1-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid → 1-(2-Aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a pressure tube containing 1-(2-aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid (550 mg, 1.44 mmol), copper(I) iodide (27.48 mg, 0.14 mmol), bis(triphenylphosphine)palladium(II) chloride (101.29 mg, 0.14 mmol) in triethylamine (4 mL) and THF (4 mL), was added 2-(pyrimidin-2-yl)but-3-yn-2-ol (427.62 mg, 2.89 mmol). The reaction was sealed and stirred at 55° C. for 1 hr. The reaction mixture was concentrated in vacuo and the crude product was purified by column chromatography (Biotage, 5-10% methanol in DCM followed by 10-20% [7M NH3 in methanol] in DCM) to give the title intermediate as an orange/brown oil: 1H NMR (250 MHz, DMSO) delta 1.92 (3H, s), 6.27 (1H, s), 6.98 (3H, s), 7.09 (1H, d, J=5.5 Hz), 7.26 (1H, d, J=9.5 Hz), 7.50 (1H, t, J=4.9 Hz), 8.20-8.41 (3H, m), 8.73-9.02 (2H, m); LC-MS: m/z=+402.00 (M+H)+.

Provenance & Evidence