X.-Y. Xie, Y.-Y. Li, W.-H. Ma et al.
European Journal of Medicinal Chemistry 209 (2021) 112906
m/z: 490.8 [Mþ1]þ (C26H35NO8: calcd mass 489.2); Anal: C 63.81, H
29.3, 21.0, 12.0; LC/MS-m/z: 504.9 [Mþ1]þ (C27H37NO8: calcd mass
7.12, N 2.81 (Calcd: C 63.79, H 7.21, N 2.86).
503.3); Anal: C 64.33, H 7.27, N 2.72 (Calcd: C 64.40, H 7.41, N 2.78).
4.1.14. 1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-3-(6,7,8-
4.1.18. 5-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-1-
(2,3,4,5-tetra-methoxy-6-methylphenyl)pentan-1-one (12)
trimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)propan-1-one (8)
1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-3-(6,7,8-trimethoxy-
1,2,3,4-tetrahydroisoquinolin-2(1H)-yl)propan-1-one was pre-
pared according to the procedure for the preparation of 6 by
reacting 5a′ with 6,7,8-trimethoxy-1,2,3,4-tetrahydroisoquinoline
and obtained as an oil in 70.4% yield. 1H NMR (400 MHz, CDCl3):
A solution of 5c (0.7 g, 2.2 mmol), 6,7-dimethoxy-1,2,3,4-
tetrahydroisoquinoline hydrochloride (0.5 g, 2.2 mmol), K2CO3
(0.3 g, 2.2 mmol) and triethylamine (1.1 g, 10.9 mmol) in n-butanol
(10 mL) was stirred at 100 ꢀC overnight. The mixture was cooled to
room temperature, filtered off the solid and concentrated. The
crude was purified by silica gel column to afford the product as a
light yellow oil (0.65 g, 61.6% yield). 1H NMR (400 MHz, CDCl3):
d
6.42 (s, 1H), 3.94 (s, 3H), 3.92 (s, 3H), 3.87 (s, 3H), 3.85e3.82 (m,
9H), 3.78 (s, 3H), 3.57 (s, 2H), 3.09 (t, J ¼ 7.0 Hz, 2H), 2.98 (t,
J ¼ 7.0 Hz, 2H), 2.82 (t, J ¼ 5.6 Hz, 2H), 2.72 (t, J ¼ 5.7 Hz, 2H), 2.09 (s,
d
6.60 (s, 1H), 6.53 (s, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.85 (s, 3H), 3.85
(s, 3H), 3.81 (s, 3H), 3.80 (s, 3H), 3.57 (s, 2H), 2.80e2.83 (m, 4H),
2.72 (t, 2H), 2.53e2.57 (m, 2H), 2.07 (s, 3H), 1.68e1.77 (m, 4H); 13
NMR (100 MHz, CDCl3): 206.8, 148.2, 147.7, 147.5, 147.2, 145.8,
3H); 13C NMR (100 MHz, CDCl3):
d 205.8, 151.9, 150.1, 148.2, 147.9,
146.0, 144.4, 139.9, 131.4, 129.8, 123.3, 120.7, 107.2, 61.9, 61.2, 61.1,
60.8, 60.6, 60.5, 56.0, 52.67, 50.8, 50.6, 43.0, 29.2, 12.0; LC/MS-m/z:
490.1 [Mþ1]þ (C26H35NO8: calcd mass 489.2); Anal: C 63.65, H 7.17,
N 2.69 (Calcd: C 63.79, H 7.21, N 2.86).
C
d
144.6, 131.8, 126.6, 126.2, 122.7, 111.3, 109.5, 61.9, 61.2, 61.1, 60.7,
58.2, 55.9, 55.8, 51.1, 44.9, 28.7, 26.8, 21.6, 12.1; LC/MS-m/z: 488.4
[Mþ1]þ (C27H37NO7: calcd mass 487.3); Anal: C 66.38, H 7.59, N 2.71
(Calcd: C 66.51, H 7.65, N 2.87).
