HCID 71288350, compound → HCID 71288994, compound

Participants

Reaction Conditions

Reaction Steps

To a 20 ml microwave vial was added 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-bromophenyl)-ethyl]-amide (62 mg, 0.10 mmol), copper (I) cyanide (18 mg, 0.20 mmol), and N-methyl-pyrrolidinone (6 ml) (HPLC grade, dried with 4A powdered molecular sieves). The resulting solution was purged with nitrogen then the vial sealed, and heated in an oil bath at 200° C. After 2.5 h the reaction was allowed to cool to room temperature over 17 h. The reaction was separated into two vials and each was independently subjected to heating in a microwave reactor at 200-230° C. for 2.5 h. The reactions were combined, diluted with water (50 ml), and extracted with ethyl acetate (50 ml) two times (5 ml of brine was added to clear phases). The organic layers were washed with brine (25 ml), combined, dried over magnesium sulfate, filtered, and further dried under a stream of nitrogen. The crude brown solid was purified by flash chromatography (4 g silicycle) with 0% to 60% EtOAc in hexanes. The appropriate fractions were combined and dried from a mixture dichloromethane and hexanes yielding 32 mg (56%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-phenyl)-ethyl]-amide as a light yellow solid.

Provenance & Evidence