4-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amine → 4-[1-(2-aminopyrimidin-4-yl)-3-(fluoromethyl)-1H-indazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

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To a solution of 4-[6-bromo-3-(fluoromethyl)-1H-indazol-1-yl]pyrimidin-2-amine (49 mg, 0.12 mmol) in piperidine (2 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (11.5 mg, 0.01 mmol), copper(I) iodide (1.9 mg, 0.01 mmol) and 2-(pyrimidin-2-yl)but-3-yn-2-ol (39 mg, 0.25 mmol). The reaction mixture was warmed to 66° C. for 2 hr. After cooling to RT, the reaction mixture was concentrated in vacuo, DCM (10 mL) was added and the solution re-evaporated to dryness in vacuo (re-evaporation process repeated twice). Purification of the residue by column chromatography (Biotage, DCM containing a 0-10% gradient of methanol) furnished a brown oil which was suspended in acetonitrile and concentrated in vacuo. The residue was re-suspended in acetonitrile (1 mL), whereupon a brown solid precipitated and was collected by filtration to furnish the title compound as a brown solid: 1H NMR (500 MHz, METHANOL-d4) delta 1.99 (3H, s), 5.75 (2H, d, J=47.92 Hz), 7.23 (1H, d, J=5.36 Hz), 7.42 (1H, dd, J=8.28, 1.02 Hz), 7.48 (1H, t, J=4.89 Hz), 7.85 (1H, d, J=8.20 Hz), 8.25 (1H, d, J=4.73 Hz), 8.88 (2H, d, J=4.89 Hz), 9.06 (1H, s); LC-MS: m/z=+390.05 (M+H)+.

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