2.3. Synthesis of 1O
Figure 1 shows the procedure for synthesizing compound 1O. Compound 2[25–27] and compound 6[28] were obtained according to previous reports.
Compound 3 (1.22 g, 10.00 mmol) and 3-bromoprop-1-yne (1.04 g, 10.00 mmol) were dissolved in 20 mL acetonitrile, potassium carbonate (2.76 g, 20.00 mmol) and potassium iodide (1.65 g, 10.00 mmol) were added and then heated to reflux for 24 hours. After the solution was cooled to room temperature, the precipitate was filtered and 50 mL dichloromethane was added, the solution was washed three times with saturated sodium chloride solution. the dichloromethane was removed under reduced pressure and the product was purified with column chromatography using ether/ethyl acetate (v/v = 4:1) as an eluent to get compound 4 (1.26 g, 8.63 mmol) with 86% yield. 1H NMR (400 MHz, DMSO-d6), δ (ppm): 3.67 (s, 1H, −C ≡ H), 5.04 (s, 2H, −CH2−), 7.14 (t, 1H, −PhH), 7.30 (d, 1H, J = 8.0 Hz, −PhH), 7.70 (q, 2H, −PhH), 10.36 (s, 1H, −CHO) (Fig. S1); ESI-MS (m/z): 161.12 [3 + H+]+; Anal. calcd for C10H8O2: C, 74.99; H, 5.03; O, 19.98%. Found: C, 74.82; H, 5.11; O, 20.07%.
To a stirring 20 mL THF solution of compound 2 (0.40 g, 0.80 mmol) and compound 4 (0.13 g, 0.80 mmol), 2 mL aqueous solutions containing anhydrous copper sulfate (0.31 g, 1.20 mmol) and sodium ascorbate (0.48 g, 2.40 mmol) were added. Then, the solution was sequentially stirred for 24 hours. Subsequently, 1 mL of ammonium hydroxide was added into the solution and kept for stirring for another half an hour. After the completion of reaction, the solvent was removed under reduced pressure and the product was purified with column chromatography using ether/ethyl acetate (v/v = 6:1) as an eluent to obtain the compound 5 (0.38 g, 0.58 mmol) with 73% yield. 1H NMR (400 MHz, DMSO-d6), δ (ppm): 1.83 (s, 3H, −CH3), 1.89 (s, 3H, −CH3), 5.33 (s, 2H, −CH2−), 5.82 (s, 2H, −CH2−), 7.10 (s, 1H, thiophene − H), 7.23 (s, 1H, thiophene − H), 7.31 (t, 1H, −PhH), 7.40 (t, 4H, −PhH), 7.59 (d, 2H, J = 8.0 Hz, −PhH), 7.67 (q, 2H, −PhH), 8.34 (s, 1H, −CH=), 10.31 (s, 1H, −CHO) (Fig. S2); ESI-MS (m/z): 660.62 [5 + H+]+; Anal. calcd for C32H23F6N3O2S2: C, 58.26; H, 3.51; N, 6.37; O, 4.85%. Found: C, 58.17; H, 3.58; N, 6.22; O, 4.97%.
Compound 5 (0.20 g, 0.30 mmol) and compound 6 (0.10 g, 0.30 mmol) were dissolved in 10 mL ethyl alcohol and then heated to reflux for 24 hours. A pale pink precipitate was formed when the solution was cooled to room temperature. The crude product was washed three times with hot ethyl alcohol and filtered to give 1O (0.15 g, 0.15 mmol, yield: 50%). 1H NMR (500 MHz, DMSO-d6), δ (ppm): 1.82 (s, 3H, −CH3), 1.89 (s, 3H, −CH3), 5.10 (s, 2H, −CH2−), 5.89 (s, 2H, −CH2−), 6.38–6.43 (m, 4H, −PhH), 6.54 (s, 2H, thiophene − H), 6.89–6.93 (t, 1H, J = 8.0 Hz, −PhH), 7.05–7.07 (d, 1H, J = 8.0 Hz, −PhH), 7.14–7.16 (d, 1H, J = 8.0 Hz, −PhH), 7.29–7.32 (m, 3H, −PhH), 7.37–7.46 (m, 4H, −PhH), 7.56–7.60 (m, 4H, −PhH), 7.85–7.87 (d, 1H, J = 8.0 Hz, −PhH), 8.17 (s, 1H, −CH=), 9.13 (s, 1H, −CH=), 9.87 (s, 2H, −OH) (Fig. S3). 13C NMR (126 MHz, DMSO-d6), δ (ppm): 164.02, 158.95, 158.80, 156.96, 152.59, 151.05, 143.97, 143.62, 143.20, 142.20, 141.63, 137.17, 134.41, 132.91, 132.15, 129.71, 129.50, 129.45, 128.63, 128.39, 127.66, 125.73, 125.40, 125.19, 124.75, 124.23, 123.99, 123.54, 123.25, 122.86, 121.52, 113.64, 112.66, 110.34, 102.92, 65.56, 61.95, 47.78, 14.48, 14.34 (Fig. S4); ESI-MS (m/z): 849.42 [1O + Na+]+; Anal. calcd for C48H55N7O6: C, 69.80; H, 6.71; N, 11.87; O, 11.62%. Found: C, 69.67; H, 6.88; N, 11.78; O, 11.67%.