Chemistry & Biodiversity
10.1002/cbdv.202000265
Chem. Biodiversity
reaction mixture was reacted for 12 h under refluxing and stirring. After the reaction mixture was cooled to rt, NaBH
4
(31 mg, 0.83 mmol) was added
batchwise. The reaction mixture was reacted for another 2 h under refluxing and stirring until it was completed according to TLC monitoring. The reaction
solution was concentrated under reduced pressure to remove the solvents. Water (10 mL) was added into the residue. The solution was extracted using
CH
concentrated under reduced pressure to remove the solvent. The residue was purified using silica gel CC eluted using a mixed solvent of CH
100:1) to yield compound 4a (96 mg, 85.8%) as a light yellow amorphous solid. IR(KBr): max 3025, 2958, 2900, 1649, 1620,1589, 1571, 1500, 1377, 809
2
Cl
2
three times (20 mL/time) in a separatory funnel. The organic layer was integrated, dried using anhydrous MgSO
4
, and filtered. The filtrate was
2
Cl /MeOH (v/v
2
=
1 1
cm ; H-NMR (400 MHz, CDCl
3
): δ 8.09 (s, 1H, ArH), 7.24 (d, J = 8.8 Hz, 1H, ArH ), 7.22 (d, J = 8.8 Hz, 1H, ArH), 6.73 (s, 1H, ArH), 6.23 (s, 2H, OCH
O), 3.82-3.88 (br, 2H, NCH CH Ar), 2.77-2.80 (m, 4H, NCH CH CH , NCH CH Ar), 1.63 (sestet, J = 7.2 Hz, 2H, CH CH CH ), 1.50-1.60 (br, 2H,
C-13), 1.03 (t, J = 7.2 Hz, 3H, CH CH ); C-NMR (100 MHz, CDCl
2
O), 6.02 (s,
2
H, OCH
2
2
2
2
2
3
2
2
2
2
3
13
NCH
2
2
2
CH
3
3
): δ 159.2, 148.1, 147.2, 146.4, 146.3, 135.5, 133.0, 132.1, 124.0, 115.9, 113.7, 111.5,
+
1
11.0, 110.4, 107.3, 102.7, 101.4, 51.6, 48.5, 40.9, 29.5, 23.0, 12.1; (+)HRESI-MS (m/z): 429.1407 [M+Na] (calcd for C23
H
22
N
2
O
5
Na, 429.1421).
13-(N-n-butyl)-aminomethyl-8-oxo-dihydrocoptisine (4b). Target compound 4b was obtained (86 mg, 49.7%) as a light yellow amorphous solid
from compound 3 (150 mg, 0.41 mmol), n-butylamine (206 μL, 2.06 mmol), and NaBH (47 mg, 1.23 mmol) using a reductive amination procedure similar
4
1 1
to that for 4a. IR(KBr): max 3307, 3013, 2928, 2900, 1633, 1585, 1506, 1371, 823 cm ; H-NMR (500 MHz, CDCl
ArH), 6.74 (s, 1H, ArH), 6.23 (s, 2H, OCH O), 6.03 (s, 2H, OCH O), 3.81-3.91 (br, 2H, NCH CH Ar), 2.75-2.86 (m, 4H, NCH
m, 6H, NCH C-13, NCH CH CH CH ), 0.97 (t, J = 7.2 Hz, 3H, NCH ); C-NMR (100 MHz, CDCl
3
): δ 8.05 (brs, 1H, ArH), 7.20-7.26 (br, 2H,
2
2
2
2
2
CH Ar, NCH CH CH CH ), 1.49-1.61
2
2
2
2
3
13
(
2
2
2
2
3
2
CH
2
CH
2
CH
3
3
): δ 159.2, 148.1, 147.2, 146.4, 146.3, 135.5, 133.1,
+
1
32.0, 124.0, 115.9, 113.7, 111.4, 111.0, 110.4, 107.3, 102.7, 101.4, 49.4, 48.5, 41.0, 31.9, 29.5, 20.6, 14.0; (+)HRESI-MS (m/z): 443.1566 [M+Na] (calcd for
C
24
H
24
N
2
O
5
Na, 443.1577).
