Efficient and rapid synthesis of highly functionalized novel symmetric 1,4-dihydropyridines using glacial acetic acid as solvent

Article abstract of DOI:10.1080/00397911.2011.576448

A new series of 1,4-dihydropyridines bearing a pyrazole moiety in the 4-position were synthesized by a variation of the classical Hantzsch synthesis. The reaction of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4a-n with 3-amino crotononitrile in the presence of glacial acetic acid afforded novel 3,5-dicyano-2,6-dimethyl 1,4-dihydropyridines 5a-n. The procedure has short reaction time (15-20 min), easy workup, and good yield of product. The structures of all synthesized compounds were well characterized by mass, infrared, ¹H and ¹³C NMR, and elemental analysis.

Full text of DOI:10.1080/00397911.2011.576448

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Efficient and Rapid Synthesis of Highly
Functionalized Novel Symmetric 1,4-
Dihydropyridines Using Glacial Acetic
Acid as Solvent
Shailesh Thakrar a , Abhay Bavishi a , Dhairya Bhavsar a , Shrey
Parekh a , Hardev Vala a , Ashish Radadiya a , Manisha Parmar a
Mahesh Savant a & Anamik Shah a
,
a Department of Chemistry, Saurashtra University, Rajkot, India
Accepted author version posted online: 08 May 2012.Version of
record first published: 18 Jul 2012.
To cite this article: Shailesh Thakrar, Abhay Bavishi, Dhairya Bhavsar, Shrey Parekh, Hardev Vala,
Ashish Radadiya, Manisha Parmar, Mahesh Savant & Anamik Shah (2012): Efficient and Rapid Synthesis
of Highly Functionalized Novel Symmetric 1,4-Dihydropyridines Using Glacial Acetic Acid as Solvent,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:22, 3269-3278
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Synthetic Communications1, 42: 3269–3278, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.576448
EFFICIENT AND RAPID SYNTHESIS OF
HIGHLY FUNCTIONALIZED NOVEL SYMMETRIC
1,4-DIHYDROPYRIDINES USING GLACIAL
ACETIC ACID AS SOLVENT
Shailesh Thakrar, Abhay Bavishi, Dhairya Bhavsar,
Shrey Parekh, Hardev Vala, Ashish Radadiya,
Manisha Parmar, Mahesh Savant, and Anamik Shah
Department of Chemistry, Saurashtra University, Rajkot, India
GRAPHICAL ABSTRACT
Abstract A new series of 1,4-dihydropyridines bearing a pyrazole moiety in the 4-position
were synthesized by a variation of the classical Hantzsch synthesis. The reaction of
1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4a–n with 3-amino crotononitrile in the presence
of glacial acetic acid afforded novel 3,5-dicyano-2,6-dimethyl 1,4-dihydropyridines 5a–n.
The procedure has short reaction time (15–20 min), easy workup, and good yield of
product. The structures of all synthesized compounds were well characterized by mass,
infrared, 1H and 13C NMR, and elemental analysis.
Keywords 1,4-Dihydro pyridines; glacial acetic acid; pyrazole aldehyde
INTRODUCTION
In the past few years, very significant attention has been given to the synthesis of
1,4-dihydropyridines because of their good biological activity.[1] 1,4-Dihydropyridine
Received December 29, 2010.
Address correspondence to Anamik Shah, Department of Chemistry, Saurashtra University,
Rajkot 360005, India. E-mail: anamik_shah@hotmail.com
3269

