Hydrochloric Acid → HCID 66787468, compound

To (3S)-3-amino-4-cyclobutyl-N-cyclopropyl-2-hydroxybutanamide (214 mg, 0.83 mmol) was added 4.0 M HCl in dioxane (11.0 mL). After 1 hour, the reaction mixture was concentrated and dried to give (3S)-3-amino-4-cyclobutyl-N-cyclopropyl-2-hydroxy-butanamide HCl salt as a white solid. To this salt was added (2S,4R)-1-((S)-2-(3-tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)-4-(5-chloro-pyridin-2-yloxy)-pyrrolidine-2-carboxylic acid in dichloromethane/N,N-dimethylformamide (1:1, 10.0 mL), 1 (3 dimethylaminopropyl)-3 ethylcarbodiimide hydrochloride (EDCI) (238 mg, 1.24 mmol), 1-hydroxybenzotriazole (HOBT) (190 mg, 1.24 mmol) and N-methylmorpholine (0.6 mL, 3.32 mmol). After 16 hours at room temperature, the reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate, brine, and dried over magnesium sulfate. The ethyl acetate layer was then filtered, concentrated under reduced pressure, and the residue purified by flash chromatography to give tert-butyl (2S)-1-((2S,4R)-4-(5-chloro-pyridin-2-yloxy)-2-((2S)-1-cyclobutyl-4-(cyclopropylamino)-3-hydroxy-4-oxobutan-2-ylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate in 58% yield.

1. concentrationthe reaction mixture was concentrated
2. customdried

ORD record

ord-4108f22d92cd4ab583a5252a818e333b

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08211897B2