2490 J ournal of Medicinal Chemistry, 2003, Vol. 46, No. 12
Silvestri et al.
6.89-7.12 (m, 2H), 7.18-7.41 (m, 2H), 7.60 (d, J ) 8.7 Hz,
1H), 7.70 and 7.96 (two broad s, 2H, disappeared on treatment
with D2O), 8.79 ppm (broad s, 1H, disappeared on treatment
with D2O). IR (Nujol): ν 1645, 3260, 3300, 3420 cm-1. Anal.
(C16H13ClN2OS (316.80)) C, H, N, S, Cl.
5-Ch lor o-3-[(4-m e t h ylp h e n yl)t h io]-1H -in d ole -2-ca r -
boxya m id e (57), yield 69%, mp 232-235 °C (from ethanol).
1H NMR (DMSO-d6): δ 2.21 (s, 3H), 6.99 and 7.08 (two d, J )
8.4 Hz, 4H), 7.30 (dd, J ) 1.8 and 8.7 Hz, 1H), 7.44 (d, J ) 1.8
Hz, 1H), 7.54 (d, J ) 8.7 Hz, 1H), 7.79 and 8.09 (two broad s,
disappeared on treatment with D2O), 12.51 ppm (broad s, 1H,
disappeared on treatment with D2O). IR (Nujol): ν 1650, 3200,
3300, and 3440 cm-1. Anal. (C16H13ClN2OS (316.80)) C, H, N,
S, Cl.
5-Ch lor o-3-[(4-flu or oph en yl)th io]-1H-in dole-2-car boxy-
a m id e (58), yield 52%, mp 210-212 °C (from ethanol). 1H
NMR (DMSO-d6): δ 7.12 (s, 2H), 7.16 (s, 2H), 7.31 (dd, J )
1.9 and 8.6 Hz, 1H), 7.46 (d, J ) 1.9 Hz, 1H), 7.55 (d, J ) 8.6
Hz, 1H), 7.81 and 8.10 (two broad s, 2H, disappeared on
treatment with D2O), 12.55 ppm (broad s, 1H, disappeared on
treatment with D2O). IR (Nujol): ν 1675, 3120, 3360, and 3440
cm-1. Anal. (C15H10ClFN2OS (320.76)) C, H, N, S, Cl, F.
5-Ch lor o-3-[(4-ch lor oph en yl)th io]-1H-in dole-2-car boxy-
a m id e (59), yield 57%, mp 232-233 °C (from ethanol). 1H
NMR (DMSO-d6): δ 7.06 (d, J ) 8.5 Hz, 2H), 7.24-7.38 (m,
3H), 7.43 (m, 1H), 7.55 (d, J ) 8.7 Hz, 1H), 7.75 and 8.08 (two
broad s, 2H, disappeared on treatment with D2O), 12.58 ppm
(broad s, 1H, disappeared on treatment with D2O). IR (Nu-
jol): ν 1660, 3200, 3320, and 3460 cm-1. Anal. (C15H10Cl2N2-
OS (337.22)) C, H, N, S, Cl.
3-(P h en ylsu lfon yl)-1H-in dole-2-car boxyam ide (70), yield
40%, mp 226-227 °C (from ethanol). 1H NMR (CD3COCD3):
δ 7.24-7.72 (m, 8H, 7H, 6H, after treatment with D2O), 7.96-
8.12 (m, 2H), 8.24 (m, 1H), 9.11 (broad s, 1H, disappeared on
treatment with D2O), 11.88 ppm (broad s, 1H, disappeared on
treatment with D2O). IR (Nujol): ν 1660, 3170, 3270, 3370
cm-1. Anal. (C15H12N2O3S (300.05)) C, H, N, S.
3-[(2-Am in o-5-ch lor op h en yl)su lfon yl]-1H-in d ole-2-ca r -
boxya m id e (71), yield 40%, mp 238-239 °C (from aqueous
1
ethanol). H NMR (CDCl3): δ 4.99 (broad s, 2H, disappeared
on treatment with D2O), 6.12 (broad s, 1H, disappeared on
treatment with D2O), 6.58 (d, J ) 8.8 Hz, 1H), 7.15-7.55 (m,
4H), 7.76 (d, J ) 2.3 Hz, 1H), 8.02 (d, J ) 7.9 Hz, 1H), 9.15
(broad s, 1H, disappeared on treatment with D2O), 10.19 ppm
(broad s, 1H, disappeared on treatment with D2O). IR (Nu-
jol): ν 1645, 3225, and 3380 cm-1. Anal. (C15H12ClN3O3S
(349.79)) C, H, N, S, Cl.
5-Ch lor o-3-[(2-m eth ylph en yl)su lfon yl]-1H-in dole-2-car -
boxya m id e (72), yield 82%, mp 260-261 °C (from ethanol).
