4.1.4. General Procedure for the Synthesis of Compounds 6–9
Compound 3 (1.0 eq) was dissolved in toluene/DMF (15 mL/5 mL), and then DBU (1.3 eq) was added. Subsequently, the mixture was stirred and heated at 100 °C, and after 30 min the respective halide (3.0 eq) was added. The reaction mixture was stirred and heated at 100 °C for 6 h and then stirred at room temperature for 24 h. The mixture was evaporated to dryness using acetonitrile to remove the toluene and DMF. The residue was purified by column flash chromatography on silica gel using CombiFlash®Rf+ (chloroform/ethyl acetate, increasing concentration gradient) with an integrated Evaporative Light Scattering Detector (ELSD) and UV detector.
Compound 6: Yield: 33.4% ESI-MS for C22H21BrO6 (m/z): [M + Na]+ 485. 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.42 (d, J = 2.1 Hz, 1H), 7.10 (dd, J = 8.4, 2.1 Hz, 1H), 6.89–6.86 (m, 1H), 6.29 (s, 2H), 4.73 (d, J = 2.5 Hz, 2H), 3.83 (s, 3H), 3.75 (s, 3H), 3.52 (s, 6H), and 2.43 (t, J = 2.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 166.57, 155.50, 152.58, 141.66, 139.21, 134.62, 130.20, 129.18, 129.08, 128.80, 111.96, 111.64, 108.09, 77.69, 74.87, 60.80, 56.25, 55.61, and 52.57.
Compound 7: Yield: 45.6% ESI-MS for C26H25BrO6 (m/z): [M + Na]+ 536. 1H NMR (401 MHz, CDCl3) δ 7.76 (s, 1H), 7.51 (d, J = 2.1 Hz, 1H), 7.40–7.32 (m, 6H), 7.18 (d, J = 8.4, 2.1 Hz, 1H), 6.94 (d, 1H), 6.35 (s, 2H), 5.26 (s, 2H), 3.91 (s, 3H), 3.82 (s, 3H), and 3.59 (s, 6H).13C NMR (101 MHz, CDCl3) δ 167.23, 155.47, 152.63, 140.94, 136.04, 134.74, 130.22, 129.63, 129.56, 129.41, 128.49, 128.07, 127.89, 111.97, 111.64, 108.10, 66.81, 60.82, 56.31, and 55.67.
Compound 8: Yield: 30.7% ESI-MS for C23H26Br2O6 (m/z): [M + Na]+ 581. 1H NMR (401 MHz, CDCl3) δ 7.72 (s, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.14 (dd, J = 8.4, 2.1 Hz, 1H), 6.95–6.92 (m, 1H), 6.35 (s, 2H), 4.22 (t, J = 6.2 Hz, 2H), 3.90 (s, J = 2.4 Hz, 3H), 3.81 (s, 3H), 3.58 (s, 6H), 3.38 (t, J = 6.5 Hz, 2H), 1.94–1.86 (m, 2H), and 1.86–1.78 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 167.34, 155.44, 152.64, 140.74, 134.59, 130.08, 129.67, 129.62, 129.37, 112.00, 111.63, 108.11, 64.29, 60.80, 56.32, 55.67, 33.03, 29.38, and 27.17.
Compound 9: Yield: 34.3% ESI-MS for C25H30Br2O6 (m/z): [M + Na]+ 609. 1H NMR (401 MHz, CDCl3) δ 7.71 (s, 1H), 7.47 (d, J = 2.1 Hz, 1H), 7.14 (dd, J = 8.4, 2.1 Hz, 1H), 6.61 (s, 1H), 6.34 (s, 2H), 4.19 (t, J = 6.5 Hz, 2H), 3.90 (s, 3H), 3.81 (s, 3H), 3.58 (s, 6H), and 1.88–1.14 (m, 8H). 13C NMR (101 MHz, CDCl3) δ 167.41, 155.38, 152.61, 140.50, 134.63, 131.07, 130.34, 130.10, 129.91, 129.72, 129.44, 126.50, 111.90, 111.73, 108.07, 105.37, 33.57, 32.49, 28.32, 27.58, and 25.05.
