Reaction #41069

Reaction equation

NaOH

3-[5-(2,4-Dimethyl-oxazol-5-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde

(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane

AcOH

NaBH(AcO)3

dichloroethane

→

title compound

5-(2,4-dimethyl-1,3-oxazol-5-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

Conditions

Workup

1. 1
   Extractionthe mixture extracted with EtOAc
2. 2
   workup.ADDITIONThe organic phase was treated with PS isocyanate resin
3. 3
   Filtrationfiltered
4. 4
   Otherevaporated under vacuum
5. 5
   OtherThe crude was purified by flash chromatography (DCM/MeOH/NH4OH 95:5:05)

Procedure

To a solution of 3-[5-(2,4-Dimethyl-oxazol-5-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep64, 74 mg, 0.28 mmol) in dichloroethane (2 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 57.4 mg, 0.25 mmol), AcOH (18.5 mg, 0.28 mmol) and NaBH(AcO)3 (65 mg, 0.31 mmol) were added portionwise at 0° C. The mixture was stirred at 0° C. for further 30 minutes. A 1N solution of NaOH was added and the mixture extracted with EtOAc. The organic phase was treated with PS isocyanate resin, filtered and evaporated under vacuum. The crude was purified by flash chromatography (DCM/MeOH/NH4OH 95:5:05) to give the title compound as free base. The free base was dissolved in dissolved in dioxane and treated with 4N HCl in dioxane (1 eq), to give the title compound as a white powder. (38 mg, 24%)

Source