Water → (R)-methyl 1-(3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoyl)pyrrolidine-2-carboxylate

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Reaction Steps

H2O (0.0177 g, 0.131 mmol, 1.1 eq) was added to a stirred solution of 3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoic acid (0.055 g, 0.119 mmol, 1 eq) in 2 ml anhydrous CH2Cl2 at 0° C. under Ar. After 30 min EDCI.HCl (0.0197 g, 0.119 mmol, 1.1 eq) was added. After 30 min 1 ml anhydrous DMF was added. In a separate flask (R)-methylpyrrolidine-2-carboxylate hydrochloride (Bachem, 0.0197 g, 0.119 mmol, 1 eq) in 2 ml anhydrous CH2Cl2 under Ar was treated with DIPEA (0.083 ml, 0.062 g, 0.476 mmol, 4 eq). After both solutions had stirred for 1 h, the active ester was treated with the free-base amine. The reaction was stirred at 0° C. to room temperature overnight. The solvent was removed in vacuo. The residue was partitioned between EtOAc/H2O and the layers were separated. The organic layer was washed with water (×3), brine (×1), and dried over Na2SO4. The inorganics were filtered off, and the solvent removed in vacuo. Purification via flash chromatography yielded 0.0208 g (0.036 mmol, 31% yield) of (R)-methyl 1-(3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoyl)pyrrolidine-2-carboxylate, which was treated under hydrolysis conditions as described herein to generate (R)-1-(3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoyl)pyrrolidine-2-carboxylic acid.

Provenance & Evidence