312
Q. Guan et al. / European Journal of Medicinal Chemistry 87 (2014) 306e315
ꢁ
1
and stirred for 4 h. The reaction was sequentially washed with
water and saturated NaHCO , dried over anhydrous MgSO , filtered
432.9959; IR nmax/cm 3387 (NeH), 1730, 1646 (C]O), 1262, 1097
3
4
(CeO), 2957, 2860 (CeH), 3103, 1592, 1523 (Ar) (KBr).
and concentrated to give the crude product, which was purified by
column chromatography on silica gel with dichloromethane/MeOH
4.1.6.6. Methyl 5-[(5-cyano-1H-indol-3-yl)sulfinyl]-1H-benzoimida-
ꢀ
(v/v ¼ 20:1).
zol-2-ylcarbamate (8f). White solid; yield: 55%; M.p.: 247e250 C;
1
6
H NMR (400 MHz, DMSO-d ): d 12.39 (s, 1H), 11.91 (s, 2H), 8.24 (s,
4
.1.6.1. Methyl 5-[(1H-indol-3-yl)sulfinyl]-1H-benzoimidazol-2-
1H), 7.82 (s, 1H), 7.77 (s, 1H), 7.64 (d, J ¼ 8.4 Hz, 1H), 7.51e7.54 (m,
ꢀ
1
13
ylcarbamate (8a). White solid; yield: 61%; M.p.: 249e252 C; H
NMR (600 MHz, DMSO-d ); 11.94 (s, 3H), 8.03 (s, 1H), 7.77 (s, 1H),
.49 (d, J ¼ 8.3 Hz, 1H), 7.45 (d, J ¼ 8.1 Hz, 1H), 7.25e7.28 (m, 2H),
.12 (t, J ¼ 14.7 Hz, 1H), 6.92 (t, J ¼ 7.4 Hz, J ¼ 14.7 Hz,
¼ 7.4 Hz, J
H), 3.75 (s, 3H); C NMR (150 MHz, DMSO-d ): 154.61, 148.77,
37.22, 137.19, 131.67, 130.20, 123.51, 122.85, 120.64, 119.24, 117.61,
14.30, 112.76, 110.50, 52.75; HRMS (ESI): calcd for C17
2H), 7.34 (dd, J
1
¼ 1.5 Hz, J
2
¼ 8.3 Hz, 1H), 3.77 (s, 3H); C NMR
6
d
(100 MHz, DMSO-d
6
): 154.55, 148.87, 139.04, 136.71, 132.06,
d
7
7
1
1
125.67, 124.33, 123.25, 120.01, 118.98, 117.48, 114.33, 110.20, 102.89,
þ
1
2
1
2
52.77; HRMS (ESI): calcd for C18
H
14
N
5
O
3
S [MþH] : 380.0812,
1
3
ꢁ1
6
d
found: 380.0826; IR
n
max/cm 3387, 3237 (NeH), 1721, 1646 (C]
O), 1264, 1105 (CeO), 2955, 2850 (CeH), 3113, 1595, 1525 (Ar), 2225
(C^N) (KBr).
1
15 4 3
H N O S
nmax/cm 3359 (NeH),
þ
ꢁ1
[
1
MþH] : 355.0859, found: 355.0852; IR
728, 1642 (C]O), 1261, 1101 (CeO), 2954, 2854 (CeH), 3039, 1593,
4.1.7. General procedure for the preparation of compounds 9aef
A stirred solution of 7aef (0.2 mmol) in THF (15 mL) was treated
with meta-chloroperbenzoic acid (0.6 mmol) and stirred for 2 h at
room temperature. The reaction was sequentially washed with
1523 (Ar) (KBr).
4
.1.6.2. Methyl 5-[(2-methyl-1H-indol-3-yl)sulfinyl]-1H-benzoimi-
dazol-2-ylcarbamate (8b). White solid; yield: 59%; M.p.:
3 4
water and saturated NaHCO , dried over anhydrous MgSO , filtered
ꢀ
1
2
58e260 C; H NMR (100 MHz, DMSO-d
6
):
d
12.06 (s, 1H), 11.89 (s,
and concentrated to give the crude product, which was purified by
column chromatography on silica gel with dichloromethane/MeOH
(v/v ¼ 50:1).
