[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)(=[O:15])=[O:14])=[C:9]([CH3:25])[CH:8]=2)[N:5]=[C:4]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=1.[F:30][C:31]1[CH:36]=[C:35]([O:37][C:38]2[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=2)[CH:34]=[CH:33][C:32]=1[NH2:45].C1C[O:49][CH2:48]C1>ClCCCl>[C:26]([C:4]1[CH:3]=[C:2]([NH:1][C:48]([NH:45][C:32]2[CH:33]=[CH:34][C:35]([O:37][C:38]3[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=3)=[CH:36][C:31]=2[F:30])=[O:49])[N:6]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)(=[O:15])=[O:14])=[C:9]([CH3:25])[CH:8]=2)[N:5]=1)([CH3:29])([CH3:28])[CH3:27]To a solution of 4-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzenesulfonamide (150 mg, 0.36 mmol) in anhydrous DCE (1 mL) was added CDT (64 mg, 0.39 mmol, 1.1 eq), and the reaction was stirred under nitrogen at 50° C. for 18 h. A solution of 2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenylamine (86 mg, 0.39 mmol, 1.1 eq) in anhydrous THF (1 mL) was added to the reaction, and the solution was stirred under at 50° C. for 3 days. The reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The crude product was purified by HPLC and recrystallized from DCM/hexane to give 55 mg (23%) of the title compound as a white solid. 1H-NMR (DMSO-d6) δ 8.92 (d, J=14.4 Hz, 2H), 8.30 (d, J=5.7 Hz, 1H), 8.07 (t, J=9 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.68 (t, J=6 Hz, 1H), 7.58 to 7.51 (m, 2H), 7.25 (dd, J=11.4, 2.4 Hz, 1H), 6.97 to 6.92 (m, 1H), 6.77 (d, J=2.4 Hz, 1H), 6.74 to 6.70 (m, 1H), 6.41 (s, 1H), 3.45 (t, J=4.5 Hz, 4H), 2.93 (q, J=6H, 2H), 2.65 (s, 3H), 2.39 (s, 3H), 2.25 (t, J=6.9 Hz, 2H), 2.20 to 2.17 (m, 4H), 1.27 (s, 9H); MS LC-MS [M+H]+=666, RT=2.26 min.
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