Reaction Steps
A mixture of (S)-1-{(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[(S)-2-((2R,3R)-3-methoxy-2-methyl-hept-6-enoylamino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (480 mg, 0.72 mmol), (R)-1-(3-vinylphenyl)ethylamine hydrochloride (159 mg, 0.86 mmol) and N,N-diisopropylethylamine (372 mg, 0.5 mL, 2.88 mmol) in acetonitrile (20 mL) was stirred at room temperature under nitrogen. 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (380 mg, 1 mmol) was added and the reaction mixture was stirred at room temperature for 24 hours. Ethyl acetate and water were added. The aqueous layer was separated and extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:1 to neat ethyl acetate to afford the title compound (331 mg, 58%) as a white foam. 1H NMR (300 MHz, CD3CN) δ0.20 (s, 6H), 0.81 (d, J=6.9 Hz, 3H), 0.82 (d, J=6.7 Hz, 3H), 0.99 (m, 9H), 1.03 (d, J=6.9 Hz, 3H), 1.40 (d, J=7.1 Hz, 3H), 1.45-2.20 (m, 7H), 2.50-2.70 (m, 2H), 2.75-2.85 (m, 1H), 2.95-3.15 (m, 2H), 3.30 (s, 3H), 3.30-3.35 (m, 1H), 3.95-4.15 (m, 2H), 4.25-4.35 (m, 1H), 4.93-5.10 (m, 4H), 5.25 (dd, J=10.9, 0.9 Hz, 1H), 5.28 (dd, J=10.9, 0.9 Hz, 1H), 5.49-5.58 (m, 1H), 5.81 (dd, J=17.6, 0.9 Hz, 1H), 5.83 (dd, J=17.6, 0.9 Hz, 1H), 6.54-6.61 (m, 1H), 6.70-6.84 (m, 5H), 7.10 (t, J=7.6 Hz, 1H), 7.24-7.43 (m, 6H). LCMS (m/z) 790 [M+H], Tr=5.91 min.
