Formamide → GSK-461364

Participants

Reaction Conditions

Reaction Steps

Formamide (1.08 mL, 26.5 mmol) followed by 25% w/w sodium methoxide in MeOH (1.82 mL, 7.6 mmol) are added to a solution of methyl 5-{6-[(4-methyl-1-piperazinyl)methyl]-1H-benzimidazol-1-yl}-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate (5.0 g, 8.95 mmol) in THF (50 mL) and toluene (10 mL) at room temperature. The reaction mixture is heated at ca 65° C. for about 18 h and then cooled to ca 30° C. The reaction mixture is diluted with EtOAc (25 mL) and H2O (25 mL) and then the biphasic mixture is separated. The organic phase is washed sequentially with H2O (25 ml), saturated aqueous Na2CO3 and finally H2O (2×25 mL). The organic phase is then concentrated by rotary evaporation and the concentrate diluted with EtOAc (30 mL) and then heated at ca 70° C. for about 1 h. The resulting suspension is then cooled to about 20° C. and stirred at this temperature for ca 18 h. The suspension is then stirred at 0-5° C. for 2 h and the product, isolated by filtration, washed with EtOAc (5 mL) and dried under vacuum at ca 25° C. to constant weight (2.93 g, 60.2%).

Provenance & Evidence