Reaction Steps
To a solution of 4-allyloxy-N-{2-[(2-benzyloxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-methyl]-3,7-dioxo-1-propyl-[1,2]diazepan-4-yl}-3,5-dichloro-benzamide (10c, diastereomers) (103 mg, 0.16 mmol) in dichloromethane (15 mL) was added DMBA followed by Pd(PPh3)4 (30 mg, 0.026 mmol), stirred at room temperature for 7 hours. The reaction mixture was washed with water, dried over anhydrous Na2SO4, filtered and purified by flash chromatography using dichloromethane/methanol (99.5/0.5 to 97/3) to afford both anti diastereomer (18 mg, 18% yield, lower Rf) and syn diastereomer (48 mg, 50% yield, higher Rf) of the title compound. 1H-NMR (500 MHz, CDCl3) for the anti diastereomer: δ 0.9-1.02 (m, 3H), 1.65-185 (m, 2H), 2.01-2.18 (m, 0.5H), 2.20-2.30 (d, 0.5H), 2.37-2.47 (m, 1H), 2.58-2.70 (m, 1H), 2.90-3.00 (m, 1H), 3.00-3.10 (m, 1H), 3.25-3.50 (m, 1H), 4.0-4.15 (m, 2H), 4.15-4.25 (d, 1H), 4.40-4.55 (m, 1H), 4.55-4.67 (m, 1H), 4.72-4.82 (d, 1H), 5.05-5.17 (m, 1H), 5.27-5.38 (m, 2H), 6.90-7.00 (d, 1H), 7.25-7.40 (m, 6H), 7.60-7.70 (m, 1H), 7.80 (s, 2H; for the syn diastereomer: δ 0.9-1.00 (m, 3H), 1.50-1.70 (m, 2H), 1.8-1.92 (m, 1H), 2.38-2.42 (m, 1H), 2.48-2.58 (m, 1H), 2.74-2.87 (m, 1H), 2.88-2.98 (m, 1H), 3.00-3.13 (m, 1H), 3.17-3.30 (m, 1H), 4.00-4.12 (m, 1H), 4.14-4.30 (d, 1H), 4.22-4.32 (m, 1H), 4.62-4.46 (d, 1H), 4.75-4.80 (m, 1H), 4.90-4.95 (d, 1H), 5.10-5.20 (m, 1H), 5.53-5.57 (d, 1H), 6.24 (s, 1H), 6.49 (d, 1H), 6.70 (d, 1H), 7.25-7.40 (m, 5H), 7.71 (s, 2H). Analytical HPLC: 8.55 min for syn diastereomer and 8.57 min for the anti diastereomer. LC-MS (ES+) for the mixture of the product: m/e=621, 623 (M+H+).
