Regioselective synthesis of novel 2-chloroquinoline derivatives of 1,4-dihydropyridines

Article abstract of DOI:10.1007/s11164-013-1085-4

Highly regioselective reaction of some substituted 2,4-dichloroquinolines with symmetrical 1,4-dihydropyridines, leading to novel quinoline derivatives of DHPs, has been achieved in the presence of powdered K₂CO ₃, as a mild and efficient base, at moderate temperature. All the synthesized compounds were characterized by use of IR, NMR, and mass spectral data.

Full text of DOI:10.1007/s11164-013-1085-4

Res Chem Intermed
DOI 10.1007/s11164-013-1085-4
Regioselective synthesis of novel 2-chloroquinoline
derivatives of 1,4-dihydropyridines
•
•
•
K. Rajesh P. Iniyavan S. Sarveswari
V. Vijayakumar
Received: 27 November 2012 / Accepted: 25 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract Highly regioselective reaction of some substituted 2,4-dichloroquino-
lines with symmetrical 1,4-dihydropyridines, leading to novel quinoline derivatives
of DHPs, has been achieved in the presence of powdered K2CO3, as a mild and
efficient base, at moderate temperature. All the synthesized compounds were
characterized by use of IR, NMR, and mass spectral data.
Keywords Hantzsch reaction ꢀ 1,4-DHPs ꢀ 2,4-Dichloroquinolines ꢀ
Regioselectivity
Introduction
Synthesis of the quinoline ring system is of major interest in the chemistry of fused
five and six-membered heterocycles, because it has many applications in
pharmaceuticals [1], and is widely present in alkaloids, therapeutics, and synthetic
analogues with interesting activity [2, 3] functioning as antimalarial [4], antiasth-
matic [5], anti-inflammatory [6], and platelet-derived growth factor receptor
tyrosine kinase (PDGF-RTK)-inhibiting agents [7]. Some quinoline derivatives and
their salts and esters can be used in the prophylaxis or treatment of arthritis,
cardiovascular diseases, diabetes, renal failure, and, particularly, eating disorders
Electronic supplementary material The online version of this article (doi:
10.1007/s11164-013-1085-4) contains supplementary material, which is available to authorized users.
K. Rajesh ꢀ P. Iniyavan ꢀ S. Sarveswari ꢀ V. Vijayakumar (&)
Centre for Organic and Medicinal Chemistry, VIT University, Vellore 632 014, Tamil Nadu, India
e-mail: kvpsvijayakumar@gmail.com
K. Rajesh
Department of Chemistry, MS Ramaiah Institute of Technology, Bangalore 560054, Karnataka,
India
123

K. Rajesh et al.
and obesity [8]. 2,4-Disubstituted quinolines with additional substituents at
positions 5 and 8 have anthelmintic properties and are also active against drug-
resistant nematodes [9]. 1,4-Dihydropyridine (1,4-DHP) derivatives are an impor-
tant class of heterocycles, owing to their potential biological activity, and they have
become valuable drugs for heart disease, with useful effects on angina, hypertension
in biological systems, and, particularly, NADH-induced biological redox reactions
[10]. DHPs, for example nifedipine, nitrendipine, and nimodipine, have found
commercial utility as calcium blockers [11, 12]. The presence of ester groups at the
3 and 5-positions on the 1,4-DHP ring is of crucial importance to their
pharmacological effects. As a result, newly synthesized generations of DHPs have
different pharmacological activity, for example anticancer [13], bronchodilating
[14], antidiabetic [15], neurotropic [16], antianginal [17], and other activity [18]. In
addition, several DHPs have anti-platelet aggregator activity [19] and act as
chemical agents in the treatment of Alzheimer’s disease [20] and as a chemo
sensitizer in tumor therapy [21]. With regard to the diversity of quinolines, 2,4-
dichloroquinolines can be key intermediates in the synthesis of 2,4-disubstituted
quinolines by stepwise substitution at the C-4 and C-2 positions, thereby introducing
new C–O bonding between the two heterocyclic nuclei, which leads to a wide range
of new structures either of biological interest or with other interesting properties.
This prompted us to conduct the work reported here, in which one of the chlorine
atoms in 2,4-dichloroquinolines is selectively replaced by 1,4-DHPs, which were
chosen on the basis of our continuous interest both in quinolines [22–29] and in 1,4-
DHPs [30–35], and their applications in medicinal chemistry.
Results and discussion
2,4-Dichloroquinolines 1a–l were synthesized by use of a method reported in the
literature [22]. The melting point, IR, 1H NMR, and mass spectral data of
compounds 1a–l were in accord with literature data (Table 1). To synthesize
molecules with highly functionalized structures, we tried to incorporate quinoline
groups with different substitution and to convert a halogen in the quinoline into a
new heteroatomic molecule, which could result new structures of high pharmaco-
logical importance or other interesting properties; this also provided the opportunity
to study regioselectivity with reference to the 2,4-dichloroquinolines and was also
expected to increase the activity of both the heterocycles chosen. As a consequence
we chose 1,4-dihydropyridines to react with 2,4-dichloroquinolines to yield new
molecular structures.
One-pot three-component reaction of b-keto ester (2 mmol), p-hydroxybenzal-
dehyde (1 mmol), and ammonium acetate (1.1 mmol) in ethanol afforded the
corresponding 1,4-dihydropyridines (1,4-DHPs) 2a (m.p. 228–230 °C) and 2b (m.p.
230–232 °C) in 86 and 83 % yield, respectively [31–34]. Although regioselective
nucleophilic substitution of 2,4-dichloroquinoline by 4-methoxybenzylalcohol in
the presence of sodium hydride [43] is known, it is not cost effective because of use
of the catalyst 15-crown-5, so powdered K2CO3 was used as a mild and efficient
base to achieve regioselective synthesis of 2,4-dichloroquinolines by reaction with
123

