One-pot synthesis and antibacterial activities of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-dione derivatives

Article abstract of DOI:10.1016/j.bmcl.2008.09.057

A one-pot and efficient method for the synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-dione derivatives by condensation reaction of barbituric acids, 1H-pyrazol-5-amines and aldehydes under solvent-free conditions is reported. These products were evaluated in vitro for their antibacterial activities.

Full text of DOI:10.1016/j.bmcl.2008.09.057

Bioorganic & Medicinal Chemistry Letters 18 (2008) 5800–5803
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
One-pot synthesis and antibacterial activities of
pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-dione derivatives
a
b
Ayoob Bazgira, , Maryam Mohammadi Khanaposhtani , Ali Abolhasani Soorki
*
a Department of Chemistry, Shahid Beheshti University, PO Box 19396-4716, Tehran, Iran
b Research Institute of Petroleum, Academic Center of Education, Culture & Research, Shahid Beheshti University, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
A one-pot and efficient method for the synthesis of pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-dione
derivatives by condensation reaction of barbituric acids, 1H-pyrazol-5-amines and aldehydes under sol-
vent-free conditions is reported. These products were evaluated in vitro for their antibacterial activities.
Ó 2008 Published by Elsevier Ltd.
Article history:
Received 2 July 2008
Revised 11 August 2008
Accepted 15 September 2008
Available online 18 September 2008
Keywords:
1H-Pyrazol-5-amines
Barbituric acid
Pyrimidopyrimidine
Thiobarbituric acid
Pyrazolopyrimidine
Polyfunctionalized heterocyclic compounds play important
roles in the drug discovery process, and analysis of drugs in late
development or on the market shows that 68% of them are hetero-
cycles.1,2 Therefore, it is not surprising that research on the synthe-
sis of polyfunctionalized heterocyclic compounds has received
significant attention.
densation products can be expected depending on the specific con-
ditions and structure of the building blocks.13–16 On the other
hand, synthesis of benzopyrimidoquinoline-diones by reaction of
naphthalene-2-amine, aldehyde and barbituric acid is reported.17
As part of our program aimed at developing new selective and
environmentally friendly methodologies for the preparation of het-
erocyclic compounds,18–24 we report an efficient, one-pot, and
three-component method for the preparation of 1H-pyrazol-
o[40,30:5,6]pyrido[2,3-d]pyrimidine-dione derivatives by condensa-
tion of 1H-pyrazol-5-amines 1, barbituric acid 2, and aromatic
aldehydes 3 under solvent-free conditions (Scheme 1).
We found that a mixture of 1H-pyrazol-5-amines 1a,b, barbitu-
ric acid 2 and aromatic aldehydes 3a–e, in the presence of a cata-
lytic amount of p-toluenesulfonic acid (p-TSA) as an inexpensive
and readily available catalyst at 100 °C for 4 h under solvent-free
conditions, afforded 4,9-dihydro-1H-pyrazolo[40,30:5,6]pyrido[2,3-
d]pyrimidine-5,7 (6H,8H)-diones 4a–j in good yields (Table 1).
The results were good in terms of yields and product purity in
the presence of p-TSA, while without p-TSA and over long period
of time (12 h) the yields of products were low (<30%).
Pyrimidopyrimidine, a condensed heterocycles have attracted
considerable interest in the recent years. Its derivatives have been
known to display a wide range of pharmacological activities as re-
gards the tyrosine kinase domain of epidermal growth factor
receptor,3 5-phosphoribosyl-1-pyrophosphate synthetase4 and
dihydrofolate reductase5 have been fully demonstrated. Numerous
reports delineate the antitumour,6 antiviral,7 antioxidant,8 and
hepatoprotective9 activity of these compounds. Similarly, in recent
years, considerable attention has been focused on the development
of new methodologist to synthesize many kinds of pyrazolopyrim-
idine ring system.10 Indeed, these compounds are, by now widely
recognized as important organic materials showing interesting
biological activities.11 In addition, fused heterocyclic systems like
pyrazolopyridopyrimidines, pyrazoloquinolines, and pyrazolopyri-
dines present interesting biological properties such as virucidal,
anticancer, fungicidal, bactericidal, and vasodilatory activities.12
Multicomponent reactions of 1H-pyrazol-5-amines, aldehydes
and CH-acid compounds have recently attracted the interest of
the synthetic community because the formation of different con-
When this reaction was carried out with aliphatic aldehyde
such as butanal or pentanal, TLC and 1H NMR spectra of the reac-
tion mixture showed a combination of starting materials and
numerous products, the yield of the expected product was very
poor.
