Ammonium Chloride → 5-methyl-1-(5-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo-[3.1.0]hex-3-yl}pentyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

Participants

Reaction Conditions

Reaction Steps

A mixture of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (41 mg), 1-(4-chloropentyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (Prep11, 50 mg) and TEA (50 μl) in DMF (0.5 mL) was heated at 100° C. overnight. Ammonium chloride was then added and the solution was extracted with dichloromethane. The organic phase was dried and concentrated in vacuo. The crude product was purified by a SCX cartridge followed by a preparative HPLC [column: ABZ plus 20×100 mm, 5 uM, mobile phase A: H2O+0.1% formic acid, mobile phase B: acetonitrile+0.1% formic acid, gradient: from 1 to 20% (B) in 10 min, flow rate: 20 mL/min, UV wavelength range: 210-350 nm, ionization: ES+, mass range: 100-900 amu (ES+)], to give 29 mg of the title compound which was further purified by flash chromatography eluting with DCM/MeOH/NH4OH from 99/1/0.1, to 98/2/0.1, to 97/3/0.1 to give the free base of the title compound (25 mg).

Provenance & Evidence