 3H), 7.79–7.91 (d, 2H,
J = 8.0Hz), 8.00–8.02 (s, 2H), 8.15 (s, 1H), 8.23 (s, 2H), 8.77
(s, 1H), 18.12 (s, 1H). 13C NMR: 30.28, 36.87, 38.08, 39.49,
39.80, 88.19, 101.27, 103.85, 104.97, 113.14, 116.15, 118.65,
120.09, 121.17, 123.74, 126.85, 128.63, 130.85, 131.82, 141.45,
143.76, 152.82, 155.22, 160.45, 161.52. MS: m/z = 513.14; Anal.
Calcd for C30H19N5O4: C, 70.17; H, 3.73; N, 13.64; O, 12.46;
found: C, 70.13; H, 3.69; N, 13.53; O, 12.43 (%).
2-Amino-4-(3-(4-chlorophneyl)-1-phenyl-1H-pyrazol-4-yl)-6-
(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile (4a). IR (cmÀ1):
3645, 3562, 3475, 3400, 3317, 3082, 3014, 2974, 2901, 2829,
1
2424, 2322, 1768, 1560, 1429, 1381, 1253, 1159, 762, 715. H
NMR (DMSO-d6) d ppm: 7.21–7.23 (d, 1H), 7.26–7.30 (t, 1H),
7.34–7.36 (d, 2H, J = 8.0 Hz), 7.38–7.40 (d, 1H), 7.51 (d, 1H),
7.55–7.60 (t, 4H), 7.85–7.87 (d, 2H, J = 8.0Hz), 7.96 (s, 2H),
8.03–8.05 (d, 1H), 8.27 (s, 1H), 8.50 (s, 1H), 18.35 (s, 1H). 13C
NMR: 38.96, 39.19, 39.39, 39.60, 39.81, 40.05, 40.25, 78.15,
78.33, 79.83, 88.69, 97.20, 102.65, 105.99, 113.04, 117.05,
119.95, 124.09, 125.07, 127.73, 129.45, 129.73, 131.75, 132.96,
134.51, 135.57, 142.82, 145.22, 153.65, 155.86, 159.65, 161.52,
166.23. MS: m/z = 531 (M+2); 533 (M + 2); Anal. Calcd for
2-Amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-4-(3-(2-
methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4f). IR
(cmÀ1): 3562, 3456, 3427, 3072, 3024, 2983, 2911, 2849, 2342,
1768, 1552, 1449, 1372, 1262, 1161, 792, 715. 1H NMR
(DMSO-d6) d ppm: 2.39 (s, 3H), 7.29–7.33 (d, 2H), 7.38–7.41
(d, 1H), 7.47 (t, 1H), 7.52 (d, 1H), 7.59–7.65 (t, 4H), 7.78–7.81
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013 An Efficient Microwave-Assisted Synthesis and Antimicrobial Activity of Novel 2-Amino
3-Cyano Pyridine Derivatives using Two Reusable Solid Acids as Catalysts
(d, 2H), 8.03–8.07 (t, 1H), 8.12 (s, 1H), 8.19 (s, 2H), 8.29 (s, 1H),
8.40 (s, 1H), 18.13 (s, 1H). 13C NMR: 31.19, 38.87, 39.08, 39.29,
39.62, 39.91, 56.22, 81.18, 82.79, 99.86, 101.23, 103.75, 111.25,
113.42, 115.74, 117.19, 118.54, 121.45, 124.09, 125.17, 129.83,
130.45, 130.67, 139.02, 143.15, 151.86, 152.65, 154.75, 160.74.