The formation of products 4a–j can be rationalized by initial
formation of heterodiene 5 by standard Knoevenagel condensation
of barbituric acid 2 and aromatic aldehyde 3. Subsequent Michael-
* Corresponding author. Fax: +98 21 22431661.
E-mail address: a_bazgir@sbu.ac.ir (A. Bazgir).
0960-894X/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.bmcl.2008.09.057

A. Bazgir et al. / Bioorg. Med. Chem. Lett. 18 (2008) 5800–5803
5801
Ar
O
Ph
Ph
O
NH
N
N
p-TSA
NH2
HN
NH
+
ArCHO
+
N
X
N
X
Solvent-free/ 100 oC
N
H
N
H
O
O
O
4 h
2
3a-e
4a-j
X= H 1a
X=NO2
1b
Scheme 1.
Table 1
Synthesis of 1H-pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidinones 4a–j
Table 2
Synthesis of 7H-pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-7-diones 7a–f
Product 4
Ar
X
Yielda (%)
Product 7
Ar
X
Yielda (%)
a
b
c
d
e
f
g
h
i
C6H5
H
H
H
H
83
80
85
92
80
83
90
84
95
84
a
b
c
d
e
f
C6H5
H
H
H
NO2
NO2
NO2
90
86
83
81
89
84
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
3-NO2-C6H5
C6H5
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
3-NO2-C6H5
4-Cl-C6H4
4-NO2-C6H5
C6H5
4-Cl-C6H4
4-NO2-C6H5
H
NO2
NO2
NO2
NO2
NO2
a
Isolated yields.
j
Encouraged by these results, we replaced the thiobarbituric acid
6 instead of barbituric acid 2 in same conditions (Scheme 3). The
reaction of 1H-pyrazol-5-amines 1a,b, and thiobarbituric 6 was
carried out with various aromatic aldehydes 3 under solvent-free
conditions at 100 °C, which also afforded 5-thioxo-1,4,5,6,8,9-
hexahydro-7H-pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-7-diones
7a–f in good yields (Table 2).
The nature of these compounds as 1:1:1 adducts was apparent
fromtheirmass spectra, whichdisplayed, in eachcase, themolecular
ion peak at appropriate m/z values. Compounds 4a–j and 7a–f are
stable solids whose structures are fully supported by IR, 1H, and
13C NMR spectroscopy, mass spectrometry, and elemental
analysis.25
a
Isolated yields.
Ph
O
O
N
NH2
N
Ar'
HN
NH
HN
NH
1
ArCHO
O
O
O
O
2
3
O
Ar
5
HN
NH
Finally, all synthesized compounds were screened for antimi-
crobial activity. The microorganisms used in this study were Esch-
erichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 85327
(Gram-negative bacteria) Enterococcus faecalis ATCC 29737, Bacillus
subtilis ATCC 465, Bacillus pumilus PTCC 1114, Micrococcus luteus
PTCC 1110, Staphylococcus aureus ATCC 25923, Staphylococcus epi-
dermidis ATCC 12228, and Sterptococcus mutans PTCC 1601
(Gram-positive bacteria). The minimum inhibitory concentration
(MIC) of the synthesized compounds determined by microdillution
method26 and compared to two commercial antibiotics (Table 3).
As can be seen from Table 3, good to improved antibacterial
activity was observed for most of the compounds against all
O
O
-H2O
NH2
4
Ar
Ar'
N
N
Ph
Scheme 2.
type addition of 1H-pyrazol-5-amines 1 to the heterodienes 5, fol-
lowed by cyclization afforded the corresponding products 4a–j and
water (Scheme 2).
Ar
O
Ph
Ph
N
S
NH
N
p-TSA
Solvent-free/ 100 oC
NH2
HN
NH
+
ArCHO
+
N
X
N
N
H
N
H
S
O
O
4 h
X
6
3
7a-f
X= H 1a
X=NO2
1b
Scheme 3.

