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T. Shinozuka et al. / Bioorg. Med. Chem. 14 (2006) 6789–6806
5.14.3. 1-(Biphenyl-3-ylamino)-N-((1S)-1-{[(4-methoxy-
phenyl)amino]methyl}propyl)cyclohexanecarboxamide
(17c). Yield: 85%; brown amorphous substance; 1H
NMR (400 MHz, CDCl3) d 0.88 (3H, t, J = 7.7 Hz),
1.24–1.48 (5H, m), 1.60–1.66 (3H, m), 1.94–2.08 (4H,
m), 3.02 (1H, dd, J = 8.1, 12.5 Hz), 3.13 (1H, dd,
J = 4.4, 12.5 Hz), 3.66 (1H, br s), 3.72 (3H, s), 4.03–
4.09 (2H, m), 6.43 (2H, d, J = 8.8 Hz), 6.60 (1H, dd,
J = 1.5, 8.1 Hz), 6.72 (2H, d, J = 8.8 Hz), 6.85 (1H, m),
7.01–7.05 (2H, m), 7.13 (1H, t, J = 8.1 Hz), 7.31 (1H,
t, J = 7.3 Hz), 7.37 (2H, t, J = 7.3 Hz), 7.53 (2H, d,
J = 7.3 Hz); IR (KBr): 3366, 2933, 2856, 1651, 1601,
1513 cmꢀ1; MS (FAB) m/z: 472 [M+H]+, 471, 250, 136.
5.14.7. 1-(Biphenyl-3-ylamino)-N-((1S)-1-{[(4-methoxy-
phenyl)amino]methyl}-3-methylbutyl)cyclohexanecarbox-
amide (17g). Yield: 88%; light yellow amorphous
substance; 1H NMR (400 MHz, CDCl3) d 0.82 (3H,
d, J = 6.6 Hz), 0.83 (3H, d, J = 6.6 Hz), 1.26–1.39
(5H, m), 1.51–1.65 (4H, m), 1.94–2.02 (4H, m), 2.99
(1H, dd, J = 7.3, 11.7 Hz), 3.11 (1H, dd, J = 4.4,
11.7 Hz), 3.73 (1H, br s), 3.73 (3H, s), 4.04 (1H, s),
4.18–4.25 (1H, m), 6.45 (2H, d, J = 8.8 Hz), 6.59
(1H, dd, J = 1.5, 8.1 Hz), 6.73 (2H, d, J = 8.8 Hz),
6.83 (1H, s), 6.99–7.02 (2H, m), 7.11 (1H, t,
J = 8.1 Hz), 7.30 (1H, t, J = 7.3 Hz), 7.36 (2H, t,
J = 7.3 Hz), 7.52 (2H, d, J = 7.3 Hz); IR (film): 3368,
2934, 2858, 1650, 1601, 1513 cmꢀ1; MS (FAB) m/z:
500 [M+H]+, 499, 250; Anal. Calcd for
C32H41N3O2Æ0.38H2O: C, 75.88; H, 8.31; N, 7.52.
Found: C, 75.90; H, 8.03; N, 8.30.
5.14.4. 1-(Biphenyl-3-ylamino)-N-((1S)-1-{[(4-methoxy-
phenyl)amino]methyl}butyl)cyclohexanecarboxamide (17d).
Yield: 72%; amorphous substance; 1H NMR (400 MHz,
CDCl3) d 0.83 (3H, t, J = 7.3 Hz), 1.24–1.70 (10H, m),
1.92–2.07 (4H, m), 3.02 (1H, dd, J = 8.1, 12.5 Hz),
3.12 (1H, dd, J = 4.4, 12.5 Hz), 3.66 (1H, s), 3.72 (3H,
s), 4.05 (1H, s), 4.09–4.18 (1H, m), 6.43 (2H, d,
J = 8.8 Hz), 6.60 (1H, dd, J = 2.2, 8.1 Hz), 6.72 (2H, d,
J = 8.8 Hz), 6.84 (1H, s), 7.01–7.04 (2H, m), 7.12 (1H,
t, J = 8.1 Hz), 7.29–7.32 (1H, m), 7.36 (2H, t,
J = 6.6 Hz), 7.53 (2H, d, J = 6.6 Hz); IR (KBr): 3366,
2932, 2857, 1651, 1601, 1513 cmꢀ1; MS (FAB) m/z:
486 [M+H]+, 485, 250; Anal. Calcd for
C31H39N3O2Æ0.32H2O: C, 75.77; H, 8.13; N, 8.55.
