1
632
A. Kathuria et al. / Bioorg. Med. Chem. 20 (2012) 1624–1638
8
64.15 cmꢀ1; 1H NMR (DMSO-d
J = 7.5 Hz, –CH CH ), 2.38 (s, 3H, H-2 ), 2.45 (s, 3H, C-4 CH
CH ), 7.23 (d, 1H, J = 7.8 Hz, H-6), 7.34–7.41 (m,
H, H-5), 7.53 (s, 1H, H-8), 10.05 (s, 1H, NH); C NMR (DMSO-
6
, 300 MHz): d 1.08 (t, 3H,
chromatography using silica gel (100–200 mesh) in methanol/
chloroform (1:99).
0
2
3
3
), 2.58
(
br s, 2H, –CH
2
3
13
1
5.1.6.1. 7-Amino-4-methylquinolin-2(1H)-one (22).
The title
d
6
, 75.5 MHz): d 12.87 and 14.14 (–CH
2
CH
3
and C-4 CH
3
), 20.21
compound (22) was obtained as yellow solid in 65% yield by fol-
lowing the above general procedure. Melting point: 271–272 °C
(Literature value = 271 °C) ; UV (MeOH) kmax: 335 and 352 nm;
0
(
–CH
2 3
CH ), 24.11 (C-2 ), 105.08, 114.89 and 115.35 (C-6, C-8 and
3
4
C-10), 124.70 (C-3), 125.64 (C-5), 141.48 (C-7), 146.13 (C-4),
1
C
0
52.04 (C-9), 160.64 (C-2), 168.93 (C-1 ); HRMS: calcd for
IR (KBr)
m
max: 3423.29, 3307.93 (NH
2
), 2920.17, 1656.23 (NHCO),
+
ꢀ1
14
H15NO
3
[M+H] 246.1085, found 246.1125.
1553.03, 1474.45, 1259.63, 1069.35, 914.48, 839.04, 689.74 cm
;
1
H NMR (DMSO-d
2H, NH ), 5.96 (s, 1H, H-3), 6.37 (s, 1H, H-8), 6.46 (d, 1H,
J = 8.4 Hz, H-6), 7.34 (d, 1H, J = 8.7 Hz, H-5), 11.18 (br s, 1H, NH);
6 3
, 300 MHz): d 2.28 (s, 3H, C-4 CH ), 5.74 (br s,
5
.1.5.3.
7-N-Acetylamino-3-hexyl-4-methylcoumarin (19).
2
The title compound (19) was obtained as light brown colour crys-
tals in 60% yield by following the general procedure. Melting
1
3
6 3
C NMR (DMSO-d , 75.5 MHz): d 18.55 (C-4 CH ), 96.85, 110.48,
point = 160 °C; UV (acetonitrile) kmax: 326 nm; IR (Nujol)
m
max
:
110.55 and 114.67 (C-3, C-6, C-8 and C-10), 125.67 (C-5), 140.81
3
1
297.88 (NH), 3113.01, 2924.71, 1730.94 (COO), 1674.98 (NHCO),
(C-9), 148.13 (C-4), 151.15 (C-7), 162.55 (C-2); ESI MS: calcd for
ꢀ1
1
+
614.95, 1590.20, 1462.44, 1265.21, 1099.24, 860.80 cm
;
H
C H
10 10
N
2
O [M] 174, found 174.
NMR (CDCl
3
, 300 MHz): d 0.88 (br s, 3H, –CH
2
0
(CH
2
)
4
CH
3
), 1.25–
1
.52 (m, 8H, –CH
2
(CH
2
)
4
3
CH ), 2.25 (s, 3H, H-2 ), 2.39 (s, 3H, C-4
5.1.6.2.
7-Amino-3-ethyl-4-methylquinolin-2(1H)-one (23).
