Allyl bromide → 2-(1-allyl-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-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (see Example 23, 396 mg, 0.68 mmol) was dissolved in DMF (4.5 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 33 mg, 0.83 mmol) was added. The reaction mixture was stirred at 0° C. for 20 min then allyl bromide (65 μl, 0.75 mmol) was added. The reaction mixture was stirred at 0° C. for 20 min and then at room temperature for 1 h. The reaction mixture was quenched with water and extracted with ethyl acetate (2×). The combined organic layers were washed with water, sat LiCl, and brine then dried over MgSO4 and concentrated. The residue was chromatographed over silica gel with 50% to 100% EtOAc/heptane to afford 388 mg (92%) of 2-(1-allyl-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 yellow foam.

Provenance & Evidence