DOI: 10.3109/14756366.2015.1016511
Novel 3-substituted amino-4-hydroxylcoumarin derivatives
5
2
830 (CH), 1690, 1640 (C ¼ O), 1599, 1538, 1493, 1455 (C ¼ C). (2R,3R)-4-(4-(4-fluorophenyl)piperazin-1-yl)-2,3-dihydroxy-N-
1
H NMR (300 MHz, DMSO-d ) d 13.21 (s, 1H, coumarin-OH), (4-hydroxy-6-methylcoumarin-3-yl)-4-oxobutanamide (6f).
6
2
D
0
9
2
7
.02 (s, 1H, NH), 7.92 (d, J ¼ 7.5 Hz, 1H, coumarin-5-H), 7.79 (d, Yellow solid; yield 15%; ½ꢁꢂ ¼ +55 (c ¼ 1, CH OH). mp 246–
3
ꢁ
H, coumarin-7,8-H), 7.54 (t, J ¼ 7.5 Hz, 1H, coumarin-6-H), 247 C; IR (KBr disk): ꢀ 3493 (OH), 3381, 3326 (NH), 2949,
.35 (d, J ¼ 7.9 Hz, 2H, benzene-3,5-H), 7.09 (d, J ¼ 8.2 Hz, 2H, 2835 (CH), 1690, 1640 (C ¼ O), 1588, 1541, 1495, 1450 (C ¼ C).
1
benzene-2,6-H), 4.55 (d, J ¼ 27.7 Hz, 2H, CH), 3.89 (m, 4H,
H NMR (300 MHz, DMSO-d ) d 13.21 (s, 1H, coumarin-OH),
6
piperazine-H), 3.45 (m, 4H, piperazine-H), 2.47 (s, 1H, OH), 2.35 9.36 (s, 1H, NH), 7.69 (s, 1H, coumarin-5-H), 7.45 (d, J ¼ 8.4 Hz,
1
3
(
s, 1H, OH). C NMR (75 MHz, DMSO-d ) d 172.95, 169.62, 1H, coumarin-7-H), 7.36 (d, J ¼ 8.5 Hz, 1H, coumarin-8-H), 7.02
6
1
1
4
60.19, 155.13, 150.85, 148.32, 132.54, 126.87, 125.32, 124.01, (d, J ¼ 8.8 Hz, 2H, benzene-3,5-H), 6.76 (d, J ¼ 8.8 Hz, 2H,
18.23, 117.15, 116.87, 116.42, 101.13, 72.42, 71.25, 48.78, benzene-2,6-H), 4.72 (d, 2H, CH), 3.75 (d, 4H, piperazine-H),
+
8.11, 44.81, 42.14. LC–MS: m/z 488 [M + H] , HRMS: calcd for 3.56 (s, 2H, OH), 3.23 (s, 4H, piperazine-H), 2.42 (s, 3H, CH ).
3
+
13
C H ClN O [M + H] , 488.1146; found, 488.1223.
2
C NMR (75 MHz, DMSO-d ) d 172.98, 169.59, 160.03, 158.82,
6
3
22
3
7
1
52.75, 150.12, 146.76, 135.45, 132.15, 128.11, 118.06, 117.60,
(
(
2R,3R)-4-(4-(4-bromophenyl)piperazin-1-yl)-2,3-dihydroxy-N- 116.95, 115.97, 102.29, 72.58, 71.23, 48.75, 48.05, 44.91, 42.21,
4-hydroxycoumarin-3-yl)-4-oxobutanamide (6c). White solid; 22.21. LC–MS: m/z 486 [M + H] , HRMS: calcd for
+
+
[M + H] , 486.1598; found, 486.1625.
yield 34%; [a]20D ¼ +22 (c ¼ 1, CH COOCH CH ). mp 190–
C
H
24
24FN
O
3
7
3
2
3
ꢁ
1
91 C; IR (KBr disk): ꢀ 3445 (OH), 3407, 3343 (NH), 2928,
830 (CH), 1691, 1640 (C ¼ O), 1606, 1540, 1492, 1455 (C ¼ C).
2
(
2R,3R)-4-(4-(4-chlorophenyl)piperazin-1-yl)-2,3-dihydroxy-N-
(4-hydroxy-6-methylcoumarin-3-yl)-4-oxobutanamide (6g).
1
H NMR (300 MHz, DMSO-d ) d 13.22 (s, 1H, coumarin-OH),
6
2
0
9
.29 (s, 1H, NH), 7.89 (d, J ¼ 7.7 Hz, 1H, coumarin-5-H), 7.72 (t,
Yellow solid; yield 11%; ½ꢁꢂ ¼ +54 (c ¼ 1.2, CH OH). mp
D
95–197 C; IR (KBr disk): ꢀ 3494 (OH), 3382, 3330 (NH), 2947,
3
J ¼ 7.7 Hz, 1H, coumarin-7-H), 7.53 (d, 2H, coumarin-6,8-H),
ꢁ
1
7
benzene-2,6-H)), 4.62 (d, 2H, CH), 3.95–3.61 (m, 4H, piperazine-
.35 (d, J ¼ 7.9 Hz, 2H, benzene-3,5-H)), 6.72 (d, J ¼ 8.1 Hz, 2H,
2
831 (CH), 1691, 1639 (C ¼ O), 1581, 1539, 1470, 1441 (C ¼ C).