4.1.15. 4-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)-1-
(2,3,4,5-tetra-methoxy-6-methylphenyl)butan-1-one (9)
A solution of 5b (0.7 g, 2.2 mmol), 6,7-dimethoxy-1,2,3,4-
tetrahydroisoquinoline hydrochloride (0.5 g, 2.2 mmol) and trie-
thylamine (1.1 g,10.9 mmol) in ethanol (10 mL) was heated to reflux
under stirring overnight. The solvent was removed in vacuum and
the crude produce was extracted with DCM, washed with brine and
dried over anhydrous sodium sulfate. After workup, the product
was purified by silica gel column to give an oil product (0.4 g, 40.7%
4.1.19. 1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-5-(5,6,7-
trimethoxy-3,4- dihydroisoquinolin-2(1H)-yl)pentan-1-one (13)
1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-5-(5,6,7-
trimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)pentan-1-one
was
prepared according to the procedure for the preparation of 12 by
reacting 5c with 25a and obtained as a yellowish oil in 57.8% yield.
1H NMR (400 MHz, CDCl3):
d 6.36 (s, 1H), 3.92 (s, 3H), 3.90 (s, 3H),
yield). 1H NMR (400 MHz, CDCl3):
d
6.60 (s, 1H), 6.53 (s, 1H), 3.92 (s,
3.85 (s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.79 (s, 3H), 3.54
(s, 2H), 2.76e2.81 (m, J ¼ 14.5, 7.1 Hz, 4H), 2.69 (t, J ¼ 5.9 Hz, 2H),
2.48e2.57 (m, 2H), 2.06 (s, 3H), 1.73e1.79 (m, J ¼ 14.1, 6.9 Hz, 2H),
1.64e1.70 (m, J ¼ 14.8, 8.6, 5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
3H), 3.90 (s, 3H), 3.84 (6H, 2MeO), 3.81 (s, 3H), 3.79 (s, 3H), 3.58 (s,
2H), 2.81e2.85 (m, 4H), 2.72e2.74 (m, 2H), 2.56e2.58 (m, 2H), 2.06
(s, 3H), 1.98e2.02 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 206.7,
148.2, 147.7, 147.5, 147.2, 145.7, 144.5, 131.8, 126.6, 126.2, 122.6, 111.3,
109.5, 61.8, 61.2, 61.1, 60.7, 57.2, 55.9, 55.6, 50.9, 42.7, 28.7, 21.0,12.0;
LC/MS-m/z: 474.0 [Mþ1]þ (C26H35NO7: calcd mass 473.2); Anal: C
65.83, H 7.44, N 3.03 (Calcd: C 65.94, H 7.45, N 2.96).
d 206.8, 151.7, 151.2, 148.2, 147.7, 145.8, 144.7, 140.4, 131.8, 122.7,
120.6, 105.4, 61.9, 61.2, 61.1, 60.9, 60.7, 60.4, 58.1, 56.1, 56.0, 50.9,
44.9, 26.8, 23.5, 21.6, 12.1; LC/MS-m/z: 518.2 [Mþ1]þ (C28H39NO8:
calcd mass 517.3); Anal: C 64.84, H 7.51, N 2.66 (Calcd: C 64.97, H
7.59, N 2.71).
4.1.16. 1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-4-(5,6,7-
trimethoxy-3,4- dihydroisoquinolin-2-yl)butan-1-one (10)
1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-4-(5,6,7-
4.1.20. 1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-5-(6,7,8-
trimethoxy-3,4- dihydroisoquinolin-2(1H)-yl)pentan-1-one (14)
1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-5-(6,7,8-trimethoxy-
3,4- dihydroisoquinolin-2(1H)-yl)pentan-1-one was prepared ac-
cording to the procedure for the preparation of 12 by reacting 5c
with 25b and obtained as a yellowish oil in 59.5% yield. 1H NMR
trimethoxy-3,4-dihydroisoquinolin-2-yl)butan-1-one was pre-
pared according to the procedure for the preparation of 9 by
reacting 5b with 25a and obtained as a yellowish oil in 60.5% yield.
