2896 J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 18
Sakowski et al.
prepared from 5t (0.33 g, 0.39 mmol) by following general
procedure D. Compound 13b is a yellow solid (0.155 g, 74%
yield): mp 116 °C; H NMR (500 MHz, DMSO-d6) δ 3.05 (s,
prepared from 5v (0.270 g, 0.32 mmol) by following general
procedure D. Compound 13d is a yellow solid (0.295 g, 87%
yield): mp 86 °C; 1H NMR (400 MHz, DMSO-d6) δ 3.05 (s, 2H),
3.57 (s, 2H), 4.17 (m, 1H), 7.31 (m, 2H), 7.39 (m, 1H), 7.47 (m,
2H), 7.62 (m, 2H), 7.65 (m, 2H), 7.74 (m, 1H), 7.80 (m, 1H),
8.44 (s, 2H), 10.18 (s, 1H), 10.91 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 24.6, 54.5, 120.6, 122.5, 124.2, 125.9, 127.9, 128.0,
128.1, 128.7, 129.2, 130.2, 130.9, 131.1,131.2, 131.9, 132.1,
132.4, 134.1, 135.1, 136.7, 143.5, 165.2, 167.0, 194.5; ESI-MS
m/z ) 41 (100), 55 (92), 105 (86), 43 (86), 159 (64), 212 (49),
37 (45), 211 (43), 539 (0.81, M+ + H). Anal. (C24H22Cl3N3O3S)
C, H, N.
1
2H), 3.53 (s, 2H), 4.17 (m, 1H), 7.18 (m, 1H), 7.30 (m, 1H),
7.48 (m, 3H), 7.58 (m, 2H), 7.63 (m, 2H), 7.73 (m, 1H), 7.79
(m, 1H), 8.46 (s, 2H), 10.20 (s, 1H), 11.00 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 24.7, 40.7, 54.5, 122.3, 124.2, 124.5,
125.2, 128.0, 128.2, 129.3, 129.9, 130.4, 130.8, 131.4, 132.3,
132.5, 132.9, 134.4, 136,0, 165.8, 167.3, 195.2; ESI-MS m/z )
398 (100), 400 (68), 424 (32), 159 (53), 55 (52), 123(45), 105
(41), 212 (37), 211 (27), 538 (0.72, M+). Anal. (C24H22Cl3N3O3S)
C, H, N.
N-(2-Ben zoyl-4-n itr op h en yl)-2-(2,6-dich lor p h en yl)a cet-
a m id e (3u ). The compound was prepared by following general
procedure A. Compound 3u is a yellow solid (1.264 g, 64%
yield): mp 172 °C; 1H NMR (500 MHz, CDCl3) δ 4.15 (s, 2H),
7.18 (m, 1H), 7.32 (m, 2H), 7. 64 (m, 2H), 7.60 (m, 3H), 8.32
(m, 1H), 8.38 (m, 1H), 8.83 (m, 1H), 11.06 (s, 1H).
N-(4-Am in o-2-ben zoylph en yl)-2-(2,6-dich lor ph en yl)acet-
a m id e (4u ). The compound was prepared from 3u (1.225 g,
2.85 mmol) by following general procedure B. Compound 4u
is a yellow solid (1.012 g, 89% yield): mp 148 °C; 1H NMR
(400 MHz, CDCl3) δ 3.52 (s, 2H), 4.03 (s, 1H), 6.69(m, 1H),
6.80 (m, 1H), 7.14 (m, 1H), 7.28 (m, 2H), 7.39 (m, 2H), 7.51
(m, 1H), 7.61 (m, 2H), 8.26 (m, 1H), 10.12 (s, 1H).
N-[[3-Benzoyl-4-[2-(2,6-dichlorphenyl)acetylamino]phen-
yl]-Nr-ter t-bu tyloxyca r bon yl-S-tr itylcystein a m id e (5u ).
The compound was prepared from 4u (0.399 g, 1.0 mmol) by
following general procedure C. Compound 5u is a yellow solid
(0.334 g, 40% yield): mp 83 °C; 1H NMR (500 MHz, CDCl3) δ
1.31 (s, 9H), 2.51 (dd, J ) 13, 5 Hz, 1H), 2.65 (dd, J ) 13, 7
Hz, 1H), 3.77 (m, 1H), 4.06 (s, 2H), 4.67 (m, 1H), 7.13 (m, 3H),
7.19 (m, 8H), 7.29 (m, 2H), 7.33 (m, 6H), 7.39 (m, 2H), 7.44
(m, 1H), 7.51 (m, 1H), 7.60 (m, 2H), 7.65 (m, 1H), 8.48 (m,
1H), 10.50 (s, 1H).
