Reaction Steps
Isoquinoline-1-carboxylic acid {2-[(2-benzyloxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-methyl]-3,7-dioxo-1-propyl-[1,2]diazepan-4-yl}-amide (10b) was synthesized from 7b and the diastereomers of 9 by the method and chromatography used to prepare 10a to afford both syn diastereomer (203 mg, 67% yield, higher Rf) and anti diastereomer (93 mg, 31% yield, lower Rf) of the title compound. 1H-NMR (500 MHz, CDCl3) for the anti diastereomer: δ 0.96-1.05 (t, 3H), 1.72-1.82 (m, 2H), 2.10-2.20 (m, 1H), 2.48-2.56 (m, 2H), 2.78-2.86 (m, 1H), 2.92-3.18 (m, 3H), 3.25-3.39 (m, 1H), 3.95-4.02 (m, 1H), 4.06-4.17 (m, 1H), 4.41-4.50 (m, 1H), 4.62-4.66 (d, 1H), 4.82-4.89 (d, 1H), 5.10-5.20 (m, 1H), 5.5 (s, 1H), 6.68 (d, 1H) 7.28-7.40 (m, 5H), 7.70-7.77 (m, 2H), 7.82-7.89 (m, 2H), 8.51 (d, 1H), 8.77 (d, 1H), 9.52 (d, 1H); for the syn diastereomer: δ 0.90-0.98 (t, 3H), 1.60-1.80 (m, 2H), 2.00-2.10 (m, 1H), 2.43-2.50 (m, 2H), 2.80-2.98 (m, 2H), 3.10-3.20 (m, 2H), 4.03-4.17 (m, 2H), 4.29-4.33 (d, 1H), 4.60-4.63 (d, 1H), 4.70-4.79 (m, 1H), 4.85-4.89 (d, 1H), 5.21-5.30 (m, 1H), 5.52 (d, 1H), 6.70 (d, 1H), 7.28-7.33 (m, 5H), 7.64-7.78 (m, 2H), 7.83-7.90 (m, 2H), 8.50 (d, 1H), 8.85 (d, 1H), 9.50 (d, 1H). Analytical HPLC: is 10.60 min for the anti diastereomer and 10.30 min for the syn diastereomer. LC-MS (ES+) for the mixture of the product: m/e 588 (M+H+).
