Reaction Steps
4-Allyloxy-N-{2-[(2-benzyloxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-methyl]-1-methanesulfonyl-3-oxo-[1,2]diazepan-4-yl}-3,5-dichloro-benzamide (26a) (178 mg, 0.26 mmol) in dichloromethane (6 mL) was treated with DMBA (45 mg, 0.29 mmol) and Pd(PPh3)4 (20 mg, 0.017 mmol) at room temperature for 16 hours. The mixture was diluted with dichloromethane (40 mL), washed with water three times. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to give a pale yellow solid, that was purified by flash chromatography using dichloromethane/methanol (99.2/0.8 to 97.5/2.5) to afford 78 mg (47% yield) of syn diastereomer (higher Rf) of the title compound and 59 mg (35% yield) of anti diastereomer (lower Rf). 1H-NMR (500 MHz, CDCl3) for the syn diastereomer: δ 1.60-1.70 (m, 1H), 1.88-1.91 (m, 1H), 2.22-2.32 (m, 2H), 2.48-2.58 (m, 1H), 2.84-2.90 (m, 1H), 3.00 (s, 3H), 3.27-3.40 (m, 1H), 4.05-4.18 (m, 2H), 4.22-4.35 (m, 1H), 4.55-4.80 (m, 2H), 4.86-4.89 (d, 1H), 5.10-5.15 (m, 1H), 5.59-5.61 (d, 1H), 6.75-6.77 (d, 1H), 7.05-7.07 (d, 1H), 7.25-7.37 (m, SH), 7.70 (s, 2H); and for the anti diastereomer: δ 1.60-1.80 (m, 1H), 1.85-1.95 (m, 1H), 2.20-2.39 (m, 2H), 2.39-2.50 (m, 1H), 3.00-3.10 (m, 1H), 3.12 (s, 3H), 3.28-3.42 (m, 1H), 4.05-4.15 (m, 2H), 4.28-4.47 (m, 2H), 4.56-4.62 (m, 1H), 4.77-4.83 (d, 1H), 5.10-5.20 (m, 1H), 5.43 (s, 1H), 6.93-6.94 (d, 1H), 7.09-7.11 (d, 1H), 7.25-7.39(m, SH), 7.80 (s, 2H). Analytical HPLC: 11.13 and 11.36 min. LC-MS (ES+) for the mixture of diastereomers: m/e=643, 645 (M+H+).
