Dimethylformamide → HCID 46244298, compound

Participants

Reaction Steps

4-(4-Methylpiperazin-1-yl)-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzoic acid hydrochloride (590 mg, 1.31 mmol) in dry DCM (10 mL), under nitrogen, was cooled with an ice bath and treated first with a drop of DMF and then with oxalyl chloride (2.62 mmol, 0.228 mmol). After stirring for 4 hours at room temperature, the solution was evaporated and the solid was dried under vacuum. The crude acid chloride was dissolved in 20 mL of dry pyridine, cooled with an ice bath and treated drop-wise with 5-[(2,5-difluorobenzyl)oxy]-1H-indazol-3-amine (300 mg, 1.09 mmol) in 15 mL of pyridine. The reaction was left overnight at 4° C. Volatiles were evaporated and the residue was diluted with water (300 mL) and extracted with EtOAc (3×300 mL). Organic phases were collected, dried over sodium sulfate and evaporated. Crude product was diluted with MeOH (10 mL) and heated at 80° C. in the presence of triethylamine (2.5 mL). After 3 hours, volatiles were evaporated and the residue was dissolved in DCM (100 mL), washed with NaHCO3 satured solution, water and brine. The organic layer was dried over sodium sulfate, filtered and evaporated under vacuum. Crude product was purified by flash chromatography over silica gel (DCM/MeOH 92:8) affording 470 mg (yield 75%) of title compound

Provenance & Evidence