4.1.5. General Procedure for the Synthesis of Compounds 10–22
Compound 3 (1.0 eq) was dissolved in CH2Cl2 (20 mL) and cooled in an ice-water bath, then DCC (1.2 eq) was added. After 20 min, the solution of HOBt in 5 mL of THF was added (0.5 eq). After 10 min a respective amine was added. The reaction mixture was stirred for 24 h. Then, the precipitated DCU was separated under reduced pressure and the filtrate was evaporated to dryness in the presence of silica gel. The residue was purified by column flash chromatography using CombiFlash®Rf+ (chloroform/ethyl acetate, increasing concentration gradient) with an integrated Evaporative Light Scattering Detector (ELSD) and UV detector.
Compound 10: Yield: 31.2% ESI-MS for C20H22BrNO5 (m/z): [M + Na]+ 458. 1H NMR (401 MHz, CDCl3) δ 7.71 (s, 1H), 7.48 (d, J = 2.1 Hz, 1H), 7.16 (dd, J = 8.4, 2.1 Hz, 1H), 6.97 (d, 1H), 6.24 (s, 2H), 3.89 (s, 3H), 3.76 (s, 3H), 3.54 (s, 6H), and 2.83 (d, J = 4.9 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 167.24, 155.95, 152.51, 137.29, 134.68, 131.54, 130.26, 129.81, 129.63, 112.69, 107.61, 60.69, 56.31, 55.51, and 26.92.
Compound 11: Yield: 34.7% ESI-MS for C23H28BrNO5 (m/z): [M + Na]+ 500. 1H NMR (401 MHz, CDCl3) δ 7.71 (s, 1H), 7.49 (d, J = 2.1 Hz, 1H), 7.17 (dd, J = 8.4, 2.1 Hz, 1H), 7.01–6.97 (m, 1H), 6.25 (s, 2H), 3.92 (s, 3H), 3.78 (s, 3H), 3.56 (s, 6H), 3.29 (dd, J = 13.1, 7.1 Hz, 2H), 1.47–1.39 (m, 2H), 1.32–1.21 (m, 2H), and 0.88 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 166.55, 155.97, 152.56, 137.33, 134.74, 131.78, 130.23, 129.92, 129.73, 112.69, 112.58, 107.64, 60.73, 56.34, 55.56, 39.88, 31.52, 19.98, and 13.65.
Compound 12: Yield: 35.8% ESI-MS for C22H22BrNO5 (m/z): [M+Na]+ 482. 1H NMR (401 MHz, CDCl3) δ 7.74 (s, 1H), 7.51 (d, J = 2.1 Hz, 1H), 7.19 (dd, J = 8.4, 2.1 Hz, 1H), 7.00 (d, 1H), 6.26 (s, 2H), 4.10 (dd, J = 5.4, 2.6 Hz, 2H), 3.92 (s, 3H), 3.78 (s, 3H), 3.56 (s, 6H), and 2.19 (t, J = 2.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 166.30, 156.12, 152.59, 138.35, 134.78, 130.85, 130.30, 129.60, 129.12, 112.78, 112.70, 107.78, 79.36, 71.51, 60.75, 56.36, 55.58, and 29.76.
Compound 13: Yield: 39.6% ESI-MS for C26H26BrNO5 (m/z): [M] 512, [M + Na]+ 536, [M + K]+ 551. 1H NMR (401 MHz, CDCl3) δ 7.79 (s, 1H), 7.53 (d, J = 2.1 Hz, 1H), 7.32–7.28 (m, 2H), 7.27–7.22 (m, 3H), 7.20 (dd, J = 8.3, 2.0 Hz, 2H), 6.97 (d, 1H), 6.28 (s, 2H), 4.53 (d, J = 5.9 Hz, 2H), 3.90 (s, 3H), 3.80 (d, J = 2.1 Hz, 3H), and 3.57 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 166.68, 156.04, 152.60, 138.15, 137.99, 134.78, 131.46, 130.25, 129.80, 129.44, 128.61, 127.37, 127.33, 112.76, 112.67, 107.71, 60.77, 56.33, 55.59, and 44.01.
