Sodium Carbonate → HCID 24986037, compound

Participants

Reaction Conditions

Reaction Steps

4-(2-Oxo-3-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-yl)benzonitrile. 6-Bromo-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one (See Example 108.B) (2.5 g, 7.60 mmol), 4-cyanophenylboronic acid (1.69 g, 11.5 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferocene]palladium (II) dichloromethane (0.62 g, 0.70 mmol) were combined in dioxane (10 mL). Sodium carbonate (0.91 g, 15.2 mmol) in water (10 mL) was added and the reaction stirred at 100° C. overnight. The cooled reaction solution was filtered through Celite and the filter cake was washed with ethyl acetate. Filtrate and ethyl acetate wash were combined and solvent removed under reduced pressure. The resulting material was purified using reverse-phase preparatory HPLC (20-80% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). Fractions containing clean product were passed through a Phenomenex Strata-X-C ion exchange column to remove TFA. The column was washed successively with water, methanol, and then 5% ammonium hydroxide in methanol. The product was released with the 5% ammonium hydroxide in methanol eluent and was concentrated on a rotary evaporator. The residue was triturated with ethyl ether in hexane to give a fine powder and dried under vacuum at 50° C. to give the desired product (1.2 g, 46%) as a white solid. MS (ESI) m/z 350.0 [M+1]+.

Provenance & Evidence