Studies on synthesis of novel pyrido[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives and their antimicrobial activity

Article abstract of DOI:10.1002/jhet.2108

A series of novel pyrido[3,2-e]tetrazolo[1,5-c]pyrimidine derivative 4 were synthesized starting from 2-amino-4-trifluoromethyl-6-phenyl nicotinonitrile 1 via construction of tetrazole followed by fusion of pyrimidine ring. All final products were screened for antibacterial and antifungal activities.

Full text of DOI:10.1002/jhet.2108

Month 2014
Studies on Synthesis of Novel Pyrido[3,2-e]tetrazolo[1,5-c]pyrimidine
Derivatives and Their Antimicrobial Activity
*
B. Veeraswamy, G. Santhosh Kumar, P. Sambasiva Rao, C. Kurumurthy, and B. Narsaiah
Fluoroorganic division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
*
E-mail: narsaiahbanda84@gmail.com
Received May 10, 2013
DOI 10.1002/jhet.2108
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel pyrido[3,2-e]tetrazolo[1,5-c]pyrimidine derivative 4 were synthesized starting from
2-amino-4-trifluoromethyl-6-phenyl nicotinonitrile 1 via construction of tetrazole followed by fusion of
pyrimidine ring. All final products were screened for antibacterial and antifungal activities.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
derivatives in two steps and screened for antibacterial
and antifungal activities.
The pyrimidine nucleus present in many biologically active
compounds [1,2] attracted the attention of researchers world
over. Pyrido[2,3-d]pyrimidine and its derivatives also display
promising activity [3,4], more specific to dihydrofolate
reductase inhibition and antitumor [5–7] as well as diuretic
properties[8]. Some of these compounds possess antimicro-
bial [9,10], antibacterial [11,12], and cytotoxic activities
[13,14]. Recently, considerable attention was focused on the
tetrazole nucleus and its incorporation into various therapeutic
agents such as anti-convulsant [15–17], anti-tubercular[18],
antihypertensive [19], and anti-depressant activity [20–22].
More recent reports on tetrazole-fused pyrimidine derivatives
claim anti-convulsant and anti-depressant activity [23] and
also antimicrobial and antioxidant activity [24]. On the basis
of the importance of pyridine, pyrimidine, and tetrazole
nuclei, we have proposed to conceive three nuclei in single
molecule and screen for diverse activity in order to find a
promising candidate.
CHEMISTRY
The 2-amino-3-cyano-4-trifluoromethyl-6-phenyl pyridine
1 was reacted with sodium azide under two sets of conditions,
that is, (i) DMF/NH4Cl at 120°C and (ii) ZnBr2/H2O under
reflux. In both cases, the product was not formed; however,
starting material was recovered. Further, compound 1 was
reacted with azido trimethyl silane in the presence of tetra
butyl ammonium fluoride at 140°C for 24 h and obtained
tetrazole derivative 2. The compound 2 on reaction with
aromatic acid chlorides in pyridine at room temperature
formed N-benzoyl derivatives 3(a–k). Compounds 3(a–k)
on refluxing in toluene using p-TSA (para toluene sulfonic
acid) as a catalyst for 2 h resulted pyrido[3,2-e]tetrazolo
[1,5-c]pyrimidine 4(a–k). Alternatively, compound 2 on reac-
tion with aliphatic acid chlorides in pyridine at 100°C resulted
directly cyclized products 4(l–p) in single step. It is attributed
to the steric factors in which alkyl groups promote cyclization,
In continuation of our efforts [25,26], we have prepared
a series of novel tetrazole-fused pyrido pyrimidine
© 2013 HeteroCorporation

B. Veeraswamy, G. Santhosh Kumar, P. Sambasiva Rao, C. Kurumurthy, and B. Narsaiah
Vol 000
whereas aryl groups required vigorous conditions in the pres-
ence of an acid catalyst. The detail of reaction is outlined in
Scheme 1, and products are tabulated in Table 1.
activity; however, all compounds do not show activity
against antibacterial and fungal strains.
