BURAN ET AL.
9 of 11
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4
1
‐(7‐Hydroxy‐4‐methyl‐2‐oxo‐2H‐chromen‐8‐ylmethyl)piperazine‐
7‐Hydroxy‐8‐[4‐(4‐hydroxyphenyl)piperazin‐1‐ylmethyl]‐4‐
methylchromen‐2‐one (24)
‐carboxylic acid ethyl ester (12)
1
1
Solid, yield 31%, m.p. 137.3°C. H‐NMR (400 MHz, CDCl
3
) δ 7.39 (d,
Solid, yield 54%, m.p. 252.9°C. H‐NMR: (400 MHz, DMSO‐d
6
) δ 7.54
J = 8.71 Hz, 1H); 6.73 (d, J = 8.71 Hz, 1H); 6.04 (s, 1H); 4.12 (q,
(d, J = 8.67 Hz, 1H); 6.79–6.75 (m, 3H); 6.64–6.60 (m, 2H); 6.13 (q,
J = 7.1 Hz, 2H); 4.03 (s, 2H); 3.53 (broad s, 4H); 2.57 (broad s, 4H);
J = 1.14 Hz, 1H); 3.93 (s, 2H); 2.97 (s, 8H); and 2.35 (d, J = 1.05 Hz,
13
1
3
2
.35 (s, 3H); and 1.22 (t, J = 7.1 Hz, 3H). C‐NMR (400 MHz, CDCl
3
)
6
3H). C‐NMR: (400 MHz, DMSO‐d ) δ 161.8, 160.5, 154.4, 153.0,
δ 161.9, 160.9, 155.2, 153.2, 124.8, 113.3, 112.4, 152.4, 110.8, 107.3,
125.7, 113.2, 112.2, 151.5, 150.9, 144.3, 122.8, 110.4, 108.8, 59.5,
6
1.6, 53.7, 52.2, 43.2, 18.7, and 14.5. HRMS (ESI) m/z, calculated for
22 2 4
52.7, 52.1, and 18.7. HRMS (ESI) m/z, calculated for C21H N O
+
+
C
18
H
22
N
2
O
5
[M+H] 347.1528; found 347.1502.
[M+H] 367.1579; found 367.1551.
7
‐Hydroxy‐4‐methyl‐8‐[4‐(4‐nitrophenyl)‐piperazin‐1‐ylmethyl]‐
chromen‐2‐one (20)
Solid, yield 47%, m.p. 222°C. H‐NMR: (400 MHz, CDCl
J = 9.4 Hz, 1H); 7.45 (d, J = 8.76 Hz, 1H); 6.86 (d, J = 9.4 Hz, 2H); 6.80
7‐Hydroxy‐4‐methyl‐8‐[4‐(4‐trifluoromethylphenyl)piperazin‐1‐
ylmethyl]chromen‐2‐one (26)
1
1
3
) δ 8.14 (d,
Solid, yield 36%, m.p. 190.2°C. H‐NMR (400 MHz, CDCl
3
) δ 7.49 (d,
= 2.0 Hz, 1H); 6.93 (d, J = 7.4 Hz,
= 2.2 Hz, 1H); 6.09 (q, J = 1.0 Hz, 1H); 4.12
(s, 2H); 3.34 (broad s, 4H); 2.81 (broad s, 4H); and 2.39 (d, J = 1.0 Hz,
1 2
J = 7.2 Hz, 2H); 7.43 (dd, J = 8.7 Hz, J
(
(
(
d, J = 8.76 Hz, 1H); 6.10 (q, J = 1.16 Hz, 1H); 4.14 (s, 2H); 3.64–3.40
2H); 6.79 (dd, J = 8.7 Hz, J
1
2
1
3
br, 4H); 2.92–2.72 (br, 4H); and 2.40 (d, J = 1.13 Hz, 3H). C‐NMR:
400 MHz, CDCl ) δ 161.8, 161.0, 154.5, 153.3, 125.8, 125.0, 113.4,
13.3, 10.9, 107.2, 53.6, 52.0, 46.9, and 18.8. HRMS (ESI) m/z,
13
3
3H). C‐NMR (400 MHz, CDCl
3
) δ 162.0, 161.0, 153.2, 152.8, 113.3,
1
112.5, 152.5, 126.4 (q, J = 3.65 Hz, J
1
2
= 7.41 Hz); 124.8, 114.9, 110.8,
+
calculated for C21
H
21
N
3
O
5
[M+H] 396.1481; found 396.1496.
