Cesium carbonate → 3-[3-(3-{4-[4-(4'-Chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 3-{3-[3-(4-bromo-benzyl)-2-imino-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid ethyl ester, hydrobromide salt (0.2 g, 0.34 mmol) in anhydrous toluene (3 ml) was added Pd(OAc)2 (33 mg, 0.077 mmol). Nitrogen was bubbled through the suspension for 10 min before BINAP (49 mg, 0.079 mmol) was added. After a further 2 min 1-(4′-chloro-biphenyl-2-ylmethyl)-piperazine (112 mg, 0.39 mmol) in degassed toluene (3 ml) was introduced and then after an additional 2 min Cs2CO3 (2.5 g, 7.69 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 5 h. After this time, the reaction was cooled to rt and filtered through Celite®. The collected solids were washed with additional dichloromethane and then the combined filtrate and washings were concentrated under reduced pressure to give the crude product. Purification by chromatography on silica eluting with 5% MeOH/dichloromethane provided 3-[3-(3-{4-[4-(4′-chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzyl}-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid ethyl ester (147 mg, 61%). HPLC-MS 715 [M+1]+, 358.

Provenance & Evidence