Hydrochloric Acid → methyl (S)-1-((S)-2-(5-(4-bromo-3-(difluoromethoxy)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

Participants

Reaction Steps

(S)-tert-Butyl 2-(5-(4-bromo-3-(difluoromethoxy)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (400 mg, 0.873 mmol) was dissolved in DCM (10 mL) and treated with HCl (4.0 M in dioxane, 2 mL). The reaction mixture was stirred at RT for 50 min, then concentrated under reduced pressure. The crude residue was treated with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (168 mg, 0.960 mmol), HATU (365 mg, 0.960 mmol) and DMF (4 mL) then cooled to 0° C. DIPEA (0.760 mL, 4.37 mmol) was added dropwise and the reaction mixture was stirred for 30 min. After warming to RT, the mixture was diluted with EtOAc and the organic solution was washed with saturated aqueous NaHCO3, and brine then dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc) to afford methyl (S)-1-((S)-2-(5-(4-bromo-3-(difluoromethoxy)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (333 mg, 74%).

Provenance & Evidence