N-(2-Ben zoyl-4-n itr op h en yl)-2-(2,5-dich lor p h en yl)a cet-
a m id e (3w ). The compound was prepared by following general
procedure A. Compound 3w is a yellow solid (1.239 g, 58%
yield): mp 143 °C; 1H NMR (500 MHz, CDCl3) δ 3.85 (s, 2H),
7.21 (m, 1H), 7.30 (m, 1H), 7.35 (m, 1H), 7.49 (m, 2H), 7.61
(m, 3H), 8.34 (m, 1H), 8.40 (m, 1H), 8.82 (m, 1H), 11.11 (s,
1H).
N-(4-Am in o-2-ben zoylph en yl)-2-(2,5-dich lor ph en yl)acet-
a m id e (4w ). The compound was prepared from 3w (1.2 g, 2.8
mmol) by following general procedure B. Compound 4w is a
yellow solid (0.928 g, 83% yield): mp 132 °C; 1H NMR (500
MHz, CDCl3) δ 3.59 (s, 2H), 3.72 (s, 2H), 6.71 (m, 1H), 6.80
(m, 1H), 7.16 (m, 1H), 7.22 (m, 1H), 7.31 (m, 1H), 7.39 (m,
2H), 7.55 (m, 1H), 7.62 (m, 2H), 8.22 (m, 1H), 10.18 (s, 1H).
N-[[3-Benzoyl-4-[2-(2,5-dichlorphenyl)acetylamino]phen-
yl]-Nr-ter t-bu tyloxyca r bon yl-S-tr itylcystein a m id e (5w ).
The compound was prepared from 4w (0.2 g, 0.5 mmol) by
following general procedure C. Compound 5w is a yellow solid
(0.215 g, 51% yield): mp 91 °C; 1H NMR (500 MHz, CDCl3) δ
1.31 (s, 9H), 2.51 (dd, J ) 13, 5 Hz, 1H), 2.66 (dd, J ) 13, 7
Hz, 1H), 3.63 (s, 1H), 3.76 (m, 2H), 4.68 (m, 1H), 7.13 (m, 4H),
7.19 (m, 8H), 7.25 (m, 1H), 7.33 (m, 6H), 7.41 (m, 2H), 7.46
(m, 1H), 7.52 (m, 1H), 7.62 (m, 2H), 7.67 (m, 1H), 8.45 (m,
1H), 10.55 (s, 1H).
N-[[3-Benzoyl-4-[2-(2,6-dichlorphenyl)acetylamino]phen-
yl]cystein a m id e Hyd r och lor id e (13c). The compound was
prepared from 5u (0.3 g, 0.35 mmol) by following general
procedure D. Compound 13c is a yellow solid (0.157 g, 77%
N-[[3-Benzoyl-4-[2-(2,5-dichlorphenyl)acetylamino]phen-
yl]cystein a m id e Hyd r och lor id e (13e). The compound was
prepared from 5w (0.49 g, 0.57 mmol) by following general
procedure D. Compound 13e is a yellow solid (0.295 g, 96%
1
yield): mp 143 °C; H NMR (400 MHz, DMSO-d6) δ 3.06 (s,
1
2H), 3.33 (m, 1H), 3.73 (s, 2H), 4.18 (s, 1H), 7.26 (m, 1H), 7.38
(m, 2H), 7.47 (m, 2H), 7.62 (m, 4H), 7.74 (m, 1H), 7.79 (m,
1H), 8.49 (s, 2H), 10.16 (s, 1H), 10.97 (s, 1H); 13C NMR (100
MHz, DMSO-d6) δ 24.6, 37.7, 54.5, 120.7, 122.6, 124.2, 127.8,
128.0, 129.1, 131.4, 132.4, 135.3, 137,4, 165.3, 166.3, 194.6;
ESI-MS m/z ) 105 (100), 212 (44), 44 (34), 211 (33), 159 (31),
237 (23), 424 (21); 502 (0.54, base). Anal. (C24H22Cl3N3O3S) C,
H, N.
yield): mp 117 °C; H NMR (500 MHz, DMSO-d6) δ 3.07 (s,
2H), 3.42 (s, 2H), 4.18 (m, 1H), 7.31 (m, 2H), 7.39 (m, 1H),
7.48 (m, 2H), 7.61 (m, 2H), 7.66 (m, 2H), 7.74 (m, 1H), 7.80
(m, 1H), 8.48 (s, 2H), 10.21 (s, 1H), 11.00 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 25.2, 39.5, 55.1, 121.1, 121.2, 123.0,
123.1, 124.8, 126.5, 128.5, 128.6, 128.7, 129.3, 129.8, 130.8,
131.6,131.7, 131.7, 132.4, 132.5, 132.7, 133.0, 134.7, 135,7,
137.2, 165.8, 167.6, 195.0; ESI-MS m/z ) 398 (100), 44 (73),
105 (59), 159 (53), 55 (52), 212 (37), 211 (27), 539 (0.64, M+
H). Anal. (C24H22Cl3N3O3S) C, H, N.
