1H NMR (400 MHz, DMSO-d6) δ 13.78 (s, 1H), 11.70 (s, 1H), 8.38 – 8.46 (m, 2H), 8.00 (s, 1H), 7.54 (dd, J
= 8.6, 1.5 Hz, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.13 – 6.99 (m, 2H), 6.56 (d, J = 7.4 Hz, 1H), 6.29 – 6.37 (m, 1H),
6.12 – 6.18 (m, 1H), 5.62 (dd, J = 10.1, 2.3 Hz, 1H), 4.19 (t, J = 5.7 Hz, 2H), 3.65 (dd, J = 5.8, 2.0 Hz, 2H). 13
C
NMR (101 MHz, DMSO-d6) δ 165.42, 152.37, 140.68, 138.52, 132.18, 129.67, 127.83, 127.53, 127.22, 127.22,
126.41, 125.75, 123.70, 123.36, 122.65, 122.11, 119.82, 117.45, 108.93, 105.69, 101.20, 98.13, 66.90, 38.96.
HRMS (ESI) m/z calcd. for C21H18F3N4O2 [M+H]+ 415.1376, found 415.1379.
5.1.16 N-(2-((2-(6-(trifluoromethyl)-1H-indazol-3-yl)-1H-indol-4-yl)oxy)ethyl)propionamide (30)
1H NMR (400 MHz, DMSO-d6) δ 13.79 (s, 1H), 11.70 (s, 1H), 8.41 (d, J = 8.5 Hz, 1H), 8.09 (t, J = 5.7 Hz,
1H), 8.00 (s, 1H), 7.54 (dd, J = 8.6, 1.5 Hz, 1H), 7.17 (d, J = 2.1 Hz, 1H), 7.11 – 7.03 (m, 2H), 6.56 (dd, J = 7.5,
1.0 Hz, 1H), 4.15 (t, J = 5.8 Hz, 2H), 3.56 (q, J = 5.8 Hz, 2H), 2.16 (q, J = 7.6 Hz, 2H), 1.03 (t, J = 7.6 Hz, 3H).
13C NMR (101 MHz, DMSO-d6) δ 173.71, 152.44, 140.67, 138.52, 129.63, 127.55, 127.23, 126.92, 126.41, 123.70,
123.36, 122.66, 122.11, 119.82, 117.47, 108.94, 105.62, 101.11, 98.17, 66.97, 38.80, 28.94, 10.37. HRMS (ESI)
m/z calcd. for C21H20F3N4O2 [M+H]+ 417.1533, found 417.1530.
5.1.17 N-(2-((2-(6-(1H-pyrazol-4-yl)-1H-indazol-3-yl)-1H-indol-4-yl)oxy)ethyl)acrylamide (31)
1H NMR (400 MHz, MeOD) δ 8.14 (d, J = 8.5 Hz, 1H), 8.07 (s, 2H), 7.72 (s, 1H), 7.52 (dd, J = 8.5, 1.4 Hz,
1H), 7.17 (s, 1H), 7.13 – 7.02 (m, 2H), 6.55 (dd, J = 7.2, 1.2 Hz, 1H), 6.40 – 6.24 (m, 2H), 5.68 (dd, J = 9.5, 2.5
Hz, 1H), 4.27 (t, J = 5.4 Hz, 2H), 3.80 (t, J = 5.4 Hz, 2H). 13C NMR (126 MHz, MeOD) δ 167.14, 152.28, 145.21,
142.42, 138.44, 138.21, 136.60, 131.63, 130.59, 129.82, 125.52, 122.58, 122.36, 120.95, 119.86, 119.79, 118.96,
105.64, 104.64, 100.19, 97.56, 66.25, 39.04. HRMS (ESI) m/z calcd. for C23H20N6O2Na [M+Na]+ 435.1540, found
435.1540.
