Acetonitrile → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide

関与物質

反応条件

反応手順

[2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(2-methyl-aziridin-1-yl)-methanone (70 mg, 0.14 mmol) was dissolved in 1:1 THF: acetonitrile (1.5 ml). 3-Cyanopyrrolidine hydrochloride (28 mg, 0.21 mmol) and N,N-diisopropylethylamine (37 ul, 0.21 mmol) were added and the reaction was heated in a microwave reactor at 120° C. for 2 h. An additional 0.5 eq of 3-cyanopyrrolidine hydrochloride and N,N-diisopropylethylamine were added and the heating was repeated twice more. Water and ethyl acetate were then added to the cooled solution. The aqueous layer was extracted twice more with ethyl acetate and the combined organics were washed with sodium chloride solution and dried over sodium sulfate. After evaporation of solvent the crude residue was purified by silica gel chromatography (ethyl acetate/dichloromethane) to give 21 mg (25%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide. (M+H)+=593.

情報源と証拠