+
N-(2-Ben zoyl-4-n itr oph en yl)-2-(3,5-dich lor ph en yl)a cet-
a m id e (3v). The compound was prepared by following general
procedure A. Compound 3v is a yellow solid (1.76 g, 57%
yield): mp 145 °C; 1H NMR (500 MHz, CDCl3) δ 3.85 (s, 2H),
7.21 (m, 1H), 7.29 (m, 1H), 7.34 (m, 1H), 7.48 (m, 2H), 7.61
(m, 3H), 8.34 (m, 1H), 8.41 (m, 1H), 8.82 (m, 1H), 11.11 (s,
1H).
N-(4-Am in o-2-ben zoylph en yl)-2-(3,5-dich lor ph en yl)acet-
a m id e (4v). The compound was prepared from 3v (1.0 g, 2.3
mmol) by following general procedure B. Compound 4v is a
yellow solid (0.882 g, 96% yield): mp 146 °C; 1H NMR (400
MHz, CDCl3) δ 3.75 (s, 2H), 6.71 (m, 1H), 6.81 (m, 1H), 7.15
(m, 1H), 7.24 (m, 1H), 7.31 (m, 1H), 7.41 (m, 2H), 7.54 (m,
1H), 7.63 (m, 2H), 8.23 (m, 1H), 10.18 (s, 1H).
N-(2-Ben zoyl-4-n itr oph en yl)-2-(2,3-dich lor ph en yl)a cet-
a m id e (3x). The compound was prepared by following general
procedure A. Compound 3x is a yellow solid (1.328 g, 62%
1
yield): mp 78 °C; H NMR (500 MHz, CDCl3) δ 3.90 (s, 2H),
7.25 (m, 1H), 7.34 (m, 1H), 7.39 (m, 1H), 7.52 (m, 2H), 7.65
(m, 3H), 8.38 (m, 1H), 8.44 (m, 1H), 8.86 (m, 1H), 11.16 (s,
1H).
N-(4-Am in o-2-ben zoylph en yl)-2-(2,3-dich lor ph en yl)acet-
a m id e (4x). The compound was prepared from 3x (1.295 g,
3.0 mmol) by following general procedure B. Compound 4x is
1
a yellow solid (1.134 g, 94% yield): mp 152 °C; H NMR (500
MHz, CDCl3) δ 3.67 (s, 2H), 3.80 (s, 2H), 6.79 (m, 1H), 6.89
(m, 1H), 7.24 (m, 1H), 7.32 (m, 1H), 7.39 (m, 1H), 7.47 (m,
2H), 7.59 (m, 1H), 7.70 (m, 2H), 8.30 (m, 1H), 10.26 (s, 1H).
N-[[3-Benzoyl-4-[2-(2,3-dichlorphenyl)acetylamino]phen-
yl]-Nr -ter t-bu tyloxyca r bon yl-S-tr itylcystein a m id e (5x).
The compound was prepared from 4x (0.399 g, 1.0 mmol) by
following general procedure C. Compound 5x is a yellow solid
(0.528 g, 63% yield): mp 94 °C; 1H NMR (500 MHz, CDCl3) δ
1.31 (s, 9H), 2.51 (dd, J ) 13, 5 Hz, 1H), 2.66 (dd, J ) 13, 7
Hz, 1H), 3.76 (s, 2H), 3.78 (m, 1H), 4.68 (m, 1H), 7.13 (m, 3H),
7.19 (m, 8H), 7.25 (m, 1H), 7.33 (m, 7H), 7.42 (m, 2H), 7.46
(m, 1H), 7.52 (m, 1H), 7.62 (m, 2H), 7.67 (m, 1H), 8.44 (m,
1H), 10.55 (s, 1H).
N-[[3-Benzoyl-4-[2-(3,5-dichlorphenyl)acetylamino]phen-
yl]-Nr-ter t-bu tyloxyca r bon yl-S-tr itylcystein a m id e (5v).
The compound was prepared from 4v (0.399 g, 1.0 mmol) by
following general procedure C. Compound 5v is a yellow solid
1
(0.29 g, 34% yield): mp 91 °C; H NMR (400 MHz, CDCl3) δ
1.31 (s, 9H), 2.51 (dd, J ) 13, 5 Hz, 1H), 2.66 (dd, J ) 13, 7
Hz, 1H), 3.76 (s, 2H), 3.78 (m, 1H), 4.69 (m, 1H), 7.13 (m, 3H),
7.19 (m, 8H), 7.25 (m, 1H), 7.33 (m, 7H), 7.43 (m, 2H), 7.48
(m, 1H), 7.52 (m, 1H), 7.62 (m, 2H), 7.67 (m, 1H), 8.43 (m,
1H), 10.54 (s, 1H).
N-[[3-Benzoyl-4-[2-(3,5-dichlorphenyl)acetylamino]phen-
yl]cystein a m id e Hyd r och lor id e (13d ). The compound was