Regioselective synthesis of novel 2-chloroquinoline derivatives
Table 1 Synthesis of compounds 1a–l
Compound
R1
R2
R3
Yield (%)
M.p. (°C)a
1a
1b
1c
1d
1e
1f
1g
1h
1i
–H
–H
–H
48
56
51
55
57
34
46
50
42
36
52
40
65–66 (66–67) [36]
92–93 (91–93) [36]
80 [37]b
–CH3
–H
–H
–H
–CH3
–H
–H
–H
–CH3
–H
81–82 (81–82) [38]
167 (168) [39]
–OCH3
–H
–H
–H
–OCH3
–H
133–134 (134) [39]
94–96 (95) [40]
106–108 (107) [41]
134
–F
–H
–H
–Cl
–H
–H
–Br
–H
1j
1k
1l
–F–Cl–H
–CH3–H–CH3
114–116 (114–116) [22]
102–104 (104–106) [38]
131 (131) [42]
2,4-Dichlorobenzo[h]quinoline
a
Literature melting points are given in brackets, with the references in square brackets
b
Although no melting point is available in the literature, synthesis of this compound has been reported
1,4-DHPs at moderate temperature, yielding 1,4-dihydropyridine derivatives of the
quinolines. We chose synthesized 1,4-dihydropyridines 2a and 2b to react with 2,4-
dichloroquinolines 1a–i, in which one of the chlorine atoms was selectively
replaced to yield new molecular structures of possibly high pharmacological
importance or with other interesting properties. Synthesis of target molecules 3a–l
and 4a–l was accomplished by stirring a mixture of substituted 2,4-dichloroquin-
oline 1a–i (1 mol), powdered K2CO3 (1.2 mol), and 1,4-DHP (2a or 2b) (1 mol) in
DMF at 70 °C for 48 h (Scheme 1). The results are listed in Table 2. Progress of the
reaction was monitored by TLC. After completion of the reaction, the reaction
mixture was poured into a beaker containing ice-cold water and stirred well; the
separated solid was filtered to dryness and purified by column chromatography on
silica gel (60–120 mesh) with petroleum ether–ethyl acetate 7:3 as mobile phase,
affording the products 3a–j and 4a–j in the pure form (Table 2). Better results were
observed with powdered K2CO3 than with the granular form, because the larger
surface area of the powdered form enables maximum reactivity of 2,4-dichloro-
quinolines with 1,4-DHPs. All the synthesized compounds were characterized by
1
use of H NMR, 13C NMR, and mass spectral data (detailed data are given in the
Experimental section). Compound 3c has been taken as a representative example of
the substituted 1,4-DHP-quinolines and its spectral characterization is described
below (Fig. 1).
Examination of the proton NMR spectrum of 3c reveals a triplet at d 1.26 ppm
with the coupling constant (J) 7.15 Hz which integrates to six protons and is
ascribed to methyl protons at C-10 and 100. A singlet at d 2.38 ppm integrating to
six protons is ascribed to the methyl protons at C-7 and 70. Another singlet at d
2.56 ppm integrates to three protons and corresponds to methyl protons on the
quinoline ring at C-210. The quartet at d 4.12 ppm with the coupling constant
123

K. Rajesh et al.
OH
OH
R
R
O
O
O
O
O
ethanol
R
R
R
CHO
O
O
Cl
O
NH
O
O
O
O
N
N
H
R3
R2
NH4OAC
DMF
O
O
O
R
2a (R=C2H5)
2b (R=CH3)
K2CO3
R1
Cl
3 (a-j) (R=C2H5)
4 (a-j) (R=CH3)
R1
R2
POCl3
COOH
COOH
R1
R2
+
H2C
5h
NH2
Cl
N
R3
R3
1 (a-j)
Scheme 1 Synthesis of 2-chloroquinoline-substituted 1,4-dihydropyridines
Table 2 Synthesis of compounds 3a–d, 3f–j and 3I; 4a–e, 4g–i, 4k and 4I
Compound
R1
R2
R3
R
Yield (%)
M.p. (°C)
3a
3b
3c
3d
3f
–H
–CH3
–H
–H
–H
–F
–H
–H
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
C2H5
CH3
71
73
67
80
62
70
74
78
67
65
82
85
74
78
72
71
69
75
61
73
172
–H
–H
174–176
180–182
172
–CH3
–H
–H
–CH3
–OCH3
–H
–H
178–180
176
3g
3h
3i
–H
–H
–Br
–F
–Cl
–H
–H
186–188
182
–H
3j
–Cl
–H
184–186
198–200
220–222
196–198
210–212
190–192
222–224
220–222
198–200
226–228
226–228
238–240
3l
2,4-Dichlorobenzo[h]quinoline
4a
4b
4c
4d
4e
4g
4h
4i
–H
–H
–H
–CH3
–H
–H
–H
CH3
–CH3
–H
–H
CH3
–H
–CH3
–H
CH3
–OCH3
–F
–H
CH3
–H
–H
CH3
–H
–Cl
–H
–H
CH3
–Br
–H
CH3
4k
4l
–CH3
–H
–CH3
–CH3
CH3
2,4-dichlorobenzo[h]quinoline
(J) 7.15 Hz integrates to four protons and arises from protons at C-9 and 90. The
singlet at d 5.06 ppm integrating to one proton is ascribed to the proton at C-4 and
the broad singlet at d 5.63 ppm integrating to one proton corresponds to the –NH
proton. The aromatic chemical shift values appeared at 6.48 (s, 1 proton at H-16),
7.03 (d, J = 8.0 Hz, 2 protons at C-13 and 130), 7.42 (d, J = 8.0 Hz, 2 protons at
123

