3258
I. Chiyanzu et al. / Bioorg. Med. Chem. 13 (2005) 3249–3261
1
.4.2. N -Piperidin-1-ylmethyl-indole-2,3-dione-3-thiosemi-
5
carbazone (5b). (0.27 g, 95%); obtained as yellow solids;
111.1, 60.9, 50.1 (2 · C) and 48.1 (2 · C). Anal. Calcd
for C H N OS: C 60.9%, H 5.6%, N 21.3%, S 8.1%.
2
0
22
6
3
3
mp 179–180 ꢁC (from ethanol) (lit. 174 ꢁC);
dH
300 MHz, DMSO-d ); 12.38 (1H, s, NNH), 9.05 (1H,
Found: C 61.3%, H 6.3%, N 18.7%, S 5.7%; HRMS
(FAB) m/z 395.16544 [M+1] , C H N OS requires
395.16541.
+
(
6
20 22
6
s, NHH), 8.69 (1H,s, NHH), 7.71 (1H, dd, J 0.9 and
.5, H-4), 7.41 (1H, ddd, J 0.9, 7.8 and 8.1, H-6), 7.26
1H, d, J 7.8, H-7), 7.17 (1H, ddd, J 1.2, 7.5 and 8.1,
H-5), 4.47 (2H, s, –NCH N–), 2.54 (4H, t, J 4.8, H-
7
(
5.5. D. General procedure for the preparation of
compounds 4
2
0
0
0
0
0
2
), 1.46 (4H, m, H-3 3 ), 1.33 (2H, m, H-4 4 ).
Equimolar quantities of ethyl-quinoline isatin derivative
(0.1 g, 0.284 mmol) and thiosemicarbazide (0.038 g,
0.284 mmol) were dissolved in warm 99.9% ethanol.
The mixture was then continuously stirred at 45 ꢁC for
5–6 h. After standing for approximately 24 h at room
temperature, a crystalline product was formed. The
product was then separated by filtration, vacuum dried
and recrystallized from acetonitrile.
1
.4.3. N -Pyrrolidin-1-ylmethyl-indole-2,3-dione-3-thio-
5
semicarbazone (5c). (0.25 g, 90%) obtained as yellow
crystals; mp 181–184 ꢁC (from ethanol) (lit. 177–
3
3
1
78 ꢁC);
d
(400 MHz, DMSO-d ); 12.29 (1H, s,
H 6
NNH), 9.03 (1H, s, NHH), 8.68 (1H, s, NHH), 7.68
1H, dd, J 1.2 and 7.6, H-4), 7.42 (1H, ddd, J 1.2, 7.2
and 8.0, H-6), 7.23 (1H, d, J 8.0, H-7), 7.12 (1H, ddd,
(
J 0.9, 7.2 and 7.6, H-5), 4.61 (2H, s, –NCH N–), 2.60
2
0
1
N -[2-(7-Chloro-quinolin-4-ylamino)-ethyl]-1H-
(
4H, br t, J 3.2, H-2 ), 1.65 (4H, m, H-3).
5.5.1.
indole-2,3-dione-3-thiosemicarbazone (4a). (0.08 g, 70%)
1
.4.4. N -Morpholin-4-ylmethyl-indole-2,3-dione-3-thio-
5
semicarbazone (5d). (0.27 g, 92%); as yellow crystals;
obtained as orange crystals; mp 167–171 ꢁC (from ace-
ꢁ
1
tonitrile); IR (KBr): m /cm 3680 (N–H), 3404 (N–
max
3
3
mp 208–210 ꢁC (from ethanol) (lit. 215–216 ꢁC); dH
300 MHz; DMSO-d ); 12.37 (1H, s, NNH), 9.05 (1H,
H), 3012 (Ar-H), 1635 (C@O), 1516 (C@N), 1140
(
(C@S); dH (400 MHz, DMSO-d ); 12.31 (1H, s,
6
6
s, NHH), 8.70 (1H, s, NHH), 7.72 (1H, dd, J 0.6 and
.2, H-4), 7.42 (1H, ddd, J 0.9, 7.5 and 8.0, H-6), 7.27
NNH), 9.02 (1H, s, NHH), 8.67 (1H, s, NHH), 8.40
00 00
(1H, d, J 5.4, H-2 ), 7.98 (1H, d, J 9.0, H-5 ), 7.76
7
00
(
H-5), 4.49 (2H, s, –NCH N–), 3.54 (4H, br s, H-3 ),
1H, d, J 8.0, H-7), 7.15 (1H, ddd, J 0.6, 7.2 and 7.5,
0
(1H, d, J 2.0, H-8 ), 7.67 (1H, dd, J 0.6 and 7.4, H-4),
00
7.38 (1H, dd, J 2.0 and 9.0, H-6 ), 7.28 (1H, ddd, J
0.6, 7.6 and 7.8, H-6), 7.10 (1H, ddd, J 0.9, 7.4 and
2
0
2
.57 (4H, br s, H-2 ).
7
H-3 ), 4.01 (2H, t, J 5.6, –CH CH NHAr), 3.65 (2H,
.6, H-5), 7.02 (1H, d, J 7.8, H-7), 6.63 (1H, d, J 5.4,
00
1
.4.5. N -4-Benzyl-piperazin-1-ylmethyl-indole-2,3-dione-
-thiosemicarbazone (5e). (0.23 g, 63%); obtained as
5
3
2
2
t, J 5.6, -CH CH NHAr); d (75 MHz); 179.4, 161.8,
2 2 C
ꢁ
1
yellow crystals; mp 187–188 ꢁC; IR (KBr): mmax/cm
152.6, 150.5, 149.7, 149.1, 143.7, 138.6, 134.1, 128.2,
124.9, 124.5, 123.7, 123.1, 118.2, 117.3, 110.3, 104.5,
74.9 and 42.4; HRMS (FAB) found m/z 425.09419
3
1
680 (N–H), 3428 (N–H), 1637 (C@O), 1505 (C@N),
123 (C@S); dH (300 MHz, DMSO-d ); 12.38 (1H, s,
6
+
NNH), 9.06 (1H, s, NHH), 8.69 (1H, s, NHH),
[M+1] , C H ClN OS] requires 425.09513. Anal.
2
0
17
6
7
0
.71 (1H, dd, J 0.9 and 7.5, H-4), 7.43 (1H, ddd, J
0
Calcd for C H ClN OSÆ0.5H O: C 55.4%, H 3.9%,
N 18.8%, S 6.9%. Found: C 55.3%, H 4.0%, N 18.8%,
S 6.9%.
20 17 6 2
0
00
.9, 7.2 and 7.8, H-6), 7.25–7.23 (5H, m, H-2 , H-3 ,
00
00
00
H-4 , H-5 and H-6 ), 7.19 (1H, d, J 7.8, H-7),
7
–
–
.17 (1H, ddd, J 0.6, 7.2 and 7.5, H-5), 4.52 (2H, s,
NCH N–), 3.43 (2H, s, –NCH Ar), 2.59 (4H, br s,
1
5.5.2. N -[2-(7-Chloro-quinolin-4-ylamino)-ethyl]-5-meth-
2
2
NCH CH NCH Ar), 2.34 (4H, br s, –NCH CH -
2
yl-1H-indole-2,3-dione-3-thiosemicarbazone (4b). The
conditions employed for the preparation of this com-
pound were those described in general procedure D.
However, 0.27 mmol of compound 1b and thiosemicarb-
azide were used.
2
2
2
2
NCH Ar); d (75 MHz); 178.7, 161.6, 143.7, 138.2,
2
C
131.0, 130.9, 128.6 (2 · C), 128.0, 126.8 (2 · C), 122.8,
120.5, 119.2, 111.1, 61.8, 52.3 (2 · C), 50.1 (2 · C) and
49.9. Anal. Calcd for C H N OS: C 62.1%, H 6.6%,
2
1
24
6
N 20.1%, S 6.6. Found: C 61.7%, H 5.9%, N 20.6%, S
6
C H N OS requires 409.18106.
+
.6%; HRMS (FAB) m/z 409.18109 [M+1] ,
(0.11 g, 89%) obtained as yellow-orange crystals; mp
227–230 ꢁC (from ethanol); IR (KBr): mmax/cm 3632
ꢁ
1
2
1
24
6
(
N–H), 3378 (N–H), 1665 (C@O), 1506 (C@N), 1127
1
5
3
.4.6. N -4-Phenyl-piperazin-1-ylmethyl-indole-2,3-dione-
-thiosemicarbazone (5f). (0.27 g, 76%) obtained yellow-
(C@S); dH (400 MHz; DMSO-d ); 12.29 (1H, s, NNH),
6
8.98 (1H, s, NHH), 8.63 (1H, s, NHH), 8.40 (1H, d, J
ꢁ1
00 00
5.6, H-2 ), 8.01 (1H, d, J 9.0, H-5 ), 7.76 (1H, d, J
2.0, H-8 ), 7.49 (1H, d, J 2.0, H-4), 7.39 (1H, dd, J 2.0
ish crystals; 188–191 ꢁC; IR (KBr): mmax/cm 3686 (N–
00
H), 3575 (N–H), 1694 (C@O), 1502 (C@N), 1127
00
(
C@S); dH (300 MHz, DMSO-d ); 12.39 (1H, s,
and 9.0, H-6 ), 7.08 (1H, dd, J 2.0 and 7.4, H-6), 7.00
0
6
0
NNH), 9.04 (1H, s, NHH), 8.69 (1H, s, NHH), 7.79
1H, dd, J 0.9 and 7.6, H-4), 7.45 (1H, ddd, J 0.9, 6.6
and 8.0, H-6), 7.18 (1H, d, J 8.0, H-7), 7.21–7.13 (5H,
(1H, d, J 7.4, H-7), 6.60 (1H, d, J 5.6, H-3 ), 3.98
(2H, t, J 5.4, –NCH CH NHAr), 3.62 (2H, t, J 5.4,
(
2
2
–NCH CH NHAr), 2.31 (3H, s, Ar–CH3); dC
2
2
0
0
00
00
m, H-2 , H-3 and 4 ), 7.10 (1H, ddd, J 0.6, 6.6 and
7
(75 MHz); 179.4, 161.8, 152.5, 150.6, 149.7 149.0,
141.6, 138.9, 134.2, 128.1, 125.3, 124.9, 124.5, 121.9,
118.2, 118.1, 110.9, 110.6, 74.9, 41.8 and 21.2; LRMS
.6, H-5), 4.59 (2H, s, –NCH N–), 3.09 (4H, br s,
2
–
NCH CH NAr), 2.76 (4H, br s, –NCH CH NAr); d
2
2
2
2
C
+
(
1
75 MHz); 178.7, 161.7, 151.0, 143.7, 131.1, 130.9,
28.8, 122.0, 120.6 (2 · C), 120.5, 119.3 (2 · C), 119.2,
(FAB) m/z 439 [5%, (M+1) ], and 307 [30%,
MꢁC H ClN ]. Anal. Calcd for C H ClN OS: C
1
8
14
3
21 19
6