Potassium Carbonate → 1-[2,4-dioxo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]-1H-pyrazole-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence