14
Z. Guo et al. / European Journal of Medicinal Chemistry 56 (2012) 10e16
7.26e7.22 (m, 4H, AreH), 7.02 (d, 1H, J ¼ 8.7 Hz, AreH), 6.22 (s, 1H,
CeH), 5.87 (s, 1H, CeH), 3.76 (s, 3H, CeH). 13C NMR (150 MHz,
5.86 (s, 1H, CH), 3.73 (s, 6H, CH3). 13C NMR (150 MHz, DMSO-d6)
d:
198.88, 169.33, 165.91, 149.60, 133.96, 133.86, 133.37, 132.45, 132.39,
129.63, 128.79, 128.66, 127.26, 126.81, 126.27, 121.33, 114.93, 71.42,
66.33, 57.09, 52.78; ESI-MS (m/z): 515.52 (M þ H).
CDCl3)
d: 199.93, 169.21, 165.67, 135.92, 133.92, 133.82, 132.68,
131.84, 131.59, 130.91, 130.44, 129.50, 128.88, 128.72, 126.21, 120.59,
67.13, 64.27, 52.77; ESI-MS (m/z): 517.36 (M ꢂ H).
5.3.9. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-5-oxo-2-
thioxo-8-(trifluoromethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-
4(5H)-yl)acetate (8i)
5.3.4. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-8-fluoro-
5-oxo-2- thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)
acetate (8d)
A light-yellow solid. Yield: 53%. M.p. 151e152 ꢀC. 1H NMR
A light-yellow solid. Yield: 58%. M.p. 140e142 ꢀC. 1H NMR
(DMSO-d6, 600 MHz):
d
12.89 (s, 1H, NeH), 7.68 (d, 1H, J ¼ 8.15 Hz,
(DMSO-d6, 600 MHz):
d
12.79 (s, 1H, NH), 7.57e7.55 (m, 3H, AreH),
AreH), 7.56 (d, 2H, J ¼ 8.5 Hz, AreH), 7.48e7.43 (m, 3H, AreH), 7.36
(s, 1H, AreH), 7.26e7.21 (m, 4H, AreH), 6.24 (s, 1H, CeH), 5.90 (s,
7.46 (d, 2H, J ¼ 8.52 Hz, AreH), 7.23 (s, 4H, AreH), 6.98e6.95 (m,1H,
AreH), 6.82 (dd, 1H, J ¼ 9.9, 2.4 Hz, AreH), 6.21 (s, 1H, CH), 5.85 (s,
1H, CeH), 3.76 (s, 3H, CeH). 13C NMR (150 MHz, DMSO-d6)
d:
1H, CH), 3.74 (s, 3H, CH3). 13C NMR (150 MHz, CDCl3)
d
: 200.48,
200.19, 169.26, 165.23, 136.84, 134.21, 133.31, 132.76, 132.73, 132.26,
132.20, 131.08, 130.54, 129.70, 129.00, 128.92, 127.28, 126.61, 124.25,
122.44, 122.14, 117.60, 70.58, 66.08, 52.92; ESI-MS (m/z): 553.24
(M þ H).
169.51, 166.40, 165.04, 163.35, 137.20, 137.13, 135.93, 133.89, 133.82,
133.78, 131.99, 131.88, 130.40, 129.53, 128.64, 126.23, 124.14, 124.12,
113.75, 113.60, 106.43, 106.26, 67.15, 64.30, 52.79; ESI-MS (m/z):
501.35 (M ꢂ H).
