反应详情

A solution of 1-(4-chloro-butyl)-5-(6-methyl-pyridin-2-yl)-1H-pyrimidine-2,4-dione (Prep51, 95 mg, 0.32 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 74 mg, 0.32 mmol), and TEA (98 μl, 1 mmol) in absolute EtOH (4 mL) was refluxed for 48 h. Then dry DIPEA (83.6 mg, 0.64 mmol) was added and the mixture placed in a microwave oven and irradiated at 125° C. for 4 hours. The solvent was removed under vacuum and the residue was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated. The residue was dissolved in DCM and treated with PS-isocyanate resin (250 mg) under stirring for 2 h. After filtration and evaporation of the solvent, the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) to give the title compound as free base.

1. customthe mixture placed in a microwave oven
2. customirradiated at 125° C. for 4 hours
3. customThe solvent was removed under vacuum
4. customthe residue was partitioned between water and ethyl acetate
5. dry with materialThe organic phase was dried (Na2SO4)
6. filtrationfiltered
7. customevaporated
8. dissolutionThe residue was dissolved in DCM
9. additiontreated with PS-isocyanate resin (250 mg)
10. filtrationAfter filtration and evaporation of the solvent
11. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)