Regioselective synthesis of novel 2-chloroquinoline derivatives
21'
CH3
10
20
21
19
18
9
13
O
O
O
22
14
12
8
6
23
15
16
7
3
N
13'
2
11
4
17
Cl
12'
5
HN
O
10'
8'
1
9'
O
7'
Fig. 1 Diethyl 4-(4-(2-chloro-7-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,
5-dicarboxylate
C-12 and 120), 7.66 (s, 1 proton at C-22), 7.84 (d, J = 8.0 Hz, 1 proton at H-20),
8.16 (d, J = 8.0 Hz, 1 proton at H-19). The chemical shift value at d 8.27 ppm
(s, –OH, 1H) of the reactant molecule 2a was not observed in the target molecule 3c
and a shift in the –NH peak from d 7.60 to d 5.63 ppm was also observed. The
signal at d 6.48 ppm (s, 1H, H-16), which is the characteristic of the H-3 proton of
quinoline, indicates formation of the target molecule 3c.
Examination of the 13C NMR spectrum of 3c reveals chemical shift values at d
14.33 (C-10, 100), 19.62 (C-7, 70), 24.21 (C-210), 39.37 (C-4), 59.84 (C-9, 90),
104.04 (C-3, 5), 105.86 (C-16), 120.30 (C-13, 130), 121.87 (C-18), 126.72 (C-19),
129.07 (C-22), 130.02 (C-12, 120), 130.44 (C-20), 135.61 (C-11), 141.75 (C-21),
144.05 (C-2, 6), 145.87 (C-23), 150.47 (C-17), 151.86 (C-14), 165.82 (C-15),
167.50 (C-8, 80). The m/z value of 3c was 521.1 [M ? 1]. The above discussion of
the spectral data clearly reveals the formation of the desired compound 3c. In a
similar way, the other compounds 3a, b, and d–l (except 3e and 3k) and
4a–l (except 4f and 4j) in this series were also characterized by spectral studies; the
data are included either in the Experimental section or as supplementary data.
Use of K2CO3 under mild experimental conditions greatly suppressed the
formation of disubstituted products and constitutional isomers, hence regioselec-
tivity was increased. A similar reaction, that of 4-chlorobenzenethiol with
2,4-dichloroquinoline at room temperature in the presence triethylamine as mild
base also leads to the 4-substituted product rather than the 2-substituted product
[44]. This is further supported by the observation that use of an acid catalyst in
absolute ethanol alone result in regioselectivity at C2 [45]. Reaction of 1b with
sodium azide at a molar ratio of 1:1 in DMF led regioselectively to 4-azido-2-
chloro-6-methylquinoline (5b) [29], which also indicates the selective reactivity at
C4 of 2,4-dichloroquinolines (Scheme 2). Compound 5b was crystallized from
CHCl3 and then subjected to single-crystal X-ray diffraction study (the ORTEP plot
is given in Fig. 2.).
123

K. Rajesh et al.
N+
N-
N
N
H3C
Cl
N
H3C
Cl
5b
NaN3/DMF
Cl
Cl
H3C
5a
N
N
N
5c
N
Scheme 2 Synthesis of 4-azido-2-chloro-6-methylquinoline (5b)
Fig. 2 ORTEP plot of 4-azido-2-chloro-6-methylquinoline (5b)
Kinetic studies reported in the literature also indicate that the chlorine at C4 of
dichloroquinolines is approximately twice as reactive toward nucleophiles as that at
C2, and that predominately an addition–elimination process occurs [46, 47]. From
these results we reach the conclusion that reaction of 2,4-dichloroquinolines and
1,4-DHPs leads to attack on C-4 rather than C-2 under the mild experimental
conditions used.
123

Regioselective synthesis of novel 2-chloroquinoline derivatives
Experimental
Solvents and reagents were commercially sourced and used without further
purification. Melting points were recorded on an Elchem microprocessor-based DT
apparatus in open capillary tubes and are uncorrected. IR spectra were obtained on
an Avatar-330 FTIR spectrophotometer (Thermo Nicolet) using KBr pellets; only
noteworthy absorption (reciprocal centimeters) is listed. NMR spectra were
recorded on Bruker 200, 300, and 500-MHz spectrometers with TMS as internal
standard (chemical shifts d in ppm). Mass spectra were obtained by HRMS and LC–
MS with an Agilent 1200 series LC and Micromass zQ spectrometer. TLC was
performed on silica gel preparative plates (S.D. Fine-Chem) and spots were
visualized in an iodine chamber. Column chromatography was performed on silica
gel (60–120 mesh).
General procedure for synthesis of diethyl 4-(4-(2-chloroquinolin-4-
yloxy)phenyl)-2,6-dimethyl-1,4-dihydro pyridine-3,5-dicarboxylate
(3a–j) (except 3e and 3k)
A mixture of substituted 2,4-dichloroquinoline 1a–j (1 mol), powdered K2CO3
(1.2 mol), and diethyl 4-(4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate (2a) (1 mol) in DMF was stirred at 70 °C for 48 h. Progress of the
reaction was monitored by TLC. After completion of reaction, the reaction mixture
was poured into a beaker containing ice cold water and stirred well. The separated
solid was filtered to dryness and purified by column chromatography on silica gel
(60–120 mesh) with pet. ether–ethyl acetate 7:3 as mobile phase, which afforded the
products 3a–j in the pure form.
Diethyl 4-(4-(2-chloroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (3a)
Yield: 71 %. m.p.: 172 °C; IR (KBr, cm-1): 3,348 (–NH stretching), 2,978
(aromatic –CH stretching), 1,696 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.25 (t,
J = 6.8 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 4.15 (q,
J = 6.8 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.62 (bs, 1 proton at
–NH), 6.50 (s, 1 proton at C-16), 7.03 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130),
7.41 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.57 (t, J = 7.0 Hz, 1 aryl proton
at C-20), 7.76 (t, J = 7.0 Hz, 1 aryl proton at C-21), 7.98 (d, J = 8.0 Hz, 1 aryl
proton at C-22), 8.30 (d, J = 8.0 Hz, 1 aryl proton at C-19); MS: m/z Calcd. For
C28H27ClN2O5: 506.1; found. 507.0 [M ? 1]; Anal Calcd for C28H27ClN2O5: C
66.33, H 5.37, N 5.53; Found: C 66.15, H 5.43, N 5.41.
Diethyl 4-(4-(2-chloro-6-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine -3,5-dicarboxylate (3b)
Yield: 73 %. m.p.: 174–176 °C; IR (KBr, cm-1): 3,347 (–NH stretching), 2,977
1
(aromatic –CH stretching), 1,694 (–C=O); H NMR (200 MHz, CDCl3) dH: 1.25
123

