Cesium carbonate → (1-{4-[6-(4-methyl-piperazin-1-yl)-4-oxo-2-phenyl-4H-chromen-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

{1-[4-(6-Bromo-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (55 mg, 0.1 mmol), 1-methylpiperazine (13 μL, 0.12 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol), (S)-BINAP (9 mg, 0.015 mmol) and cesium carbonate (46 mg, 0.14 mmol) were suspended in toluene (1.0 mL) in a microwave vial. The vial was sealed, evacuated and flushed twice with nitrogen. The mixture was heated in a microwave at 150° C. for 30 min. Further tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol) and (S)-BINAP (9 mg, 0.015 mmol) were added to the vial and the mixture heated conventionally at 110° C. for 24 hours. The mixture was cooled to RT, dissolved in methanol and loaded onto an SCX-2 cartridge. The cartridge was washed repeatedly with methanol before eluting with 2M ammonia in methanol solution. The eluent was collected and concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2, gradient 3%-4% 2M ammonia in methanol/DCM) to afford the title compound as a yellow oil (15 mg, 27%). LCMS (Method B): RT=3.74 min, M+H+=566.

Provenance & Evidence