3270
S. THAKRAR ET AL.
(DHP)–containing drugs such as nifedipine 1, amlodipine 2, and felodipine 3 have
been found to be useful as calcium channel blockers[2–4] (Fig. 1) and are used most
frequently as cardiovascular agents for the treatment of hypertension.[5]
1,4-DHPs were first synthesized by the Hantzsch method[6] using a ketoester, alde-
hydes and ammonia under reflux in methanol or ethanol, which takes longer time and
gives poor yields.[8,9] Over the past few years, a great variety of 1,4-DHPs have been
synthesized that have different substitutions on the C3 and C5 positions of the DHP
ring[7] using various procedures such as microwaves,[10] ionic liquids,[11] high tempera-
ture at reflux,[12] TMSCl-NaI,[13] InCl2,[14] I2,[15] baker’s yeast,[16] catalysts,[17] and metal
triflates.[18] Even though a large number of modified methods have been reported[19]
under improved conditions, most of the reported methods suffer from some drawbacks
such as unsatisfactory yields, high temperature, harsh reaction conditions, long reaction
time, and lengthy workup procedure.[20] Thus, the development of a method for the
preparation of 1,4-DHP derivatives is an active area of research and there is a scope
for further improvement toward milder reaction conditions and greater product yields.
The 1,4-DHPs having dicyano groups at the 3 and 5 positions and various
symmetric and asymmetric DHPs have been reported in the literature.[21] Earlier,
we reported 1,4-DHP derivatives by conventional methods using benzoyl acetone,
aldehyde, and ammonium acetate in methanol that exhibit potent multidrug resist-
ance (MDR) reversal activity in tumor cell lines.[22] In addition, the structures of
DHPs containing dicyano at the 3 and 5 positions were established by x-ray study.[23]
Moreover, the pyrazole framework–containing compounds are well known for
antimicrobial,[24] anti-inflammatory,[24] analgesic,[24] anti-HIV, anticancer, and
hypoglycemic activities.[25] Numerous pyrazoles are utilized as insecticides and pes-
ticides because of their herbicidal and fungicidal activity.[26] Recently, pyrazoles con-
taining aryl substitutents emerged as p38 kinase inhibitors with antiparasitic
activities.[27] These findings prompted us to synthesize pyrazole-containing DHPs
functionalized with dicyano groups for biological interest.
Our ongoing interest in the synthesis of highly functionalized DHPs by various
methods[28,29] has prompted us to report a rapid, facile, and efficient synthesis of
Figure 1. Biologically active pyridine derivatives.

NOVEL SYNTHESIS OF SYMMETRIC 1,4-DHP
3271
Scheme 1. Synthesis of dicyano, dimethyl, and pyrazole functionalized dihydropyridines. (a) Glacial
CH3COOH, EtOH, stirring, 1 h; (b) DMF–POCl3=70–80 ꢀC, reflux 5–6 h; and (c) 3-amino crotononitrile,
glacial CH3COOH=60 ꢀC, 15–20 min.
pyrazole, dicyano, and dimethyl functionalized 1, 4-DHP derivatives using the
modified Hantzsch method (Scheme 1).
RESULTS AND DISCUSSION
Indeed, the reaction of 4a and 4b with crotononitrile was observed at 50 ꢀC and
requires 30 min, and the yields were 80% and 82%. When the reaction was conducted
at 60 ꢀC, it afforded the product in 90% and 92% yields. However, the temperature
affects the product yield. When the reaction observed at 80 ꢀC and 100 ꢀC, the yield
of products was less (Table 1).
All the pyrazole aldehydes (4a–n) have been synthesized by the reported
procedure using phenyl hydrazine and substituted acetophenone followed by
Vilsmeier–Haack reaction.[25] The reaction of pyrazole aldehydes 4a–n and 3-amino
crotononitrile in glacial acetic acid at 60 ꢀC afforded title molecules 5a–n with good
yields in 15–25 min, and the results are depicted in Table 2.
Table 1. Optimization of yield for the synthesis of 5a and 5b
Entry
Compound
Temp. (ꢀC)
Time (min)
Yielda
%
1
2
3
4
5
6
7
8
5a
5b
5a
5b
5a
5b
5a
5b
50
50
30
30
15
16
14
16
12
14
80
82
90
92
70
75
71
73
60
60
80
80
100
100
aIsolated yields after purification.

3272
S. THAKRAR ET AL.
Table 2. Synthesis of dihydropyridines 5a–n
Entry
Substitution R
Time (min)
Yielda
%
5a
5b
5c
5d
5e
5f
H
15
16
15
25
10
15
25
15
15
10
15
15
10
15
90
92
90
91
87
88
86
92
88
91
89
90
92
90
4-CH3
4-Cl
4-NO2
2-OH
2-OCH3
3-NO2
4-F
5g
5h
5i
4-Br
5j
2-OH
4-CF3
3-Cl
5k
5l
5m
5n
4-OCH3
3-OH
aIsolated yields after purification.