2
H), 8.00 (s, 1H), 7.85 (m, 1H), 7.65 (d, J ¼ 8.3 Hz, 1H), 7.49 (d,
J ¼ 8.3 Hz, 1H), 7.36 (m, 1H), 7.13e7.16 (m, 2H), 3.76 (s, 3H), 2.68 (s,
1
3
3
H); C NMR (100 MHz, DMSO-d
6
): d 154.66,148.69,141.40,138.06,
1
37.29, 135.83, 129.08, 124.53, 122.08, 120.43, 118.71, 117.49, 114.31,
4.1.7.1. Methyl 5-[(1H-indol-3-yl)sulfonyl]-1H-benzoimidazol-2-
ꢀ
1
1
C
3
13.07, 111.74, 110.37, 52.78, 11.95; HRMS (ESI): calcd for
ylcarbamate (9a). White solid; yield: 72%; M.p.: 222e224 C; H
NMR (400 MHz, DMSO-d ): 12.33 (s, 3H), 8.12 (s, 1H), 8.06 (s, 1H),
7.77 (d, J ¼ 7.1 Hz, 1H), 7.66 (d, J ¼ 5.4 Hz, 1H), 7.48e7.50 (d,
þ
ꢁ1
18
17
H N
4
O
3
S [MþH] : 369.1016, found: 369.1018; IR
n
max/cm
6
d
301 (NeH), 1732, 1645 (C]O), 1274, 1086 (CeO), 2953, 2854
13
(
CeH), 3067, 1594, 1524 (Ar) (KBr).
J ¼ 7.4 Hz, 2H), 7.16e7.22 (m, 2H), 3.73 (s, 3H); C NMR (150 MHz,
DMSO-d ): 154.42, 149.74, 136.60, 136.02, 131.01, 123.29, 123.21,
6
d
4
.1.6.3. Methyl
5-[(5-fluoro-2-methyl-1H-indol-3-yl)sulfinyl]-1H-
119.77, 118.84, 116.27, 112.97, 52.88; HRMS (ESI): calcd for
þ
ꢁ1
benzoimidazol-2-ylcarbamate (8c). White solid; yield: 68%; M.p.:
C
17
H
15
N
4
O
4
S [MþH] : 371.0809, found: 371.0805; IR
nmax/cm
ꢀ
1
2
1
75e280 C; H NMR (400 MHz, DMSO-d
H), 7.49 (d, J ¼ 8.4 Hz, 1H), 7.34 (dd, J ¼ 4.5 Hz, J
¼ 2.1 Hz, J ¼ 9.3 Hz,1H), 6.77 (dd,
¼ 9.8 Hz, 1H), 3.76 (s, 3H), 2.66 (s, 3H); C NMR
100 MHz, DMSO-d ):
156.10e158.42 (d, J ¼ 233.3 Hz), 154.63,
48.78, 143.08, 136.90, 132.45, 124.83e124.94 (d, J ¼ 10.9 Hz),
17.42, 114.45, 113.41, 113.36, 112.89e112.99 (d, J ¼ 10.9 Hz),
6
):
d
11.94 (s, 3H), 7.75 (s,
3412, 3348 (NeH), 1735, 1651 (C]O), 1275, 1097 (CeO), 2955, 2854
(CeH), 3105, 1595, 1527 (Ar) (KBr).
1
2
¼ 8.8 Hz, 1H),
7
.22 (d, J ¼ 8.4 Hz,1H), 6.89 (td, J
1
2
13
J
1
¼ 2.1 Hz, J
2
4.1.7.2. Methyl 5-[(2-methyl-1H-indol-3-yl)sulfonyl]-1H-benzoimi-
ꢀ
(
1
1
6
d
dazol-2-ylcarbamate (9b). White solid; yield: 69%; M.p.: >300 C;
1
6
H NMR (400 MHz, DMSO-d ): d 11.78 (s, 3H), 7.75 (s, 1H), 7.46 (d,
J ¼ 8.3 Hz, 1H), 7.33 (d, J ¼ 8.1 Hz, 1H), 7.20 (d, J ¼ 8.1 Hz, 1H), 7.11 (d,
J ¼ 8.0 Hz, 1H), 7.03 (t, J ¼ 7.9 Hz, J ¼ 14.9 Hz, 1H), 6.83 (t,
¼ 7.9 Hz, J ¼ 14.9 Hz, 1H), 3.76 (s, 3H), 2.67 (s, 3H); C NMR
(100 MHz, DMSO-d ): 154.45, 149.71, 141.42, 136.92, 134.69,
1
5
3
09.95e110.21 (d, J ¼ 23.6 Hz), 103.53e103.77 (d, J ¼ 23.6 Hz),
1
2
þ
13
2.79, 12.06; HRMS (ESI): (calcd for C18
87.0922, found: 387.0925; IR
H
16FN
4
O
3
S [MþH] :
J
1
2
ꢁ1
n
max/cm 3363 (NeH), 1723, 1645
6
d
(
(
C]O), 1260, 1108 (CeO), 2960, 2850 (CeH), 3033, 1593, 1527 (Ar)
KBr).
125.07, 122.56, 121.53, 119.21, 118.79, 114.61, 112.40, 111.84, 111.37,
þ
52.94; HRMS (ESI): calcd for C18
H
17
N
4
O
4
S [MþH] : 385.0965,
ꢁ1
found: 385.0962; IR
1260, 1087 (CeO), 2953, 2855 (CeH), 3067, 1592, 1528 (Ar) (KBr).
nmax/cm 3390 (NeH), 1734, 1643 (C]O),
4
.1.6.4. Methyl
5-[(5-chloro-2-methyl-1H-indol-3-yl)sulfinyl]-1H-
benzoimidazol-2-ylcarbamate (8d). White solid; yield: 62%; M.p.:
ꢀ
1
>
7
300 C; H NMR (400 MHz, DMSO-d
.76 (s, 1H), 7.50 (d, J ¼ 8.2 Hz, 1H), 7.36 (d, J ¼ 8.6 Hz, 1H), 7.22 (d,
J ¼ 8.2 Hz, 1H), 7.13 (s, 1H), 7.06 (d, J ¼ 8.6 Hz, 1H), 3.77 (s, 3H), 2.67
s, 3H); 13C NMR (150 MHz, DMSO-d
): 154.64, 148.80, 142.71,
36.87, 134.36, 131.68, 128.83, 125.54, 124.82, 122.04, 117.77, 117.25,
13.4, 112.99, 52.73, 12.01; HRMS (ESI): calcd for C18 16ClN
max/cm 3389 (NeH),
720, 1645 (C]O), 1259, 1106 (CeO), 2961, 2868 (CeH), 3081, 1595,
6
):
d
12.01 (s,1H),11.86 (s, 2H),
4.1.7.3. Methyl
5-[(5-fluoro-2-methyl-1H-indol-3-yl)sulfonyl]-1H-
benzoimidazol-2-ylcarbamate (9c). White solid; yield: 62%; M.p.:
ꢀ
1
240e242 C; H NMR (400 MHz, DMSO-d
6
):
¼ 8.4 Hz, 1H), 7.55 (dd, J
¼ 9.9 Hz, 1H), 7.50 (d, J ¼ 8.4 Hz, 1H), 7.37 (dd, J
¼ 8.8 Hz, 1H), 7.02 (td, J ¼ 2.5 Hz, J ¼ 9.3 Hz, 1H), 3.77 (s, 3H),
d12.22 (s, 3H), 8.01 (s,
(
1
1
[
1
1
6
d
1H), 7.66 (dd, J
1
¼ 1.5 Hz, J
2
1
¼ 2.5 Hz,
J
J
2
1
¼ 4.6 Hz,
H
4
O
3
S
2
1
2
þ
ꢁ1
13
MþH] : 403.0626, found: 403.0627; IR
n
6
2.66 (s, 3H); C NMR (100 MHz, DMSO-d ): d 157.10e159.43 (d,
J ¼ 233.3 Hz), 154.45, 149.81, 143.14, 136.54, 131.26, 125.59e125.70
527 (Ar) (KBr).
(d, J ¼ 11.2 Hz), 119.19, 114.76, 113.15e113.25 (d, J ¼ 11.2 Hz), 111.78,
111.74, 110.52e110.77 (d,
J
¼
25.4 Hz), 103.75e104.00 (d,
4
.1.6.5. Methyl 5-[(5-bromo-1H-indol-3-yl)sulfinyl]-1H-benzoimida-
zol-2-ylcarbamate (8e). White solid; yield: 63%; M.p.: 263e267 C;
H NMR (400 MHz, DMSO-d
J ¼ 25.4 Hz), 52.91, 12.79; HRMS (ESI): calcd for C18
H16FN
4 4
O S
ꢀ
þ
ꢁ1
[MþNa] : 425.0696, found: 425.0741; IR
nmax/cm 3392, 3302
1
6
):
d
12.08 (s, 1H), 11.84 (s, 2H), 8.10 (s,
(NeH), 1731, 1642 (C]O), 1260, 1101 (CeO), 2955, 2871(CeH),
1
H), 7.78 (s, 1H), 7.52 (d, J ¼ 8.2 Hz, 1H), 7.44e7.45 (m, 2H),
3073, 1587, 1528 (Ar) (KBr).
13
7.26e7.31 (m, 2H), 3.77 (s, 3H); C NMR (100 MHz, DMSO-d
6
):
d
167.16,154.57,148.83,136.90,136.00,131.91,131.69,131.34,128.86,
4.1.7.4. Methyl 5-[(5-chloro-2-methyl-1H-indol-3-yl)sulfonyl]-1H-
1
25.55, 125.20, 121.42, 117.52, 117.31, 114.91, 113.17, 52.80; HRMS
benzoimidazol-2-ylcarbamate (9d). White solid; yield: 66%; M.p.:
þ
ꢀ
1
(
ESI): calcd for
C
17
H14BrN
4
O
3
S
[MþH] : 432.9965, found:
262e264 C; H NMR (400 MHz, DMSO-d ): d 12.30 (s, 1H), 11.90 (s,
6