Y. Yu et al. / Bioorg. Med. Chem. 11 (2003) 1475–1491
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(1H, d, J=2.5), 6.45 (1H, dd, J=8.3, 2.4), 7.12–7.16
(3H, m), 7.42 (1H, dd, J=8.4, 1.7), 7.72–7.77 (2H, m);
13C NMR d 55.7, 56.4, 101.6, 104.8, 106.6, 106.8, 121.5,
126.4, 126.8, 127.2, 128.5, 129.9, 132.0, 135.6, 145.3,
150.0, 150.3, 160.5; HRMS (EI) calcd for C19H19NO3
m/z: 309.1365; found: 309.1355.
solution of 25 (500 mg, 1.5 mmol) and the trimethyl(ni-
troaryl)stannane 35, (0.6 g, 1.83 mmol) in THF (30 mL)
at room temperature and stirred for 0.5 h. The mixture
was then refluxed under N2 overnight. After cooling,
THF was evaporated and ethyl acetate was added to the
residue. The solution was washed with water. The
organic layer was filtered through Celite 545 and then
washed with brine, dried (Na2SO4), and evaporated in
vacuo. The residue was chromatographed using a 70:30
mixture of hexanes/ethyl acetate to give 38 in 42% yield;
1H NMR d 3.92 (3H, s), 6.19 (2H, s), 6.76 (1H, s), 7.12
(1H, d, J=2.5), 7.18 (1H, d, J=8.3), 7.28 (1H, dd,
J=9.0, 2.3), 7.70 (1H, s), 7.85 (1H, d, J=9.2), 7.93 (1H,
d, J=8.4); 13C NMR d 56.08, 100.59, 103.93, 106.31,
110.70, 121.54, 124.07, 126.47, 128.71, 129.55, 130.33,
130.99, 131.23, 142.83, 148.92, 152.07, 160.68.
6-(2-Amino-5-benzyloxy-4-methoxyphenyl)-2,3-dimethoxy-
naphthalene (33) and 6-(2-amino-5-hydroxy-4-methoxy-
phenyl)-2,3-dimethoxynaphthalene (34). Compound 29
(50 mg, 0.112 mmol) was hydrogenated in ethyl acetate
(40 mL) at 30 lb/inch2 using 10% palladium on carbon
(15 mg) as catalyst for 16 h. The solution was passed
through a Celite 545 bed and the catalyst was washed
with ethyl acetate (10 mLÂ3). Concentration of the
ethyl acetate solution in vacuo gave the crude product.
Column chromatography was performed using a 35:65
mixture of hexanes/ethyl acetate as eluting solvent to
give compounds 33 and 34.
6-(4,5-Methylenedioxy-2-nitrophenyl)-2-methoxynaph-
thalene (39). Tetrakis(triphenylphosphine)palladium(0)
(120 mg) and cuprous bromide (20 mg) were added to a
solution of 2-bromo-6-methoxynaphthalene (0.3 g, 1.27
mmol) and trimethyl(3,4-methylenedioxy-6-nitrophe-
nyl)stannane 35 (0.45 g, 1.37 mmol) in THF (30 mL) at
room temperature and the mixture stirred for 0.5 h. The
mixture was then refluxed under N2 for 16 h. After
cooling, THF was evaporated and 50 mL ethyl acetate
was added to the residue. The solution was washed with
water, filtered through Celite 545, then washed with
brine, dried (Na2SO4), and evaporated in vacuo. The
residue was chromatographed using a 80:20 mixture of
hexanes/ethyl acetate to give the desired product 39
6-(2-Amino-5-benzyloxy-4-methoxyphenyl)-2,3-dimethoxy-
naphthalene (33). The higher Rf material on thin layer
chromatography proved to be compound 33. The yield
was 34 mg (73%); 1H NMR d 3.90 (3H, s), 4.01 (3H, s),
4.02 (3H, s), 5.08 (2H, s), 6.42 (1H, s), 6.87 (1H, s), 7.12
(1H, s), 7.15 (1H, s), 7.33–7.48 (6H, m), 7.71–7.75 (2H,
m); 13C NMR d 56.4, 56.4, 56.5, 73.1, 101.5, 106.6,
106.8, 119.1, 120.0, 126.2, 126.8, 127.3, 128.2, 128.2,
128.5, 128.9, 129.9, 135.6, 138.2, 138.9, 141.7, 150.1,
150.3, 150.9; HRMS (EI) calcd for C26H25NO4 m/z:
415.1784; found: 415.1775.
