1-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid → 1-(2-aminopyrimidin-4-yl)-6-[(3R)-3-hydroxy-3-(5-methyl-1,2,4-oxadiazol-3-yl)but-1-yn-1-yl]-1H-indazole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-aminopyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (150 mg, 0.39 mmol) in piperidine (1.5 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (45.5 mg, 0.04 mmol), copper(I) iodide (7.4 mg, 0.04 mmol) and (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (120 mg, 0.79 mmol). The reaction was warmed to 35° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo and the residue purified by silica gel flash column chromatography (eluent: DCM containing a 1-15% MeOH gradient followed by 85:15 DCM:7M ammonia in methanol). The partially purified product was suspended in 2M aqueous citric acid (3 mL) and extracted with 3:1 chloroform/isopropanol (5×5 mL). The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo to furnish the title compound as a yellow-brown solid: 1H NMR (500 MHz, DMSO) delta 1.91 (3H, s), 2.64 (3H, s), 6.81 (1H, s), 7.27 (1H, d, J=5.9 Hz), 7.54 (1H, dd, J=8.4, 1.2 Hz), 7.80 (2H, s), 8.22 (1H, d, J=8.3 Hz), 8.42 (1H, d, J=6.0 Hz), 8.97 (1H, s), 13.92 (1H, s); LC-MS: m/z=+406.00 (M+H)+.

Provenance & Evidence