107.4, 53.7, 52.3, 47.9, and 18.7. HRMS (ESI) m/z, calculated for
+
C H F N O
22 21 3 2 3
[M+H] 419.1504; found 419.1483.
2
‐[4‐(7‐Hydroxy‐4‐methyl‐2‐oxo‐2H‐chromen‐8‐ylmethyl)‐
piperazin‐1‐yl]benzonitrile (21)
7‐Hydroxy‐4‐methyl‐8‐(4‐naphthalen‐2‐ylmethyl‐piperazin‐1‐
1
Solid, yield 28%, m.p. > 300°C. H‐NMR (400 MHz, CDCl
3
) δ 7.59 (dd,
= 7.5 Hz,
= 1.0, Hz,
= 7.60 Hz, 1H), 7.01 (d, J = 7.0 Hz, 1H); 6.79 (d, J = 8.72 Hz, 1H), 6.10
ylmethyl)chromen‐2‐one (31)
1
J
1
J
3
J
2
= 1.38 Hz,
J
2
= 7.68 Hz, 1H); 7.51 (ddd,
J
1
= 1.6 Hz,
J
2
Solid, yield 38%, m.p. 155.2°C. H‐NMR (400 MHz, CDCl
3
) δ 9.64 (s,
= 8.3 Hz, 1H); 7.43 (d, J = 8.7 Hz, 1H); 7.06 (td, J
1
1H, OH); 8.27 (d, J = 8.29 Hz, 1H); 7.84 (d, J = 7.80 Hz, 1H); 7.84–7.37
(m, 6H); 6.76 (d, J = 7.80, 1H); 6.05 (q, J = 1.1 Hz, 1H); 4.03 (s, 2H);
13
(
q, J = 1.21 Hz, 1H); 4.17 (s, 2H); 3.41–3.17 (br, 4H); 2.95–2.80 (br, 4H);
3.92 (s, 2H); 2.86–2.44 (broad s, 8H); and 2.34 (s, 3H). C‐NMR
(400 MHz, CDCl ) δ 162.5, 161.2, 153.3, 152.5, 128.1, 113.3, 112.2,
1
3
and 2.39 (d, J = 1.20 Hz, 3H). C‐NMR (400 MHz, CDCl
3
) δ 162.0,
3
1
61.1, 154.9, 152.5, 124.8, 113.3, 112.5, 153.2, 134.4, 133.9, 122.41,
133.8, 133.4, 132.4, 128.3, 127.4, 125.8, 125.7, 125.0, 124.6, 110.5,
1
18.8, 106.4, 118.1, 110.9, 107.5, 53.7, 52.5, 51.2, and 18.8. HRMS
107.6, 60.8, 53.7, 52.8, 52.6, and 18.7. HRMS (ESI) m/z, calculated for
+
+
(
ESI) m/z, calculated for C22
H N O
21 3 3
[M+H] 376.1583; 376.1563.
C
26
H
26
N
2
O
5
[M+H] 415.1943; found 415.1915.
