Pyridoquinolones containing azetidinones: Synthesis and their biological evaluation

Article abstract of DOI:10.1007/s00044-011-9728-8

A series of pyridoquinolone 4-oxo-1,4-dihydro( 40-methyl-60-chloropyrido[2, 3-h])quinoline-3-[N-(substituted phenyl methylidine)]carbohydrazide 3a-j and 4-oxo-1, 4-dihydro(4′-methyl-6′-chloropyrido[2,3-h])-3-[N-{(3- chloro- 2-oxo-4-(substituted phenyl) azetidine-1-yl)amino}carbonyl] quinoline 4a-j have been synthesized via 4-oxo-1, 4-dihydro-(4′-methyl-6′- chloropyrido[2,3-h])quinoline carboxylate 1. All the compounds were proved by IR, ¹H-NMR, ¹³C-NMR spectral studies and elemental analysis. Antibacterial activities (MIC) against E. coli, P. aeruginosa, S. aureus and S. pyogenes, and antifungal activities against C. albicans, A. niger and A. clavatus were screened, whereas selected compounds were screened against Mycobacterium tuberculosis H37Rv and compared with standard drugs.

Full text of DOI:10.1007/s00044-011-9728-8

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:2044–2055
DOI 10.1007/s00044-011-9728-8
ORIGINAL RESEARCH
Pyridoquinolones containing azetidinones: synthesis and their
biological evaluation
•
Navin B. Patel Kunal K. Pathak
Received: 2 December 2010 / Accepted: 21 June 2011 / Published online: 10 July 2011
ꢀ Springer Science+Business Media, LLC 2011
Abstract A series of pyridoquinolone 4-oxo-1,4-dihy-
dro(40-methyl-60-chloropyrido[2,3-h])quinoline-3-[N-(substi-
tuted phenyl methylidine)]carbohydrazide 3a–j and 4-oxo-1,
4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-{(3-chl-
oro-2-oxo-4-(substituted phenyl) azetidine-1-yl)amino}ca-
rbonyl] quinoline 4a–j have been synthesized via 4-oxo-1,
4-dihydro-(40-methyl-60-chloropyrido[2,3-h])quinoline car-
boxylate 1. All the compounds were proved by IR, 1H-NMR,
13C-NMR spectral studies and elemental analysis. Anti-
bacterial activities (MIC) against E. coli, P. aeruginosa,
S. aureus and S. pyogenes, and antifungal activities against
C. albicans, A. niger and A. clavatus were screened, whereas
selected compounds were screened against Mycobacterium
tuberculosis H37Rv and compared with standard drugs.
during chloroquine synthesis (Norris and Mandell, 1988;
Leverkusan, 1999). Since then structural modifications have
resulted in an important class of fluoroquinolones, which
have improved coverage of gram-positive organisms.
Quinolones rapidly inhibit DNA synthesis by promoting
cleavage of bacterial DNA in the DNA-enzyme complexes
of DNA gyrase and type IV topoisomerase, resulting in rapid
bacterial death (Hooper, 1999).
Various substituted quinolone drugs like ciprofloxacin,
norfloxacin, ofloxacin, levofloxacin, sparfloxacin, gati-
floxacin, moxifloxacin, trovafloxacin, etc. have clinical
applications in the disease of genitourinary tract infections,
upper and lower respiratory infections, gastrointestinal
infections, gynaecological infections, sexually transmitted
diseases, some skin and soft tissue infections (Oliphant,
2002; Wolfson and Hooper, 1989; Hooper and Wolfson,
1991; Fang et al., 1991; Sabbaj et al., 1986; Hooper, 2000;
Centers for diesease control and prevention, 1998).
Keywords Pyridoquinolone ꢀ Schiff base ꢀ Azetidinone ꢀ
Antibacterial ꢀ Antifungal ꢀ Antitubarcular activity
Fluorinated pyridoquinolones have been synthesized by
Lee and Chang (Lee et al., 1992) and their biological
activity has been studied. We have concentrated on non-
fluorinated pyridoquinolones, synthesized several com-
pounds by incorporating various substituted urea, thiourea
and piperazine compounds at C-3 position and studied their
antimicrobial activities (Patel and Chauhan, 2005; Patel
and Patel, 2010; Patel et al., 2010a; Patel and Modi, 2010;
Patel et al., 2010b), and found that these compounds
showed good antimicrobial activities.
Introduction
Quinolones are very important family of antibacterial agents
that are widely prescribed for the treatment of infections in
humans. The 4-pyridone-3-carboxylic acid associated with a
5, 6-fused aromatic ring is the common chemical feature of
bactericidal quinolones. In the resulting bicyclic ring, the 1-,
5-, 6-, 7- and 8-positions are the major targets of chemical
variation (Emami et al., 2005). The first quinolone, nalidixic
acid was introduced in 1962. The substance was discov-
ered by George Lesher and coworkers in a distillate
Furthermore the 2-azetidinones, commonly known as
b-lactam unit is a crucial structural feature of one class of
significant antibiotics and its stereo chemistry is very
important to their biological activities. Traditionally,
b-lactam is a part of the structure of broad spectrum antibiotic
class of drugs: penicillins and cephalosporins (Toraskar et al.,
2010). Azetidinones were reported to posses antibacterial
N. B. Patel (&) ꢀ K. K. Pathak
Department of Chemistry, Veer Narmad South Gujarat
University, Surat 395007, Gujarat, India
e-mail: drnavin@satyam.net.in
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Med Chem Res (2012) 21:2044–2055
2045
Cl
Cl
Cl
N
Cl
N
O
O
.
2H2O
NH2NH2
DMF
CH HN
3
O
HN
CH
O
3
HN
OC H
2
5
NH
2
1
2
R
OHC
DMF
N
O
CH HN
O
N
3
R
HN
3a-j
CH
ClCH2COCl
Triethyl amine
DMF
N
O
O
R
CH HN
3
HN
N
4a-j
O
Cl
a
b
c
d
e
f
g
h
i
j
3
4
-H
-H
2-Cl 4-Cl 4-CH3 2-OCH3 4-OCH3 3-OCH3, 4-OH 2-O
2-OH, 3-NO2
2-OH, 5-NO2,
2-OH, 5-NO2,
2-Cl 4-Cl 4-CH3 2-OCH3 4-OCH3 3-OCH3, 4-OH 2-OH 2-OH, 3-NO2
Scheme 1 Synthetic route of compounds 3a–j and 4a–j
(Patel and Patel, 2011), antifungal (Bhat et al., 2007), anti-
tubercular (Chikhalia et al., 2006; Rajasekaran et al., 2010),
anticancer (Veinberg et al., 2003), anticonvulsant (Kumar
et al., 2009a), anti-HIV (Mukund et al., 1998), anti-inflam-
matory (Kumar et al. 2009b), ACAT and cholesterol
absorption inhibitor (Burnett et al., 1994) activities.
Result and discussion
Chemistry
Schiff base derivatives 4-oxo-1,4-dihydro(40-methyl-60-chlo-
ropyrido[2,3-h])quinoline-3-[N-(substituted phenyl meth-
ylidine)]carbohydrazide 3a–j and azetidinones; 4-oxo-1,
4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N{(3-chloro-
2-oxo-4-(substituted phenyl) azetidine-1-yl) amino}car-
bonyl]quinoline 4a–j were synthesized; which is illustrated
in the Scheme 1. The structures of all the compounds
Limited study has been carried out on pyridoquinolone-
based azetidinone scaffold, in view of this, we have selected
this scaffold for further studies and enhanced our study to
prepare pyridoquinolone analogues incorporating various
azetidinones via substituted Schiff bases at C-3 position,
which were screened for antibacterial and antifungal
activities as well as antitubercular activity against H37Rv.
1
were confirmed by elemental analysis, IR, H-NMR and
13C-NMR spectral data.
123

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Med Chem Res (2012) 21:2044–2055
Compounds 3a–j and 4a–j were confirmed by IR-
and A. clavatus compared with both nystatin and
griseofulvin.
spectra (cm-1) absorption bands at 3424 (NH), 2925, 2842
(C–H), 1725 ([C=O), 1638 (amide-I), 1620 (–N=CH–),
1536 (amide-II), 1317 (C–N), 1240 (amide-III), 790 (C–Cl);
other bands at 3230 (O–H), 1536, 1357 (NO2, sym, asym),
1228, 1012 (C–O–C) were also observed due to substituted
aldehydes. When compound 2 was reacted with substituted
aldehydes, Schiff bases 3a–j were formed which was
confirmed by strong –N=CH– stretching band at
Compounds 4c (R=4-Cl), 4d (R=4-CH3), 4e (R=2-
OCH3) and 4j (R=2-OH, 5-NO2) showed relatively strong
activity against C. albicans compared with griseofulvin;
however, 4b (R=2-Cl) showed relatively strong activity
against C. albicans compared with nystatin and showed
relatively strong activity against A. niger, and A. clavatus
compared with griseofulvin.
1
1620 cm-1. The H-NMR showed singlet at d 8.66, 7.46,
Selected compounds were screened against Mycobac-
terium tuberculosis (Table 2). Compounds 3i (R=2-OH,
3-NO2) and 4c (R=4-Cl) showed better activity among all
the compounds, but poorer activity with isoniazide.
2.72 of H2, H5 and -CH3; whereas doublet at d 12.40, 8.32
and 7.84 of [NH, H5 and H6 of pyridoquinolone ring,
respectively, singlet at d 7.5 of –N=CH– showed the
presence of Schiff base in 3a–j, which disappeared when it
was converted to azetidinones 4a–j and which was con-
firmed by doublet at d 3.32 and 3.23 due to H3 and H4 of
ß-lactam ring, respectively. This was also confirmed by the
13C-NMR for azetidinone ring signal of C=O at 166.6 the.
Conclusions
•
•
When parent compound was converted into hydrazide,
activity increased against gram-negative bacteria but
decreased against gram-positive bacteria.
Antimicrobial activity
Schiff base derivatives with 4-methoxy and 2-hydroxy-
5-nitro substitution displayed strong activity against
E. coli compared with ampicillin; with 2-chloro,
3-methoxy-4-hydroxy and 2-hydroxy substitution dis-
played strong activity against S. aureus.
In vitro antimicrobial activities of all compounds were
carried out by broth dilution method (Rattan, 2000), and
MIC were screened against two gram-negative E. coli,
P. aeruginosa; two gram-positive S. aureus, S. pyogenes
bacteria, three fungal species C. albicans, A. niger,
A. clavatus, and the selected compounds were screened
against Mycobacterium tuberculosis H37Rv. Ampicillin,
chloramphenicol, ciprofloxacin and norfloxacin for anti-
bacterial; nystatin and griseofulvin for antifungal and iso-
niazide for antitubercular were used as standard drugs.
From the results (Table 1), the activity of 2 increased
against both gram-negative, while decreased against both
gram-positive bacteria. Compounds 3e (R=2-OCH3), and 3j
(R=2-OH, 5-NO2) showed relatively strong activity against
both E. coli and P. aeruginosa; however, 3g (R=3-OCH3,
4-OH), 3h (R=2–OH) showed relatively strong activity
against S. aureus compared with ampicillin. All the Schiff
bases showed relatively poor activity against S. pyogenes.
Compounds 4a (R=–H), 4c (R=4-Cl), 4 h (R=2-OH), 4i
(R=2-OH, 3-NO2) showed relatively strong activity against
E. coli; however, 4c (R=4-Cl) showed relatively strong
activity against P. aeruginosa compared with ampicillin.
Remaining compounds were poor in activity compared
with other drugs.
•
•
Azetidinones with 4-chloro, 2-hydroxy and 2-hydroxy-
3-nitro substitution displayed strong activity against
E. coli; however, 4-chloro substitution displayed rela-
tively strong activity against P. aeruginosa.
All the Schiff bases showed relatively strong activity
against fungal species C. albicans and retained its
activity when converted into azetidinones but poor
against A. niger and A. clavatus.
