反应详情

温度

150 °C

5-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione (Prep10, 150 mg, 0.282 mmol) copper (1+) iodide (59.1 mg, 0.310 mmol), N,N-dimethylglycine (32.0 mg, 0.310 mmol) and K2CO3 (86 mg, 0.620 mmol) were dissolved in Dimethyl Sulfoxide (DMSO) (2 ml) to give a light blue solution with a white precipitate. To this mixture, 3-(trifluoromethyl)-1,4,5,7-tetrahydropyrano[3,4-c]pyrazole (P38, 179 mg, 0.931 mmol) was added. After 18 h shaking at 150° C., the reaction mixture was diluted with EtOAc (5 ml) and the organic phase was washed with water (4×10 ml), then brine (5 ml), dried over Na2SO4, then filtered and the solvent evaporated. The obtained crude was passed through an SCX cartridge and eluted with 2M solution of ammonia in MeOH. The obtained mixture was iteratively purified (two times) by preparative LC-MS. The obtained fraction was passed through an SCX cartridge and eluted with 2M solution of ammonia. Obtained 8.8 mg of the title compound.

1. customto give a light blue solution with a white precipitate
2. washthe organic phase was washed with water (4×10 ml)
3. dry with materialbrine (5 ml), dried over Na2SO4
4. filtrationfiltered
5. customthe solvent evaporated
6. customThe obtained crude
7. washeluted with 2M solution of ammonia in MeOH
8. customThe obtained mixture was iteratively purified (two times) by preparative LC-MS
9. washeluted with 2M solution of ammonia