© 2019 IJSRSET | Volume 6 | Issue 3 | Print ISSN: 2395-1990 | Online ISSN : 2394-4099

Themed Section : Engineering and Technology

DOI : https://doi.org/10.32628/IJSRSET

Chemistry and biological evaluation of some new 1,2,3,4-tetrahydro-

n-(substitutedphenyl)-6-methyl-2-oxo-4-[3-phenyl-1-(pyridine-4-
carbonyl)-1h-pyrazol-4-yl]pyrimidine-5-carboxamide
Chetan C. Rathod*1, Manish J. Solanki2, Haresh K. Ram3
1Department of Chemistry, Shri Jagdishprasad Jhabarmal Tibrewala University in Jhunjhunu, Rajasthan, India

2C. U. Shah Science College Ahmedabad, Gujarat, India

3Department of Chemistry, Tolani College of Arts & Science, Adipur, Gujarat, India

E-mail :- ram.haresh2007@gmail.com

ABSTRACT
An proficient Synthesis of a novel series of Chemistry and biological evaluation of some new 1,2,3,4-
tetrahydro-n-(substitutedphenyl)-6-methyl-2-oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1h-pyrazol-4-
yl]pyrimidine-5-carboxamide (4a-j) was accomplished from 3-phenyl-1-(pyridin-4-ylcarbonyl)-1-H-pyrazole-
4-carbaldehyde, substituted aceto-acetanilide and in acidic medium. and then after the cooling product was
obtained. All the recently synthesized compounds were characterized by the Mass, IR, 1H-NMR and mass
spectroscopic techniques and by elemental analyses. The newly synthesized compounds were assessed for their
antibacterial and antifungal activity.
Keywords: - 3-phenyl-1-(pyridin-4-ylcarbonyl)-1-H-pyrazole-4-carbaldehyde, urea, substituted aceto-
acetanilide, ethanol and conc. HCl.

I. INTRODUCTION Meanwhile, Schiff bases are attracting much interest

from synthetic and biological aspects.[10–12]
Pyridine and pyrimidine derivatives have founded
great interest in recent medicinal research, being REACTION SCHEME
effective within the treatment of varied malignancies,
like chronic myelocytic leukemia, carcinoma and
idiopathic pulmonary fibrosis. Pyrimidine and
pyridine rings are main classes of compounds to their
broad-spectrum of biological activities. Most of the
FDA approved drugs show a pyridine or pyrimidine
core bearing different substituents. Aim of this review
is to explain the foremost recent reports during this
field, with regard to the new discovered pyridine- or
II. EXPERMENTAL DETAIL
pyrimidine-based drugs, Pyrimidine derivatives and
heterocycle containing pyrimidine have a substantial
TYPICAL UNTRIED PROCEDURE
attention. Thanks to the wide spectrum of interesting
A mixture of 3-phenyl-1-(pyridin-4-ylcarbonyl)-
biological activities observed in these compounds, like
1Hpyrazole- 4-carbaldehyde, 1-4-methyl
anticancer [1,2] antiviral,[3] antitumor,[4] anti-
phenylbutane-1,3-dione and Thiourea in ethanol
inflammatory[5,6] and antimicrobial activities.[7–9]