MS: m/z = 527.50; Anal. Calcd for C31H21N5O4: C, 70.58; H,
4.01; N, 13.28; O, 12.13; found: C, 70.51; H, 3.99; N, 13.15; O,
2-Amino-4-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-
'(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)nicotinonitrile (4k). IR
(cmÀ1): 35562, 3420, 3069, 2991, 2849, 2342, 1777, 1582, 1429,
1372, 1273, 1140, 758, 719. 1H NMR (DMSO-d6) d ppm: 2.47
(s, 3H), 7.20–7.23 (d, 1H), 7.25–7.30 (t, 1H), 7.34–7.36 (d, 2H,
J= 8.0 Hz), 7.56 (d, 1H), 7.59–7.66 (t, 4H), 7.80–7.82 (d, 2H,
J= 8.0 Hz), 7.99 (s, 2H), 8.14–8.17 (d, 1H), 8.39 (s, 1H), 8.48
(s, 1H), 18.25 (s, 1H). 13C NMR: 17.98, 31.78, 38.87, 39.08, 39.39,
39.61, 39.71, 88.18, 99.01, 101.89, 104.54, 113.15, 117.04, 120.48,
125.19, 126.17, 127.83, 128.55, 129.71, 131.51, 132.92, 141.32,
143.05, 145.76, 147.65, 151.56, 155.65, 161.75. MS: m/z=545 (M+),
547 (M + 2); Anal. Calcd for C31H20ClN5O3: C, 68.20; H, 3.69; N,
12.06 (%).
2-Amino-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-4-(3-(3-
nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4g). IR
(cmÀ1): 3552, 3450, 3417, 3062, 3034, 2984, 2901, 2839, 2332,
1767, 1562, 1565, 1439, 1382, 1263, 1154, 794, 717 702. 1H
NMR (DMSO-d6) d ppm: 7.28–7.31 (d, 2H), 7.37–7.40 (d, 1H),
7.45 (t, 1H), 7.51 (d, 1H), 7.58–7.65 (t, 4H), 7.77–7.81 (d, 2H),
8.02–8.05 (t, 1H), 8.10 (s, 1H), 8.18 (s, 2H), 8.28 (s, 1H), 8.39
(s, 1H), 18.12 (s, 1H). 13C NMR: 31.08, 37.97, 38.18, 39.19,
39.68, 39.71, 40.11, 40.20, 79.83, 81.69, 88.91, 97.12, 101.55,
103.61, 113.13, 115.17, 119.43, 121.23, 123.34, 126.09, 127.07,
128.45, 130.57, 132.92, 141.32, 143.71, 143.67, 145.86, 155.65,
159.08, 161.56. MS: m/z = 542.0; Anal. Calcd for C30H18N6O5: C,
66.42; H, 3.34; N, 15.49; O, 14.75; found: C, 66.34; H, 3.16; N,
12.83; O, 8.79; found: C, 68.23; H, 3.51; N, 12.71; O, 8.89 (%).
2-Amino-6-(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)-4-
'(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4l). IR
(cmÀ1): 3550, 3470, 3407, 3092, 2974, 2921, 2859, 2322,
1
1787, 1563, 1571, 1432, 1381, 1262, 1168, 751, 711. H NMR
(DMSO-d6) d ppm: 2.57 (s, 3H), 7.20–7.23 (d, 1H), 7.25–7.29
(t, 1H), 7.32–7.34 (d, 2H, J= 8.0 Hz), 7.52 (d, 1H), 7.55–7.61
(t, 4H), 7.70–7.72 (d, 2H, J= 8.0 Hz), 7.89 (s, 2H), 8.16–8.19
(d, 1H), 8.38 (s, 1H), 8.49 (s, 1H), 18.35 (s, 1H). 13C NMR: 18.58,
30.19, 37.87, 38.08, 38.49, 39.61, 39.91, 83.79, 101.34, 103.90,
103.34, 113.19, 115.17, 118.14, 119.15, 124.19, 126.17, 127.73,
128.85, 131.58, 132.83, 140.21, 143.75, 146.86, 151.81, 153.65,
155.65, 161.76. MS: m/z= 556.15; Anal. Calcd for C31H20N6O5: C,
66.90; H, 3.62; N, 15.10; O, 14.37; found: C, 66.83; H, 3.61; N,
15.31; O, 14.62 (%).