3-(N-n-pentyl)-aminomethyl-8-oxo-dihydrocoptisine (4c). Target compound 4c was obtained (68 mg, 57.1%) as a light yellow amorphous solid
from compound 3 (100 mg, 0.28 mmol), n-pentylamine (161 μL, 1.38 mmol), and NaBH (31 mg, 0.83 mmol) using a reductive amination procedure similar
1
4
1 1
to that for 4a. IR(KBr): max 3040, 3020, 2933, 2899, 1644, 1617, 1564, 1503, 1375, 808 cm ; H-NMR (500 MHz, CDCl
ArH), 6.74 (s, 1H, ArH), 6.23 (s, 2H, OCH O), 6.03 (s, 2H, OCH O), 3.81-3.91 (br, 2H, NCH CH Ar), 2.73-2.85 (m, 4H, NCH
m, 8H, NCH C-13, NCH (CH CH ), 0.93 (t, J = 5.6 Hz, 3H, NCH ); C-NMR (100 MHz, CDCl
3
): 8.05 (brs, 1H, ArH), 7.20-7.25 (br, 2H,
2
2
2
2
2
(CH CH , NCH CH Ar), 1.40-1.61
2
)
3
3
2
2
13
(
2
2
)
2 3
3
2
(CH
2 3
) CH
3
3
): δ 159.2, 148.1, 147.2, 146.4, 146.3, 135.5, 133.1,
+
1
32.1, 124.0, 115.9, 113.7, 111.4, 111.0, 110.4, 107.3, 102.7, 101.4, 49.7, 48.5, 41.0, 29.6, 29.5, 29.4, 22.6, 14.1; (+)HRESI-MS (m/z): 457.1720 [M+Na] (calcd
26 2 5
for C25H N O Na, 457.1734).
13-(N-n-hexyl)-aminomethyl-8-oxo-dihydrocoptisine (4d). Target compound 4d was obtained (104 mg, 84.2%) as a light yellow amorphous solid
4
from compound 3 (100 mg, 0.28 mmol), n-hexylamine (184 μL, 1.38 mmol), and NaBH (31 mg, 0.83 mmol) using a reductive amination procedure similar
1 1
to that for 4a. IR(KBr): max 3050, 3023, 2956, 2927, 1644, 1618, 1568, 1373, 807 cm ; H-NMR (400 MHz, CDCl
ArH), 6.74 (s, 1H, ArH), 6.24 (s, 2H, OCH O), 6.03 (s, 2H, OCH O), 3.78-3.92 (br, 2H, NCH CH Ar), 2.73-2.85 (m, 4H, NCH
m, 10H, NCH C-13, NCH (CH CH ), 0.91 (t, J = 6.8 Hz, 3H, NCH ); C-NMR (100 MHz, CDCl
3
): δ 8.06 (brs, 1H, ArH), 7.21-7.26 (br, 2H,
2
2
2
2
2
(CH CH , NCH CH Ar), 1.33-1.60
2
)
4
3
2
2
13
(
2
2
)
2 4
3
2
(CH
)
2 4
CH
3
3
): δ 159.2, 148.1, 147.2, 146.4, 146.3, 135.5, 133.1,
+
1
32.0, 124.0, 115.9, 113.7, 111.4, 111.0, 110.4, 107.3, 102.7, 101.4, 49.7, 48.5, 41.0, 31.8, 29.7, 29.5, 27.2, 22.7, 14.1; (+)HRESI-MS (m/z): 471.1877 [M+Na]
calcd for C26 Na, 471.1890).
