Cesium carbonate → 1-(4-{4-[2-(4-Chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 1-(4-bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (60 mg, 0.13 mmol) in anhydrous toluene (2 ml) was added Pd(OAc)2 (0.3 mg, 0.7 □mol). Nitrogen was bubbled through the suspension for 10 min before BINAP (8 mg, 11 □mol) was added. After a further 2 min 1-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine (48 mg, 0.14 mmol) in degassed toluene (2 ml) was introduced and then after a additional 2 min Cs2CO3 (0.86 g, 2.6 mmol) was added and the reaction was stirred for 2 min. Throughout all of the additions nitrogen was continuously bubbled through the reaction mixture. The reaction was then sealed and heated to 95° C. where it was maintained for 2 h. After this time, the reaction was cooled to rt and additional Pd(OAc)2 and BINAP were introduced. The reaction was then sealed and heated to 95° C. where it was maintained for a further 22 h. The mixture was cooled to rt and filtered through Celite®. The collected solids were washed with additional toluene and dichloromethane and then the combined filtrate and washings were concentrated under reduced pressure to give the crude product. After purification by preparative HPLC, the product was redissolved in dichloromethane and washed with saturated NaHCO3 and H2O. The organic phase was separated, dried (Na2SO4) and filtered to provide 1-(4-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (10 mg, 11%). HPLC-MS 692 [M+1]+, 347 (100%).

Provenance & Evidence