Experimental
General
Melting points were determined on a Kofler melting point
apparatus and are uncorrected. Conversions of reactions
were monitored by TLC using Merck silica gel 60 F254
1
plates, and spots were visualized under UV radiation. H
and 13C-NMR spectra were recorded in DMSO-d6 solvent
on Bruker Avance II-400 spectrometer at 400 MHz and
100 MHz, respectively, the chemical shifts are reported in
part per million (d ppm) using tetramethylsilane (TMS) as
an internal standard. IR spectra were recorded in the range
of 4000–600 cm-1 on a Thermo Scientific Nicolet iS10
FT-IR spectrometer using KBr pellets. Elemental analyses
were performed on a Heraeus Carlo Erba 1180 CHN
analyzer.
Activity of 2 decreased against all fungal species
C. albicans, A. niger and A. clavatus. Compounds 3a (R=-
H), 3b (R=2-Cl), 3d (R=4-CH3), 3g (R=3-OCH3, 4-OH), 3i
(R=2-OH, 3-NO2) and 3j (R=2-OH, 5-NO2) showed rela-
tively strong activity against C. albicans compared with
nystatin; however, 3h (R=2-OH) showed relatively strong
activity against C. albicans compared with griseofulvin. 3c
(R=4-Cl) showed relatively strong activity against A. niger
123

Med Chem Res (2012) 21:2044–2055
2047
Table 1 Antibacterial and antifungal activity of synthesized compounds
Compd.
Antibacterial activity
Minimal inhibition concentration (lg/ml)
Gram negative
Gram positive
Fungal species
E. coli
P. aeruginosa
S. aureus
S. pyogenes
C. albicans
A. niger
A. clavatus
1
250
100
250
500
500
200
100
250
500
250
150
62.5
100
200
100
250
500
250
250
100
62.5
250
100
50
250
200
250
500
1000
250
250
500
500
250
200
100
250
250
100
250
1000
250
500
200
200
500
100
50
150
250
200
100
250
250
250
500
100
100
500
200
250
200
500
250
250
500
1000
500
500
500
250
50
100
200
250
200
250
250
250
500
200
200
500
250
250
200
500
250
500
500
1000
500
500
500
100
50
200
500
250
250
500
250
500
500
250
100
200
200
500
100
200
200
250
500
1000
500
500
250
1000
[1000
[1000
500
1000
[1000
[1000
[1000
250
2
3a
3b
3c
3d
3e
3f
250
500
500
1000
500
1000
500
3
1000
500
1000
500
g
3
h
3i
500
500
3j
1000
[1000
250
1000
[1000
250
4a
4b
4c
4d
4e
4f
500
500
[1000
[1000
[1000
500
[1000
[1000
[1000
500
4
g
4
1000
[1000
500
1000
[1000
500
h
4i
4j
Ampicillin
Chloramphenicol
Ciprofloxacin
Norfloxacin
Nystatin
25
25
50
50
10
10
10
10
100
500
100
100
100
100
Griseofulvin
Table 2 Anti tubercular
activity table
General procedure for synthesis of compound 3a–j
and 4a–j
Compds
MIC values lg/ml
of M. tuberculosis
H37Rv
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido
[2,3-h])quinolone-3-carboxylate (1)
1
500
200
250
500
200
62.5
500
250
100
500
200
2
3e
The parent compound 1 was prepared from 2-chloro-4-
methyl quinoline which underwent a nitration (Krahler and
Burger, 1941), and reduction (Gamble et al., 2007) was
followed by condensation (Lee and Chang, 1994) with
diethyl ethoxy methylene malonate and cyclization (Lee
and Chang, 1996) in diphenyl ether.
3
g
3
h
3i
3j
4a
4c
2-Chloro-4-methyl quinoline under nitration using
fuming HNO3 and conc. H2SO4 (98%) formed 2-chloro-4-
methyl-5-nitro quinoline, which on reduction by using Fe/
Isoniazide was considered as a
standard drug: 0.20 lg/ml 99%
inhibition
4
h
4i
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Med Chem Res (2012) 21:2044–2055
CH3COOH formed 2-chloro-4-methyl-5-amino quinoline,
followed by condensation with diethyl ethoxy methylene
malonate to give (2-chloro-4-methyl quinolin-5-yl)amino]
methylenemalonate; 0.01 mol of the obtained product was
suspended in 30 ml of diphenyl ether and refluxed for 3 h
at 250ꢁC, the reaction mixture was cooled to room tem-
perature and kept it to settle for one day. The resulting solid
was filtered and washed with petroleum ether and recrys-
tallized from DMF to give pure product of 1.
crushed ice, and the product was filtered, washed with
water and recrystallized from DMF to give 3.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(phenyl methylidine)] carbohydrazide (3a)
Yield = 60%, m.p. 256–258ꢁC; IR (KBr) cm-1: 3424 (NH),
2925, 2842 (C–H), 1725 ([C=O), 1638 (amide-I), 1620
(–N=CH–), 1536 (amide-II), 1317 (C–N), 1240 (amide-
1
III), 790 (C–Cl); H NMR (DMSO-d6): d 12.40 (d, 1H,
Yield = 60%, m.p. 280–282ꢁC; IR (KBr) cm-1: 3417
(NH), 2920, 2845 (C–H), 1725 ([C=O), 1340 (C–N), 780
(C–Cl); 1H NMR (DMSO-d6): d 12.40 (d, 1H, NH), 8.66 (s,
1H, H2), 8.35 (d, 1H, H5), 7.80 (d, 1H, H6), 7.46 (s, 1H, H5’ of
pyrido), 4.32 (q, 2H, CH2), 2.74 (s, 3H, CH3 of pyrido), 1.40
(t, 3H, CH3); 13C NMR (DMSO-d6): d 187, 172.7, 154.2,
148, 145.5, 138.1, 136.6, 129, 122, 120.2, 117.1, 110.1,
108.7, 40.1, 18, 13.4; Anal. Calcd. for C16H13ClN2O3: C
60.67, H 4.14, N 8.84. Found: C 60.62, H 4.10, N 8.81.
