P. Xu, P. Shen, H. Wang et al.
European Journal of Medicinal Chemistry 218 (2021) 113394
furfural then 3-bromopropionitrile, and 0.1 g (22% for 3 steps) of 5b
432.1237, found 432.1241.
ꢁ
1
was obtained as a yellow solid. mp 215e221 C. HNMR(300 MHz,
DMSO‑d ):
6
d
¼ 11.88 (s, 1H), 8.65 (s, 1H), 8.49 (s, 1H), 7.95 (s, 1H),
4.1.26. 3-(4-(2-(Trifluoromethyl)imidazo[4,5-d]pyrrolo[2,3-b]
pyridin-1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5g)
Synthesized using the procedure 1, 6 and 5 using tri-
fluoroacetaldehyde then 3-bromopropionitrile, and 0.2 g (33% for 3
7
5
2
.34 (t, J ¼ 3.0 Hz, 1H), 6.32 (d, J ¼ 6.0 Hz, 1H), 6.21 (t, J ¼ 3.0 Hz, 1H),
.95 (t, J ¼ 3.0 Hz, 1H), 4.61 (t, J ¼ 6.0 Hz, 2H), 3.26 (t, J ¼ 6.0 Hz, 2H)
.36 (s, 3H) ppm; 13C NMR (75 MHz, DMSO‑d
154.37, 145.63,
43.32, 142.66, 138.23, 135.85, 135.51, 134.01, 129.74, 124.61, 118.80,
6
) d
ꢁ
1
steps) of 5g was obtained as a white solid. mp 218e222 C.
1
1
18.74, 113.49, 108.52, 104.57, 96.45, 48.04, 19.19, 13.71 ppm; HRMS
HNMR(300 MHz, DMSO‑d
6
):
d
¼ 12.18 (s, 1H), 8.84 (s, 1H), 8.56 (s,
þ
(
ESI): m/z [MþH] .Calcd for C19
H
16
N
7
O 358.1411, found 358.1425.
1H), 8.04 (s, 1H), 7.45 (t, J ¼ 3.0 Hz, 1H), 6.05 (d, J ¼ 3.0 Hz, 1H), 4.61
13
(
t, J ¼ 6.0 Hz, 2H), 3.25 (t, J ¼ 6.0 Hz, 2H) ppm; C NMR (75 MHz,
4.1.22. 3-(4-(2-(3-Hydroxyphenyl)imidazo[4,5-d]pyrrolo[2,3-b]
DMSO‑d 146.31, 139.10, 138.59, 138.09, 137.05, 136.31, 132.02,
6
) d
pyridin-1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5c)
Synthesized using the procedure 1, and
hydroxybenzaldehyde then 3-bromopropionitrile, and 0.2 g (16%
129.84, 125.29, 120.89, 118.68, 117.30, 116.51, 104.31, 97.01, 48.05,
þ
6
5
using 3-
19.10 ppm; HRMS (ESI): m/z [MþH] .Calcd for C15
11 3 7
H F N 346.1023,
found 346.1049.
ꢁ
for 3 steps) of 5c was obtained as a gray solid. mp 247e250 C.
1
HNMR(300 MHz, DMSO‑d
H), 8.41 (s, 1H), 7.86 (s, 1H), 7.34 (t, J ¼ 3.0 Hz, 1H), 7.26 (t,
6
):
d
¼ 11.87 (s, 1H), 9.66 (s, 1H), 8.69 (s,
4.1.27. 3-(4-(2-(Thiophen-2-yl)imidazo[4,5-d]pyrrolo[2,3-b]
pyridin-1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5h)
Synthesized using the procedure 1, 6 and 5 using 2-
thenaldehyde then 3-bromopropionitrile, and 0.2 g (22% for 3
1
J ¼ 3.0 Hz, 1H), 7.19 (t, J ¼ 9.0 Hz, 1H), 7.07 (t, J ¼ 3.0 Hz, 1H),
6
3
1
.87e6.83 (m, 1H), 6.00 (t, J ¼ 3.0 Hz, 1H), 4.56 (t, J ¼ 6.0 Hz, 2H),
1
3
ꢁ
.21 (t, J ¼ 6.0 Hz, 2H) ppm; C NMR (75 MHz, DMSO‑d
6
)
d
157.65,
steps) of 5h was obtained as a light yellow solid. mp 221e226 C.