Compound 14: Yield: 40.9% ESI-MS for C25H24BrNO5 (m/z): [M + Na]+ 520. 1H NMR (401 MHz, CDCl3) δ 7.84 (s, 1H), 7.61 (d, J = 2.1 Hz, 1H), 7.48 (dt, J = 8.7, 1.7 Hz, 3H), 7.31–7.27 (m, 4H), 7.12–7.07 (m, 1H), 7.07–7.04 (d, 1H), 6.30 (s, 2H), 3.96 (s, 3H), 3.81 (s, 3H), and 3.59 (s, 6H).13C NMR (101 MHz, CDCl3) δ 164.61, 156.32, 152.66, 138.68, 137.69, 134.95, 131.87, 130.44, 129.68, 129.13, 128.88, 124.48, 119.91, 112.94, 112.90, 107.86, 60.78, and 56.40, 55.62.
Compound 15: Yield: 25.4% ESI-MS for C25H24BrNO5 (m/z): [M] 557, [M + Na]+ 581, [M + K]+ 595. 1H NMR (401 MHz, CDCl3) δ 8.00 (dd, J = 8.1, 1.2 Hz, 1H), 7.70 (s, 1H), 7.66–7.58 (m, J = 9.0, 7.7, 1.5 Hz, 2H), 7.47 (d, J = 2.1 Hz, 1H), 7.46–7.41 (m, 1H), 7.15 (dd, J = 8.4, 2.1 Hz, 1H), 7.00 (d, 1H), 6.39 (t, J = 6.4 Hz, 1H), 6.25 (s, 2H), 4.71 (d, J = 6.4 Hz, 2H), 3.91 (s, 4H), 3.78 (s, 3H), and 3.55 (s, 7H). 13C NMR (101 MHz, CDCl3) δ 166.84, 156.09, 152.57, 138.04, 134.67, 133.87, 133.40, 132.01, 131.24, 130.04, 129.63, 129.12, 128.59, 125.01, 112.75, 112.70, 107.76, 60.73, 56.34, 55.57, and 41.88.
Compound 16: Yield: 23.6% ESI-MS for C26H25BrClNO5 (m/z): [M + Na]+ 570. 1H NMR (401 MHz, CDCl3) δ 7.75 (s, 1H), 7.53 (d, J = 2.1 Hz, 1H), 7.37–7.31 (m, 3H), 7.24–7.18 (m, 4H), 7.00–6.98 (m, 1H), 6.27 (s, 2H), 4.57 (d, J = 6.1 Hz, 2H), 3.92 (s, 3H), 3.79 (s, 3H), and 3.57 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 166.69, 156.12, 152.65, 138.04, 135.47, 134.84, 131.43, 130.31, 130.04, 129.82, 129.52, 129.44, 128.86, 127.03, 112.78, 112.73, 107.80, 60.82, 56.42, 55.65, and 42.31.
Compound 17: Yield: 25.1% ESI-MS for C26H25BrClNO5 (m/z): [M+Na]+ 570. 1H NMR (401 MHz, CDCl3) δ 7.78 (s, 1H), 7.55–7.53 (m, 1H), 7.24–7.19 (m, 5H), 7.13–7.10 (m, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.28 (s, 2H), 4.49 (d, J = 6.1 Hz, 2H), 3.91 (s, 3H), 3.80 (d, J = 1.1 Hz, 3H), and 3.58 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 166.83, 156.18, 152.68, 140.37, 138.34, 134.84, 131.26, 130.31, 129.92, 129.75, 129.41, 127.56, 127.53, 125.54, 112.88, 112.82, 107.86, 60.82, 56.42, 55.66, and 43.47.
