2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]amide → 2-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-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-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (190 mg, 0.37 mmol) and 6-chloro-3-tributylstannyl-1H-indazole (crude form step 1, 619 mg, 0.70 mmol) were dissolved in DMF (3.4 ml). The flask was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium(0) (22 mg, 0.019 mmol) and copper(I) iodide (15 mg, 0.079 mmol) were added. The reaction mixture was stirred at 90° C. in an oil bath for 3 h then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then concentrated. The residue was absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH) then triturated with diethyl ether/ethyl acetate to afford 159 mg (73%) of 2-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a light brown powder.

Provenance & Evidence