1
50.93, 145.56, 138.25, 136.49, 135.68, 133.84, 131.18, 129.86, 129.55,
HNMR(300 MHz, DMSO‑d
6
):
d
¼ 11.94 (s, 1H), 8.69 (s, 1H), 8.57 (s,
1
24.45, 119.89, 119.64, 118.73, 117.04, 116.29, 104.76, 96.65, 47.97,
1H), 8.04 (s, 1H), 7.74 (d, J ¼ 6.0 Hz, 1H), 7.37 (t, J ¼ 3.0 Hz, 1H), 7.22
(d, J ¼ 3.0 Hz,1H), 7.10 (t, J ¼ 4.5 Hz,1H), 5.96 (d, J ¼ 3.0 Hz,1H), 4.65
þ
19.17 ppm; HRMS (ESI): m/z [MþH] .Calcd for C20
H
16
N
7
O 370.1411,
13
found 370.1425.
(t, J ¼ 6.0 Hz, 2H), 3.30 (t, J ¼ 6.0 Hz, 2H) ppm; C NMR (75 MHz,
6
DMSO‑d ) d 146.22, 145.67, 138.58, 136.44, 135.42, 133.90, 132.46,
4
.1.23. 3-(4-(2-(5-Methylthiophen-2-yl)imidazo[4,5-d]pyrrolo[2,3-
130.23, 129.51, 128.30, 124.67, 120.51, 118.75, 104.62, 96.43, 64.50,
þ
b]pyridin-1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5d)
Synthesized using the procedure 1, and
48.12, 19.29 ppm; HRMS (ESI): m/z [MþH] .Calcd for C18
14 7
H N S
6
5
using 5-
360.1026, found 360.1033.
methylthiophene-2-carboxaldehyde then 3-bromopropionitrile,
and 0.1 g (17% for 3 steps) of 5d was obtained as a light yellow solid.
4.1.28. 3-(4-(2-(Thiazol-2-yl)imidazo[4,5-d]pyrrolo[2,3-b]pyridin-
1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5i)
Synthesized using the procedure 1, 6 and 5 using 2-
thiazolecarboxaldehyde then 3-bromopropionitrile, and 0.2 g
ꢁ
1
mp 210e216 C. HNMR(300 MHz, DMSO‑d
6
):
d
¼ 11.86 (s, 1H), 8.64
(
s, 1H), 8.52 (s, 1H), 7.98 (s, 1H), 7.33 (t, J ¼ 3.0 Hz, 1H), 7.03 (d,
J ¼ 3.0 Hz, 1H), 6.78 (d, J ¼ 3.0 Hz, 1H), 5.92 (t, J ¼ 3.0 Hz, 1H), 4.62
13
(
d, J ¼ 6.0 Hz, 2H), 3.27 (d, J ¼ 6.0 Hz, 2H), 2.47 (s, 3H) ppm; C NMR
75 MHz, DMSO‑d 146.32, 145.59, 143.22, 138.52, 136.31, 135.24,
33.88, 130.18, 129.84, 128.52, 126.81, 124.60, 118.77, 118.67, 104.58,
(31% for 3 steps) of 5i was obtained as a yellow solid. mp
ꢁ
1
(
6
)
d
247e250 C. HNMR(300 MHz, DMSO‑d
6
):
d
¼ 12.04 (s, 1H), 8.76 (s,
1
9
C
1H), 8.44 (s, 1H), 7.95e7.91 (m, 3H), 7.38 (t, J ¼ 3.0 Hz, 1H), 6.04 (t,
J ¼ 3.0 Hz, 1H), 4.59 (t, J ¼ 6.0 Hz, 2H), 3.25 (t, J ¼ 6.0 Hz, 2H) ppm;
þ
6.35, 48.09, 19.26, 15.27 ppm; HRMS (ESI): m/z [MþH] .Calcd for
13
19
H
16
N
7
S 374.1182, found 374.1195.
6
C NMR (75 MHz, DMSO‑d ) d 157.89, 145.93, 144.50, 138.49,
136.63, 136.15, 135.26, 133.75, 132.31, 129.71, 124.78, 123.35, 120.51,
4
.1.24. 3-(4-(2-(2-Chlorophenyl)imidazo[4,5-d]pyrrolo[2,3-b]
pyridin-1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5e)
Synthesized using the procedure 1, and
118.88, 114.62, 104.62, 97.09, 70.39, 64.50, 61.55, 52.70, 49.75, 47.93,
þ
19.20 ppm; HRMS (ESI): m/z [MþH] .Calcd for C17
13 8
H N S 361.0978,
6
5
using 2-
found 361.2340.