2-Amino-4-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-
(4-hydroxy-2-oxo-2H-chromen-3-yl)nicotinonitrile (4h). IR (cmÀ1):
3602, 3430, 3407, 3061, 3024, 2994, 2911, 2849, 2339, 1777,
1
1560, 1449, 1389, 1253, 1169, 790, 710. H NMR (DMSO-d6) d
ppm: 7.24–7.27 (d, 1H), 7.26–7.31 (t, 1H), 7.44–7.46 (d, 2H,
J = 8.0 Hz), 7.48–7.50 (d, 1H), 7.55 (d, 1H), 7.57–7.61 (t, 4H),
7.86–7.88 (d, 2H, J = 8.0 Hz), 7.98 (s, 2H), 8.13–8.15 (d, 1H),
8.37 (s, 1H), 8.52 (s, 1H), 18.25 (s, 1H). 13C NMR: 32.19,
39.87, 39.98, 40.01, 40.11, 83.79, 99.90, 101.78, 103.76,
113.52, 115.21, 117.56, 120.04, 123.43, 124.89, 126.07, 127.73,
128.59, 131.57, 141.32, 143.65, 145.86, 155.65, 159.81, 161.76.
MS: m/z = 515 (M+), 517 (M + 2); Anal. Calcd for C30H18FN5O3:
C, 69.90; H, 3.52; N, 13.54; O, 9.31; found: C, 69.80; H, 3.41; N,
15.07; O, 14.49 (%).
2-Amino-6-(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)-4-
(3-(2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile
(4m). IR (cmÀ1): 3552, 3452, 3407, 3063, 3014, 2983, 2911,
2890, 2330, 1787, 1561, 1429, 1382, 1253, 1161, 761, 717. 1H
NMR (DMSO-d6) d ppm: 2.89 (s, 3H), 4.98 (s, 1H), 6.84–6.87
(d, 1H), 6.91–6.94 (s, 1H), 7.19–7.25 (t, 1H), 7.28 (t, 1H),
7.37–7.41 (t, 4H), 7.55–7.58 (t, 1H), 7.79–7.81 (d, 2H,
J = 8.0 Hz), 8.03 (s, 1H), 8.14 (s, 1H), 8.24 (s, 2H), 8.78
(s, 1H), 18.12 (s, 1H). 13C NMR: 17.98, 31.28, 37.97, 39.28,
39.19, 39.61, 39.91, 84.69, 99.89, 101.23, 103.34, 113.24,
118.14, 119.15, 119.49, 124.09, 126.17, 128.73, 129.45, 131.67,
132.92, 143.28, 145.75, 150.86, 152.34, 155.75, 159.09, 161.78,
166.87. MS: m/z= 527.16; Anal. Calcd for C31H21N5O4: C,
70.58; H, 4.01; N, 13.28; O, 12.13; found: C, 70.53; H, 4.01; N,
13.33; O, 9.25 (%).
2-Amino-4-(1,3-diphenyl-1H-pyrazol-4-yl)-6-(4-hydroxy-8-methyl-
2-oxo-2H-chromen-3-yl)nicotinonitrile (4i). IR (cmÀ1): 3562,
3421, 3402, 3042, 3014, 2984, 2819, 2232, 1760, 1572, 1429,
1
1372, 1269, 1161, 792, 707. H NMR (DMSO-d6) d ppm: 2.39
(s, 3H), 7.22–7.25 (d, 1H), 7.29–7.33 (t, 1H), 7.37–7.41 (t, 4H),
7.47–7.55 (m, 5H), 7.59–7.64 (d, 2H), 8.29 (s, 1H), 8.45 (s, 2H),
8.55 (s, 1H), 17.25 (s, 1H). 13C NMR: 17.68, 20.98, 38.97, 39.18,
39.38, 39.59, 39.80, 40.01, 40.22, 78.10, 78.43, 78.75, 99.49,
112.52, 118.09, 124.27, 125.43, 126.71, 127.14, 128.42, 127.67,
127.93, 127.97, 128.55, 128.96, 132.62, 139.49, 141.84, 150.63.