NH), 8.80 (s, 1H, [CONH), 8.66 (s, 1H, H2), 8.32 (d, 1H,
H5), 7.84 (d, 1H, H6), 7.5 (s, 1H, –N=CH–), 7.46 (s, 1H,
H
5’ of pyrido), 7.2–8.4 (m, 5H, Ar–H), 2.72 (s, 3H, CH3 of
pyrido); 13C NMR (DMSO-d6): d 185.7, 171.4, 155.9,
154.1, 149.7, 144.1, 138, 136.2, 131.1, 130.4, 129, 128.2,
127.6, 122.1, 120, 116.9, 109.2, 108.7, 18.4; Anal. Calcd.
for C21H15ClN4O2: C 64.54, H 3.87, N 14.34. Found: C
64.58, H 3.82, N 14.30.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(2-chlorophenyl methylidine)]carbohydrazide
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido
[2,3-h])quinolone-3-carbohydrazide (2)
(3b) Yield = 62%, m.p. 251–253ꢁC; IR (KBr) cm-1
:
3415 (NH), 2922, 2830 (C–H), 1717 ([C=O), 1670
(amide-I), 1627 (–N=CH–), 1525 (amide-II), 1317 (C–N),
1250 (amide-III), 778 (C–Cl); 1H NMR (DMSO-d6): d
12.42 (d, 1H, NH), 8.82 (s, 1H,[CONH), 8.65 (s, 1H, H2),
8.33 (d, 1H, H5), 7.86 (d, 1H, H6), 7.46 (s, 1H, –N=CH–),
7.41 (s, 1H, H5’ of pyrido), 7.30–8.55 (m, 4H, Ar–H), 2.70
(s, 3H, CH3 of pyrido); 13C NMR (DMSO-d6): d 180.7,
172.4, 155.1, 154.2, 149.3, 144.4, 138.2, 136.3, 134.4,
131.4, 130.3, 129, 128.3, 127.9, 122.4, 119.7, 116.7, 108.9,
108.1, 17.7; Anal. Calcd. for C21H14Cl2N4O2: C 59.31, H
3.32, N 13.17. Found: C 59.35, H 3.37, N 13.12.
A mixture of 1 (0.005 mol) and hydrazine hydrate
(0.01 mol) in 30 ml DMF was refluxed on water bath for
6 h. Conversion of reaction was periodically observed by
TLC using mobile phase toluene to methanol (9:1). The
reaction mixture was concentrated by distilled-off solvent
and poured into crushed ice. The solid separated, was
washed with water, dried and recrystallized from DMF, and
the crystals of 2 were obtained.
Yield = 64%, m.p. 250–252ꢁC; IR (KBr) cm-1: 3410
(NH), 2915, 2847 (C–H), 1719 ([C=O), 1645 (amide-I),
1530 (amide-II), 1320 (C–N), 1244 (amide-III), 784
(C–Cl); 1H NMR (DMSO-d6): d 12.42 (d, 1H, NH), 8.84 (s,
1H,[CO–NH), 8.62 (s, 1H, H2), 8.33 (d, 1H, H5), 7.82 (d,
1H, H6), 7.44 (s, 1H, H5’ of pyrido), 4.36 (s, 2H, –NH2),
2.75 (s, 3H, CH3 of pyrido); 13C NMR (DMSO-d6): d
185.5, 170.6, 153.3, 149.9, 144.4, 137, 136.1, 127.2, 122.3,
120.1, 117.7, 109.9, 108.4, 18.2; Anal. Calcd. for
C14H11ClN4O2: C 55.55, H 3.66 N 18.51. Found: C 55.50,
H 3.62, N 18.48.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(4-chlorophenyl methylidine)]carbohydrazide
(3c) Yield = 56%, m.p. 255–257ꢁC; IR (KBr) cm-1: 3395
(NH), 2928, 2842 (C–H), 1719 ([C=O), 1637 (amide-I),
1620 (–N=CH–), 1531 (amide-II), 1322 (C–N), 1254
1
(amide-III), 796 (C–Cl); H NMR (DMSO-d6): d 12.46 (d,
1H, NH), 8.70 (s, 1H, [CONH), 8.60 (s, 1H, H2), 8.38 (d,
1H, H5), 7.80 (d, 1H, H6), 7.50 (s, 1H, –N=CH–), 7.45 (s,
1H, H5’ of pyrido), 7.42-8.45 (m, 4H, Ar–H), 2.72 (s, 3H,
CH3 of pyrido); 13C NMR (DMSO-d6): d 182.6, 172.9,
154.4, 153.2, 148.7, 144.1, 138.6, 135.3, 131.9, 130.1,
129.2, 128.4, 126.4, 120.9, 119.4, 117.6, 108.9, 108, 17.9;
Anal. Calcd. for C21H14Cl2N4O2: C 59.31, H 3.32, N 13.17.
Found: C 59.37, H 3.25, N 13.22.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido
[2,3-h])quinoline-3-[N-(substituted phenyl
methylidine)]carbohydrazide (3a–j)
An equimolar amount of 2 (0.005 mol) and substituted
aromatic aldehyde (0.005 mol), along with 2–3 drops of
glacial acetic acid were taken in 10 ml of dry DMF, and the
reaction mixture was refluxed for 4–6 h on water bath.
Conversion of reaction was periodically observed by TLC
using mobile phase toluene to methanol (9:1). After the
completion of the reaction mixture, it was poured into
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(4-methylphenyl methylidine)]carbohydrazide
(3d) Yield = 58%, m.p. 262-264ꢁC; IR (KBr) cm-1: 3414
(NH), 2917, 2845 (C–H), 1717 ([C=O), 1645 (amide-I),
1617 (–N=CH–), 1531 (amide-II), 1321 (C–N), 1238
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Med Chem Res (2012) 21:2044–2055
2049
1
(amide-III), 782 (C–Cl); H NMR (DMSO-d6): d 12.40 (d,
13C NMR (DMSO-d6): d 185.3, 172.5, 160.2, 155.5, 152.4,
145.4, 141.7, 138.2, 136, 134.5, 133.9, 130.7, 128.4, 125.9,
120.1, 119.1, 117.3, 110.4, 108.1, 55.7, 18.1; Anal. Calcd.
for C22H17ClN4O4: C 60.49, H 3.92, N 12.83. Found: C
60.55, H 3.88, N 12.80.
