反应详情

A mixture of 3-(4-methoxy-2-phenoxy-phenylamino)-phthalic acid (0.60 g, 1.6 mmol) and rac-α-aminoglutarimide hydrochloride (0.26 g, 1.6 mmol) in pyridine (10 mL) were heated to reflux for 20 hours. The mixture was cooled and evaporated under vacuum. The residue was dissolved in ethyl acetate (100 mL) and washed with dilute aqueous HCl (3×100 mL) and water (100 mL), and then evaporated under vacuum. The residue was purified by ISCO silica gel flash chromatography using a methylene chloride-methanol gradient, eluting 0.66 g of the product, an orange solid, at 95:5 methylene chloride-methanol, in 89% yield: mp 142-144° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 60/40 CH3CN/0.1% H3PO4, 4.71 min (96.79%); 1H NMR (DMSO-d6) δ 1.98-2.04 (m, 1H), 2.49-2.61 (m, 2H), 2.81-2.90 (m, 1H), 3.73 (s, 3H), 5.06 (dd, J=12.8 Hz, J=5.3 Hz, 1H), 6.58 (d, J=2.8 Hz, 1H), 6.84 (dd, J=8.8, J=2.8 Hz, 1H), 6.90-6.94 (m, 2H), 7.04-7.10 (m, 2H), 7.16 (d, J=7.0 Hz, 1H), 7.27-7.34 (m, 2H), 7.45 (d, J=8.7 Hz, 1H), 7.57 (dd, J=8.3 Hz, J=7.4 Hz, 1H), 7.95 (s, 1H), 11.10 (s, 1H); 13C NMR (DMSO-d6) δ 22.1, 30.9, 48.6, 55.5, 105.9, 109.6, 110.7, 112.6, 117.9, 118.7, 122.8, 123.5, 127.2, 129.9, 132.0, 136.0, 144.0, 151.1, 156.2, 157.8, 167.1, 168.5, 169.9, 172.8; Anal. calcd For C26H21N3O6.0.3H2O: C, 65.49; H, 4.55; N, 8.84. Found: C, 65.43; H, 4.29; N, 8.73.

1. temperaturewere heated
2. temperatureto reflux for 20 hours
3. temperatureThe mixture was cooled
4. customevaporated under vacuum
5. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
6. washwashed with dilute aqueous HCl (3×100 mL) and water (100 mL)
7. customevaporated under vacuum
8. customThe residue was purified by ISCO silica gel flash chromatography
9. washeluting 0.66 g of the product
10. customHPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 60/40 CH3CN/0.1% H3PO4, 4.71 min (96.79%)