1716 J ournal of Medicinal Chemistry, 1996, Vol. 39, No. 8
Vaccaro et al.
3.27 (1H, m), 2.76 (1H, m), 2.55 (1H, m), 2.10 (1H, m), 1.61
(1H, m). CHN: calcd for C30H27NO2 C ) 83.11, H ) 6.28, N
) 3.23; found C ) 82.94, H ) 6.27, N ) 3.36. HRMS: calcd
for C30H27NO2, 433.2042; found, 433.2050. MS (CI): 434 (M+,
100), 212 (31). Mp: 210-211 °C. TLC: Rf ) 0.35 (40% EtOAc/
hexane), UV, Ce stain. Purification: recrystallization from
CH2Cl2/hexane. Yield: 67%.
N-(tr a n s-2-P h en yl-6-h ydr oxy-1,2,3,4-tetr ah ydr on aph th -
1-yl)d ip h en yla ceta m id e (5l). Prepared from trans 5k . 1H
NMR (200 MHz, DMSO/CDCl3): 8.91 (1H, s, OH), 8.25 (1H,
d, J ) 9.2 Hz, NH), 7.16 (10H, m, Ar), 7.04 (3H, m, Ar), 6.76
(1H, d, J ) 8.4 Hz), 6.68 (2H, m, Ar), 6.44 (2H, m, Ar), 5,19
(1H, t, J ) 9.l7 Hz, NCH), 4.78 (1H, s, OCH3), 2.84 (2H, m),
2.70 (1H, m), 2.52 (1H, m), 2.00 (1H, m). MS (FAB): 434 (M+,
21), 223 (100). IR (KBr): 3397, 3169, 2926, 1639, 1582, 1534,
1495, 1249, 701 cm-1. CHN: calcd for C30H27NO2 C ) 83.11,
H ) 6.27, N ) 3.23; found C ) 82.97, H ) 6.00, N ) 3.09. Mp:
248-250 °C, white crystals. TLC: Rf ) 0.38 (10% EtOAc/CH2-
Cl2), Ce stain. Purification: recrystallized from CH2Cl2/MeOH.
Yield: 87%.
2.77 (2H, m), 2.68 (1H, m), 1.93 (2H, m). CHN: calcd for
C30H27NO3 C ) 80.15, H ) 6.05, N ) 3.12; found C ) 79.71, H
) 6.04, N ) 3.24. HRMS: calcd for C30H27NO3: 450.2069 found
450.2075. MS (CI): 450 (M+, 96), 239 (41), 212 (100). Mp:
246-247 °C. TLC: Rf ) 0.16 (5% MeOH/CH2Cl2), UV, Ce
stain.
N-[cis-2-(4-H yd r oxyp h en yl)-7-h yd r oxy-1,2,3,4-t et r a -
h yd r on a p h th yl]d ip h en yla ceta m id e (5q). Prepared from
9d by method 5. 1H NMR (400 MHz, DMSO): 8.34 (1H, d, J
) 9.84 Hz), (2H, m, Ar), 7.22 (3H, m, Ar), 7.18 (3H, m, Ar),
7.02 (2H, d, J ) 8.44 Hz, Ar), 6.92 (1H, d, J ) 8.24 Hz, Ar),
6.59 (6H, m, Ar), 5.24 (1H, dd, J ) 4.6, 9.8 Hz, NCHCH), 4.81
(1H, s, Ph2CH), 3.04 (1H, m), 2.77 (2H, m), 2.24 (1H, m), 1.81
(1H, m). CHN: calcd for C30H27NO3 C ) 80.15, H ) 6.06, N
) 3.12; found C ) 79.90, H ) 6.01, N ) 3.22. MS (FAB): 450
(M+, 97), 238 (100), 211 (51). Mp: 244-245 °C. TLC: Rf )
0.17 (5% MeOH/CH2Cl2), UV, Ce stain.