7
‐Hydroxy‐8‐[4‐(4‐methoxy‐phenyl)‐piperazin‐1‐ylmethyl]‐4‐
7‐Hydroxy‐4‐methyl‐8‐(4‐pyridin‐2‐yl‐piperazin‐1‐yl)chromen‐2‐
methyl‐chromen‐2‐one (22)
Solid, yield 62%, m.p. > 300°C. H‐NMR (400 MHz, CDCl
one (32)
1
1
3
) δ 7.42 (d,
Solid, yield 51%, m.p. 200.8°C. H‐NMR (400 MHz, CDCl
3
) δ 10.75 (s,
J = 8.74 Hz, 1H); 6.92–6.82 (m, 4H); 6.78 (d, J = 8.76 Hz, 1H); 6.09 (q,
1H, OH); 8.16 (dd, J
1
= 1.56 Hz, J
2
= 5.33 Hz, 1H), 7.46 (m, 1H); 7.40
J = 1.18 Hz, 1H); 4.12 (s, 2H); 3,76 (s, 3H); 3.27–2.70 (br, 8H); and
(d, J = 8.75 Hz, 1H); 6.76 (d, J = 8.75 Hz, 1H); 6.64–6.61 (m, 2H); 6.05
1
3
2
1
5
.39 (d, J = 1.17 Hz, 3H). C‐NMR (400 MHz, CDCl
3
) δ 162.2, 161.2,
(s, 1H); 4.08 (s, 2H); 3.63 (broad s, 4H); 2.73 (broad s, 4H); and 2.35
13
54, 153, 145, 124, 112.3, 152.5, 118.6, 114.5, 113.4, 110.7, 107.5,
3
(s, 3H). C‐NMR (400 MHz, CDCl ) δ 162.1, 161.0, 147.9, 137.5,
5.5, 53.8, 52.7, 50.6, and 18.8. HRMS (ESI) m/z, calculated for
113.3, 107.4, 159.0, 153.2, 152.5, 124.7, 112.3, 110.7, 113.3, 107.1,
+
C
22
H
24
N
2
O
4
[M+H] 381.1736; found 381.1720.
53.8, 52.3, 44.9, and 18.7. HRMS (ESI) m/z, calculated for
+
C
20
H
21
N
3
O
3
[M+H] 352.1583; found 352.1589.
8
‐[4‐(4‐Chlorobenzyl)piperazin‐1‐ylmethyl]‐7‐hydroxy‐4‐
methylchromen‐2‐one (23)
Solid, yield 38%, m.p. 185.2°C. H‐NMR (400 MHz, CDCl
7‐Hydroxy‐4‐methyl‐8‐piperidin‐1‐ylmethyl‐chromen‐2‐one (33)
1
1
3
) δ 7.40 (d,
Solid, yield 50%, m.p. 132.3°C. H‐NMR (400 MHz, CDCl
3
) δ 12.3 (s,
= 8.74 Hz,
J = 8.72 Hz, 1H); 7.29–7.23 (m, 4H); 6.74 (d, J = 8.76 Hz, 1H); 6.07 (q,
1H, OH); 7.35 (d, J = 8.75 Hz, 1H); 6.70 (dd, J
1
= 1.35 Hz, J
2
J = 1.20 Hz, 1H); 4.06 (s, 2H); 3.49 (s, 2H); 3.05–2.46 (br, 8H); and
1H); 6.01 (broad s, 1H); 3.97 (s, 2H); 2.67–2.10 (broad s, 7H); 2.33 (s,
13
1
3
2
1
1
.37 (d, J = 1.19 Hz, 3H). C‐NMR (400 MHz, CDCl
3
): δ 162.4, 161.2,
3
3H); and 1.63 (broad s, 6H). C‐NMR (400 MHz, CDCl ) δ 163.0,
53.2, 152.5, 124.6, 113.3, 112.2, 136.2, 132.9, 130.2, 128.4, 110.6,
161.2, 153.3, 152.4, 124.4, 113.3, 111.9, 110.3, 107.7, 54.6, 53.8,
07.5, 61.8, 53.8, 52.6, 52.5, and 18.8. HRMS (ESI) m/z, calculated for
25.6, 23.6, and 18.7. HRMS (ESI) m/z, calculated for C16H19NO
3
+
+
C
22
H
23ClN
2
O
3
[M+H] 399.1397; found 399.1401.
[M+H] 274.1364; found 274.1369.