1H, NH), 8.74 (s, 1H, [CONH), 8.63 (s, 1H, H2), 8.29 (d,
1H, H5), 7.85 (d, 1H, H6), 7.48 (s, 1H, –N=CH–), 7.40 (s,
1H, H5’ of pyrido), 7.0–8.55 (m, 4H, Ar–H), 2.74 (s, 3H,
CH3 of pyrido), 1.6 (s, 3H, -CH3);); 13C NMR (DMSO-d6):
d 182.2, 171.4, 154.9, 153.1, 147.6, 144, 138.2, 134.3,
130.7, 130, 129.1, 127.9, 126.2, 120.4, 119, 116.9, 110.1,
108, 22.4, 18.1; Anal. Calcd. for C22H17ClN4O2: C 65.27,
H 4.23, N 13.84. Found: C, 65.32, H 4.27, N 13.90.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(2-hydroxy phenyl methylidine)]carbohydraz-
ide (3h) Yield = 62%, m.p. 258–260ꢁC; IR (KBr) cm-1
:
3399 (NH), 3222 (O–H), 2928, 2830 (C–H), 1725 ([C=O),
1647 (amide-I), 1624 (–N=CH–), 1527 (amide-II), 1319
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(-2-methoxy phenyl methylidine)]carbohydraz-
1
(C–N), 1242 (amide-III), 792 (C–Cl); H NMR (DMSO-
ide (3e) Yield = 62%, m.p. 270–272ꢁC; IR (KBr) cm-1
:
d6): d 12.44 (d, 1H, NH), 8.78 (s, 1H, [CONH), 8.63 (s,
1H, H2), 8.41 (d, 1H, H5), 7.78 (d, 1H, H6), 7.51 (s, 1H,
–N=CH–), 7.38 (s, 1H, H5’ of pyrido), 7.30–8.50 (m, 4H,
Ar–H), 4.95 (s, 1H, –OH), 2.68 (s, 3H, CH3 of pyrido); 13
C
3410 (NH), 2924, 2850 (C–H), 1721 ([C=O), 1639
(amide-I), 1629 (–N=CH–), 1533 (amide-II), 1322 (C–N),
1
1237 (amide-III), 1230, 1025 (C–O–C), 792 (C–Cl); H
NMR (DMSO-d6): d 12.48 (d, 1H, NH), 8.80 (s, 1H,
[CONH), 8.60 (s, 1H, H2), 8.33 (d, 1H, H5), 7.82 (d, 1H,
H6), 7.46 (s, 1H, –N=CH–), 7.41 (s, 1H, H5’ of pyrido),
7.25–8.40 (m, 4H, Ar–H), 3.77 (s, 3H, –OCH3), 2.75 (s,
3H, CH3 of pyrido); 13C NMR (DMSO-d6): d 180.4, 172.6,
164.4, 155.5, 152.4, 147.1, 143.8, 137.2, 136.2, 134.1,
130.4, 129.4, 128.1, 126.7, 120.1, 119, 117.7, 110, 108.2,
54.2, 18.2; Anal. Calcd. for C22H17ClN4O3: C 62.79, H
4.07, N 13.31. Found: C 62.70, H 4.02, N 13.35.
NMR (DMSO-d6): d 184.2, 169.4, 158.1, 154.7, 152.1,
146.1, 141.4, 138.9, 136.2, 134.6, 133.2, 131.2, 128.9,
126.2, 120.4, 119, 117.7, 110, 108.7, 18.9; Anal. Calcd. for
C21H15ClN4O3: C 62.00, H 3.72, N 13.77. Found: C 62.10,
H 3.76, N 13.71 (Fig. 1).
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(2-hydroxy-3-nitro phenyl methylidine)]carbo-
hydrazide (3i) Yield = 60%, m.p. 255-257ꢁC; IR (KBr)
cm-1: 3417 (NH), 3224 (O–H), 2922, 2844 (C–H), 1717
([C=O), 1645 (amide-I), 1621 (–N=CH–), 1529 (amide-
II), 1536, 1357 (NO2, sym, asym), 1317 (C–N), 1246
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(-4-methoxy phenyl methylidine)]carbohydraz-
ide (3f) Yield = 62%, m.p. 263–265ꢁC; IR (KBr) cm-1
:
(amide-III), 793 (C–Cl); H NMR (DMSO-d6): d 12.38 (d,
1
3405 (NH), 2924, 2856 (C–H), 1725 ([C=O), 1644
(amide-I), 1622 (–N=CH–), 1531 (amide-II), 1319 (C–N),
1H, NH), 8.70 (s, 1H, [CONH), 8.61 (s, 1H, H2), 8.38 (d,
1H, H5), 7.75 (d, 1H, H6), 7.49 (s, 1H, –N=CH–), 7.42 (s,
1H, H5’ of pyrido), 7.38–8.40 (m, 3H, Ar–H), 4.92 (s, 1H,
–OH), 2.72 (s, 3H, CH3 of pyrido); 13C NMR (DMSO-d6):
d 183.1, 170.5, 159.2, 155.5, 151, 146.4, 141.7, 139.2, 136,
134.1, 133.6, 132.1, 130.7, 128.4, 126.5, 121.5, 120.1,
117.6, 110.4, 108.6, 18.7; Anal. Calcd. for C21H14ClN5O5:
C 55.82, H 3.12, N 15.50. Found: C 55.90, H 3.18, N 15.42.
1
1240 (amide-III), 1228, 1012 (C–O–C), 786 (C–Cl); H
NMR (DMSO-d6): d 12.50 (d, 1H, NH), 8.78 (s, 1H,
[CONH), 8.63 (s, 1H, H2), 8.30 (d, 1H, H5), 7.84 (d, 1H,
0
H6), 7.48 (s, 1H, –N=CH–), 7.40 (s, 1H, H5 of pyrido),
7.42–8.48 (m, 4H, Ar–H), 3.70 (s, 3H, –OCH3), 2.68 (s,
3H, CH3 of pyrido); 13C NMR (DMSO-d6): d 186.2,
172.1,166.5, 155.2, 152.1, 146.1, 142.9, 137.7, 136.4, 134,
130.2, 128.9, 126.5, 120.3, 119.4, 117.1, 109.9, 108.4,
56.3, 18.7; Anal. Calcd. for C22H17ClN4O3: C 62.79, H
4.07, N 13.31. Found: C 62.82, H 4.12, N 13.36.
Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quino-
line-3-[N-(2-hydroxy-5-nitro phenyl methylidine)]carbo-
hydrazide (3j) Yield = 58%, m.p. 250–252ꢁC; IR (KBr)
cm-1: 3422 (NH), 3217 (O–H), 2920, 2837 (C–H), 1721
([C=O), 1648 (amide-I), 1617 (–N=CH–), 1533 (amide-
II), 1532, 1352 (NO2, sym, asym), 1322 (C–N), 1248
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])quin-
oline-3-[N-(3-methoxy-4-hydroxy phenyl methylidine)]car-
bohydrazide (3g) Yield = 65%, m.p. 254–256ꢁC; IR
(KBr) cm-1: 3407 (NH), 3230 (O–H), 2930, 2849 (C–H),
1720 ([C=O), 1641 (amide-I), 1619 (–N=CH–), 1533
(amide-II), 1324 (C–N), 1236 (amide-III), 1223, 1017
1
(amide-III), 787 (C–Cl); H NMR (DMSO-d6): d 12.44 (d,
1H, NH), 8.75 (s, 1H, [CONH), 8.64 (s, 1H, H2), 8.34 (d,
1H, H5), 7.80 (d, 1H, H6), 7.51 (s, 1H, –N=CH–), 7.43 (s,
1H, H5’ of pyrido), 7.25-8.35 (m, 3H, Ar–H), 4.90 (s, 1H,
–OH), 2.68 (s, 3H, CH3 of pyrido); 13C NMR (DMSO-d6):
d 184.2, 171.6, 161.1, 154.9, 151.2, 146.7, 142.4, 139.7,
136.2, 134.5, 133.4, 132, 130.4, 127.2, 126.9, 121.4, 119.7,
117.1, 110.2, 109.1, 18.2; Anal. Calcd. for C21H14ClN5O5:
C 55.82, H 3.12, N 15.50. Found: C 55.86, H 3.17, N 15.61.
1
(C–O–C), 790 (C–Cl); H NMR (DMSO-d6): d 12.40 (d,
1H, NH), 8.76 (s, 1H, [CONH), 8.64 (s, 1H, H2), 8.36 (d,
1H, H5), 7.82 (d, 1H, H6), 7.47 (s, 1H, –N=CH–), 7.39 (s,
1H, H5’ of pyrido), 7.25–8.30 (m, 3H, Ar–H), 4.90 (s, 1H,
–OH), 3.72 (s, 3H, –OCH3), 2.72 (s, 3H, CH3 of pyrido);
123

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Med Chem Res (2012) 21:2044–2055
Cl
N
O
CH HN
3
O
N
HO
HN
CH
a
1
Fig. 1 a IR, b H-NMR, c 13C-NMR spectra of compound (3h)
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-
[N-{(3-chloro-2-oxo-4-(substituted phenyl) azetidine-1-yl)
amino}carbonyl]quinoline (4a–j)
3.23 (d, 1H, CH–Cl of azetidinone), 2.70 (s, 3H, CH3 of
pyrido); 13C NMR (DMSO-d6): d 184.2, 169.4, 166.6,
156.1, 150.5, 144.2, 142.2, 138, 136.4, 129.6, 128.2,127,
125.5, 122.1, 120.6, 117.9, 110.2, 108.4, 65.3, 62.4, 18;
Anal. Calcd. for C23H16Cl2N4O3: C 59.11, H 3.45, N 11.99.
Found: C 59.17, H 3.40, N 11.80.
Chloroacetyl chloride (0.0025 mol) was added drop wise
into the solution of 3 (0.0025 mol) in DMF (50 ml) under
stirring below 10ꢁC, and triethyl amine (0.0025 mol) was
added into reaction mixture and refluxed for 14–18 h.
Conversion of reaction was periodically observed by TLC
using mobile phase toluene to methanol (9:1). Reaction
mixture was concentrated by distilled-off solvent and
poured into crushed ice. The product filtered, washed with
water and recrystallized from DMF to give 4.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(2-chloro phenyl)azetidine-1-yl)amino}
carbonyl]quinoline (4b) Yield = 65%, m.p. 260–262ꢁC;
IR (KBr) cm-1: 3421 (NH), 2930, 2850 (C–H), 1717
([C=O), 1668 (amide-I), 1526 (amide-II), 1323 (C–N),
1243 (amide-III), 786 (C–Cl); 1H NMR (DMSO-d6): d
12.50 (d, 1H, NH), 8.70 (s, 1H,[CONH), 8.60 (s, 1H, H2),
8.37 (d, 1H, H5), 7.85 (d, 1H, H6), 7.46 (s, 1H, H5’ of
pyrido), 7.4-8.40 (m, 4H, Ar–H), 3.30 (d, 1H, CH of aze-
tidinone), 3.21 (d, 1H, CH–Cl of azetidinone), 2.68 (s, 3H,
CH3 of pyrido); 13C NMR (DMSO-d6): d 184.6, 169.1,
166.2, 155.9, 150.9, 143.7, 141.5, 138.7, 136.1, 134.7,
129.5, 128.7, 127.1, 124.6, 121.7, 120.1, 117.2, 109.7,
108.1, 65.5, 62.7, 18.4; Anal. Calcd. for C23H15Cl3N4O3:
C 55.06, H 3.01, N 11.17. Found: C 55.01, H 3.07, N
11.12.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-
[N-{(3-chloro-2-oxo-4-phenyl azetidine-1-yl)amino}car-
bonyl]quinoline (4a) Yield = 62%, m.p. 265–267ꢁC; IR
(KBr) cm-1: 3418 (NH), 2922, 2840 (C–H), 1719 ([C=O),
1646 (amide-I), 1525 (amide-II), 1327 (C–N), 1239
1
(amide-III), 790 (C–Cl); H NMR (DMSO-d6): d 12.40 (d,
1H, NH), 8.64 (s, 1H, [CONH), 8.67 (s, 1H, H2), 8.34 (d,
1H, H5), 7.81 (d, 1H, H6), 7.47 (s, 1H, H5’ of pyrido),
7.24–8.45 (m, 5H, Ar–H), 3.32 (d, 1H, CH of azetidinone),
123

Med Chem Res (2012) 21:2044–2055
2051
Fig. 1 contiuned
123

2052
Med Chem Res (2012) 21:2044–2055
Cl
N
O
CH HN
3
O
N
HN
OCH
3
O
Cl
a
1
Fig. 2 a IR, b H-NMR c 13C-NMR spectra of compound (4e)
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
12.58 (d, 1H, NH), 8.76 (s, 1H,[CONH), 8.66 (s, 1H, H2),
8.28 (d, 1H, H5), 7.77 (d, 1H, H6), 7.39 (s, 1H, H5’ of
pyrido), 7.45–8.30 (m, 4H, Ar–H), 3.34 (d, 1H, CH of
azetidinone), 3.24 (d, 1H, CH-Cl of azetidinone), 2.75 (s,
3H, CH3 of pyrido), 1.48 (s, 3H, -CH3); 13C NMR (DMSO-
d6): d 185.4, 168.9, 164.7, 155.6, 150.5, 145.1, 141.3,
138.2, 136.1, 129.3, 127.9, 126.1, 125.1, 120.1, 119.7,
117.2, 110, 108.1, 64.5, 63.4, 22.4, 18.1; Anal. Calcd. for
C24H18Cl2N4O3: C 59.89, H 3.77, N 11.64. Found: C
59.80, H 3.72, N 11.69.
