[Br:1][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.C([N-]C(C)C)(C)C.[Li+].[F:27][CH:28]([F:32])[C:29](=[O:31])[CH3:30]>C1COCC1>[NH2:17][C:13]1[N:12]=[C:11]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)[C:6]([CH2:18][C:29]([CH3:30])([OH:31])[CH:28]([F:32])[F:27])=[N:7]2)[CH:16]=[CH:15][N:14]=1To a solution of 4-(6-bromo-3-methyl-1H-indazol-1-yl)pyrimidin-2-amine (500 mg, 1.64 mmol) in dry THF (5 mL) at −78° C. under an atmosphere of nitrogen, was introduced lithium diisopropylamide (2.1 mL of a 2M solution in THF, 4.11 mmol). After 5 minutes, a solution of 1,1-difluoropropan-2-one (0.4 mL, 4.93 mmol) in dry THF (2 mL) was added. The reaction mixture was warmed to RT after 20 minutes at −78° C. After 30 minutes at RT, the reaction mixture was quenched (5 mL of sat. aq. ammonium chloride) and concentrated in vacuo. The residue was diluted with DCM (10 mL), washed with water (2 mL) and the organic extract dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash chromatography (Biotage, elution with DCM containing a 1-12% gradient of MeOH) furnished the title compound as a yellow solid: 1H NMR (500 MHz, CDCl3) delta 1.36 (3H, s), 3.19 (1H, d, J=15.1 Hz), 3.34 (1H, d, J=14.9 Hz), 3.40 (1H, s), 5.17 (2H, s), 5.67 (1H, t, J=56.3 Hz), 7.24 (1H, d, J=8.5, 1.5 Hz), 7.45 (1H, dd, J=8.5, 1.5 Hz), 7.61 (1H, d, J=8.5 Hz), 8.32 (1H, d, J=5.6 Hz), 9.00 (1H, d, J=1.4 Hz); LC-MS: m/z=+397.90/399.90 (M+H)+.
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