MS: m/z = 511.53; Anal. Calcd for C31H21N5O3: C, 72.79; H,
4.14; N, 13.69; O, 9.38; found: C, 72.83; H, 4.11; N,13.59; O,
13.17; O, 12.11 (%).
2-Amino-6-(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)-4-
(3-(2-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile
(4n). IR (cmÀ1): 3651, 3420, 3407, 3052, 3014, 2994, 2921, 2829,
1
2341, 1787, 1562, 1433, 1372, 1262, 1161, 764, 714. H NMR
(DMSO-d6) d ppm: 2.49 (s, 3H), 3.12 (s, 3H), 7.28–7.33 (d, 2H),
7.37–7.41 (d, 1H), 7.48 (t, 1H), 7.53 (d, 1H), 7.58–7.66 (t, 4H),
7.79–7.82 (d, 2H), 8.04–8.07 (t, 1H), 8.18 (s, 2H), 8.28 (s, 1H),
8.41 (s, 1H), 18.23 (s, 1H). 13C NMR: 16.58, 30.88, 36.97, 39.18,
39.40, 56.72, 57.67, 88.08, 99.08, 101.25, 104.67, 111.90,
113.76, 118.14, 119.15, 119.49, 125.19, 126.09, 131.57,
132.92, 140.22, 141.65, 145.86, 155.65, 159.90, 164.67. MS: m/
z = 541.56; Anal. Calcd for C32H23N5O4: C, 70.97; H, 4.28; N,
9.39 (%).
2-Amino-6-(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)-4-
(1-phenyl-3-(p-tolyl)-1H-pyrazol-4-yl)nicotinonitrile (4j). IR (cmÀ1):
3602, 3431, 3407, 3012, 2981, 2829, 2331, 1768, 1572, 1419,
1
1381, 1261, 1161, 764, 727. H NMR (DMSO-d6) d ppm: 2.34
(s, 6H), 7.17–7.20 (m, 3H), 7.35–7.39 (t, 1H), 7.44–7.46 (d, 2H,
J = 8.0 Hz), 7.52–7.56 (t, 2H), 7.84–7.85 (d, 1H), 7.96–7.98
(d, 2H, J = 8.0 Hz), 8.17–8.19 (d, 2H, J = 8.0 Hz), 8.37 (s, 2H),
8.88 (s, 1H), 17.72 (s, 1H). 13C NMR: 15.12, 20.92, 38.92, 39.13,
39.34, 39.55, 39.76, 39.97, 40.18, 78.40, 78.73, 79.06, 91.45,
117.43, 118.51, 119.05, 124.88, 127.30, 129.04, 129.40, 137.58,
138.93, 150.04, 151.16, 153.32. MS: m/z = 525 (M+); Anal. Calcd
for C32H23N5O3: C, 73.13; H, 4.41; N, 13.33; O, 9.13; found: C,
73.03; H, 4.31; N, 13.17; O, 9.10 (%).
12.93; O, 11.82; found: C, 70.83; H, 4.21; N, 12.87; O, 11.75 (%).
2-Amino-6-(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)-4-
(3-(3-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4o). IR
(cmÀ1): 3602, 3490, 3457, 3012, 3031, 2994, 2981, 2829, 2382,
1777, 1563, 1429, 1381, 1253, 1161, 755, 702. 1H NMR
(DMSO-d6) d ppm: 2.89(s, 3H), 7.26–7.30 (d, 1H), 7.37–7.40
(d, 2H), 7.43 (t, 1H), 7.53 (d, 1H), 7.59–7.66 (t, 4H), 7.78–7.81
(d, 2H), 8.09 (s, 1H), 8.17 (s, 2H), 8.29 (s, 1H), 8.37 (s, 1H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Thakrar, A. Bavishi, A. Radadiya, H. Vala, S. Parekh, D. Bhavsar, R. Chaniyara, and A. Shah Vol 000
18.22 (s, 1H). 13C NMR: 16.98, 30.17, 37.87, 38.19, 39.49, 39.61,
39.71, 88.19, 97.81, 101.97, 102.79, 106.07, 113.14, 117.87,
119.21, 122.76, 123.45, 125.19, 127.07, 127.83, 129.45, 129.91,
131.50, 132.92, 133.49, 143.75, 145.36, 152.79, 155.35, 161.45.