CONCLUSION
During the reaction procedure, we observed that the time taken by 5d and 5g is
more than for other synthesized DHPs. All of the compounds prepared by this
method gave better yields in shorter reaction times without any purification. In con-
clusion, we have reported a facile, highly efficient, and high-yielding procedure for the
preparation of 1,4-DHPs for biological interest. The present procedure is general and
convenient for the synthesis of dicyano, dimethyl, and pyrazole functionalized
symmetric DHPs. Moreover, the cyano group makes further transformation possible.
MATERIALS AND METHODS
Melting points were determined in open capillary tubes and are uncorrected.
Formation of the compounds was routinely checked by thin-layer chromatography
(TLC) on silica-gel-G plates 0.5 mm thick, and spots were located by iodine and ultra-
violet (UV). Infrared (IR) spectra were recorded on a Shimadzu FT-IR-8400 instru-
ment using the KBr pellet method. Mass spectra were recorded on a Shimadzu
1
GC-MS-QP-2010 model using the direct injection probe technique. H NMR was
determined in CDCl3=DMSO solution on a Bruker Ac 400-MHz spectrometer.
Elemental analysis of the all the synthesized compounds was carried out on an
Elemental Vario EL III Carlo Erba 1108 model, and the results are in agreement with
the structures assigned.
All the pyrazole aldehyde derivatives were prepared by reported methods.[25]
Experimental Procedure
A mixture of pyrazole aldehyde (0.01 mol) and 3-amino crotononitrile
(0.02 mol) in glacial CH3COOH was stirred for 1 h at 60–70 ꢀC in a Stoppard flask.
The reaction mixture was kept at room temperature for half an hour. During the

NOVEL SYNTHESIS OF SYMMETRIC 1,4-DHP
3273
reaction, the progress and the completion of reaction were checked by silica-gel-G
F254 thin-layer chromatography (TLC) using ethyl acetate–hexane (3:2) as a mobile
phase. After the reaction completed, the reaction mixture was kept at room tempera-
ture for 1 h and the crystalline product was separated by filtration. The solid product
was obtained after cooling and then filtered and washed with acetic acid and hexane.
Physical Data
1,4-Dihydro-2,6-dimethyl-4-(1,3-diphenyl-1H-prazol-4-yl)pyridine-3,5-
dicarbonitrile (5a). IR (cmꢁ1): 3286, 3109, 3012, 2841, 2195, 1664, 1597, 1518,
1
1448, 1329, 1284, 705; H NMR (DMSO-d6) d ppm: 1.94 (s, 6H), 4.59 (s, 1H),
7.32–7.50 (m, 5H), 7.55–7.59 (t, 3H), 7.86–7.91 (d, 2H), 8.36 (s, 1H), 9.25 (s, 1H);
13C NMR: 17.58, 31.18, 38.97, 39.18, 39.39, 39.60, 39.81, 40.01, 40.22, 78.18, 78.71,
78.83, 82.69, 118.04, 119.05, 119.45, 125.09, 126.07, 127.73, 128.45, 128.73, 128.75,
128.96, 129.51, 130.57, 132.82, 139.22, 143.65, 145.86, 155.65; MS: m=z ¼ 377(Mþ).
Anal. calcd. for C24H19N5: C, 76.37; H, 5.07; N, 18.55. Found: C, 76.29; H, 5.04;
N, 18.50.
