Reaction Steps
A mixture of acid 18 (300 mg, 1.11 mmol), 40% aqueous Me2NH (2.81 mL, 22.2 mmol), Na2CO3 (295 mg, 2.78 mmol), and water (20 mL) was stirred at 100° C. for 1.5 h. After cooling to room temperature the solvent was removed in vacuo, the residue was dissolved in water (15 mL), and the resulting solution was acidified with 2 M HCl. Then, the solution was evaporated to dryness and the resulting crude product was purified by column chromatography on silica gel (MeOH/CH2Cl2, 10:1, 1% conc. HCl) to provide a green solid which was dissolved in water. Insoluble silica gel was removed by filtration, the water was removed under reduced pressure and the residue was dried in vacuo to give 19 (343 mg, 98%) as a grey-green solid. 1H NMR (300 MHz, DMSO-d6): δ=2.87 (s, 6 H, NMe2), 3.49 (t, J=5.0 Hz, 2 H, 2′-H2), 3.82 (s, 3 H, OMe), 4.34 (t, J=5.0 Hz, 2 H, 1′-H2), 6.94 (s, 1 H, 7-H), 6.97 (d, J=1.8 Hz, 1 H, 3-H), 7.23 (s, 1 H, 4-H), 10.99 (sbr, 1 H, NH+), 11.50 (sbr, 1 H, NH), 12.60 (sbr, 1 H, CO2H) ppm; 13C NMR (50.3 MHz, DMSO-d6): δ=42.7 (NMe2), 55.2 (C-2′), 55.6 (OMe), 64.5 (C-1′), 94.8 (C-7), 106.2 (C-4), 107.5 (C-3), 119.7 (C-3a), 127.0 (C-2), 133.2 (C-7a), 143.4 (C-5), 149.4 (C-6), 162.4 (C═O) ppm; MS (70 eV, EI): m/z (%)=278 (7) [M−HCl]+, 58 (100) [CH2NMe2]+; C14H19ClN2O4 (314.76): calcd. 278.1267 [M−HCl]+, found 278.1267.