MS: m/z = 556.53; Anal. Calcd for C31H20N6O5: C, 66.90; H,
3.62; N, 15.10; O, 14.37; found: C, 66.91; H, 3.51; N, 15.07; O,
for C32H22ClN5O3: C, 68.63; H, 3.96; N, 12.51; O, 8.57; found:
C, 68.53; H, 3.91; N, 12.41; O, 8.47 (%).
2-Amino-6-(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)-
4-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4t).
IR (cmÀ1): 3556, 3456, 3467, 3162, 3024, 2994, 2981, 2829,
1
2331, 1768, 1562, 1560, 1429, 1392, 1253, 1161, 754, 707. H
NMR (DMSO-d6) d ppm: 2.99 (s, 3H), 3.24 (s, 3H), 7.26–7.29
(d, 1H), 7.32–7.35 (t, 1H), 7.37–7.39 (d, 2H, J= 8.0 Hz), 7.50
(d, 1H), 7.60–7.66 (t, 4H), 7.90–7.92 (d, 2H, J= 8.0 Hz), 8.20
(s, 2H), 8.54 (s, 1H), 8.68 (s, 1H), 18.18 (s, 1H). 13C NMR: 17.98,
22.67, 30.19, 39.97, 82.89, 99.78, 101.56, 103.77, 113.23,
117.14, 119.15, 123.34, 124.54, 125.19, 126.17, 129.71, 131.67,
133.82, 143.75, 145.76, 151.25, 152.56, 155.65, 159.75, 161.25.
MS: m/z= 570.55; Anal. Calcd for C32H22N6O5: C, 67.36; H, 3.89;
14.39 (%).
2-Amino-4-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-
(4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl)nicotinonitrile (4p). IR
(cmÀ1): 3552, 3450, 3417, 3062, 3034, 2984, 2901, 2839, 2332, 1767,
1562, 1439, 1382, 1263, 1160, 754, 717. 1H NMR (DMSO-d6) d ppm:
2.48 (s, 3H), 7.21–7.24 (d, 1H), 7.29–7.32 (t, 1H), 7.34–7.36 (d, 2H,
J= 8.0 Hz), 7.53 (d, 1H), 7.57–7.64 (t, 4H), 7.72–7.74 (d, 2H,
J= 8.0 Hz), 7.88 (s, 2H), 8.18–8.21 (d, 1H), 8.39 (s, 1H), 8.50
(s, 1H), 18.45 (s, 1H). 13C NMR: 15.11, 30.78, 35.88, 38.96, 39.17,
39.38, 39.59, 39.79, 40.00, 40.21, 78.07, 78.40, 78.73, 85.53, 91.43,
109.34, 115.01, 116.02, 117.94, 118.53, 118.78, 118.98, 122.63,
124.79, 126.72, 128.32, 129.32, 129.66, 134.11, 138.73, 149.02,
150.51, 151.12, 153.10, 153.23, 154.80, 160.69, 161.93, 178.01.
MS: m/z= 529 (M+), 531 (M + 2); Anal. Calcd for C31H20FN5O3: C,
70.31; H, 3.81; N, 13.23; O, 9.06; found: C, 70.21; H, 3.71; N,
N, 14.73; O, 14.02; found: C, 67.33; H, 3.81; N, 14.67; O, 14.06 (%).
