7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine → 4-hydroxy-3,3-dimethyl-4-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-butyronitrile

Participants

Reaction Conditions

Reaction Steps

Propyl magnesium chloride lithium chloride (1.3 M solution in THF, 1.7 mL, 2.2 mmol) was added to 3 mL of tetrahydrofuran cooled to −78° C. A solution of 7-iodo-5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine (0.250 g, 0.440 mmol) in 2 mL of tetrahydrofuran was slowly added, and the mixture was stirred at −78° C. for 2 h. A solution of 3,3-dimethyl-4-oxo-butyronitrile (0.241 g, 2.17 mmol) in 2 mL of tetrahydrofuran was added dropwise, and the mixture was stirred, allowing to slowly warm to RT, for 19 h, then quenched with 100 mL of a sat. aq. NaHCO3 solution. The resulting mixture was extracted with 100 mL of ethyl acetate, and the organic layer was dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0→50% EtOAc/hexanes) afforded 0.152 g (62%) of 4-hydroxy-3,3-dimethyl-4-[5-triisopropylsilanyl-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-butyronitrile as a yellow oil.

Provenance & Evidence