Sodium Iodide → 2-iodo-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

A 5 ml microwave vial was charged with 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 (252 mg, 0.45 mmol), sodium iodide (112 mg, 0.75 mmol) and copper(I) iodide (8 mg, 0.04 mmol). The vial was evacuated, backfilled with argon then toluene (0.4 ml) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.015 ml, 0.095 mmol) were added via syringe. The vial was sealed and the reaction mixture was stirred at 110° C. in an oil bath for 22 h. The reaction was cooled to room temperature and 5-chloro-1H-indazole (57 mg, 0.37 mmol) and potassium phosphate tribasic (167 mg, 0.79 mmol) were added. The vial was again evacuated, backfilled with argon, sealed and stirred at 110° C. in an oil bath for 19 h. The reaction was cooled to room temperature, filtered through Celite and washed with ethyl acetate. The filtrate was concentrated and the residue was purified by chromatography over silica gel with MeOH/CH2Cl2 (0.5% NH4OH) (gradient 0-2.5% MeOH) to give 53 mg (22%) of 2-(5-chloro-indazol-1-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 as a yellow oil and 76 mg (33%) of 2-iodo-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 as a light brown solid.

Provenance & Evidence