CH
3
), 2.64 (t, 2H, J = 7.6 Hz, –CH
2
2
(CH )
4 3
CH ), 7.54 (d, 1H,
The title compound (23) was obtained as yellow solid in 65% yield
J = 8.7 Hz, H-6), 7.64 (s, 1H, H-8), 7.84 (d, 1H, J = 8.4 Hz, H-5),
by following the above general procedure. Melting point: 280–
1
3
8
(
3
.35 (s, 1H, NH); C NMR (CDCl
–CH (CH CH and C-4 CH ), 21.99, 24.09, 26.81, 28.09, 28.59,
1.04 (C-2 , –(CH CH ), 105.09, 114.90 and 115.34 (C-6, C-8 and
3
, 75.5 MHz): d 13.87 and 14.42
281 °C; UV (MeOH)
3459.26, 3363.28 (NH
1417.38, 1333.30, 1263.33, 1058.13, 879.67, 781.94, 690.30 cm
k
max: 336 and 349 nm; IR (KBr)
), 2962.89, 1624.72 (NHCO), 1555.37,
m
max
:
2
2
0
)
4
3
3
2
ꢀ1
2
)
5
3
;
1
C-10), 123.49 (C-3), 125.64 (C-5), 141.17 (C-7), 146.38 (C-4),
H NMR (DMSO-d
2.30 (s, 3H, C-4 CH
2H, NH ), 6.3 (s, 1H, H-8), 6.47 (dd, 1H, J = 1.2 and 8.4 Hz, H-6),
.38 (d, 1H, J = 8.7 Hz, H-5), 11.19 (br s, 1H, NH); C NMR
(DMSO-d , 75.5 MHz): d 13.73 and 14.30 (–CH CH and C-4 CH ),
19.37 (–CH CH ), 96.78, 110.53 and 110.95 (C-6, C-8 and C-10),
125.44 (C-3), 126.17 (C-5), 139.05 (C-9), 141.99 (C-4), 150.05 (C-
6
, 300 MHz): d 1.00 (t, 3H, J = 7.4 Hz, –CH
2 3
CH ),
0
1
C
52.04 (C-9), 160.80 (C-2), 168.92 (C-1 ); HRMS: calcd for
3
), 2.56 (q, 2H, J = 7.4 Hz, –CH CH ), 5.60 (br s,
2
3
+
18
H23NO
3
[M+H] 302.1678, found 302.1746.
2
13
7
5
.1.5.4.
7-N-Acetylamino-3-decyl-4-methylcoumarin (20).
6
2
3
3
The title compound (20) was obtained as light yellow colour crys-
tals in 60% yield by following the general procedure. Melting
point = 148–150 °C; UV (acetonitrile) kmax: 296 and 326 nm; IR
2
3
+
7), 162.14 (C-2). HRMS: calcd for C12
found 225.0998.
14 2
H N O [M+Na] 225.1004,
(
Nujol)
mmax: 3321.03 (NH), 3192.27, 3107.29, 2922.50, 1732.71
(
COO), 1673.95 (NHCO), 1624.77, 1614.53, 1536.35, 1256.52,
ꢀ1
1
1
3
3
7
8
083.00, 871.14 cm
H, –CH (CH CH ), 1.25–1.49 (m, 16H, –CH
H, H-2 ), 2.40 (s, 3H, C-4 CH ), 2.64 (br s, 2H, –CH
.54 (d, 1H, J = 9.3 Hz, H-6), 7.64 (br s, 1H, H-5), 7.82 (s, 1H, H-8),
;
H NMR (CDCl
3
, 300 MHz): d 0.87 (br s,
(CH CH ), 2.25 (s,
(CH CH ),
5.1.6.3. 7-Amino-4-(trifluoromethyl)quinolin-2(1H)-one (24).
The title compound (24) was obtained as yellow solid in 70% yield
by following the above general procedure. Melting point: 274 °C
2
0
2
)
8
3
2
2
)
8
3
3
2
2
)
4
3
3
5
(Literature value = 274 °C) ; UV (MeOH) kmax: 352 nm; IR (KBr)
max: 3365.74, 3239.82 (NH ), 2930.56, 1647.95 (NHCO), 1554.42,
1478.31, 1282.65, 1259.44, 1175.51, 1130.41, 969.84, 868.46,
1
3
.37 (s, 1H, NH); C NMR (CDCl
(CH CH and C-4 CH
3
, 75.5 MHz): d 13.87 and 14.41
), 20.99 (C-2 ), 22.03, 24.10, 26.82,
m
2
0
(
–CH
2
)
2 8
3
3
ꢀ
1
1
2
1
5
8.10, 28.64, 28.81, 28.92, 28.92, 31.23 (–(CH
2
)
9
CH
3
), 105.12,
659.01 cm
NH
), 6.34, 6.37 (2 ꢁ s, 2H, H-3 and H-8), 6.47 (d, 1H, J = 8.4 Hz,
H-6), 7.26 (d, 1H, J = 6.9 Hz, H-5), 11.73 (br s, 1H, NH); C NMR
(DMSO-d , 75.5 MHz): d 96.67, 103.46 (C-6 and C-8), 111.79 and
113.42 (C-3 and C-10), 121.02 (C-5), 125.08 (C-9), 136.53–137.33
–CF ), 142.11 (C-4), 152.07 (C-7), 160.87 (C-2); HRMS: calcd for
;
6
H NMR (DMSO-d , 300 MHz): d 6.06 (br s, 2H,
14.91 and 115.35 (C-6, C-8 and C-10), 123.50 (C-3), 125.58 (C-
), 141.48 (C-7), 146.33 (C-4), 152.06 (C-9), 160.80 (C-2), 168.91
2
13
0
+
(
C-1 ); HRMS: calcd for C22
H31NO
3
[M+H] 358.2337, found
6
3
58.2377.
