反应详情

A solution of 1-(4-chloro-butyl)-5-(2,4-dimethyl-oxazol-5-yl)-1H-pyrimidine-2,4-dione (Prep65, 100 mg, 0.34 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 68 mg, 0.3 mmol), and DIPEA (130 mg, 1 mmol) in absolute EtOH (3 ml) was placed in a microwave oven and irradiated at 130° C. for 3 hours. The solvent was removed under vacuum and the residue was partitioned between water and ethyl acetate. The organic phase was evaporated, the crude dissolved in dichloromethane and treated with PS-isocyanate resin (400 mg) under stirring for 3 h. After filtration, the solvent was evaporated and the crude purified by preparative LC-MS. The residue was loaded over a SCX cartridge eluting with MeOH and the product obtained was treated with 4N HCl in dioxane (1 eq), to give the title compound as a white powder. (43 mg, 24% yield).

1. customirradiated at 130° C. for 3 hours
2. customThe solvent was removed under vacuum
3. customthe residue was partitioned between water and ethyl acetate
4. customThe organic phase was evaporated
5. dissolutionthe crude dissolved in dichloromethane
6. additiontreated with PS-isocyanate resin (400 mg)
7. filtrationAfter filtration
8. customthe solvent was evaporated
9. customthe crude purified by preparative LC-MS
10. washeluting with MeOH
11. customthe product obtained