Hydrochloric Acid → HCID 178483083, compound

Participants

Reaction Steps

To a glass flask were added 18-crown-6 (647 mg, 2.45 mmol), 4-Bromo-1-iodo-2-trifluoromethoxy-benzene (770 mg, 2.10 mmol), cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step C of example 9 (500 mg, 1.75 mmol), sodium tert-butoxide (235 mg, 2.45 mmol), tris(dibenzylideneacetone)dipalladium (160 mg, 0.175 mmol), (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (160 mg, 0.175 mmol) and THF (3.5 mL). The reaction mixture was stirred at reflux 18 hr. The mixture was filtered through a pad of celite, concentrated, and purified by flash chromatography (NH-silica gel, 33% EtOAc in hexane) to give a pale yellow oil. To a solution of above oil in Et2O (2 mL) was added 4 M hydrogen chloride in EtOAc (0.3 mL). The mixture was stirred at ambient temperature for 30 min and concentrated. A solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-[4-(4-bromo-2-trifluoromethoxy-phenylamino)-cyclohexyl]-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (189 mg, 18%) as a white solid.

Provenance & Evidence