Full Papers
doi.org/10.1002/cmdc.202100122
ChemMedChem
1
15.9 (1 C), 112.0 (2 C), 41.7 (1 C), 28.7 (1 C), 19.4 (1 C), 12.3 (1 C),
CDCl ) δ 166.7 (1 C), 161.2 (d, J=245.0 Hz, 1 C, CÀ F), 156.9 (1 C),
3
+
9.5 (2 C); HRMS-ESI (m/z): [M+H] calcd for C H N S 518.2121,
155.1 (d, J=233.75 Hz, 1 C), 147.1 (1 C), 146.1 (1 C), 143.0 (1 C),
30
27
7
found 518.2108; HPLC: t =12.60 min, 99.26% (DW/acetonitrile
142.6 (1 C), 142.2 (1 C), 136.1 (1 C), 129.7 (1 C), 129.5 (1 C), 127.2 (d,
2 C, J=7.5 Hz), 125.5 (1 C), 120.6 (1 C), 116.0 (1 C), 115.9 (1 C), 114.6
R
60:40).
(
7
+
1
d, 2 C, J=22.5 Hz), 114.2 (d, 2 C, J=21.25 Hz), 112.6 (d, 2 C, J=
N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]
thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)
.5 Hz), 41.8 (1 C), 28.7 (1 C), 12.3 (1 C), 9.5 (2 C); HRMS-ESI (m/z): [M
+
H] calcd for C H F N S 540.1777, found 540.1763; HPLC: t =
29 23 2 7 R
aniline (21a): Yellow powdery crystals. Yield: 70% (0.09 g); mp:
8.41 min, 99.33% (DW/acetonitrile 60:40).
1
1
50–151°C; H NMR (300 MHz, CDCl ) δ ppm 12.16 (s, 1H,
3
imidazole-NH), 7.78 (br s, 2H, ArH), 7.28 (t, 1H, J=9.0 Hz, ArH), 7.11
t, 2H, J=7.5 Hz, ArH), 6.93 (t, 2H, J=9.0 Hz, ArH), 6.82 (d, 2H, J=
N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]
thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-
methylaniline (21e): Yellow powdery crystals. Yield: 63% (0.08 g);
(
9
.0 Hz, ArH), 6.72 (t, 1H, J=6.0 Hz, ArH), 6.46 (d, 2H, J=6.0 Hz, ArH),
1
4
.62 (s, 1H, NH), 4.44 (s, 2H, NHCH ), 2.18 (m, 1H, CH), 2.09 (s, 3H,
CH ), 1.13–1.11 (m, 2H, CH ), 0.98 (m, 2H, CH ); C NMR (125 MHz,
mp: 110–111°C; H NMR (300 MHz, CDCl ) δ ppm 11.43 (s, 1H,
2
3
13
imidazole-NH), 7.71 (br s, 2H, ArH), 7.23 (t, 1H, J=7.5 Hz, ArH), 7.11
(d, 1H, J=9.0 Hz, ArH), 7.05 (d, 1H, J=9.0 Hz, ArH), 6.88–6.81 (m,
3
2
2
CDCl ) δ 166.7 (1 C), 161.2 (d, J=245.0 Hz, CÀ F), 158.9 (1 C), 157.0
3
(1 C), 147.4 (1 C), 146.3 (1 C), 146.1 (1 C), 142.9 (1 C), 142.2 (1 C),
3H, ArH), 6.78–6.69 (m, 3H, ArH), 4.56 (s, 2H, NHCH ), 4.32 (s, 1H,
2
1
36.0 (1 C), 129.6 (d, 2 C, J=25.0 Hz), 128.2 (2 C), 127.3 (1 C), 127.2
NH), 2.26 (br s, 4H, CH and CH ), 2.04 (s, 3H, CH ), 1.14 (br s, 2H,
3
3
1
3
(1 C), 125.5 (1 C), 120.5 (1 C), 117.1 (1 C), 115.9 (1 C), 114.2 (d, 2 C,
CH ), 0.99 (br s, 2H, CH ); C NMR (125 MHz, CDCl ) δ 166.4 (1 C),
2
2
3
J=22.5 Hz), 111.8 (2 C), 41.3 (1 C), 28.7 (1 C), 12.3 (1 C), 9.5 (2 C);
161.1 (d, J=245.0 Hz, 1 C, CÀ F), 156.8 (1 C), 147.1 (1 C), 145.9 (1 C),
144.5 (1 C), 143.1 (1 C), 142.1 (1 C), 135.9 (1 C), 129.6 (1 C), 129.5
(1 C), 129.2 (1 C), 127.2 (d, 2 C, J=8.75 Hz), 126.2 (1 C), 125.5 (1 C),
+
HRMS-ESI (m/z): [M+H] calcd for C H FN S 522.1871, found
29
24
7
5
22.1859; HPLC: t =12.98 min, 99.91% (DW/acetonitrile 60:40).
