Reaction Steps
Compound 12 (84 mg, 0.27 mmol) was dissolved in MeOH (4 mL), and then acetic anhydride (28 μL, 0.30 mmol) was added. The reaction mixture was refluxed for 30 min. The reaction solvent was removed by evaporation, and then the residue was dissolved in CH2Cl2 (30 mL), and washed with H2O (3×10 mL). The organic layer was collected, dried over Na2SO4, filtered, concentrated and purified by silica column chromatography (40% EtOAc in hexanes) to afford methyl 2-((2-acetamido-5-methoxyphenyl)ethynyl)-4-methoxybenzoate in 81.8% (78 mg) yield as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 9.30 (1H, s, NH), 8.51 (1H, d, J=9.6 Hz, Ar), 8.03 (1H, d, J=8.8 Hz, Ar), 7.14 (1H, s, Ar), 7.01 (1H, s, Ar), 6.93 (1H, d, J=9.6 Hz, Ar), 6.89 (1H, d, J=8.8 Hz, Ar), 3.88 (6H, s, 2×OCH3), 3.79 (3H, s, OCH3), 2.39 (3H, s, CH3); 13C-NMR (CDCl3, 100 MHz) δ 169.8, 166.0, 162.7, 154.9, 135.3, 132.8, 126.2, 122.5, 121.2, 118.2, 116.7, 116.2, 114.9, 112.4, 94.6, 91.0, 55.8, 55.7, 52.3, 24.6; MS (ESI) m/z Calcd for C20H19NO5 (M+): 353.1, Found: 352.0 (M−H+). LiOH.H2O (25 mg, 0.60 mmol) was added to a solution of methyl 2-((2-acetamido-5-methoxyphenyl)ethynyl)-4-methoxybenzoate (41 mg, 0.12 mmol) in THF/MeOH/H2O (ratio=3:1:1, 2 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was neutralized by adding 1M HCl (aq) and partitioned between EtOAc and sat'd NaH2PO4 (aq). The organic layer was collected, dried over Na2SO4, filtered, concentrated and dried under vacuum to afford compound 13 in 99.5% (40 mg) yield as a brown solid. 1H-NMR (DMSO-d6, 400 MHz) δ 9.69 (1H, s, NH), 8.27 (1H, d, J=8.4 Hz, Ar), 8.01 (1H, d, J=8.0 Hz, Ar), 7.19 (1H, s, Ar), 7.08 (1H, s, Ar), 7.06 (1H, d, J=8.0 Hz, Ar), 6.99 (1H, d, J=8.4 Hz, Ar), 3.87 (3H, s, OCH3), 3.77 (3H, s, OCH3), 2.26 (3H, s, CH3); 13C-NMR (DMSO-d6, 100 MHz) δ 169.5, 167.6, 161.4, 154.8, 135.0, 133.1, 124.3, 121.6, 117.5, 116.6, 115.6, 115.2, 113.2, 96.1, 89.8, 56.0, 55.7, 24.5; MS (ESI) m/z Calcd for C19H17NO5 (M+): 339.1, Found: 338.1 (M−H+).
