Page 23 of 44
Journal of Medicinal Chemistry
d, J =7.9 Hz), 7.87 (1H, dd, J = 8.2, 7.9 Hz), 7.51 (1H, brs), 12.26 (1H, brs), 9.41 (1H, brs), 7.75 (1H, dd, J = 7.5, 1.5 Hz),
1
2
3
4
5
6
7
8
7.49 (1H, brs), 7.37 (1H, dd, J = 8.2, 7.9 Hz), 3.91 (2H, s),
3.67 (2H, s), 2.93 (2H, brt, J = 5.3 Hz), 2.63 (2H, brt, J = 5.3
Hz). 13C-NMR (100 MHz, DMSO-d6), δ(ppm): 182.0, 167.3,
163.9, 151.4, 148.1, 148.1, 142.3, 136.6, 135.3, 134.3, 130.7, 130.6,
129.2, 129.2, 127.3, 127.2, 123.6, 122.7, 114.5, 54.6, 49.4, 23.7.
HRMS (ESI)+ calculated for C22H19Cl2N4O4S, [M+H]+: m/z
505.0518, found 505.0504.
7.63 (1H, dd, J = 8.0, 1.4 Hz), 7.59 (1H, td, J = 8.0, 1.5 Hz),
7.52 (1H, td, J = 7.5, 1.4 Hz), 7.50 (1H, m), 7.35 (1H, m), 7.33
(1H, m), 7.29 (1H, m), 5.13 (2H, s), 4.20 (2H, brt, J = 5.4
Hz), 2.98 (2H, brt, J = 5.4 Hz). 13C-NMR (100 MHz, DMSO-
d6), δ(ppm): 182.0, 167.3, 162.9, 142.7, 138.6, 134.1, 133.0,
132.5, 131.8, 130.9, 130.6, 130.4, 129.8, 129.4, 128.4, 128.2,
127.7, 124.0, 117.7, 47.6, 45.7, 25.8. HRMS (ESI)+ calculated
for C22H19Cl2N4O2S2, [M+H]+: m/z 505.0332, found
505.0326.
9
6-(2,4-Dichlorobenzyl)-2-(3-nitrobenzamido)-
4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
carboxamide (21v). White solid, mp 198-200, yield 62.3%.
1H-NMR (400 MHz, DMSO-d6), δ(ppm): 12.16 (1H, brs),
8.79 (1H, t, J = 1.8 Hz), 8.47 (1H, d, J = 8.2 Hz), 8.40 (1H, d,
J = 8.0 Hz), 7.86 (1H, dd, J = 8.2, 8.0 Hz), 7.61 (1H, brs),
7.58 (1H, d, J = 8.2 Hz), 7.44 (1H, d, J = 8.2 Hz), 3.79 (2H,
2-(2-Chlorobenzamido)-N6-(2-chlorophenyl)-4,7-
dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxamide
(22ad). White solid, mp 208-210, yield 66.5%. H-NMR
1
(400 MHz, DMSO-d6), δ(ppm): 12.28 (1H, brs), 8.38 (1H,
brs), 7.74 (1H, dd, J = 7.4, 1.4 Hz), 7.62 (1H, dd, J = 8.0, 1.5
Hz), 7.59 (1H, td, J = 8.0, 1.6 Hz), 7.52 (2H, m), 7.47 (1H, dd,
J = 8.0, 1.4 Hz), 7.45 (1H, td, J =7.6, 1.5 Hz), .7.16 (1H, t, J
=7.9, 1.7 Hz), 4.67 (2H, s), 3.75 (2H, t, J = 5.6 Hz), 2.90 (2H,
t, J = 5.6 Hz). 13C-NMR (100 MHz, DMSO-d6), δ(ppm):
168.8, 162.4, 154.8, 142.2, 136.4, 133.7, 132.5, 130.4, 130.1,
129.9, 129.2, 128.7, 128.5, 127.7, 127.4, 127.2, 125.8, 124.0,
117.2, 42.7, 41.3, 25.4. HRMS (ESI)+ calculated for
C22H19Cl2N4O3S, [M+H]+: m/z 489.0587, found 489.0555.
13
s), 3.65 (2H, s), 2.85 (2H, m), 2.67 (2H, m). C-NMR (100
MHz, DMSO-d6), δ(ppm): 168.0, 163.9, 159.5, 148.1, 135.3,
134.7, 133.0, 132.8, 132.6, 130.7, 129.2, 127.8, 127.3, 127.0,
126.9, 125.6, 123.6, 120.9, 114.5, 50.7, 49.3, 24.1. HRMS (ESI)+
calculated for C22H19Cl2N4O4S, [M+H]+: m/z 505.0517,
found 505.0504.
2-(2-Chlorobenzamido)-6-(phenylcarbamothioyl)-
4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-
carboxamide (22aa). White solid, mp 167-170, yield
2-(2-Chlorobenzamido)-6-((2-
fluorophenyl)carbamothioyl)-4,5,6,7-
1
68.4%. H-NMR (400 MHz, DMSO-d6), δ(ppm): 12.94 (1H,
brs), 9.50 (1H, brs), 7.89 (1H, m), 7.84 (1H, d, J = 7.8 Hz),
7.74 (1H, d, J = 8.0 Hz), 7.64 (1H, dd, J = 8.0, 7.8 Hz), 7.32
(3H, m), 7.13 (1H, m), 5.09 (2H,s), 4.21 (2H, brt, J = 5.1 Hz),
3.01 (2H, brt, J = 5.1 Hz). 13C-NMR (100 MHz, DMSO-d6),
δ(ppm): 181.7, 167.8, 161.7, 144.1, 141.3, 134.7, 134.3, 132.9,
131.6, 129.4, 128.5, 128.5, 127.5, 126.2, 126.1, 126.1, 125.1, 123.9,
116.8, 47.6, 45.8, 25.8. HRMS (ESI)+ calculated for
C22H20ClN4O2S2, [M+H]+: m/z 471.0722, found 471.0716.
tetrahydrothieno[2,3-c]pyridine-3-carboxamide
(22ae). White solid, mp 213-215, yield 78.3%. 1H-NMR (400
MHz, DMSO-d6), δ(ppm): 12.26 (1H, brs), 9.32 (1H, brs),
7.75 (1H, dd, J = 7.4, 1.1 Hz), 7.61 (1H, m), 7.60 (1H, m), 7.52
(1H, td, J = 7.5, 1.5 Hz), 7.28 (1H, m), 7.27 (1H, m), 7.19 (1H,
m), 7.18 (1H, m), 5.11 (2H, s), , 4.20 (2H, t, J = 5.2 Hz), 2.98
(2H, t, J = 5.2 Hz). 13C-NMR (100 MHz, DMSO-d6), δ(ppm):
182.3, 167.3, 162.9, 157.9 (245.0 Hz), 142.8, 134.1, 133.0, 130.9,
130.8, 130.6, 130.4, 129.4, 129.1 (12.1 Hz), 128.3 (7.8 Hz), 128.2,
124.5 (3.1 Hz), 123.9, 117.6, 116.2 (20.1 Hz), 47.6, 45.9, 25.8.
HRMS (ESI)+ calculated for C22H19ClFN4O2S2, [M+H]+: m/z
489.0622, found 489.0613.
2-(2-Chlorobenzamido)-6-(naphthalen-1-
ylcarbamothioyl)-4,5,6,7-tetrahydrothieno[2,3-
c]pyridine-3-carboxamide (22ab). White solid, mp 151-
1
154, yield 64.3%. H-NMR (400 MHz, DMSO-d6), δ(ppm):
12.91 (1H, brs), 9.71 (1H, brs), 7.95 (1H, m) 7.91 (1H, m), 7.87
(1H, m), 7.86 (2H, dd, J = 7.6, 6.4 Hz), 7.75 (1H, d, J = 8.0
Hz), 7.66 (1H, dd, J = 8.0, 7.6 Hz), 7.54 (1H, d, J = 8.0 Hz),
7.51 (1H, m), 7.50 (1H, dd, J = 6.8, 3.0 Hz), 7.36 (1H, d, J =
7.2 Hz), 5.22 (2H, s), 4.30 (2H, brt, J = 5.4 Hz), 3.09 (2H,
brt, J = 5.4 Hz). 13C-NMR (100 MHz, DMSO-d6), δ(ppm):
182.7, 167.9, 161.8, 144.1, 137.6, 134.8, 134.4, 134.3, 132.9, 131.6,
131.2, 129.5, 128.4, 127.5, 127.5, 127.1, 126.7, 126.4, 126.4, 126.2,
126.0, 124.2, 117.0, 55.4, 47.7, 45.7. HRMS (ESI)+ calculated
for C26H22ClN4O2S2, [M+H]+: m/z 521.0885, found 521.0873.
6-((2-Bromophenyl)carbamothioyl)-2-(2-
chlorobenzamido)-4,5,6,7-tetrahydrothieno[2,3-
c]pyridine-3-carboxamide (22af). White solid, mp 215-
1
216, yield 77.0%. H-NMR (400 MHz, DMSO-d6), δ(ppm):
12.26 (1H, brs), 9.43 (1H, brs), 7.75 (1H, dd, J = 7.6, 1.5 Hz),
7.66 (1H, dd, J = 8.0, 1.2 Hz), 7.63 (1H, dd, J = 8.0, 1.2 Hz),
7.59 (1H, td, J = 8.0, 1.2 Hz), 7.52 (1H, td, J = 7.6, 1.5 Hz),
7.39 (1H, td, J = 8.0, 1.2 Hz), 7.33 (1H, dd, J = 7.9, 1.7 Hz),
7.21 (1H, td, J = 7.9, 1.7 Hz), 5.13 (2H, s), 4.20 (2H, t, J = 5.3
Hz), 2.98 (2H, t, J = 5.3 Hz). 13C-NMR (100 MHz, DMSO-
d6), δ(ppm): 181.9, 167.2, 162.9, 142.7, 140.0, 134.1, 133.0,
132.9, 132.0, 130.9, 130.6, 130.4, 129.4, 128.7, 128.3, 128.2,
124.0, 123.7, 117.7, 47.6, 45.7, 25.9. HRMS (ESI)+ calculated
for C21H19BrClN4O2S2, [M+H]+: m/z 548.9821, found
2-(2-Chlorobenzamido)-6-((2-chlorophenyl)
carbamothioyl)-4,5,6,7-tetrahydrothieno[2,3-
c]pyridine-3-carboxamide (22ac). White solid, mp 158-
1
160, yield 62.5%. H-NMR (400 MHz, DMSO-d6), δ(ppm):
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