Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:18])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH2:17])[N:12]=2)=[CH:4][CH:3]=1.N1CCCCC1.[S:25]1[CH:29]=[CH:28][N:27]=[C:26]1[C:30]([OH:34])([C:32]#[CH:33])[CH3:31]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([C:33]#[C:32][C:30]([C:26]4[S:25][CH:29]=[CH:28][N:27]=4)([OH:34])[CH3:31])[CH:10]=3)[C:6]([CH3:18])=[N:7]2)[CH:16]=[CH:15][N:14]=1To a mixture of 4-(6-bromo-3-methyl-1H-indazol-1-yl)pyrimidin-2-amine (5-a) (240 mg, 0.489 mmol) and piperidine (1.2 mL) was added tetrakis(triphenylphosphine)palladium (53.5 mg, 0.049 mmol), copper(I) iodide (9.3 mg, 0.049 mmol) and 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (I-1) (150 mg, 0.978 mmol). The reaction was purged with N2 and stirred at 60° C. for 1.5 hr. The reaction mixture was concentrated in vacuo. EtOAc (2 mL) was added to the residue and concentration in vacuo was repeated. The resultant residue was purified by flash chromatography (Isolute column, 100% DCM to 3% MeOH in DCM) to afford the title compound as a white solid: 1H NMR (250 MHz, DMSO) δ 1.87-1.97 (3H, m), 2.56 (3H, s), 6.91-7.00 (1H, m), 7.01-7.07 (1H, m), 7.10-7.23 (1H, m), 7.29-7.40 (1H, m), 7.65-7.73 (1H, m), 7.74-7.80 (1H, m), 7.81-7.90 (1H, m), 8.19-8.32 (1H, m), 8.76-8.92 (1H, m); LC-MS: m/z=+377.5 (M+H)+.
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