{(3-chloro-2-oxo-4-(4-chloro phenyl)azetidine-1-yl)amino}
carbonyl]quinoline (4c) Yield = 58%, m.p. 256–258ꢁC;
IR (KBr) cm-1: 3405 (NH), 2918, 2836 (C–H), 1722
([C=O), 1637 (amide-I), 1534 (amide-II), 1318 (C–N),
1245 (amide-III), 787 (C–Cl); 1H NMR (DMSO-d6): d
12.55 (d, 1H, NH), 8.75 (s, 1H,[CONH), 8.64 (s, 1H, H2),
8.30 (d, 1H, H5), 7.80 (d, 1H, H6), 7.41 (s, 1H, H5’ of
pyrido), 7.45-8.40 (m, 4H, Ar–H), 3.31 (d, 1H, CH of
azetidinone), 3.19 (d, 1H, CH-Cl of azetidinone), 2.71 (s,
3H, CH3 of pyrido); 13C NMR (DMSO-d6): d 185.1, 169.4,
165.5, 155.4, 150.1, 144.5, 141.6, 137.5, 136.2, 129.1,
128.4, 126.7, 124.5, 120.5, 119.9, 117.1, 110.2, 108.2,
64.7, 63.1, 17.9; Anal. Calcd. for C23H15Cl3N4O3: C 55.06,
H 3.01, N 11.17. Found: C 55.10, H 3.07, N 11.25.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(2-methoxy-phenyl)azetidine-1-yl)amino}
carbonyl]quinoline (4e) Yield = 62%, m.p. 272–274ꢁC;
IR (KBr) cm-1: 3420 (NH), 2933, 2853 (C–H), 1720
([C=O), 1648 (amide-I), 1530 (amide-II), 1320 (C–N),
1
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(4-methyl phenyl)azetidine-1-yl)amino}
carbonyl]quinoline (4d) Yield = 61%, m.p. 261–263ꢁC;
IR (KBr) cm-1: 3407 (NH), 2927, 2834 (C–H), 1725
([C=O), 1640 (amide-I), 1536 (amide-II), 1319 (C–N),
1243 (amide-III), 790 (C–Cl); 1H NMR (DMSO-d6): d
1246 (amide-III), 1236, 1020 (C–O–C), 789 (C–Cl); H
NMR (DMSO-d6): d 12.55 (d, 1H, NH), 8.80 (s, 1H,
[CONH), 8.68 (s, 1H, H2), 8.30 (d, 1H, H5), 7.80 (d, 1H,
0
H6), 7.41 (s, 1H, H5 of pyrido), 7.45–8.40 (m, 4H, Ar–H),
3.31 (d, 1H, CH of azetidinone), 3.70 (s, 3H, -OCH3), 3.19
(d, 1H, CH-Cl of azetidinone), 2.71 (s, 3H, CH3 of
123

Med Chem Res (2012) 21:2044–2055
2053
Fig. 2 continued
123

2054
Med Chem Res (2012) 21:2044–2055
pyrido);); 13C NMR (DMSO-d6): d 182.6, 171.5, 166.2,
161.5, 154.9, 149.9, 145.2, 141.3, 137.5, 135.7, 130.9,
128.4, 125.9, 124.1, 120.7, 119.1, 117.5, 109.9, 108.2,
64.5, 62.9, 55.4, 18.4; Anal. Calcd. for C24H18Cl2N4O4: C
57.96, H 3.65, N 11.27. Found: C 57.99, H 3.60, N 11.22
(Fig. 2).
(DMSO-d6): d 185.1, 173.2, 166.7, 156.7, 151.9, 150.1,
144.7, 142.5, 138.9, 136.6, 135.1, 131.4, 129.5, 124.7,
120.1, 119.1, 117.7, 110.1, 108.7, 64.7, 62.2, 18.1; Anal.
Calcd. for C23H16Cl2N4O4: C 57.16, H 3.34, N 11.59.
Found: C 57.22, H 3.30, N 11.51.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(2-hydroxy-3-nitro phenyl(azetidine-1-
yl)amino}carbonyl]quinoline (4i) Yield = 55%, m.p.
266-268ꢁC; IR (KBr) cm-1: 3417 (NH), 3236 (O–H),
2920, 2841 (C–H), 1723 ([C=O), 1643 (amide-I), 1530
(amide-II), 1540, 1351 (NO2, sym, asym), 1318 (C–N),
1243 (amide-III), 792 (C–Cl); 1H NMR (DMSO-d6): d
12.58 (d, 1H, NH), 8.82 (s, 1H,[CONH), 8.66 (s, 1H, H2),
8.30 (d, 1H, H5), 7.74 (d, 1H, H6), 7.38 (s, 1H, H5’ of
pyrido), 7.44–8.52 (m, 3H, Ar–H), 4.90 (s, 1H, -OH), 3.33
(d, 1H, CH of azetidinone), 3.20 (d, 1H, CH-Cl of aze-
tidinone), 2.66 (s, 3H, CH3 of pyrido); 13C NMR (DMSO-
d6): d 183.5, 171.7, 166.2, 155.5, 152.2, 150.4, 144.2,
141.7, 138.3, 136.5, 135.1, 131.3, 128.9, 126.6, 125.2,
120.2, 119.7, 117.2, 110.2, 108.5, 65.1, 62.6, 18.9; Anal.
