Potassium Carbonate → 5-(5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide

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To a CEM microwave tube containing the crude (5-{[(2-ethylbutyl)amino]methyl}-2-thienyl)boronic acid (48 mg, 0.199 mmol) was added a solution of 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (65 mg, 0.157 mmol) in dioxane (1.75 mL), a solution of K2CO3 (130 mg, 0.942 mmol) in H2O (0.25 mL), and tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.0079 mmol). The reaction was heated in a CEM microwave for 30 min at 150° C. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH), eluting in sequence with MeOH (3 mL) and a 2 M solution of NH3/MeOH (9 mL). The NH3/MeOH fraction was dried under a stream of nitrogen at 50° C., and the crude product was taken up in dimethyl sulfoxide (1.1 mL) and purified on an Agilent MDAP (Zorbax Eclipse XDB-C18 column: 21.2×100 mm) eluting at 20 mL per min for 1 min with 10% CH3CN/H2O (0.1% TFA) then a linear gradient of 10% CH3CN/H2O (0.1% TFA) to 95% CH3CN/H2O (0.1% TFA) over 8 min and holding at the final concentration for 30 sec. The fractions containing product were filtered through a 2 g Pharmasil CHQAX column (polymer bound ammonium hydroxide; United Chemical Technologies) to remove TFA and concentrated under a stream of nitrogen at 50° C. to give impure title compound. The impure title compound was repurified on an Agilent MDAP and free based with the ammonium hydroxide column as shown above to give 8.5 mg of the title compound (10%).

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