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4A molecular sieves (0.3 g) was added at room temperature. The
resulting mixture was stirred at room temperature for 6 h. The
mixture was diluted with EtOAc and filtered through a pad of Celite.
The organic layer was collected and the crude product was purified
by flash chromatography (EtOAc/hexane) to yield the substituted
benzophenone.
by flash chromatography (EtOAc/hexane) to afford the desired
compound.
4.1.9.1. (2-Amino-4-methoxyphenyl)(3,4,5-trimethoxy-2-(methox-
ymethoxy)phenyl)methanone (24d). The title compound was ob-
tained from compound 24c (600 mg, 1.5 mmol) according to
general procedure D (400 mg, 72%). 1H NMR (300 MHz, CDCl3):
d
3.08 (s, 3H), 3.88 (s, 3H), 3.90 (s, 3H), 3.97 (s, 3H), 3.99 (s, 3H), 4.93
4.1.8.1. (4-(Methylamino)phenyl)(3,4,5-trimethoxy-2-(methox-
ymethoxy)phenyl)methanone (24a). The title compound was ob-
tained from 4-(methylamino)benzaldehyde (600 mg, 4.44 mmol)
according to general procedure C (330 mg, 21%). 1H NMR (500 MHz,
(s, 2H), 6.66e6.71 (m, 2H), 7.04 (s, 1H), 7.69e7.74 (m, 1H).
4.1.9.2. (3-Amino-4-methoxyphenyl)(3,4,5-trimethoxy-2-(methox-
ymethoxy)phenyl)methanone (24g). The title compound was ob-
tained from compound 24f (710 mg, 1.8 mmol) according to general
CDCl3):
d 3.09 (s, 3H), 3.27 (s, 3H), 3.74 (s, 3H), 3.87 (s, 3H), 4.81
(s, 2H). 6.60 (s, 1H), 7.19 (d, 2H, J ¼ 8.5 Hz), 7.83 (d, 2H, J ¼ 8.5 Hz),
procedure D (516 mg, 78%). 1H NMR (300 MHz, CDCl3):
d 3.23
8.60 (s, 1H).
(s, 3H), 3.80 (s, 3H), 3.90e3.95 (m, 12H), 4.93 (s, 2H), 6.61 (s, 1H),
6.78 (d, 1H, J ¼ 8.4 Hz), 7.22 (dd, 1H, J ¼ 2.1, 8.4 Hz), 7.31 (d, 1H,
J ¼ 1.8 Hz).
4.1.8.2. (4-Methoxy-2-(methoxymethoxy)phenyl)(3,4,5-trimethoxy-
2-(methoxymethoxy)phenyl)methanone (24b). The title compound
was obtained from 4-methoxy-2-(methoxymethoxy)benzaldehyde
(500 mg, 2.55 mmol) according to general procedure C (510 mg,
4.1.10. General procedure E for cleavage of methoxymethoxy group
to provide 9e15
47%). 1H NMR (300 MHz, CDCl3):
d3.26 (s, 3H) 3.30 (s, 3H) 3.79
2 N HCl (5 mL) was added at room temperature to a stirred
solution of MOM-protected 2-hydroxybenzophenone (1 equiv) in
MeOH (5 mL) and the resulting mixture was stirred for 4 h. The
solution was evaporated in vacuo and diluted with water. The
diluted solution was extracted with EtOAc. The organic layer was
collected and the crude product was purified by flash chromatog-
(s, 3H) 3.82 (s, 3H), 3.88 (s, 3H), 3.91 (s, 3H), 4.83 (s, 2H), 4.98 (s, 2H),
6.56 (dd,1H, J ¼ 2.4, 8.7 Hz), 6.66 (d,1H, J ¼ 2.4 Hz), 6.73 (s,1H), 7.59
(d, 1H, J ¼ 8.7 Hz).
4.1.8.3. (4-Methoxy-2-nitrophenyl)(3,4,5-trimethoxy-2-(methox-
ymethoxy)phenyl)methanone (24c). The title compound was ob-
tained from 4-methoxy-2-nitrobenzaldehyde (800 mg, 4.42 mmol)
according to general procedure C (760 mg, 42%). 1H NMR (300 MHz,
raphy
(EtOAc/hexane)
to
afford
the
substituted
2-
hydroxybenzophenone.
CDCl3):
d 3.23 (s, 3H), 3.82 (s, 3H), 3.83 (s, 3H), 3.90 (s, 3H), 3.94
4.1.10.1. (2-Hydroxy-3,4,5-trimethoxyphenyl)(4-(methylamino)
phenyl)methanone (9). The title compound was obtained from
compound 24a (365 mg, 1.0 mmol) according to general procedure
(s, 3H), 4.74 (s, 1H), 7.03 (s, 1H), 7.13 (dd, 1H, J ¼ 2.4, 8.4 Hz), 7.41e
7.47 (m, 2H).
E (301 mg, 83%). 1H NMR (500 MHz, CDCl3):
d
2.93 (d, 3H, J ¼ 4.5 Hz,
4.1.8.4. (3-Fluoro-4-methoxyphenyl)(3,4,5-trimethoxy-2-(methox-
ymethoxy)phenyl)methanone (24e). The title compound was ob-
tained from 3-fluoro-4-methoxybenzaldehyde (200 mg, 1.3 mmol)
according to general procedure C (130 mg, 22%). 1H NMR (300 MHz,
NCH3), 3.76 (s, 3H), 3.97 (s, 3H), 4.05 (s, 3H), 4.33 (brs, 1H), 6.63
(d, 2H, J ¼ 9.0 Hz), 6.96 (s, 1H), 7.63 (d, 2H, J ¼ 8.5 Hz), 12.13 (s, 1H).
