HCID 68181646, compound → HCID 68181829, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-amino-5-chloropyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (400 mg, 0.96 mmol) in piperidine (4 mL) was introduced tetrakis(triphenylphosphine)palladium (0) (111 mg, 0.10 mmol), copper(I) iodide (18.3 mg, 0.10 mmol) and (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (292 mg, 1.92 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 compound was dissolved in DCM (20 mL) and washed with 2M aqueous citric acid (10 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to furnish the title compound as a dark oil: 1H NMR (500 MHz, DMSO) delta 1.86 (3H, s), 2.62 (3H, s), 6.80 (1H, s), 7.53-7.35 (3H, m), 8.09 (1H, s), 8.23 (1H, d, J=8.4 Hz), 8.56 (1H, s); LC-MS: m/z=+439.90 (M+H)+. This compound, with LC-MS purity=65% UV, was used in the next step without further purification.

Provenance & Evidence