1595, 1544, 1478, 1372, 1296, 1255, 1163, 1111, 772 and 733 cm−1;
dH (500 MHz, CDCl3) 7.38 (0.3 H, dd, J 7.5, 1.5, ArH), 7.29 (0.7 H,
dd, J 7.5, 1.5, ArH), 7.24–7.1 (5.7 H, m, ArH), 7.08 (1 H, t, J 7.5,
ArH), 7.01 (0.3 H, m, ArH), 6.93 (0.7 H, t, J 8.5, ArH), 6.92 (0.3 H,
t, J 8.5, ArH), 6.50 (1.4 H, d, J 8.5, ArH), 6.49 (0.6 H, d, J 8.5,
ArH), 5.35 (0.7 H, d, J 9.5, HCHO), 5.33 and 5.26 (each 0.3 H,
d, J 10.5, HCHO), 5.24 (0.7 H, d, J 9.5, HCHO), 5.08 (0.7 H, d,
J 15, 1-H), 4.87 and 4.39 (each 0.3 H, d, J 16.5, 1-H), 4.05 (0.7 H,
d, J 15, 1-Hꢀ), 4.00–3.53 (11 H, m, 3-H2, 4-H, NCH2Ph, and 2 ×
OCH3), 3.2 (2 H, br. s, OH), 2.78–2.27 (4 H, overlapping m, 2ꢀ-H2
and 3ꢀ-H2), 1.64 (2.1 H, s, 5-CH3) and 1.50 (0.9 H, s, 5-CH3); dc
(125 MHz, CDCl3) 171.88, 171.49, 153.59, 153.37, 142.74, 139.80,
139.06, 138.88, 137.50, 136.13, 136.08, 134.97, 133.75, 133.28,
133.12, 128.41, 128.39, 128.35, 128.22, 127.11, 127.06, 126.91,
124.06, 124.01, 105.23, 80.24, 79.53, 78.64, 76.51, 56.08, 56.05,
53.86, 53.63, 51.63, 50.81, 46.91, 46.05, 44.88, 44.59, 32.96, 32.35,
26.21 and 26.11; m/z (ES) 521 (M+ + 1, 7%), 196 (69), 192 (56),
169 (29), 153 (94) and 110 (100).
692.2636); mmax 3464, 1597, 1543, 1493, 1478, 1370, 1347, 1296,
1254, 1162, 1110, 1034, 774 and 732 cm−1; dH (300 MHz, CDCl3)
7.95 (1 H, d, J 7.5, ArH), 7.73–7.60 (3 H, m, ArH), 7.47 (1 H,
dd, J 7.5, 1.5, ArH), 7.40–7.32 (5 H, m, ArH), 7.18 (1 H, t, J
7.5, ArH), 7.03 (1 H, t, J 8.5, ArH), 7.00 (1 H, dd, J 7.5, 1.5,
ArH), 6.62 (2 H, d, J 8.5, ArH), 5.47 and 5.46 (each 1 H, d, J
16, HCHO), 5.26 (1 H, br. s, OH), 4.62 and 4.50 (each 1 H, d, J
15.5, NHCHPh), 3.89 (6 H, s, 2 × OCH3), 3.75 (1 H, m, 4-H),
3.62 and 3.51 (each 1 H, d, J 14.5, 1-H), 3.31 (2 H, t, J 7.5, 3ꢀ-H2),
2.89 (2 H, br. d, J 2.5, 3-H2), 2.50 and 2.39 (each 1 H, m, 1ꢀ-H),
1.78–1.52 (2 H, m, 2ꢀ-H2) and 1.61 (3 H, s, 5-CH3); dC (75 MHz,
CDCl3) 153.75, 148.19, 143.89, 138.06, 136.85, 136.21, 136.04,
133.80, 133.75, 133.64, 132.32, 132.13, 131.26, 129.04, 128.54,
128.28, 127.14, 124.50, 123.98, 105.54, 80.46, 78.74, 75.90, 62.82,
59.79, 56.35, 55.79, 52.34, 46.28, 26.61 and 25.63; m/z (ES) 714
(M+ + 23, 15), 692 (M+ + 1, 15), 179 (12), 133 (12) and 101 (100).
6-[(2,6-Dimethoxyphenoxy)methyl]-5-hydroxy-5-methyl-2-[3-(N-
2-nitrophenylsulfonyl-N-phenyl-methyl)aminopropyl]-2,3,4,5-
tetrahydro-[1H]-2-benzazepin-4-one 34
(4RS,5SR)-4,5-Dihydroxy-6-[(2,6-dimethoxyphenoxy)methyl]-5-
methyl-2-[3-(N-2-nitrophenyl-sulfonyl-N-phenylmethyl)-
aminopropyl]-2,3,4,5-tetrahydro-[1H]-2-benzazepine 33
Dimethyl sulfoxide (0.120 cm3, 1.70 mmol) in dichloromethane
(2 cm3) was added to oxalyl chloride (89 lL, 1.02 mmol)
in dichloromethane (2 cm3) at −78 ◦C and the mixture was
stirred for 30 min before the diol 33 (234 mg, 0.39 mmol) in
dichloromethane (5 cm3) was added. After a further 30 min,
triethylamine (0.283 cm3, 2.03 mmol) was added and the mixture
was allowed to warm to 0 ◦C and stirred for an additional
30 min. Water (20 cm3) was added and the mixture was extracted
with ether (4 × 20 cm3). The organic extracts were washed with
brine, dried (Na2SO4) and concentrated under reduced pressure.
