反应详情

5-((8-chloro-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-2-fluorobenzoic acid (103) (0.2 g, 0.60 mmol), 4-ethoxypiperidine (0.078 g, 0.60 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (0.251 g, 0.78 mmol) were dissolved in DMF (10 mL), to this was added DIPEA (0.136 mL, 0.78 mmol) and the reaction was stirred for 1 hour. The solvent was evaporated to dryness and the gum was dissolved in acetonitrile (4 mL) and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired compound as a white foam (0.052 g, 19.49%); 1H NMR (400.132 MHz, CDCl3) δ 1.20 (3H, t), 1.59-1.48 (1H, m), 1.81-1.63 (2H, m), 1.94-1.89 (1H, m), 3.16-3.07 (1H, m), 3.57-3.45 (4H, m), 4.09-4.00 (1H, m), 4.65 (2H, s), 6.99 (1H, t), 7.17-7.13 (2H, m), 7.26 (1H, s), 7.66 (1H, t), 7.80 (1H, dd), 8.49 (1H, dd); NH missing; m/z (LC-MS, ESI+), RT=2.08 (M+H 444).

1. customThe solvent was evaporated to dryness
2. dissolutionthe gum was dissolved in acetonitrile (4 mL)
3. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
4. additionFractions containing the desired compound
5. customwere evaporated to dryness