1H NMR (400 MHz, CDCl3):
d 6.36 (s, 1H), 3.92 (s, 3H), 3.89 (s, 3H),
3.85 (s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.78 (s, 3H), 3.56
(s, 2H), 2.83 (t, J ¼ 7.2 Hz, 2H), 2.77 (t, J ¼ 5.6 Hz, 2H), 2.71 (t,
J ¼ 5.6 Hz, 2H), 2.57 (t, J ¼ 7.3 Hz, 2H), 2.05 (s, 3H), 1.97e2.02 (m,
(100 MHz, CDCl3): d 6.41 (s, 1H), 3.92 (s, 3H), 3.90 (s, 3H), 3.87 (s,
3H), 3.83 (s, 3H), 3.82 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.54 (s, 2H),
2.78e2.82 (m, 4H), 2.68 (t, J ¼ 5.8 Hz, 2H), 2.51e2.61 (m, 2H), 2.06
(s, 3H), 1.73e1.79 (m, 2H), 1.66e1.71 (m, 2H); 13C NMR (100 MHz,
J ¼ 14.5, 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 206.7,151.7,151.2,
148.2, 147.7, 145.7, 144.5, 140.4, 131.8, 122.6, 120.6, 105.3, 61.9, 61.2,
61.1, 60.1, 60.7, 60.4, 57.3, 56.0, 55.9, 50.7, 42.7, 29.7, 23.5, 21.0, 12.0;
LC/MS-m/z: 504.2 [Mþ1]þ (C27H37NO8: calcd mass 503.3); Anal: C
64.29, H 7.30, N 2.63 (Calcd: C 64.40, H 7.41, N 2.78).
CDCl3): d 206.8, 151.9, 150.0, 148.2, 147.7, 145.8, 144.6, 139.9, 131.9,
130.0, 122.7, 121.0, 107.2, 61.9, 61.2, 61.1, 60.8, 60.7, 60.5, 58.4, 56.0,
51.1, 50.7, 44.9, 29.3, 26.8, 21.6, 12.0; LC/MS-m/z: 518.0 [Mþ1]þ
(C28H39NO8: calcd mass 517.3); Anal: C 64.81, H 7.57, N 2.48 (Calcd:
C 64.97, H 7.59, N 2.71).
4.1.17. 1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-4-(6,7,8-
trimethoxy-3,4- dihydroisoquinolin-2(1H)-yl)butan-1-one (11)
1-(2,3,4,5-Tetramethoxy-6-methylphenyl)-4-(6,7,8-trimethoxy-
3,4-dihydroisoquinolin-2(1H)-yl)butan-1-one was prepared ac-
cording to the procedure for the preparation of 9 by reacting 5b
with 25b and obtained as a yellowish oil in 71.8% yield. 1H NMR
4.1.21. 6-(6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-1-
(2,3,4,5- tetramethoxy-6-methylphenyl)hexan-1-one (15)
To a flask was added with 6-bromo-1-(2,3,4,5-tetramethoxy-6-
methylphenyl) hexan-1-one 5d (0.5 g, 1.28 mmol), 6,7-
dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (0.29 g,
1.26 mmol), K2CO3 (0.35 g, 2.52 mmol) and triethylamine (0.26 g,
2.52 mmol) in isopropanol (15 mL) was stirred at refluxing over-
night. The mixture was cooled to room temperature, filtered off the
solid and concentrated. The crude was purified by silica gel column
to afford the product as a light yellow oil (0.30 g, yield 47.9%). 1H
(400 MHz, CDCl3):
d 6.41 (s, 1H), 3.92 (s, 3H), 3.89 (s, 3H), 3.87 (s,
3H), 3.83 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.78 (s, 3H), 3.55 (s, 2H),
2.81e2.85 (m, 4H), 2.69 (t, J ¼ 5.8 Hz, 2H), 2.60 (t, J ¼ 7.3 Hz, 2H),
2.06 (s, 3H), 1.97e2.02 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 206.7,
151.9, 150.0,148.2,147.7, 145.7, 144.5, 139.9,131.9,130.0,122.6,121.0,
107.2, 61.9, 61.2, 61.1, 60.9, 60.7, 60.5, 57.5, 56.0, 50.9, 50.4, 42.8,
NMR (400 MHz, CDCl3): d 6.59 (s, 1H), 6.52 (s, 1H), 3.92 (s, 3H), 3.90
8