反应详情

温度

110 °C

Copper(1+) iodide (50.1 mg, 0.263 mmol), (1R,2R)—N,N′-dimethyl-1,2-cyclohexanediamine methyl[(1R,2R)-2-(methylamino)cyclohexyl]amine (0.166 ml, 1.053 mmol), 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, 133 mg, 0.263 mmol) and K2CO3 (76 mg, 0.553 mmol) were dissolved in Toluene (1 ml) to give a blue suspension with a white precipitate. 1H-pyrazole-3-carbonitrile (commercially available from Tyger, 29.4 mg, 0.316 mmol) was added thereto. After shaking at 110° C. for 18 h, the reaction mixture was filtered and the solvent evaporated. The obtained residue was purified by flash chromatography (eluent: pure EtOAc for 4CV, then from pure EtOAc to EtOAc/MeOH 9:1 in 10 CV, then EtOAc/MeOH 9:1 for 10 CV; 12M column) to obtain 14.5 mg of our target compound that was further purified on a SCX cartridge and eluted with a 2M solution of ammonia in MeOH. The resulting solution was evaporated in vacuo to obtained 10.9 mg of title compound as a white solid.

1. customto give a blue suspension with a white precipitate
2. filtrationthe reaction mixture was filtered
3. customthe solvent evaporated
4. customThe obtained residue was purified by flash chromatography (eluent
5. custom12M column) to obtain 14.5 mg of our target compound that
6. customwas further purified on a SCX cartridge
7. washeluted with a 2M solution of ammonia in MeOH
8. customThe resulting solution was evaporated in vacuo