K. Rajesh et al.
(t, J = 6.9 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 2.55 (s, 3
protons at C-200), 4.15 (q, J = 6.9 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at
C-4), 5.63 (bs, 1 proton at –NH), 6.47 (s, 1 proton at C-16), 7.02 (d, J = 8.0 Hz, 2
aryl protons at C-13, 130), 7.40 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.58 (d,
J = 9.0 Hz, 1 aryl proton at C-21), 7.87 (d, J = 9.0 Hz, 1 aryl proton at C-22), 8.06
(s, 1 aryl proton at C-19); LC–MS: m/z Calcd. For C29H29ClN2O5: 520.1; found.
521.2 [M ? 1]; Anal Calcd for C29H29ClN2O5: C 66.85, H 5.61, N 5.38; Found: C
67.53, H 5.50, N 5.33.
Diethyl 4-(4-(2-chloro-7-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (3c)
Yield: 67 %. m.p.: 180–182 °C; IR (KBr, cm-1): 3,305 (–NH stretching), 2,980
(aromatic –CH stretching), 1,695 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.26 (t,
J = 7.2 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 2.56 (s, 3 protons
at C-210), 4.12 (q, J = 7.2 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.63
(s, 1 proton at –NH), 6.48 (s, 1 proton at C-16), 7.03 (d, J = 8.0 Hz, 2 aryl protons
at C-13, 130), 7.41 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.66 (s, 1 aryl proton
at C-22), 7.84 (d, J = 8.0 Hz, 1 aryl proton at C-20), 8.16 (d, J = 8.0 Hz, 1 aryl
proton at C-19); 13C NMR (125 MHz, CDCl3) dC: 14.33 (C-10, 100), 19.62 (C-7, 70),
24.21 (C-210), 39.37 (C-4), 59.84 (C-9, 90), 104.04 (C-3, 5), 105.86 (C-16), 120.30
(C-13, 130), 121.87 (C-18), 126.72 (C-19), 129.07 (C-22), 130.02 (C-12, 120),
130.44 (C-20), 135.61 (C-11), 141.75 (C-21), 144.05 (C-2, 6), 145.87 (C-23),
150.47 (C-17), 151.86 (C-14), 165.82 (C-15), 167.50 (C-8, 80); MS: m/z Calcd. For
C29H29ClN2O5: 520.1; found. 521.1 [M ? 1]; Anal Calcd for C29H29ClN2O5: C
66.85, H 5.61, N 5.38; Found: C 66.73, H 5.53, N 5.29.
Diethyl 4-(4-(2-chloro-8-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (3d)
Yield: 80 %. m.p.: 172 °C; IR (KBr, cm-1): 3,348 (–NH stretching), 2,977
(aromatic –CH stretching), 1,695 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.26 (t,
J = 7.2 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 2.62 (s, 3 protons
at C-220), 4.12 (q, J = 7.2 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.63
(s, 1 proton at –NH), 6.49 (s, 1 proton at C-16), 7.12 (d, J = 8.0 Hz, 2 aryl protons
at C-13, 130), 7.42 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.49 (t, J = 6.0 Hz,
1 aryl proton at C-20), 7.63 (d, J = 6.0 Hz, 1 aryl proton at C-21), 8.12 (d,
J = 8.0 Hz, 1 aryl proton at C-19); HRMS: m/z Calcd. For C29H29ClN2O5:
520.1765; found. 520.1758 [M?].
Diethyl 4-(4-(2-chloro-8-methoxyquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (3f)
Yield: 62 %. m.p.: 178–180 °C; IR (KBr, cm-1): 3,329 (–NH stretching), 2976
(aromatic –CH stretching), 1,686 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.26 (t,
J = 7.2 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 4.06 (s, 3 protons
123