5.3.10. Methyl 2-(3-(4-chlorophenyl)-5-oxo-2-thioxo-8-
(trifluoromethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-
2-(4-fluorophenyl)acetate (8j)
5.3.5. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-7,8-difluoro-
5-oxo-2- thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)
acetate (8e)
A light-yellow solid. Yield: 59%. M.p. 132e135 ꢀC. 1H NMR
A yellow solid. Yield: 69%. M.p. 94e95 ꢀC. 1H NMR (DMSO-d6,
(DMSO-d6, 600 MHz):
d
12.89 (s, 1H, NeH), 7.68 (d, 1H, J ¼ 8.25 Hz,
600 MHz):
d
12.77 (s, 1H, NH), 7.52 (d, 2H, J ¼ 8.52 Hz, AreH), 7.48
AreH), 7.62e7.60 (m, 2H, AreH), 7.44 (d, 1H, J ¼ 7.45 Hz, AreH),
7.36 (s, 1H, AreH), 7.26e7.21 (m, 6H, AreH), 6.27 (s, 1H, CeH),
(dd, 1H, J ¼ 8.58, 10.62 Hz, AreH), 7.44 (d, 2H, J ¼ 8.64 Hz, AreH),
7.25 (d, 2H, J ¼ 8.82 Hz, AreH), 7.21 (d, 2H, J ¼ 7.98 Hz, AreH),
7.04 (dd, 1H, J ¼ 11.2, 7.00 Hz, AreH), 6.20 (s, 1H, CH), 5.86 (s, 1H,
5.84 (s, 1H, CeH), 3.75 (s, 3H, CeH). 13C NMR (150 MHz, CDCl3)
d:
200.50,169.69,166.14,164.20,162.54,135.76,134.23,134.00,133.95,
132.56, 132.51, 132.25, 131.91, 130.28, 128.73, 127.46, 126.22, 122.16,
116.56, 116.42, 66.91, 64.40, 52.82; ESI-MS (m/z): 537.13 (M þ H).
CH), 3.73 (s, 3H, CH3). 13C NMR (150 MHz, CDCl3)
d: 200.05, 169.42,
165.29, 164.28, 164.26, 164.14, 136.06, 134.53, 134.42, 134.07, 134.02,
133.96, 131.87, 131.80, 130.14, 129.58, 128.84, 126.13, 67.08, 64.43,
52.89; ESI-MS (m/z): 519.53 (M ꢂ H).
5.3.11. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-8-
methoxy-5-oxo-2-thioxo- 2,3-dihydro-1H-benzo[e][1,4]diazepin-
4(5H)-yl)acetate (8k)
5.3.6. Methyl 2-(8-chloro-3-(4-fluorophenyl)-5-oxo-2-thioxo-2,3-
dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-fluorophenyl)
acetate (8f)
A light-yellow solid. Yield: 56%. M.p. 135e136 ꢀC. 1H NMR
(DMSO-d6, 600 MHz):
d
12.64 (s, 1H, NeH), 7.54 (d, 2H, J ¼ 8.40 Hz,
A yellow solid. Yield: 70%. M.p. 143e144 ꢀC. 1H NMR (DMSO-d6,
AreH), 7.54e7.45 (m, 3H, AreH), 7.23 (s, 4H, AreH), 6.69 (dd, 1H,
J ¼ 2.00, 6.65 Hz, AreH), 6.54 (d, 1H, J ¼ 1.6 Hz, AreH), 6.18 (s, 1H,
CeH), 5.82 (s, 1H, CeH), 3.73 (s, 3H, CeH), 3.69 (s, 3H, CeH); 13C
600 MHz):
d
12.75 (s, 1H, NH), 7.59 (d, 1H, J ¼ 5.52 Hz, AreH), 7.58
(d, 1H, J ¼ 5.46 Hz, AreH), 7.47 (d, 1H, J ¼ 8.58 Hz, AreH), 7.24e7.19
(m, 4H, AreH), 7.13 (dd, 1H, J ¼ 2.10, 8.52 Hz, AreH), 7.06 (d, 1H,
J ¼ 1.98 Hz, AreH), 6.98 (t, 2H, J ¼ 8.82 Hz, AreH), 6.23 (s, 1H, CH),
NMR (150 MHz, DMSO-d6) d: 199.57, 169.57, 166.00, 162.11, 138.05,
134.03, 133.93, 133.24, 132.75, 132.47, 132.33, 128.91, 128.78, 127.20,
120.48, 112.23, 105.25, 70.75, 65.92, 55.94, 52.74; ESI-MS (m/z): 513
(M ꢂ H).
5.78 (s, 1H, CH), 3.29 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d:
200.43, 169.64, 165.49, (163.71, 162.60), (161.75, 160.66), 137.52,
136.63, 132.91, 132.84, 130.64, 130.03, 127.50, 126.77, 125.83, 120.02,
116.01, 115.89, 70.01, 65.72, 52.80; ESI-MS (m/z): 487.43 (M þ H).