1H NMR (DMSO-d6): δ 2.39 (s, 3H), 7.27-7.64 (m, 5H), 7.81
(d, J ) 1.7 Hz, 1H), 8.03 (dd, J ) 1.1 and 7.9 Hz, 1H), 8.23
and 8.29 (two partially overlapped broad s, 2H, disappeared
on treatment with D2O), 13.11 ppm (broad s, 1H, disappeared
on treatment with D2O). IR (Nujol): ν 1670, 3290, 3220, 3410
cm-1. Anal. (C16H13ClN2O3S (348.80)) C, H, N, S, Cl.
5-Ch lor o-3-[(3-m eth ylph en yl)su lfon yl]-1H-in dole-2-car -
boxya m id e (73), yield 87%, mp 265-268 °C (from aqueous
ethanol). 1H NMR (DMSO-d6): δ 2.36 (s, 3H), 7.34 (m, 1H),
7.40-7.58 (m, 3H), 7.77-7.88 (m, 2H), 7.95 (m, 1H), 8.24 and
8.47 (two broad s, 1H, disappeared on treatment with D2O),
13.02 ppm (broad s, 1H, disappeared on treatment with D2O).
IR (Nujol): ν 1650, 3180, 3380 cm-1. Anal. (C16H13ClN2O3S
(348.80)) C, H, N, S, Cl.
5-Ch lor o-3-[(4-isop r op ylp h en yl)th io]-1H-in d ole-2-ca r -
boxya m id e (60), yield 75%, mp 195 °C (from ethanol). 1H
NMR (DMSO-d6): δ 1.12 (d, J ) 6.7 Hz, 6H), 2.79 (sp, J ) 6.7
Hz, 1H), 7.02 and 7.14 (two d, J ) 8.2 Hz, 4H), 7.29 (dd, J )
1.6 and 8.7 Hz, 1H), 7.46 (d, J ) 1.6 Hz, 1H), 7.55 (d, J ) 8.7
Hz, 1H), 7.79 and 8.02 (two broad s, 2H, disappeared on
treatment with D2O), 12.48 ppm (broad s, 1H, disappeared on
5-Ch lor o-3-[(4-m eth ylph en yl)su lfon yl]-1H-in dole-2-car -
1
boxya m id e (74), yield 90%, mp >300 °C (from ethanol). H
NMR (DMSO-d6): δ 2.33 (s, 3H), 7.28-7.46 (m, 3H), 7.54 (d,
J ) 8.7 Hz, 1H), 7.86-7.99 (m, 3H), 8.27 and 8.51 (two broad
s, disappeared on treatment with D2O), 13.08 ppm (broad s,
1H, disappeared on treatment with D2O). IR (Nujol): ν 1660,
3200, and 3380 cm-1. Anal. (C16H13ClN2O3S (348.80)) C, H, N,
S, Cl.
treatment with D2O). IR (Nujol): ν 1640, 3280, and 3370 cm-1
Anal. (C18H17ClN2OS (344.85)) C, H, N, S, Cl.
.
5-Ch lor o-3-[(4-ter t-bu tylp h en yl)th io]-1H-in d ole-2-ca r -
boxya m id e (61), yield 100%, mp 234-235 °C (from ethanol).
1H NMR (DMSO-d6): δ 1.20 (s, 9H), 7.01 (d, J ) 8.5 Hz, 2H),
7.22-7.34 (m, 3H), 7.47 (d, J ) 1.9 Hz, 1H), 7.55 (d, J ) 8.7
Hz,1H), 7.78 and 8.00 (two broad s, 2H, disappeared on
treatment with D2O), 12.46 ppm (broad s, 1H, disappeared on
treatment with D2O). IR (Nujol): ν 1630-50, 3160, 3280, 3420
cm-1. Anal. (C19H19ClN2OS (358.82)) C, H, N, S, Cl.
5-Ch lor o-3-[(4-flu or op h en yl)su lfon yl]-1H-in d ole-2-ca r -
boxya m id e (75), yield 94%, mp 229-230 °C (from ethanol).
1H NMR (DMSO-d6): δ 7.29-7.58 (m, 4H), 7.95 (m, 1H), 8.07-
8.21 (m, 2H), 8.24 and 8.47 (two broad s, 2H, disappeared on
treatment with D2O), 13.11 ppm (broad s, 1H, disappeared on
treatment with D2O). IR (Nujol): ν 1650, 3150, 3230 cm-1
Anal. (C15H10ClFN2O3S (352.76)) C, H, N, S, Cl, F.
.
5-Ch lor o-3-[(3,5-d im eth ylp h en yl)th io]-1H-in d ole-2-ca r -
boxya m id e (62), yield 91%, mp 201-203 °C (from ethanol).
1H NMR (DMSO-d6): δ 2.14 (s, 6H), 6.69 (m, 2H), 6.79 (m,
1H), 7.30 (dd, J ) 1.6 and 8.6 Hz, 1H), 7.44 (d, J ) 1.6 Hz,
1H), 7.55 (d, J ) 8.6 Hz, 1H), 7.73 and 8.01 (two broad s, 2H,
disappeared on treatment with D2O), 12.46 ppm (broad s, 1H,
disappeared on treatment with D2O). IR (Nujol): ν 1650, 3260,
and 3440 cm-1. Anal. (C17H15ClN2OS (330.83)) C, H, N, S, Cl.
5-Ch lor o-3-[(2,6-d ich lor op h en yl)th io]-1H-in d ole-2-ca r -
boxya m id e (63), yield 97%, mp 242-245 °C (from ethanol).
1H NMR (DMSO-d6): δ 7.12 (dd, J ) 0.6 and 2.0 Hz, 1H), 7.20
(dd, J ) 2.0 and 8.7 Hz, 1H), 7.38 (dd, J ) 7.0 and 8.9 Hz,
1H), 7.46 (dd, J ) 0.6 and 8.7 Hz, 1H), 7.52-7.59 (two d, J )
7.0 and 8.9 Hz, 2H), 7.74 and 8.03 (two broad s, 2H, disap-
peared on treatment with D2O), 12.25 ppm (broad s, 1H,
disappeared on treatment with D2O). IR (Nujol): ν 1630, 3180,
and 3380 cm-1. Anal. (C15H9Cl3N2OS (371.66)) C, H, N, S, Cl.
5-Ch lor o-3-[(2-a m in o-5-ch lor op h en yl)th io]-1H-in d ole-
2-ca r boxya m id e (64), yield 85%, mp 233-235 °C (from
ethanol). 1H NMR (DMSO-d6): δ 5.70 (broad s, 2H, disap-
peared on treatment with D2O), 6.71 (d, J ) 8.6 Hz, 1H), 6.76
(d, J ) 2.4 Hz, 1H), 6.97 (dd, J ) 2.4 and 8.6 Hz, 1H), 7.29
(dd, J ) 1.9 and 8.7 Hz, 1H), 7.52 (d, J ) 8.7 Hz, 1H), 7.56 (d,
J ) 1.9 Hz, 1H), 7.88 and 8.10 (two broad s, 2H, disappeared
on treatment with D2O), 12.40 ppm (broad s, 1H, disappeared
on treatment with D2O). IR (Nujol): ν 1670, 3100, 3310, 3370,
and 3420 cm-1. Anal. (C15H11Cl2N3OS (352.24)) C, H, N, S, Cl.
5-Ch lor o-3-[(4-ch lor op h en yl)su lfon yl]-1H-in d ole-2-ca r -
boxya m id e (76), yield 90%, mp >300 °C (from ethanol). H
1
NMR (DMSO-d6): δ 7.36 (m, 1H), 7.55 (d, J ) 8.6 Hz, 1H),
7.68 (d, J ) 8.2 Hz, 2H), 7.94 (m, 1H), 8.07 (d, J ) 8.2 Hz,
2H), 8.23 and 8.45 (two broad s, 2H, disappeared on treatment
with D2O), 13.15 ppm (broad s, 1H, disappeared on treatment
with D2O). IR (Nujol): ν 1650, 3150, 3230, and 3440 cm-1
Anal. (C15H10Cl2N2O3S (369.22)) C, H, N, S, Cl.
.
5-Ch lor o-3-[(4-isop r op ylp h en yl)su lfon yl]-1H-in d ole-2-
ca r boxya m id e (77), yield 79%, mp 272-275 °C (from etha-
nol). 1H NMR (DMSO-d6): δ 1.15 (d, J ) 6.8 Hz, 6H), 2.92
(sp, J ) 6.8 Hz, 1H), 7.35 (dd, J ) 1.9 and 8.6 Hz, 1H), 7.46
(d, J ) 8.4 Hz, 2H), 7.55 (d, J ) 8.6 Hz, 1H), 7.90 and 8.02 (m,
3H), 8.24 and 8.50 (two broad s, 2H, disappeared on treatment
with D2O), 13.03 ppm (broad s, 1H, disappeared on treatment
with D2O). IR (Nujol): ν 1660, 3140, and 3380 cm-1. Anal.
(C18H17ClN2O3S (376.66)) C, H, N, S, Cl.
5-Ch lor o-3-[(4-ter t-bu tylp h en yl)su lfon yl]-1H-in d ole-2-
ca r boxya m id e (78), yield 100%, mp 276-277 °C (from
ethanol). 1H NMR (DMSO-d6): δ 1.25 (s, 9H), 7.44 (dd, J )
1.9 and 8.7 Hz, 1H), 7.54 (d, J ) 8.7 Hz, 1H), 7.61 and 7.94
(two d, J ) 8.6 Hz, 4H), 7.98 (d, J ) 1.9 Hz, 1H), 8.22 and
8.48 (two broad s, 2H, disappeared on treatment with D2O),
12.99 ppm (broad s, 1H, disappeared on treatment with D2O).
IR (Nujol): ν 1660, 3180, 3280, and 3430 cm-1. Anal. (C19H19
ClN2O3S (390.88)) C, H, N, S, Cl.
-