4-Cyanophenylboronic acid → HCID 68736154, compound

Participants

Reaction Steps

Dissolve 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (9.19 g, 30.8 mmol) and 4-cyanobenzeneboronic acid (5.18 g, 35.2 mmol) in N,N-dimethylacetamide (90 mL) and water (35 mL), purge with nitrogen for 0.5 hr. and then add tetrakis(triphenylphosphine)palladium(0) (0.170 g, 0.15 mmol). Heat for 3 hr. at 110° C., allow to cool about 1.5 hr. to room temperature, filter and then dry the solid in an oven overnight to give 3′-(4-cyanophenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester as a white solid (9.94 g, 88%). MS (ES): m/z=366 [M+H]+. Add 4 M HCl in 1,4-dioxane (10 mL) to 3′-(4-cyanophenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (3.29 g, 9.0 mmol). Add more 4 M HCl in 1,4-dioxane (10 mL) to the reaction mixture and heat at 40° C. for 3 hr. Filter off the solid and wash with a mixture of 1,4-dioxane/isohexane to give the dihydrochloride salt as a yellow solid (4.2 g). MS (ES): m/z=266 [M+H]+. Dissolve the dihydrochloride in water (20 mL), add 2 N sodium hydroxide (10 mL), extract with DCM and concentrate the DCM extract to give the title preparation as a yellow solid (1.8 g). MS (ES): m/z=266 [M+H]+.

Provenance & Evidence