S. Hou, X. Yang, Y. Yang et al.
European Journal of Medicinal Chemistry 220 (2021) 113482
387.1928, found: 387.1927.
compound 5. White solid, 31% yield. m.p. 221e222 ꢀC. HPLC anal-
ysis: retention time 3.686 min, 99.65% pure. 1H NMR (300 MHz,
5.1.1.6. 3-(5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)-N-
(2-methoxyethyl)benzamide (10). Compound 10 was prepared from
intermediates 7-d (155 mg, 0.44 mmol) and 10-c (134 mg,
0.44 mmol) according to a similar procedure to that for compound
5. White solid, 27% yield. m.p. 132e135 ꢀC. HPLC analysis: retention
DMSO‑d6)
d
13.63 (s,1H), 8.86 (s,1H), 8.49 (s, 1H), 8.22 (d, J ¼ 6.7 Hz,
2H), 8.06 (d, J ¼ 8.7 Hz, 1H), 7.81 (d, J ¼ 9.0 Hz, 2H), 7.66 (s, 2H), 7.54
(s, 1H), 5.41 (s, 2H), 4.34e4.57 (m, 1H), 3.30 (s, 3H), 1.43 (d,
J ¼ 9.0 Hz, 6H). 13C NMR (75 MHz, DMSO‑d6)
d153.60,142.56,142.21,
138.02, 134.04, 133.21, 130.26, 128.78, 127.49, 125.70, 125.56, 123.91,
122.95,122.23,120.45,111.97, 81.64, 56.60, 48.11, 23.53. HRMS-EI m/
z [MþH]þ calcd for C26H21ClN5O2: 414.2037, found: 414.2034.
time 3.272 min, 99.80% pure. 1H NMR (300 MHz, DMSO‑d6)
d 13.68
(s, 1H), 8.85 (s, 1H), 8.70 (s, 1H), 8.45 (s, 1H), 8.25 (s, 1H), 8.15 (d,
J ¼ 7.8 Hz,1H), 7.88 (d, J ¼ 7.3 Hz,1H), 7.78 (d, J ¼ 8.4 Hz,1H), 7.61 (d,
J ¼ 8.1 Hz, 2H), 4.45 (m, 1H), 3.45 (m, 4H), 3.25 (m, 3H), 1.42 (d,
5.1.1.11. 3-(3-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)phenyl)-5-(4-
isopropyl-4H-1,2,4-triazol-3-yl)-1H-indazole (15). Compound 15
was prepared from intermediates 7-d (166 mg, 0.47 mmol) and 15-
c (161 mg, 0.47 mmol) according to a similar procedure to that for
compound 5. White solid, 34% yield. m.p. 112e125 ꢀC. HPLC anal-
ysis: retention time 4.302 min, 98.95% pure. 1H NMR
J ¼ 6.6 Hz, 6H). 13C NMR (75 MHz, DMSO‑d6)
d 166.60, 153.41,
143.86, 142.49, 142.23, 135.62, 133.72, 129.96, 129.53, 127.51, 127.27,
125.98, 122.15, 120.90, 120.41, 111.92, 70.90, 58.38, 47.91, 39.53,
23.69. HRMS-EI m/z [MþH]þ calcd for C26H21ClN5O2: 405.2034,
found: 405.2035.
(300 MHz,DMSO‑d6) d 13.55 (s, 1H), 8.86 (s, 1H), 8.53 (s, 1H), 8.22 (d,
5.1.1.7. 3-(5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)-N-
(1-methyl-1H-pyrazol-4-yl)benzamide (11). Compound 11 was pre-
pared from intermediates 7-d (184 mg, 0.52 mmol) and 11-c
(170 mg, 0.52 mmol) according to a similar procedure to that for
compound 5. White solid, 29% yield. m.p. 123e126 ꢀC. HPLC anal-
ysis: retention time 3.294 min, 97.85% pure. 1H NMR (300 MHz,
J ¼ 13.4 Hz, 2H), 8.04 (s, 1H), 7.74e7.86 (m, 2H), 7.60e7.72 (m, 2H),
7.53 (t, J ¼ 7.7 Hz, 1H), 5.56 (q, J ¼ 5.8 Hz, 1H), 4.48e4.60 (m, 1H),
3.21e3.53 (m, 2H), 1.65 (d, J ¼ 6.0 Hz, 3H), 1.44 (d, J ¼ 6.7 Hz, 6H),
1.06 (t, J ¼ 7.0 Hz, 3H). 13C NMR (75 MHz, DMSO‑d6)
d 153.42,
144.58, 142.50, 142.17, 136.82, 134.28, 133.59, 130.00, 127.59, 125.80,
125.48, 125.33, 123.95, 122.65, 122.09, 120.74, 120.54, 111.80, 86.94,
63.54, 47.87, 23.71, 21.63, 15.20. HRMS-EI m/z [MþH]þ calcd for
DMSO‑d6)
d
10.62 (s, 1H), 8.87 (s, 1H), 8.56 (d, J ¼ 9.1 Hz,1H), 8.29 (s,
1H), 8.22 (d, J ¼ 7.9 Hz, 1H), 8.07 (s, 1H), 8.00 (d, J ¼ 7.9 Hz, 1H), 7.81
(d, J ¼ 8.6 Hz, 1H), 7.66 (dd, J ¼ 15.7, 8.1 Hz, 2H), 7.59 (s, 1H), 4.52 (m,
1H), 3.84 (s, 3H), 1.43 (d, J ¼ 6.7 Hz, 6H). 13C NMR (75 MHz,
C26H21ClN5O2: 442.2350, found: 442.2350.