2-Amino-6-(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)-
4-(3-(2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile
(4u). IR (cmÀ1): 3612, 3460, 3427, 3065, 3014, 2994, 2911,
1
2839, 2332, 1767, 1562, 1449, 1383, 1253, 1169, 759, 717. H
NMR (DMSO-d6) d ppm: 2.38 (s, 3H), 2.89 (s, 3H), 4.87 (s, 1H),
7.22–7.24 (d, 1H), 7.27–7.30 (t, 1H), 7.37–7.40 (d, 1H), 7.49
(d, 1H), 7.53 (d, 1H), 7.54–7.60 (t, 4H), 7.78–7.85 (d, 1H), 8.02–
8.05 (d, 1H), 8.37 (d, 2H), 8.51 (s, 1H), 8.39 (s, 1H), 18.72 (s,
1H). 13C NMR: 17.25, 23.46, 30.19, 37.87, 38.19, 39.38,
39.61, 39.91, 88.08, 99.90, 101.82, 103.87, 113.24, 117.65,
119.40, 121.35, 123.34, 125.19, 128.49, 128.79, 131.67,
132.80, 133.42, 143.75, 144.76, 150.32, 151.67, 155.85,
159.67, 161.98. MS: m/z = 541.56; Anal. Calcd for
C32H23N5O4: C, 70.97; H, 4.28; N, 12.93; O, 11.82; found: C,
13.21; O, 9.01 (%).
2-Amino-4-(1,3-diphenyl-1H-pyrazol-4-yl)-6-(4-hydroxy-5,8-
dimethyl-2-oxo-2H-chromen-3-yl)nicotinonitrile (4q). IR (cmÀ1):
3642, 3451, 3427, 3069, 3014, 2994, 2831, 2334, 1787, 1564,
1
1439, 1382, 1269, 1159, 759, 711. H NMR (DMSO-d6) d ppm:
2.48 (s, 3H), 3.02 (s, 3H), 7.36–7.38 (d, 2H, J = 8.0 Hz), 7.36–
7.41 (t, 4H), 7.53 (d, 1H), 7.55–7.61 (t, 4H), 7.77–7.79 (d, 2H,
J = 8.0 Hz), 8.13–8.15 (d, 1H), 8.55 (s, 1H), 8.36 (s, 1H), 18.41
(s, 1H). 13C NMR: 27.90, 33.99, 38.96, 39.17, 39.38, 39.59,
39.80, 40.01, 40.22, 78.01, 78.34, 78.67, 112.51, 118.10, 118.80,
124.24, 125.43, 125.71, 126.93, 127.08, 127.42, 127.67, 127.93,
127.97, 128.54, 128.94, 132.61, 137.77, 139.49, 141.83, 145.52,
150.67. MS: m/z = 525.56; Anal. Calcd for C32H23N5O3: C, 73.13;
H, 4.41; N, 13.33; O, 9.13; found: C, 73.05; H, 4.31; N, 13.27;
70.83; H, 4.17; N, 12.77; O, 11.74 (%).
2-Amino-6-(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)-
4-(3-(2-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile
(4v). IR (cmÀ1): 3552, 3458, 3034, 2901, 2849, 2342, 1777, 1561,
1
1439, 1382, 1261, 1161, 758, 712. H NMR (DMSO-d6) d ppm:
2.48 (s, 3H), 2.79 (s, 3H), 3.02 (s, 3H), 7.29–7.33 (d, 2H),
7.49 (s, 1H), 7.54 (d, 1H), 7.59–7.66 (t, 4H), 7.77–7.82 (d, 2H),
8.03–8.07 (t, 1H), 8.19 (s, 2H), 8.29 (s, 1H), 8.42 (s, 1H), 18.13
(s, 1H). 13C NMR: 17.98, 22.32, 31.89, 37.96, 56.76, 83.79,
98.56, 102.45, 104.34, 111.04, 113.23, 117.25, 119.15, 119.46,
121.25, 123.43, 124.35, 126.17, 128.30, 129.73, 129.91, 130.67,
131.72, 133.32, 138.32, 143.66, 145.06, 150.23, 152.23, 157.65.