Regioselective synthesis of novel 2-chloroquinoline derivatives
at C-220), 4.13 (q, J = 7.2 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.71
(s, 1 proton at –NH), 6.54 (s, 1 proton at C-16), 7.03 (d, J = 8.0 Hz, 2 aryl protons
at C-13, 130), 7.13 (d, J = 8.0 Hz, 1 aryl proton at C-21), 7.41 (d, J = 8.0 Hz, 2 aryl
protons at C-12, 120), 7.49 (t, J = 7.0 Hz, 1 aryl proton at C-20), 7.86 (d,
J = 8.0 Hz, 1 aryl proton at C-19); 13C NMR (125 MHz, CDCl3) dC: 14.32 (C-10,
100), 19.53 (C-7, 70), 39.33 (C-4), 56.02 (C-220), 59.80 (C-9, 90), 103.90 (C-3, 5),
105.50 (C-16), 109.60 (C-21), 113.55 (C-19), 120.33 (C-13,130), 121.57 (C-18),
126.52 (C-20), 130.04 (C-12, 120), 140.37 (C-11), 144.22 (C-2, 6), 146.12 (C-23),
150.50 (C-17), 151.77 (C-14), 154.50 (C-22), 163.53 (C-15), 167.53 (C-8, 80); MS:
m/z Calcd. For C29H29ClN2O6: 536.1; found. 537.1 [M ? 1]; Anal Calcd for
C29H29ClN2O6: C 64.86, H 5.44, N 5.22; Found: C 65.01, H 5.54, N 5.17.
Diethyl 4-(4-(2-chloro-6-quinolines-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (3g)
Yield: 70 %. m.p.: 176 °C; IR (KBr, cm-1): 3,350 (–NH stretching), 2,979
(aromatic –CH stretching), 1,693 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.25 (t,
J = 7.2 Hz, 6 protons at C-10, 100), 2.39 (s, 6 protons at C-7, 70), 4.14 (q,
J = 7.2 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.63 (s, 1 proton at
–NH), 6.52 (s, 1 proton at C-16), 7.02 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130),
7.41 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.52 (t, 1 aryl proton at C-21),
7.87–8.02 (m, 2 aryl protons at C-19, 22); 13C NMR (125 MHz, CDCl3) dC: 14.33
(C-10, 100), 19.67 (C-7, 70), 39.41 (C-4), 59.85 (C-9, 90), 104.06 (C-3, 5), 105.18
(C-16), 106.16 (C-19, J2C-F = 23.75 Hz), 120.30 (C-13, 130), 120.87 (C-21,
J2C-F = 23.75 Hz), 121.21 (C-18, JC3 -F = 12.5 Hz), 130.15 (C-12, 120), 130.66
(C-22, J3C-F = 10 Hz), 143.98 (C-2, 6), 145.62 (C-23), 146.26 (C-11), 150.61
(C-15), 151.53 (C-17), 159.47 (C-14), 162.26 (C-20, J1C-F = 206.25 Hz), 167.45
(C-8, 80); HRMS: m/z Calcd. For C28H26ClFN2O5: 524.1514; found. 524.1527 [M?].
Diethyl 4-(4-(2,7-dichloroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-dihydro
pyridine-3,5-dicarboxylate (3h)
Yield: 74 %. m.p.: 186–188 °C; IR (KBr, cm-1): 3,347 (–NH stretching), 2,978
(aromatic –CH stretching), 1,694 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.25 (t,
J = 7.5 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 4.12 (q,
J = 7.5 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.63 (s, 1 proton at
–NH), 6.48 (s, 1 proton at C-16), 7.01 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130),
7.40 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.67 (d, J = 8.0 Hz, 1 aryl proton
at C-20), 7.90 (d, J = 8.0 Hz, 1 aryl proton at C-19), 8.27 (s, 1 aryl proton at C-22);
13C NMR (125 MHz, CDCl3) dC: 14.33 (C-10, 100), 19.68 (C-7, 70), 39.42 (C-4),
59.85 (C-9, 90), 104.07 (C-3, 5), 105.36 (C-16), 120.28 (C-13, 130), 121.15 (C-18),
121.28 (C-19), 129.79 (C-20), 130.17 (C-12, 120), 132.00 (C-21), 132.37 (C-22),
143.96 (C-2, 6), 146.32 (C-11), 147.02 (C-23), 151.45 (C-17), 151.63 (C-14),
162.70 (C-15), 167.44 (C-8, 80); MS: m/z Calcd. For C28H26Cl2N2O5: 540.1; found.
541.1 [M ? 1]; Anal Calcd for C28H26Cl2N2O5: C 62.11, H 4.84, N 5.17; Found: C
62.60, H 4.75, N 5.08.
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Diethyl 4-(4-(6-bromo-2-chloroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (3i)
Yield: 78 %. m.p.: 182 °C; IR (KBr, cm-1): 3,349 (–NH stretching), 2,978
1
(aromatic –CH stretching), 1696 (–C=O); H NMR (200 MHz, CDCl3) dH: 1.25 (t,
J = 7.5 Hz, 6 protons at C-10, 100), 2.39 (s, 6 protons at C-7, 70), 4.12 (q,
J = 7.5 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.60 (s, 1 proton at
–NH), 6.51 (s, 1 proton at C-16), 7.02 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130),
7.41 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.83–7.88 (m, 2 aryl protons at
C-21, 22), 8.46 (s, 1 aryl proton at C-19); HRMS: m/z Calcd. For C28H26BrClN2O5:
584.0714; found. 584.0726 [M?], 586.0699 [M ? 2].
Diethyl 4-(4-(2,7-dichloro-6-fluoroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (3j)
Yield: 67 %. m.p.: 184–186 °C; IR (KBr, cm-1): 3,347 (–NH stretching), 2,970
(aromatic –CH stretching), 1,697 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.26 (t,
J = 7.5 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 4.12 (q,
J = 7.5 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.64 (s, 1 proton at
–NH), 6.56 (d, J = 22 Hz, 1 proton at C-16, splitting experienced due to F at C-20),
7.02 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130), 7.42 (d, J = 8.0 Hz, 2 aryl protons
at C-12, 120), 7.59 (d, J = 8.0 Hz, 1 aryl proton at C-22), 7.87-8.07 (m, 1 aryl
proton at C-19); MS: m/z Calcd. For C28H25Cl2FN2O5: 558.1; found. 559.0
[M ? 1]; Anal Calcd for C28H25Cl2FN2O5: C 60.12, H 4.50, N 5.01; Found: C
59.62, H 4.39, N 4.86.
Diethyl 4-(4-(2-chlorobenzo[h]quinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (3l)
Yield: 65 %. m.p.: 198–200 °C; IR (KBr, cm-1): 3,340 (–NH stretching), 2,965
(aromatic –CH stretching), 1,697 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 1.26 (t,
J = 7.5 Hz, 6 protons at C-10, 100), 2.38 (s, 6 protons at C-7, 70), 4.13 (q,
J = 7.5 Hz, 4 protons at C-9, 90), 5.06 (s, 1 proton at C-4), 5.62 (s, 1 proton at
–NH), 6.68 (s, 1 proton at C-16), 7.05 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130),
7.41 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.69-7.95 (m, 4 aryl protons at
C-20, 210, 2100, 2200), 8.18 (d, J = 8.0 Hz, 1 aryl proton at C-19), 9.19 (d,
J = 8.0 Hz, 1 aryl proton at C-220); 13C NMR (125 MHz, CDCl3) dC: 14.30 (C-10,
100), 19.70 (C-7, 70), 39.43 (C-4), 59.85 (C-9, 90), 104.11 (C-3, 5), 106.39 (C-16),
117.57 (C-18), 120.29 (C-13, 130), 120.73 (C-19), 125.05 (C-220), 127.23 (C-210),
127.78 (C-2100), 128.73 (C-2200), 130.07(C-12, 120), 130.28 (C-20), 130.61 (C-22),
134.25 (C-11), 143.97 (C-2, 6), 145.90 (C-23), 147.48 (C-21), 150.41 (C-17),
152.10 (C-14), 163.35 (C-15), 167.49 (C-8, 80); MS: m/z Calcd. For C32H29ClN2O5:
556.1; found. 557.1 [M ? 1]; Anal Calcd for C32H29ClN2O5: C 69.00, H 5.25, N
5.03; Found: C 69.73, H 5.17, N 5.16.
123