5802
A. Bazgir et al. / Bioorg. Med. Chem. Lett. 18 (2008) 5800–5803
Table 3
MIC (lg/ml) values of products 4 and 7
Products
Standard
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
7a
7b
7c
7d
7e
7f
Tetracycline
Gentamicin
Bacillus subtilis
Bacillus pumilus
2
<2
<2
2
4
2
<2
64
4
<2
<2
32
2
2
2
2
58
2
<2
<2
30
2
2
2
<2
2
2
2
2
2
2
<2
<2
2
6
4
2
8
6
4
8
4
2
6
6
2
6
4
2
4
4
8
8
4
<2
4
4
4
4
4
4
8
8
4
16
16
4
4
3
4
8
6
6
14
12
3
4
4
3
7
8
5
13
14
4
4
3
6
6
8
6
12
16
4
4
4
6
8
8
6
10
14
4
8
4
4
<2
2
*
*
*
*
*
Micrococcus luteus
Staphylococcus aureus
Staphylococcus epidermidis
Sterptococcus mutans
Escherichia coli
4
4
4
2
2
2
2
18
<2
4
4
20
28
<2
6
2
28
32
<2
4
4
32
24
<2
4
2
28
26
<2
6
2
30
<2
<2
2
<2
<2
2
*
4
*
8
Enterococcus faecalis
Pseudomonas aeruginosa
*
8
2
2
2
32
*
*Not active.
13. Quiroga, J.; Portilla, J.; Serrano, H.; Abonía, R.; Insuasty, B.; Nogueras, M.; Cobo,
J. Tetrahedron Lett. 2007, 48, 1987.
14. Shi, C.-L.; Shi, D.-Q.; Kim, S. H.; Huang, Z.-B.; Ji, S.-B.; Ji, M. Tetrahedron 2008, 64,
2425.
15. Quiroga, J.; Insuasty, B.; Hormaza, A.; Saitz, C.; Jullian, C. J. Heterocycl. Chem.
1998, 35, 575.
16. Quiroga, J.; Mejía, D.; Insuasty, B.; Abonía, R.; Nogueras, M.; Sánchez, A.; Cobo,
J.; Low, J. N. Tetrahedron 2001, 57, 6947.
17. Kozlov, N. G.; Basalaeva, L. I. Russ. J. Org. Chem. 2007, 43, 432.
18. Bazgir, A.; Seyyedhamzeh, M.; Yasaei, Z.; Mirzaei, P. Tetrahedron Lett. 2007, 48,
8790.
19. Sayyafi, M.; Seyyedhamzeh, M.; Khavasi, H. R.; Bazgir, A. Tetrahedron 2008, 64,
2375.
20. Dabiri, M.; Arvin-Nezhad, H.; Khavasi, H. R.; Bazgir, A. J. Heterocycl. Chem. 2007,
44, 1009.
21. Dabiri, M.; Azimi, S. C.; Arvin-Nezhad, H.; Bazgir, A. Heterocycles 2008, 75, 87.
22. Dabiri, M.; Delbari, A. S.; Bazgir, A. Synlett 2007, 821.
23. Dabiri, M.; Arvin-Nezhad, H.; Khavasi, H. R.; Bazgir, A. Tetrahedron 2007, 63,
1770.
species of Gram-positive and Gram-negative bacteria used in the
study. Compounds 4a–j were found to be more active than Tetra-
cycline against B. pumilus, M. luteus, S. mutans, E. coli, and P. aeru-
ginosa. Almost, all of the compounds were found to be more
active than Gentamicin against all tested strains. Compounds 7a–
f were found to be more active than Tetracycline against B. pumilus,
E. coli, and P. aeruginosa. The results indicate that introduction of
–Cl and –Br at aldehyde moiety, thereby producing analogues 4b
and 4c, respectively, decrease the activity against E. faecalis and
S. aureu (MIC: 30, 32, 58, 64 lg/ml). On the other hand, in other
cases of each class of products, types of substitution on aldehyde
moiety have not affected the antibacterial activity. 1,3-Diphenyl-
4,9-dihydro-1H-pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-5,7(6H,
8H)-diones 4a–e were more active than the corresponding ones of
the series 7a–c, reinforcing the pharmacophoric contribution of
carbonyl moiety relative to thiocarbonyl moiety to the mechanism
of action against the all of the tested bacteria except 4b,c against E.
faecalis and S. aureus. Decreasing of the activity was observed in the
case of 4f–g relative to 4a–e due to replacing H by NO2 on N-phe-
nyl ring in pyrazole moiety except 4b,c against E. faecalis and S.
aureus.
In summary, the synthesis and screening of antibacterial activ-
ity for a novel series of pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidine-
dione derivatives was investigated. Almost most of the compounds
exhibited good to excellent antibacterial activity against all the
tested strains.
24. Dabiri, M.; Delbari, A. S.; Bazgir, A. Heterocycles 2007, 71, 543.
25. Procedure for the preparation of 1,3,4-triphenyl-4,9-dihydro-1H-pyrazolo[40,30:5,6]
pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione (4a):
A mixture of barbituric acid
(1 mmol), 1,3-diphenyl-1H-pyrazol-5-amine (1 mmol), benzaldehyde (1.2 mmol)
and p-TSA (0.1 g) was heated at 100 °C for 4 h (TLC). After cooling, the reaction
mixture was washed with water (15 ml) and residue recrystallized from EtOH to
afford the pure product 4a. White powder (83%); mp: 297 °C dec. IR (KBr) (mmax
/
cmꢀ1): 3212, 3064, 1706, 1636. MS (EI, 70 eV) m/z (%): 433 (M+, 90), 356 (100),
313 (10). 1H NMR (300 MHz, DMSO-d6): dH (ppm) 5.33 (1H, s, CH), 7.04–7.74
(15H, m, H–Ar), 9.15 (1H, br s, NH), 10.08 (1H, br s, NH), 10.74 (1H, s, NH). 13C
NMR (DMSO-d6): dC (ppm) 35.9, 89.8, 102.0, 123.5, 126.5, 127.1, 128.3, 128.8,
130.3, 133.2, 137.7, 138.2, 145.4, 146.5, 147.7, 150.1, 163.3. Anal. Calcd for
C26H19N5O2: C, 72.04; H, 4.42; N, 16.16%. Found: C, 72.09; H, 4.37; N, 16.10%.
Selected characterization data.
4-(4-Chlorophenyl)-1,3-diphenyl-4,9-dihydro-1H-pyrazolo[40,30:5,6]pyrido[2,3-d]
pyrimidine-5,7 (6H,8H)-dione (4b): White powder (80%); mp: 320 °C dec. IR (KBr)
(m
max/cmꢀ1): 3212, 3060, 1710, 1635. MS (EI, 70 eV) m/z (%): 467 (M+, 60), 356
(100), 77 (20). 1HNMR (300 MHz, DMSO-d6):dH (ppm) 5.37 (1H, s, CH), 7.17–7.71
(14H, m, H–Ar), 9.16 (1H, br s, NH), 10.09 (1H, br s, NH), 10.76 (1H, s, NH). 13C
NMR (DMSO-d6): dC (ppm) 35.6, 89.3, 101.4, 123.5, 127.1, 128.2, 128.4, 128.8,
130.2, 131.0, 133.0, 137.6, 138.1, 145.3, 145.5, 147.8, 150.1, 163.3. Anal. Calcd for
C26H18ClN5O2: C, 66.74; H, 3.88; N, 14.97%. Found: C, 66.69; H, 3.82; N, 14.90%.
4-(4-Methylphenyl)-1,3-diphenyl-4,9-dihydro-1H-pyrazolo[40,30:5,6]pyrido[2,3-
d]pyrimidine-5,7 (6H,8H)-dione (4d): White powder (92%); mp: 314 °C dec. IR
Acknowledgment
We gratefully acknowledge financial support from the Research
Council of Shahid Beheshti University.
(KBr) (m
max/cmꢀ1): 3231, 3058, 1730, 1623. MS (EI, 70 eV) m/z (%): 447 (M+, 40),
References and notes
445 (100), 356 (50). 1H NMR (300 MHz, DMSO-d6): dH (ppm) 2.15 (3H, s, CH3),
5.33 (1H, s, CH), 6.94–7.75(14H, m, H–Ar), 9.11 (1H, brs, NH), 10.09 (1H, brs, NH),
10.75 (1H, s, NH). 13C NMR (DMSO-d6): dC (ppm) 21.0, 35.6, 90.1, 102.1, 123.5,
127.1, 128.2, 128.3, 128.8, 128.9, 130.3, 133.3, 135.5, 137.7, 138.2, 143.6, 145.3,
147.7, 150.1, 163.3. Anal. Calcd for C27H21N5O2: C, 72.47; H, 4.73; N, 15.65%.
Found: C, 72.42; H, 4.69; N, 15.59%.
1. Dömling, A.; Ugi, I. Angew. Chem. Int., Ed. Engl. 2000, 39, 3168.
2. Dömling, A. Chem. Rev. 2006, 106, 17.
3. Rewcastle, G. W.; Bridges, A. J.; Fry, D. W.; Rubin, J. R.; Denny, W. A. J. Med.
Chem. 1997, 40, 1820.
