Reaction Steps
A solution of (S)-1-{(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (658 mg, 1.086 mmol) 2f, prepared as described earlier, (R)-6-vinyl-indan-1-ol (208.7 mg, 1.303 mmol) and 4-dimethylaminopyridine (132.7 mg, 1.086 mmol) in anhydrous dichloromethane (20 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (340.6 mg, 1.738 mmol). After overnight stirring at room temperature the volatiles were removed in vacuo and the residue was purified by silica gel chromatography using a 50 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1 to afford the title compound (762 mg, 95%) as a white solid. 1H NMR (300 MHz, CDCl3) δ0.13-0.22 (m, 6H), 0.86-0.99 (m, 15H), 1.47 (s, 10H), 1.72-1.91 (m, 3H), 1.99-2.20 (m, 2H), 2.43-2.60 (m, 2H), 2.66-2.78 (m, 1H), 2.81-3.01 (m, 3H), 3.04-3.17 (m, 1H), 3.91-4.01 (m, 1H), 4.33 (br d, J=12.7 Hz, 1H), 5.03-5.11 (m, 1H), 5.22-5.33 (m, 1H), 5.70-5.82 (m, 2H), 6.21 (dd, J=3.6, 6.9 Hz, 1H), 6.49 (d, J=8.5 Hz, 1H), 6.57-6.65 (m, 2H), 6.68-6.74 (m, 1H), 6.75-6.85 (m, 2H), 6.92 (app t, J=7.6 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.48 (s, 1H). LCMS (m/z) 771.4 [M+Na], Tr=6.05 min.
