Example 133
Step 1: tert-butyl (2S)-2-(3-cyano-3-hydroxypropyl)pyrrolidine-1-carboxylate. To a solution of tert-butyl (S)-2-(3-oxopropyl)pyrrolidine-1-carboxylate (114 mg, 0.5 mmol) in DCM (1 mL) was added Et3N (0.1 mL) and acetone cyanohydrin (0.1 mL, 1.2 mmol). The mixture was stirred at r.t. over night. The solution was concentrated by vacuum and purified by silica gel column to afford the title product (120 mg) as colorless oil. MS: [M+1]+ 255.
Step 2: 2-hydroxy-4-((S)-pyrrolidin-2-yl)butanoic acid. To a solution of tert-butyl (2S)-2-(3-cyano-3-hydroxypropyl)pyrrolidine-1-carboxylate (60 mg, 0.23 mmol) in dioxane (0.8 mL) was added HCl (con., 0.8 mL). The mixture was stirred at 100° C. overnight. After cooling to r.t., dioxane was removed by evaporation. The residue was washed by EtOAc (0.5 mL×2). The aqueous phase was collected and evaporated to give a crude product which was used directly in the next step without purification. MS: [M+1]+ 174.
Step 3: 4-((S)-1-(7,8-dichloro-4-(1H-imidazol-1-yl)quinolin-2-yl)pyrrolidin-2-yl)-2-hydroxybutanoic acid (I-817). The title compound was prepared essentially by the same methods as for I-664. MS: [M+1]+ 435.