13C NMR (75 MHz, CDCl3):
d 30.0, 56.6, 61.1, 61.3, 110.6, 111.1, 114.4,
126.0, 132.1, 141.6, 144.5, 148.7, 152.7, 152.8, 198.2. HRMS-ESI calcd.
CDCl3):
d 3.19 (s, 3H), 3.82 (s, 3H), 3.94e3.95 (m, 9H), 4.90 (s, 2H),
for C17H20NO5 [M þ H]þ 318.1341, found 318.1340.
6.63 (s, 1H), 6.94e7.00 (m, 1H), 7.59e7.66 (m, 2H).
4.1.10.2. (2-Hydroxy-3,4,5-trimethoxyphenyl)(2-hydroxy-4-
methoxyphenyl)methanone (11). The title compound was obtained
from compound 24b (423 mg, 1.0 mmol) according to general
4.1.8.5. (4-Methoxy-3-nitrophenyl)(3,4,5-trimethoxy-2-(methox-
ymethoxy)phenyl)methanone (24f). The title compound was ob-
tained from 4-methoxy-3-nitrobenzaldehyde (603 mg, 1.3 mmol)
according to general procedure C (1 g, 75%). 1H NMR (300 MHz,
procedure E (272 mg, 81%). 1H NMR (500 MHz, CDCl3):
d 3.77
(s, 3H), 3.84 (s, 3H), 3.94 (s, 3H), 4.01 (s, 3H), 6.44 (dd, 1H, J ¼ 2.0,
CDCl3):
d 3.17 (s, 3H), 3.84 (s, 3H), 3.95 (s, 3H), 3.97 (s, 3H), 4.04 (s,
9.0 Hz), 6.50 (d, 1H, J ¼ 2.0 Hz), 6.79 (s, 1H), 7.54 (d, 1H, J ¼ 9.0 Hz),
9.50 (s, 1H), 11.64 (s, 1H). 13C NMR (75 MHz, CDCl3):
d 55.0, 56.0,
3H), 4.89 (s, 2H), 6.68 (s, 1H), 7.14 (d, 1H, J ¼ 8.7 Hz), 8.08 (d, 1H,
J ¼ 2.1, 8.7 Hz), 8.32 (d, 1H, J ¼ 2.1 Hz).
60.6, 100.9, 106.7, 108.9, 113.0, 115.6, 134.3, 141.0, 145.0, 147.2, 148.1,
164.7, 165.5, 198.7. HRMS-ESI calcd. for C17H19O7 [M þ H]þ 335.1131,
found 335.1143.
4.1. 8. 6. (4-(Dimethylamino)phenyl)(2-hydroxy-3, 4, 5-
trimethoxyphenyl)methanone (10). The title compound was ob-
tained from 4-(dimethylamino)benzaldehyde (370 mg, 2.5 mmol)
according to general procedure C (380 mg, 46%). 1H NMR (500 MHz,
4.1.10.3. (2-Amino-4-methoxyphenyl)(2-hydroxy-3,4,5-
trimethoxyphenyl)methanone (12). The title compound was ob-
tained from compound 24d (320 mg, 0.79 mmol) according to
general procedure E (221 mg, 84%). 1H NMR (500 MHz, CDCl3):
CDCl3):
d 3.03 (s, 6H), 3.79 (s, 3H), 3.86 (s, 3H), 3.91 (s, 3H), 6.61
(d, 2H, J ¼ 11.0 Hz), 6.63 (s, 1H), 7.28 (d, 2H, J ¼ 11.5 Hz). 13C NMR
(75 MHz, CDCl3):
d 39.9, 56.0, 60.7, 61.0, 106.9, 110.4, 125.3, 127.6,
d
3.88 (s, 3H), 3.90 (s, 3H), 3.98 (s, 3H), 4.03 (s, 3H), 6.29 (s, 1H), 6.65
132.6, 140.5, 144.4, 145.0, 147.6, 153.5, 194.0. HRMS-ESI calcd. for
(dd, 1H, J ¼ 2.0, 9.5 Hz), 6.67e6.68 (m, 1H), 7.14 (s, 1H), 7.89 (d, 1H,
C
18H22NO5 [M þ H]þ 332.1498, found 332.1499.
J ¼ 9.5 Hz). 13C NMR (75 MHz, CDCl3):
d
55.1, 56.2, 60.8, 61.1, 88.8,
106.5, 109.1, 111.9, 119.5, 123.9, 140.9, 141.7, 144.1, 146.7, 159.1, 161.4,
161.8. HRMS-ESI calcd. for C17H20NO6 [M þ H]þ 334.1291, found
334.1190.
4.1.9. General procedure D for reduction of nitro group to provide
24d and 24g
To a solution of nitro compound (1 equiv) in isopropanol and
water (5:1, 0.1 M) iron powder (2 equiv) and ammonium chloride
(2 equiv) was added. The mixture was heated to reflux for 2 h and
then diluted with EtOAc. The mixture was filtered off with celite
and the organic layer was collected. The crude product was purified
4.1.10.4. (3-Fluoro-4-methoxyphenyl)(2-hydroxy-3,4,5-
trimethoxyphenyl)methanone (13). The title compound was ob-
tained from compound 24e (140 mg, 0.37 mmol) according to
general procedure E (110 mg, 88%). 1H NMR (300 MHz, CDCl3):