4-(tert-Butyl)-2-(tributylstannyl)pyridine → 2-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Participants

Reaction Conditions

Reaction Steps

In a round-bottomed flask 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (95 mg, 0.17 mmol) and 4-tert-butyl-2-(tributylstannyl)pyridine (141 mg, 0.20 mmol) were dissolved in DMF (1.6 mL). The reaction mixture was evacuated and backfilled with Argon. Tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.009 mmol) and copper (I) iodide (7 mg, 0.037 mmol) were added. The reaction mixture was stirred at 90° C. overnight. The reaction mixture was cooled to room temperature, quenched with 5 mL water and extracted with 50 mL diethyl ether (2×). The combined organic layers were washed twice with 5 mL water and once with 5 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 24 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH). All fractions containing product were combined and concentrated to provide 68 mg (59%) of 2-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

Provenance & Evidence