IJSRSET2183179 | Received : 05 May 2019 | Accepted : 20 May 2019 | May-June-2019 [ 6 (3) : 427-433]
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with few drops of conc. HCl was heated under reflux
on a steam bath for 6 hrs. The reaction mixture was
cooled to room temperature, filtered and remove the
insoluble impurities, diluted with water, and kept
overnight. The solid, thus separated, was filtered,
washed well with water and crystallized from ethanol
as light yellow yield.
1,2,3,4-tetrahydro-N-(4-methoxyphenyl)-6-methyl-
2-oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4a)
Yield: 65%; mp 120ºC; Anal. Calcd. for C28H24N6O4: C,
66.13; H, 4.76; N, 16.53. Found: C, 66.14; H, 4.78; N,
16.50%; MS: m/z 508; IR (cm-1): 3371 (N-H stretching
of secondary amine), 3076 (C-H stretching of
aromatic ring), 1668 (C=O stretching of amide), 1576
(C=N stretching of pyrzol ring), 1513
deformation of pyrimidine ring), 1471
stretching of aromatic ring), 1284 (C-N stretching);
MS: m/z 523; 1H NMR (DMSO-d6) δ ppm: 2.278 (s, 3H,
-CH3), 3.522 (s, 3H, -OCH3), 5.451 (s, 1H, -
asymmetric CH of formed ring), 6.501-7.989 (m, 17H,
m, Ar-H, pyrazole-H, pyrimidine ring-H).
1,2,3,4-tetrahydro-N-(3-methoxyphenyl)-6-methyl-
2-oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4b)
Yield: 70%; mp 123ºC; Anal. Calcd. for C28H24N6O4:
66.13; H, 4.76; N, 16.53; Found: C, 66.17; H, 4.79; N,
16.47%; IR (cm ): 3366 (N-H stretching of secondary
-1
amine), 3056 (C-H stretching of aromatic ring), 1662
(C=O stretching of amide), 1563 (C=N stretching of
pyrzol ring), 1510 (N-H deformation of pyrimidine
ring), 1466 (C=C stretching of aromatic ring), 1286
(C-N stretching); MS: m/z 523; H NMR (DMSO-d6) δ
1 oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
ppm: 2.266 (s, 3H, -CH3), 3.512 (s, 3H, -OCH3), 5.435
(s, 1H, -asymmetric CH of formed ring), 6.652-7.846
(m, 17H, m, Ar-H, pyrazole-H, pyrimidine ring-H).
1,2,3,4-tetrahydro-N-(2-methoxyphenyl)-6-methyl-
2-oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4c)
International Journal of Scientific Research in Science, Engineering and Technology (www.ijsrset.com)
Yield: 71%; mp 113ºC; Anal. Calcd. for C28H24N6O4: C,
66.13; H, 4.76; N, 16.53; Found: C, 66.15; H, 4.80; N,
16.49%; IR (cm-1): 3345 (N-H stretching of secondary
amine), 3052 (C-H stretching of aromatic ring), 1669
(C=O stretching of amide), 1561 (C=N stretching of
pyrzol ring), 1513 (N-H deformation of pyrimidine
ring), 1460 (C=C stretching of aromatic ring), 1280
(C-N stretching); MS: m/z 523; 1H NMR (DMSO-d6) δ
ppm: 2.231 (s, 3H, -CH3), 3.534 (s, 3H, -OCH3), 5.412
(s, 1H, -asymmetric CH of formed ring), 6.611-7.832
(m, 17H, m, Ar-H, pyrazole-H, pyrimidine ring-H).
1,2,3,4-tetrahydro-N-(4-methylphenyl)-6-methyl-2-
oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4d)
Yield: 66%; mp 117ºC; Anal. Calcd. for C28H24N6O3: C,
(N-H 68.28; H, 4.91; N, 17.06; Found: C, 68.24; H, 4.96; N,
(C=C 17.00%; MS: m/z 492.
1,2,3,4-tetrahydro-N-(3-methylphenyl)-6-methyl-2-
oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4e)
Yield: 69%; mp 121ºC; Anal. Calcd. for C28H24N6O3: C,
68.28; H, 4.91; N, 17.06; Found: C, 68.27; H, 4.94; N,
17.08%; MS: m/z 492.
1,2,3,4-tetrahydro-N-(2-methylphenyl)-6-methyl-2-
oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4f)
Yield: 73%; mp 131ºC; Anal. Calcd. for C28H24N6O3:
68.28; H, 4.91; N, 17.06; Found: C, 68.26; H, 4.90; N,
17.01%; MS: m/z 492.
1,2,3,4-tetrahydro-N-(4-nitrophenyl)-6-methyl-2-
pyrazol-4-yl]pyrimidine-5-carboxamide (4g)
Yield: 70%; mp 137ºC; Anal. Calcd. for C27H21N7O5: C,
61.95; H, 4.04; N, 18.73; Found: C, 61.92; H, 4.01; N,
18.70%; IR (cm-1): 3360 (N-H stretching of secondary
amine), 3080 (C-H stretching of aromatic ring), 1630
(C=O stretching of amide), 1587 (C=N stretching of
pyrzol ring), 1505 (N-H deformation of pyrimidine
ring), 1470 (C=C stretching of aromatic ring), 1299
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(C-N stretching); MS: m/z 523; 1H NMR (DMSO-d6) δ
ppm: 2.281 (s, 3H, -CH3), 5.456 (s, 1H, -asymmetric
CH of formed ring), 6.596-7.964 (m, 18H, m, Ar-H,