MS: m/z = 555.19; Anal. Calcd for C33H25N5O4: C, 71.34; H,
4.54; N, 12.61; O, 11.52; found: C, 71.23; H, 4.41; N, 12.57; O,
O, 9.08 (%).
2-Amino-6-(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)-
4-(1-phenyl-3-(p-tolyl)-1H-pyrazol-4-yl)nicotinonitrile (4r). IR
(cmÀ1): 3602, 3460, 3417, 3068, 3024, 2989, 2911, 2829,
1
2342, 1747, 1532, 1439, 1382, 1268, 1169, 748, 719. H NMR
(DMSO-d6) d ppm: 2.79 (s, 3H), 3.04 (s, 3H), 3.14 (s, 3H),
7.22–7.26 (d, 1H), 7.26–7.32 (t, 1H), 7.36–7.38 (d, 2H,
J = 8.0 Hz), 7.52 (d, 1H), 7.56–7.60 (t, 4H), 7.83–7.85 (d, 2H,
J = 8.0 Hz), 8.28 (s, 2H), 8.51 (s, 1H), 8.45 (s, 1H), 18.58
(s, 1H). 13C NMR: 15.34, 20.91, 23.08, 35.87, 39.16, 39.37,
39.58, 39.79, 40.00, 78.12, 78.45, 78.78, 85.79, 99.49, 117.22,
117.51, 118.47, 122.70, 126.07, 127.25, 128.92, 129.02,
129.26, 137.50, 138.92, 149.32, 161.94. MS: m/z = 539.58;
Anal. Calcd for C33H25N5O3: C, 73.46; H, 4.67; N, 12.98; O,
11.41(%).
2-Amino-6-(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)-
4-(3-(3-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)nicotinonitrile (4w).
IR (cmÀ1): 3612, 3455, 3447, 3062, 3014, 2974, 2849, 2334,
1769, 1569, 1561, 1449, 1384, 1264, 1164, 769, 719. 1H NMR
(DMSO-d6) d ppm: 2.99 (s, 3H), 3.24 (s, 3H), 7.27–7.30 (d, 2H),
7.36–7.38 (d, 2H, J= 8.0 Hz), 7.40 (t, 1H), 7.52 (d, 1H), 7.56–7.60
(t, 4H), 7.79–7.81 (d, 2H, J= 8.0 Hz), 8.04–8.07 (s, 1H), 8.26
(s, 1H), 8.36 (s, 1H), 18.32 (s, 1H). 13C NMR: 17.78, 22.17, 30.98,
38.79, 39.08, 88.19, 98.12, 101.43, 103.23, 113.04, 117.15, 119.55,
122.09, 123.17, 128.73, 128.40, 128.83, 131.57, 132.92, 143.85,
145.76, 148.75, 152.23, 155.75, 159.32, 161.12. MS: m/z= 570.55;
Anal. Calcd for C32H22N6O5: C, 67.36; H, 3.89; N, 14.73; O, 14.02;
8.90; found: C, 73.33; H, 4.61; N, 12.97; O, 8.84 (%).
