反应详情

To a solution of 5 mL of trifluoroacetic acid under nitrogen is add 364 mg of 2-[7-fluoro-3-(1-tertbutoxycarbonyl-indazol-3-ylmethyl)-2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 66. After stirring at ambient temperature for 20 min, the reaction mixture is evaporated in vacuo and the residue is partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer is back-extracted with dichloromethane. The organic layers were combined, washed with aqueous sodium hydroxide (1N), dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue is triturated with hexane, the hexane is removed in vacuo, and the residual solid is dried under high vacuum to provide 286 mg of the title compound as a white solid: 1H NMR (300 MHz, CDCl3) δ8.67 (s, br, 1H), 8.56 (dd, 1H, J=1.5, 5.2), 8.10 (d, 1H, J=8.1), 7.82 (d, 1H, J=8.1), 7.52 (dd, 1H, J=5.3, 8.3), 7.35 (m, 3H), 7.14 (m, 3H), 7.03 (m, 1H), 6.96 (m, 3H), 6.61 (dd, 1H, J=2.7, 8.9), 4.92 (m, 1H), 4.51 (d, 1H, J=15.8), 4.29 (dd, 1H, J=5.8, 7.7), 4.05 (d, 1H, J=16.0), 3.84 (s, 3H), 3.78 (dd, 1H, J=7.8, 16.4), 3.61 (dd, 1H, J=5.9, 16.2), 1.03 (d, 6H, J=6.8); low resolution MS (FAB)m/e 607 (MH+).

1. customthe reaction mixture is evaporated in vacuo
2. customthe residue is partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
3. customThe layers were separated
4. extractionthe aqueous layer is back-extracted with dichloromethane
5. washwashed with aqueous sodium hydroxide (1N)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe residue is triturated with hexane
10. customthe hexane is removed in vacuo
11. customthe residual solid is dried under high vacuum