R
1
2
21.6 (1 C), 120.5 (1 C), 117.1 (1 C), 116.0 (1 C), 115.8 (1 C), 114.3 (d,
N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]
C, J=21.25 Hz), 109.4 (1 C), 41.7 (1 C), 28.7 (1 C), 22.9 (1 C), 12.4
thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-
fluoroaniline (21b): Yellow powdery crystals. Yield: 42% (0.05 g);
+
(1 C), 9.5 (2 C); HRMS-ESI (m/z): [M+H] calcd for C H FN S
30
26
7
5
36.2027, found 536.2015; HPLC: t =11.09 min, 98.71% (DW/
1
R
mp: 100–101°C; H NMR (300 MHz, CDCl ) δ ppm 11.56 (s, 1H,
3
acetonitrile 55:45).
imidazole-NH), 7.68–7.64 (m, 2H, ArH), 7.30 (t, 1H, J=7.5 Hz, ArH),
.02–6.96 (m, 2H, ArH), 6.89–6.78 (m, 5H, ArH), 6.73–6.70 (m, 1H,
7
N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]
ArH), 4.72 (s, 1H, NH), 4.61 (s, 2H, NHCH ), 2.42 (s, 3H, CH ), 2.19–
thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)-3-
methylaniline (21f): Yellow powdery crystals. Yield: 59% (0.08 g);
2
3
1
3
2
.17 (m,1H, CH), 1.18–1.11 (m, 2H, CH ), 1.03–0.97 (m, 2H, CH ); C
2
2
1
NMR (125 MHz, CDCl ) δ 166.5 (1 C), 160.2 (d, J=245.0 Hz, 1 C, CÀ F),
mp: 126–128°C; H NMR (300 MHz, CDCl ) δ ppm 11.72 (s, 1H,
3
3
1
1
1
1
1
1
59.5 (1 C), 156.4 (1 C), 151.0 (1 C), 150.7 (d, J=238.75 Hz, 1 C),
46.9 (1 C), 143.3 (1 C), 142.1 (1 C), 136.8 (1 C), 134.8 (d, J=
1.25 Hz, 1 C), 129.4 (d, J=3.75 Hz, 1 C), 127.1 (d, 2 C, J=8.75 Hz),
23.8 (1 C), 123.7 (1 C), 120.7 (1 C), 120.6 (1 C), 117.1 (d, J=6.25 Hz,
C), 116.1 (1 C), 114.2 (d, 2 C, J=21.25 Hz), 113.6 (d, J=17.5 Hz,
imidazole-NH), 7.74 (br s, 2H, ArH), 7.26–7.23 (m, 1H, ArH), 7.02 (t,
1H, J=7.5 Hz, ArH), 6.91 (t, 2H, J=7.5 Hz, ArH), 6.81 (d, 2H, J=
6.0 Hz, ArH), 6.56 (d, 1H, J=6.0 Hz, ArH), 6.35 (d, 2H, J=6.0 Hz, ArH),
4.48 (br s, 3H, NH and NHCH ), 2.22 (br s, 4H, CH and CH ), 2.18 (s,
2
3
1
3
3H, CH ), 1.14–1.11 (m, 2H, CH ), 0.99 (br s, 2H, CH ); C NMR
3
2
2
C), 111.8 (d, J=3.75 Hz, 1 C), 41.3 (1 C), 28.7 (1 C), 12.3 (1 C), 9.5
(125 MHz, CDCl ) δ 166.6 (1 C), 161.2 (d, J=245.0 Hz, 1 C, CÀ F),
3
+
(2 C); HRMS-ESI (m/z): [M+H] calcd for C H F N S 540.1777,
156.9 (1 C), 147.3 (1 C), 146.4 (1 C), 146.0 (1 C), 143.0 (1 C), 142.1
(1 C), 138.0 (1 C), 135.9 (1 C), 129.6 (1 C), 129.5 (1 C), 128.2 (1 C),
127.2 (d, 2 C, J=8.75 Hz), 125.5 (1 C), 120.4 (1 C), 118.2 (1 C), 116.0
29
23
2
7
found 540.1763; HPLC: t =15.36 min, 99.73% (DW/acetonitrile
R
60:40).
