Reaction Steps
(1R,2S,5S)-3-((S)-3,3-dimethyl-2-(3-(trifluoromethyl)phenylamino)butanoyl)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid (0.043 g, 0.10 mmol), 3-(chloroamino)-4-cyclobutyl-2-oxobutanamide (0.031 g, 0.14 mmol), 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDCI, 0.030 g, 0.16 mmol), 1-hydroxybenzotriazole hydrate (HOBt-H2O, 0.005 g, 0.03 mmol) in MeCN (3 mL) was added N-Methylmorpholine (d=0.920) (0.015 ml, 0.14 mmol) in MeCN (1 mL) dropwise over 40 minutes. The mixture was stirred at rt for 2 hrs and saturated KHSO4 (3 mL) was added, extracted with EtOAc (2×10 mL). The combined EtOAc extracts was washed with brine (10 mL), dried over sodium sulfate. After removal of solvent, the residue was purified by chromatography (Hexane:Ethyl acetate=1:1) to give the (1R,2S,5S)—N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-((S)-3,3-dimethyl-2-(3-trifluoromethyl)phenylamino)butanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide (0.017 g, 29%) as white solid. MS: Calcd.: 564; Found: [M+H]+ 565. 1H NMR (400 MHz, d6-DMSO) δ 8.23 (m, 1H), 7.96 & 7.89 (s, 1H), 7.71 & 7.67 (s, 1H), 7.17 (m, 1H), 7.06 (s, 1H), 6.92 (m, 1H), 6.76 (m, 1H), 5.67 (d, J=10.8 Hz, 1H), 4.93 & 4.75 (m, 1H), 4.17 (s, 1H), 3.99 (m, 1H), 3.82 (m, 1H), 3.68 (m, 1H), 2.29 (m, 1H), 1.91 (m, 2H), 1.70 (m, 3H), 1.58 (m, 2H), 1.43 (m, 1H), 1.20 (m, 1H), 0.92-1.00 (m, 14H), 0.61 (s, 1H), 0.57 (s, 1H).