pyrazole-H, pyrimidine ring-H).
1,2,3,4-tetrahydro-N-(3-nitrophenyl)-6-methyl-2-
oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4h)
Yield: 71%; mp 130ºC; Anal. Calcd. for C27H21N7O5: C,
61.95; H, 4.04; N, 18.73; Found: C, 61.90; H, 4.05; N,
18.72%; IR (cm-1): 3330 (N-H stretching of secondary
amine), 3067 (C-H stretching of aromatic ring), 1625
(C=O stretching of amide), 1604 (C=N stretching of
pyrzol ring), 1511 (N-H deformation of pyrimidine
ring), 1446 (C=C stretching of aromatic ring), 1265
(C-N stretching); MS: m/z 523; H NMR (DMSO-d6) δ
1 standards.
ppm: 2.281 (s, 3H, -CH3), 5.828 (s, 1H, -asymmetric -
CH of formed ring), 6.946-7.925 (m, 17H, m, Ar-H,
pyrazole-H,).
1,2,3,4-tetrahydro-N-(2-nitrophenyl)-6-methyl-2-
oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4i)
Yield: 67%; mp 125ºC; Anal. Calcd. for C27H21N7O5 : C,
61.95; H, 4.04; N, 18.73; O, 15.28; Found: C, 61.94; H,
4.08; N, 18.70; O, 15.24%; MS: m/z 523.
1,2,3,4-tetrahydro-N-(4-chlorophenyl)-6-methyl-2-
oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1H-
pyrazol-4-yl]pyrimidine-5-carboxamide (4j)
Yield: 75%; mp 141ºC; Anal. Calcd. for C27H21ClN6O3:
C, 63.22; H, 4.13; Cl, 6.91; N, 16.38; Found: C, 63.26;
H, 4.14; Cl, 6.93; N, 16.33%; MS: m/z 512.
III. ANTIMICROBIAL ACTIVITY
Biological evaluation of synthesized Indole-3-yl-
glyoxylamide derivatives.
All of the synthesized compounds were tested for
their antibacterial and antifungal activity (MIC) in
vitro by broth dilution method15-17with two Gram-
positive bacteria Streptococcus pyogenes MTCC 442
and Staphylococcus aureus MTCC-96 and two
Gram-negative bacteria Escherichia coli MTCC 443
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and Pseudomonas aeruginosa MTCC 1688 and three
fungal strains Aspergillus Niger MTCC 282 Candida
albicans MTCC Aspergillus clavatus
227 and
MTCC1323.here we are Candida albicans MTCC 227
here we are taking ampicillin ,nystatin ,narfloxacine
this method is ,gentamycin chloramphenicol,
ciprofloxacin, norfloxacin, nystatin and greseofulvin
as standard drugs. This all strains are collected from
MTCC.
The minimal inhibitory concentration (MIC) values
for all the newly synthesized compounds, defined as
the lowest concentration of the compound preventing
the visible growth, were determined by using micro
dilution broth method according to NCCLS
21
Minimal Inhibition Concentration [MIC]
The important benefit of Broth Dilution Method is
that it can easily convertible too MIC Serial dilutions
were prepared in primary and secondary screening.
1. The control tube containing no antibiotic is
immediately subcultured (before inoculation) by
spreading a loopful evenly over a quarter of plate
of medium suitable for the growth of the test
organism and put for incubation at 37 0C
overnight.
2. The MIC of the control organism is read to check
the accuracy of the drug concentrations.
3. The lowest concentration inhibiting growth of
the organism is recorded as the MIC.
4. The amount of growth from the control tube
before incubation (which represents the original
inoculums) is compared.
Methods used for primary and secondary screening
Each synthesized compounds was diluted obtaining
2000 μg mL-1 concentration, as a stock solution. Size
of inoculum is set to 108 cfu (colony forming unit)
per milliliter fot test.this is done by comparing the
turbidity of tubes.
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Primary screen: In primary screening 1000 μg mL-1,
500 μg mL-1 and 250 μg mL-1 concentrations of the
synthesized compounds were taken. The active
synthesized drugs found in this primary screening
were further tested in a second set of dilution against
all microorganisms.
Secondary screen: The compounds found active in
primary screening were similarly diluted to obtain
200 μg mL-1, 100 μg mL-1, 50 μg mL-1, 25 μg mL-1, 12.5
μg mL-1, and 6.250 μg mL-1 concentrations.
Reading Result: MIC is the inhibition zone which is
created by hughest dilution taken. The result of this is
much affected by the size of the inoculums. The test
mixture should contain 108 organism/mL.