Found: C, 75.76; H, 7.79; N, 8.61.
5.14.8. 1-(Biphenyl-3-ylamino)-N-{(1S)-2-[(4-methoxy-
phenyl)amino]-1-phenylethyl}cyclohexanecarboxamide (17h).
Yield: 96%; white amorphous substance; 1H NMR
(400 MHz, CDCl3) d 1.31–2.05 (10H, m), 3.31–3.41
(3H, m), 3.70 (3H, s), 4.07 (1H, s), 5.19–5.24 (1H,
m), 6.39 (2H, d, J = 8.8 Hz), 6.59 (1H, dd, J = 2.2,
8.1 Hz), 6.68 (2H, d, J = 8.8 Hz), 6.82 (1H, s), 7.04
(1H, d, J = 8.1 Hz), 7.17 (1H, t, J = 7.3 Hz), 7.21–
7.26 (5H, m), 7.30–7.33 (1H, m), 7.37 (2H, t,
J = 7.3 Hz), 7.48 (2H, d, J = 7.3 Hz), 7.64 (1H, d,
J = 8.1 Hz); IR (KBr): 3369, 2934, 1658, 1601,
1513 cmꢀ1; MS (FAB) m/z: 520 [M+H]+, 519, 250.
5.14.5. 1-(Biphenyl-3-ylamino)-N-((1S)-1-{[(4-methoxy-
phenyl)amino]methyl}pentyl)cyclohexanecarboxamide (17e).
Yield: 68%; amorphous substance; 1H NMR (400 MHz,
CDCl3) d 0.72 (3H, t, J = 6.6 Hz), 1.11–1.63 (12H, m),
1.88–2.00 (4H, m), 2.95 (1H, dd, J = 8.1, 12.5 Hz),
3.05 (1H, dd, J = 4.4, 12.5 Hz), 3.60 (1H, s), 3.65 (3H,
s), 3.98 (1H, s), 4.02–4.09 (1H, m), 6.37 (2H, d,
J = 8.8 Hz), 6.52 (1H, dd, J = 1.5, 8.1 Hz), 6.65 (2H, d,
J = 8.8 Hz), 6.77 (1H, s), 6.96 (2H, t, J = 7.3 Hz), 7.05
(1H, t, J = 8.1 Hz), 7.21–7.25 (1H, m), 7.29 (2H, t,
J = 7.3 Hz), 7.46 (2H, d, J = 7.3 Hz); IR (KBr): 3366,
3054, 3029, 2931, 1651, 1601, 1574, 1513 cmꢀ1; MS
(FAB) m/z: 500 [M+H]+, 499, 250, 136; Anal. Calcd
for C32H41N3O2Æ0.30H2O: C, 76.09; H, 8.30; N, 8.32.
Found: C, 76.10; H, 8.43; N, 8.30.
5.14.9. N-{(1S)-1-Benzyl-2-[(4-methoxyphenyl)amino]eth-
yl}-1-(biphenyl-3-ylamino)cyclohexanecarboxamide (17i).
