Z. Sang et al. / Bioorg. Med. Chem. 23 (2015) 668–680
677
1
1
H), 4.13–4.10 (m, 1H), 4.01–3.99 (m, 1H), 3.99 (s, 3H), 3.94 (s, 3H),
.37 (s, 6H), 1.33 (s, 6H). HRMS (ESI) m/z calcd for C24 28NO
7
4.1.6.19. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
N,N-diethylcarbamate (16c). Compound 11 was treated with
13c according to general procedure to get the product 16c as light
H
+
[
M+H] : 442.1866, found: 442.1862.
yellow solid, 98.7% HPLC purity, yield: 74.7%, mp: 146.5–147.2 °C.
1
4
.1.6.13.
4-(5-Hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-
H NMR (400 MHz, CDCl
3
) d 7.70 (d, J = 7.2 Hz, 1H), 7.65 (t,
= 7.2 Hz,
= 1.2 Hz, 1H), 6.83 (s, 1H) , 6.69 (s, 1H), 3.99 (s, 6H), 3.92 (s,
3H), 3.48 (q, J = 14.0 Hz, J = 7.2 Hz, 2H), 3.42 (q, J = 14.0 Hz,
= 7.2 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H), 1.23 (t, J = 7.2 Hz, 3H). HRMS
yl)phenyl morpholine-N-carboxylate (15e). Compound 10 was
treated with 13e according to general procedure to get the product
J = 2.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.28 (dd, J
1
J
2
1
5e as yellow solid, 97.5% HPLC purity, yield: 92.5%, mp: 202–
1
2
1
1
2
03.4 °C. H NMR (400 MHz, CDCl
3
) d 12.63 (s, 1H), 7.91 (d,
J
2
+
J = 8.8 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H), 6.65 (s, 1H), 6.57 (s, 1H),
7
(ESI) m/z calcd for C23H26NO [M+H] : 428.1709, found: 428.1708.
3
2
.98 (s, 3H), 3.93 (s, 3H), 3.78 (t, J = 4.8 Hz, 4H), 3.73–3.70 (m,
H), 3.61–3.59 (m, 2H). HRMS (ESI) m/z calcd for C22
H22NO
8
4.1.6.20. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
N,N-diisopropylcarbamate (16d). Compound 11 was treated
with 13d according to general procedure to get the product 16d
+
[
M+H] : 428.1345, found: 428.1346.
4
.1.6.14.
4-(5-Hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-
as light yellow solid, 98.9% HPLC purity, yield: 55.7%, mp: 171.1–
1
yl)phenyl piperidine-N-carboxylate (15f). Compound 10 was
treated with 13f according to general procedure to get the product
172.8 °C. H NMR (400 MHz, CDCl
(t, J = 2.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.29 (dd, J
J
2
3
) d 7.89 (d, J = 8.0 Hz, 1H), 7.64
= 8.4 Hz,
= 1.2 Hz, 1H), 6.85 (s, 1H), 6.77 (s, 1H), 4.10 (m, 1H), 4.01–3.99
(m, 1H), 3.99 (s, 6H), 3.93 (s, 3H), 1.38 (s, 6H), 1.33–1.31 (m, 6H).
1
1
5f as yellow solid, 98.0% HPLC purity, yield: 70.5%, mp: 172–
1
1
3
72.8 °C. H NMR (400 MHz, CDCl ) d 12.70 (s, 1H), 7.90 (d,
+
J = 8.8 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 6.65 (s, 1H), 6.57 (s, 1H),
7
HRMS (ESI) m/z calcd for C25H30NO [M+H] : 456.2022, found:
3
1
4
.98 (s, 6H), 3.93 (s, 3H), 3.64–3.62 (m, 2H), 3.55–3.53 (m, 2H),
.68–1.66 (m, 6H). HRMS (ESI) m/z calcd for C23H24NO [M+H] :
7
26.1553, found: 426.1549.
456.2030.
+
4.1.6.21. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
morpholine-N-carboxylate (16e). Compound 11 was treated
with 13e according to general procedure to get the product 16e
4
.1.6.15.
4-(5-Hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-
0
as light brown solid, 98.0% HPLC purity, yield: 69.8%, mp: 205.7–
yl)phenyl-N-methylpiperazine-N -carboxylate
pound 10 was treated with 13g according to general procedure
to get the product 15g as light yellow solid, 98.5% HPLC purity,
yield: 67.8%, mp: 174.8–175.9 °C. H NMR (400 MHz, CDCl
(15g). Com-
1
2
(
06.8 °C. H NMR (400 MHz, CDCl
3
) d 7.73 (d, J = 8.0 Hz, 1H), 7.66
= 7.2 Hz,
J2 = 1.6 Hz, 1H), 6.82 (s, 1H) , 6.69 (s, 1H), 3.99 (s, 6H), 3.93 (s,
H), 3.79 (t, J = 4.4 Hz, 4H), 3.74–3.72 (m, 2H), 3.62–3.60 (m, 2H).
t, J = 1.6 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.28 (dd, J
1
1
3
) d
3
1
(
3
2.68 (s, 1H), 7.90 (d, J = 7.6 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 6.65
s, 1H), 6.57 (s, 1H), 3.98 (s, 3H), 3.92 (s, 3H), 3.76–3.74 (m, 2H),
.66–3.64 (m, 2H), 2.54–2.52 (m, 4H), 2.40–2.38 (m, 3H). HRMS
+
8
HRMS (ESI) m/z calcd for C23H24NO [M+H] : 442.1502, found:
4
42.1490.
+
(
25 2 7
ESI) m/z calcd for C23H N O [M+H] : 441.1662, found: 441.1666.