Table-1: In vitro Antibacterial Screening Results for (4a-j)

Code Minimal inhibition concentration (µg mL-1 )

Gram-positive Gram-negative
S.a. S. p. E.c. P.a.
4a 450 500 350 400
4b 300 500 150 350
4c 250 350 540 450
4d 450 300 450 300
4e 150 450 550 450
4f 400 400 500 500
4g 350 500 150 350
4h 300 350 500 550
4i 350 450 350 150
4j 350 400 350 350
Ampicillin 250 100 100 100
Chloramphenicol 50 50 50 50
Norfloxacin 10 10 10 10

Antibacterial Activity

The antimicrobial activity evolution of the newly synthesized compound showed that 4e exhibited
maximum antibacterial activity against Staphylococcus aureus. Compound 4b and 4g exhibit excellent
activity against E. coli. at 150 μg mL-1. Compounds 4i showed very good activity against Pseudomonas
aeruginosa at 150 μg mL-1minimum antibacterial activity showed by 4h compounds against Pseudomonas
aeruginosa. Rest of the compounds were found to be good to moderate inhibitors against tested microbial
strains.

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Fig.-1: Antibacterial Activity of 4a-j

Table-2: In vitro Anti-Fungal Activity Screening Results for 4a-j

Minimal inhibition concentration (µg mL-1

Code
)
Fungal species
C. a. A. n. A.c.
4a 500 500 350
4b 300 400 350
4c 350 320 300
4d 100 400 450
4e 350 450 500
4f 450 450 500
4g 300 500 300
4h 350 450 400
4i 350 520 300
4j 150 500 350
Ampicillin 250 100 100
Chloramphenicol 50 50 50
Norfloxacin 10 10 10

Antifungal Activity

Antifungal screening of these compound results that compound 4d & 4j showed excellent antifungal activity
against Candida albicans. While remaining all compounds were good to moderate inhibitors.

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Fig.-2: Antifungal Activity of 4a-j

IV. CONCLUSION VI. REFERENCES

[1] M. M. Kandeel, S. M. Ali, E. K. A. Abed El Ali, M.

Here 1,2,3,4-tetrahydro-n-(substitutedphenyl)-6-
methyl-2-oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-
1h-pyrazol-4-yl]pyrimidine-5-carboxamide
were synthesized and evaluated for antimicrobial
activity. Compound 4e exhibited
antimicrobial activity. The results of in vitro
antifungal activity revealed that the synthesized
compound 4f have potential antifungal activities.
Some of these compounds can be further optimized
and developed as a lead compound.
V. ACKNOWLEDGEMENT
The authors (Chetan C. Rathod, Manish J. Solanki&
Haresh K. Ram) are thankful to the M.G. Science
Institute, Ahmedabad, and Gujarat for the support.
The authors extended thank to the C. U. Shah Science
College, Ahmedabad, Gujarat and Shri Jagdishprasad
Jhabarmal Tibrewala University in
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Cite this Article

Chetan C. Rathod, Manish J. Solanki, Haresh K. Ram,

"Chemistry and biological evaluation of some new
1,2,3,4-tetrahydro-n-(substitutedphenyl)-6-methyl-
2-oxo-4-[3-phenyl-1-(pyridine-4-carbonyl)-1h-
pyrazol-4-yl]pyrimidine-5-carboxamide",
International Journal of Scientific Research in
Science, Engineering and Technology (IJSRSET),
Online ISSN : 2394-4099, Print ISSN : 2395-1990,
Volume 6 Issue 3, pp. 427-433, May-June 2019.
Journal URL : https://ijsrset.com/IJSRSET2183179

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