1 C), 115.8 (1 C), 114.2 (d, 2 C, J=21.25 Hz), 112.9 (1 C), 109.1 (1 C),
N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]
thiadiazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-3-
fluoroaniline (21c): Yellow powdery crystals. Yield: 52% (0.07 g);
1.6 (1 C), 28.7 (1 C), 20.6 (1 C), 12.3 (1 C), 9.5 (2 C); HRMS-ESI (m/z):
+
3
0
2
6
7
R
0.59 min, 98.50% (DW/acetonitrile 55:45).
1
mp: 156–158°C; H NMR (300 MHz, CDCl ) δ ppm 12.54 (s, 1H,
3
imidazole-NH), 7.79 (s, 2H, ArH), 7.31 (t, 1H, J=9.0 Hz, ArH), 7.01–
6
.96 (m, 3H, ArH), 6.82 (d, 2H, J=6.0 Hz, ArH), 6.36 (t, 1H, J=7.5 Hz,
ArH), 6.11–6.01 (m, 2H, ArH), 4.92 (s, 1H, NH), 4.38 (s, 2H, NHCH2),
1
2
2
2
.16–2.14 (m, 4H, CH and CH ), 1.11–1.09 (m, 2H, CH ), 0.95 (br s,
3
2
3
13
H, CH2); C NMR (125 MHz, CDCl ) δ 167.1 (1 C), 162.9 (d, J=
3
41.25 Hz, 1 C, CÀ F), 161.3 (d, J=245.0 Hz, 1 C), 157.1 (1 C), 147.9
(d, J=11.25 Hz, 1 C), 147.0 (1 C), 146.1 (1 C), 142.8 (1 C), 142.4 (1 C),
2
3
1
3
1
1
36.2 (1 C), 129.8 (1 C), 129.4 (d, J=2.5 Hz, 1 C), 129.3 (d, 2 C, J=
0.0 Hz, 1 C), 127.3 (d, J=8.75 Hz, 1 C), 125.7 (1 C), 120.6 (1 C), 116.2
3
2
2
3
(1 C), 115.8 (1 C), 114.2 (d, 2 C, J=21.25 Hz), 107.4 (1 C), 103.3 (d,
J=21.25 Hz, 1 C), 98.61 (1 C), 98.4 (1 C), 41.1 (1 C), 28.7 (1 C), 12.3
+
(
1 C), 9.5 (2 C); HRMS-ESI (m/z): [M+H] calcd for C H F N S
29 23 2 7
5
40.1777, found 540.1762; HPLC: t =15.47 min, 99.36% (DW/
R
+
acetonitrile 60:40).
C H FN S 536.2027, found 536.2016; HPLC: t =9.78 min, 99.01%
3
0
26
7
R
N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]
(DW/acetonitrile 55:45).
thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)-4-
fluoroaniline (21d): Yellow powdery crystals. Yield: 56% (0.07 g);
N-((4-(2-Cyclopropyl-6-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-
(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline (22a): Yellow
1
mp: 106–108°C; H NMR (300 MHz, CDCl ) δ ppm 12.19 (s, 1H,
3
1
imidazole-NH), 7.73 (br s, 2H, ArH), 7.27 (t, 1H, J=7.5 Hz, ArH), 6.89
t, 2H, J=9.0 Hz, ArH), 6.82–6.75 (m, 4H, ArH), 6.37–6.33 (m, 2H,
powdery crystals. Yield: 67% (0.07 g); mp: 126–128°C; H NMR
(
(300 MHz, CDCl ) δ ppm 11.96 (s, 1H, imidazole-NH), 7.37 (t, 1H, J=
3
ArH), 4.55 (s, 1H, NH), 4.34 (s, 2H, NHCH ), 2.16–2.12 (m, 4H, CH and
7.5 Hz, ArH), 7.08 (t, 2H, J=7.5 Hz, ArH), 6.93 (br s, 2H, ArH), 6.86 (d,
1H, J=9.0 Hz, ArH), 6.47 (t, 2H, J=7.5 Hz, ArH), 4.64 (s, 1H, NH), 4.40
2
13
CH ), 1.11–1.09 (m, 2H, CH ), 0.95 (br s, 2H, CH ); C NMR (125 MHz,
3
2
2
ChemMedChem 2021, 16, 1–13
9
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