2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → HCID 68161647, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (cis)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinamine di-hydrochloride (for a preparation see intermediate 61) (250 mg, 0.700 mmol), sodium tert-butoxide (235 mg, 2.449 mmol), 2-bromo-5-fluoropyridine (123 mg, 0.700 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (DavePhos) (55.0 mg, 0.140 mmol) and tris(dibenzylideneacetone)dipalladium(0) (64.1 mg, 0.070 mmol) was stirred in toluene (12 mL) at 70° C. under nitrogen for 2 h. An extra portion of 2-bromo-5-fluoropyridine (123 mg, 0.700 mmol), sodium tert-butoxyde (81 mg, 0.84 mmol), Davephos (55.0 mg, 0.140 mmol) and tris(dibenzylideneacetone)dipalladium(0) (64.1 mg, 0.070 mmol) was added after having cooled the mixture down. The resulting mixture was stirred at 70° C. under nitrogen for 12 h then was cooled to room temperature and concentrated in vacuo. The residue was suspended in 10% MeOH in DCM (100 mL) and filtered through celite. The insoluble material was rinsed with 10% MeOH in DCM (2×50 mL) and the combined filtrate and washings were concentrated in vacuo. The residue was partitioned between DCM (50 mL) and a saturated NaHCO3 aqueous solution and the layers were separated. The aqueous phase was extracted with DCM (50 mL) and AcOEt (50 mL). The combined organic phases were washed with brine (50 mL), dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient:0 to 5% MeOH in DCM) gave a residue which was further purified by MDAP (modifier: ammonium formate) to give (cis)-1-acetyl-N-(5-fluoro-2-pyridinyl)-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinamine (36.5 mg, 0.096 mmol, 14%) as a colourless solid.

Provenance & Evidence