Potassium Carbonate → 5-(3-methyl-1H-pyrazol-1-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

Participants

Reaction Conditions

Reaction Steps

Copper iodide (56.5 mg, 0.297 mmol), (1R,2R)—N,N′-dimethyl-1,2-cyclohexanediamine methyl[(1R,2R)-2-(methylamino)cyclohexyl]amine (169 mg, 1.187 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, 150 mg, 0.297 mmol) and K2CO3 (86 mg, 0.623 mmol) were dissolved in Toluene (1.5 ml) to give a blue suspension with a white precipitate. 3-methyl-1H-pyrazole (commercially available from ABCR, 0.029 ml, 0.356 mmol) was added thereto. After shaking at 110° C. for 18 h, the reaction mixture was filtered and the solvent evaporated. The obtained crude was dissolved in 20 mL of DCM and 500 mg of PS-thiol resin and 2.0 g of MP-isocyanate resin were added to blue solution. The obtained suspension was shaken for 2 h at 35° C., then filtered and the solvent evaporated. The resulting mixture was iteratively purified (two times) by preparative LC-MS. Obtained 51.8 mg of the title compound.

Provenance & Evidence