1
H NMR (300 MHz, DMSO-d ) d 13.35 (s, 1H, coumarin-OH),
6
1
H), 3.21 (s, 4H, piperazine-H), 2.86 (s, 2H, OH). C NMR
3
9
.42 (s, 1H, NH), 7.62 (s, 1H, coumarin-5-H), 7.46 (d, J ¼ 8.5 Hz,
(
75 MHz, DMSO-d ) d 173.68, 169.59, 160.07, 153.82, 150.81,
6
1H, coumarin-7-H), 7.35 (d, J ¼ 8.5 Hz, 1H, coumarin-8-H), 7.30
1
1
50.27, 132.60, 131.95, 125.15, 124.08, 118.06, 116.60, 116.58,
10.87, 103.85, 72.52, 71.23, 48.66, 48.17, 44.85, 42.14. LC–MS:
(
d, J ¼ 8.1 Hz, 2H, benzene-3,5-H), 6.65 (d, J ¼ 8.1 Hz, 2H,
benzene-2,6-H), 4.85 (s, 2H, CH), 3.82 (s, 4H, piperazine-H),
3.28 (s, 4H, piperazine-H), 2.91 (s, 2H, OH), 2.35 (s, 3H, CH ).
+
+
m/z 532 [M + H] , HRMS: calcd for C H BrN O [M + H] ,
2
3
22
3
7
3
1
3
5
32.0641; found, 532.0665.
C NMR (75 MHz, DMSO-d ) d 173.52, 169.55, 160.09, 157.13,
6
1
1
2
51.35, 148.22, 135.87, 132.58, 129.87, 128.46, 127.13, 118.07,
17.25, 116.62, 101.25, 72.85, 71.21, 48.77, 48.12, 44.84, 42.14,
(
(
2R,3R)-4-(4-(4-methylphenyl)piperazin-1-yl)-2,3-dihydroxy-N-
4-hydroxycoumarin-3-yl)-4-oxobutanamide (6d). Yellow solid;
+
1.20. LC–MS: m/z 502 [M + H] , HRMS: calcd for
2
0
ꢁ
+
[M + H] , 502.1303; found, 502.1326.
yield 19%; ½ꢁꢂ ¼ +41 (c ¼ 1.1, CH OH). mp 195–197 C; IR
D
3
C
H
24
24ClN
O
3
7
(
(
KBr disk): ꢀ 3446 (OH), 3405, 3344 (NH), 2959, 2931, 2829
CH), 1690, 1639 (C ¼ O), 1600, 1541, 1495, 1456 (C ¼ C).
1
(2R,3R)-4-(4-(4-bromophenyl)piperazin-1-yl)-2,3-dihydroxy-N-
4-hydroxy-6-methylcoumarin-3-yl)-4-oxobutanamide (6h).
H NMR (300 MHz, DMSO-d ) d 13.20 (s, 1H, coumarin-OH),
6
(
9
.40 (s, 1H, NH), 7.91 (d, J ¼ 7.8 Hz, 1H, coumarin-5-H), 7.68 (t,
20
Light yellow solid; yield 33%; ½ꢁꢂ ¼ +47 (c ¼ 1, CH OH). mp
D
99–200 C; IR (KBr disk): ꢀ 3495 (OH), 3378, 3329 (NH), 2946,
3
J ¼ 7.8 Hz, 1H, coumarin-7-H), 7.44 (dd, J ¼ 12.2, 7.9 Hz, 2H,
coumarin-6,8-H), 7.06 (d, J ¼ 8.2 Hz, 2H, benzene-3,5-H)), 6.89
ꢁ
1
2
830 (CH), 1690, 1638 (C ¼ O), 1587, 1541, 1475, 1445 (C ¼ C).
(
d, J ¼ 8.3 Hz, 2H, benzene-2,6-H)), 4.82 (s, 1H, CH), 4.52 (s, 1H,
1
H NMR (300 MHz, DMSO-d ) d 13.22 (s, 1H, coumarin-OH),
6
CH), 4.03 (d, J ¼ 7.1 Hz, 2H, OH), 3.85–3.51 (m, 4H, piperazine-
1
H), 3.14 (s, 4H, piperazine-H), 2.21 (s, 3H, CH ). C NMR
3
9.39 (s, 1H, NH), 7.70 (s, 1H, coumarin-5-H), 7.48 (d, J ¼ 8.4 Hz,
3
1
H, coumarin-7-H), 7.36 (t, J ¼ 7.5 Hz, 3H, coumarin-8-H,
(
1
1
75 MHz, DMSO-d ) d 173.42, 169.81, 160.14, 155.82, 150.56,
6
benzene-3,5-H), 6.94 (d, J ¼ 8.8 Hz, 2H, benzene-2,6-H), 4.82
s, 1H, CH), 4.52 (s, 1H, CH), 3.72 (d, J ¼ 17.0 Hz, 4H,
piperazine-H), 3.60 (s, 2H, OH), 3.20 (s, 4H, piperazine-H),
48.35, 132.41, 128.15, 126.52, 125.42, 124.31, 118.07, 116.60,
12.87, 101.16, 72.78, 71.12, 48.63, 48.27, 44.92, 42.12. LC–MS:
(
+
+
m/z 468 [M + H] , HRMS: calcd for C H N O [M + H] ,
2
4
4
25
3
7
13
2
1
1
4
.41 (s, 3H, CH3). C NMR (75 MHz, DMSO-d ) d 173.59,
6
68.1693; found, 468.1725.