Compound 18: Yield: 26.7% ESI-MS for C26H25BrClNO5 (m/z): [M + Na]+ 570. 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.46 (d, J = 2.1 Hz, 1H), 7.22–7.07 (m, 6H), 6.93–6.90 (m, 1H), 6.20 (s, 2H), 4.40 (d, J = 6.0 Hz, 2H), 3.84 (s, 3H), 3.73 (s, 3H), and 3.50 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 166.74, 156.07, 152.59, 138.69, 138.21, 136.75, 134.75, 133.10, 131.20, 130.23, 129.69, 129.32, 128.92, 128.79, 128.75, 128.71, 112.77, 112.71, 107.71, 60.77, 56.36, 56.34, 55.57, and 43.32.
Compound 19: Yield: 35.9% ESI-MS for C25H32BrNO5 (m/z): [M]+ 506, [M + Na]+ 528, [M+K]+ 544. 1H NMR (401 MHz, CDCl3) δ 7.57 (d, J = 2.1 Hz, 1H), 7.27 (dd, J = 8.2, 1.9 Hz, 1H), 6.83–6.80 (m, 1H), 6.50 (s, 1H), 6.36 (s, 2H), 3.86 (s, 3H), 3.80–3.79 (m, 3H), 3.61 (s, 6H), 3.27 (d, J = 41.7 Hz, 4H), 1.43–1.25 (m, 4H), and 0.93–0.76 (m, 6H).13C NMR (101 MHz, CDCl3) δ 170.95, 155.45, 152.76, 137.84, 135.97, 133.51, 130.44, 129.25, 129.18, 129.06, 111.67, 111.43, 106.55, 60.77, 56.18, 55.80, 50.24, 24.88, and 11.26.
Compound 20: Yield: 37.4% ESI-MS for C27H36BrNO5 (m/z): [M]+ 534, [M + Na]+ 556. 1H NMR (600 MHz, CDCl3) δ 7.52 (d, J = 2.2 Hz, 1H), 7.22 (dd, J = 8.5, 2.2 Hz, 1H), 6.77–6.76 (m, 1H), 6.46 (s, 1H), 6.31 (s, 2H), 3.81 (s, 3H), 3.75 (d, J = 1.9 Hz, 3H), 3.57 (s, 6H), 3.34–3.16 (m, 4H), and 1.32–0.75 (m, 14H). 13C NMR (151 MHz, CDCl3) δ 170.89, 155.51, 152.83, 136.03, 133.60, 130.53, 129.25, 129.07, 111.71, 111.48, 106.55, 60.84, 56.25, 55.84, 48.43, 33.90, 19.96, and 13.81.
Compound 21: Yield: 32.2% ESI-MS for C23H26BrNO6 (m/z): [M + Na]+ 514. 1HNMR (400 MHz, CDCl3) δ 7.51 (d, J = 2.2 Hz, 1H), 7.21 (dd, 1H), 6.79 (d, 1H), 6.52 (s, 1H), 6.32 (s, 2H), 3.82 (s, 3H), 3.75 (s, 3H), and 3.61–3.48 (m, J = 20.0 Hz, 14H). 13C NMR (101 MHz, CDCl3) δ 169.79, 155.55, 152.74, 137.96, 134.14, 133.40, 130.42, 129.94, 129.18, 128.85, 111.78, 111.57, 106.51, 66.61, 60.77, 56.19, 56.18, 55.75, and 55.75.
Compound 22: Yield: 19.4% ESI-MS for C33H32BrNO5 (m/z): [M]+ 602, [M + Na]+ 624. 1H NMR (600 MHz, CDCl3) δ 7.53 (s, 1H), 7.28–7.18 (m, 11H), 6.72 (d, 1H), 6.52 (s, 1H), 6.18 (s, 2H), 4.57 (s, 2H), 4.40 (s, 2H), 3.80 (s, 3H), 3.73 (s, 3H), and 3.53 (s, 6H). 13C NMR (151 MHz, CDCl3) δ 171.70, 155.64, 152.79, 134.87, 133.64, 130.14, 129.99, 129.43, 128.82, 128.69, 127.51, 111.79, 111.67, 106.56, 60.83, 56.27, 55.83, and 29.64.