Compound 68
N-allyl-N-(((2R,3S,4S)-1-allyl-3-(4-bromophenyl)-4-((trityloxy)methyl)azetidin-2-yl)methyl)-1-methyl-1H-imidazole-2-sulfonamide
From: Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme
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Compound data: 1H NMR
Compound data: 13C NMR
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
A solution of sulfonamide intermediate 67 (3.18 g, 4.56 mmol) dissolved in 100 mL of dry DMF, was treated with K2CO3 (3.2 g, 23 mmol, 5 equiv.) followed by allyl bromide (1.5 mL, 18.2 mmol, 4 equiv.), and stirred overnight at 25 °C. The solution was evaporated to a residue under vacuum, and dissolved in 200 mL EtOAc. The organic layer was washed 5 times with saturated NaCl solution (50 mL), dried over Na2SO4, and evaporated to a residue under vacuum. Purification by column chromatography (20 → 70% EtOAc/hexanes) and evaporation of the collected fractions gave 2.89 g of the title compound 68 (86%, 3.92 mmol), a white amorphous solid. High resolution mass, calculated for C40H41BrN4O3S [M+H]+ = 737.2156, found 737.2142, Δ = -1.9 ppm. 1H NMR (400 MHz, CDCl3) δ 7.53 – 7.43 (m, 8H), 7.36 – 7.29 (m, 6H), 7.29 – 7.21 (m, 5H), 7.06 (d, J = 1.0 Hz, 1H), 6.91 (s, 1H), 5.88 (ddt, J = 16.9, 10.1, 6.7 Hz, 1H), 5.75 (ddt, J = 16.8, 10.1, 6.5 Hz, 1H), 5.24 (dd, J = 17.1, 1.8 Hz, 1H), 5.16 (dd, J = 13.6, 1.6 Hz, 1H), 5.11 (td, J = 9.0, 1.5 Hz, 2H), 4.14 (td, J = 19.8, 16.0, 7.0 Hz, 2H), 3.88 (s, 3H), 3.63 (d, J = 3.7 Hz, 2H), 3.43 (d, J = 4.6 Hz, 3H), 3.40 (d, J = 6.5 Hz, 1H), 3.36 – 3.25 (m, 3H), 3.23 (dd, J = 8.6, 4.2 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 144.14 (3C), 143.51, 139.88, 135.16, 133.41, 131.35 (2C), 129.77 (2C), 128.78 (6C), 128.16, 127.80 (6C), 126.98 (3C), 124.50, 120.28, 118.82, 118.08, 86.61, 69.06, 68.48, 66.86, 61.05, 53.44, 52.57, 43.50, 34.83.
