Acetic Acid → 5-(6-methyl-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-[5-(6-Methyl-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep59, 90 mg, 0.35 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 71 mg, 0.31 mmol) and AcOH (21 mg, 0.35 mmol) in dichloroethane (2 mL), NaBH(AcO)3 (77 mg, 0.36 mmol) was added portionwise at 0° C. The mixture was stirred at 0° C. for further 45 minutes, then a 1N solution of NaOH was added and the mixture extracted with EtOAc. The organic phase was dried and evaporated, the residue redissolved in DCM and treated with PS-isocyanate resin (400 mg) under stirring for 4 h. After filtration, the solvent was evaporated under vacuum, and the crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-0.5) to give the title compound (65 mg, 40% yield) as free base.

Provenance & Evidence