3-(N-n-heptyl)-aminomethyl-8-oxo-dihydrocoptisine (4e). Target compound 4e was obtained (85 mg, 66.9%) as a light yellow amorphous solid
from compound 3 (100 mg, 0.28 mmol), n-peptylamine (208 μL, 1.38 mmol), and NaBH (31 mg, 0,83 mmol) using a reductive amination procedure similar
to that for 4a. IR(KBr): max 3045, 3021, 2923, 1643, 1620, 1585, 1502, 1373, 809 cm ; H-NMR (400 MHz, DMSO-d ): δ 8.05 (brs, 1H, ArH), 7.42 (d, J = 8.4 Hz,
H, ArH), 7.38 (d, J = 8.4 Hz, 1H, ArH), 6.97 (s, 1H, ArH), 6.21 (s, 2H, OCH O), 6.08 (s, 2H, OCH O), 3.64-3.74 (br, 2H, NCH CH Ar), 2.78, 2.69 (2×br, 2×2H,
NCH (CH CH , NCH CH Ar), 1.28-1.57 (m, 12H, NCH C-13, NCH (CH CH ), 0.87 (t, J = 6.8 Hz, 3H, NCH ); C-NMR (100 MHz, CDCl ): δ 159.2,
(
28 2 5
H N O
1
4
1 1
6
1
2
2
2
2
13
2
)
2 5
3
2
2
2
2
)
2 5
3
2
(CH
)
2 5
CH
3
3
148.2, 147.2, 146.4, 146.4, 135.6, 133.1, 131.9, 123.9, 116.0, 113.8, 111.4, 110.9, 110.4, 107.4, 102.8, 101.4, 49.6, 48.3, 41.0, 31.8, 29.7, 29.5, 29.2, 27.4, 22.7,
+
1
4.1; (+)HRESI-MS (m/z): 485.2034 [M+Na] (calcd for C27
H
30
N
2
O
5
Na, 485.2047).
1
3-(N-n-octyl)-aminomethyl-8-oxo-dihydrocoptisine (4f). Target compound 4f was obtained (85 mg, 64.8%) as a light yellow amorphous solid
from compound 3 (100 mg, 0.28 mmol), n-octylamine (230 μL, 1.38 mmol), and NaBH (31 mg, 0.83 mmol) using a reductive amination procedure similar
to that for 4a. IR(KBr): max 3047, 3020, 2956, 2919, 1643, 1620, 1586, 1503, 1373, 810 cm ; H-NMR (400 MHz, CDCl
H, ArH), 6.74 (s, 1H, ArH), 6.23 (s, 2H, OCH O), 6.03 (s, 2H, OCH O), 3.80-3.93 (br, 2H, NCH CH Ar), 2.71-2.88 (br, 4H, NCH
.62 (m, 14H, NCH C-13, NCH (CH CH ), 0.84-0.95 (br, 3H, NCH ); C-NMR (100 MHz, CDCl ): δ 159.2, 148.1, 147.2, 146.4, 146.3, 135.6, 133.1,
31.9, 123.9, 116.0, 113.8, 111.3, 111.0, 110.4, 107.4, 102.8, 101.4, 49.6, 48.4, 41.0, 31.9, 29.7, 29.5, 29.5, 29.3, 27.5, 22.7, 14.1; (+)HRESI-MS (m/z): 499.2187
4
1 1
3
): δ 8.05 (brs, 1H, ArH), 7.20-7.26 (br,
2
2
2
2
2
2
(CH CH , NCH CH Ar), 1.31-
2
)
6
3
2
2
13
1
2
2
)
2 6
3
2
(CH
2 6
) CH
3
3
1
+
[
M+Na] (calcd for C28
H
32
N
2
O
5
Na, 499.2203).
13-(N-n-nonyl)-aminomethyl-8-oxo-dihydrocoptisine (4g). Target compound 4g was obtained (93 mg, 68.9%) as a light yellow amorphous solid
from compound 3 (100 mg, 0.28 mmol), n-nonylamine (254 μL, 1.38 mmol), and NaBH (31 mg, 0.83 mmol) using a reductive amination procedure similar
4
1 1
to that for 4a. IR(KBr): max 3028, 3007, 2951, 2921, 1643, 1618, 1589, 1572, 1376, 808 cm ; H-NMR (400 MHz, CDCl
3
): δ 8.04 (brs, 1H, ArH), 7.20-7.26 (br,
2H, ArH), 6.74 (s, 1H, ArH), 6.24 (s, 2H, OCH
2
O), 6.03 (s, 2H, OCH
2
O), 3.77-3.97 (br, 2H, NCH
2
CH
2
Ar), 2.68-2.93 (br, 4H, NCH (CH CH , NCH CH Ar), 1.29-
2
2
)
7
3
2
2
6
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