Regioselective synthesis of novel 2-chloroquinoline derivatives
General procedure for synthesis of dimethyl 4-(4-(2-chloroquinolin-4-
yloxy)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
(4a–j) (except 4f and 4j)
A mixture of substituted 2,4-dichloroquinoline 1a–j (1 mol), powdered K2CO3
(1.2 mol), and dimethyl 4-(4-hydroxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (2b) (1 mol) in DMF was stirred at 70 °C for 48 h. Progress of
the reaction was monitored by TLC. After the completion of reaction, the reaction
mixture was poured into a beaker containing ice cold water and stirred well. The
separated solid was filtered to dryness and purified by column chromatography on
silica gel (60–120 mesh) with pet. ether–ethyl acetate 7:3 as mobile phase, which
afforded the products 4a–j in the pure form.
Dimethyl 4-(4-(2-chloroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4a)
Yield: 82 %. m.p.: 220–222 °C; IR (KBr, cm-1): 3,345 (–NH stretching), 2,947
(aromatic –CH stretching), 1,697 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 2.38 (s,
6 protons at C-7, 70), 3.70 (s, 6 protons at C-9, 90), 5.08 (s, 1 proton at C-4), 5.73 (s,
1 proton at –NH), 6.55 (s, 1 proton at C-16), 7.02 (d, J = 8.0 Hz, 2 aryl protons at
C-13, 130), 7.40 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.57 (t, J = 7.5 Hz, 1
aryl proton at C-20), 7.78 (t, J = 8.0 Hz, 1 aryl proton at C-21), 7.98 (d,
J = 7.5 Hz, 1 aryl proton at C-22), 8.24 (d, J = 8.0 Hz, 1 aryl proton at C-19); 13
C
NMR (125 MHz, CDCl3) dC: 19.64 (C-7, 70), 39.01 (C-4), 51.09 (C-9, 90), 103.78
(C-3, 5), 104.83 (C-16), 117.61 (C-18), 120.49 (C-13, 130), 122.04 (C-19), 126.36
(C-20), 128.17 (C-22), 129.69 (C-12, 120), 131.16 (C-21), 144.41 (C-2, 6), 145.65
(C-11), 148.68 (C-23), 151.29 (C-17), 151.86 (C-14), 163.45 (C-15), 167.91 (C-8,
80); HRMS: m/z Calcd. For C26H23ClN2O5: 478.1295; found. 478.1286 [M?].
Dimethyl 4-(4-(2-chloro-6-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4b)
Yield: 85 %. m.p.: 196–198 °C; IR (KBr, cm-1): 3,337 (–NH stretching), 2,946
(aromatic –CH stretching), 1,696 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 2.38 (s,
6 protons at C-7, 70), 2.59 (s, 3 protons at C-200), 3.69 (s, 6 protons at C-9, 90), 5.01
(s, 1 proton at C-4), 5.69 (s, 1 proton at –NH), 6.48 (s, 1 proton at C-16), 7.01 (d,
J = 8.0 Hz, 2 aryl protons at C-13, 130), 7.33 (d, J = 8.0 Hz, 2 aryl protons at C-12,
120), 7.55 (d, J = 8.0 Hz, 1 aryl proton at C-21), 7.84 (d, J = 8.0 Hz, 1 aryl proton
at C-22), 8.01 (s, 1 aryl proton at C-19); HRMS: m/z Calcd. For C27H25ClN2O5:
492.1452; found. 492.1465 [M?].
Dimethyl 4-(4-(2-chloro-7-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4c)
Yield: 74 %. m.p.: 210–212 °C; IR (KBr, cm-1): 3,355 (–NH stretching), 2,941
1
(aromatic –CH stretching), 1,695 (–C=O); H NMR (200 MHz, CDCl3) dH: 2.38
123

K. Rajesh et al.
(s, 6 protons at C-7, 70), 2.56 (s, 3 protons at C-210), 3.70 (s, 6 protons at C-9, 90),
5.05 (s, 1 proton at C-4), 5.73 (s, 1 proton at –NH), 6.49 (s, 1 proton at C-16), 7.07
(d, J = 6.0 Hz, 2 aryl protons at C-13, 130), 7.40 (d, J = 6.0 Hz, 2 aryl protons at
C-12, 120), 7.66 (s, 1 aryl proton at C-22), 7.82 (d, J = 8.0 Hz, 1 aryl proton at
C-20), 8.17 (d, J = 8.0 Hz, 1 aryl proton at C-19); MS: m/z Calcd. For
C27H25ClN2O5: 492.1; found. 493.1 [M ? 1]; Anal Calcd for C27H25ClN2O5: C
65.79, H 5.11, N 5.68; Found: C 66.46, H 4.98, N 5.58.
Dimethyl 4-(4-(2-chloro-8-methylquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4d)
Yield: 78 %. m.p.: 190–192 °C; IR (KBr, cm-1): 3,358 (–NH stretching), 2,940
(aromatic –CH stretching), 1,696 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 2.38 (s,
6 protons at C-7, 70), 2.57 (s, 3 protons at C-220), 3.70 (s, 6 protons at C-9, 90), 5.08
(s, 1 proton at C-4), 5.72 (s, 1 proton at –NH), 6.53 (s, 1 proton at C-16), 7.03 (d,
J = 8.0 Hz, 2 aryl protons at C-13, 130), 7.41 (d, J = 8.0 Hz, 2 aryl protons at C-12,
120), 7.62 (t, J = 8.0 Hz, 1 aryl proton at C-20), 7.85 (d, J = 8.0 Hz, 1 aryl proton
at C-21), 8.22 (d, J = 8.0 Hz, 1 aryl proton at C-19); 13C NMR (125 MHz, CDCl3)
dC: 18.15 (C-220), 19.66 (C-7, 70), 38.98 (C-4), 51.09 (C-9, 90), 103.83 (C-3, 5),
104.75 (C-16), 117.14 (C-18), 119.76 (C-19), 120.47 (C-13, 130), 125.99 (C-20),
129.62 (C-12, 120), 131.31 (C-21), 136.34 (C-22), 144.34 (C-2, 6), 145.42 (C-11),
147.91 (C-17), 150.14 (C-23), 152.09 (C-14), 163.52 (C-15), 167.90 (C-8, 80); MS:
m/z Calcd. For C27H25ClN2O5: 492.1; found. 493.1 [M ? 1]; Anal Calcd for
C27H25ClN2O5: C 65.79, H 5.11, N 5.68; Found: C 65.67, H 4.98, N 5.60.
Dimethyl 4-(4-(2-chloro-6-methoxyquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4e)
Yield: 72 %. m.p.: 222–224 °C; IR (KBr, cm-1): 3,337 (–NH stretching), 2925
(aromatic –CH stretching), 1,695 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 2.39 (s,
6 protons at C-7, 70), 3.70 (s, 6 protons at C-9, 90), 3.94 (s, 3 protons at C-200), 5.08
(s, 1 proton at C-4), 5.72 (s, 1 proton at –NH), 6.53 (s, 1 proton at C-16), 7.04 (d,
J = 8.0 Hz, 2 aryl protons at C-13, 130), 7.39 (d, J = 10 Hz, 2 aryl protons at C-12,
120), 7.51–7.53 (m, 1 aryl proton at C-21), 7.86–7.96 (m, 2 aryl protons at C-19, 22);
13C NMR (125 MHz, CDCl3) dC: 19.66 (C-7, 70), 39.02 (C-4), 51.08 (C-9, 90), 55.66
(C-200), 99.94 (C-19), 103.83 (C-3, 5), 105.15 (C-16), 118.54 (C-18), 120.46 (C-13,
130), 121.26 (C-21), 123.51 (C-22), 129.68 (C-12, 120), 144.33 (C-2, 6), 144.53
(C-11), 145.54 (C-23), 148.54 (C-17), 152.00 (C-14), 157.90 (C-20), 162.41 (C-15),
167.89 (C-8, 80); MS: m/z Calcd. For C27H25ClN2O6: 508.1; found. 509.1 [M ? 1];
Anal Calcd for C27H25ClN2O6: C 63.72, H 4.95, N 5.50; Found: C 62.93, H 5.08, N
5.42.
123