69.61, 160.05, 153.85, 151.26, 150.19, 135.15, 132.60, 131.95,
27.12, 118.05, 116.90, 116.58, 115.21, 104.02, 72.56, 71.25,
(
(
2R,3R)-4-(4-(4-methoxyphenyl)piperazin-1-yl)-2,3-dihydroxy-N-
4-hydroxycoumarin-3-yl)-4-oxobutanamide (6e). Yellow solid;
+
8.69, 48.15, 44.79, 42.08, 21.23. LC–MS: m/z 546 [M + H] ,
+
2
0
ꢁ
HRMS: calcd for C H BrN O [M + H] , 546.0798; found,
2
5
4
24
3 7
yield 15%; ½ꢁꢂ ¼ +62 (c ¼ 1, CH OH). mp 222–224 C; IR (KBr
D
disk): ꢀ 3445 (OH), 3404, 3340 (NH), 3000, 2930, 2829 (CH),
3
46.0822.
1
1
(
690, 1640 (C ¼ O), 1601, 1545, 1496, 1458 (C ¼ C). H NMR
300 MHz, DMSO-d ) d 13.21 (s, 1H, coumarin-OH), 9.36 (s, 1H, (2R,3R)-4-(4-(4-methylphenyl)piperazin-1-yl)-2,3-dihydroxy-N-
6
NH), 7.98 (d, J ¼ 7.5 Hz, 1H, coumarin-5-H), 7.54 (dd, J ¼ 15.9, (4-hydroxy-6-methylcoumarin-3-yl)-4-oxobutanamide
(6i).
2
D
0
8
.1 Hz, 1H, coumarin-7-H), 7.35 (t, J ¼ 7.8 Hz, 2H, coumarin-6,8- Yellow solid; yield 21%; ½ꢁꢂ ¼ +43 (c ¼ 1, CH OH). mp 217–
3
ꢁ
H), 6.93 (d, J ¼ 9.0 Hz, 2H, benzene-3,5-H), 6.86 (d, J ¼ 9.0 Hz, 218 C; IR (KBr disk): ꢀ 3500 (OH), 3382, 3330 (NH), 2962,
H, benzene-2,6-H), 4.81 (d, J ¼ 4.3 Hz, 1H, CH), 4.12 (d, 2945, 2830 (CH), 1691, 1636 (C ¼ O), 1581, 1540, 1474, 1441
2
1
J ¼ 4.4 Hz, 1H, CH), 3.97 (t, J ¼ 14.9 Hz, 2H, piperazine-H), 3.78 (C ¼ C). H NMR (300 MHz, DMSO-d ) d 13.19(s, 1H, coumarin-
6
(s, 3H, OCH ), 3.73 (s, 2H, piperazine-H), 3.16 (s, 2H, OH), 9.36 (s, 1H, NH), 7.53 (s, 1H, coumarin-5-H), 7.21 (s, 2H,
3
piperazine-H), 3.10–2.89 (m, 2H, piperazine-H), 2.63 (s, 2H, benzene-3,5-H), 7.14 (s, 2H, benzene-2,6-H), 7.04 (d, J ¼ 8.2 Hz,
1
3
OH). C NMR (75 MHz, DMSO-d ) d 173.45, 169.60, 160.02, 2H, coumarin-7,8-H), 5.14 (s, 1H, CH), 4.68 (s, 1H, CH), 4.21–
6
1
1
4
53.78, 150.52, 149.87, 148.27, 132.59, 125.41, 124.01, 117.96, 3.79 (m, 4H, piperazine-H), 3.47 (d, J ¼ 22.0 Hz, 4H, piperazine-
3 3
1
3
C
16.95, 116.42, 114.58, 99.89, 72.51, 71.32, 48.55, 48.16, 44.89, H), 3.25 (s, 2H, OH), 2.33 (s, 3H, CH ), 2.26 (s, 3H, CH ).
+
2.09. LC–MS: m/z 484 [M + H] , HRMS: calcd for C H N O
NMR (75 MHz, DMSO-d ) d 173.62, 169.60, 160.04, 155.81,
2
4
25
3
8
6
+
[M + H] , 484.1642; found, 484.1692.