Water → 2-(2-chlorothiazol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, 1,4-dioxane (3 mL) was purged with argon gas. 2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (100 mg, 0.173 mmol), 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiazole (128 mg, 0.519 mmol), palladium tetrakis(triphenylphosphine) (10 mg, 0.009 mmol), and then cesium carbonate (113 mg, 0.346 mmol) were added. The reaction vessel was sealed and heated in a microwave reactor at 170° C. for 1 h. Additional 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiazole (90 mg, 0.366 mmol) and palladium tetrakis(triphenylphosphine) (6 mg, 0.005 mmol) were added and the reaction was resubjected at 170° C. for 2 h. The reaction was cooled and water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to yield 39 mg (36%) of 2-(2-chlorothiazol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide. (M+Na)+=638.

Provenance & Evidence