(
3
+
5
.1.5.5.
7-N-Acetylamino-4-trifluoromethylcoumarin (21).
10 7 3 2
C H F N O [M+H] 229.0583, found 229.0582.
The title compound (21) was obtained as brown colour crystals
in 76% yield by following the general procedure. Melting
5.1.7. General procedure for the synthesis of N-(2-oxo-1,2-
dihydroquinolin-7-yl)acetamides (25–27)
30
point = 178–180 °C (Literature value = 227 °C) ; UV (acetonitrile)
max: 337 nm; IR (KBr) max: 3337.75 (NH), 3071.84, 2925.07,
712.25 (COO), 1621.47 (NHCO), 1586.99, 1515.30, 1240.08,
k
m
7-Aminoquinolin-2(1H)-ones (1.0 g, 22–24) were added to a
solution of acetic anhydride and acetic acid (1:4, 10 ml). The
mixture was refluxed for 6 h and poured on ice. The precipitate
was filtered and washed with water and ether to yield 7-N-acetyl-
1
1
3
ꢀ
1
1
023.68, 858.46 cm
6
; H NMR (DMSO-d , 300 MHz): d 2.14 (s,
0
H, H-2 ), 6.89 (s, 1H, H-3), 7.53–7.67 (m, 2H, H-5 and H-6), 7.91
13
36
(
s, 1H, H-8), 10.54 (br s, 1H, NH); C NMR (DMSO-d
6
, 75.5 MHz):
quinolin-2-ones (25–27).
0
d 24.19 (C-2 ), 105.91, 107.98, 114.20 and 115.77 (C-3, C-6, C-8
and C-10), 123.49 (C-5), 125.35 (d, J = 276.3 Hz, –CF
3
), 138.98–
5.1.7.1. N-(4-Methyl-2-oxo-1,2-dihydroquinolin-7-yl) acetamide
1
2
2
39.82 (q, J = 31.7 Hz, C-4), 143.49 (C-7), 154.72 (C-9) 158.61 (C-
(25).
The title compound (25) was obtained as brown crystals
0
+
), 169.39 (C-1 ); ESI MS: calcd for C12
H
8
F
3
NO
3
[M+H] 272, found
in 60% yield by following the general procedure. Melting point:
3
4
72.
300 °C (Literature value = 300 °C) ; UV (MeOH) kmax: 331 and
47 nm; IR (KBr) max: 3417.52 (NH), 3130.05, 1673.47 (NHC-
OCH ), 1644.18 (NHCO), 1574.00, 1453.17, 1281.91, 1074.76,
3
m
5
2
.1.6. General procedure for the synthesis of 7-aminoquinolin-
(1H)-one (22–24)
3
ꢀ1
1
987.98, 812.16, 683.74 cm
2.09 (s, 3H, H-2 ), 2.38 (s, 3H, C-4 CH
;
6
H NMR (DMSO-d , 300 MHz): d
0
1
,3-Diaminobenzene (1.0 g, 9.3 mmol), was added to substi-
3
), 6.26 (s, 1H, H-3), 7.30 (d,
tuted ethyl acetoacetates (1.2 equiv, 2–3, 6) and the mixture was
refluxed for 20 h. It was then poured on ice (100 g) and the precip-
itate was filtered. The product was obtained through column
1H, J = 8.7 Hz, H-6), 7.62 (d, 1H, J = 8.7 Hz, H-5), 7.99 (s, 1H, H-8),
1
3
10.197, 11.53 (2 ꢁ br s, 2H, 2 ꢁ NHCO);
6
C NMR (DMSO-d ,
0
75.5 MHz): d 18.44 (C-4 CH
3
), 24.18 (C-2 ), 104.37 and 113.48 (C-