Sodium hydride → 2-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-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, 120 mg, 0.21 mmol) was dissolved in DMF (1.3 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 12 mg, 0.31 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min then a solution of methanesulfonic acid 2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (131 mg, 0.62 mmol) in DMF (0.5 ml) was added. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature for 48 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 to give 2-[6-chloro-1-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-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 viscous oil which was used without further purification.

Provenance & Evidence