EXPERIMENTAL
RESULTS AND DISCUSSION
Antimicrobial activity
Melting points of all compounds were recorded on
Cassia Siamia (VMP-AM) melting point apparatus and
were uncorrected. IR spectra were recorded on a Perkin-Elmer
FT-IR 240-C spectrophotometer using KBr optics. 1H NMR
spectra were recorded on 500 and 300 MHz in CDCl3,
DMSO-d6 using TMS as internal standard. EI and chemical
ionization mass spectra were recorded on a VG 7070 H instru-
ment at 70 eV. All high-resolution spectra were recorded on
QSTARXL hybrid MS/MS system (Applied Biosystems,
USA) under electrospray ionization. All reactions were moni-
tored by TLC on pre-coated silica gel 60 F254 (mesh); spots
were visualized with UV light. Merck silica gel (60–120
meshes) was used for column chromatography.
In vitro antibacterial assays.
Compounds 4a–p
were dissolved in acetone and screened for in vitro
antibacterial activity against gram-positive (Bacillus subtilis,
Staphylococcus aureus, and Staphylococcus epidermidis)
and gram-negative (Pseudomonas aeruginosa, Escherichia
coli, and Klebsiella pneumoniae) bacteria. The Minimum
Inhibitory Concentration (MIC) values of the compounds
were compared with those obtained with penicillin and
streptomycin. However, no compounds showed significant
activity against all species of gram-positive and gram-
negative bacteria.
General procedure for the preparation of 6-phenyl-3-(1H-
tetrazol-5-yl)-4-(trifluoromethyl) pyridin-2-amine (2).
Amino-6-phenyl-4-(trifluoromethyl)nicotinonitrile (2.78 g,
2-
In vitro antifungal activity assays.
Compounds 4a–p
1
were screened against the fungal strains, namely. Candida
albicans (MTCC 227), Saccharomyces cerevisiae (MTCC
36) and filamentous fungal cultures such as Aspergillus
niger (MTCC 1344), and Candida rugosa (NCIM 3462)
by agar cup diffusion method. The strains were obtained
from the Institute of Microbial Technology, Chandigarh,
India. All compounds did not show significant activity up
to the concentration of 150 μg.
9.1 mmol), azidotrimethylsilane (1.56 g, 13.6 mmol), tetrabutyl
ammonium fluoride(1.43 g, 4.55 mL, 4.5 mmol, 1 N in THF)
was taken in sealed tube and heated to 140° for 24 h, cooled at
room temperature, treated with crushed ice, and neutralized
with 1 N HCl. Extracted thrice with ethyl acetate, combined
extracts were washed with water till washings are neutral to
pH and dried over sodium sulfate and concentrated under
vacuum, and crude product residue was purified by washing
with CHCl3.
Yield: 2.0 g (71.65%), mp: 136°C, IR (KBr) cmÀ1: 3456,
3318 (NH2), 3195 (N–H), 1647 (C═N) 1H NMR (DMSO6,
300 MHz) δ: 6.05 (s, 2H, NH2), 7.37 (s, 1H, Ar–H), 7.41–
7.51 (m, 3H, Ar–H), 8.01–8.06 (m, 2H, Ar–H), ESI-mass:
307 (M+ + H).
CONCLUSION
A series of novel pyrido[3,2-e]tetrazolo [1,5-c]pyrimidine
derivatives were synthesized and screened for antimicrobial
Scheme 1. Preparation of pyrido[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives 4.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
The Pyrimidine Nucleus Present in Many Biologically Active Compounds [1,2] and
Attracted the Attention of Researchers World Over
Table 1
Physical properties of pyrido[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives 4.
S. No.
Compound no.
R
Mp (°C)
Yield (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
C6H5
255
227
245
250
235
231
219
215
225
228
220
235
215
233
231
199
227
250
243
202
232
225
78.54
73.68
74.08
81.51
77.37
83.91
59.70
51.89
44.95
45.27
53.57
60.50
55.99
52.40
42.85
75.24
64.92
69.53
53.36
59.83
55.55
41.12
4-FC6H4
3-Cl C6H4
3-Br C6H4
4-CN C6H4
4-MeO C6H4
C6H5
4-FC6H4
3-Cl C6H4
3-Br C6H4
4-CN C6H4
4-MeO C6H4
3-NO2 C6H4
4-Me C6H4
3-MeO C6H4
3-F C6H4
4-Cl C6H4
CH3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
4m
4n
4o
4p
C2H5
C3H7
CH(CH3)2
C(CH3)3
General procedure for the preparation of N-(6-phenyl-3-
(1H-tetrazol-5-yl)-4-(trifluoromethyl) pyridin-2-yl)benzamide
derivatives (3a–k). Substituted benzoyl chloride (0.78 mmol)
in DCM was slowly added to compound 2 (200 mg, 0.65 mmol)
in 2 mL pyridine over 15 min at room temperature and stirred
for 2 h. After completion of reaction, crushed ice was added,
neutralized with 1 N HCl, and extracted thrice with ethyl
acetate. Combined extracts were washed with water till
washings are neutral to pH and dried over anhy. Na2SO4
concentrated under vacuum, and crude product residue was
purified by washing with chloroform. However, compounds
3(g–k) were directly used without further purification.
