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

Temperatur

0 °C

A solution of 3-(2,4-dioxo-5-pyrazin-2-yl-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde (Prep127, 0.38 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 86 mg, 0.38 mmol), and AcOH (26 μl) in dichloroethane-MeOH (10-0.5, 4 ml) was cooled to 0° C. NaBH(AcO)3 (84 mg, 0.40 mmol) was added portionwise. The mixture was stirred at 0° C. for further one hour and then basified with 1N NaOH. The product was extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred overnight in the presence of PS-isocyanate. The mixture was filtered and the solvent evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98-2-0.2) to give 78 mg of the title compound (45% yield).

1. extractionThe product was extracted with DCM
2. dry with materialThe organic phase was dried (Na2SO4)
3. customevaporated
4. dissolutionThe residue was redissolved in DCM
5. stirringstirred overnight in the presence of PS-isocyanate
6. filtrationThe mixture was filtered
7. customthe solvent evaporated
8. customThe crude was purified by flash chromatography
9. washeluting with DCM-MeOH—NH4OH (98-2-0.2)

ORD-Eintrag

ord-149b00dae9604dfbb56229b89e70d7dc

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07727988B2