Sodium hydride → (S)-tert-butyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyrazin-2-yl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

A 60% dispersion of NaH (75 mg, 1.9 mmol) was added to a stirred solution of (S)-tert-butyl 2-(6-bromo-1H-imidazo[4,5-b]pyrazin-2-yl)pyrrolidine-1-carboxylate (627 mg, 1.70 mmol) in DMF (15 mL) and the reaction was stirred for 1.5 h at room temperature. Then SEM-Cl (0.30 mL, 1.7 mmol) was added and the reaction was stirred overnight. The reaction was diluted with water (˜30 mL) and EtOAc (˜35 mL), the layers were separated and the organic layer was washed with brine (30 mL), dried (MgSO4), filtered and concentrated. The crude yellow oil was purified by flash chromatography (40 g SiO2, 20-30% EtOAc/hexanes) to yield (S)-tert-butyl 2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyrazin-2-yl)pyrrolidine-1-carboxylate (421 mg) as a clear colorless oil and (S)-tert-butyl 2-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyrazin-2-yl)pyrrolidine-1-carboxylate (345 mg) as a clear colorless oil. The absolute regiochemistry of the SEM group was not established unambiguously, the names (and structures) may be exchanged in these intermediates.

Provenance & Evidence