1,4-Dihydro-2,6-dimethyl-4-(1-phenyl-3-p-Tolyl-1H-pyrazol-4-yl)pyridine-
3,5-dicarbonitrile (5b). IR (cmꢁ1): 3296, 3126, 2993, 2839, 2198, 1662,1595, 1508,
1
1448, 1354, 1292, 756, 686; H NMR (DMSO-d6) d ppm: 1.95 (s, 6H), 2.39 (s, 3H),
4.57 (s, 1H), 7.22–7.24 (d, 2H, J ¼ 8.0 Hz), 7.26–7.29 (t, 1H), 7.43–7.50 (m, 4H),
7.76–7.80 (d, 2H, J ¼ 8.0 Hz), 8.09 (s, 1H), 9.05 (s, 1H); 13C NMR: 17.59, 31.19,
38.96, 39.19, 39.40, 39.62, 39.82, 40.03, 40.23, 78.15, 78.75, 78.83, 82.66, 118.14,
118.35, 119.35, 123.09, 125.07, 127.73, 128.55, 128.43, 128.45, 128.56, 129.54,
129.65, 130.50, 132.92, 139.21, 145.66, 149.86; MS: m=z ¼ 391 (Mþ). Anal. calcd.
for C25H21N5: C, 76.70; H, 5.41; N, 17.89. Found: C, 76.66; H, 5.36; N, 17.81.
4-(3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-2,6-dimethyl
pyridine-3,5-dicarbonitile (5c). IR (cmꢁ1): 3290, 3126, 3016, 2993, 2839, 2200,
1
1662, 1599, 1545, 1446, 1357, 1294, 754, 690; H NMR (DMSO-d6) d ppm: 1.86
(s, 6H), 4.48 (s, 1H), 7.18–7.22 (t, 1H), 7.31–7.33 (d, 2H), 7.34–7.38 (t, 2H),
7.48–7.51 (d, 2H, J ¼ 8.0 Hz), 7.66–7.68 (d, 2H), 7.95 (s, 1H), 8.90 (s, 1H),
13C NMR: 17.49, 38.86, 39.06, 39.17, 39.69, 40.01, 40.11, 78.08, 78.74, 82.31,
118.18, 118.08, 120.10, 126.40, 126.64, 127.82, 128.32, 129.37, 134.98, 139.53,
147.32, 147.76, 149.70; MS: m=z ¼ 411 (Mþ), 413 (Mþ2). Anal. calcd. for
C24H18ClN5: C, 69.98; H, 4.40; N, 17.00. Found: C, 69.89; H, 4.40; N, 16.98.
1,4-Dihydro-2,6-dimethyl-4-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)
pyridine-3,5-dicarbonitrile (5d). IR (cmꢁ1): 3296, 3129, 2998, 2836, 2210, 1668,
1
1599, 1540, 1365, 1510, 1458, 1356, 1296, 758, 688; H NMR (DMSO-d6) d ppm:
1.93 (s, 6H), 4.71 (s, 1H), 7.31–7.35 (t, 1H), 7.48–7.52 (t, 2H), 7.86–7.88 (d, 2H,
J ¼ 8.0 Hz), 7.89–7.91 (d, 2H, J ¼ 8.0 Hz), 8.29–8.32 (d, 2H), 8.47 (s, 1H), 9.34
(s, 1H); 13C NMR: 17.59, 31.30, 38.96, 39.16, 39.37, 39.79, 40.00, 40.21, 78.18,
78.84, 82.41, 118.28, 118.88, 123.10, 125.50, 126.54, 128.92, 129.22, 129.27, 138.98,
139.63, 146.22, 146.86, 148.79; MS: m=z ¼ 422 (Mþ). Anal. calcd. for C24H18
N6O2: C, 68.24; H, 4.29; N, 19.89; O, 7.57. Found: C, 68.14; H, 4.25; N, 19.80;
O, 7.49.