Regioselective synthesis of novel 2-chloroquinoline derivatives
Dimethyl 4-(4-(2-chloro-6-fluoroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4g)
Yield: 71 %. m.p.: 220–222 °C; IR (KBr, cm-1): 3,340 (–NH stretching), 2949
(aromatic –CH stretching), 1,696 (–C=O); 1H NMR (200 MHz, CDCl3) dH: 2.39 (s,
6 protons at C-7, 70), 3.70 (s, 6 protons at C-9, 90), 5.08 (s, 1 proton at C-4), 5.72 (s,
1 proton at –NH), 6.56 (s, 1 proton at C-16), 7.03 (d, J = 9.0 Hz, 2 aryl protons at
C-13, 130), 7.39 (d, J = 9 Hz, 2 aryl protons at C-12, 120), 7.45-7.50 (m, 1 aryl
proton at C-21), 7.86-8.02 (m, 2 aryl protons at C-19, 22); 13C NMR (125 MHz,
CDCl3) dC: 19.65 (C-7, 70), 39.02 (C-4), 51.10 (C-9, 90), 103.77 (C-3, 5), 105.24
(C-16), 106.16 (C-19, J2C-F = 23.75 Hz), 120.43 (C-13, 130), 121.07 (C-21, JC-
2
= 25 Hz), 121.25 (C-18, J3C-F = 10 Hz), 129.75 (C-12, 120), 130.66 (C-22, JC-
= 8.75 Hz), 144.40 (C-2, 6), 145.62 (C-23), 145.83 (C-11), 150.60 (C-15),
F
3
F
151.62 (C-17), 159.47 (C-14), 162.20 (C-20, J1C-F = 190 Hz), 167.89 (C-8, 80); LC–
MS: m/z Calcd. For C26H22ClFN2O5: 496.1; found. 497.0 [M ? 1]; Anal Calcd for
C26H22ClFN2O5: C 62.84, H 4.46, N 5.64; Found: C 63.44, H 4.38, N 5.47.
Dimethyl 4-(4-(2,7-dichloroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate (4h)
Yield: 69 %. m.p.: 198–200 °C; IR (KBr, cm-1): 3,356 (–NH stretching), 2947
1
(aromatic –CH stretching), 1730, 1695 (–C=O); H-NMR (200 MHz, CDCl3) dH:
2.39 (s, 6 protons at C-7, 70), 3.70 (s, 6 protons at C-9, 90), 5.08 (s, 1 proton at C-4),
5.72 (bs, 1 proton at –NH), 6.55 (s, 1 proton at C-16), 7.02 (d, J = 8 Hz, 2 aryl
protons at C-13, 130), 7.39 (d, J = 8 Hz, 2 aryl protons at C-12, 120), 7.69 (d,
J = 8 Hz, 1 aryl proton at C-20), 7.92 (d, J = 8 Hz, 1 aryl proton at C-19), 8.26 (s,
1 aryl proton at C-22); HRMS: m/z Calcd. For C26H22Cl2N2O5: 512.0906; found.
512.0914 [M?].
Dimethyl 4-(4-(6-bromo-2-chloroquinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4i)
Yield: 75 %. m.p.: 226–228 °C; IR (KBr, cm-1): 3,339 (–NH stretching), 2,940
1
(aromatic –CH stretching), 1696 (–C=O); H NMR (200 MHz, CDCl3) dH: 2.38 (s,
6 protons at C-7, 70), 3.70 (s, 6 protons at C-9, 90), 5.08 (s, 1 proton at C-4), 5.72 (s,
1 proton at –NH), 6.54 (s, 1 proton at C-16), 7.04 (d, J = 8.0 Hz, 2 aryl protons at
C-13, 130), 7.43 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.82-7.85 (m, 2 aryl
protons at C-21, 22), 8.36 (s, 1 aryl proton at C-19); 13C NMR (125 MHz, CDCl3)
dC: 19.73 (C-7, 70), 39.09 (C-4), 59.16 (C-9, 90), 103.79 (C-3, 5), 105.37 (C-16),
116.32 (C-18), 120.35 (C-20), 120.43 (C-13, 130), 121.62 (C-19), 124.57 (C-22),
129.80 (C-12, 120), 134.60 (C-21), 144.37 (C-2, 6), 145.90 (C-11), 147.25 (C-23),
151.51 (C-17), 151.76 (C-14), 162.47 (C-15), 167.88 (C-8, 80); MS: m/z Calcd. For
C26H22BrClN2O5: 556.0; found. 557.0 [M ? 1], 559 [M ? 3]. Anal Calcd for
C26H22BrClN2O5: C 55.98, H 3.98, N 5.02; Found: C 55.57, H 3.90, N 4.89.
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K. Rajesh et al.
Dimethyl 4-(4-(2-chloro-6,8-dimethylquinolin-4-yloxy)phenyl)-2,6-dimethyl-
1,4-dihydro pyridine-3,5-dicarboxylate (4k)
Yield: 61 %. m.p.: 226–228 °C; IR (KBr, cm-1): 3,349 (–NH stretching), 2,948
1
(aromatic –CH stretching), 1695 (–C=O); H NMR (200 MHz, CDCl3) dH: 2.39 (s,
6 protons at C-7, 70), 2.50 (s, 3 protons at C-220), 2.72 (s, 3 protons at C-200), 3.70 (s,
6 protons at C-9, 90), 5.07 (s, 1 proton at C-4), 5.70 (s, 1 proton at –NH), 6.50 (s, 1
proton at C-16), 7.01 (d, J = 8.0 Hz, 2 aryl protons at C-13, 130), 7.36 (d,
J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.45 (s, 1 aryl proton at C-21), 7.90 (s, 1
13
aryl proton at C-19); C NMR (125 MHz, CDCl3) dC: 18.03 (C-220), 19.66 (C-7,
70), 21.65 (C-200), 38.97 (C-4), 51.08 (C-9, 90), 103.84 (C-3, 5), 104.83 (C-16),
116.88 (C-18), 118.62 (C-19), 120.40 (C-13, 130), 129.59 (C-12, 120), 133.48 (C-
21), 135.93 (C-22), 135.96 (C-20), 144.31 (C-2, 6), 145.30 (C-11), 146.48 (C-17),
149.16 (C-14), 152.21 (C-23), 162.99 (C-15), 167.91 (C-8, 80); MS: m/z Calcd. For
C28H27ClN2O5: 506.1; found. 507.0 [M ? 1]; Anal Calcd for C28H27ClN2O5: C
66.33, H 5.37, N 5.53; Found: C 67.05, H 5.45, N 5.39.
Dimethyl 4-(4-(2-chlorobenzo[h]quinolin-4-yloxy)phenyl)-2,6-dimethyl-1,4-
dihydro pyridine-3,5-dicarboxylate (4l)
Yield: 73 %. m.p.: 238–240 °C; IR (KBr, cm-1): 3,354 (–NH stretching), 2946
1
(aromatic –CH stretching), 1695 (–C=O); H NMR (200 MHz, CDCl3) dH: 2.39 (s,
6 protons at C-7, 70), 3.70 (s, 6 protons at C-9, 90), 5.08 (s, 1 proton at C-4), 5.73 (bs,
1 proton at –NH), 6.72 (s, 1 proton at C-16), 7.05 (d, J = 8.0 Hz, 2 aryl protons at
C-13, 130), 7.38 (d, J = 8.0 Hz, 2 aryl protons at C-12, 120), 7.69-7.74 (m, 2 aryl
protons at C-2200, 2100), 7.83–7.90 (m, 2 aryl protons at C-20, 210), 8.16 (d,
J = 8.0 Hz, 1 aryl proton at C-19), 9.18 (d, J = 8.0 Hz, 1 aryl proton at C-220); 13C
NMR (125 MHz, CDCl3) dC: 19.66 (C-7, 70), 39.00 (C-4), 51.10 (C-9, 90), 103.84
(C-3, 5), 106.44 (C-16), 117.62 (C-18), 118.60 (C-19), 120.40 (C-13, 130), 125.02
(C-220), 127.17 (C-210), 127.29 (C-2100), 127.75 (C-2200), 128.73 (C-20), 129.67
(C-12, 120), 130.28 (C-22), 134.25 (C-21), 144.35 (C-2, 6), 145.44 (C-11), 147.50
(C-17), 150.39 (C-23), 152.21 (C-14), 163.22 (C-15), 167.92 (C-8, 80); MS: m/
z Calcd. For C30H25ClN2O5: 528.1; found. 529.1 [M ? 1]; Anal Calcd for
C30H25ClN2O5: C 68.12, H 4.76, N 5.30; Found: C 67.94, H 4.93, N 5.22.
Conclusion
2-Chloroquinoline derivatives of 1,4-dihydropyridines have been synthesized with
high regioselectivity by reaction of 2,4-dichloroquinolines and 1,4-DHPs in
presence of powdered K2CO3 as base, in DMF, at moderate temperature.
Acknowledgments We are grateful for financial support from the Department of Science and
Technology, Government of India (grant no. SR/FTP/CS-108/2006) and VIT University, Vellore, for
providing research facilities.
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Regioselective synthesis of novel 2-chloroquinoline derivatives
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