Benzeneacetonitrile, 4-bromo- → 2-[4-[[8-(4-Fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]amino]phenyl]acetonitrile

Participants

Reaction Conditions

Reaction Steps

8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (98 mg, 0.42 mmol), 2-(4-bromophenyl)acetonitrile (83 mg, 0.42 mmol), Cesium carbonate (206 mg, 0.63 mmol), Palladium(II) acetate (9.47 mg, 0.04 mmol) and 2-(Dicyclohexylphosphino)biphenyl (14.79 mg, 0.04 mmol) were added to a 2-5 mL microwave vial. The vial was capped and flushed with nitrogen. dioxane (2 mL) was added and the vial was flushed with additional nitrogen before it was heated by microwave irradiation at 120°C for 1.5h. PALLADIUM(II) ACETATE (10 mg, 0.04 mmol) and 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (14 mg, 0.04 mmol) were added and the mixture was heated for 45+30 min at 120° in a microwave reactor.Water (2 ml) and dichloromethane (10 ml) was added and the mixture was added to a phase separator tube. The organic phase was collected and evaporated. The solvents were evaporated and the residue was purified by column chromatography on silica eluting with gradients of methanol and ammonia in dichloromethane. The solvents were evaporated to give EN04671-48-001 (55 mg, 0.158 mmol, 37.5 %). Ca 88% pure according to LC-UV. The residue was dissolved in MeCN (2 ml) and the solution was passed through a syringe filter. Water was added to give a cloudy mixture (sample-002). Not possible to isolate solid by filtration. The solvents were evaporated to give EN04671-48-002. Not pure. EtOAc (2ml) and DCM (0.5 ml) and two drops of methanol were added. Most solid into solution. The mixture was passed through a syringe filter. The filter was rinsed with EtOAc (1 ml). Heptane was added until a solid started to form. The mixture was left for 1 h (sample -003). The mixture was filtered, everything passed through the filter. The solvents were evaporated and the residue was dissolved in MeCN and purified by preparative HPLC. Fr 1-2 were pooled and evaporated to give EN04671-48-004 (6.7 mg, 0.019 mmol, 4.57 %). Fr 3-6 were pooled and evaporated.

Provenance & Evidence