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 2,2,2-trichloro-ethyl ester (987 mg, 1.337 mmol) in tetrahydrofuran (20 mL) was treated with sodium bicarbonate (337 mg, 4.011 mmol) and 3-Iodo-benzylamine (467 mg, 2.005 mmol). After overnight stirring, ethyl acetate and silica were added and the volatiles removed in vacuo. The product was purified by silica gel chromatography using iso-hexanes/ethyl acetate, 1:0 then 1:2 to afford the title compound (374 mg, 34%) as a white solid. 1H NMR (300 MHz, CDCl3) δ0.17 (s, 3H), 0.18 (s 3H), 0.81 (d, J=6.9 Hz, 3H), 0.86 (d, J=7.1 Hz, 3H), 0.97 (s, 9H), 1.46 (s, 9H), 1.61-1.70 (m, 2H), 1.73-1.83 (m, 1H), 1.84-1.94 (m, 1H), 1.96-2.05 (m, 1H), 2.53-2.66 (m, 1H), 2.81-3.01 (m, 3H), 3.34-3.45 (m, 1H), 3.74 (t, J=6.0 Hz, 1H), 3.98-4.09 (m, 1H), 4.31-4.51 (m, 2H), 4.79-4.88 (m, 1H), 5.75 (q, J=8.7 Hz, 1H), 6.38-6.49 (m, 1H), 6.67-6.73 (m, 1H), 6.74-6.78 (m, 1H), 6.84 (d, J=7.6 Hz, 1H), 7.03-7.15 (m, 2H), 7.31 (s, 1H), 7.33-7.43 (m, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.67 (s, 1H).
