2-(Pyrimidin-2-yl)but-3-yn-2-ol → 1-(2-amino-6-chloropyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]-1H-indazole-3-carboxylic acid

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of 1-(2-amino-6-chloropyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (750 mg, 1.81 mmol) in 1:1 triethylamine/dry THF (12 mL) was introduced bis(triphenylphosphine)palladium(II) chloride (127 mg, 0.18 mmol), copper(I) iodide (34 mg, 0.18 mmol) and 2-(pyrimidin-2-yl)but-3-yn-2-ol (535 mg, 3.61 mmol). The reaction mixture was warmed to 55° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo to furnish the crude title compound: 1H NMR (500 MHz, DMSO) delta 1.92 (3H, s), 6.26 (1H, s), 7.09 (1H, s), 7.39 (1H, d, J=8.2 Hz), 7.51 (1H, t, J=4.9 Hz), 8.23 (1H, d, J=8.6 Hz), 8.82 (1H, s), 8.90 (2H, d, J=4.9 Hz); LC-MS: m/z=+436.05/437.70 (M+H)+. This compound, with LC-MS purity=91% UV, was used in the next step without further purification.

Herkunft & Nachweise