(0.29 g) in 71% yield; mp 165–167 ꢁC; H NMR d 3.94
1
6-(2-Amino-5-hydroxy-4-methoxyphenyl)-2,3-dimethoxy-
naphthalene (34). The lower Rf material on thin layer
chromatography proved to be compound 34. The yield
was 6 mg (16%); IR (KBr) 3432, 2937, 2364, 1625, 1508,
(3H, s), 6.14 (2H, s), 6.88 (1H, s), 7.16–7.21 (2H, m),
7.31 (1H, dd, J=8.5, 1.9), 7.47 (1H, s), 7.67–7.77 (3H,
m); 13C NMR d 55.9, 103.5, 105.9, 106.2, 111.7, 119.9,
126.9, 127.0, 127.6, 129.2, 130.1, 133.8, 133.9, 134.5,
143.4, 147.5, 151.5, 158.6; HRMS (EI) calcd for
C18H13NO5 m/z: 323.0794; found: 323.0788.
1
1459, 1252, 1232 cmÀ1; H NMR d 3.88 (3H, s), 4.01
(3H, s), 4.02 (3H, s), 6.40 (1H, s), 6.85 (1H, s), 7.12 (1H,
s), 7.15 (1H, s), 7.41 (1H, dd, J=8.4, 1.7); 7.73 (1H, d,
J=1.5), 7.74 (1H, d, J=8.3); 13C NMR d 56.4, 100.5,
106.6, 106.8, 116.9, 121.1, 126.3, 126.8, 127.3, 128.5,
129.9, 135.5, 137.2, 139.1, 147.1, 150.1, 150.3.
7-(4,5-Methylenedioxy-2-nitrophenyl)-3-methoxynaphth-
alene (40). Tetrakis(triphenylphosphine)palladium(0)
(120 mg) and cuprous bromide (20 mg) were added to a
solution of 7-methoxy-2-trifluoromethanesulfonyl-
oxynaphthalene 37 (336 mg, 1.1 mmol) and tri-
methyl(nitroaryl)stannane 35 (300 mg, 0.92 mmol) in
THF (30 mL) at room temperature and the mixture was
stirred for 0.5 h. The mixture was then refluxed under
N2 overnight. After cooling, THF was evaporated in
vacuo and ethyl acetate (30 mL) was added to the resi-
due. The solution was washed with water. The organic
layer was filtered through Celite 545 bed, then washed
with brine, dried (Na2SO4), and evaporated in vacuo.
The residue was chromatographed using a 80:20 mix-
ture of hexanes/ethyl acetate to give 40 (100 mg) in 34%
yield; 1H NMR d 3.92 (3H, s), 6.15 (2H, s), 6.88 (1H, s),
7.13–7.23 (3H, m), 7.48 (1H, s), 7.64 (1H, s), 7.74–7.81
(2H, m); 13C NMR d 55.8, 103.5, 105.9, 106.5, 111.6,
119.8, 124.1, 126.0, 128.5, 128.7, 129.8, 133.9, 135.0,
136.6, 143.4, 147.6, 151.5, 158.6; HRMS (EI) calcd for
C18H13NO5 m/z: 323.0794; found: 323.0787.
7-Methoxy-2-trifluoromethanesulfonyloxynaphthalene (37).
A solution of 7-methoxy-2-naphthol (0.75 g, 4.3 mmol)
in THF (10 mL) was added to a suspension of sodium
hydride (60 wt%, 205 mg, 5.1 mmol) in THF (10 mL)
cooled by ice bath and stirred for 1.5 h. A solution of N-
phenyltrifluoromethanesulfonimide (1.55 g, 4.34 mmol)
in THF (10 mL) was then added, and the reaction mix-
ture was stirred for 9 h. After evaporation of the solvent
in vacuo, the residue was mixed with silica gel (4 g) and
then chromatographed using 500:18 hexanes/ethyl ace-
tate to give 37 (1.19 g) in 90% yield; mp 34 ꢁC (lit31
34 ꢁC); H NMR 3.93 (3H, s), 7.13–7.25 (3H, m), 7.65
1
(1H, d, J=2.5), 7.77 (1H, d, J=9.1), 7.83 (1H, d, J=8.8);
13C NMR d 55.9, 106.3, 116.1, 117.5, 118.5, 120.8, 122.5,
128.3, 129.9, 130.7, 135.4, 148.3, 159.4; HRMS (EI) calcd
for C12H9SO4F3 m/z: 306.0174; found: 306.0176.
6-(4,5-Methylenedioxy-2-nitrophenyl)-2,3-dimethoxynaph-
thalene (38). Tetrakis(triphenylphosphine)palladium(0)
(126 mg) and cuprous bromide (21 mg) were added to a
6-(2-Amino-4,5-methylenedioxyphenyl)-2,3-dimethoxy-
naphthalene (41). 6-(4,5-Methylenedioxy-2-nitrophe-