Lithium bromide salts, extraction

Under our best conditions, tra s-A,A/ -dimethylcyclohexyl-1,2-diamine, Cul, and KOH in aqueous acetonitrile produced up to 87% solution yield of the desired isomer (2), with a 20 1 0.5 ratio of regioisomers with respect to the triazole. The potassium salt was not crystalline, and as such, had excellent solubility in the reaction medium (ca. >40mg/mL). In contrast, the lithium salt and the freebase form of azaindole 2 had <2 mg/mL solubility. Thus, to isolate the lithium salt, after extraction of the reaction mixture with aqueous KOH, we performed a salt metathesis from potassium to lithium by the simple addition of lithium bromide. This resulted in the direct crystallization of the product in excellent yield and quality. Under these conditions, the lithium salt was isolated as a potassium bromide co-crystal. This co-crystal form demonstrated greatly enhanced filtration rates versus the free-base form of 2, due to its improved crystal morphology (Scheme 29). 

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