3274
S. THAKRAR ET AL.
1,4-Dihyro-4-(3-(2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5e). IR (cmꢁ1): 3610, 3294, 312, 2990, 2830,
1
2208, 1661, 1592, 1508, 1456, 1360, 1240, 1298, 752, 678; H NMR (DMSO-d6) d
ppm: 1.91 (s, 6H), 4.57 (s, 1H), 6.83–6.87 (t, 1H), 6.94–6.96 (d, 1H, J ¼ 8.0 Hz),
7.17–7.21 (t, 1H), 7.26–7.29 (t, 1H), 7.33–7.35(d, 1H, J ¼ 8.0 Hz), 7.44–7.48 (t,
2H), 7.79–7.81(d, 2H, J ¼ 8.0 Hz), 8.24(s, 1H), 8.98(s, 1H), 9.52(s, 1H); 13C NMR:
17.55, 31.37, 38.94, 39.15, 39.36, 39.78, 39.99, 40.20, 77.97, 78.63, 82.34, 115.43,
117.86, 118.31, 118.97, 119.13, 125.93, 125.98, 126.99, 129.13, 129.21, 130.63,
139.12, 145.95, 149.32, 155.29. MS: m=z ¼ 393 (Mþ). Anal. calcd. for C24H19N5O:
C, 73.27; H, 4.87; N, 17.80; O, 4.07. Found: C, 73.23; H, 4.79; N, 17.73; O, 4.03.
1,4-Dihydro-4-(3-(2-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dim-
ethyl-pyridine-3,5-dicarbonitrile (5f). IR (cmꢁ1): 3298, 3120, 2996, 2832, 2210,
1
1660, 1582, 1518, 1466, 1361, 1310, 1299, 751, 670; H NMR (DMSO-d6) d ppm:
1.92 (s, 6H), 3.81 (s, 3H), 4.38 (s, 1H), 6.96–7.02 (q, 2H), 7.25–7.29 (t, 2H),
7.35–7.39 (t, 2H), 7.43–7.46 (t, 2H), 7.74–7.76 (d, 2H, J ¼ 8.0 Hz), 7.98 (s, 1H),
8.74 (s, 1H); 13C NMR: 17.48, 31.44, 38.95, 39.16, 39.37, 39.58, 39.79, 40.00,
40.21, 54.75, 77.06, 77.71, 82.64, 109.89, 118.13, 118.96, 119.67, 121.41, 125.76,
125.85, 125.93, 128.86, 129.45, 131.71, 145.53, 149.05, 156.87; MS: m=z ¼ 407
(Mþ). Anal. calcd. for C25H21N5O: C, 73.69; H, 5.19; N, 17.19; O, 3.93. Found:
C, 73.61; H, 5.17; N, 4.05; O, 3.90.
1,4-Dihydro-2,6-dimethyl-4-(3-(3-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)
pyridine-3,5-dicarbonitrile (5g). IR (cmꢁ1): 3292, 3121, 2986, 2842, 2201, 1662,
1
1572, 1542 1508, 1476, 1360, 1289, 750, 671; H NMR (DMSO-d6) d ppm: 1.91 (s,
6H), 4.73 (s, 1H), 7.31–7.35 (t, 1H), 7.48–7.62 (t, 2H), 7.71–7.75 (t, 1H), 7.88–7.91
(d, 2H), 8.03–8.07 (t,1H), 8.27–8.28 (d, 1H), 8.41–8.42 (s, 1H), 8.46 (s, 1H), 9.34
(s, 1H), 13C NMR: 17.50, 31.55, 38.95, 39.16, 39.37, 39.58, 39.79, 40.00, 40.21,
78.14, 78.79, 82.25, 118.23, 118.76, 119.55, 122.49, 122.95, 124.46, 126.45, 128.49,
129.22, 129.37, 129.55, 134.63, 134.78, 138.98, 146.40, 147.40, 149.01; MS: m=
z ¼ 422 (Mþ). Anal. calcd. for C24H18N6O2: C, 68.24; H, 4.29; N, 19.89; O, 7.57.
Found: C, 68.14; H, 4.16; N, 19.81; O, 7.47.
4-(3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5h). IR (cmꢁ1): 3298, 3124, 2996, 2852, 2208,
1
1666, 1582, 1518, 1486, 1360, 1299, 753, 672; H NMR (DMSO-d6) d ppm: 1.94
(s, 6H), 4.57 (s, 1H), 7.29–7.31 (d, 2H, J ¼ 8.0 Hz), 7.36–7.45 (t, 1H), 7.58–7.69
(m, 4H), 7.96–7.98 (d, 2H, J ¼ 8.0 Hz), 8.05 (s, 1H), 9.02 (s, 1H); 13C NMR: 17.73,
33.02, 38.96, 39.17, 39.38, 39.58, 39.79, 40.00, 40.21, 78.20, 78.53, 78.86, 80.35,
118.14, 118.80, 123.67, 124.76, 125.11, 125.20, 133.80, 147.73, 155.61, 155.68,
174.99; MS: m=z ¼ 395 (Mþ), 397 (Mþ2). Anal. calcd. for C24H18FN5: C, 72.90;
H, 4.59; N, 17.71. Found: C, 72.83; H, 4.51; N, 17.57.
