Acetic Acid → HCID 25252823, compound

Participants

Reaction Steps

[5-(4,5-dimethyl-1,3-thiazol-2-yl)-2,4-dioxo-3-(phenylcarbonyl)-3,4-dihydro-1(2H)-pyrimidinyl]propanal (Prep18, 0.098 mmol from previous reaction considered quantitative) was dissolved in Acetonitrile (1.500 ml). (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep4, 0.022 g, 0.098 mmol) was added and to the resulting slurry 1,2-Dichloroethane (DCE) (1.5 ml) and Acetic acid (0.011 ml, 0.196 mmol) were added. The resulting clear and dark yellow solution was stirred at rt for 10 minutes then it was cooled to 0° C. and sodium triacetoxyborohydryde (0.023 g, 0.108 mmol) was added in one portion. The mixture was stirred while the temperature slowly rose to rt (ca 5 hrs). The mixture was diluted with EtOAc (20 mL) washed with aqueous saturated NaHCO3 and extracted with EtOAc (2×5 mL). The organics were combined and dried (Na2O4, rotary evaporator) to afford a crude that was purified by silica chromatography, eluting with DCM:MeOH 100:0 to 9:1 to afford a yellow foam that was purified by SCX (5 g) eluting with DCM, MeOH, Ammonia 1M in MeOH (10 mL each) to afford 36 mg of compound that was further purified by Fraction Lynx. Product fraction was dried to afford 5 mg of impure title compound that was filtered through an SCX cartridge (500 mg) eluting with DCM, MeOH, Ammonia 2M in MeOH. Fraction from ammonia was dried to afford the title compound as a white solid (3 mg)

Provenance & Evidence