4
.1.6.22. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
piperidine-N-carboxylate (16f). Compound 11 was treated with
13f according to general procedure to get the product 16f as yellow
solid, 98.2% HPLC purity, yield: 74.3%, mp: 141.7–142.4 °C. H NMR
4
.1.6.16.
4-(5-Hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-
0
yl)phenyl-N-benzylpiperazine-N -carboxylate (15h).
pound 10 was treated with 13h according to general procedure
to get the product 15h as yellow solid, 98.3% HPLC purity, yield:
Com-
1
(
400 MHz, CDCl
3
) d 7.70 (d, J = 7.6 Hz, 1H), 7.65 (t, J = 2.0 Hz, 1H),
= 8.0 Hz, J = 1.2 Hz, 1H), 6.83
s, 1H), 6.69 (s, 1H), 3.99 (s, 6H), 3.93 (s, 3H), 3.66–3.64 (m, 2H),
1
7.49 (t, J = 8.0 Hz, 1H), 7.28 (dd, J
(
1
2
8
1
5.6%, mp: 193.2–194.8 °C. H NMR (400 MHz, CDCl
H), 7.89 (d, J = 8.4 Hz, 2H), 7.26–7.35 (m, 7H), 6.64 (s, 1H), 6.56
3
) d 12.68 (s,
3
C
.55–3.53 (m, 2H), 1.69–1.67 (m, 6H). HRMS (ESI) m/z calcd for
H26NO [M+H] : 440.1709, found: 440.1705.
24 7
(
(
s, 1H), 3.97 (s, 3H), 3.92 (s, 3H), 3.71–3.69 (m, 2H), 3.59–3.57
m, 4H), 2.52 (t, J = 4.8 Hz, 4H). HRMS (ESI) m/z calcd for
+
+
C
29
H
29
N
2
O
7
[M+H] : 517.1975, found: 517.1968.
4
.1.6.23. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
0
N-methylpiperazine-N -carboxylate (16g).
Compound 11
4
.1.6.17. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
was treated with 13g according to general procedure to get the
N,N-dimethylcarbamate (16a). Compound 11 was treated with
3a according to general procedure to get the product 16a as clay-
product 16g as light yellow solid, 97.6% HPLC purity, yield:
1
1
7
4.9%, mp: 165.2–166.4 °C. H NMR (400 MHz, CDCl
3
) d 7.70 (d,
1
bank solid, 97.8% HPLC purity, yield: 82.6%, mp: 133.8–134.7 °C. H
NMR (400 MHz, CDCl ) d 7.70 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 1.6 Hz,
H), 7.50 (t, J = 8.0 Hz, 1H), 7.28 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H),
.83 (s, 1H), 6.68 (s, 1H), 3.99 (s, 6H), 3.93 (s, 3H), 3.14 (s, 3H),
J = 8.0 Hz, 1H), 7.64 (t, J = 2.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.27
dd, J = 8.0 Hz, J = 1.2 Hz, 1H), 6.81 (s, 1H), 6.65 (s, 1H), 3.98 (s,
H), 3.91 (s, 3H), 3.76–3.74 (m, 2H), 3.64–3.63 (m, 2H), 2.52–
.50 (m, 4H), 2.39–2.37 (m, 3H). HRMS (ESI) m/z calcd for
3
(
1
2
1
6
3
4
1
2
6
2
C
+
.06 (s, 3H). HRMS (ESI) m/z calcd for C21
00.1396, found: 400.1393.
H22NO
7
[M+H] :
+
24
27 2 7
H N O [M+H] : 455.1818, found: 455.1810.
4
.1.6.24. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
0
4
.1.6.18. 3-(5,6,7-Trimethoxy-4-oxo-4H-chromen-2-yl)phenyl
N-benzylpiperazine-N -carboxylate (16h). Compound 11 was
treated with 13h according to general procedure to get the product
16h as light brown solid, 98.6% HPLC purity, yield: 79.6%, mp:
N-ethyl-N-methylcarbamate (16b). Compound 11 was treated
with 13b according to general procedure to get the product 16b
as claybank solid, 97.5% HPLC purity, yield: 70.9%, mp: 96.2–
1
160.1–161.1 °C. H NMR (400 MHz, CDCl ) d 7.70 (d, J = 8.0 Hz,
3
1
9
(
6
7.8 °C. H NMR (400 MHz, CDCl
3
) d 7.71 (d, J = 8.0 Hz, 1H), 7.66
1H), 7.65 (t, J = 1.6 Hz, 1H), 7.49 (t, J = 8.4 Hz, 1H), 7.28–7.36 (m,
6H), 6.82 (s, 1H), 6.66 (s, 1H), 3.99 (s, 6H), 3.92 (s, 3H), 3.73–3.71
(m, 2H), 3.61–3.59 (m, 4H), 2.54 (t, J = 4.8 Hz, 4H). HRMS (ESI) m/z
d, J = 2.4 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.30 (d, J = 2.4 Hz, 1H),
.84 (s, 1H), 6.76 (s, 1H), 4.00 (s, 6H), 3.93 (s, 3H), 3.53 (q,
= 13.6 Hz, J = 7.2 Hz, 1H), 3.45 (q, J = 13.6 Hz, J = 7.2 Hz, 1H),
.12 (s, 3/2H), 3.03 (s, 3/2H), 1.29 (t, J = 7.2 Hz, 3/2H), 1.23 (t,
J = 7.2 Hz, 3/2H). HRMS (ESI) m/z calcd for C22
14.1553, found: 414.1550.
+
J
1
2
1
2
calcd for C30H31N O [M+H] : 531.2131, found: 531.2128.
2
7
3
+
H24NO
7
[M+H] :
4.1.6.25. 3-(5-Hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phe-
nyl N,N-dimethyl carbamate (17a). Compound 12 was treated
4