[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[C:23]([F:24])=[CH:22][C:21]([NH2:25])=[C:20]([Cl:26])[CH:19]=4)=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[NH2:30][CH:31]1[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.C(Cl)Cl.O>[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:19]=[C:20]([Cl:26])[C:21]([NH2:25])=[CH:22][C:23]=4[F:24])=[C:11]3[C:10]([NH:30][CH:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[N:9]2)=[CH:5][CH:4]=14-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorobenzenamine (200 mg, 0.38 mmol) was added into a suspension of 4-amino-1-methylpiperidine (131 mg, 1.14 mmol), Cu(I)I (14.5 mg, 0.0762 mmol), K2CO3 (263 mg, 1.91 mmol) and L-proline (17.6 mg, 0.152 mmol) in DMSO (6 mL) and the reaction mixture was heated at 100° C. for 12 hours. The reaction with diluted with CH2Cl2 and water (10 mL) was added. The organic layer was then washed with water (10 mL), brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (5% MeOH in CH2Cl2) to afford the product (130 mg, 66.7% yield) as a brown oil. LRMS (APCI pos) m/e 511.1 (M+H).
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