Acetic Acid → 8-Chloro-5-methyl-1-(3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-4-yl)-5,6-dihydro-4h-2,3,5,10b-tetraaza-benzo[e]azulene trihydrochloride

Participants

Reaction Steps

Acetic acid (3 ml, 52 mmol) was added to a solution of the amine of example 4b (10 g, 26 mmol) in dichloromethane (100 ml) followed by formaldehyde (37% w/v aqueous, 3.2 ml, 39 mmol). In a separate vessel sodium triacetoxyborohydride (6.7 g, 31 mmol) was slurried in dichloromethane and cooled to <10° C. The imine solution was then added dropwise to the cold slurry over 15 minutes. The reaction mixture was stirred at room temperature for 0.5 hours, after which time the reaction mixture was partitioned between 2N aqueous sodium hydroxide solution and dichloromethane. The organic phase was then washed three times with a 50% aqueous solution of sodium metabisulfite, followed by a final water wash. The dichloromethane solution was distilled to half volume before adding EtOAc and further distilled to remove the remaining dichloromethane. EtOH was added and the reaction mixture heated for a further 0.5 hours, before cooling to 10° C. and isolating the product as a white solid. The solid was dried under vacuum at 50° C. for 16 hours to afford the title compound (7.48 g).

Provenance & Evidence