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

Participants

Reaction Steps

To a solution of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (269 mg, 1.186 mmol) in acetonitrile (4 mL), Titanuim (IV) isopropoxide (0.434 mL, 1.482 mmol) and a solution of 3-[5-(2,4-dimethyl-1,3-thiazol-5-yl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]propanal (Prep36, 276 mg, 0.988 mmol) in acetonitrile (6 mL) were added and the mixture was stirred at rt for 20 minutes. Afterwards, it was cooled to 0° C. and Sodiumtriacetoxyboronhydride (314 mg, 1.482 mmol) was added. The mixture was stirred at rt for 1.5 h, then quenched with water. Acetonitrile was eliminated under reduced pressure and the aqueous residue was extracted with DCM. Organic phase was washed with NaHCO3 saturated solution, dried and concentrated under vacuum. Crude product was purified by flash chromatography (eluent: DCM/MeOH/NH3 97:3:0.1) affording the title compound (E37, 200 mg, 0.408 mmol) as a white solid.

Provenance & Evidence