Potassium Carbonate → 1-[2-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-thiazol-4-ylmethyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-chloro-thiazol-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (30 mg, 0.072 mmol) in N-methylpyrrolidinone (2 ml) was added 1-biphenyl-2-ylmethyl-piperazine (18 mg, 0.072 mmol), CuI (14 mg, 0.072 mmol) and K2CO3 (15 mg, 0.11 mmol). The reaction was heated in a microwave at 190° C. for a total of 1.5 h. After this time, the suspension was cooled to rt and filtered through Celite®. The collected solids were washed with dichloromethane and then the combined filtrate and washings were washed with H2O. The aqueous phase was extracted with additional dichloromethane and the combined organic fractions were then washed with brine, dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified by preparative HPLC. The product was free-based by partitioning between a saturated solution of NaHCO3 and dichloromethane. The organic layer was then separated, dried (Na2SO4), filtered and concentrated under reduced pressure to give 1-[2-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-thiazol-4-ylmethyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (3.6 mg, 8%). HPLC-MS 633 [M+1]+, 317 (100%).

Provenance & Evidence