Calcd. for C23H15Cl2N5O6: C 52.29, H 2.86, N 13.26.
Found: C 52.34, H 2.80, N 13.31.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(4-methoxy phenyl)azetidine-1-yl)amino}
carbonyl]quinoline (4f) Yield = 56%, m.p. 271–273ꢁC;
IR (KBr) cm-1: 3418 (NH), 2933, 2850 (C–H), 1721
([C=O), 1647 (amide-I), 1534 (amide-II), 1319 (C–N),
1
1248 (amide-III), 1231, 1030 (C–O–C), 791 (C–Cl); H
NMR (DMSO-d6): d 12.40 (d, 1H, NH), 8.71 (s, 1H,
[CONH), 8.66 (s, 1H, H2), 8.37 (d, 1H, H5), 7.80 (d, 1H,
H6), 7.44 (s, 1H, H5’ of pyrido), 7.35–8.48 (m, 4H, Ar–H),
3.28 (d, 1H, CH of azetidinone), 3.17 (d, 1H, CH–Cl of
azetidinone), 3.74 (s, 3H, –OCH3), 2.66 (s, 3H, CH3 of
pyrido); 13C NMR (DMSO-d6): d 184.1, 170.7, 165.7,
160.1, 155.1, 150.1, 145.4, 140.9, 137.7, 135.2, 131.5,
128.9, 125.2, 120.7, 119.2, 117.1, 110.2, 108.4, 64.6, 62.4,
56.1, 18.1; Anal. Calcd. for C24H18Cl2N4O4: C 57.96, H
3.65, N 11.27. Found: C 58.02, H 3.60, N 11.21.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(3-methoxy-4-hydroxy phenyl)azeti-
dine-1-yl)amino}carbonyl]quinoline (4g) Yield = 62%,
m.p. 276-278ꢁC; IR (KBr) cm-1: 3425 (NH), 3234 (O–H),
2930, 2855 (C–H), 1717 ([C=O), 1640 (amide-I), 1529
(amide-II), 1323 (C–N), 1243 (amide-III), 1225, 1022
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(2-hydroxy-5-nitro phenyl)azetidine-1-
yl)amino}carbonyl]quinoline (4j) Yield = 58%, m.p.
268–270ꢁC; IR (KBr) cm-1: 3420 (NH), 3240 (O–H),
2933, 2841 (C–H), 1723 ([C=O), 1640 (amide-I), 1534
(amide-II), 1538, 1360 (NO2, sym, asym), 1317 (C–N),
1246 (amide-III), 794 (C–Cl); 1H NMR (DMSO-d6): d
12.56 (d, 1H, NH), 8.62 (s, 1H,[CONH), 8.61 (s, 1H, H2),
8.36 (d, 1H, H5), 7.78 (d, 1H, H6), 7.40 (s, 1H, H5’ of
pyrido), 7.40–8.55 (m, 3H, Ar–H), 4.96 (s, 1H, –OH), 3.30
(d, 1H, CH of azetidinone), 3.23 (d, 1H, CH-Cl of
azetidinone), 2.68 (s, 3H, CH3 of pyrido); 13C NMR
(DMSO-d6): d 184.4, 172.6, 166.4, 156.1, 152.7, 150.1,
145.1, 142.4, 138.5, 136.1, 135.1, 131.2, 129.1, 126.9,
125.1, 120.7, 120.1, 117.5, 110.1, 108.7, 64.4, 62.5, 18.5;
Anal. Calcd. for C23H15Cl2N5O6: C 52.29, H 2.86, N 13.26.
Found: C 52.36, H 2.79, N 13.18.
1
(C–O–C), 787 (C–Cl); H NMR (DMSO-d6): d 12.50 (d,
1H, NH), 8.80 (s, 1H, [CONH), 8.62 (s, 1H, H2), 8.31 (d,
1H, H5), 7.76 (d, 1H, H6), 7.38 (s, 1H, H5’ of pyrido), 7.48-
8.40 (m, 3H, Ar–H), 4.95 (s, 1H, -OH), 3.76 (s, 3H,
–OCH3), 3.32 (d, 1H, CH of azetidinone), 3.20 (d, 1H, CH-
Cl of azetidinone), 2.70 (s, 3H, CH3 of pyrido); 13C NMR
(DMSO-d6): d 184.2, 172.4, 166.2, 160.4, 156.4, 151.2,
150.4, 145.3, 141.4, 138.3, 134.9, 131.1, 129.2, 125.1,
120.2, 119.6, 117.2, 110.7, 108.1, 64.2, 62.1, 55.7, 18.9;
Anal. Calcd. for C24H18Cl2N4O5: C 56.15, H 3.53, N 10.91.
Found: C 56.22, H 3.45, N 10.84.
4-Oxo-1,4-dihydro(40-methyl-60-chloropyrido[2,3-h])-3-[N-
{(3-chloro-2-oxo-4-(2-hydroxy phenyl)azetidine-1-yl)amino}
carbonyl]quinoline (4h) Yield = 65%, m.p. 275-277ꢁC;
IR (KBr) cm-1: 3422 (NH), 3240 (O–H), 2910, 2830
(C–H), 1716 ([C=O), 1648 (amide-I), 1527 (amide-II),
1320 (C–N), 1242 (amide-III), 789 (C–Cl); 1H NMR
(DMSO-d6): d 12.42 (d, 1H, NH), 8.76 (s, 1H, [CONH),
8.64 (s, 1H, H2), 8.35 (d, 1H, H5), 7.78 (d, 1H, H6), 7.46 (s,
Acknowledgments The authors wish to thank the Professor and
Head, Department of Chemistry, VNSGU, Surat, for research facili-
ties and D. Rajani, Microcare Laboratory, Surat, for antimicrobial
activity. The authors also thank S.A.I.F., Chandigarh for spectral
analysis.
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