t r a n s-N -[2-(4-H yd r oxyp h e n yl)in d a n -1-yl]d ip h e n yl-
a ceta m id e (4). Prepared from 8 by method 7. 1H NMR (200
MHz, CDCl3): 8.14 (2H, m), 7.74 (1H, d, J ) 8 Hz), 7.51 (1H,
d, J ) 8 Hz), 7.24 (14H, m), 5.79 (2H, m), 4.95 (1H, s), 3.37
(2H, m), 3.18 (1H, m). CHN: calcd for C29H25NO2 C ) 83.03,
H ) 6.01, N ) 3.34; found C ) 82.71, H ) 6.34, N ) 3.21. Mp:
188-190 °C. MS (CI): 420 (M+, 100), 208 (72).
cis-N-[2-(4-Hyd r oxyp h en yl)in d a n -1-yl]d ip h en yla ceta -
m id e (4). Prepared from 8 by method 7.1H NMR (400 MHz,
CDCl3): 7.17 (10H, m), 6.99 (2H, d, J ) 7.5 Hz), 6.92 (2H, d,
J ) 7.6 Hz), 6.70 (2H, d, J ) 8.6 Hz), 6.53 (2H, d, J ) 8.6 Hz),
5.82 (1H, t, J ) 8.2 Hz), 5.70 (1H, s), 5.40 (1H, d, J ) 9.2 Hz),
4.74 (1H, s), 3.86 (1H, dt, J ) 4.0, 7.8 Hz), 3.30 (1H, dd, J )
7.9, 16.2 Hz), 3.05 (1H, dd, J ) 4.0, 16.2 Hz). CHN: calcd for
C29H25NO2 C ) 83.03, H ) 6.01, N ) 3.34; found C ) 83.15, H
) 6.12, N ) 3.07. MS (CI): 420 (M+, 100). Mp: 136.5-139
°C.
N-(cis-2-P h en yl-6-h yd r oxy-1,2,3,4-t et r a h yd r on a p h t h -
1-yl)d ip h en yla ceta m id e (5l). Prepared from cis 5k . 1H
NMR (300 MHz, DMSO/CDCl3): 8.40 (1H, d, J ) 9.8 Hz), 7.23
(11H, m, Ar), 7.10 (2H, m, Ar), 6.92 (1H, J ) 9.21 Hz), 5.54
(2H, m, Ar), 6.52 (2H, m, Ar), 5.29 (1H, dd, J ) 4.8, 9.8 Hz),
4.78 (1H, PhCH), 3.15 (1H, m), 2.82 (2H, m), 2.34 (1H, m),
1.93 (1H, m). MS (EI): 434 (M+, 16), 224 (100), 167 (19), 91
(12). CHN: calcd for C30H27NO2 C ) 83.11, H ) 6.27, N )
3.23; found C ) 81.68, H ) 6.15, N ) 2.97. Mp: 248-250 °C.
HRMS: calcd for C30H27NO2, 433.2042; found, 433.2027. IR
(KBr): 3312, 3308, 3075, 3043, 2947, 1656, 1542, 1497, 1270,
701 cm-1
. Mp: 254-255 °C. TLC: Rf ) 0.25 (40% EtOAc/
CH2Cl2), UV, Ce stain. Purification: recrystallized from CH2-
Cl2/hexane.
N-(tr a n s-2-P h en yl-7-h ydr oxy-1,2,3,4-tetr ah ydr on aph th -
1-yl)d ip h en yla ceta m id e (5n ). Prepared from trans 5m . 1H
NMR (300 MHz, CDCl3): 7.30 (3H, m, Ar), 7.13 (9H, m, Ar),
6.92 (2H, d, J ) 6.2 Hz, Ar), 6.85 (1H, d, J ) 8.2 Hz, Ar), 6.58
(3H, m, Ar), 6.50 (1H, d, J ) 2.5 Hz, Ar), 5.55 (1H, m, NCH),
5.43 (1H, m, NCHCH), 4.79 (1H, s, Ph2CH), 2.73 (2H, m), 2.52
(1H, m), 1.96 (2H, m). CHN: calcd for C30H27NO2 C ) 83.11,
H ) 6.28, N ) 3.23; found C ) 82.75, H ) 6.25, N ) 3.34.
