Tetrahydrofuran → {6-Chloro-3-[7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-acetic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

In a 20 mL pear-shaped 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 (80 mg, 0.14 mmol) was combined with THF (3 ml) to give a light yellow solution. It was cooled to 0° C. and potassium tert-butoxide (19 mg, 0.17 mmol) was added. It was stirred at 0° C. for 30 min and tert-butyl 2-bromoacetate (22 μl, 0.14 mmol) was added dropwise and the reaction was stirred at 0° C. for 1 h. The reaction mixture was diluted with aqueous NH4Cl and water, then extracted with Et2O (2×30 ml). The combined organics were washed with water and brine then dried over MgSO4 and concentrated. The crude residue was purified by SiO2 chromatography (5% to 80% EtOAc/CH2Cl2) to isolate 35 mg (37%) {6-Chloro-3-[7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-acetic acid tert-butyl ester as a foaming solid. MS: (M+H)+=694.

Provenance & Evidence