4-(3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5i). IR (cmꢁ1): 3288, 3104, 2986, 2862, 2218,
1
1656, 1580, 1508, 1496, 1289, 754, 689, H NMR (DMSO-d6) d ppm: 1.86 (s, 6H),
4.71 (s, 1H), 7.32–7.34 ( d, 2H, J ¼ 8.0 Hz), 7.46–7.51 (t, 1H), 7.53–7.60 (m, 4H),
7.86–7.88 (d, 2H, J ¼ 8.0 Hz), 8.81 (s, 1H), 8.99 (s, 1H); 13C NMR: 17.49, 38.76,
39.26, 39.47, 39.69, 40.05, 40.61, 78.08, 78.74, 82.31, 117.18, 119.38, 120.15,

NOVEL SYNTHESIS OF SYMMETRIC 1,4-DHP
3275
123.60, 126.59, 128.72, 129.42, 138.78, 139.73, 147.22, 149.86, 150.79, MS: m=z ¼ 455
(Mþ), 357 (Mþ2). Anal. calcd. for C24H18BrN5: C, 63.17; H, 3.98; N, 15.35 Found:
C, 63.13; H, 3.71; N, 15.25.
1,4-Dihydro-4-(3-(4-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5j). IR (cmꢁ1): 3510, 3311, 3104, 2998, 2862,
1
2218, 1676, 1588, 1528, 1485, 1298, 1245, 745, 686 H NMR (DMSO-d6) d ppm:
1.98 (s, 6H), 4.61 (s, 1H), 7.12–7.14 (d, 2H, J ¼ 8.0 Hz), 7.36–7.39 (t, 1H), 7.53–
7.60 (m, 4H), 7.76–7.78 (d, 2H, J ¼ 8.0 Hz), 7.91 (s, 1H), 8.04 (s, 1H), 8.82 (s, 1H),
13C NMR: 17.66, 38.96, 39.16, 39.37, 39.71, 40.16, 40.31, 82.52, 117.27, 119.80,
121.30, 123.51, 126.53, 128.72, 129.42, 130.27, 139.73, 147.32, 148.46, 149.87,
159.09; MS: m=z ¼ 393 (Mþ). Anal. calcd. for C24H19N5O: C, 73.27; H, 4.87; N,
17.80; O, 4.07. Found: C, 73.03; H, 4.71; N, 17.77; O, 4.01.
4-(3-(4-(Trifluoromethyl)phenyl)-1-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-
2,6-dimethyl-pyridine-3,5-dicarbonitrile (5k). IR (cmꢁ1): 3282, 3024, 2976,
1
2882, 2228, 1665, 1538, 1370, 1279, 763, 689; H NMR (DMSO-d6) d ppm: 1.92
(s, 6H), 4.61 (s, 1H), 7.32–7.34 (d, 2H, J ¼ 8.0 Hz), 7.46–7.49 (t, 1H), 7.53–7.60
(m, 4H), 7.88–7.90 (d, 2H, J ¼ 8.0 Hz), 8.69 (s, 1H), 8.85 (s, 1H); 13C NMR:
17.61, 38.76, 38.96, 39.47, 39.81, 40.26, 40.51, 82.51, 116.88, 117.88, 123.10,
125.60, 126.74, 128.82, 129.23, 149.87, 158.79; MS: m=z ¼ 445 (Mþ), 447 (Mþ2).
Anal. calcd. for C25H18F3N5: C, 67.41; H, 4.07; F, 12.80; N, 15.72. Found: C,
67.23; H, 4.01; F, 12.77; N, 15.61.