5.1.18 N-(1-(((2-(6-(difluoromethyl)-1H-indazol-3-yl)-1H-indol-4-yl)oxy)methyl)cyclopropyl)acrylamide (32)
1H NMR (400 MHz, MeOD) δ 8.27 (d, J = 8.5 Hz, 1H), 7.76 (s, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.18 (d, J =
0.8 Hz, 1H), 7.11 – 6.99 (m, 2H), 6.86 (t, J = 56.2 Hz, 1H), 6.49 (dd, J = 7.4, 1.1 Hz, 1H), 6.28 – 6.19 (m, 2H),
5.64 – 5.60 (m, 1H), 4.24 (s, 2H), 1.08 – 0.95 (m, 4H). 13C NMR (101 MHz, MeOD) δ 167.70, 152.69, 141.03,
138.65, 138.27, 133.32 (t, J = 7.4, 23.2 Hz), 130.82, 129.36, 125.47, 122.75, 121.32, 119.89, 117.64 (t, J = 5.1 Hz),
115.21 (t, J = 237.1 Hz), 107.98, 104.58, 100.72, 97.78, 71.71, 32.34, 11.01. 19F NMR (376 MHz, MeOD) δ
-110.73. HRMS (ESI) m/z calcd. for C23H21F2N4O2 [M+H]+ 423.1627, found 423.1629.
5.1.19 1-(3-((2-(6-(Difluoromethyl)-1H-indazol-3-yl)-1H-indol-4-yl)oxy)azetidin-1-yl)prop-2-en-1-one (33)
1H NMR (500 MHz, MeOD) δ 8.28 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.19 (s, 1H),
7.16 (d, J = 8.1 Hz, 1H), 7.08 (t, J = 7.9 Hz, 1H), 6.94 (t, J = 56.2 Hz, 1H), 6.40 (dd, J = 17.0, 10.3 Hz, 1H), 6.33 –
6.26 (m, 2H), 5.77 (dd, J = 10.3, 1.9 Hz, 1H), 5.25 (dt, J = 6.3, 2.7 Hz, 1H), 4.79 (dd, J = 9.6, 6.6 Hz, 1H), 4.56
(dd, J = 11.3, 6.5 Hz, 1H), 4.42 (dd, J = 9.9, 3.6 Hz, 1H), 4.20 (dd, J = 11.3, 3.6 Hz, 1H). 13C NMR (126 MHz,
MeOD) δ 166.33, 149.84, 140.96, 138.47, 133.30 (t, J = 22.3 Hz), 129.91, 126.90, 125.75, 122.58, 121.36, 121.31,
119.64, 117.82 (t, J = 5.1 Hz), 115.20 (t, J = 237.2 Hz), 107.90 (t, J = 7.5 Hz), 105.40, 100.31, 97.37, 65.46, 57.57,
55.18, 48.44. HRMS (ESI) m/z calcd. for C22H19F2N4O2 [M+H]+ 409.1471, found 409.1475.
5.1.20 1-(3-((2-(6-(Difluoromethyl)-1H-indazol-3-yl)-1H-indol-4-yl)oxy)pyrrolidin-1-yl)prop-2-en-1-one (34)
1H NMR (500 MHz, Acetone-d6) δ 12.76 (s, 1H), 10.86 (s, 1H), 8.33 (d, J = 8.4 Hz, 1H), 7.89 (s, 1H), 7.47
(d, J = 8.4 Hz, 1H), 7.32 – 6.94 (m, 4H), 6.82 – 6.54 (m, 2H), 6.40 – 6.24 (m, 1H), 5.65 (ddd, J = 25.7, 10.2, 2.5
Hz, 1H), 5.29 (dt, J = 35.3, 3.8 Hz, 1H), 4.10 – 3.69 (m, 5H), 2.51 – 2.19 (m, 2H). 13C NMR (126 MHz,
Acetone-d6) δ 163.77, 163.75, 150.77 (d, J = 9.1 Hz), 141.19, 138.49, 133.02 (td, J = 22.2, 2.2 Hz), 130.10 (d, J =
9.7 Hz), 129.48, 129.44, 129.32, 126.18, 123.05, 121.60 (d, J = 20.5 Hz), 120.79 (d, J = 5.4 Hz), 118.11 (q, J = 5.3
Hz), 115.41 (t, J = 236.7 Hz), 108.54 (q, J = 7.1, 6.5 Hz), 105.42, 105.38, 105.31, 102.51 (d, J = 8.2 Hz), 97.78 (d,
J = 6.7 Hz), 77.06, 75.33, 51.74 (d, J = 47.9 Hz), 44.51, 43.91, 31.76. HRMS (ESI) m/z calcd. for C23H21F2N4O2
[M+H]+ 423.1627, found 423.1622.