3-Bromo-N-(6-phenyl-3-(1H-tetrazol-5-yl)-4-(trifluoromethyl)
pyridin-2-yl)benzamide (3d).
Yield: 260 mg (81.51%), mp:
250°C, IR (KBr) cm:À1 3236 (NH), 1673 (ÀC═O) 1H NMR
(DMSO6, 500 MHz) δ: 7.30–7.36 (t, 1H, Ar–H, J = 7.74 Hz),
7.51–7.57 (m, 3H, Ar–H), 7.62–7.68 (m, 1H, Ar–H), 7.77–7.82
(d, 1H, Ar–H, J = 7.74 Hz), 8.03 (s, 1H, Ar–H), 8.03 (s, 1H,
Ar–H), 8.11–8.17 (m, 2H, Ar–H), 10.86 (s, 1H, N–H), ESI-
Mass: 489 (M+ + H).
4-Cyano-N-(6-phenyl-3-(1H-tetrazol-5-yl)-4-(trifluoromethyl)
pyridin-2-yl)benzamide (3e). Yield: 220 g (77.37%), mp: 235°
1
C, IR (KBr) cmÀ: 1 3277 (NH), 2232 ÀCN), 1664 (ÀC═O) H
NMR (DMSO6, 500 MHz) δ: 7.43–7.49 (m, 3H, Ar–H), 7.67–
7.72 (m, 2H, Ar–H), 7.88–7.92 (d, 2H, Ar–H, J = 7.91 Hz),
8.03 (s, 1H, Ar–H), 8.04–8.08 (m, 2H, Ar–H), 11.16 (s, 1H,
N–H), ESI-Mass: 436 (M+ + H).
N-(6-phenyl-3-(1H-tetrazol-5-yl)-4-(trifluoromethyl)pyridin-2-yl)
benzamide (3a).
(KBr) cmÀ1: 3277 (NH), 1661 (–C═O) 1H NMR (DMSO6,
500 MHz) δ: 7.39–7.44 (m, 2H, Ar–H), 7.48–7.54 (m, 4H,
Yield: 210 mg (78.54%), mp: 255°C, IR
4-Methoxy-N-(6-phenyl-3-(1H-tetrazol-5-yl)-4-(trifluoromethyl)
pyridin-2-yl)benzamide (3f). Yield: 240 g (83.91%), mp: 231°C
Ar–H), 7.81–7.84 (m, 2H, Ar–H), 8.07 (s, 1H, Ar–H), 8.13–
8.16 (m, 2H, Ar–H), 10.66 (s, 1H, N–H), ESI-Mass: 410
(M+ + H).
1
IR (KBr) cmÀ: 1 3253 (NH), 1652 (ÀC═O) H NMR (DMSO6,
500 MHz) δ: 3.85 (s, 3H, ÀOCH3), 6.85–6.95 (d, 2H, Ar–H,
J = 8.68 Hz), 7.47–7.60 (m, 3H, Ar–H), 7.77–7.87 (d, 2H, Ar–
H, J = 8.68 Hz), 8.04 (s, 1H, Ar–H), 8.09–8.19 (m, 2H, Ar–H),
10.45 (s, 1H, N–H), ESI-Mass: 441 (M+ + H).
4-Fluoro-N-(6-phenyl-3-(1H-tetrazol-5-yl)-4-(trifluoromethyl)
pyridin-2-yl)benzamide (3b).