2-Amino-4-(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-
(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)nicotinonitrile
(4s). IR (cmÀ1): 3552, 3450, 3417, 3061, 3031, 2974, 2911, 2839,
1
2332, 1767, 1561, 1438, 1381, 1262, 1162, 795, 717. H NMR
(DMSO-d6) d ppm: 2.89 (s, 3H), 3.14 (s, 3H), 7.24–7.27
(d, 1H), 7.26–7.31 (t, 1H), 7.38–7.40 (d, 2H, J = 8.0 Hz), 7.55
(d, 1H), 7.57–7.64 (t, 4H), 7.88–7.90 (d, 2H, J = 8.0 Hz), 8.29
(s, 2H), 8.52 (s, 1H), 8.66 (s, 1H), 18.48 (s, 1H). 13C NMR:
18.68, 22.75, 31.19, 38.87, 39.08, 39.19, 39.61, 39.91, 82.60,
98.90, 101.21, 103.44, 118.14, 119.55, 120.55, 123.19, 126.06,
128.63, 129.61, 131.58, 132.72, 143.69, 145.76, 147.76, 151.45,
155.75, 161.80. MS: m/z = 559 (M+), 561 (M + 2); Anal. Calcd
found: C, 67.23; H, 3.81; N, 14.67; O, 14.01 (%).
2-Amino-4-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-6-
(4-hydroxy-5,8-dimethyl-2-oxo-2H-chromen-3-yl)nicotinonitrile
(4x). IR (cmÀ1): 3562, 3456, 3427, 3092, 3084, 2901, 2899,
1
2342, 1787, 1563, 1449, 1342, 1264, 1164, 768, 707. H NMR
(DMSO-d6) d ppm: 2.89 (s, 3H), 3.14 (s, 3H), 7.27–7.30 (d, 1H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013 An Efficient Microwave-Assisted Synthesis and Antimicrobial Activity of Novel 2-Amino
3-Cyano Pyridine Derivatives using Two Reusable Solid Acids as Catalysts
[18] (a) Shin, K. D.; Lee, M. Y.; Shin, D. S.; Lee, S.; Son, K. H.;
7.34–7.38 (t, 1H), 7.47–7.49 (d, 2H, J = 8.0 Hz), 7.51 (d, 1H),
7.62–7.68 (t, 4H), 7.92–7.94 (d, 2H, J = 8.0 Hz), 8.31 (s, 2H),
8.64 (s, 1H), 8.78 (s, 1H), 18.17 (s, 1H). 13C NMR: 17.68,
22.32, 32.28, 88.8, 97.56, 101.24, 103.43, 113.23, 116.32,
117.68, 118.02, 119.65, 123.43, 126.19, 129.61, 131.57, 133.92,
143.85, 145.76, 150.98, 152.23, 155.75, 159.67, 161.23. MS:
m/z = 543 (M+), 545 (M + 2); Anal. Calcd for C32H22FN5O3:
C, 70.71; H, 4.08; N, 12.88; O, 8.83; found: C, 70.65; H, 4.02;
N, 12.79; O, 8.72 (%).
Koh, S.; Paik, Y. K.; Kwon, B. M.; Han, D. C. J. Biol Chem 2005, 280,
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Liu, X. H.; Cui, P.; Song, B. A.; Bhadury, P. S.; Zhu, H. L.; Wang,
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Acknowledgments. The authors are thankful to FIST-DST and
SAP-UGC for their generous financial and instrumentation
support. Special thanks are due to “National Facility for Drug
Discovery through New Chemical Entities (NCE’s) Development
and Instrumentation Support to Small Manufacturing Pharma
Enterprises” Program under Drug and Pharma Research Support
(DPRS) jointly funded by Department of Science and Technology,
New Delhi, Government of Gujarat Industries Commissionerate and
Saurashtra University, Rajkot.
[20] (a) Graneto, M. J.; Kurumbail, R. G.; Vazquez, M. L.; Shieh,
H. S.; Pawlitz, J. L.; Williams, J. M.; Stallings, W. C.; Geng, L.; Naraian,
A. S.; Koszyk, F. J.; Stealey, M. A.; Xu, X. D.; Weier, R. M.; Hanson, G.
J.; Mourey, R. J.; Compton, R. P.; Mnich, S. J.; Anderson, G. D.;
Monahan, J. B.; Devraj, R. J Med Chem 2007, 50, 5712. (b) Kuettel, S.;
Zambon, A.; Kaiser, M.; Brun, R.; Scapozza, L.; Perozzo, R. J Med Chem
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet