Triethylamine → HCID 131730835, compound

Participants

Reaction Steps

To a solution of 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 (0.50 g, 0.89 mmol) (5:1 mix of 5-Br and 5-Cl) in DMF (3 mL) were added sequentially triethylamine (0.50 mL, 3.56 mmol), ethynyltrimethylsilane (0.15 mL, 1.07 mmol), Pd(PPh3)2Cl2 (31.2 mg, 0.045 mmol), and copper (I) iodide (8.5 mg, 0.045 mmol). Upon the addition of CuI all solids dissolved. The reaction mixture was stirred at room temperature for 30 min then heated at 50° C. for 1 h. The reaction mixture was cooled to room temperature, quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (50% to 100% EtOAc/hexanes) to isolate 430 mg (83%) of 542-trimethylsilanyl-ethoxymethyl)-2-trimethylsilanylethynyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a brown foamy solid. NMR showed a trace of unreacted 5-Cl pyrrolopyrazine present.

Provenance & Evidence