Yield: 205 mg (73.68%), mp:
227°C, IR (KBr) cm:À1 3280(NH), 1659 (ÀC═O) 1H NMR
(DMSO6, 300 MHz) δ: 7.07–7.15 (t, 2H, Ar–H, J = 8.49 Hz),
7.51–7.57 (m, 3H, Ar–H), 7.86–7.94 (dd, 2H, Ar–H, J = 5.47
and 8.30 Hz), 8.05 (s, 1H, Ar–H), 8.11–8.17 (t, 2H, Ar–H,
J = 3.58 Hz), 10.61(s, 1H, N–H), ESI-Mass: 429 (M+ + H).
3-Chloro-N-(6-phenyl-3-(1H-tetrazol-5-yl)-4-(trifluoromethyl)
General procedure for the preparation of 5-Subst
ituted-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo
[1,5-c]pyrimidine derivatives (4a–k).
Compounds 3a–k
(0.47 mmol) and para toluene sulfonic acid (0.100 g) were
dissolved in 5 mL toluene and heated to reflux for 2–3 h.
After completion of reaction, toluene was removed under
vacuum, and residue was purified by washing with MeOH.
5,8-Diphenyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo[1,5-c]
pyridin-2-yl)benzamide (3c).
Yield: 215 mg (74.08%), mp:
245°C, IR (KBr) cm:À1 3243 (NH), 1673 (ÀC═O) 1H NMR
(DMSO6, 500 MHz) δ: 7.28–7.34 (t, 1H, Ar–H, J = 7.91 Hz),
7.40–7.47 (m, 4H, Ar–H), 7.64–7.68 (m, 1H, Ar–H), 7.79
(s, 1H, Ar–H), 8.00 (s, 1H, Ar–H), 8.03–8.08 (m, 2H, Ar–H),
10.79 (s, 1H, N–H), ESI-Mass: 445 (M+ + H).
pyrimidine (4a).
Yield: 110 mg (59.70%), mp: 219°C, IR
(KBr) cmÀ1: 1595 (C═N) 1H NMR (CDCl3, 300 MHz) δ: 7.56–
7.64 (m, 3H, Ar–H), 7.65–7.78 (m, 3H, Ar–H), 8.31–8.36 (m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

B. Veeraswamy, G. Santhosh Kumar, P. Sambasiva Rao, C. Kurumurthy, and B. Narsaiah
Vol 000
2H, Ar–H), 8.48 (s, 1H, Ar–H), 8.83–8.88 (m, 2H, Ar–H), ESI-
Mass: 393 (M+ + H), HRMS: m/z Calcd. for C20H12N6F3
([M + H]+): 393.10672. Found: 393.10701.
5-(3-Methoxyphenyl)-8-phenyl-10-(trifluoromethyl)pyrido
[3,2-e]tetrazolo[1,5-c]pyrimidine (4i). Yield: 85 mg
(42.85%), mp: 231°C, IR (KBr) cmÀ1: 1593 (–C═N) 1H
NMR (DMSO6, 300 MHz) δ: 3.93 (s, 3H,–CH3), 7.38–7.44 (m,
1H, Ar–H), 7.63–7.73 (m, 4H, Ar–H), 8.02–8.07 (m, 1H, Ar–H),
8.09–8.15 (d, 1H, Ar–H, J = 7.93 Hz), 8.46–8.53 (m, 2H,Ar–H),
8.82 (s, 1H, Ar–H) ESI-Mass: 423 (M+ + H) HRMS: m/z Calcd.
for C21H14ON6F3 ([M + H]+): 423.11722. Found: 423.11697.
5-(3-Fluorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
5-(4-Fluorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine (4b).
Yield: 100 mg (51.89%), mp:
215°C, IR (KBr) cmÀ1 1600(C═N) 1H NMR (DMSO6,
:
500 MHz) δ: 7.40–7.46 (t, 2H, Ar–H, J = 8.08 Hz), 7.58–7.64 (m,
3H, Ar–H), 8.37–8.434 (m, 2H, Ar–H), 8.58 (s, 1H, Ar–H), 8.82–
8.88 (m, 2H, Ar–H) ESI-Mass: 411 (M+ + H) HRMS: m/z Calcd.
for C20H10N6F4Na ([M + Na]+): 433.07922. Found: 433.07953.
5-(3-Chlorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine (4j).
