Compound 69
(8R,9S,10S,Z)-9-(4-bromophenyl)-6-((1-methyl-1H-imidazol-2-yl)sulfonyl)-10-((trityloxy)methyl)-1,6-diazabicyclo[6.2.0]dec-3-ene
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.
The bis-allyl intermediate 68 (1.44 mg, 1.96 mmol) was dissolved in CH2Cl2 (1.5 L, final dilution ≈1.3 mM) and purged by vigorously bubbling with argon gas for 1 hour. The solution was treated with Grubb’s second-generation catalyst dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II) (330 mg, 0.39 mmmol, 0.2 equiv.) and heated to reflux for 24 h. In this case, the reaction did not go to completion, therefore, the solution was treated with additional 0.2 equiv. of catalyst and heated for additional 48 h. The solution was evaporated to a residue under vacuum, followed by purification by column chromatography two times (10 → 70% EtOAc/hexanes) and evaporation of the collected fractions gave 0.497 g of title macrocycle compound 69 (36%, 0.70 mmol), a yellow amorphous solid. High resolution mass, calculated for C38H37BrN4O3S [M+H]+ = 709.1843, found 709.1830, Δ = -1.83 ppm. 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.41 (m, 9H), 7.36 – 7.30 (m, 6H), 7.30 – 7.20 (m, 2H), 7.10 – 7.01 (m, 3H), 6.97 – 6.90 (m, 1H), 5.92 (ddd, J = 17.5, 7.7, 1.0 Hz, 1H), 5.69 (dd, J = 31.3, 10.7 Hz, 1H), 4.48 (dd, J = 15.1, 8.0 Hz, 1H), 4.12 (ddt, J = 23.9, 16.7, 7.8 Hz, 1H), 3.98 (d, J = 13.7 Hz, 2H), 3.89 (s, 3H), 3.82 – 3.71 (m, 1H), 3.62 – 3.42 (m, 3H), 3.42 – 3.25 (m, 2H), 3.16 (t, J = 8.0, 7.0 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 143.86 (3C), 143.28, 138.11, 131.69, 130.57, 129.15, 128.69 (6C), 128.10, 127.94 (6C), 127.17 (3C), 126.34, 124.66, 120.97, 87.06, 71.49, 70.90, 67.08, 66.25, 57.77, 54.24, 45.54, 42.23, 34.66, 29.74.