5.3.12. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-9-
methyl-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-
4(5H)-yl)acetate (8l)
5.3.7. Methyl 2-(7-chloro-3-(4-chlorophenyl)-5-oxo-2-thioxo-2,3-
dihydro-1H-benzo[e][1,4]diazepin-4(5H)-yl)-2-(4-fluorophenyl)
acetate (8g)
A light-yellow solid. Yield: 50%. M.p. 240e241 ꢀC. 1H NMR
(DMSO-d6, 600 MHz):
d
11.97 (s, 1H, CeH), 7.58 (d, 2H, J ¼ 8.5 Hz,
A light-yellow solid. Yield: 73%. M.p. 120e123 ꢀC. 1H NMR
AreH), 7.44 (d, 2H, J ¼ 8.55 Hz, AreH), 7.30 (d, 1H, J ¼ 7.65 Hz,
AreH), 7.21e7.12 (m, 5H, AreH), 7.01 (t, 1H, J ¼ 7.7 Hz, AreH), 6.12
(s, 1H, CeH), 5.88 (s, 1H, CeH), 3.76 (s, 3H, CeH), 2.18 (s, 3H, CeH);
(DMSO-d6, 600 MHz):
d
12.70 (s, 1H, NH), 7.53 (d, 1H, J ¼ 5.52 Hz,
AreH), 7.52 (d, 1H, J ¼ 5.28 Hz, AreH), 7.49 (d, 1H, J ¼ 2.52 Hz,
AreH), 7.38 (dd, 1H, J ¼ 2.58, 8.70 Hz, AreH), 7.25e7.17 (m, 6H,
AreH), 6.97 (d, 1H, J ¼ 8.7 Hz, AreH), 6.16 (s, 1H, CH), 5.76 (s, 1H,
13C NMR (150 MHz, DMSO-d6)
d: 199.92, 169.38, 166.52, 135.09,
133.93, 133.83, 133.47, 132.50, 132.28, 130.11, 128.77, 128.65, 127.86,
126.71, 126.64, 71.51, 66.42, 52.81, 17.94; ESI-MS (m/z): 499.28
(M þ H).
CH), 3.71 (s, 3H, CH3). 13C NMR (150 MHz, CDCl3)
d: 199.70, 169.59,
165.92, 164.13, 162.47, 139.19, 134.17, 133.84, 132.61, 132.55, 132.50,
131.97, 131.45, 130.73, 129.84, 128.80, 128.69, 126.23, 124.45, 123.95,
120.98, 67.10, 64.33, 52.78; ESI-MS (m/z): 503.64 (M þ H).
5.3.13. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-7-
methyl-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-
4(5H)-yl)acetate (8m)
5.3.8. Methyl 2-(4-chlorophenyl)-2-(3-(4-chlorophenyl)-9-
methoxy-5-oxo-2-thioxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-
4(5H)-yl)acetate (8h)
A light-yellow solid. Yield: 71%. M.p. 220e222 ꢀC. 1H NMR
(DMSO-d6, 600 MHz):
d
12.67 (s, 1H, NeH), 7.54 (d, 2H, J ¼ 8.5 Hz,
A light-yellow solid. Yield: 62%. M.p. 123e125 ꢀC. 1H NMR
AreH), 7.45 (d, 2H, J ¼ 8.55 Hz, AreH), 7.32 (d, 1H, J ¼ 1.25 Hz,
AreH), 7.24e7.20 (m, 4H, AreH), 7.14 (dd, 1H, J ¼ 1.55, 8.35 Hz,
AreH), 6.88 (d, 1H, J ¼ 8.3 Hz, AreH), 6.17 (s, 1H, CeH), 5.87 (s, 1H,
CeH), 3.74 (s, 3H, CeH), 2.16 (s, 3H, CeH); 13C NMR (150 MHz,
(DMSO-d6, 600 MHz):
d
11.70 (s, 1H, NH), 7.59 (d, 2H, J ¼ 5.52 Hz,
AreH), 7.42 (d, 2H, J ¼ 8.58 Hz, AreH), 7.17 (s, 4H, AreH), 7.06e7.01
(m, 2H, AreH), 6.98 (dd,1H, J ¼ 1.50, 7.92 Hz, AreH), 6.12 (s,1H, CH),