4. Fry, D. W.; Becker, M. A.; Switzer, R. L. Mol. Pharm. 1995, 47, 810.
5. Gready, J. E.; McKinlay, C.; Gebauer, M. G. Eur. J. Med. Chem. 2003, 38, 719.
6. Sanghvi, Y. S.; Larson, S. B.; Matsumoto, S. S.; Nord, L. D.; Smee, D. F.; Willis, R.
C.; Avery, T. H.; Robins, R. K.; Revankar, G. R. J. Med. Chem. 1989, 32, 3629.
7. Tenser, R. B.; Gaydos, A.; Hay, K. A. Antimicrob. Agents Chemother. 2001, 45,
3657.
8. Nizamuddin-Mishra, M.; Srivastava, M. K.; Khan, M. H. Indian J. Chem. 2001, 40,
49.
9. Ram, V. J.; Goel, A.; Sarkhel, S.; Maulik, P. R. Bioorg. Med. Chem. 2002, 10,
1275.
10. Elnagdi, M. H.; Al-awadi, N.; Erian, A. N. In Compensative Heterocyclic Chemistry
II, 1st ed.; Katritzky, A. R., Rees, C. W., Scriven, E. F. V. Eds.; Pergamon Press:
Oxford, 1996; Vol. 7, p 431.
11. Elnagdi, M. H.; Elmoghayar, M. R. H.; Elgemeie, G. F. Adv. Heterocycl. Chem.
1984, 41, 319.
1-(4-Nitrophenyl)-3,4-diphenyl-4,9-dihydro-1H-pyrazolo[40,30:5,6]pyrido[2,3-
d]pyrimidine-5,7 (6H,8H)-dione (4f): Yellow powder (83%); mp: 324 °C dec. IR
(KBr) (
m
max/cmꢀ1): 3216, 3064, 1727, 1624. MS (EI, 70 eV) m/z (%): 476 (M+ꢀ2,
100), 446 (80), 429 (30). 1H NMR (300 MHz, DMSO-d6): dH (ppm) 5.33 (1H, s, CH),
7.02–7.67 (10H, m, H–Ar), 8.04 (2H, d, J = 8.9 Hz, H–Ar), 8.45 (2H, d, J = 8.9 Hz, H–
Ar), 9.34 (1H, br s, NH), 10.37 (1H, br s, NH), 10.81 (1H, s, NH). 13C NMR (DMSO-
d6): dC (ppm) 35.9, 90.4, 103.5, 122.9, 125.7, 126.6, 127.3, 128.3, 128.4, 128.9,
132.6, 138.5, 143.5, 145.4, 145.7, 146.1, 149.4, 150.2, 163.3. Anal. Calcd for
C26H18N6O4: C, 65.27; H, 3.79; N, 17.56%. Found: C, 65.31; H, 3.85; N, 17.48%.
4-(4-Methylphenyl)-1-(4-nitrophenyl)-3-phenyl-4,9-dihydro-1H-pyrazolo[40,30:5,6]-
pyrido[2,3-d]pyrimidine-5,7 (6H,8H)-dione (4i): Yellow powder (95%); mp: 330 °C
dec. IR (KBr) (m
max/cmꢀ1): 3217, 3007, 1722, 1617. MS (EI, 70 eV) m/z (%): 492
(M+ꢀ2, 100), 460 (90), 407 (10). 1H NMR (300 MHz, DMSO-d6): dH (ppm) 2.15
(3H, s, CH3), 5.29 (1H, s, CH), 6.93–7.68 (9H, m, H–Ar), 8.03 (2H, d, J = 9.0 Hz, H–
Ar), 8.46 (2H, d, J = 8.9 Hz, H–Ar), 9.35 (1H, br s, NH), 10.35 (1H, br s, NH), 10.78
(1H, s, NH). 13C NMR (DMSO-d6): dC (ppm) 21.0, 35.4, 90.5, 103.6, 122.9, 125.7,
12. Ahluwalia, V. K.; Dahiya, A.; Garg, V. J. Indian J. Chem. 1997, 36B, 88. and
references sited therein.