Yield: 86%; light yellow amorphous substance; 1H
NMR (400 MHz, CDCl3) d 1.24–2.04 (10H, m),
2.86 (2H, d, J = 6.6 Hz), 3.04 (1H, dd, J = 7.3,
12.5 Hz), 3.16 (1H, dd, J = 4.4, 12.5 Hz), 3.60 (1H,
s), 3.71 (3H, s), 3.99 (1H, s), 4.37–4.47 (1H, m),
6.38 (2H, d, J = 8.8 Hz), 6.52 (1H, d, J = 8.1 Hz),
6.69 (2H, d, J = 8.8 Hz), 6.82 (1H, s), 7.02 (1H,
d, J = 8.1 Hz), 7.08–7.25 (7H, m), 7.29–7.32 (1H,
m), 7.37 (2H, t, J = 6.6 Hz), 7.53 (2H, d,
J = 7.3 Hz); IR (KBr): 3369, 2934, 2956, 1654,
1601, 1513 cmꢀ1
;
MS (FAB) m/z: 534 [M+H]+,
533, 250; Anal. Calcd for C35H39N3O2Æ0.54H2O: C,
77.36; H, 7.43; N, 7.73. Found: C, 77.35; H,
7.51; N, 7.80.
5.14.6. 1-(Biphenyl-3-ylamino)-N-((1S)-1-{[(4-methoxy-
phenyl)amino]methyl}-2-methylpropyl)cyclohexanecarboxa-
mide (17f). Yield: 64%; brown amorphous substance; 1H
NMR (400 MHz, CDCl3) d 0.87 (3H, d, J = 6.6 Hz),
0.91 (3H, d, J = 7.3 Hz), 1.22–1.43 (3H, m), 1.58–1.69
(3H, m), 1.83–1.91 (1H, m), 1.94–2.05 (4H, m), 2.98
(1H, dd, J = 8.8, 11.7 Hz), 3.17 (1H, dd, J = 4.4,
11.7 Hz), 3.64 (1H, br s), 3.73 (3H, s), 3.97–4.04 (1H,
m), 4.06 (1H, s), 6.41 (2H, dd, J = 8.8 Hz), 6.61 (1H,
dd, J = 1.5, 8.1 Hz), 6.71 (2H, d, J = 8.8 Hz), 6.85–6.86
(1H, m), 7.01 (1H, d, J = 8.1 Hz), 7.10 (1H, t,
J = 8.1 Hz), 7.14 (1H, d, J = 9.5 Hz), 7.30 (1H, t,
J = 7.3 Hz), 7.36 (2H, t, J = 7.3 Hz), 7.52 (2H, d,
J = 7.3 Hz); IR (KBr): 3368, 2932, 2857, 1654, 1601,
1513 cmꢀ1; MS (FAB) m/z: 486 [M+H]+, 485, 250,
136; Anal. Calcd for C31H39N3O2Æ0.44H2O: C, 75.43;
H, 8.14; N, 8.51. Found: C, 75.50; H, 7.79; N, 8.41.
5.14.10. 1-(Biphenyl-3-ylamino)-N-((1S)-1-{[(4-methoxy-
phenyl)amino]methyl}-3-phenylpropyl)cyclohexanecarb-
oxamide (17j). Yield: 97%; amorphous substance; 1H
NMR (400 MHz, CDCl3) d 1.29–2.04 (12H, m),
2.53–2.66 (2H, m), 3.06 (1H, dd, J = 7.3, 12.5 Hz),
3.14 (1H, dd, J = 5.1, 12.5 Hz), 3.60 (1H, s), 3.71 (3H,
s), 4.05 (1H, s), 4.14–4.22 (1H, m), 6.41 (2H, d,
J = 8.8 Hz), 6.61 (1H, d, J = 1.5, 8.1 Hz), 6.70 (2H, d,
J = 8.8 Hz), 6.86 (1H, s), 7.00–7.87 (11H, m),
7.52 (2H, d, J = 7.3 Hz); IR (KBr): 3367, 2935, 2856,
1653, 1602, 1513 cmꢀ1; MS (FAB) m/z: 548 [M+H]+,
547, 250; Anal. Calcd for C36H41N3O2Æ0.84H2O: C,
76.82; H, 7.64; N, 7.47. Found: C, 76.68; H, 7.54; N,
7.61.