5.1.1.12. 5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-3-(3-(1-methyl-1H-
pyrazol-4-yl)phenyl)-1H-indazole (16). Compound 16 was prepared
from intermediates 7-d (173 mg, 0.49 mmol) and 16-c (139 mg,
0.49 mmol) according to a similar procedure to that for compound
5. White solid, 32% yield. m.p. 165e168 ꢀC. HPLC analysis: retention
DMSO‑d6)
d 176.67, 163.73, 153.40, 143.84, 142.50, 142.23, 135.37,
133.87, 130.66, 130.17, 129.73, 127.58, 127.44, 126.09, 122.24, 122.09,
120.95, 120.43, 111.94, 104.36, 47.94, 39.17, 23.68. HRMS-EI m/z
[MþH]þ calcd for C26H21ClN5O2: 427.1989, found: 427.1991.
time 3.612 min, 99.19% pure. 1H NMR (300 MHz, DMSO‑d6)
d 13.60
5.1.1.8. 5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-3-(3-(methylsulfonyl)
phenyl)-1H-indazole (12). Compound 12 was prepared from in-
termediates 7-d (187 mg, 0.53 mmol) and 12-b (150 mg,
0.53 mmol) according to a similar procedure to that for compound
5. White solid, 34% yield. m.p. 256e269 ꢀC. HPLC analysis: retention
(s, 1H), 8.87 (d, J ¼ 2.7 Hz, 1H), 8.25 (s, 2H), 8.14 (s, 1H), 7.96 (s, 1H),
7.80 (d, J ¼ 8.5 Hz, 1H), 7.62 (s, 2H), 7.53 (s, 1H), 4.40e4.59 (m, 1H),
3.89 (s, 3H), 1.44 (d, J ¼ 8.5 Hz, 6H). 13C NMR (75 MHz, DMSO‑d6)
d
153.55,144.65,142.51, 142.18,136.59,134.11,133.69, 130.11,128.59,
127.48, 125.28, 123.73, 122.15, 120.51, 111.86, 48.01, 40.22, 23.60.
HRMS-EI m/z [MþH]þ calcd for C26H21ClN5O2: 384.1931, found:
384.1930.
time 3.155 min, 95.04% pure. 1H NMR (300 MHz, DMSO‑d6)
d 13.77
(s, 1H), 8.84 (d, J ¼ 12.0 Hz, 1H), 8.48 (s, 1H), 8.38 (d, J ¼ 7.9 Hz, 1H),
8.27 (s, 1H), 7.96 (d, J ¼ 7.9 Hz, 1H), 7.85e7.77 (m, 1H), 7.64 (d,
J ¼ 8.9 Hz, 1H), 7.52 (d, J ¼ 9.7 Hz, 1H), 4.62e4.34 (m, 1H), 3.29 (s,
5.1.1.13. 5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-3-(3-(1-(tetrahydro-
3H), 1.41 (d, J ¼ 7.5 Hz, 6H). 13C NMR (100 MHz, DMSO‑d6)
d
153.33,
2H-pyran-4-yl)-1H-pyrazol-4-yl)phenyl)-1H-indazole
(17).
142.83, 142.52, 142.29, 142.13, 134.76, 132.11, 130.84, 127.78, 126.76,
125.26, 121.85, 121.32, 120.31, 112.08, 47.94, 43.99, 23.72. HRMS-EI
m/z [MþH]þ calcd for C26H21ClN5O2: 382.1332, found: 382.1331.