A. Bazgir et al. / Bioorg. Med. Chem. Lett. 18 (2008) 5800–5803
5803
127.2, 128.2, 128.9, 132.6, 135.6, 138.5, 143.2, 143.5, 145.3, 145.7, 149.3, 150.2,
163.3. Anal. Calcd forC27H20N6O4:C, 65.85; H, 4.09; N, 17.06%. Found: C, 65.90; H,
4.14; N, 17.11%.
Ar), 9.05 (1H, br s, NH), 11.86 (1H, br s, NH), 12.22 (1H, s, NH). 13C NMR (DMSO-
d6): dC (ppm) 35.6, 94.6, 103.0, 122.9, 125.7, 127.2, 128.3, 128.5, 128.6, 128.9,
132.3, 136.8, 143.2, 144.8, 145.4, 145.8, 149.5, 160.8, 173.7. Anal. Calcd for
C26H18N6O3S: C, 63.15; H, 3.67; N, 16.99%. Found: C, 63.20; H, 3.63; N, 16.92%.
4-(4-Chlorophenyl)-1-(4-nitrophenyl)-3-phenyl-5-thioxo-1,4,5,6,8,9-hexahydro-
7H-pyrazolo[40,30:5,6] pyrido[2,3-d]pyrimidine-7-dione (7f): Yellow powder
4-(4-Nitrophenyl)-1,3-diphenyl-5-thioxo-1,4,5,6,8,9-hexahydro-7H-pyrazolo[40,30:-
5,6] pyrido[2,3-d]pyrimidine-7-dione (7c): Yellow powder (83%); mp: 234 °C dec.
IR (KBr) (
m
max/cmꢀ1): 3242, 3084, 1733, 1647. MS (EI, 70 eV) m/z (%): 492 (M+ꢀ2,
100), 392 (60), 77 (90). 1H NMR (300 MHz, DMSO-d6): dH (ppm) 5.57 (1H, s, CH),
7.23–8.07 (14H, m, H–Ar), 9.26 (1H, br s, NH), 10.19 (1H, br s, NH), 10.82 (1H, s,
NH). 13C NMR (DMSO-d6): dC (ppm) 36.1, 88.7, 100.9, 121.6, 122.9, 123.6, 127.2,
128.5, 128.8, 129.7, 130.3, 132.8, 135.2, 137.5, 138.1, 145.8, 147.6, 148.3, 150.1,
163.4. Anal. Calcd for C26H18N6O3S: C, 63.15; H, 3.67; N, 16.99%. Found: C, 63.09;
H, 3.71; N, 16.93%.
(84%); mp: 234 °C dec. IR (KBr) (m
max/cmꢀ1): 3188, 3005, 1712, 1627. MS (EI,
70 eV) m/z (%): 526 (M+ꢀ2, 100), 496 (90), 77 (70). 1H NMR (300 MHz, DMSO-d6):
dH (ppm) 5.38 (1H, s, CH), 7.16–7.64 (9H, m, H–Ar), 8.01 (2H, d, J = 9.1 Hz, H–Ar),
8.44 (2H, d, J = 9.0 Hz, H–Ar), 9.34 (1H, br s, NH), 11.88 (1H, br s, NH), 12.26 (1H, s,
NH). 13C NMR (DMSO-d6): dC (ppm) 35.6, 94.1, 102.4, 122.8, 125.7, 127.2, 128.2,
128.9, 130.4, 131.4, 132.3, 137.7, 143.2, 144.3, 144.7, 148.8, 149.5, 160.8, 173.9.
Anal. Calcd for C26H17ClN6O3S: C, 59.04; H, 3.24; N, 15.89%. Found: C, 58.99; H,
3.19; N, 15.95%.
1-(4-Nitrophenyl)-3,4-diphenyl-5-thioxo-1,4,5,6,8,9-hexahydro-7H-pyrazolo[40,30:5,6]
pyrido[2,3-d]pyrimidine-7-dione (7d): Yellow powder (81%); mp: 285 °C dec. IR
(KBr) (
m
max/cmꢀ1): 3208, 3091, 1786, 1625. MS (EI, 70 eV) m/z (%): 492 (M+ꢀ2,
26. NCCLS, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria, which
Grows Aerobically, 5th ed., Approved Standard M7-A5, NCCLS, Villanova, PA,
2000.
100), 462 (60), 172 (30). 1H NMR (300 MHz, DMSO-d6): dH (ppm) 5.32 (1H, s, CH),
7.04–7.71 (10H, m, H–Ar), 8.01 (2H, d, J = 8.8 Hz, H–Ar), 8.43 (2H, d, J = 8.8 Hz, H–