4-(3-(3-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1,4-dihydro-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5l). IR (cmꢁ1): 3278, 3034, 2976, 2892, 2202,
1
1656, 1572, 1528, 1496, 1289, 761, 698; H NMR (DMSO-d6) d ppm: 1.94 (s, 6H),
4.54 (s, 1H), 7.24–7.26 (d, 2H, J ¼ 8.0 Hz), 7.30–7.34 (t, 1H), 7.47–7.55 (m, 5H),
8.79 (s, 1H), 8.88 (s, 1H), 8.95 (s, 1H); 13C NMR: 17.49, 39.06, 39.26, 39.47,
39.70, 40.10, 40.41, 78.48, 78.74, 82.51, 117.48, 118.87, 123.15, 126.50, 126.64,
129.02, 129.32, 129.57, 134.4, 134.9, 138.98, 140.73, 147.42, 149.76, 150.79; MS:
m=z ¼ 411 (Mþ), 413 (Mþ2). Anal. calcd. for C24H18ClN5: C, 69.98; H, 4.40; Cl,
8.61; N, 17.00. Found: C, 69.83; H, 4.41; Cl, 8.57; N, 16.91.
1,4-Dihydro-4-(3-(3-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5m). IR (cmꢁ1): 3308, 3024, 2966, 2882, 2215,
1
1676, 1562, 1538, 1476, 1279, 762, 699; H NMR (DMSO-d6) d ppm: 1.88 (s, 6H),
2.69 (s, 3H), 4.67 (s, 1H), 7.19 (d, 1H), 7.27–7.30 (t, 1H), 7.42–7.51 (m, 6H), 8.19
(s, 1H), 8.71 (s, 1H), 9.01 (s, 1H); 13C NMR: 17.61, 39.60, 39.76, 39.97, 40.05,
40.25, 54.53, 78.08, 78.94, 82.91, 113.28, 114.91, 117.88, 119.10, 120.25, 123.51,
126.74, 129.72, 130.27, 130.27, 134.78, 139.43, 143.32, 147.76, 149.89, 160.51; MS:
m=z ¼ 407 (Mþ). Anal. calcd. for C25H21N5O: C, 73.69; H, 5.19; N, 17.19; O, 3.93.
Found: C, 73.53; H, 5.01; N, 17.07; O, 3.82.
1,4-Dihydro-4-(3-(3-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dime-
thyl-pyridine-3,5-dicarbonitrile (5n). IR (cmꢁ1): 3570, 3299, 3134, 2976, 2853,
1
2207, 1656, 1592, 1508, 1489, 1391, 1289, 751, 692; H NMR (DMSO-d6) d ppm:
1.94 (s, 6H), 4.62 (s, 1H), 7.21–7.23 (t, 1H), 7.47–7.56 (m, 4H), 7.62–7.65 (d, 1H),
7.78–7.81 (d, 2H), 8.29 (s, 1H), 8.44 (s, 1H), 8.59 (s, 1H), 9.15 (s, 1H); 13C NMR:

3276
S. THAKRAR ET AL.
18.09, 38.76, 39.26, 39.47, 39.69, 40.09, 40.31, 78.28, 78.74, 82.53, 115.29, 117.19,
119.81, 121.11, 123.52, 126.54, 129.72, 129.87, 130.88, 134.73, 147.32, 147.76,
149.68,158.61; MS: m=z ¼ 393 (Mþ). Anal. calcd. for C24H19N5O: C, 73.27; H,
4.87; N, 17.80; O, 4.07. Found: C, 73.83; H, 4.71; N, 17.77; O, 3.99.
ACKNOWLEDGMENTS
The authors are thankful to the Funding for Infrastructure in Science and
Technology–Department of Science and Technology and Special Assistant Pro-
gramme (SAP)–University Grants Commission for their generous financial and
instrumentation support. Special thanks are due to the National Facility for Drug
Discovery through New Chemical Entities (NCEs) Development and Instrumen-
tation Support to Small Manufacturing Pharma Enterprises Program under the
Drug and Pharma Research Support jointly funded by the Department of Science
and Technology, New Delhi, Government of Gujarat Industries Commissionerate,
and Saurashtra University, Rajkot.
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