Compound 17 was prepared from intermediates 7-d (177 mg,
0.50 mmol) and 17-c (178 mg, 0.50 mmol) according to a similar
procedure to that for compound 5. White solid, 28% yield. m.p.
140e143 ꢀC. HPLC analysis: retention time 3.708 min, 97.81% pure.
5.1.1.9. N-(3-(5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-1H-indazol-3-yl)
phenyl)ethanesulfonamide (13). Compound 13 was prepared from
intermediates 7-d (177 mg, 0.50 mmol) and 13-b (156 mg,
0.50 mmol) according to a similar procedure to that for compound
5. White solid, 27% yield. m.p. 140e143 ꢀC. HPLC analysis: retention
1H NMR (300 MHz, DMSO‑d6)
d
8.85 (d, J ¼ 6.1 Hz, 1H), 8.40 (s, 1H),
8.22 (d, J ¼ 8.4 Hz,1H), 8.16 (s,1H), 7.99 (d, J ¼ 5.7 Hz,1H), 7.87e7.67
(m, 2H), 7.44e7.68 (m, 3H), 4.35e4.58 (m, 2H), 3.91e4.04 (m, 2H),
3.42e3.55 (m, 2H), 1.93e2.07 (m, 4H), 1.43 (t, J ¼ 6.3 Hz, 6H). 13
C
NMR (75 MHz, DMSO‑d6)
d 153.53, 144.69, 142.54, 142.18, 136.38,
time 3.228 min, 95.17% pure. 1H NMR (300 MHz, DMSO‑d6)
d
13.63
134.11, 133.79, 130.10, 127.58, 127.52, 125.85, 125.31, 123.78, 122.20,
121.82,120.54, 111.88, 66.37, 57.83, 48.00, 33.36, 23.61. HRMS-EI m/z
[MþH]þ calcd for C26H21ClN5O2: 454.2350, found: 454.2350.
(s, 1H), 8.86 (s, 1H), 8.22 (s, 1H), 7.88 (s, 1H), 7.78 (d, J ¼ 8.7 Hz, 1H),
7.73e7.64 (m,1H), 7.59 (d, J ¼ 8.7 Hz,1H), 7.44 (t, J ¼ 7.9 Hz,1H), 7.25
(d, J ¼ 8.1 Hz,1H), 4.38e4.49 (m,1H), 3.09 (q, 2H), 1.42 (d, J ¼ 6.7 Hz,
6H), 1.06 (t, J ¼ 7.0 Hz, 3H). 13C NMR (100 MHz, DMSO‑d6)
d
153.51,
5.1.1.14. 5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-3-(3-(1-methyl-1H-
pyrazol-5-yl)phenyl)-1H-indazole (18). Compound 18 was prepared
from intermediates 7-d (173 mg, 0.49 mmol) and 18-c (139 mg,
0.49 mmol) according to a similar procedure to that for compound
5. White solid, 31% yield. m.p. 150e153 ꢀC. HPLC analysis: retention
143.91, 142.43, 142.24, 139.55, 134.73, 130.53, 127.51, 122.48, 122.13,
120.96, 120.42, 118.99, 118.05, 111.93, 47.95, 45.63, 23.65, 8.51.
HRMS-EI m/z [MþH]þ calcd for C26H21ClN5O2: 411.1598, found:
411.1596.
time 3.795 min, 98.13% pure. 1H NMR (300 MHz, DMSO‑d6)
d 13.65
5.1.1.10. 5-(4-isopropyl-4H-1,2,4-triazol-3-yl)-3-(3-(1-(methox-
ymethyl)-1H-pyrazol-4-yl)phenyl)-1H-indazole (14). Compound 14
was prepared from intermediates 7-d (170 mg, 0.48 mmol) and 14-
c (150 mg, 0.48 mmol) according to a similar procedure to that for
(s, 1H), 8.85 (s, 1H), 8.26 (s, 1H), 8.06e8.12 (m, 2H), 7.80 (d,
J ¼ 7.9 Hz, 1H), 7.55e7.70 (m, 3H), 7.50 (s, 1H), 6.51 (s, 1H),
4.52e4.40 (m, 1H), 3.91 (s, 3H), 1.42 (d, J ¼ 6.3 Hz, 6H). 13C NMR
(100 MHz, DMSO‑d6)
d 153.53, 144.00, 142.99, 142.48, 142.22,
11