Compound 67
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
Compound data: COSY
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
A mixture of 3 g of intermediate 64 (5.46 mmol, source B) was treated with DIBAL (27.5 mmol), followed by the the workup up procedure by Fieser & Fieser (Wiley, New York, 1967), as described above. The resulting amine intermediate was dissolved in CH2Cl2, treated with 2,6-lutidine (2.2 mL, 19 mmol), followed by 1-methyl-1H-imidazole-2-sulfonyl chloride (1 g, 17.5 mmmol), and stirred overnight at 25 °C. The solution was treated with ethylenediamine (2.7 mL, 40 mmol) for 10 min, diluted with EtOAc (150 mL), washed with 0.5 M citrate solution, then washed saturated NaHCO3, dried over Na2SO4, and evaporated to a residue under vacuum. Purification by column chromatography (40 → 100% EtOAc/hexanes) and evaporation of the collected fractions gave 3.18 g of the title compound 67 (83%, 4.56 mmol), a white amorphous solid. High resolution mass, calculated for C37H37BrN4O3S [M+H]+ = 697.1843, found 697.1830, Δ = -1.86 ppm. 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.42 (m, 8H), 7.37 – 7.30 (m, 6H), 7.30 – 7.24 (m, 3H), 7.16 (s, 1H), 7.14 (s, 1H), 7.06 (d, J = 1.1 Hz, 1H), 6.93 (s, 1H), 6.22 (s, 1H), 5.88 (dddd, J = 17.30, 9.70, 7.00, 6.00 Hz, 1H), 5.23 (dd, J = 17.1, 1.8 Hz, 1H), 5.08 (dd, J = 10.1, 1.8 Hz, 1H), 3.88 (s, 3H), 3.54 – 3.42 (m, 2H), 3.34 (tdd, J = 15.3, 12.8, 6.9 Hz, 6H), 3.22 (dd, J = 13.1, 7.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 143.99 (3C), 143.41, 139.18, 134.92, 131.50 (2C), 129.39 (2C), 128.73 (6C), 128.13, 127.87 (6C), 127.06 (3C), 124.69, 120.52, 118.29, 86.85, 68.23, 67.97, 66.41, 60.30, 45.43, 40.93, 34.84.