Yield: 145 mg (75.24%), mp:
199°C, IR(KBr)cmÀ1 1589 (C═N) 1H NMR (DMSO6,
:
500 MHz) δ: 7.43–7.48 (t, 1H, Ar–H, J= 8.084 Hz), 7.57–7.61 (m,
3H, Ar–H), 7.65–7.70 (m, 1H, Ar–H), 8.29–8.34 (m, 2H, Ar–H),
tetrazolo[1,5-c]pyrimidine (4c).
Yield: 90 mg (44.95%), mp:
225°C, IR (KBr) cmÀ: 1 1594 (C═N) 1H NMR (DMSO6,
500 MHz) δ: 7.58–7.62 (m, 3H, Ar–H), 7.62–7.67 (t, 1H, Ar–
H, J = 8.0 Hz), 7.71–7.75 (d, 1H, Ar–H, J = 8.0 Hz), 8.32–8.37
(m, 2H, Ar–H), 8.50 (s, 1H, Ar–H), 8.79–8.82 (d, 1H, Ar–H,
J = 7.0 Hz), 8.85 (s, 1H, Ar–H) ESI-Mass: 427 (M+ + H)
HRMS: m/z Calcd. for C20H11N6ClF3([M + H]+): 427.06778.
Found: 427.06803.
8.46–8.49
(m, 1H, Ar–H), 8.52 (s, 1H, Ar–H), 8.58–8.61 (m,
1H, Ar–H,) ESI-Mass: 411 (M+ + H) HRMS: m/z Calcd. for
C20H10N6F4Na ([M + Na]+): 433.07922. Found: 433.07894.
5-(4-Chlorophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine (4k).
Yield: 130 mg (64.92%), mp:
227°C, IR (KBr) cmÀ: 1 1594 (C═N) 1H NMR (DMSO6,
500 MHz) δ: 7.62–7.65 (m, 3H, Ar–H), 7.70–7.72 (m, 2H, Ar–H),
8.36–8.39 (m, 2H, Ar–H), 8.59 (s, 1H, Ar–H), 8.76–8.79 (m, 2H,
Ar–H), ESI-Mass : 427 (M+ + H) HRMS: m/z Calcd. for
C20H11N6ClF3 ([M + H]+): 427.06778. Found: 427.06835.
5-(3-Bromophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine (4d). Yield: 100 mg (45.27%), mp:
228°C, IR (KBr) cmÀ: 1 1594 (C═N) 1H NMR (DMSO6,
300 MHz) δ: 7.56–7.61 (t, 1H, Ar–H, J = 7.91 Hz), 7.62–7.65
(m, 3H, Ar–H), 7.87–7.91 (d, 1H, Ar–H, J = 7.91 Hz), 8.32–
8.37 (m, 2H, Ar–H), 8.53 (s, 1H, Ar–H), 8.79–8.82 (d, 1H, Ar–
H, J = 9.1 Hz), 8.98 (s, 1H, Ar–H) ESI-Mass: 493 (M+ + Na)
HRMS: m/z Calcd. for C20H11BrN6F3 ([M + H]+): 471.01807.
Found: 471.01765.
General procedure for the preparation of 5-substituted-
8-phenyl-10-(trifluoromethyl)pyrido [3,2-e] tetrazolo[1,5-c]
pyrimidine derivatives (4l–p).
Aliphatic acid chlorides
(0.78 mmol) were slowly added to compound
2
(200 mg,
0.65mmol) in 2 mL pyridine over 15 min at room temperature and
the temperature was raised to 100°C and kept for 4–6 h. After
completion of the reaction, reaction mixture was cooled at room
temperature, neutralized with 1 N HCl, extracted thrice with ethyl
acetate. Combined extracts were washed with water and dried
over anhy. Na2SO4, concentrated under vacuum to obtain crude
product, and purified by washing with MeOH.
5-Methyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo
[1,5-c]pyrimidine (4l). Yield: 150 mg (69.53%), mp: 250°C, IR
(KBr) cmÀ: 1 1638 (–C═N) 1H NMR (CDCl3, 300 MHz) δ: 3.35
4-[8-Phenyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo[1,5-c]
pyrimidin-5-yl]benzonitrile (4e).