HRMS: calcd for C30H27NO2, 433.2042; found, 433.2041. MS
(CI): 434 (M+, 100). Mp: 220-222 °C. TLC: Rf ) 0.15 (30%
EtOAc/CH2Cl2), UV, Ce stain. Purification: recrystallized
from CH2Cl2 /hexane. Yield: 66%.
N -[cis-6,7,8,9-Te t r a h yd r o-6-(4-h yd r oxyp h e n yl)-5H -
ben zocycloh ep ten -5-yl]d ip h en yla ceta m id e (6). Prepared
from 10 by method 6. 1H NMR (200 MHz, CDCl3): 7.19 (6H,
m, Ar), 7.08 (2H, dt, J ) 1.9, 6.6 Hz, Ar), 7.00 (6H, m, Ar),
6.60 (2H, d, J ) 8.4 Hz, Ar), 6.51 (2H, d, J ) 8.6 Hz, Ar), 5.33
(1H, d, J ) 3.5 Hz, NCHCH), 4.84 (1H, s, Ph2CH), 2.92 (1H,
dt, J ) 3.6, 11.4 Hz), 2.80 (1H, m), 2.41 (1H, m), 1.78 (4H, m),
1.55 (1H, m), 1.39 (1H, t, J ) 11.6 Hz). MS (CI): 448 (M + 1,
100), 236 (72). IR (KBr): 3410, 3236, 3060, 3045, 3025, 2918,
2854, 1651, 1597, 1582, 1452, 1364, 1233, 1207, 822 cm-1
.
CHN: calcd for C31H29NO2 C ) 83.19, H ) 6.53, N ) 3.13;
found C ) 83.46, H ) 6.59, N ) 3.08. Mp: 196.5-197.5 °C,
white crystals. TLC: Rf ) 0.11 (5% EtOAc/CH2Cl2), Ce, UV.
Purification: SiO2 chromatography (5-10% EtOAc/CH2Cl2),
further purified by recrystallization from CH2Cl2/MeOH.
Yield: 44%, white solid.
N-[tr a n s-6,7,8,9-Tet r a h yd r o-6-(4-h yd r oxyp h en yl)-5H-
ben zocycloh ep ten -5-yl]d ip h en yla ceta m id e (6). Prepared
from 10 by method 8. 1H NMR (200 MHz, CDCl3/CD3OD):
7.26-6.66 (18H, m, Ar), 6.14 (1H, d, J ) 9 Hz, NH), 5.40 (1H,
t, J ) 9.3 Hz, CHN), 4.61 (1H, s, PhCH), 3.69 (3H, s, OCH3),
3.19 (1H, m), 2.94 (1H, m), 2.65 (1H, m), 2.44 (1H, m), 1.82
(3H, m). MS (FAB): 462 (M+, 85), 307 (50), 289 (40), 250 (100),
212 (40). IR (KBr): 3464, 3295, 2930, 1648, 1550, 1513, 1248,
1034, 744 cm-1. CHN: calcd for C31H29NO2 C ) 83.19, H )
6.53, N ) 3.13; found C ) 83.31, H ) 6.53, N ) 2.79. Mp:
235-235.5 °C, fluffy white solid. TLC: Rf ) 0.43 (5% EtOAc/
CH2Cl2), UV, Ce stain. Purification: chromatography (0-5%
EtOAc/CH2Cl2), recrystallized from EtOH/EtOAc. Yield: 87%,
white solid.
N -[cis-3-(4-H yd r oxyp h e n yl)-3,4-d ih yd r o-2H -b e n zo-
p yr a n -4-yl]d ip h en yla ceta m id e (7). Prepared from 11 by
method 5.1H NMR (300 MHz, CDCl3): 7.16 (9H, m), 6.94 (2H,
m), 6.81 (6H, m), 6.48 (2H, d, J ) 8.6 Hz), 5.61 (2H, m), 4.74
(1H, s), 4.38 (1H, dd, J ) 3.0, 11 Hz), 3.97 (1H, dd, J ) 10.9,
13.7 Hz), 3.36 (1H, m). MS (FAB): 436 (M+, 100), 316 (15),
225 (25). CHN: calcd for C29H25NO3 C ) 79.98, H ) 5.79, N
) 3.22 found C ) 79.97, H ) 5.80, N ) 3.31. Mp: 154-156
°C, white solid. TLC: Rf ) 0.21 (5% EtOAc/CH2Cl2), UV, Ce
stain. Purification: recrystallized from CH2Cl2/MeOH.