Chromatography of the residue using ethyl acetate–light petroleum
(75 : 25 → 100 : 0) as eluent gave the title compound 34 (191 mg,
82%) as a pale yellow gum (found: M+ + H, 690.2477. C36H40N3O9S
requires M, 690.2480); mmax 3444, 2360, 1714, 1595, 1544, 1477,
1369, 1296, 1255, 1163, 1113, 1021 and 782 cm−1; dH (300 MHz,
CDCl3) 7.86–7.77 (2 H, m, ArH), 7.73–7.61 (3 H, m, ArH), 7.38–
7.21 (6 H, m, ArH), 7.05 (1 H, t, J 8.5, ArH), 6.94 (1 H, d, J 7.5,
ArH), 6.64 (2 H, d, J 8.5, ArH), 5.60 and 5.29 (each 1 H, d, J 12,
HCHO), 4.91 (1 H, br s, OH), 4.59 and 4.48 (each 1 H, d, J 15.5,
NHCHPh), 3.88 (6 H, s, OCH3), 3.69 (1 H, d, J 16, 3-H), 3.67 (1 H,
d, J 18, 1-H), 3.54 (1 H, d, J 16, 3-Hꢀ), 3.35–3.25 (3 H, m, 1-Hꢀ and
3ꢀ-H2), 2.50 and 2.37 (each 1 H, m, 1ꢀ-H), 1.89 (3 H, s, 5-CH3) and
1.80–1.51 (2 H, m, 2ꢀ-H2); dC (75 MHz, CDCl3) 208.90, 154.11,
148.12, 140.39, 138.39, 136.99, 136.25, 134.82, 133.91, 133.44,
132.36, 131.27, 131.21, 129.37, 129.07, 128.54, 128.32, 127.42,
124.44, 124.10, 105.56, 81.79, 73.36, 63.44, 59.90, 56.35, 53.77,
52.48, 46.18, 26.42 and 26.26; m/z (ES) 712 (M+ + 23, 12%) and
690 (M+ + 1, 100).
The amide 31 (318 mg, 0.61 mmol) in tetrahydrofuran (5.1 cm3)
was added to borane (1 M in tetrahydrofuran, 3.06 cm3,
3.06 mmol) at 0 ◦C, and the mixture was stirred at room
◦
temperature for 16 h then cooled to 0 C and aqueous hydrogen
chloride (1 M, 5.1 cm3) was added. The mixture was heated
under reflux for 45 min and aqueous sodium hydroxide (1 M,
10 cm3) was added followed by dichloromethane (20 cm3). The
layers were separated and the aqueous phase was extracted with
dichloromethane (3 × 20 cm3). The organic extracts were washed
with water, brine, dried (MgSO4) and concentrated under reduced
pressure to give the amine 32 (304 mg) as a colourless gum
(found: M+ + H, 507.2856. C30H39N2O5 requires M, 507.2853);
mmax 3480, 3302, 1596, 1494, 1478, 1372, 1296, 1254, 1223, 1111,
1034, 910, 772, 733 and 700 cm−1; dH (300 MHz, CD3OD) 7.63
(1 H, dd, J 7.5, 2, ArH), 7.34–7.23 (3 H, m, ArH), 7.23–7.11 (4 H,
m, ArH), 7.06 (1 H, t, J 8.5, ArH), 6.71 (2 H, d, J 8.5, ArH), 5.58
and 5.29 (each 1 H, d, J 11, HCHO), 3.94–3.81 (3 H, m, 4-H and
NCH2Ph), 3.86 (6 H, s, 2 × OCH3), 3.82 and 3.76 (each 1 H, d, J
13, 1-H), 3.06 (1 H, dd, J 12.5, 2, 3-H), 2.93 (1 H, br. dd, J 13, 4.5,
3-Hꢀ), 2.79 (2 H, t, J 6.5, 3ꢀ-H2), 2.68 (2 H, t, J 6.5, 1ꢀ-H2), 1.84
(2 H, m, 2ꢀ-H2) and 1.69 (3 H, s, 5-CH3); dC (75 MHz, CDCl3)
153.77, 144.05, 138.24, 137.00, 135.58, 134.80, 133.38, 132.23,
129.27, 129.06, 128.36, 127.07, 123.97, 105.58, 80.14, 78.63, 75.80,
64.76, 58.62, 56.39, 52.35, 47.80, 25.58 and 25.07; m/z (ES) 545
(M+ + 39, 2%), 529 (M+ + 23, 16) and 507 (M+ + 1, 100).
2-Nitrobenzenesulfonyl chloride (136 mg, 0.61 mmol) was
added to the amine 32 (310 mg, 0.61 mmol), triethylamine
(0.128 cm3, 0.92 mmol), 4-dimethylaminopyridine (1.5 mg) in
dichloromethane (8 cm3) and the mixture was stirred at room
temperature for 16 h. Water (20 cm3) was added and the aqueous
phase was extracted with dichloromethane (4 × 20 cm3). The
organic extracts were washed with brine, dried (MgSO4) and
concentrated under reduced pressure. Chromatography of the
residue using methanol–dichloromethane (0 : 100 → 2 : 98) as
eluent gave the title compound 33 (314 mg, 74% from 31) as a pale
yellow gum (found: M+ + H, 692.2630. C36H42N3O9S requires M,
6-[(2,6-Dimethoxyphenoxy)methyl]-5-hydroxy-5-methyl-2-[3-(N-
phenylmethyl)aminopropyl]-2,3,4,5-tetrahydro-[1H]-2-
benzazepin-4-one 2
Thiophenol (38 lL, 0.37 mmol) was added to a suspension of
the sulfonamide 34 (86 mg, 0.13 mmol) and anhydrous potassium
carbonate (69 mg, 0.50 mmol) in acetonitrile (2.09 cm3) and the
mixture was stirred for 16 h at room temperature then concentrated
under reduced pressure. The residue was partitioned between
2166 | Org. Biomol. Chem., 2008, 6, 2158–2167
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