Yield: 105 mg (53.57%),
mp: 220°C, IR (KBr) cmÀ1: 1597 (C═N), 2231 (–CN) 1H
NMR (CDCl3, 500 MHz) δ: 7.62–7.72 (m, 3H, Ar–H), 8.03–
8.08 (d, 2H, Ar–H, J = 8.49 Hz), 8.35–8.41 (m, 2H, Ar–H), 8.62
(s, 1H, Ar–H), 8.88–8.93 (d, 2H, Ar–H, J = 8.49 Hz) ESI-Mass:
418 (M+ + H) HRMS: m/z Calcd. for C21H11N7F3 ([M + H]+):
418.10260. Found: 418.10225.
5-(4-Methoxyphenyl)-8-phenyl-10-(trifluoromethyl)pyrido
[3,2-e]tetrazolo[1,5-c]pyrimidine (4f).
Yield: 120 mg
(s, 3H, CH3), 7.59–7.64 (m, 3H, Ar–H), 8.31–8.37
(m, 2H,
(60.50%), mp: 235°C, IR (KBr) cmÀ: 1 1600 (–C═N) 1H
NMR (DMSO6, 500 MHz) δ: 3.97 (s, 3H,–CH3), 7.13–7.20
(m, 2H, Ar–H), 7.57–7.65 (m, 3H, Ar–H), 8.28–8.36 (m, 2H,
Ar–H), 8.45 (s, 1H, Ar–H), 8.88–8.95 (m, 2H, Ar–H), ESI-
Mass: 423 (M+ + H) HRMS: m/z Calcd. for C21H14ON6F3
([M + H]+): 423.11722. Found: 423.11757.
Ar–H), 8.51 (s, 1H, Ar–H), ESI-Mass: 331 (M+ + H) HRMS:
m/z Calcd. for C15H10N6F3 ([M + H]+): 331.09115. Found:
331.09136.
5-Ethyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo
[1,5-c]pyrimidine (4m). Yield: 120 mg (53.36%), mp: 243°C,
1
IR (KBr) cmÀ: 1 1634(–C═N) H NMR (DMSO6, 300 MHz) δ:
5-(3-Nitrophenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine(4g).
1.66–1.73 (t, 3H,–CH3, J = 7.36 Hz), 3.65–3.74(q, 2H, CH2,
J = 7.36 Hz), 7.61–7.65 (m, 3H, Ar–H), 8.33–8.37 (m, 2H,
Ar–H), 8.55 (s, 1H, Ar–H), ESI-Mass: 367 (M+ + Na) HRMS:
m/z Calcd. for C16H12N6F3 ([M + H]+): 345.10641. Found:
345.10701.
Yield:115 g (55.99%), mp:
215°C, IR (KBr) cmÀ1: 1595 (C═N), 1527 (–NO2) 1H NMR
(CDCl3, 500 MHz) δ: 7.59–7.69 (m, 3H, Ar–H), 7.89–7.98 (t,
1H, Ar–H, J = 8.30 Hz), 8.32–8.41 (m, 2H, Ar–H), 8.60–8.65
(d, 2H, Ar–H, J = 8.30 Hz), 9.19–9.25 (d, 1H, Ar–H,
J = 8.30 Hz), 9.72 (s, 1H, Ar–H) ESI-Mass: 438 (M+ + H)
HRMS: m/z Calcd. for C20H11O2N7F3 ([M + H]+): 438.09263.
Found: 438.09307.
8-Phenyl-5-propyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo
[1,5-c]pyrimidine (4n). Yield: 140 mg (59.83%), mp: 202°C,
1
IR (KBr) cmÀ: 1 1631 (–C═N) H NMR (DMSO6, 300 MHz) δ:
1.18–1.28 (t, 3H,–CH3, J = 7.76 Hz), 2.15–2.23 (m, 2H,–CH2),
3.60–3.65 (t, 2H,–CH2, J = 7.76 Hz), 7.60–7.64 (m, 3H, Ar–H),
8.32–8.37 (m, 2H, Ar–H), 8.54 (s, 1H, Ar–H), ESI-Mass: 359
(M+ + H) HRMS: m/z Calcd. for C17H14N6F3 ([M + H]+):
359.12247. Found: 359.12266.
8-Phenyl-5-(propan-2-yl)-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine (4o). Yield: 130mg (55.55%), mp:
232°C, IR(KBr) cm:À1 1629 (–C═N) 1H NMR (CDCl3, 300 MHz)
δ: 1.68–1.71 (d, 6H,–CH3, J = 7.55 Hz), 4.15–4.26 (m, 1H,–CH),
5-(4-Methylphenyl)-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]
tetrazolo[1,5-c]pyrimidine (4h).