N-[tr a n s-3-(4-Hyd r oxyp h en yl)-3,4-d ih yd r o-2H-ben zo-
p yr a n -4-yl]d ip h en yla ceta m id e (7). Prepared from 11 by
N-(cis-2-P h en yl-7-h yd r oxy-1,2,3,4-t et r a h yd r on a p h t h -
1-yl)d ip h en yla ceta m id e (5n ). Prepared from cis 5m . 1H
NMR (300 MHz, CDCl3): 7.53 (1H, bs), 7.40 (3H, m, Ar), 7.28
(6H, m, Ar), 7.15 (2H, dd, J ) 2.2, 7.7 Hz, Ar), 7.00 (3H, m,
Ar), 6.78 (4H, m, Ar), 5.80 (1H, d, J ) 10.4 Hz, NCH), 5.56
(1H, dd, J ) 5.0, 10.0 Hz, NCHCH), 4.83 (1H, s, Ph2CH), 3.29
(1H, m), 2.81 (2H, m), 2.10 (2H, m). CHN: calcd for C30H27
-
NO2 C ) 83.11, H ) 6.28, N ) 3.23; found C ) 82.88, H )
6.21, N ) 3.16. HRMS: calcd for C30H27NO2, 433.2042; found,
433.2039. MS (CI): 434 (M+, 100). Mp: 177-178 °C. TLC:
Rf ) 0.44 (40% EtOAc/CH2Cl2), UV, Ce stain. Purification:
SiO2 chromatography (40% EtOAc/hexane). Yield: 83%.
N-(tr a n s-2-P h en yl-8-h ydr oxy-1,2,3,4-tetr ah ydr on aph th -
1-yl)d ip h en yla ceta m id e (50). Prepared from 9i by method
8. 1H NMR (300 MHz, CDCl3): 7.26 (9H, m, Ar), 7.11 (5H, m,
Ar), 6.87 (3H, m, Ar), 6.62 (1H, d, J ) 7.4 Hz, Ar), 5.80 (1H,
m, NCH), 5.56 (1H, dd, J ) 6.6, 9.1 Hz, NCHCH), 4.92 (1H, s,
Ph2CH), 2.78 (1H, m), 2.66 (1H, m), 1.94 (2H, m), 1.53 (1H,
m). CHN: calcd for C30H27NO2 C ) 83.11, H ) 6.28, N ) 3.23;
found C ) 82.88, H ) 6.20, N ) 3.43. MS (FAB): 434 (M+,
52), 222 (100), 211 (79). Mp: 218-219 °C. TLC: Rf ) 0.56
(5% MeOH/CH2Cl2), UV, Ce stain. Purification: SiO2 chro-
matography (20% EtOAc/hexane). Yield: 61%.
N-[tr a n s-2-(4-H yd r oxyp h en yl)-7-h yd r oxy-1,2,3,4-t et -
r a h yd r on a p h th -1-yl]d ip h en yla ceta m id e (5q). Prepared
from trans 5p . 1H NMR (400 MHz, DMSO): 8.49 (1H, d, J )
9.2 Hz, NH), 7.32 (2H, m, Ar), 7.25 (3H, m, Ar), 7.12 (3H, m,
Ar), 7.03 (2H, d, J ) 8.2 Hz, Ar), 6.89 (1H, d, J ) 8.2 Hz, Ar),
6.63 (4H, m, Ar), 6.57 (1H, d, J )8.4 Hz, Ar), 6.45 (1H, d, J )
2.1 Hz, Ar), 5.10 (1H, t, J ) 9.5 Hz, CHN), 4.83 (1H, s, PhCH),