chlorobenzaldehyde then 3-bromopropionitrile, and 0.1 g (21%
for 3 steps) of 5e was obtained as a light green solid. mp
4.1.29. 3-(4-(2-(Thiazol-5-yl)imidazo[4,5-d]pyrrolo[2,3-b]pyridin-
1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5j)
Synthesized using the procedure 1, 6 and 5 using thiazole-5-
carboxaldehyde then 3-bromopropionitrile, and 0.2 g (19% for 3
ꢁ
1
1
1
7
86e191 C. HNMR(300 MHz, DMSO‑d
H), 8.29 (s, 1H), 7.70 (d, J ¼ 9.0 Hz, 2H), 7.55 (t, J ¼ 3.0 Hz, 2H),
.44e7.52 (m,1H), 7.39 (t, J ¼ 3.0 Hz,1H), 6.16 (t, J ¼ 3.0 Hz,1H), 4.46
6
):
d
¼ 11.93 (s, 1H), 8.72 (s,
13
ꢁ
(
t, J ¼ 6.0 Hz, 2H) 3.12 (t, J ¼ 6.0 Hz, 2H) ppm; C NMR (75 MHz,
DMSO‑d 149.44, 145.60, 137.55, 135.83, 134.93, 134.02, 133.74,
33.22, 132.17, 129.88, 129.80, 128.90, 127.47, 124.63, 118.62, 118.27,
steps) of 5j was obtained as a dark yellow solid. mp 227e231 C.
1
6
)
d
HNMR(300 MHz, DMSO‑d
6
):
d
¼ 11.98 (s, 1H), 9.20 (s, 1H), 8.70 (s,
1
1H), 8.56 (s, 1H), 8.01 (d, J ¼ 6.0 Hz, 2H), 7.37 (t, J ¼ 3.0 Hz, 1H), 5.97
(d, J ¼ 3.0 Hz, 1H), 4.64 (t, J ¼ 6.0 Hz, 2H), 3.27 (t, J ¼ 6.0 Hz, 2H)
þ
104.56, 96.73, 47.82, 19.04 ppm; HRMS (ESI): m/z [MþH] .Calcd for
13
C
20-
H
15ClN 388.1072, found 388.1102.
7
6
ppm; C NMR (75 MHz, DMSO‑d ) d 156.69, 145.70, 144.30, 143.13,
1
38.53, 136.36, 135.59, 134.08, 130.36, 128.12, 124.81, 118.82, 118.08,
þ
4
[
.1.25. 3-(4-(2-(4-(Methylsulfonyl)phenyl)imidazo[4,5-d]pyrrolo
2,3-b]pyridin-1(6H)-yl)-1H-pyrazol-1-yl)propanenitrile (5f)
Synthesized using the procedure 1, and using 4-
methylsulphonyl benzaldehyde then 3-bromopropionitrile, and
.1 g (31% for 3 steps) of 5f was obtained as a dark yellow solid. mp
104.55, 96.50, 48.18, 19.26 ppm; HRMS (ESI): m/z [MþH] .Calcd for
17 13 8
C H N
S 361.0978, found 361.2341.
6
5
4.1.30. 3-(4-(Imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)-1H-
pyrazol-1-yl)propanenitrile (5k)
0
ꢁ
1
198e203 C. HNMR(300 MHz, DMSO‑d
6
):
H), 8.49 (s, 1H), 8.03e7.96 (m, 4H), 7.92 (s, 1H), 7.39 (t, J ¼ 3.0 Hz,
H), 6.04 (d, J ¼ 3.0 Hz, 1H), 4.59 (t, J ¼ 7.5 Hz, 2H), 3.28 (s, 3H), 3.23
d
¼ 11.97 (s, 1H), 8.77 (s,
Synthesized using the procedure 2,
6 and 5 using 3-
1
1
bromopropionitrile, and 0.1 g (15% for 3 steps) of 5k was ob-
ꢁ
1
tained as a light white solid. mp 258e262 C. HNMR(300 MHz,
DMSO‑d ):
¼ 11.94 (s, 1H), 8.68 (s, 1H), 8.51 (s, 1H), 8.32 (s, 1H),
8.04 (s, 1H), 7.42 (t, J ¼ 3.0 Hz, 1H), 6.36 (t, J ¼ 4.5 Hz, 1H), 4.58 (t,
13
(
1
1
t, J ¼ 7.5 Hz, 2H) ppm; C NMR (75 MHz, DMSO‑d
45.68,141.54,138.28, 136.68,136.08,134.74,134.00, 129.95, 129.86,
27.54, 124.72, 119.15, 118.75, 104.68, 96.79, 48.03, 43.79,
6
)
d
149.14,
6
d
13
J ¼ 6.0 Hz, 2H), 3.23 (t, J ¼ 6.0 Hz, 2H) ppm; C NMR (75 MHz,
DMSO‑d 157.67, 150.90, 145.57, 138.27, 136.51, 135.69, 133.84,
þ
19.29 ppm; HRMS (ESI): m/z [MþH] .Calcd for C21
18
H N
7
O
2
S
6
) d
14