Yield: 100 mg (52.40%), mp:
233°C, IR (KBr) cmÀ1: 1598(C═N) H NMR (CDCl3, 300 MHz)
δ: 2.54 (s, 3H,–CH3), 7.48–7.51 (d, 2H, Ar–H, J=7.65Hz), 7.60–
7.64 (m, 3H, Ar–H), 8.31–8.36 (m, 2H, Ar–H,) 8.48 (s, 1H, Ar–H),
8.73–8.77 (d, 2H, Ar–H, J= 7.65 Hz) ESI-Mass: 407 (M+ +H)
HRMS: m/z Calcd. for C21H14N6F3 ([M + H]+): 407.12259. Found:
407.12266.
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
The Pyrimidine Nucleus Present in Many Biologically Active Compounds [1,2] and
Attracted the Attention of Researchers World Over
[9] Parmar, K.; Suthar, B.; Suthar, A.; Maheta, A. J Heterocycl
Chem 2009, 46, 975.
[10] Koeckkritz, P.; Ruhmann, C.; Fieblinger, D.; Schroeder, C.;
Joksch, B.; Heider, B.; Weiher, B. Liebscher J Ger Offen DE 4, 117,
802 [Chem Abstr 1993, 118, 191550s].
[11] Narayana, B.; Ram Rao, A.; Shanthan Rao, P. Eur J Med
Chem 2009, 44, 1369.
[12] Kanth, S.; Reddy, G.; Kishore, K.; Shanthan Rao, P.; Narsaiah,
B.; Murthy, U. Eur J Med Chem 2006, 41, 1011.
7.60–7.63 (m, 3H, Ar–H), 8.30–8.33 (m, 2H, Ar–H), 8.48 (s, 1H,
Ar–H), ESI-Mass: 359 (M+ + H) HRMS: m/z Calcd. for
C17H14N6F3 ([M + H]+): 359.12247. Found: 359.12321.
5-tert-Butyl-8-phenyl-10-(trifluoromethyl)pyrido[3,2-e]tetrazolo
[1,5-c]pyrimidine(4p). Yield: 0.100 g (41.12%), mp: 225°C, IR
(KBr) cmÀ: 1 1622(–C═N) 1H NMR (DMSO6, 300 MHz) δ: 1.83 (s,
9H,–CH3), 7.60–7.70 (m, 3H, Ar–H), 8.32–8.39 (m, 2H, Ar–H),
8.54 (s, 1H, Ar–H), ESI-Mass: 373 (M+ + H) HRMS: m/z Calcd.
for C18H16N6F3 ([M + H]+): 373.13885 Found: 373.13798.
[13] El-Subbagh, H. I.; Abuzaid, S. M.; Mahran, M. A.; Badria, F.
A.; Al-Obaid, A. M. J Med Chem 2000, 43, 2915.
[14] Ashalatha, B. V.; Narayana, B.; Vijaya Raj, K. K.; Suchetha
Kumari, N. Eur J Med Chem 2007, 42, 719.
Acknowledgments. The authors are thankful to the Director, IICT,
Hyderabad, India for her constant encouragement. The authors
(B. Veeraswamy, G. Santhosh Kumar, P. Sambasiva Rao, and C.
Kurumurthy,) are also thankful to CSIR, New Delhi for the grant
of Senior Research Fellowship.
[15] Sun, X. Y.; Wei, C. X.; Deng, X. Q.; Sun, Z. G.; Quan, Z. S.
Pharmacol Rep 2010, 62, 273.
[16] Sun, X. Y.; Wei, C. X.; Deng, X. Q.; Sun, Z. G.; Quan, Z. S.
Arzneimittelforschung 2010, 60, 289.
[17] Alhano, C.; Cupello, A.; Mainardi, P.; Scarrone, S.; Favale, E.
Neurochem Res 2006, 31, 509.
[18] Chitra, S.; Paul, N.; Muthusubramanian, S.; Manisankar, P.;
Yogeeswari, P.; Sriram, D. Eur J Med Chem 2011, 46, 4897.
[19] Nicolaï, E.; Curé, G.; Goyard, J.; Kirchner, M.; Teulonl, J. M.;
Versignyz, A. Eur J Med Chem 1995, 30, 365.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet